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Bringing HCC Patients Hope Through Trials, Advanced Treatments
For Reena Salgia, MD, the most rewarding part about working with patients with hepatocellular carcinoma is being there for their entire journey, thanks to advancements in treatment. “It brings a smile to my face just to think about it,” says Dr. Salgia, medical director of Henry Ford Health’s Liver Cancer Clinic in Detroit.
Hepatocellular carcinoma accounts for 80% of all liver cancer. When she first entered the field, Dr. Salgia often heard that survival rates 5 years after diagnosis were less than 10%. Over the last decade however, “I’ve seen an expansion in the procedural options that we offer these patients. We have an array of options both surgically as well as procedurally,” she said.
Especially over the last three to four years, “we’ve seen meaningful responses for patients with medications that we previously didn’t have in our toolbox. That’s really been exciting, along with continued involvement in clinical trials and being able to offer patients a number of different approaches to their care of liver cancer,” said Dr. Salgia.
A regular attendee and presenter at national GI meetings, Dr. Salgia participated in AGA’s Women’s Executive Leadership Conference in 2023. Her academic resume includes a long list of clinical trials to assess treatments for patients at different stages of hepatocellular carcinoma.
In an interview, she discussed the highlights of her career as a researcher and mentor of fellows, and how she guides and supports her transplant patients.
What drove you to pursue the field of hepatology and transplant hepatology?
I came across this field during my fourth year of medical school. I didn’t know anything about hepatology when I reached that stage and had the opportunity to do an elective. I just fell in love with the specialty. I liked the complex pathophysiology of liver disease, the long-term follow-up and care of patients. It appealed to the type of science that I had enjoyed back in college.
As I went into my GI fellowship training, I got to learn more about the field of transplant medicine. For instance, how you can take these patients who are incredibly ill, really at a very vulnerable point of their illness, and then offer them great hope and see their lives turn around afterwards. When I had the opportunity to see patients go from end stage liver disease to such significant improvement in their quality of life, and restoring their physical functioning beyond what we would’ve ever imagined when they were ill, it reaffirmed my interest in both hepatology as well as in transplant medicine.
How do you help those patients waiting on transplant lists for a liver?
We are intimately involved in their care all the way through their journey with liver disease, up until the time of physically getting the liver transplant, which is performed by our colleagues in transplant surgery. From the time they are transplanted, we are involved in their inpatient and outpatient post-transplant care. We’ve helped to get them on the transplant list with the work of the multidisciplinary team. If there are opportunities to help them understand their position on the list or obtaining exceptions—though that is done in a very objective fashion through the regulatory system—we help to guide them through that journey.
You’ve worked on many studies that involve treatments for hepatocellular carcinoma. Can you highlight a paper that yielded clinically significant benefits?
What really stands out the most to me was our site’s involvement in the IMbrave150 trial, which was published in 2020. This multicenter study made a big difference in the outcomes and treatments for patients, as it brought the adoption of first-line immunotherapy (atezolizumab plus bevacizumab) for patients with advanced hepatocellular carcinoma. I remember vividly the patients we had the opportunity to enroll in that trial – some who we continue to care for today. This stands out as one of the trials that I was involved in that had a lasting impact.
What were the clinical endpoints and key results of that trial?
The endpoint was to see an improvement in overall survival utilizing immunotherapy, compared with the prior standard of care then available, oral therapy. The results led to the adoption and FDA approval of immunotherapy in the first line setting for advanced unresectable hepatocellular carcinoma patients.
What are some of the highlights of serving as director of Henry Ford’s fellowship program?
Education is my passion. I went into medical training feeling that at some point I would love to blend in teaching in a formal role. Becoming program director of the gastroenterology and hepatology fellowship at Henry Ford in 2018 was one of the most meaningful things that I’ve had the opportunity to do in my career. I get to see trainees who are at a very impressionable point of their journey go on to become gastroenterologists and then launch into their first job and really develop in this field. Seeing them come in day one, not knowing how to hold a scope or do a procedure on a patient of this nature, then quickly evolve over the first year and grow over three years to achieve this specialty training [is rewarding]. I’ve learned a lot from the fellows along the way. I think of them as an extension of my family. We have 15 fellows currently in our program and we’ll be growing this summer. So that’s really been a highlight of my career thus far.
What fears did you have to push past to get to where you are in your career?
I think that there have been a few. One is certainly the fear of making the wrong choice with your first career opportunity. I did choose to leave my comfort zone from where I had done my training. I met that with some fear, but also excitement for new opportunities of personal and professional growth.
Another fear is: Am I going to be able to be ambitious in this field? Can I pursue research, become a program director, and do things that my role models and mentors were able to achieve? There’s also the fear of being able to balance a busy work life with a busy home life and figuring out how to do both well and minimize the guilt on both sides. I have a family with two girls. They are definitely a top priority.
What teacher or mentor had the greatest impact on you?
Helen Te, MD, a hepatologist at the University of Chicago. When I was a medical student there, I had the opportunity to work with her and saw her passion for this field. She really had so much enthusiasm for teaching and was a big part of why I started to fall in love with liver disease.
Karen Kim, MD, now the dean of Penn State College of Medicine, was one of my assigned mentors as a medical student. She helped me explore the fields where there were opportunities for residency and helped me make the decision to go into internal medicine, which often is a key deciding point for medical students. She was also a very influential teacher. The other individual who stands out is my fellowship program director, Hari Sree Conjeevaram, MD, MSc, at University of Michigan Health. He exhibited the qualities as an educator and program director that helped me recognize that education was something that I wanted to pursue in a formal fashion once I moved on in my career.
Describe how you would spend a free Saturday afternoon.
Likely taking a hike or go to a park with my family, enjoying the outdoors and spending time with them.
Lightning Round
If you weren’t a gastroenterologist, what would you be?
Philanthropist
Favorite city in U.S. besides the one you live in?
Chicago
Place you most want to travel?
New Zealand
Favorite breakfast?
Avocado toast
Favorite ice cream flavor?
Cookies and cream
How many cups of coffee do you drink per day?
Two…or more
Cat person or dog person?
Dog
Texting or talking?
Talk
Favorite season?
Autumn
Favorite type of music?
Pop
Favorite movie genre?
Action
For Reena Salgia, MD, the most rewarding part about working with patients with hepatocellular carcinoma is being there for their entire journey, thanks to advancements in treatment. “It brings a smile to my face just to think about it,” says Dr. Salgia, medical director of Henry Ford Health’s Liver Cancer Clinic in Detroit.
Hepatocellular carcinoma accounts for 80% of all liver cancer. When she first entered the field, Dr. Salgia often heard that survival rates 5 years after diagnosis were less than 10%. Over the last decade however, “I’ve seen an expansion in the procedural options that we offer these patients. We have an array of options both surgically as well as procedurally,” she said.
Especially over the last three to four years, “we’ve seen meaningful responses for patients with medications that we previously didn’t have in our toolbox. That’s really been exciting, along with continued involvement in clinical trials and being able to offer patients a number of different approaches to their care of liver cancer,” said Dr. Salgia.
A regular attendee and presenter at national GI meetings, Dr. Salgia participated in AGA’s Women’s Executive Leadership Conference in 2023. Her academic resume includes a long list of clinical trials to assess treatments for patients at different stages of hepatocellular carcinoma.
In an interview, she discussed the highlights of her career as a researcher and mentor of fellows, and how she guides and supports her transplant patients.
What drove you to pursue the field of hepatology and transplant hepatology?
I came across this field during my fourth year of medical school. I didn’t know anything about hepatology when I reached that stage and had the opportunity to do an elective. I just fell in love with the specialty. I liked the complex pathophysiology of liver disease, the long-term follow-up and care of patients. It appealed to the type of science that I had enjoyed back in college.
As I went into my GI fellowship training, I got to learn more about the field of transplant medicine. For instance, how you can take these patients who are incredibly ill, really at a very vulnerable point of their illness, and then offer them great hope and see their lives turn around afterwards. When I had the opportunity to see patients go from end stage liver disease to such significant improvement in their quality of life, and restoring their physical functioning beyond what we would’ve ever imagined when they were ill, it reaffirmed my interest in both hepatology as well as in transplant medicine.
How do you help those patients waiting on transplant lists for a liver?
We are intimately involved in their care all the way through their journey with liver disease, up until the time of physically getting the liver transplant, which is performed by our colleagues in transplant surgery. From the time they are transplanted, we are involved in their inpatient and outpatient post-transplant care. We’ve helped to get them on the transplant list with the work of the multidisciplinary team. If there are opportunities to help them understand their position on the list or obtaining exceptions—though that is done in a very objective fashion through the regulatory system—we help to guide them through that journey.
You’ve worked on many studies that involve treatments for hepatocellular carcinoma. Can you highlight a paper that yielded clinically significant benefits?
What really stands out the most to me was our site’s involvement in the IMbrave150 trial, which was published in 2020. This multicenter study made a big difference in the outcomes and treatments for patients, as it brought the adoption of first-line immunotherapy (atezolizumab plus bevacizumab) for patients with advanced hepatocellular carcinoma. I remember vividly the patients we had the opportunity to enroll in that trial – some who we continue to care for today. This stands out as one of the trials that I was involved in that had a lasting impact.
