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MASLD often is worse in slim patients
PARIS — Although metabolic liver diseases are mainly seen in patients with obesity or type 2 diabetes, studies have shown that non-alcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), also affects slim patients. Moreover, the condition could be particularly severe in this population.
A recent study carried out using data from the French Constance cohort showed that of the 25,753 patients with MASLD, 16.3% were lean (BMI of less than 25 kg/m²). In addition, 50% of these patients had no metabolic risk factors.
These slim patients with MASLD were most often young patients, for the most part female, and less likely to present with symptoms of metabolic syndrome. Asian patients were overrepresented in this group.
“These patients probably have genetic and/or environmental risk factors,” commented senior author Lawrence Serfaty, MD, PhD, head of the metabolic liver unit at the new Strasbourg public hospital, during a press conference at the Paris NASH meeting.
The disease was more severe in slim subjects. Overall, 3.6% of the slim subjects had advanced fibrosis (Forns index > 6.9) vs 1.7% of patients with overweight or obesity (P < .001), regardless of demographic variables, metabolic risk factors, and lifestyle. They also had higher alanine aminotransferase levels.
In addition, over the course of a mean follow-up of 3.8 years, liver events (eg, cirrhosis, decompensated cirrhosis, and liver cancer), chronic kidney diseases, and all-cause mortality were much more common in these patients than in patients with overweight or obesity (adjusted hazard ratios of 5.84, 2.49, and 3.01, respectively). It should be noted that these clinical results were linked to fibrosis severity in both slim and overweight subjects with MASLD.
Nonetheless, cardiovascular events remained more common in patients with overweight or obesity, suggesting that obesity itself is a major risk factor for cardiovascular diseases, regardless of MASLD.
“Armed with these results, which confirm those obtained from other studies, we must seek to understand the pathogenesis of the disease in slim patients and study the role of the microbiota, genetics, and diet, as well as determining the effects of alcohol and tobacco, consumption of which was slightly more common in this subpopulation,” said Dr. Serfaty.
According to the study authors, sarcopenia and bile acids could also be involved in the pathogenesis of MASLD in slim patients. The researchers concluded that “due to the relatively low rate of MASLD in slim subjects, screening should target patients presenting with metabolic anomalies and/or unexplained cytolysis.”
This article was translated from the Medscape French edition.
PARIS — Although metabolic liver diseases are mainly seen in patients with obesity or type 2 diabetes, studies have shown that non-alcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), also affects slim patients. Moreover, the condition could be particularly severe in this population.
A recent study carried out using data from the French Constance cohort showed that of the 25,753 patients with MASLD, 16.3% were lean (BMI of less than 25 kg/m²). In addition, 50% of these patients had no metabolic risk factors.
These slim patients with MASLD were most often young patients, for the most part female, and less likely to present with symptoms of metabolic syndrome. Asian patients were overrepresented in this group.
“These patients probably have genetic and/or environmental risk factors,” commented senior author Lawrence Serfaty, MD, PhD, head of the metabolic liver unit at the new Strasbourg public hospital, during a press conference at the Paris NASH meeting.
The disease was more severe in slim subjects. Overall, 3.6% of the slim subjects had advanced fibrosis (Forns index > 6.9) vs 1.7% of patients with overweight or obesity (P < .001), regardless of demographic variables, metabolic risk factors, and lifestyle. They also had higher alanine aminotransferase levels.
In addition, over the course of a mean follow-up of 3.8 years, liver events (eg, cirrhosis, decompensated cirrhosis, and liver cancer), chronic kidney diseases, and all-cause mortality were much more common in these patients than in patients with overweight or obesity (adjusted hazard ratios of 5.84, 2.49, and 3.01, respectively). It should be noted that these clinical results were linked to fibrosis severity in both slim and overweight subjects with MASLD.
Nonetheless, cardiovascular events remained more common in patients with overweight or obesity, suggesting that obesity itself is a major risk factor for cardiovascular diseases, regardless of MASLD.
“Armed with these results, which confirm those obtained from other studies, we must seek to understand the pathogenesis of the disease in slim patients and study the role of the microbiota, genetics, and diet, as well as determining the effects of alcohol and tobacco, consumption of which was slightly more common in this subpopulation,” said Dr. Serfaty.
According to the study authors, sarcopenia and bile acids could also be involved in the pathogenesis of MASLD in slim patients. The researchers concluded that “due to the relatively low rate of MASLD in slim subjects, screening should target patients presenting with metabolic anomalies and/or unexplained cytolysis.”
This article was translated from the Medscape French edition.
PARIS — Although metabolic liver diseases are mainly seen in patients with obesity or type 2 diabetes, studies have shown that non-alcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), also affects slim patients. Moreover, the condition could be particularly severe in this population.
A recent study carried out using data from the French Constance cohort showed that of the 25,753 patients with MASLD, 16.3% were lean (BMI of less than 25 kg/m²). In addition, 50% of these patients had no metabolic risk factors.
These slim patients with MASLD were most often young patients, for the most part female, and less likely to present with symptoms of metabolic syndrome. Asian patients were overrepresented in this group.
“These patients probably have genetic and/or environmental risk factors,” commented senior author Lawrence Serfaty, MD, PhD, head of the metabolic liver unit at the new Strasbourg public hospital, during a press conference at the Paris NASH meeting.
The disease was more severe in slim subjects. Overall, 3.6% of the slim subjects had advanced fibrosis (Forns index > 6.9) vs 1.7% of patients with overweight or obesity (P < .001), regardless of demographic variables, metabolic risk factors, and lifestyle. They also had higher alanine aminotransferase levels.
In addition, over the course of a mean follow-up of 3.8 years, liver events (eg, cirrhosis, decompensated cirrhosis, and liver cancer), chronic kidney diseases, and all-cause mortality were much more common in these patients than in patients with overweight or obesity (adjusted hazard ratios of 5.84, 2.49, and 3.01, respectively). It should be noted that these clinical results were linked to fibrosis severity in both slim and overweight subjects with MASLD.
Nonetheless, cardiovascular events remained more common in patients with overweight or obesity, suggesting that obesity itself is a major risk factor for cardiovascular diseases, regardless of MASLD.
“Armed with these results, which confirm those obtained from other studies, we must seek to understand the pathogenesis of the disease in slim patients and study the role of the microbiota, genetics, and diet, as well as determining the effects of alcohol and tobacco, consumption of which was slightly more common in this subpopulation,” said Dr. Serfaty.
According to the study authors, sarcopenia and bile acids could also be involved in the pathogenesis of MASLD in slim patients. The researchers concluded that “due to the relatively low rate of MASLD in slim subjects, screening should target patients presenting with metabolic anomalies and/or unexplained cytolysis.”
This article was translated from the Medscape French edition.
FDA approves first 2 gene-editing therapies for sickle cell
These “milestone treatments” mark the first cell-based gene therapies for this debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States.
The two therapies are exagamglogene autotemcel, or exa-cel (Casgevy; Vertex Pharmaceuticals and Crispr Therapeutics), and lovotibeglogene autotemcel, or lovo-cel (Lyfgenia; bluebird bio).
“The approval of the first gene therapies for [sickle cell disease] represents a tremendous step forward for the [sickle cell] community, which has been historically overlooked and underfunded,” said Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, in a statement from the American Society of Hematology, following the approval.
“We are excited to advance the field, especially for individuals whose lives have been severely disrupted by the disease, by approving two cell-based gene therapies today,” Nicole Verdun, MD, of the FDA’s Center for Biologics Evaluation and Research, added in an agency press release.
Sickle cell disease involves a mutation in hemoglobin, a protein in red blood cells that provides oxygen to tissues. The mutation leads red blood cells to develop a crescent or sickle shape, which can restrict blood flow and cause severe pain and organ damage, known as vaso-occlusive events or crises.
Treatment options prior to these approvals primarily included red blood transfusions and hydroxyurea alongside pain management. The only potential curative option has been allogeneic hematopoietic stem cell transplantation, but that comes with significant risks and most patients don’t have an appropriate donor.
Exa-cel
Exa-cel uses CRISPR gene-editing technology. Before the infusion, patients undergo myeloablative conditioning, which removes cells from the bone marrow. These cells are genetically modified to produce fetal hemoglobin. Patients then receive an infusion of the edited cells, which can help restore normal hemoglobin production.
The FDA approval was based on data from the pivotal CLIMB SCD-121 trial. In an October advisory committee meeting, the FDA highlighted trial data demonstrating that 29 of 31 patients reached the trial’s primary endpoint: freedom from severe vaso-occlusive crises over a 12-month period. In addition, 28 of these patients remained free of vaso-occlusive crises for almost 2 years.