What were the clinical endpoints and key results of that trial?
The endpoint was to see an improvement in overall survival utilizing immunotherapy, compared with the prior standard of care then available, oral therapy. The results led to the adoption and FDA approval of immunotherapy in the first line setting for advanced unresectable hepatocellular carcinoma patients.
What are some of the highlights of serving as director of Henry Ford’s fellowship program?
Education is my passion. I went into medical training feeling that at some point I would love to blend in teaching in a formal role. Becoming program director of the gastroenterology and hepatology fellowship at Henry Ford in 2018 was one of the most meaningful things that I’ve had the opportunity to do in my career. I get to see trainees who are at a very impressionable point of their journey go on to become gastroenterologists and then launch into their first job and really develop in this field. Seeing them come in day one, not knowing how to hold a scope or do a procedure on a patient of this nature, then quickly evolve over the first year and grow over three years to achieve this specialty training [is rewarding]. I’ve learned a lot from the fellows along the way. I think of them as an extension of my family. We have 15 fellows currently in our program and we’ll be growing this summer. So that’s really been a highlight of my career thus far.
What fears did you have to push past to get to where you are in your career?
I think that there have been a few. One is certainly the fear of making the wrong choice with your first career opportunity. I did choose to leave my comfort zone from where I had done my training. I met that with some fear, but also excitement for new opportunities of personal and professional growth.
Another fear is: Am I going to be able to be ambitious in this field? Can I pursue research, become a program director, and do things that my role models and mentors were able to achieve? There’s also the fear of being able to balance a busy work life with a busy home life and figuring out how to do both well and minimize the guilt on both sides. I have a family with two girls. They are definitely a top priority.
What teacher or mentor had the greatest impact on you?
Helen Te, MD, a hepatologist at the University of Chicago. When I was a medical student there, I had the opportunity to work with her and saw her passion for this field. She really had so much enthusiasm for teaching and was a big part of why I started to fall in love with liver disease.
Karen Kim, MD, now the dean of Penn State College of Medicine, was one of my assigned mentors as a medical student. She helped me explore the fields where there were opportunities for residency and helped me make the decision to go into internal medicine, which often is a key deciding point for medical students. She was also a very influential teacher. The other individual who stands out is my fellowship program director, Hari Sree Conjeevaram, MD, MSc, at University of Michigan Health. He exhibited the qualities as an educator and program director that helped me recognize that education was something that I wanted to pursue in a formal fashion once I moved on in my career.
Describe how you would spend a free Saturday afternoon.
Likely taking a hike or go to a park with my family, enjoying the outdoors and spending time with them.
Lightning Round
If you weren’t a gastroenterologist, what would you be?
Philanthropist
Favorite city in U.S. besides the one you live in?
Chicago
Place you most want to travel?
New Zealand
Favorite breakfast?
Avocado toast
Favorite ice cream flavor?
Cookies and cream
How many cups of coffee do you drink per day?
Two…or more
Cat person or dog person?
Dog
Texting or talking?
Talk
Favorite season?
Autumn
Favorite type of music?
Pop
Favorite movie genre?
Action
For Reena Salgia, MD, the most rewarding part about working with patients with hepatocellular carcinoma is being there for their entire journey, thanks to advancements in treatment. “It brings a smile to my face just to think about it,” says Dr. Salgia, medical director of Henry Ford Health’s Liver Cancer Clinic in Detroit.
Hepatocellular carcinoma accounts for 80% of all liver cancer. When she first entered the field, Dr. Salgia often heard that survival rates 5 years after diagnosis were less than 10%. Over the last decade however, “I’ve seen an expansion in the procedural options that we offer these patients. We have an array of options both surgically as well as procedurally,” she said.
Especially over the last three to four years, “we’ve seen meaningful responses for patients with medications that we previously didn’t have in our toolbox. That’s really been exciting, along with continued involvement in clinical trials and being able to offer patients a number of different approaches to their care of liver cancer,” said Dr. Salgia.
A regular attendee and presenter at national GI meetings, Dr. Salgia participated in AGA’s Women’s Executive Leadership Conference in 2023. Her academic resume includes a long list of clinical trials to assess treatments for patients at different stages of hepatocellular carcinoma.
In an interview, she discussed the highlights of her career as a researcher and mentor of fellows, and how she guides and supports her transplant patients.
What drove you to pursue the field of hepatology and transplant hepatology?
I came across this field during my fourth year of medical school. I didn’t know anything about hepatology when I reached that stage and had the opportunity to do an elective. I just fell in love with the specialty. I liked the complex pathophysiology of liver disease, the long-term follow-up and care of patients. It appealed to the type of science that I had enjoyed back in college.
As I went into my GI fellowship training, I got to learn more about the field of transplant medicine. For instance, how you can take these patients who are incredibly ill, really at a very vulnerable point of their illness, and then offer them great hope and see their lives turn around afterwards. When I had the opportunity to see patients go from end stage liver disease to such significant improvement in their quality of life, and restoring their physical functioning beyond what we would’ve ever imagined when they were ill, it reaffirmed my interest in both hepatology as well as in transplant medicine.
How do you help those patients waiting on transplant lists for a liver?
We are intimately involved in their care all the way through their journey with liver disease, up until the time of physically getting the liver transplant, which is performed by our colleagues in transplant surgery. From the time they are transplanted, we are involved in their inpatient and outpatient post-transplant care. We’ve helped to get them on the transplant list with the work of the multidisciplinary team. If there are opportunities to help them understand their position on the list or obtaining exceptions—though that is done in a very objective fashion through the regulatory system—we help to guide them through that journey.
You’ve worked on many studies that involve treatments for hepatocellular carcinoma. Can you highlight a paper that yielded clinically significant benefits?
What really stands out the most to me was our site’s involvement in the IMbrave150 trial, which was published in 2020. This multicenter study made a big difference in the outcomes and treatments for patients, as it brought the adoption of first-line immunotherapy (atezolizumab plus bevacizumab) for patients with advanced hepatocellular carcinoma. I remember vividly the patients we had the opportunity to enroll in that trial – some who we continue to care for today. This stands out as one of the trials that I was involved in that had a lasting impact.
What were the clinical endpoints and key results of that trial?
The endpoint was to see an improvement in overall survival utilizing immunotherapy, compared with the prior standard of care then available, oral therapy. The results led to the adoption and FDA approval of immunotherapy in the first line setting for advanced unresectable hepatocellular carcinoma patients.
What are some of the highlights of serving as director of Henry Ford’s fellowship program?
Education is my passion. I went into medical training feeling that at some point I would love to blend in teaching in a formal role. Becoming program director of the gastroenterology and hepatology fellowship at Henry Ford in 2018 was one of the most meaningful things that I’ve had the opportunity to do in my career. I get to see trainees who are at a very impressionable point of their journey go on to become gastroenterologists and then launch into their first job and really develop in this field. Seeing them come in day one, not knowing how to hold a scope or do a procedure on a patient of this nature, then quickly evolve over the first year and grow over three years to achieve this specialty training [is rewarding]. I’ve learned a lot from the fellows along the way. I think of them as an extension of my family. We have 15 fellows currently in our program and we’ll be growing this summer. So that’s really been a highlight of my career thus far.
What fears did you have to push past to get to where you are in your career?
I think that there have been a few. One is certainly the fear of making the wrong choice with your first career opportunity. I did choose to leave my comfort zone from where I had done my training. I met that with some fear, but also excitement for new opportunities of personal and professional growth.
Another fear is: Am I going to be able to be ambitious in this field? Can I pursue research, become a program director, and do things that my role models and mentors were able to achieve? There’s also the fear of being able to balance a busy work life with a busy home life and figuring out how to do both well and minimize the guilt on both sides. I have a family with two girls. They are definitely a top priority.
What teacher or mentor had the greatest impact on you?
Helen Te, MD, a hepatologist at the University of Chicago. When I was a medical student there, I had the opportunity to work with her and saw her passion for this field. She really had so much enthusiasm for teaching and was a big part of why I started to fall in love with liver disease.
Karen Kim, MD, now the dean of Penn State College of Medicine, was one of my assigned mentors as a medical student. She helped me explore the fields where there were opportunities for residency and helped me make the decision to go into internal medicine, which often is a key deciding point for medical students. She was also a very influential teacher. The other individual who stands out is my fellowship program director, Hari Sree Conjeevaram, MD, MSc, at University of Michigan Health. He exhibited the qualities as an educator and program director that helped me recognize that education was something that I wanted to pursue in a formal fashion once I moved on in my career.
Describe how you would spend a free Saturday afternoon.
Likely taking a hike or go to a park with my family, enjoying the outdoors and spending time with them.
Lightning Round
If you weren’t a gastroenterologist, what would you be?
Philanthropist
Favorite city in U.S. besides the one you live in?
Chicago
Place you most want to travel?
New Zealand
Favorite breakfast?
Avocado toast
Favorite ice cream flavor?
Cookies and cream
How many cups of coffee do you drink per day?
Two…or more
Cat person or dog person?