The committee noted that one of the 31 patients died about 9 months after receiving an exa-cel infusion.
The cell-based gene therapy also increased both fetal and total hemoglobin, with total hemoglobin levels increasing to > 11 g/dL by month 3 and remaining at that level afterward. No patients experienced graft failure or rejection.
The most common side effects included low platelets and white blood cell counts, mouth sores, nausea, musculoskeletal pain, vomiting, and febrile neutropenia.
Exa-cel could “provide a one-time functional cure” for patients with severe sickle cell disease, according to Franco Locatelli, MD, of Sapienza University of Rome, who presented initial findings last year.
While the current approval is for patients with infusion-dependent sickle cell disease, exa-cel is also being evaluated in patients with another blood disorder, beta-thalassemia.
Lovo-cel
Lovo-cel, a cell-based gene therapy, uses a different technology — a lentiviral vector, or gene delivery vehicle — that can also genetically modify a patient’s blood stem cells.
Like exa-cel, lovo-cel is a one-time, single-dose infusion that contains the patient’s modified cells. Before the infusion, patients undergo myeloablative conditioning. The patient’s stem cells are then genetically modified to allow them to produce the most common form of hemoglobin, HbA
This approval was based on data from a single-arm, 24-month study in patients aged 12-50 years who had sickle cell disease and a history of vaso-occlusive events.
Overall, 88% of patients (28 of 32) achieved complete resolution of vaso-occlusive events 6-18 months after the infusion.
The most common side effects included stomatitis; febrile neutropenia; and low platelet, white blood cell, and red blood cell counts.
The FDA noted that hematologic cancer has occurred in patients treated with lovo-cel, and the label includes a black-box warning about the risk.
Dr. Brodsky noted, however, that “while these new gene therapies are potentially life-changing for individuals living with [sickle cell disease], they must be accessible to be effective.”
Access is a potential concern. Exa-cel and lovo-cel could cost about $2 million.
A version of this article appeared on Medscape.com.
These “milestone treatments” mark the first cell-based gene therapies for this debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States.
The two therapies are exagamglogene autotemcel, or exa-cel (Casgevy; Vertex Pharmaceuticals and Crispr Therapeutics), and lovotibeglogene autotemcel, or lovo-cel (Lyfgenia; bluebird bio).
“The approval of the first gene therapies for [sickle cell disease] represents a tremendous step forward for the [sickle cell] community, which has been historically overlooked and underfunded,” said Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, in a statement from the American Society of Hematology, following the approval.
“We are excited to advance the field, especially for individuals whose lives have been severely disrupted by the disease, by approving two cell-based gene therapies today,” Nicole Verdun, MD, of the FDA’s Center for Biologics Evaluation and Research, added in an agency press release.
Sickle cell disease involves a mutation in hemoglobin, a protein in red blood cells that provides oxygen to tissues. The mutation leads red blood cells to develop a crescent or sickle shape, which can restrict blood flow and cause severe pain and organ damage, known as vaso-occlusive events or crises.
Treatment options prior to these approvals primarily included red blood transfusions and hydroxyurea alongside pain management. The only potential curative option has been allogeneic hematopoietic stem cell transplantation, but that comes with significant risks and most patients don’t have an appropriate donor.
Exa-cel
Exa-cel uses CRISPR gene-editing technology. Before the infusion, patients undergo myeloablative conditioning, which removes cells from the bone marrow. These cells are genetically modified to produce fetal hemoglobin. Patients then receive an infusion of the edited cells, which can help restore normal hemoglobin production.
The FDA approval was based on data from the pivotal CLIMB SCD-121 trial. In an October advisory committee meeting, the FDA highlighted trial data demonstrating that 29 of 31 patients reached the trial’s primary endpoint: freedom from severe vaso-occlusive crises over a 12-month period. In addition, 28 of these patients remained free of vaso-occlusive crises for almost 2 years.
The committee noted that one of the 31 patients died about 9 months after receiving an exa-cel infusion.
The cell-based gene therapy also increased both fetal and total hemoglobin, with total hemoglobin levels increasing to > 11 g/dL by month 3 and remaining at that level afterward. No patients experienced graft failure or rejection.
The most common side effects included low platelets and white blood cell counts, mouth sores, nausea, musculoskeletal pain, vomiting, and febrile neutropenia.
Exa-cel could “provide a one-time functional cure” for patients with severe sickle cell disease, according to Franco Locatelli, MD, of Sapienza University of Rome, who presented initial findings last year.
While the current approval is for patients with infusion-dependent sickle cell disease, exa-cel is also being evaluated in patients with another blood disorder, beta-thalassemia.
Lovo-cel
Lovo-cel, a cell-based gene therapy, uses a different technology — a lentiviral vector, or gene delivery vehicle — that can also genetically modify a patient’s blood stem cells.
Like exa-cel, lovo-cel is a one-time, single-dose infusion that contains the patient’s modified cells. Before the infusion, patients undergo myeloablative conditioning. The patient’s stem cells are then genetically modified to allow them to produce the most common form of hemoglobin, HbA
This approval was based on data from a single-arm, 24-month study in patients aged 12-50 years who had sickle cell disease and a history of vaso-occlusive events.
Overall, 88% of patients (28 of 32) achieved complete resolution of vaso-occlusive events 6-18 months after the infusion.
The most common side effects included stomatitis; febrile neutropenia; and low platelet, white blood cell, and red blood cell counts.
The FDA noted that hematologic cancer has occurred in patients treated with lovo-cel, and the label includes a black-box warning about the risk.
Dr. Brodsky noted, however, that “while these new gene therapies are potentially life-changing for individuals living with [sickle cell disease], they must be accessible to be effective.”
Access is a potential concern. Exa-cel and lovo-cel could cost about $2 million.
A version of this article appeared on Medscape.com.
These “milestone treatments” mark the first cell-based gene therapies for this debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States.
The two therapies are exagamglogene autotemcel, or exa-cel (Casgevy; Vertex Pharmaceuticals and Crispr Therapeutics), and lovotibeglogene autotemcel, or lovo-cel (Lyfgenia; bluebird bio).
“The approval of the first gene therapies for [sickle cell disease] represents a tremendous step forward for the [sickle cell] community, which has been historically overlooked and underfunded,” said Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, in a statement from the American Society of Hematology, following the approval.
“We are excited to advance the field, especially for individuals whose lives have been severely disrupted by the disease, by approving two cell-based gene therapies today,” Nicole Verdun, MD, of the FDA’s Center for Biologics Evaluation and Research, added in an agency press release.
Sickle cell disease involves a mutation in hemoglobin, a protein in red blood cells that provides oxygen to tissues. The mutation leads red blood cells to develop a crescent or sickle shape, which can restrict blood flow and cause severe pain and organ damage, known as vaso-occlusive events or crises.
Treatment options prior to these approvals primarily included red blood transfusions and hydroxyurea alongside pain management. The only potential curative option has been allogeneic hematopoietic stem cell transplantation, but that comes with significant risks and most patients don’t have an appropriate donor.
Exa-cel
Exa-cel uses CRISPR gene-editing technology. Before the infusion, patients undergo myeloablative conditioning, which removes cells from the bone marrow. These cells are genetically modified to produce fetal hemoglobin. Patients then receive an infusion of the edited cells, which can help restore normal hemoglobin production.
The FDA approval was based on data from the pivotal CLIMB SCD-121 trial. In an October advisory committee meeting, the FDA highlighted trial data demonstrating that 29 of 31 patients reached the trial’s primary endpoint: freedom from severe vaso-occlusive crises over a 12-month period. In addition, 28 of these patients remained free of vaso-occlusive crises for almost 2 years.
The committee noted that one of the 31 patients died about 9 months after receiving an exa-cel infusion.
The cell-based gene therapy also increased both fetal and total hemoglobin, with total hemoglobin levels increasing to > 11 g/dL by month 3 and remaining at that level afterward. No patients experienced graft failure or rejection.
The most common side effects included low platelets and white blood cell counts, mouth sores, nausea, musculoskeletal pain, vomiting, and febrile neutropenia.
Exa-cel could “provide a one-time functional cure” for patients with severe sickle cell disease, according to Franco Locatelli, MD, of Sapienza University of Rome, who presented initial findings last year.
While the current approval is for patients with infusion-dependent sickle cell disease, exa-cel is also being evaluated in patients with another blood disorder, beta-thalassemia.
Lovo-cel
Lovo-cel, a cell-based gene therapy, uses a different technology — a lentiviral vector, or gene delivery vehicle — that can also genetically modify a patient’s blood stem cells.
Like exa-cel, lovo-cel is a one-time, single-dose infusion that contains the patient’s modified cells. Before the infusion, patients undergo myeloablative conditioning. The patient’s stem cells are then genetically modified to allow them to produce the most common form of hemoglobin, HbA
This approval was based on data from a single-arm, 24-month study in patients aged 12-50 years who had sickle cell disease and a history of vaso-occlusive events.
Overall, 88% of patients (28 of 32) achieved complete resolution of vaso-occlusive events 6-18 months after the infusion.
The most common side effects included stomatitis; febrile neutropenia; and low platelet, white blood cell, and red blood cell counts.
The FDA noted that hematologic cancer has occurred in patients treated with lovo-cel, and the label includes a black-box warning about the risk.
Dr. Brodsky noted, however, that “while these new gene therapies are potentially life-changing for individuals living with [sickle cell disease], they must be accessible to be effective.”
Access is a potential concern. Exa-cel and lovo-cel could cost about $2 million.
A version of this article appeared on Medscape.com.
More than one-third of adults in the US could have NAFLD by 2050
, according to investigators.
These findings suggest that health care systems should prepare for “large increases” in cases of hepatocellular carcinoma (HCC) and need for liver transplants, reported lead author Phuc Le, PhD, MPH, of the Cleveland Clinic, and colleagues.
“Following the alarming rise in prevalence of obesity and diabetes, NAFLD is projected to become the leading indication for liver transplant in the United States in the next decade,” Dr. Le and colleagues wrote in their abstract for the annual meeting of the American Association for the Study of Liver Diseases. “A better understanding of the clinical burden associated with NAFLD will enable health systems to prepare to meet this imminent demand from patients.”
To this end, Dr. Le and colleagues developed an agent-based state transition model to predict future prevalence of NAFLD and associated outcomes.
In the first part of the model, the investigators simulated population growth in the United States using Census Bureau data, including new births and immigration, from the year 2000 onward. The second part of the model simulated natural progression of NAFLD in adults via 14 associated conditions and events, including steatosis, nonalcoholic steatohepatitis (NASH), HCC, liver transplants, liver-related mortality, and others.
By first comparing simulated findings with actual findings between 2000 and 2018, the investigators confirmed that their model could reliably predict the intended epidemiological parameters.
Next, they turned their model toward the future.
It predicted that the prevalence of NAFLD among US adults will rise from 27.8% in 2020 to 34.3% in 2050. Over the same timeframe, prevalence of NASH is predicted to increase from 20.0% to 21.8%, proportion of NAFLD cases developing cirrhosis is expected to increase from 1.9% to 3.1%, and liver-related mortality is estimated to rise from 0.4% to 1% of all deaths.
The model also predicted that the burden of HCC will increase from 10,400 to 19,300 new cases per year, while liver transplant burden will more than double, from 1,700 to 4,200 transplants per year.
“Our model forecasts substantial clinical burden of NAFLD over the next three decades,” Dr. Le said in a virtual press conference. “And in the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant.”
During the press conference, Norah Terrault, MD, president of the AASLD from the University of Southern California, Los Angeles, noted that all of the reported outcomes, including increasing rates of liver cancer, cirrhosis, and transplants are “potentially preventable.”
Dr. Terrault went on to suggest ways of combating this increasing burden of NAFLD, which she referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), the name now recommended by the AASLD.
“There’s no way we’re going to be able to transplant our way out of this,” Dr. Terrault said. “We need to be bringing greater awareness both to patients, as well as to providers about how we seek out the diagnosis. And we need to bring greater awareness to the population around the things that contribute to MASLD.”
Rates of obesity and diabetes continue to rise, Dr. Terrault said, explaining why MASLD is more common than ever. To counteract these trends, she called for greater awareness of driving factors, such as dietary choices and sedentary lifestyle.
“These are all really important messages that we want to get out to the population, and are really the cornerstones for how we approach the management of patients who have MASLD,” Dr. Terrault said.
In discussion with Dr. Terrault, Dr. Le agreed that increased education may help stem the rising tide of disease, while treatment advances could also increase the odds of a brighter future.
“If we improve our management of NAFLD, or NAFLD-related comorbidities, and if we can develop an effective treatment for NAFLD, then obviously the future would not be so dark,” Dr. Le said, noting promising phase 3 data that would be presented at the meeting. “We are hopeful that the future of disease burden will not be as bad as our model predicts.”
The study was funded by the Agency for Healthcare Research and Quality. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings suggest that health care systems should prepare for “large increases” in cases of hepatocellular carcinoma (HCC) and need for liver transplants, reported lead author Phuc Le, PhD, MPH, of the Cleveland Clinic, and colleagues.
“Following the alarming rise in prevalence of obesity and diabetes, NAFLD is projected to become the leading indication for liver transplant in the United States in the next decade,” Dr. Le and colleagues wrote in their abstract for the annual meeting of the American Association for the Study of Liver Diseases. “A better understanding of the clinical burden associated with NAFLD will enable health systems to prepare to meet this imminent demand from patients.”
To this end, Dr. Le and colleagues developed an agent-based state transition model to predict future prevalence of NAFLD and associated outcomes.
In the first part of the model, the investigators simulated population growth in the United States using Census Bureau data, including new births and immigration, from the year 2000 onward. The second part of the model simulated natural progression of NAFLD in adults via 14 associated conditions and events, including steatosis, nonalcoholic steatohepatitis (NASH), HCC, liver transplants, liver-related mortality, and others.
By first comparing simulated findings with actual findings between 2000 and 2018, the investigators confirmed that their model could reliably predict the intended epidemiological parameters.
Next, they turned their model toward the future.
It predicted that the prevalence of NAFLD among US adults will rise from 27.8% in 2020 to 34.3% in 2050. Over the same timeframe, prevalence of NASH is predicted to increase from 20.0% to 21.8%, proportion of NAFLD cases developing cirrhosis is expected to increase from 1.9% to 3.1%, and liver-related mortality is estimated to rise from 0.4% to 1% of all deaths.
The model also predicted that the burden of HCC will increase from 10,400 to 19,300 new cases per year, while liver transplant burden will more than double, from 1,700 to 4,200 transplants per year.
“Our model forecasts substantial clinical burden of NAFLD over the next three decades,” Dr. Le said in a virtual press conference. “And in the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant.”
During the press conference, Norah Terrault, MD, president of the AASLD from the University of Southern California, Los Angeles, noted that all of the reported outcomes, including increasing rates of liver cancer, cirrhosis, and transplants are “potentially preventable.”
Dr. Terrault went on to suggest ways of combating this increasing burden of NAFLD, which she referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), the name now recommended by the AASLD.
“There’s no way we’re going to be able to transplant our way out of this,” Dr. Terrault said. “We need to be bringing greater awareness both to patients, as well as to providers about how we seek out the diagnosis. And we need to bring greater awareness to the population around the things that contribute to MASLD.”
Rates of obesity and diabetes continue to rise, Dr. Terrault said, explaining why MASLD is more common than ever. To counteract these trends, she called for greater awareness of driving factors, such as dietary choices and sedentary lifestyle.
“These are all really important messages that we want to get out to the population, and are really the cornerstones for how we approach the management of patients who have MASLD,” Dr. Terrault said.
In discussion with Dr. Terrault, Dr. Le agreed that increased education may help stem the rising tide of disease, while treatment advances could also increase the odds of a brighter future.
“If we improve our management of NAFLD, or NAFLD-related comorbidities, and if we can develop an effective treatment for NAFLD, then obviously the future would not be so dark,” Dr. Le said, noting promising phase 3 data that would be presented at the meeting. “We are hopeful that the future of disease burden will not be as bad as our model predicts.”
The study was funded by the Agency for Healthcare Research and Quality. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings suggest that health care systems should prepare for “large increases” in cases of hepatocellular carcinoma (HCC) and need for liver transplants, reported lead author Phuc Le, PhD, MPH, of the Cleveland Clinic, and colleagues.
“Following the alarming rise in prevalence of obesity and diabetes, NAFLD is projected to become the leading indication for liver transplant in the United States in the next decade,” Dr. Le and colleagues wrote in their abstract for the annual meeting of the American Association for the Study of Liver Diseases. “A better understanding of the clinical burden associated with NAFLD will enable health systems to prepare to meet this imminent demand from patients.”
To this end, Dr. Le and colleagues developed an agent-based state transition model to predict future prevalence of NAFLD and associated outcomes.