Dog
Texting or talking?
Talk
Favorite season?
Autumn
Favorite type of music?
Pop
Favorite movie genre?
Action
Giving the Smallest GI Transplant Patients a New Lease On Life
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
Neighborhood Determinants of Health Adversely Impact MASLD
These health mediators should be considered along with individual SDOH in clinical care and healthcare quality and equity improvement, a large retrospective study of adults with MASLD at a multi-state healthcare institution concluded.
Across quartiles, patients in the most disadvantaged neighborhoods (according to home addresses) vs the least disadvantaged had worse outcomes and were also disproportionately Hispanic, Black, and Native American/Alaska Native, more often Spanish-speaking in primary language, and more often uninsured or on Medicaid, according to Karn Wijarnpreecha, MD, MPH, of the Division of Gastroenterology and Hepatology at University of Arizona College of Medicine–Phoenix, and colleagues writing in Clinical Gastroenterology and Hepatology.
Even after adjustment for measures in the Social Deprivation Index (SDI), the incidence of death, cirrhosis, diabetes mellitus (DM), and major adverse cardiovascular events (MACE) was higher in Native American/Alaska Native patients compared with their non-Hispanic White counterparts. The SDI is a composite measure of seven demographic characteristics from the American Community Survey, with scores ranging from 1 to 100 and weighted based on characteristics from national percentile rankings.
Aligning with the growing prevalence of obesity and DM, MASLD has increased substantially over the past three decades, and is now the leading cause of chronic liver disease in this country and the world.
This rise in prevalence has underscored health disparities in MASLD and prompted research into linkd between liver disease and SDOH, defined as the conditions under which people are born, grow, live, work, and age. These are fundamental drivers of health disparities, including those in MASLD.
Study Details
Primary outcomes were MASLD burden, mortality, and comorbidities by neighborhood SDOH, assessed using the SDI in cross-sectional and longitudinal analyses.
A total of 69,191 adult patients (more than 50% female) diagnosed with MASLD were included, 45,003 of whom had at least 365 days of follow-up. They were treated from July 2012 to June 2023 in Banner Health Systems, a network that includes primary-, secondary-, and tertiary-care centers in Arizona, Colorado, Wyoming, Nevada, Nebraska, and California.
The median follow-up time was 48 months. Among patients across SDI quartiles (age range 49 to 62 years), 1390 patients (3.1%) died, 902 (2.0%) developed cirrhosis, 1087 (2.4%) developed LRE, 6537 (14.5%) developed DM, 2057 (4.6%) developed cancer, and 5409 (12.0%) developed MACE.
Those living in the most disadvantaged quartile of neighborhoods compared with the least had the following higher odds:
- cirrhosis, adjusted odds ratio [aOR], 1.42 (P < .001)
- any cardiovascular (CVD) disease, aOR, 1.20 (P < .001),
- coronary artery disease, aOR, 1.17 (P < .001)
- congestive heart failure, aOR, 1.43 (P < .001)
- cerebrovascular accident, aOR, 1.19 (P = .001)
- DM, aOR, 1.57 (P < .001)
- hypertension, aOR, 1.38 (P < .001).
They also had increased incidence of death (adjusted hazard ratio [aHR], 1.47; P < .001), LRE (aHR, 1.31; P = .012), DM (aHR, 1.47; P < .001), and MACE (aHR, 1.24; P < .001).
The study expands upon previous SDOH-related research in liver disease and is the largest analysis of neighborhood-level SDOH in patients with MASLD to date. “Our findings are consistent with a recent study by Chen et al of over 15,900 patients with MASLD in Michigan that found neighborhood-level social disadvantage was associated with increased mortality and incident LREs and CVD,” Wijarnpreecha and colleagues wrote.
“Beyond screening patients for individual-level SDOH, neighborhood-level determinants of health should also be considered, as they are important mediators between the environment and the individual,” they added, calling for studies to better understand the specific neighborhood SDOH that drive the disparate outcomes. In practice, integration of these measures into medical records might inform clinicians which patients would benefit from social services or help guide quality improvement projects and community partnerships.
Wijarnpreecha had no conflicts of interest to disclose. Several coauthors reported research support, consulting/advisory work, or stock ownership for various private-sector companies.
The sprectrum of steatotic liver disease (SLD) including metabolic dysfunction associated steatotic liver disease (MASLD) is increasing in the United Statues. 38% of adults and 7-14% of children currently have MASLD and it is projected that by 2040 the prevalence rate for MASLD will be higher than 55% in US adults. Fortunately, most will not develop serious liver disease. However, even a small subset is impacted, significant liver related morbidity and mortality will be the result.
Yet, concentrating only on the liver misses the substantial impact of other metabolic outcomes associated with MASLD. Equally important, at risk MASLD is treatable with lifestyle modifications, pharmacotherapy and surgical options which improve liver related outcomes, metabolic complications, and all-cause mortality. When over half of the US has a disease that requires individuals to navigate a complex care pathway that includes screening, staging, and risk modification across multiple metabolic conditions, any factor that can help identify those in need for targeted interventions is paramount. And personalization that allows someone to effectively traverse the care pathway allows for the most successful outcome.
Social determinants of health (SDOH) are complex but not insurmountable. By recognizing the contribution of SDOH, studies can be designed to discover which factors drive disparate outcomes on a granular level. This can then support funding and policy changes to address these elements. It is already well established that food insecurity is associated with both prevalence of MASLD and liver-related mortality. Policies to address the issues related to poverty can be prioritized and their impact measured.
This study also highlights the importance of needs by neighborhood. Culture has an impact on diet which is inextricably linked to MASLD. Acculturation, or the process of adapting to a new culture, is associated with poor health, physical inactivity, and poor diet but is also recognized. Western diets are high in saturated fat and refined carbohydrates which then increase risk of obesity and MASLD. In neighborhoods where culturally tailored interventions can improve health outcomes, community-based programs are imperative. In conclusion, a holistic approach that acknowledges and integrates cultural practices and preferences into MASLD prevention and management strategies can improve treatment adherence and outcomes, particularly for high-risk populations.
Nancy S. Reau, MD, AGAF, is professor and section chief of hepatology in the Division of Digestive Diseases and Nutrition at Rush University, Chicago. She has no disclosures in relation to this commentary.
The sprectrum of steatotic liver disease (SLD) including metabolic dysfunction associated steatotic liver disease (MASLD) is increasing in the United Statues. 38% of adults and 7-14% of children currently have MASLD and it is projected that by 2040 the prevalence rate for MASLD will be higher than 55% in US adults. Fortunately, most will not develop serious liver disease. However, even a small subset is impacted, significant liver related morbidity and mortality will be the result.
Yet, concentrating only on the liver misses the substantial impact of other metabolic outcomes associated with MASLD. Equally important, at risk MASLD is treatable with lifestyle modifications, pharmacotherapy and surgical options which improve liver related outcomes, metabolic complications, and all-cause mortality. When over half of the US has a disease that requires individuals to navigate a complex care pathway that includes screening, staging, and risk modification across multiple metabolic conditions, any factor that can help identify those in need for targeted interventions is paramount. And personalization that allows someone to effectively traverse the care pathway allows for the most successful outcome.
Social determinants of health (SDOH) are complex but not insurmountable. By recognizing the contribution of SDOH, studies can be designed to discover which factors drive disparate outcomes on a granular level. This can then support funding and policy changes to address these elements. It is already well established that food insecurity is associated with both prevalence of MASLD and liver-related mortality. Policies to address the issues related to poverty can be prioritized and their impact measured.
This study also highlights the importance of needs by neighborhood. Culture has an impact on diet which is inextricably linked to MASLD. Acculturation, or the process of adapting to a new culture, is associated with poor health, physical inactivity, and poor diet but is also recognized. Western diets are high in saturated fat and refined carbohydrates which then increase risk of obesity and MASLD. In neighborhoods where culturally tailored interventions can improve health outcomes, community-based programs are imperative. In conclusion, a holistic approach that acknowledges and integrates cultural practices and preferences into MASLD prevention and management strategies can improve treatment adherence and outcomes, particularly for high-risk populations.
Nancy S. Reau, MD, AGAF, is professor and section chief of hepatology in the Division of Digestive Diseases and Nutrition at Rush University, Chicago. She has no disclosures in relation to this commentary.
The sprectrum of steatotic liver disease (SLD) including metabolic dysfunction associated steatotic liver disease (MASLD) is increasing in the United Statues. 38% of adults and 7-14% of children currently have MASLD and it is projected that by 2040 the prevalence rate for MASLD will be higher than 55% in US adults. Fortunately, most will not develop serious liver disease. However, even a small subset is impacted, significant liver related morbidity and mortality will be the result.
Yet, concentrating only on the liver misses the substantial impact of other metabolic outcomes associated with MASLD. Equally important, at risk MASLD is treatable with lifestyle modifications, pharmacotherapy and surgical options which improve liver related outcomes, metabolic complications, and all-cause mortality. When over half of the US has a disease that requires individuals to navigate a complex care pathway that includes screening, staging, and risk modification across multiple metabolic conditions, any factor that can help identify those in need for targeted interventions is paramount. And personalization that allows someone to effectively traverse the care pathway allows for the most successful outcome.
Social determinants of health (SDOH) are complex but not insurmountable. By recognizing the contribution of SDOH, studies can be designed to discover which factors drive disparate outcomes on a granular level. This can then support funding and policy changes to address these elements. It is already well established that food insecurity is associated with both prevalence of MASLD and liver-related mortality. Policies to address the issues related to poverty can be prioritized and their impact measured.
This study also highlights the importance of needs by neighborhood. Culture has an impact on diet which is inextricably linked to MASLD. Acculturation, or the process of adapting to a new culture, is associated with poor health, physical inactivity, and poor diet but is also recognized. Western diets are high in saturated fat and refined carbohydrates which then increase risk of obesity and MASLD. In neighborhoods where culturally tailored interventions can improve health outcomes, community-based programs are imperative. In conclusion, a holistic approach that acknowledges and integrates cultural practices and preferences into MASLD prevention and management strategies can improve treatment adherence and outcomes, particularly for high-risk populations.
Nancy S. Reau, MD, AGAF, is professor and section chief of hepatology in the Division of Digestive Diseases and Nutrition at Rush University, Chicago. She has no disclosures in relation to this commentary.
These health mediators should be considered along with individual SDOH in clinical care and healthcare quality and equity improvement, a large retrospective study of adults with MASLD at a multi-state healthcare institution concluded.
Across quartiles, patients in the most disadvantaged neighborhoods (according to home addresses) vs the least disadvantaged had worse outcomes and were also disproportionately Hispanic, Black, and Native American/Alaska Native, more often Spanish-speaking in primary language, and more often uninsured or on Medicaid, according to Karn Wijarnpreecha, MD, MPH, of the Division of Gastroenterology and Hepatology at University of Arizona College of Medicine–Phoenix, and colleagues writing in Clinical Gastroenterology and Hepatology.
Even after adjustment for measures in the Social Deprivation Index (SDI), the incidence of death, cirrhosis, diabetes mellitus (DM), and major adverse cardiovascular events (MACE) was higher in Native American/Alaska Native patients compared with their non-Hispanic White counterparts. The SDI is a composite measure of seven demographic characteristics from the American Community Survey, with scores ranging from 1 to 100 and weighted based on characteristics from national percentile rankings.
Aligning with the growing prevalence of obesity and DM, MASLD has increased substantially over the past three decades, and is now the leading cause of chronic liver disease in this country and the world.
This rise in prevalence has underscored health disparities in MASLD and prompted research into linkd between liver disease and SDOH, defined as the conditions under which people are born, grow, live, work, and age. These are fundamental drivers of health disparities, including those in MASLD.
Study Details
Primary outcomes were MASLD burden, mortality, and comorbidities by neighborhood SDOH, assessed using the SDI in cross-sectional and longitudinal analyses.
A total of 69,191 adult patients (more than 50% female) diagnosed with MASLD were included, 45,003 of whom had at least 365 days of follow-up. They were treated from July 2012 to June 2023 in Banner Health Systems, a network that includes primary-, secondary-, and tertiary-care centers in Arizona, Colorado, Wyoming, Nevada, Nebraska, and California.
The median follow-up time was 48 months. Among patients across SDI quartiles (age range 49 to 62 years), 1390 patients (3.1%) died, 902 (2.0%) developed cirrhosis, 1087 (2.4%) developed LRE, 6537 (14.5%) developed DM, 2057 (4.6%) developed cancer, and 5409 (12.0%) developed MACE.
Those living in the most disadvantaged quartile of neighborhoods compared with the least had the following higher odds:
- cirrhosis, adjusted odds ratio [aOR], 1.42 (P < .001)
- any cardiovascular (CVD) disease, aOR, 1.20 (P < .001),
- coronary artery disease, aOR, 1.17 (P < .001)
- congestive heart failure, aOR, 1.43 (P < .001)
- cerebrovascular accident, aOR, 1.19 (P = .001)
- DM, aOR, 1.57 (P < .001)
- hypertension, aOR, 1.38 (P < .001).
They also had increased incidence of death (adjusted hazard ratio [aHR], 1.47; P < .001), LRE (aHR, 1.31; P = .012), DM (aHR, 1.47; P < .001), and MACE (aHR, 1.24; P < .001).
The study expands upon previous SDOH-related research in liver disease and is the largest analysis of neighborhood-level SDOH in patients with MASLD to date. “Our findings are consistent with a recent study by Chen et al of over 15,900 patients with MASLD in Michigan that found neighborhood-level social disadvantage was associated with increased mortality and incident LREs and CVD,” Wijarnpreecha and colleagues wrote.
“Beyond screening patients for individual-level SDOH, neighborhood-level determinants of health should also be considered, as they are important mediators between the environment and the individual,” they added, calling for studies to better understand the specific neighborhood SDOH that drive the disparate outcomes. In practice, integration of these measures into medical records might inform clinicians which patients would benefit from social services or help guide quality improvement projects and community partnerships.
Wijarnpreecha had no conflicts of interest to disclose. Several coauthors reported research support, consulting/advisory work, or stock ownership for various private-sector companies.
These health mediators should be considered along with individual SDOH in clinical care and healthcare quality and equity improvement, a large retrospective study of adults with MASLD at a multi-state healthcare institution concluded.
Across quartiles, patients in the most disadvantaged neighborhoods (according to home addresses) vs the least disadvantaged had worse outcomes and were also disproportionately Hispanic, Black, and Native American/Alaska Native, more often Spanish-speaking in primary language, and more often uninsured or on Medicaid, according to Karn Wijarnpreecha, MD, MPH, of the Division of Gastroenterology and Hepatology at University of Arizona College of Medicine–Phoenix, and colleagues writing in Clinical Gastroenterology and Hepatology.
Even after adjustment for measures in the Social Deprivation Index (SDI), the incidence of death, cirrhosis, diabetes mellitus (DM), and major adverse cardiovascular events (MACE) was higher in Native American/Alaska Native patients compared with their non-Hispanic White counterparts. The SDI is a composite measure of seven demographic characteristics from the American Community Survey, with scores ranging from 1 to 100 and weighted based on characteristics from national percentile rankings.
Aligning with the growing prevalence of obesity and DM, MASLD has increased substantially over the past three decades, and is now the leading cause of chronic liver disease in this country and the world.
This rise in prevalence has underscored health disparities in MASLD and prompted research into linkd between liver disease and SDOH, defined as the conditions under which people are born, grow, live, work, and age. These are fundamental drivers of health disparities, including those in MASLD.
Study Details
Primary outcomes were MASLD burden, mortality, and comorbidities by neighborhood SDOH, assessed using the SDI in cross-sectional and longitudinal analyses.
A total of 69,191 adult patients (more than 50% female) diagnosed with MASLD were included, 45,003 of whom had at least 365 days of follow-up. They were treated from July 2012 to June 2023 in Banner Health Systems, a network that includes primary-, secondary-, and tertiary-care centers in Arizona, Colorado, Wyoming, Nevada, Nebraska, and California.
The median follow-up time was 48 months. Among patients across SDI quartiles (age range 49 to 62 years), 1390 patients (3.1%) died, 902 (2.0%) developed cirrhosis, 1087 (2.4%) developed LRE, 6537 (14.5%) developed DM, 2057 (4.6%) developed cancer, and 5409 (12.0%) developed MACE.
Those living in the most disadvantaged quartile of neighborhoods compared with the least had the following higher odds:
- cirrhosis, adjusted odds ratio [aOR], 1.42 (P < .001)
- any cardiovascular (CVD) disease, aOR, 1.20 (P < .001),
- coronary artery disease, aOR, 1.17 (P < .001)
- congestive heart failure, aOR, 1.43 (P < .001)
- cerebrovascular accident, aOR, 1.19 (P = .001)
- DM, aOR, 1.57 (P < .001)
- hypertension, aOR, 1.38 (P < .001).
They also had increased incidence of death (adjusted hazard ratio [aHR], 1.47; P < .001), LRE (aHR, 1.31; P = .012), DM (aHR, 1.47; P < .001), and MACE (aHR, 1.24; P < .001).
The study expands upon previous SDOH-related research in liver disease and is the largest analysis of neighborhood-level SDOH in patients with MASLD to date. “Our findings are consistent with a recent study by Chen et al of over 15,900 patients with MASLD in Michigan that found neighborhood-level social disadvantage was associated with increased mortality and incident LREs and CVD,” Wijarnpreecha and colleagues wrote.
“Beyond screening patients for individual-level SDOH, neighborhood-level determinants of health should also be considered, as they are important mediators between the environment and the individual,” they added, calling for studies to better understand the specific neighborhood SDOH that drive the disparate outcomes. In practice, integration of these measures into medical records might inform clinicians which patients would benefit from social services or help guide quality improvement projects and community partnerships.
Wijarnpreecha had no conflicts of interest to disclose. Several coauthors reported research support, consulting/advisory work, or stock ownership for various private-sector companies.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Journal Highlights: January-April 2025
Esophagus/Motility
Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.
Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.
Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.
Small Bowel
Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.
Colon
Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.
Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.