In the first part of the model, the investigators simulated population growth in the United States using Census Bureau data, including new births and immigration, from the year 2000 onward. The second part of the model simulated natural progression of NAFLD in adults via 14 associated conditions and events, including steatosis, nonalcoholic steatohepatitis (NASH), HCC, liver transplants, liver-related mortality, and others.
By first comparing simulated findings with actual findings between 2000 and 2018, the investigators confirmed that their model could reliably predict the intended epidemiological parameters.
Next, they turned their model toward the future.
It predicted that the prevalence of NAFLD among US adults will rise from 27.8% in 2020 to 34.3% in 2050. Over the same timeframe, prevalence of NASH is predicted to increase from 20.0% to 21.8%, proportion of NAFLD cases developing cirrhosis is expected to increase from 1.9% to 3.1%, and liver-related mortality is estimated to rise from 0.4% to 1% of all deaths.
The model also predicted that the burden of HCC will increase from 10,400 to 19,300 new cases per year, while liver transplant burden will more than double, from 1,700 to 4,200 transplants per year.
“Our model forecasts substantial clinical burden of NAFLD over the next three decades,” Dr. Le said in a virtual press conference. “And in the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant.”
During the press conference, Norah Terrault, MD, president of the AASLD from the University of Southern California, Los Angeles, noted that all of the reported outcomes, including increasing rates of liver cancer, cirrhosis, and transplants are “potentially preventable.”
Dr. Terrault went on to suggest ways of combating this increasing burden of NAFLD, which she referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), the name now recommended by the AASLD.
“There’s no way we’re going to be able to transplant our way out of this,” Dr. Terrault said. “We need to be bringing greater awareness both to patients, as well as to providers about how we seek out the diagnosis. And we need to bring greater awareness to the population around the things that contribute to MASLD.”
Rates of obesity and diabetes continue to rise, Dr. Terrault said, explaining why MASLD is more common than ever. To counteract these trends, she called for greater awareness of driving factors, such as dietary choices and sedentary lifestyle.
“These are all really important messages that we want to get out to the population, and are really the cornerstones for how we approach the management of patients who have MASLD,” Dr. Terrault said.
In discussion with Dr. Terrault, Dr. Le agreed that increased education may help stem the rising tide of disease, while treatment advances could also increase the odds of a brighter future.
“If we improve our management of NAFLD, or NAFLD-related comorbidities, and if we can develop an effective treatment for NAFLD, then obviously the future would not be so dark,” Dr. Le said, noting promising phase 3 data that would be presented at the meeting. “We are hopeful that the future of disease burden will not be as bad as our model predicts.”
The study was funded by the Agency for Healthcare Research and Quality. The investigators disclosed no conflicts of interest.
AT THE LIVER MEETING
New insights into how omega-3 fatty acids improve NASH
TOPLINE:
that contributes to liver fibrosis and progression to cirrhosis and liver cancer, new data suggest.
METHODOLOGY:
- Because omega-3 polyunsaturated fatty acids have been shown to reduce hepatic dysfunction in NASH, but the molecular underpinnings of this action were elusive, researchers conducted a multiomic network analysis applied to a mouse model of Western diet–induced NASH to identify the key mechanisms involved.
- They also performed a meta-analysis of human liver cancer transcriptome data to evaluate which aspects of NASH pathogenesis leading to cancer are reversed by omega-3 polyunsaturated fatty acids.
TAKEAWAY:
- BTC, an epidermal growth factor–binding protein, was consistently upregulated in liver cancer and downregulated by omega-3 polyunsaturated fatty acids in mice and humans with NASH.
- BTC promotes NASH fibrosis by activating dormant hepatic stellate cells to produce transforming growth factor beta-2 and increase collagen production. It also exacerbates toll-like receptor-dependent inflammatory processes in NASH.
- By downregulating BTC, omega-3 polyunsaturated fatty acids have therapeutic potential in NASH and could serve as a novel drug target.
IN PRACTICE:
“BTC represents a candidate master regulator inducing two most important factors (collagens and integrins) contributing to liver fibrosis and consequently promoting liver cancer,” the researchers write. “Future studies should investigate if BTC-triggered gene expression signatures can serve as biomarkers guiding personalized [omega-3 polyunsaturated fatty acid] therapy, as targets of new NAFLD/NASH drugs, and finally as a predictors of hepatic cancer risk in humans.”
SOURCE:
The study, with lead first author Jyothi Padiadpu, PhD, Oregon State University College of Pharmacy, Corvallis, was published online in EMBO Molecular Medicine (2023. doi: 10.15252/emmm.202318367).
LIMITATIONS:
The study authors report no limitations. However, the findings are based on mouse model and human transcriptome data.
DISCLOSURES:
This research was supported by the National Institute of Diabetes and Digestive Kidney Diseases and the U.S. Department of Agriculture. The authors report no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
that contributes to liver fibrosis and progression to cirrhosis and liver cancer, new data suggest.
METHODOLOGY:
- Because omega-3 polyunsaturated fatty acids have been shown to reduce hepatic dysfunction in NASH, but the molecular underpinnings of this action were elusive, researchers conducted a multiomic network analysis applied to a mouse model of Western diet–induced NASH to identify the key mechanisms involved.
- They also performed a meta-analysis of human liver cancer transcriptome data to evaluate which aspects of NASH pathogenesis leading to cancer are reversed by omega-3 polyunsaturated fatty acids.
TAKEAWAY:
- BTC, an epidermal growth factor–binding protein, was consistently upregulated in liver cancer and downregulated by omega-3 polyunsaturated fatty acids in mice and humans with NASH.
- BTC promotes NASH fibrosis by activating dormant hepatic stellate cells to produce transforming growth factor beta-2 and increase collagen production. It also exacerbates toll-like receptor-dependent inflammatory processes in NASH.
- By downregulating BTC, omega-3 polyunsaturated fatty acids have therapeutic potential in NASH and could serve as a novel drug target.
IN PRACTICE:
“BTC represents a candidate master regulator inducing two most important factors (collagens and integrins) contributing to liver fibrosis and consequently promoting liver cancer,” the researchers write. “Future studies should investigate if BTC-triggered gene expression signatures can serve as biomarkers guiding personalized [omega-3 polyunsaturated fatty acid] therapy, as targets of new NAFLD/NASH drugs, and finally as a predictors of hepatic cancer risk in humans.”
SOURCE:
The study, with lead first author Jyothi Padiadpu, PhD, Oregon State University College of Pharmacy, Corvallis, was published online in EMBO Molecular Medicine (2023. doi: 10.15252/emmm.202318367).
LIMITATIONS:
The study authors report no limitations. However, the findings are based on mouse model and human transcriptome data.
DISCLOSURES:
This research was supported by the National Institute of Diabetes and Digestive Kidney Diseases and the U.S. Department of Agriculture. The authors report no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
that contributes to liver fibrosis and progression to cirrhosis and liver cancer, new data suggest.
METHODOLOGY:
- Because omega-3 polyunsaturated fatty acids have been shown to reduce hepatic dysfunction in NASH, but the molecular underpinnings of this action were elusive, researchers conducted a multiomic network analysis applied to a mouse model of Western diet–induced NASH to identify the key mechanisms involved.
- They also performed a meta-analysis of human liver cancer transcriptome data to evaluate which aspects of NASH pathogenesis leading to cancer are reversed by omega-3 polyunsaturated fatty acids.
TAKEAWAY:
- BTC, an epidermal growth factor–binding protein, was consistently upregulated in liver cancer and downregulated by omega-3 polyunsaturated fatty acids in mice and humans with NASH.
- BTC promotes NASH fibrosis by activating dormant hepatic stellate cells to produce transforming growth factor beta-2 and increase collagen production. It also exacerbates toll-like receptor-dependent inflammatory processes in NASH.
- By downregulating BTC, omega-3 polyunsaturated fatty acids have therapeutic potential in NASH and could serve as a novel drug target.
IN PRACTICE:
“BTC represents a candidate master regulator inducing two most important factors (collagens and integrins) contributing to liver fibrosis and consequently promoting liver cancer,” the researchers write. “Future studies should investigate if BTC-triggered gene expression signatures can serve as biomarkers guiding personalized [omega-3 polyunsaturated fatty acid] therapy, as targets of new NAFLD/NASH drugs, and finally as a predictors of hepatic cancer risk in humans.”
SOURCE:
The study, with lead first author Jyothi Padiadpu, PhD, Oregon State University College of Pharmacy, Corvallis, was published online in EMBO Molecular Medicine (2023. doi: 10.15252/emmm.202318367).
LIMITATIONS:
The study authors report no limitations. However, the findings are based on mouse model and human transcriptome data.
DISCLOSURES:
This research was supported by the National Institute of Diabetes and Digestive Kidney Diseases and the U.S. Department of Agriculture. The authors report no conflicts of interest.
A version of this article appeared on Medscape.com.
Diagnosing patients with sarcoidosis
A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?
A. Erythrocyte sedimentation rate
B. C-reactive protein
C. Lymphocyte count
D. Antinuclear antibodies
The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.1 Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.
Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.2 Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).
Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.3 The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).
Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)2 vitamin D, which is the active form of vitamin D.
Several studies have looked at the diagnostic utility of 1,25(OH)2 vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)2 vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.4 They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)2 vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)2D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).
Kavathia et al. looked at whether elevated 1,25(OH)2 vitamin D levels predicted chronicity of sarcoidosis.5 A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)2 vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)2 vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).
Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.6 Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)2 vitamin D level checked.
Pearl: Lymphocyte count and 1,25(OH)2 vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)2 vitamin D levels monitored.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.
2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.
3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.
4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.
5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.
6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.
A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?
A. Erythrocyte sedimentation rate
B. C-reactive protein
C. Lymphocyte count
D. Antinuclear antibodies
The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.1 Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.
Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.2 Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).
Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.3 The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).
Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)2 vitamin D, which is the active form of vitamin D.
Several studies have looked at the diagnostic utility of 1,25(OH)2 vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)2 vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.4 They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)2 vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)2D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).
Kavathia et al. looked at whether elevated 1,25(OH)2 vitamin D levels predicted chronicity of sarcoidosis.5 A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)2 vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)2 vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).
Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.6 Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)2 vitamin D level checked.
Pearl: Lymphocyte count and 1,25(OH)2 vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)2 vitamin D levels monitored.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.
2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.
3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.
4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.
5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.
6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.
A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?
A. Erythrocyte sedimentation rate
B. C-reactive protein
C. Lymphocyte count
D. Antinuclear antibodies
The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.1 Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.
Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.2 Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).
Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.3 The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).
Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)2 vitamin D, which is the active form of vitamin D.
Several studies have looked at the diagnostic utility of 1,25(OH)2 vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)2 vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.4 They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)2 vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)2D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).
Kavathia et al. looked at whether elevated 1,25(OH)2 vitamin D levels predicted chronicity of sarcoidosis.5 A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)2 vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)2 vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).
Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.6 Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)2 vitamin D level checked.
Pearl: Lymphocyte count and 1,25(OH)2 vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)2 vitamin D levels monitored.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.
2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.
3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.
4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.
5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.
6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.
Weight-loss drugs improve liver measures, too
BOSTON – With the current demand for type 2 diabetes drugs that both improve glycemic control and help patients shed large amounts of weight, liver specialists have speculated that the metabolic benefits could also extend to the liver.
Spoiler alert: they do.
, reported Takamasa Ohki, MD, PhD, and colleagues from the department of gastroenterology at Mitsui Memorial Hospital in Tokyo.
“Body weight reduction within 8 weeks after administration of these agents was an independent factor [that] contributed to rapid improvement of ALT. Maintenance of body weight and T2DM after normalization of ALT was also very important,” they wrote in a scientific poster presented at the annual meeting of the American Association for the Study of Liver Diseases.
The biggest losers benefit most
Dr. Ohki and colleagues evaluated the effectiveness of SGLT-2 inhibitors and GLP-1 agonists as treatment of MAFLD for patients with T2DM.
They conducted a retrospective study of 233 patients who had both conditions and who received either of the drug classes at their institution from June 2010 through December 2021; the most recent follow-up was in December 2022. The primary endpoint of the study was normalization of ALT values.
A total of 54 patients had a 3% or greater reduction in body weight within 8 weeks of beginning treatment with their respective drugs. The researchers found that for 47 of these patients (87%), ALT values normalized; the 12-, 24-, and 36-month cumulative normalization rates were 61%, 73%, and 80%, respectively.
In contrast, among the 179 patients who did not lose weight as robustly or rapidly, 137 (76.5%) demonstrated normalization of ALT, with cumulative normalization rates of 41%, 59% and 69%, respectively (P < .01).
In multivariate analysis that controlled for age, sex, smoking, hypertension, dyslipidemia, weight reduction, and antidiabetes drug use, body weight reduction of at least 3% within 8 weeks of beginning treatment with either an SLT-2 or GLP-1 agent was associated independently with normalization of ALT, with a hazard ratio (HR) of 0.67 (P = .028).
Improvement of T2DM was an independent predictor for ALT normalization (HR, 0.64; P = .015).
Other factors contributing to ALT normalization included use of sulfonylurea (HR, 0.63; P < .01) and insulin (HR, 0.54; P < .01).
In all, 103 of the 184 patients with initial normalization of ALT values experienced a recurrence of ALT elevation during follow-up. In multivariate analysis, body weight gain and exacerbation of T2DM were independent factors for ALT reexacerbation (HR, 0.52 and 0.48, respectively; P < .01 for both comparisons).
Duration of effect uncertain
Philip A. Newsome, PhD, FRCPE, professor of experimental hepatology and honorary consultant hepatologist at the University of Birmingham, England, who was not involved in the study, has conducted research into the metabolic effects of SGLT-2 inhibitors and GLP-1 agonists. In an interview, he said that both drug classes are likely to have positive near-term effects on metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through their effects on glucose control and reduction in associated comorbidities.
“The unknown question,” he added, is what will happen in the long term. “I think there are some uncertainties around what proportion of patients will essentially be downstaged or downgraded such that they don’t develop any other problem; I suspect that will be the case in very many patients. However, I suspect there will also be a large proportion that end up requiring additional therapy above and beyond weight loss,” said Dr. Newsome.
The investigators did not report a funding source for the study. Dr. Ohki and colleagues have disclosed no relevant financial relationships. Dr. Newsome has consulted on behalf of his institution with Novo Nordisk, BMS, Gilead, Pfizer, Poxel, and Intercept and has received a grant from Pharmaxis and Boehringer Ingelheim.
A version of this article appeared on Medscape.com.
BOSTON – With the current demand for type 2 diabetes drugs that both improve glycemic control and help patients shed large amounts of weight, liver specialists have speculated that the metabolic benefits could also extend to the liver.
Spoiler alert: they do.
, reported Takamasa Ohki, MD, PhD, and colleagues from the department of gastroenterology at Mitsui Memorial Hospital in Tokyo.
“Body weight reduction within 8 weeks after administration of these agents was an independent factor [that] contributed to rapid improvement of ALT. Maintenance of body weight and T2DM after normalization of ALT was also very important,” they wrote in a scientific poster presented at the annual meeting of the American Association for the Study of Liver Diseases.
The biggest losers benefit most
Dr. Ohki and colleagues evaluated the effectiveness of SGLT-2 inhibitors and GLP-1 agonists as treatment of MAFLD for patients with T2DM.
They conducted a retrospective study of 233 patients who had both conditions and who received either of the drug classes at their institution from June 2010 through December 2021; the most recent follow-up was in December 2022. The primary endpoint of the study was normalization of ALT values.
A total of 54 patients had a 3% or greater reduction in body weight within 8 weeks of beginning treatment with their respective drugs. The researchers found that for 47 of these patients (87%), ALT values normalized; the 12-, 24-, and 36-month cumulative normalization rates were 61%, 73%, and 80%, respectively.
In contrast, among the 179 patients who did not lose weight as robustly or rapidly, 137 (76.5%) demonstrated normalization of ALT, with cumulative normalization rates of 41%, 59% and 69%, respectively (P < .01).
In multivariate analysis that controlled for age, sex, smoking, hypertension, dyslipidemia, weight reduction, and antidiabetes drug use, body weight reduction of at least 3% within 8 weeks of beginning treatment with either an SLT-2 or GLP-1 agent was associated independently with normalization of ALT, with a hazard ratio (HR) of 0.67 (P = .028).
Improvement of T2DM was an independent predictor for ALT normalization (HR, 0.64; P = .015).
Other factors contributing to ALT normalization included use of sulfonylurea (HR, 0.63; P < .01) and insulin (HR, 0.54; P < .01).
In all, 103 of the 184 patients with initial normalization of ALT values experienced a recurrence of ALT elevation during follow-up. In multivariate analysis, body weight gain and exacerbation of T2DM were independent factors for ALT reexacerbation (HR, 0.52 and 0.48, respectively; P < .01 for both comparisons).
Duration of effect uncertain
Philip A. Newsome, PhD, FRCPE, professor of experimental hepatology and honorary consultant hepatologist at the University of Birmingham, England, who was not involved in the study, has conducted research into the metabolic effects of SGLT-2 inhibitors and GLP-1 agonists. In an interview, he said that both drug classes are likely to have positive near-term effects on metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through their effects on glucose control and reduction in associated comorbidities.