Inflammatory Bowel Disease
Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.
Pancreas
Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.
Hepatology
Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.
Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.
Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.
Miscellaneous
Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.
Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.
Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Esophagus/Motility
Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.
Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.
Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.
Small Bowel
Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.
Colon
Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.
Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.
Inflammatory Bowel Disease
Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.
Pancreas
Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.
Hepatology
Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.
Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.
Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.
Miscellaneous
Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.
Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.
Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Esophagus/Motility
Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.
Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.
Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.
Small Bowel
Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.
Colon
Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.
Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.
Inflammatory Bowel Disease
Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.
Pancreas
Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.
Hepatology
Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.
Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.
Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.
Miscellaneous
Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.
Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.
Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Hepatic Encephalopathy: Improve Diagnosis, Management, and Care
.1 HE can be deceptively subtle or profoundly severe, presenting with a wide clinical spectrum – from mild cognitive slowing to life-threatening coma. Without clear disease biomarkers, HE remains a diagnosis of exclusion, making it critical for clinicians to remain vigilant, especially in patients with chronic liver disease (CLD).
The incidence of CLD is climbing, fueled by rising rates of alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatitis C, which is often undiagnosed. For example:
- More than 2 million Americans had alcohol-associated cirrhosis as of 2017.2
- Currently, 38% of all adults and 7–14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%.3
- The economic burden is staggering – from $1 billion4 in 2003 to over $7 billion5 in hospital costs for cirrhosis-related admissions today.
These figures aren’t just statistics – they represent a growing population of patients who are at risk of developing HE, sometimes without ever receiving a proper diagnosis or follow-up care.
Because HE mimics many other forms of neurological dysfunction – delirium, alcohol intoxication, diabetes-related confusion – it can be easy to miss or misdiagnose. But differentiating HE from other causes of altered mental status is critical, especially for patients who may ultimately require liver transplantation.6, 7
Moreover, patients frequently leave the hospital without adequate education or maintenance medication for episodic overt HE. Without coordinated follow-up between primary care, hepatology, and caregivers, these patients are at risk for recurrence.
To close these practice gaps, education is key. AGA’s course, “Missing the Mark: Hepatic Encephalopathy,” provides clinicians with up-to-date guidance on:
- The changing epidemiology of cirrhosis and undiagnosed cirrhosis for patients with liver disease.
- Assessment guidelines and best practices for HE diagnosis and management.
- How to develop transition-of-care plans with patients, caretakers, and specialty providers after an initial HE diagnosis.
Take the course today: https://tinyurl.com/3muwhmj5
Don’t wait until HE is an emergency. Equip yourself with the tools to recognize it earlier, treat it effectively, and coordinate better care.
References
1. Wolf, DC. Hepatic Encephalopathy. Medscape. 2020 May 1. Retrieved from: https://emedicine.medscape.com/article/186101-overview
2. Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease A review. JAMA. 2021 Jul. doi:10.1001/jama.2021.7683.
3. Younossi ZM, et al. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2025 Feb. doi: 10.3350/cmh.2024.0431.
4. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug. doi: 10.1002/hep.27210.
5. Desai AP, et al. Increasing Economic Burden in Hospitalized Patients With Cirrhosis: Analysis of a National Database. Clin Transl Gastroenterol. 2019 Jul. doi: 10.14309/ctg.0000000000000062.
6. Serper M, et al. Hepatic encephalopathy predicts early post-transplant cognitive and functional impairment: The Livcog cohort study. Hepatol Commun. 2025 Apr. doi: 10.1097/HC9.0000000000000696.
7. Montagnese S, Bajaj JS. Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues. Drugs. 2019 Jan. doi: 10.1007/s40265-018-1019-y.
.1 HE can be deceptively subtle or profoundly severe, presenting with a wide clinical spectrum – from mild cognitive slowing to life-threatening coma. Without clear disease biomarkers, HE remains a diagnosis of exclusion, making it critical for clinicians to remain vigilant, especially in patients with chronic liver disease (CLD).
The incidence of CLD is climbing, fueled by rising rates of alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatitis C, which is often undiagnosed. For example:
- More than 2 million Americans had alcohol-associated cirrhosis as of 2017.2
- Currently, 38% of all adults and 7–14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%.3
- The economic burden is staggering – from $1 billion4 in 2003 to over $7 billion5 in hospital costs for cirrhosis-related admissions today.
These figures aren’t just statistics – they represent a growing population of patients who are at risk of developing HE, sometimes without ever receiving a proper diagnosis or follow-up care.
Because HE mimics many other forms of neurological dysfunction – delirium, alcohol intoxication, diabetes-related confusion – it can be easy to miss or misdiagnose. But differentiating HE from other causes of altered mental status is critical, especially for patients who may ultimately require liver transplantation.6, 7
Moreover, patients frequently leave the hospital without adequate education or maintenance medication for episodic overt HE. Without coordinated follow-up between primary care, hepatology, and caregivers, these patients are at risk for recurrence.
To close these practice gaps, education is key. AGA’s course, “Missing the Mark: Hepatic Encephalopathy,” provides clinicians with up-to-date guidance on:
- The changing epidemiology of cirrhosis and undiagnosed cirrhosis for patients with liver disease.
- Assessment guidelines and best practices for HE diagnosis and management.
- How to develop transition-of-care plans with patients, caretakers, and specialty providers after an initial HE diagnosis.
Take the course today: https://tinyurl.com/3muwhmj5
Don’t wait until HE is an emergency. Equip yourself with the tools to recognize it earlier, treat it effectively, and coordinate better care.
References
1. Wolf, DC. Hepatic Encephalopathy. Medscape. 2020 May 1. Retrieved from: https://emedicine.medscape.com/article/186101-overview
2. Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease A review. JAMA. 2021 Jul. doi:10.1001/jama.2021.7683.
3. Younossi ZM, et al. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2025 Feb. doi: 10.3350/cmh.2024.0431.
4. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug. doi: 10.1002/hep.27210.
5. Desai AP, et al. Increasing Economic Burden in Hospitalized Patients With Cirrhosis: Analysis of a National Database. Clin Transl Gastroenterol. 2019 Jul. doi: 10.14309/ctg.0000000000000062.
6. Serper M, et al. Hepatic encephalopathy predicts early post-transplant cognitive and functional impairment: The Livcog cohort study. Hepatol Commun. 2025 Apr. doi: 10.1097/HC9.0000000000000696.
7. Montagnese S, Bajaj JS. Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues. Drugs. 2019 Jan. doi: 10.1007/s40265-018-1019-y.
.1 HE can be deceptively subtle or profoundly severe, presenting with a wide clinical spectrum – from mild cognitive slowing to life-threatening coma. Without clear disease biomarkers, HE remains a diagnosis of exclusion, making it critical for clinicians to remain vigilant, especially in patients with chronic liver disease (CLD).
The incidence of CLD is climbing, fueled by rising rates of alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatitis C, which is often undiagnosed. For example:
- More than 2 million Americans had alcohol-associated cirrhosis as of 2017.2
- Currently, 38% of all adults and 7–14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%.3
- The economic burden is staggering – from $1 billion4 in 2003 to over $7 billion5 in hospital costs for cirrhosis-related admissions today.
These figures aren’t just statistics – they represent a growing population of patients who are at risk of developing HE, sometimes without ever receiving a proper diagnosis or follow-up care.
Because HE mimics many other forms of neurological dysfunction – delirium, alcohol intoxication, diabetes-related confusion – it can be easy to miss or misdiagnose. But differentiating HE from other causes of altered mental status is critical, especially for patients who may ultimately require liver transplantation.6, 7
Moreover, patients frequently leave the hospital without adequate education or maintenance medication for episodic overt HE. Without coordinated follow-up between primary care, hepatology, and caregivers, these patients are at risk for recurrence.
To close these practice gaps, education is key. AGA’s course, “Missing the Mark: Hepatic Encephalopathy,” provides clinicians with up-to-date guidance on:
- The changing epidemiology of cirrhosis and undiagnosed cirrhosis for patients with liver disease.
- Assessment guidelines and best practices for HE diagnosis and management.
- How to develop transition-of-care plans with patients, caretakers, and specialty providers after an initial HE diagnosis.
Take the course today: https://tinyurl.com/3muwhmj5
Don’t wait until HE is an emergency. Equip yourself with the tools to recognize it earlier, treat it effectively, and coordinate better care.
References
1. Wolf, DC. Hepatic Encephalopathy. Medscape. 2020 May 1. Retrieved from: https://emedicine.medscape.com/article/186101-overview
2. Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease A review. JAMA. 2021 Jul. doi:10.1001/jama.2021.7683.
3. Younossi ZM, et al. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2025 Feb. doi: 10.3350/cmh.2024.0431.
4. Vilstrup H, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug. doi: 10.1002/hep.27210.
5. Desai AP, et al. Increasing Economic Burden in Hospitalized Patients With Cirrhosis: Analysis of a National Database. Clin Transl Gastroenterol. 2019 Jul. doi: 10.14309/ctg.0000000000000062.
6. Serper M, et al. Hepatic encephalopathy predicts early post-transplant cognitive and functional impairment: The Livcog cohort study. Hepatol Commun. 2025 Apr. doi: 10.1097/HC9.0000000000000696.
7. Montagnese S, Bajaj JS. Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues. Drugs. 2019 Jan. doi: 10.1007/s40265-018-1019-y.
MASH Driving Global Epidemic of Primary Liver Cancer
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
GLP-1s Treat and Even Reverse Some Forms of Liver Disease
In the past two decades, the global prevalence of metabolic dysfunction–associated steatohepatitis (MASH) has increased dramatically as a result of the obesity epidemic. Researchers project that by 2040, rates of MASH will increase by 55%. Prior to that most liver diseases were caused by alcohol use and hepatitis C, a viral infection that primarily affects the liver.
MASH, a preventable form of liver disease previously called nonalcoholic fatty liver disease, is caused by a buildup of visceral fat cells that accumulate on top of the internal organs, in this case the liver, and keep it from functioning properly. The liver’s primary role is to filter blood, nutrients, and bile used for digestion, as well as to remove toxins from the body. Excess fat cells blanket the liver and keep it from working at full capacity.
Fat cells are also metabolically active and can cause a chronic state of inflammation in the part of the body where they reside. Over time, these fat cells can cause cirrhosis of the liver, or permanent scarring. Once patients reach this stage, the only option is a liver transplant.
New Research on GLP-1 Agonists and MASH
Until recently, the lone treatment for early-stage MASH was weight loss to reduce the number of fat cells that surround the internal organs. But new research has shown that glucagon-like peptide 1 (GLP-1) agonists can reduce and even reverse the condition. In a study published in April, researchers were able to show that semaglutide resolved fatty liver and inflammation in over 60% of cases and decreased scar tissue in just over a third of patients.
“These findings suggest that semaglutide may prevent fatty liver disease from progressing to cirrhosis and can indeed reverse the course of the disease,” said Arun J. Sanyal, MD, study author and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University in Richmond, Virginia.
Another study published last year had a similar finding, showing that GLP-1 agonists were associated with less progression of the disease and reduced mortality in patients with MASH and diabetes. Another large-scale observational study found that GLP-1s reduced the risk for hepatic failure, which occurs when the liver is unable to perform basic functions, as well as liver cancer, both of which are downstream consequences of MASH.
How GLP-1s Improve Liver Function
“These medications reduce fat burden, which results in fat loss everywhere, including around the liver,” said Ziyad Al-Aly, MD, an assistant professor in the Division of General Medicine & Geriatrics at Washington University School of Medicine in St. Louis. “When fat cells are reduced in size and volume, the normal liver cells have more room to grow and function.”
These medications also seem to work on reducing the inflammation and oxidative stress caused by metabolic disease, which allows for a better environment for the liver to function.
“Fat is not an inert tissue, it’s metabolically active, causing a slow burn to all the cells surrounding it,” said Al-Aly. These medications keep the disease from progressing and reduce scarring, which improves the damage that’s already been done, he said.
Changing How Liver Disease Is Diagnosed
Physicians need to be vigilant in the way that they screen for the condition, said Charu Sawhney, DO, MPH, of Harbor Health in Round Rock, Texas. She said that if liver enzymes appear even slightly elevated, there still could be a reason to utilize GLP-1s to prevent later-stage MASH.
“Normal levels for liver enzymes in some patients can be lower than what labs show,” said Sawhney. This is especially true if a patient has other metabolic risk factors such as diabetes, obesity, or high cholesterol.
If liver enzymes continue to go up even after diet and lifestyle changes, patients might require liver imaging, specifically a wave-based ultrasound called elastography, which measures the elasticity or stiffness of tissues on the liver and can judge if certain portions of it have scarred or hardened. When liver cells change texture and become harder, the scan can estimate levels of fibrosis and, therefore, the stage of MASH that a patient is in.
Additionally, the severity of fatty liver disease depends on other factors besides weight and can sometimes be surprising.
“How bad fatty liver disease is in a patient isn’t always related to how much weight someone has gained,” said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.
It’s important for physicians to realize that some patients with fatty liver disease might not have obesity as would be expected. For these patients, adipose tissue seems to accumulate on the liver before it does on other parts of the body. This could be related to the quality of our food system, including the use of sugar substitutes like high fructose corn syrup, which research has shown is even harder on the liver. There might also be a genetic propensity toward fat storage around the organs.
A New Way to Treat MASH
, said Francavilla. Right now, there’s not an official approval from the US Food and Drug Administration (FDA) for prescribing GLP-1s in patients with MASH, but Francavilla hopes that it’s forthcoming.
“It will be really exciting to have these medications as a treatment option because right now there’s only one medication, and it’s for people who have pretty advanced fatty liver disease,” said Francavilla. This medication, called resmetirom, is approved by the FDA to target a protein in the liver to reduce fat and inflammation and scarring. But GLP-1s can be used much earlier to prevent the condition.
“With so many cases of MASH happening so much younger, it’s a disease that physicians really need to take seriously,” said Sawhney.
A version of this article appeared on Medscape.com.
In the past two decades, the global prevalence of metabolic dysfunction–associated steatohepatitis (MASH) has increased dramatically as a result of the obesity epidemic. Researchers project that by 2040, rates of MASH will increase by 55%. Prior to that most liver diseases were caused by alcohol use and hepatitis C, a viral infection that primarily affects the liver.
MASH, a preventable form of liver disease previously called nonalcoholic fatty liver disease, is caused by a buildup of visceral fat cells that accumulate on top of the internal organs, in this case the liver, and keep it from functioning properly. The liver’s primary role is to filter blood, nutrients, and bile used for digestion, as well as to remove toxins from the body. Excess fat cells blanket the liver and keep it from working at full capacity.
Fat cells are also metabolically active and can cause a chronic state of inflammation in the part of the body where they reside. Over time, these fat cells can cause cirrhosis of the liver, or permanent scarring. Once patients reach this stage, the only option is a liver transplant.
New Research on GLP-1 Agonists and MASH
Until recently, the lone treatment for early-stage MASH was weight loss to reduce the number of fat cells that surround the internal organs. But new research has shown that glucagon-like peptide 1 (GLP-1) agonists can reduce and even reverse the condition. In a study published in April, researchers were able to show that semaglutide resolved fatty liver and inflammation in over 60% of cases and decreased scar tissue in just over a third of patients.
“These findings suggest that semaglutide may prevent fatty liver disease from progressing to cirrhosis and can indeed reverse the course of the disease,” said Arun J. Sanyal, MD, study author and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University in Richmond, Virginia.
Another study published last year had a similar finding, showing that GLP-1 agonists were associated with less progression of the disease and reduced mortality in patients with MASH and diabetes. Another large-scale observational study found that GLP-1s reduced the risk for hepatic failure, which occurs when the liver is unable to perform basic functions, as well as liver cancer, both of which are downstream consequences of MASH.
How GLP-1s Improve Liver Function
“These medications reduce fat burden, which results in fat loss everywhere, including around the liver,” said Ziyad Al-Aly, MD, an assistant professor in the Division of General Medicine & Geriatrics at Washington University School of Medicine in St. Louis. “When fat cells are reduced in size and volume, the normal liver cells have more room to grow and function.”
These medications also seem to work on reducing the inflammation and oxidative stress caused by metabolic disease, which allows for a better environment for the liver to function.
“Fat is not an inert tissue, it’s metabolically active, causing a slow burn to all the cells surrounding it,” said Al-Aly. These medications keep the disease from progressing and reduce scarring, which improves the damage that’s already been done, he said.
Changing How Liver Disease Is Diagnosed
Physicians need to be vigilant in the way that they screen for the condition, said Charu Sawhney, DO, MPH, of Harbor Health in Round Rock, Texas. She said that if liver enzymes appear even slightly elevated, there still could be a reason to utilize GLP-1s to prevent later-stage MASH.
“Normal levels for liver enzymes in some patients can be lower than what labs show,” said Sawhney. This is especially true if a patient has other metabolic risk factors such as diabetes, obesity, or high cholesterol.
If liver enzymes continue to go up even after diet and lifestyle changes, patients might require liver imaging, specifically a wave-based ultrasound called elastography, which measures the elasticity or stiffness of tissues on the liver and can judge if certain portions of it have scarred or hardened. When liver cells change texture and become harder, the scan can estimate levels of fibrosis and, therefore, the stage of MASH that a patient is in.
Additionally, the severity of fatty liver disease depends on other factors besides weight and can sometimes be surprising.
“How bad fatty liver disease is in a patient isn’t always related to how much weight someone has gained,” said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.
It’s important for physicians to realize that some patients with fatty liver disease might not have obesity as would be expected. For these patients, adipose tissue seems to accumulate on the liver before it does on other parts of the body. This could be related to the quality of our food system, including the use of sugar substitutes like high fructose corn syrup, which research has shown is even harder on the liver. There might also be a genetic propensity toward fat storage around the organs.
A New Way to Treat MASH
, said Francavilla. Right now, there’s not an official approval from the US Food and Drug Administration (FDA) for prescribing GLP-1s in patients with MASH, but Francavilla hopes that it’s forthcoming.
“It will be really exciting to have these medications as a treatment option because right now there’s only one medication, and it’s for people who have pretty advanced fatty liver disease,” said Francavilla. This medication, called resmetirom, is approved by the FDA to target a protein in the liver to reduce fat and inflammation and scarring. But GLP-1s can be used much earlier to prevent the condition.
“With so many cases of MASH happening so much younger, it’s a disease that physicians really need to take seriously,” said Sawhney.
A version of this article appeared on Medscape.com.
In the past two decades, the global prevalence of metabolic dysfunction–associated steatohepatitis (MASH) has increased dramatically as a result of the obesity epidemic. Researchers project that by 2040, rates of MASH will increase by 55%. Prior to that most liver diseases were caused by alcohol use and hepatitis C, a viral infection that primarily affects the liver.
MASH, a preventable form of liver disease previously called nonalcoholic fatty liver disease, is caused by a buildup of visceral fat cells that accumulate on top of the internal organs, in this case the liver, and keep it from functioning properly. The liver’s primary role is to filter blood, nutrients, and bile used for digestion, as well as to remove toxins from the body. Excess fat cells blanket the liver and keep it from working at full capacity.
Fat cells are also metabolically active and can cause a chronic state of inflammation in the part of the body where they reside. Over time, these fat cells can cause cirrhosis of the liver, or permanent scarring. Once patients reach this stage, the only option is a liver transplant.
New Research on GLP-1 Agonists and MASH
Until recently, the lone treatment for early-stage MASH was weight loss to reduce the number of fat cells that surround the internal organs. But new research has shown that glucagon-like peptide 1 (GLP-1) agonists can reduce and even reverse the condition. In a study published in April, researchers were able to show that semaglutide resolved fatty liver and inflammation in over 60% of cases and decreased scar tissue in just over a third of patients.
“These findings suggest that semaglutide may prevent fatty liver disease from progressing to cirrhosis and can indeed reverse the course of the disease,” said Arun J. Sanyal, MD, study author and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University in Richmond, Virginia.
Another study published last year had a similar finding, showing that GLP-1 agonists were associated with less progression of the disease and reduced mortality in patients with MASH and diabetes. Another large-scale observational study found that GLP-1s reduced the risk for hepatic failure, which occurs when the liver is unable to perform basic functions, as well as liver cancer, both of which are downstream consequences of MASH.
How GLP-1s Improve Liver Function
“These medications reduce fat burden, which results in fat loss everywhere, including around the liver,” said Ziyad Al-Aly, MD, an assistant professor in the Division of General Medicine & Geriatrics at Washington University School of Medicine in St. Louis. “When fat cells are reduced in size and volume, the normal liver cells have more room to grow and function.”
These medications also seem to work on reducing the inflammation and oxidative stress caused by metabolic disease, which allows for a better environment for the liver to function.
“Fat is not an inert tissue, it’s metabolically active, causing a slow burn to all the cells surrounding it,” said Al-Aly. These medications keep the disease from progressing and reduce scarring, which improves the damage that’s already been done, he said.
Changing How Liver Disease Is Diagnosed
Physicians need to be vigilant in the way that they screen for the condition, said Charu Sawhney, DO, MPH, of Harbor Health in Round Rock, Texas. She said that if liver enzymes appear even slightly elevated, there still could be a reason to utilize GLP-1s to prevent later-stage MASH.
“Normal levels for liver enzymes in some patients can be lower than what labs show,” said Sawhney. This is especially true if a patient has other metabolic risk factors such as diabetes, obesity, or high cholesterol.
If liver enzymes continue to go up even after diet and lifestyle changes, patients might require liver imaging, specifically a wave-based ultrasound called elastography, which measures the elasticity or stiffness of tissues on the liver and can judge if certain portions of it have scarred or hardened. When liver cells change texture and become harder, the scan can estimate levels of fibrosis and, therefore, the stage of MASH that a patient is in.
Additionally, the severity of fatty liver disease depends on other factors besides weight and can sometimes be surprising.
“How bad fatty liver disease is in a patient isn’t always related to how much weight someone has gained,” said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.
It’s important for physicians to realize that some patients with fatty liver disease might not have obesity as would be expected. For these patients, adipose tissue seems to accumulate on the liver before it does on other parts of the body. This could be related to the quality of our food system, including the use of sugar substitutes like high fructose corn syrup, which research has shown is even harder on the liver. There might also be a genetic propensity toward fat storage around the organs.
A New Way to Treat MASH
, said Francavilla. Right now, there’s not an official approval from the US Food and Drug Administration (FDA) for prescribing GLP-1s in patients with MASH, but Francavilla hopes that it’s forthcoming.
“It will be really exciting to have these medications as a treatment option because right now there’s only one medication, and it’s for people who have pretty advanced fatty liver disease,” said Francavilla. This medication, called resmetirom, is approved by the FDA to target a protein in the liver to reduce fat and inflammation and scarring. But GLP-1s can be used much earlier to prevent the condition.
“With so many cases of MASH happening so much younger, it’s a disease that physicians really need to take seriously,” said Sawhney.
A version of this article appeared on Medscape.com.
Clinicians Can Prescribe the Cure for Hepatitis C: Most Kids Never Get It
HCV cases in children are rising, yet access to treatment is limited, especially for Black children, according to a new retrospective cohort analysis published in Pediatrics. Treatment entails direct-acting antiviral agents, for which 95% of patients have no detectable trace of the virus 12 weeks after treatment.
“HCV is a silent killer,” said Megan Rose Curtis, MD, MS, the lead author of the study. “It can be asymptomatic for many years until the third decade of life if a child is infected perinatally” and does not receive treatment.
The prevalence of HCV in pregnant people jumped 16-fold between 1998 and 2018 to 5.3 cases per every 1000 pregnancies, and these patients can transmit the disease perinatally. Many people are unaware they are infected.
Curtis, based at Washington University in St. Louis School of Medicine, St. Louis, Missouri, and her team analyzed electronic medical records of children diagnosed with HCV born over an 18-year period starting in 2000 using the TriNetX Research Network. They also included data on prescriptions for direct-acting antivirals, appointments with healthcare providers, and race and ethnicity.
The sample included 928 children with HCV (52.3% women; 55.9% White) and excluded children whose HCV had spontaneously cleared.
A little over one third (32%) of children had seen a clinician for HCV care, which was defined as having in their record an antiviral prescription, a fibrosis stage, an order for an HCV genotype test, or a diagnosis of the disease.
Even fewer children (12%) were prescribed an antiviral.
Children with certain characteristics were more likely to receive care, the researchers found. For instance, children born between 2014 and 2018 (P = .008) and those diagnosed at age 0-3 years (P = .03) were most likely to see a clinician and receive treatment.
The current recommended treatment regimen for pediatric HCV — glecaprevir/pibrentasvir (Mavyret) or sofosbuvir/velpatasvir (Epclusa) — became available in 2017.
Hispanic/Latinx and White children were 120% and 240% more likely than Black children, respectively, to have received care (odds ratio [OR], 2.20; 95% CI, 1.05-4.59 and OR, 3.44; 95% CI, 1.89-6.28). Children living in southern states were less likely to have seen a doctor for HCV treatment.
Curtis said children might not receive treatment because their caregivers do not bring them to follow-up appointments, possibly because they struggle with stable housing or transportation. Insurance companies also sometimes will not pay for the treatment.
“If you have a golden opportunity to see someone in your office, it might be the only chance someone offers them HCV treatment. It can have a huge and transformative impact on someone’s life,” she said.
Jenelle Ferry, MD, a neonatologist at Pediatrix Medical Group in Tampa, Florida, said clinicians should routinely screen children and refer caregivers to a pediatric hepatologist for further management.
Pediatricians who suspect HCV in their patients should order a test for viral nucleic acid or viral load or request a polymerase chain reaction test.
Curtis noted that more than half of children clear the infection on their own by age 3, the age at which treatment can also begin. Treatment may also not be the right option for those who cannot swallow the medicine, which is available in oral pellets for children.
Greg Marchand, MD, an OB/GYN at the Marchand Institute for Minimally Invasive Surgery in Mesa, Arizona, said the research illuminates a “huge missed opportunity” to help children.
“If left untreated, these children risk serious liver complications like cirrhosis, liver cancer, high medical costs, and even death,” he said.
Marchand said clinicians must be aware of the guidelines for testing people who are pregnant and infants. In 2020, the US Centers for Disease Control and Prevention recommended universal HCV antibody screening during every pregnancy.
“There’s still hope that treatment rates will improve as both doctors and families become more familiar with” the newer drugs, he said.
No financial disclosures were reported.
The authors of this study were supported by various grants and awards, including from the National Institutes of Health, the James and Audrey Foster MGH Research Scholar Award, the Charles A. King Trust Postdoctoral Research Fellowship, and the Boston University Clinical and Translational Science Institute.
A version of this article appeared on Medscape.com.
HCV cases in children are rising, yet access to treatment is limited, especially for Black children, according to a new retrospective cohort analysis published in Pediatrics. Treatment entails direct-acting antiviral agents, for which 95% of patients have no detectable trace of the virus 12 weeks after treatment.
“HCV is a silent killer,” said Megan Rose Curtis, MD, MS, the lead author of the study. “It can be asymptomatic for many years until the third decade of life if a child is infected perinatally” and does not receive treatment.
The prevalence of HCV in pregnant people jumped 16-fold between 1998 and 2018 to 5.3 cases per every 1000 pregnancies, and these patients can transmit the disease perinatally. Many people are unaware they are infected.
Curtis, based at Washington University in St. Louis School of Medicine, St. Louis, Missouri, and her team analyzed electronic medical records of children diagnosed with HCV born over an 18-year period starting in 2000 using the TriNetX Research Network. They also included data on prescriptions for direct-acting antivirals, appointments with healthcare providers, and race and ethnicity.
The sample included 928 children with HCV (52.3% women; 55.9% White) and excluded children whose HCV had spontaneously cleared.
A little over one third (32%) of children had seen a clinician for HCV care, which was defined as having in their record an antiviral prescription, a fibrosis stage, an order for an HCV genotype test, or a diagnosis of the disease.
Even fewer children (12%) were prescribed an antiviral.
Children with certain characteristics were more likely to receive care, the researchers found. For instance, children born between 2014 and 2018 (P = .008) and those diagnosed at age 0-3 years (P = .03) were most likely to see a clinician and receive treatment.
The current recommended treatment regimen for pediatric HCV — glecaprevir/pibrentasvir (Mavyret) or sofosbuvir/velpatasvir (Epclusa) — became available in 2017.
Hispanic/Latinx and White children were 120% and 240% more likely than Black children, respectively, to have received care (odds ratio [OR], 2.20; 95% CI, 1.05-4.59 and OR, 3.44; 95% CI, 1.89-6.28). Children living in southern states were less likely to have seen a doctor for HCV treatment.
Curtis said children might not receive treatment because their caregivers do not bring them to follow-up appointments, possibly because they struggle with stable housing or transportation. Insurance companies also sometimes will not pay for the treatment.
“If you have a golden opportunity to see someone in your office, it might be the only chance someone offers them HCV treatment. It can have a huge and transformative impact on someone’s life,” she said.
Jenelle Ferry, MD, a neonatologist at Pediatrix Medical Group in Tampa, Florida, said clinicians should routinely screen children and refer caregivers to a pediatric hepatologist for further management.
Pediatricians who suspect HCV in their patients should order a test for viral nucleic acid or viral load or request a polymerase chain reaction test.
Curtis noted that more than half of children clear the infection on their own by age 3, the age at which treatment can also begin. Treatment may also not be the right option for those who cannot swallow the medicine, which is available in oral pellets for children.
Greg Marchand, MD, an OB/GYN at the Marchand Institute for Minimally Invasive Surgery in Mesa, Arizona, said the research illuminates a “huge missed opportunity” to help children.
“If left untreated, these children risk serious liver complications like cirrhosis, liver cancer, high medical costs, and even death,” he said.
Marchand said clinicians must be aware of the guidelines for testing people who are pregnant and infants. In 2020, the US Centers for Disease Control and Prevention recommended universal HCV antibody screening during every pregnancy.
“There’s still hope that treatment rates will improve as both doctors and families become more familiar with” the newer drugs, he said.
No financial disclosures were reported.
The authors of this study were supported by various grants and awards, including from the National Institutes of Health, the James and Audrey Foster MGH Research Scholar Award, the Charles A. King Trust Postdoctoral Research Fellowship, and the Boston University Clinical and Translational Science Institute.
A version of this article appeared on Medscape.com.
HCV cases in children are rising, yet access to treatment is limited, especially for Black children, according to a new retrospective cohort analysis published in Pediatrics. Treatment entails direct-acting antiviral agents, for which 95% of patients have no detectable trace of the virus 12 weeks after treatment.
“HCV is a silent killer,” said Megan Rose Curtis, MD, MS, the lead author of the study. “It can be asymptomatic for many years until the third decade of life if a child is infected perinatally” and does not receive treatment.
The prevalence of HCV in pregnant people jumped 16-fold between 1998 and 2018 to 5.3 cases per every 1000 pregnancies, and these patients can transmit the disease perinatally. Many people are unaware they are infected.
Curtis, based at Washington University in St. Louis School of Medicine, St. Louis, Missouri, and her team analyzed electronic medical records of children diagnosed with HCV born over an 18-year period starting in 2000 using the TriNetX Research Network. They also included data on prescriptions for direct-acting antivirals, appointments with healthcare providers, and race and ethnicity.
The sample included 928 children with HCV (52.3% women; 55.9% White) and excluded children whose HCV had spontaneously cleared.
A little over one third (32%) of children had seen a clinician for HCV care, which was defined as having in their record an antiviral prescription, a fibrosis stage, an order for an HCV genotype test, or a diagnosis of the disease.
Even fewer children (12%) were prescribed an antiviral.
Children with certain characteristics were more likely to receive care, the researchers found. For instance, children born between 2014 and 2018 (P = .008) and those diagnosed at age 0-3 years (P = .03) were most likely to see a clinician and receive treatment.
The current recommended treatment regimen for pediatric HCV — glecaprevir/pibrentasvir (Mavyret) or sofosbuvir/velpatasvir (Epclusa) — became available in 2017.
Hispanic/Latinx and White children were 120% and 240% more likely than Black children, respectively, to have received care (odds ratio [OR], 2.20; 95% CI, 1.05-4.59 and OR, 3.44; 95% CI, 1.89-6.28). Children living in southern states were less likely to have seen a doctor for HCV treatment.
Curtis said children might not receive treatment because their caregivers do not bring them to follow-up appointments, possibly because they struggle with stable housing or transportation. Insurance companies also sometimes will not pay for the treatment.
“If you have a golden opportunity to see someone in your office, it might be the only chance someone offers them HCV treatment. It can have a huge and transformative impact on someone’s life,” she said.
Jenelle Ferry, MD, a neonatologist at Pediatrix Medical Group in Tampa, Florida, said clinicians should routinely screen children and refer caregivers to a pediatric hepatologist for further management.
Pediatricians who suspect HCV in their patients should order a test for viral nucleic acid or viral load or request a polymerase chain reaction test.
Curtis noted that more than half of children clear the infection on their own by age 3, the age at which treatment can also begin. Treatment may also not be the right option for those who cannot swallow the medicine, which is available in oral pellets for children.
Greg Marchand, MD, an OB/GYN at the Marchand Institute for Minimally Invasive Surgery in Mesa, Arizona, said the research illuminates a “huge missed opportunity” to help children.
“If left untreated, these children risk serious liver complications like cirrhosis, liver cancer, high medical costs, and even death,” he said.
Marchand said clinicians must be aware of the guidelines for testing people who are pregnant and infants. In 2020, the US Centers for Disease Control and Prevention recommended universal HCV antibody screening during every pregnancy.
“There’s still hope that treatment rates will improve as both doctors and families become more familiar with” the newer drugs, he said.
No financial disclosures were reported.
The authors of this study were supported by various grants and awards, including from the National Institutes of Health, the James and Audrey Foster MGH Research Scholar Award, the Charles A. King Trust Postdoctoral Research Fellowship, and the Boston University Clinical and Translational Science Institute.
A version of this article appeared on Medscape.com.
Once-Monthly Efimosfermin Leads to Significant MASH Improvement in Phase 2 Trial
SAN DIEGO — , according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.
An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.
MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.
The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.
The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.
Primary endpoints were safety and tolerability.
Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.
Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.
Positive Results
“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”
After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).
The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.
Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.
Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.
“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.
Hopeful Development
“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.
The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.
Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.
Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.
An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.
MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.
The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.
The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.
Primary endpoints were safety and tolerability.
Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.
Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.
Positive Results
“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”
After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).
The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.
Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.
Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.
“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.
Hopeful Development
“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.
The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.
Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.
Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.
An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.
MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.
The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.
The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.
Primary endpoints were safety and tolerability.
Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.
Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.
Positive Results
“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”
After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).
The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.
Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.
Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.
“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.
Hopeful Development
“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.
The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.
Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.
Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Semaglutide Therapy Improves Liver Histology in MASH
, an ongoing randomized placebo-controlled trial reported.
The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.
Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.
A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.
“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.”
Study Details
From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.
All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.
Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).
In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.
Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).
A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001).
In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001).
The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms.
The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit.
Gastrointestinal adverse events were more common in the semaglutide group.
Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”
Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.”
“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.”
He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”
According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”
This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.
A version of this article appeared on Medscape.com.
, an ongoing randomized placebo-controlled trial reported.
The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.
Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.
A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.
“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.”
Study Details
From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.
All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.
Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).
In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.
Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).
A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001).
In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001).
The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms.
The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit.
Gastrointestinal adverse events were more common in the semaglutide group.
Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”
Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.”
“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.”
He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”
According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”
This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.
A version of this article appeared on Medscape.com.
, an ongoing randomized placebo-controlled trial reported.
The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.
Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.
A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.
“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.”
Study Details
From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.
All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.
Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).
In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.
Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).
A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001).
In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001).
The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms.
The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit.
Gastrointestinal adverse events were more common in the semaglutide group.
Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”
Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.”
“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.”
He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”
According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”
This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.
A version of this article appeared on Medscape.com.