“The unknown question,” he added, is what will happen in the long term. “I think there are some uncertainties around what proportion of patients will essentially be downstaged or downgraded such that they don’t develop any other problem; I suspect that will be the case in very many patients. However, I suspect there will also be a large proportion that end up requiring additional therapy above and beyond weight loss,” said Dr. Newsome.
The investigators did not report a funding source for the study. Dr. Ohki and colleagues have disclosed no relevant financial relationships. Dr. Newsome has consulted on behalf of his institution with Novo Nordisk, BMS, Gilead, Pfizer, Poxel, and Intercept and has received a grant from Pharmaxis and Boehringer Ingelheim.
A version of this article appeared on Medscape.com.
BOSTON – With the current demand for type 2 diabetes drugs that both improve glycemic control and help patients shed large amounts of weight, liver specialists have speculated that the metabolic benefits could also extend to the liver.
Spoiler alert: they do.
, reported Takamasa Ohki, MD, PhD, and colleagues from the department of gastroenterology at Mitsui Memorial Hospital in Tokyo.
“Body weight reduction within 8 weeks after administration of these agents was an independent factor [that] contributed to rapid improvement of ALT. Maintenance of body weight and T2DM after normalization of ALT was also very important,” they wrote in a scientific poster presented at the annual meeting of the American Association for the Study of Liver Diseases.
The biggest losers benefit most
Dr. Ohki and colleagues evaluated the effectiveness of SGLT-2 inhibitors and GLP-1 agonists as treatment of MAFLD for patients with T2DM.
They conducted a retrospective study of 233 patients who had both conditions and who received either of the drug classes at their institution from June 2010 through December 2021; the most recent follow-up was in December 2022. The primary endpoint of the study was normalization of ALT values.
A total of 54 patients had a 3% or greater reduction in body weight within 8 weeks of beginning treatment with their respective drugs. The researchers found that for 47 of these patients (87%), ALT values normalized; the 12-, 24-, and 36-month cumulative normalization rates were 61%, 73%, and 80%, respectively.
In contrast, among the 179 patients who did not lose weight as robustly or rapidly, 137 (76.5%) demonstrated normalization of ALT, with cumulative normalization rates of 41%, 59% and 69%, respectively (P < .01).
In multivariate analysis that controlled for age, sex, smoking, hypertension, dyslipidemia, weight reduction, and antidiabetes drug use, body weight reduction of at least 3% within 8 weeks of beginning treatment with either an SLT-2 or GLP-1 agent was associated independently with normalization of ALT, with a hazard ratio (HR) of 0.67 (P = .028).
Improvement of T2DM was an independent predictor for ALT normalization (HR, 0.64; P = .015).
Other factors contributing to ALT normalization included use of sulfonylurea (HR, 0.63; P < .01) and insulin (HR, 0.54; P < .01).
In all, 103 of the 184 patients with initial normalization of ALT values experienced a recurrence of ALT elevation during follow-up. In multivariate analysis, body weight gain and exacerbation of T2DM were independent factors for ALT reexacerbation (HR, 0.52 and 0.48, respectively; P < .01 for both comparisons).
Duration of effect uncertain
Philip A. Newsome, PhD, FRCPE, professor of experimental hepatology and honorary consultant hepatologist at the University of Birmingham, England, who was not involved in the study, has conducted research into the metabolic effects of SGLT-2 inhibitors and GLP-1 agonists. In an interview, he said that both drug classes are likely to have positive near-term effects on metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through their effects on glucose control and reduction in associated comorbidities.
“The unknown question,” he added, is what will happen in the long term. “I think there are some uncertainties around what proportion of patients will essentially be downstaged or downgraded such that they don’t develop any other problem; I suspect that will be the case in very many patients. However, I suspect there will also be a large proportion that end up requiring additional therapy above and beyond weight loss,” said Dr. Newsome.
The investigators did not report a funding source for the study. Dr. Ohki and colleagues have disclosed no relevant financial relationships. Dr. Newsome has consulted on behalf of his institution with Novo Nordisk, BMS, Gilead, Pfizer, Poxel, and Intercept and has received a grant from Pharmaxis and Boehringer Ingelheim.
A version of this article appeared on Medscape.com.
AT THE LIVER MEETING
MASLD, MASH projected to grow by 23% in the U.S. through 2050
BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.
That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.
“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.
The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.
Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
Validated model
They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.
As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.
The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.
In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.
The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
A “tsunami” of liver disease
In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.
“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.
“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.
Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.
The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.
A version of this article first appeared on Medscape.com.
BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.
That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.
“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.
The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.
Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
Validated model
They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.
As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.
The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.
In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.
The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
A “tsunami” of liver disease
In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.
“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.
“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.
Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.
The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.
A version of this article first appeared on Medscape.com.
BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.
That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.
“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.
The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.
Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
Validated model
They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.
As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.
The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.
In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.
The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
A “tsunami” of liver disease
In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.
“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.
“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.
Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.
The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.
A version of this article first appeared on Medscape.com.
AT THE LIVER MEETING
Test all perinatally exposed infants for HCV: CDC
In utero–exposed infants should be tested at 2-6 months of life, much earlier than the current strategy of testing at 18 months.
HCV infection, which can lead to liver fibrosis and cirrhosis, liver failure, hepatic cancer, and transplant, will develop in 6%-7% of all perinatally exposed infants and children. Curative therapy with direct-acting antivirals can be administered starting at age 3, the CDC noted in Morbidity and Mortality Week Report (MMWR).
About 70% of children 18 months and older are not being tested with the current strategy of anti-HCV testing.
This current MMWR report supplements the 2020 CDC recommendations for adult HCV screening, which includes universal screening among pregnant persons during each pregnancy.
The new recommendations
- Perinatally exposed infants should receive a nucleic acid amplification test for HCV RNA at 2-6 months of age to identify those who might develop chronic HCV infection if not treated.
- Those with detectable HCV RNA should be managed in consultation with an expert in pediatric HCV.
- Infants with undetectable HCV RNA do not require further follow-up unless clinically warranted.
“Testing perinatally exposed infants beginning at age 2 months with a NAT for HCV RNA is cost-effective and allows for earlier linkage to care, appropriate evaluation, and the opportunity to provide curative, life-saving therapy,” the MMWR report said.
A growing problem
The CDC noted that rates of HCV infections during pregnancy are on the rise, corresponding with the ongoing opioid crisis and intravenous drug use.
Yet most perinatally exposed children are not tested for HCV infection and are not referred for hepatitis C care. Reasons might include lack of awareness of perinatal exposure by pediatric providers, lack of regular pediatric care among exposed children, and switching of health care providers before the former recommended testing age of 18 months.
The CDC’s testing recommendation is welcome news to Dawnette A. Lewis, MD, a maternal fetal medicine specialist at Northwell Health in New Hyde Park, N.Y. “As opposed to data for hep B and HIV, we have traditionally had little information and experience regarding the transmission and impact of hep C in pregnant women and their babies. We’ve been having that conversation about the lack of information for some time, and now there’s an opportunity to get evolving data on hep C and how it affects the baby, ” she said.
In her view, mothers will likely be quite accepting of testing for their infants. “It could be integrated into the routine newborn screening panel, so there should not be barriers to accessibility if they’re getting prenatal and neonatal care.”
Commenting on HCV testing for babies in an interview at his institution, Ravi R. Jhaveri, MD, division head of pediatric infectious diseases at Northwestern Medicine’s Ann & Robert H. Lurie Children’s Hospital of Chicago, said, “This is a terrific way to capitalize on the fact that infants already come to the doctor for many visits during the first months of life for their vaccines and their well-child check. And so this should be an easy way to streamline our testing strategy and hopefully lose many fewer patients.”
Northwestern Medicine is an innovative clinic offering HCV testing and treatment outside of clinical trials for pregnant women and their infants with the goal of preventing transmission from mother to child.
Northwestern is launching a clinical trial of treatment for HCV-positive pregnant patients during regular prenatal care. “With very simple treatments similar to taking a prenatal vitamin, it would be easy and seamless to fit into the existing schedule,” said Lyn Yee, MD, a Northwestern maternal-fetal medicine specialist.
Dr. Yee stressed that eliminating hepatitis C will likely be one of the most significant health advancements of the decade.
Dr. Lewis, Dr. Jhaveri, and Dr. Yee had no relevant conflicts of interest to declare with regard to their comments.
In utero–exposed infants should be tested at 2-6 months of life, much earlier than the current strategy of testing at 18 months.
HCV infection, which can lead to liver fibrosis and cirrhosis, liver failure, hepatic cancer, and transplant, will develop in 6%-7% of all perinatally exposed infants and children. Curative therapy with direct-acting antivirals can be administered starting at age 3, the CDC noted in Morbidity and Mortality Week Report (MMWR).
About 70% of children 18 months and older are not being tested with the current strategy of anti-HCV testing.
This current MMWR report supplements the 2020 CDC recommendations for adult HCV screening, which includes universal screening among pregnant persons during each pregnancy.
The new recommendations
- Perinatally exposed infants should receive a nucleic acid amplification test for HCV RNA at 2-6 months of age to identify those who might develop chronic HCV infection if not treated.
- Those with detectable HCV RNA should be managed in consultation with an expert in pediatric HCV.
- Infants with undetectable HCV RNA do not require further follow-up unless clinically warranted.
“Testing perinatally exposed infants beginning at age 2 months with a NAT for HCV RNA is cost-effective and allows for earlier linkage to care, appropriate evaluation, and the opportunity to provide curative, life-saving therapy,” the MMWR report said.
A growing problem
The CDC noted that rates of HCV infections during pregnancy are on the rise, corresponding with the ongoing opioid crisis and intravenous drug use.
Yet most perinatally exposed children are not tested for HCV infection and are not referred for hepatitis C care. Reasons might include lack of awareness of perinatal exposure by pediatric providers, lack of regular pediatric care among exposed children, and switching of health care providers before the former recommended testing age of 18 months.
The CDC’s testing recommendation is welcome news to Dawnette A. Lewis, MD, a maternal fetal medicine specialist at Northwell Health in New Hyde Park, N.Y. “As opposed to data for hep B and HIV, we have traditionally had little information and experience regarding the transmission and impact of hep C in pregnant women and their babies. We’ve been having that conversation about the lack of information for some time, and now there’s an opportunity to get evolving data on hep C and how it affects the baby, ” she said.
In her view, mothers will likely be quite accepting of testing for their infants. “It could be integrated into the routine newborn screening panel, so there should not be barriers to accessibility if they’re getting prenatal and neonatal care.”
Commenting on HCV testing for babies in an interview at his institution, Ravi R. Jhaveri, MD, division head of pediatric infectious diseases at Northwestern Medicine’s Ann & Robert H. Lurie Children’s Hospital of Chicago, said, “This is a terrific way to capitalize on the fact that infants already come to the doctor for many visits during the first months of life for their vaccines and their well-child check. And so this should be an easy way to streamline our testing strategy and hopefully lose many fewer patients.”
Northwestern Medicine is an innovative clinic offering HCV testing and treatment outside of clinical trials for pregnant women and their infants with the goal of preventing transmission from mother to child.
Northwestern is launching a clinical trial of treatment for HCV-positive pregnant patients during regular prenatal care. “With very simple treatments similar to taking a prenatal vitamin, it would be easy and seamless to fit into the existing schedule,” said Lyn Yee, MD, a Northwestern maternal-fetal medicine specialist.
Dr. Yee stressed that eliminating hepatitis C will likely be one of the most significant health advancements of the decade.
Dr. Lewis, Dr. Jhaveri, and Dr. Yee had no relevant conflicts of interest to declare with regard to their comments.
In utero–exposed infants should be tested at 2-6 months of life, much earlier than the current strategy of testing at 18 months.
HCV infection, which can lead to liver fibrosis and cirrhosis, liver failure, hepatic cancer, and transplant, will develop in 6%-7% of all perinatally exposed infants and children. Curative therapy with direct-acting antivirals can be administered starting at age 3, the CDC noted in Morbidity and Mortality Week Report (MMWR).
About 70% of children 18 months and older are not being tested with the current strategy of anti-HCV testing.
This current MMWR report supplements the 2020 CDC recommendations for adult HCV screening, which includes universal screening among pregnant persons during each pregnancy.
The new recommendations
- Perinatally exposed infants should receive a nucleic acid amplification test for HCV RNA at 2-6 months of age to identify those who might develop chronic HCV infection if not treated.
- Those with detectable HCV RNA should be managed in consultation with an expert in pediatric HCV.
- Infants with undetectable HCV RNA do not require further follow-up unless clinically warranted.
“Testing perinatally exposed infants beginning at age 2 months with a NAT for HCV RNA is cost-effective and allows for earlier linkage to care, appropriate evaluation, and the opportunity to provide curative, life-saving therapy,” the MMWR report said.
A growing problem
The CDC noted that rates of HCV infections during pregnancy are on the rise, corresponding with the ongoing opioid crisis and intravenous drug use.
Yet most perinatally exposed children are not tested for HCV infection and are not referred for hepatitis C care. Reasons might include lack of awareness of perinatal exposure by pediatric providers, lack of regular pediatric care among exposed children, and switching of health care providers before the former recommended testing age of 18 months.
The CDC’s testing recommendation is welcome news to Dawnette A. Lewis, MD, a maternal fetal medicine specialist at Northwell Health in New Hyde Park, N.Y. “As opposed to data for hep B and HIV, we have traditionally had little information and experience regarding the transmission and impact of hep C in pregnant women and their babies. We’ve been having that conversation about the lack of information for some time, and now there’s an opportunity to get evolving data on hep C and how it affects the baby, ” she said.
In her view, mothers will likely be quite accepting of testing for their infants. “It could be integrated into the routine newborn screening panel, so there should not be barriers to accessibility if they’re getting prenatal and neonatal care.”
Commenting on HCV testing for babies in an interview at his institution, Ravi R. Jhaveri, MD, division head of pediatric infectious diseases at Northwestern Medicine’s Ann & Robert H. Lurie Children’s Hospital of Chicago, said, “This is a terrific way to capitalize on the fact that infants already come to the doctor for many visits during the first months of life for their vaccines and their well-child check. And so this should be an easy way to streamline our testing strategy and hopefully lose many fewer patients.”
Northwestern Medicine is an innovative clinic offering HCV testing and treatment outside of clinical trials for pregnant women and their infants with the goal of preventing transmission from mother to child.
Northwestern is launching a clinical trial of treatment for HCV-positive pregnant patients during regular prenatal care. “With very simple treatments similar to taking a prenatal vitamin, it would be easy and seamless to fit into the existing schedule,” said Lyn Yee, MD, a Northwestern maternal-fetal medicine specialist.
Dr. Yee stressed that eliminating hepatitis C will likely be one of the most significant health advancements of the decade.
Dr. Lewis, Dr. Jhaveri, and Dr. Yee had no relevant conflicts of interest to declare with regard to their comments.
Tech encourages HIV prevention among women
Access to technology, particularly cellphones, is tied to a higher awareness of pre-exposure prophylaxis (PrEP) in women, according to survey results presented at the Association of Nurses in AIDS Care 2023 Annual Meeting.
Those with limited access to technology, older women, and women who had been incarcerated were also less likely to be aware of their medication options.
Researchers collected responses from 206 women in New York and Philadelphia by computer survey. The women were HIV negative and eligible to receive medication but were not currently taking any.
Most participants were Black (61%) or Hispanic (24%), and the average age of participants was 39 years. Nearly 60% of the group reported they were not aware of PrEP.
Younger women, Hispanic women, women who had not been incarcerated, and women with access to technology were most likely to be aware that they could take medication to prevent HIV.
“Women who utilized their cell phones for activities such as texting, emailing, watching videos, playing games, downloading apps, and accessing social media were more likely to be aware of PrEP,” point out the researchers led by Su Kyung Kim, PhD, WHNP-BC, an assistant professor at Thomas Jefferson University, Philadelphia.
These findings could help direct efforts to increase awareness among women where uptake has remained low, the researchers report. “Mobile technologies, in particular, offer a nimble, customizable, and accessible way to reach this target population and increase awareness of PrEP.”
A version of this article first appeared on Medscape.com.
Access to technology, particularly cellphones, is tied to a higher awareness of pre-exposure prophylaxis (PrEP) in women, according to survey results presented at the Association of Nurses in AIDS Care 2023 Annual Meeting.
Those with limited access to technology, older women, and women who had been incarcerated were also less likely to be aware of their medication options.
Researchers collected responses from 206 women in New York and Philadelphia by computer survey. The women were HIV negative and eligible to receive medication but were not currently taking any.
Most participants were Black (61%) or Hispanic (24%), and the average age of participants was 39 years. Nearly 60% of the group reported they were not aware of PrEP.
Younger women, Hispanic women, women who had not been incarcerated, and women with access to technology were most likely to be aware that they could take medication to prevent HIV.
“Women who utilized their cell phones for activities such as texting, emailing, watching videos, playing games, downloading apps, and accessing social media were more likely to be aware of PrEP,” point out the researchers led by Su Kyung Kim, PhD, WHNP-BC, an assistant professor at Thomas Jefferson University, Philadelphia.
These findings could help direct efforts to increase awareness among women where uptake has remained low, the researchers report. “Mobile technologies, in particular, offer a nimble, customizable, and accessible way to reach this target population and increase awareness of PrEP.”
A version of this article first appeared on Medscape.com.
Access to technology, particularly cellphones, is tied to a higher awareness of pre-exposure prophylaxis (PrEP) in women, according to survey results presented at the Association of Nurses in AIDS Care 2023 Annual Meeting.
Those with limited access to technology, older women, and women who had been incarcerated were also less likely to be aware of their medication options.
Researchers collected responses from 206 women in New York and Philadelphia by computer survey. The women were HIV negative and eligible to receive medication but were not currently taking any.
Most participants were Black (61%) or Hispanic (24%), and the average age of participants was 39 years. Nearly 60% of the group reported they were not aware of PrEP.
Younger women, Hispanic women, women who had not been incarcerated, and women with access to technology were most likely to be aware that they could take medication to prevent HIV.
“Women who utilized their cell phones for activities such as texting, emailing, watching videos, playing games, downloading apps, and accessing social media were more likely to be aware of PrEP,” point out the researchers led by Su Kyung Kim, PhD, WHNP-BC, an assistant professor at Thomas Jefferson University, Philadelphia.
These findings could help direct efforts to increase awareness among women where uptake has remained low, the researchers report. “Mobile technologies, in particular, offer a nimble, customizable, and accessible way to reach this target population and increase awareness of PrEP.”
A version of this article first appeared on Medscape.com.
MASLD linked to increased risk for various clinical outcomes
TOPLINE:
Metabolic dysfunction–associated steatotic liver disease (MASLD) significantly raises the risk for cardiovascular, metabolic, oncologic, and other outcomes, a new meta-analysis suggests.
METHODOLOGY:
- Researchers conducted a comprehensive meta-analysis of studies to investigate longitudinal clinical outcomes associated with MASLD, previously known as nonalcoholic fatty liver disease.
- They identified 129 original studies that evaluated the longitudinal risks for incident clinical outcomes in patients with MASLD vs those without the disease.
- Investigators calculated pooled risk estimates for clinical outcomes in patients with MASLD and those without MASLD, with MASLD being diagnosed by imaging, biopsy, blood tests, or ICD codes.
TAKEAWAY:
- MASLD was associated with a significant increased risk for cardiovascular disease outcomes (hazard ratio, 1.43), metabolic outcomes such as incident hypertension (HR, 1.75), prediabetes (HR, 1.69), diabetes (HR, 2.56), metabolic syndrome (HR, 2.57), chronic kidney disease (HR, 1.38), and various liver-related outcomes (HR, 3.92).
- Patients with advanced MASLD had a significantly greater risk (P = .02) of developing diabetes than did their peers with less severe MASLD (HR, 1.63), compared with persons without MASLD.
- MASLD was also associated with all cancers (HR, 1.54); the highest risk was seen for hepatocellular carcinoma (HR, 4.37).
- Subgroup analyses stratified by sex found no significant differences in the risks observed between men and women with MASLD.
IN PRACTICE:
“It is imperative to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to recognition and treatment beyond that of the hepatologist alone,” the authors wrote. “The growing prevalence of MASLD will remain a major global health threat that requires effective disease management frameworks to be put in place.”
SOURCE:
The study, with co–first authors Kai En Chan and Elden Yen Hng Ong, National University of Singapore, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The results depend on the validity of the original studies, and residual confounding factors may have biased the reported results. The study is also limited in its inclusion of large population-based studies using ICD codes that may result in misclassification bias. There was no examination of longitudinal outcomes in patients with histologically confirmed MASLD.
DISCLOSURES:
The study had no funding. Some authors reported research support, consulting fees, or stock options from pharmaceutical companies.
A version of this article appeared on Medscape.com.
TOPLINE:
Metabolic dysfunction–associated steatotic liver disease (MASLD) significantly raises the risk for cardiovascular, metabolic, oncologic, and other outcomes, a new meta-analysis suggests.
METHODOLOGY:
- Researchers conducted a comprehensive meta-analysis of studies to investigate longitudinal clinical outcomes associated with MASLD, previously known as nonalcoholic fatty liver disease.
- They identified 129 original studies that evaluated the longitudinal risks for incident clinical outcomes in patients with MASLD vs those without the disease.
- Investigators calculated pooled risk estimates for clinical outcomes in patients with MASLD and those without MASLD, with MASLD being diagnosed by imaging, biopsy, blood tests, or ICD codes.
TAKEAWAY:
- MASLD was associated with a significant increased risk for cardiovascular disease outcomes (hazard ratio, 1.43), metabolic outcomes such as incident hypertension (HR, 1.75), prediabetes (HR, 1.69), diabetes (HR, 2.56), metabolic syndrome (HR, 2.57), chronic kidney disease (HR, 1.38), and various liver-related outcomes (HR, 3.92).
- Patients with advanced MASLD had a significantly greater risk (P = .02) of developing diabetes than did their peers with less severe MASLD (HR, 1.63), compared with persons without MASLD.
- MASLD was also associated with all cancers (HR, 1.54); the highest risk was seen for hepatocellular carcinoma (HR, 4.37).
- Subgroup analyses stratified by sex found no significant differences in the risks observed between men and women with MASLD.
IN PRACTICE:
“It is imperative to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to recognition and treatment beyond that of the hepatologist alone,” the authors wrote. “The growing prevalence of MASLD will remain a major global health threat that requires effective disease management frameworks to be put in place.”
SOURCE:
The study, with co–first authors Kai En Chan and Elden Yen Hng Ong, National University of Singapore, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The results depend on the validity of the original studies, and residual confounding factors may have biased the reported results. The study is also limited in its inclusion of large population-based studies using ICD codes that may result in misclassification bias. There was no examination of longitudinal outcomes in patients with histologically confirmed MASLD.
DISCLOSURES:
The study had no funding. Some authors reported research support, consulting fees, or stock options from pharmaceutical companies.
A version of this article appeared on Medscape.com.
TOPLINE:
Metabolic dysfunction–associated steatotic liver disease (MASLD) significantly raises the risk for cardiovascular, metabolic, oncologic, and other outcomes, a new meta-analysis suggests.
METHODOLOGY:
- Researchers conducted a comprehensive meta-analysis of studies to investigate longitudinal clinical outcomes associated with MASLD, previously known as nonalcoholic fatty liver disease.
- They identified 129 original studies that evaluated the longitudinal risks for incident clinical outcomes in patients with MASLD vs those without the disease.
- Investigators calculated pooled risk estimates for clinical outcomes in patients with MASLD and those without MASLD, with MASLD being diagnosed by imaging, biopsy, blood tests, or ICD codes.
TAKEAWAY:
- MASLD was associated with a significant increased risk for cardiovascular disease outcomes (hazard ratio, 1.43), metabolic outcomes such as incident hypertension (HR, 1.75), prediabetes (HR, 1.69), diabetes (HR, 2.56), metabolic syndrome (HR, 2.57), chronic kidney disease (HR, 1.38), and various liver-related outcomes (HR, 3.92).
- Patients with advanced MASLD had a significantly greater risk (P = .02) of developing diabetes than did their peers with less severe MASLD (HR, 1.63), compared with persons without MASLD.
- MASLD was also associated with all cancers (HR, 1.54); the highest risk was seen for hepatocellular carcinoma (HR, 4.37).
- Subgroup analyses stratified by sex found no significant differences in the risks observed between men and women with MASLD.
IN PRACTICE:
“It is imperative to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to recognition and treatment beyond that of the hepatologist alone,” the authors wrote. “The growing prevalence of MASLD will remain a major global health threat that requires effective disease management frameworks to be put in place.”
SOURCE:
The study, with co–first authors Kai En Chan and Elden Yen Hng Ong, National University of Singapore, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The results depend on the validity of the original studies, and residual confounding factors may have biased the reported results. The study is also limited in its inclusion of large population-based studies using ICD codes that may result in misclassification bias. There was no examination of longitudinal outcomes in patients with histologically confirmed MASLD.
DISCLOSURES:
The study had no funding. Some authors reported research support, consulting fees, or stock options from pharmaceutical companies.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY