Hepatology

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

Replacing meat with plant-based proteins for just one meal reduced ammonia levels in patients with cirrhosis, a proof-of-concept study showed.

High levels of serum ammonia after protein loads may predict poor outcomes, including hepatic encephalopathy (HE), in patients with cirrhosis, whereas vegetable protein diets are associated with decreased serum ammonia, according to Jasmohan Bajaj, MD, a gastroenterologist at Virginia Commonwealth University School of Medicine and the Richmond VA Medical Center, Richmond, Virginia, and colleagues.

However, changing from meat-based to non–meat-based meals is difficult to do over a long period.

“Previous studies have changed people’s diets completely, expecting them to be on a meatless or vegetarian diet with a similar amount of protein when they’ve been eating meat their entire life,” Dr. Bajaj told this news organization. “That’s not really sustainable in the long run.”

“Our hope is that occasional meal substitutions would be beneficial,” he said. “This study is a first step toward seeing if that works.”

The study was published online on May 2 in Clinical and Translational Gastroenterology.

Meal Type Affects Ammonia Levels Differently

The researchers randomized 30 men with cirrhosis and on a traditional Western meat-based diet into three groups, where they received a pork/beef burger, a vegetarian bean burger, or a burger made of vegan meat substitute. The burgers provided 20 g of protein each, and all meals contained low-fat potato chips, a whole-grain bun, water, and no condiments.

The participants’ median age was 66 years in the meat and vegetarian arms and 71 years in the vegan arm. About half had diabetes, and half had prior HE and were evenly distributed across the treatment arms. Cirrhosis etiologies included hepatitis C virus infection, alcohol, and metabolic-associated steatohepatitis.

Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between and within groups.

In the 3 days prior to the intervention, participants had similar intakes of red meat, poultry, fish, eggs, bread, cheese, rice, fruits, vegetables, yogurt, coffee, tea, and carbonated caffeinated and decaffeinated beverages.

Blood for metabolomics and ammonia was drawn at baseline and hourly for 3 hours post-meal while patients were under observation. All participants completed the entire meal, as shown subsequently by markers of food consumption, and none developed HE symptoms during the observation period.

The composition of the stool microbiome was similar at baseline across groups and remained unchanged. However, serum ammonia increased from baseline in the meat group but not in the vegetarian or vegan groups. The serum microbiome was not analyzed because of the low yield.

Serum metabolomics showed beneficial changes over time associated with branched-chain amino acid metabolism and urea cycle, phospholipid, and acylcarnitine levels in the vegetarian and vegan meal groups compared with the meat-based group.

In contrast, alterations in lipid profiles (higher sphingomyelins and lower lysophospholipids) were seen in the meat group.

The study was limited by its relatively small sample size, focus on the impact of only one meal, and lack of clinical outcomes, sarcopenia assessment, cognitive testing, or urine collection.

“Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis,” the authors concluded.

The next step “is to substitute one meal two or three times a week, so we can move forward with this analysis and eventually be able to show that the liver is in better shape,” Dr. Bajaj said.

Meanwhile, clinicians should encourage patients with liver disease who eat meat regularly to try to substitute it with protein from plant or dairy sources, at least occasionally, he said. When doing so, “clinicians should ask their patients’ preferences before assuming that they will do everything that you ask them to do because nutrition in cirrhosis is really critical — not only what they eat but also when they eat. Working with a dietitian, like we did in our study, is critical, or at least having access to one if you don’t have one in your practice.”

Positive Results From a Simple Change

Commenting on the study, Nancy S. Reau, MD, section chief, hepatology and associate director of organ transplantation at Rush Medical College in Chicago, said, “My biggest concern is making sure patients are ingesting enough quality protein and calories because anorexia is a common complication in cirrhosis, and sarcopenia is associated with poor outcomes.

“You don’t want to suggest a change that will result in eating less or skipping a meal,” she said. So, “it is encouraging to see that suggesting a small change, just one meal a day, that may not impact calorie intake could have positive results.”

Dr. Reau added that “it is great to see evidence that this small change also could be a way of decreasing the risk of HE while not compromising on patient nutrition.”

Larger studies with outcome data showing that this approach could prevent readmission in patients hospitalized for HE would be helpful, she said.

The study was partly supported by the ACG Clinical Research Award, VA Merit Review 2I01CX001076, I01CX002472, and NIAAA RO1AA29398. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
 

A version of this article appeared on Medscape.com.

Replacing meat with plant-based proteins for just one meal reduced ammonia levels in patients with cirrhosis, a proof-of-concept study showed.

High levels of serum ammonia after protein loads may predict poor outcomes, including hepatic encephalopathy (HE), in patients with cirrhosis, whereas vegetable protein diets are associated with decreased serum ammonia, according to Jasmohan Bajaj, MD, a gastroenterologist at Virginia Commonwealth University School of Medicine and the Richmond VA Medical Center, Richmond, Virginia, and colleagues.

However, changing from meat-based to non–meat-based meals is difficult to do over a long period.

“Previous studies have changed people’s diets completely, expecting them to be on a meatless or vegetarian diet with a similar amount of protein when they’ve been eating meat their entire life,” Dr. Bajaj told this news organization. “That’s not really sustainable in the long run.”

“Our hope is that occasional meal substitutions would be beneficial,” he said. “This study is a first step toward seeing if that works.”

The study was published online on May 2 in Clinical and Translational Gastroenterology.

Meal Type Affects Ammonia Levels Differently

The researchers randomized 30 men with cirrhosis and on a traditional Western meat-based diet into three groups, where they received a pork/beef burger, a vegetarian bean burger, or a burger made of vegan meat substitute. The burgers provided 20 g of protein each, and all meals contained low-fat potato chips, a whole-grain bun, water, and no condiments.

The participants’ median age was 66 years in the meat and vegetarian arms and 71 years in the vegan arm. About half had diabetes, and half had prior HE and were evenly distributed across the treatment arms. Cirrhosis etiologies included hepatitis C virus infection, alcohol, and metabolic-associated steatohepatitis.

Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between and within groups.

In the 3 days prior to the intervention, participants had similar intakes of red meat, poultry, fish, eggs, bread, cheese, rice, fruits, vegetables, yogurt, coffee, tea, and carbonated caffeinated and decaffeinated beverages.

Blood for metabolomics and ammonia was drawn at baseline and hourly for 3 hours post-meal while patients were under observation. All participants completed the entire meal, as shown subsequently by markers of food consumption, and none developed HE symptoms during the observation period.

The composition of the stool microbiome was similar at baseline across groups and remained unchanged. However, serum ammonia increased from baseline in the meat group but not in the vegetarian or vegan groups. The serum microbiome was not analyzed because of the low yield.

Serum metabolomics showed beneficial changes over time associated with branched-chain amino acid metabolism and urea cycle, phospholipid, and acylcarnitine levels in the vegetarian and vegan meal groups compared with the meat-based group.

In contrast, alterations in lipid profiles (higher sphingomyelins and lower lysophospholipids) were seen in the meat group.

The study was limited by its relatively small sample size, focus on the impact of only one meal, and lack of clinical outcomes, sarcopenia assessment, cognitive testing, or urine collection.

“Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis,” the authors concluded.

The next step “is to substitute one meal two or three times a week, so we can move forward with this analysis and eventually be able to show that the liver is in better shape,” Dr. Bajaj said.

Meanwhile, clinicians should encourage patients with liver disease who eat meat regularly to try to substitute it with protein from plant or dairy sources, at least occasionally, he said. When doing so, “clinicians should ask their patients’ preferences before assuming that they will do everything that you ask them to do because nutrition in cirrhosis is really critical — not only what they eat but also when they eat. Working with a dietitian, like we did in our study, is critical, or at least having access to one if you don’t have one in your practice.”

Positive Results From a Simple Change

Commenting on the study, Nancy S. Reau, MD, section chief, hepatology and associate director of organ transplantation at Rush Medical College in Chicago, said, “My biggest concern is making sure patients are ingesting enough quality protein and calories because anorexia is a common complication in cirrhosis, and sarcopenia is associated with poor outcomes.

“You don’t want to suggest a change that will result in eating less or skipping a meal,” she said. So, “it is encouraging to see that suggesting a small change, just one meal a day, that may not impact calorie intake could have positive results.”

Dr. Reau added that “it is great to see evidence that this small change also could be a way of decreasing the risk of HE while not compromising on patient nutrition.”

Larger studies with outcome data showing that this approach could prevent readmission in patients hospitalized for HE would be helpful, she said.

The study was partly supported by the ACG Clinical Research Award, VA Merit Review 2I01CX001076, I01CX002472, and NIAAA RO1AA29398. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
 

A version of this article appeared on Medscape.com.

Replacing meat with plant-based proteins for just one meal reduced ammonia levels in patients with cirrhosis, a proof-of-concept study showed.

High levels of serum ammonia after protein loads may predict poor outcomes, including hepatic encephalopathy (HE), in patients with cirrhosis, whereas vegetable protein diets are associated with decreased serum ammonia, according to Jasmohan Bajaj, MD, a gastroenterologist at Virginia Commonwealth University School of Medicine and the Richmond VA Medical Center, Richmond, Virginia, and colleagues.

However, changing from meat-based to non–meat-based meals is difficult to do over a long period.

“Previous studies have changed people’s diets completely, expecting them to be on a meatless or vegetarian diet with a similar amount of protein when they’ve been eating meat their entire life,” Dr. Bajaj told this news organization. “That’s not really sustainable in the long run.”

“Our hope is that occasional meal substitutions would be beneficial,” he said. “This study is a first step toward seeing if that works.”

The study was published online on May 2 in Clinical and Translational Gastroenterology.

Meal Type Affects Ammonia Levels Differently

The researchers randomized 30 men with cirrhosis and on a traditional Western meat-based diet into three groups, where they received a pork/beef burger, a vegetarian bean burger, or a burger made of vegan meat substitute. The burgers provided 20 g of protein each, and all meals contained low-fat potato chips, a whole-grain bun, water, and no condiments.

The participants’ median age was 66 years in the meat and vegetarian arms and 71 years in the vegan arm. About half had diabetes, and half had prior HE and were evenly distributed across the treatment arms. Cirrhosis etiologies included hepatitis C virus infection, alcohol, and metabolic-associated steatohepatitis.

Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between and within groups.

In the 3 days prior to the intervention, participants had similar intakes of red meat, poultry, fish, eggs, bread, cheese, rice, fruits, vegetables, yogurt, coffee, tea, and carbonated caffeinated and decaffeinated beverages.

Blood for metabolomics and ammonia was drawn at baseline and hourly for 3 hours post-meal while patients were under observation. All participants completed the entire meal, as shown subsequently by markers of food consumption, and none developed HE symptoms during the observation period.

The composition of the stool microbiome was similar at baseline across groups and remained unchanged. However, serum ammonia increased from baseline in the meat group but not in the vegetarian or vegan groups. The serum microbiome was not analyzed because of the low yield.

Serum metabolomics showed beneficial changes over time associated with branched-chain amino acid metabolism and urea cycle, phospholipid, and acylcarnitine levels in the vegetarian and vegan meal groups compared with the meat-based group.

In contrast, alterations in lipid profiles (higher sphingomyelins and lower lysophospholipids) were seen in the meat group.

The study was limited by its relatively small sample size, focus on the impact of only one meal, and lack of clinical outcomes, sarcopenia assessment, cognitive testing, or urine collection.

“Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis,” the authors concluded.

The next step “is to substitute one meal two or three times a week, so we can move forward with this analysis and eventually be able to show that the liver is in better shape,” Dr. Bajaj said.

Meanwhile, clinicians should encourage patients with liver disease who eat meat regularly to try to substitute it with protein from plant or dairy sources, at least occasionally, he said. When doing so, “clinicians should ask their patients’ preferences before assuming that they will do everything that you ask them to do because nutrition in cirrhosis is really critical — not only what they eat but also when they eat. Working with a dietitian, like we did in our study, is critical, or at least having access to one if you don’t have one in your practice.”

Positive Results From a Simple Change

Commenting on the study, Nancy S. Reau, MD, section chief, hepatology and associate director of organ transplantation at Rush Medical College in Chicago, said, “My biggest concern is making sure patients are ingesting enough quality protein and calories because anorexia is a common complication in cirrhosis, and sarcopenia is associated with poor outcomes.

“You don’t want to suggest a change that will result in eating less or skipping a meal,” she said. So, “it is encouraging to see that suggesting a small change, just one meal a day, that may not impact calorie intake could have positive results.”

Dr. Reau added that “it is great to see evidence that this small change also could be a way of decreasing the risk of HE while not compromising on patient nutrition.”

Larger studies with outcome data showing that this approach could prevent readmission in patients hospitalized for HE would be helpful, she said.

The study was partly supported by the ACG Clinical Research Award, VA Merit Review 2I01CX001076, I01CX002472, and NIAAA RO1AA29398. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
 

A version of this article appeared on Medscape.com.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) this week recommended new contraindications on the coadministration of the protease inhibitor atazanavir (Reyataz, Bristol-Myers Squibb) with antineoplastic agents encorafenib and ivosidenib (atazanavir may significantly increase blood levels and thus side effects), and with the anticonvulsants carbamazepine, phenobarbital, and phenytoin (which may decrease serum levels of atazanavir). 

The new rules alter sections 4.3 and 4.5 of the summary of product characteristics (SmPC) to reclassify drug–drug interactions with the new contraindications.

Atazanavir is an orally administered drug, used in combination with low-dose ritonavir (Norvir) to boost its pharmacokinetics. It is indicated for the treatment of HIV-1 infected adults and pediatric patients 3 months of age and older in combination with other antiretroviral medicinal products. A combination preparation boosted with cobicistat (Evotaz) is also available.

The drug is an azapeptide HIV-1 protease inhibitor (PI) that selectively inhibits the virus-specific processing of viral Gag-Pol proteins in HIV-1 infected cells, thus preventing formation of mature virions and infection of other cells. This prevents the virus from multiplying and slows the spread of infection. Based on available virological and clinical data from adult patients, no benefit is expected in patients with HIV strains resistant to multiple protease inhibitors (four or more PI mutations).

Therapy with atazanavir is intended to be initiated by a physician experienced in the management of HIV infection, with the choice of atazanavir in treatment-experienced adult and pediatric patients based on individual viral resistance testing and the patient’s treatment history. The standard dose is 300 mg atazanavir taken with 100 mg ritonavir once daily with food.

Atazanavir is already contraindicated in combination or coadministration with a wide variety of other agents:

• Coadministration with simvastatin or lovastatin [statins – risk of increased blood levels with atazanavir].
• Combination with the anti-TB antibiotic rifampicin.
• Combination with the PDE5 inhibitor sildenafil when used for the treatment of pulmonary arterial hypertension only.
• Coadministration with substrates of the CYP3A4 isoform of cytochrome P450 that have narrow therapeutic windows (eg, quetiapine, lurasidone, alfuzosin, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, triazolam, oral midazolam, lomitapide, and ergot alkaloids).
• Coadministration with grazoprevir-containing products, including elbasvir/grazoprevir fixed dose combination (hepatitis C drug combination; atazanavir increases its blood levels).
• Coadministration with glecaprevir/pibrentasvir fixed dose combination (hepatitis C drug combination; increased hepatotoxicity due to increased bilirubin concentration).
• Coadministration with products containing St. John’s wort (Hypericum perforatum).

The EMA said detailed recommendations for the use of atazanavir will be described in the updated SmPC, which will be published in the revised European public assessment report after a decision on this change to the marketing authorization has been granted by the European Commission.

A version of this article appeared on Medscape.com.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) this week recommended new contraindications on the coadministration of the protease inhibitor atazanavir (Reyataz, Bristol-Myers Squibb) with antineoplastic agents encorafenib and ivosidenib (atazanavir may significantly increase blood levels and thus side effects), and with the anticonvulsants carbamazepine, phenobarbital, and phenytoin (which may decrease serum levels of atazanavir). 

The new rules alter sections 4.3 and 4.5 of the summary of product characteristics (SmPC) to reclassify drug–drug interactions with the new contraindications.

Atazanavir is an orally administered drug, used in combination with low-dose ritonavir (Norvir) to boost its pharmacokinetics. It is indicated for the treatment of HIV-1 infected adults and pediatric patients 3 months of age and older in combination with other antiretroviral medicinal products. A combination preparation boosted with cobicistat (Evotaz) is also available.

The drug is an azapeptide HIV-1 protease inhibitor (PI) that selectively inhibits the virus-specific processing of viral Gag-Pol proteins in HIV-1 infected cells, thus preventing formation of mature virions and infection of other cells. This prevents the virus from multiplying and slows the spread of infection. Based on available virological and clinical data from adult patients, no benefit is expected in patients with HIV strains resistant to multiple protease inhibitors (four or more PI mutations).

Therapy with atazanavir is intended to be initiated by a physician experienced in the management of HIV infection, with the choice of atazanavir in treatment-experienced adult and pediatric patients based on individual viral resistance testing and the patient’s treatment history. The standard dose is 300 mg atazanavir taken with 100 mg ritonavir once daily with food.

Atazanavir is already contraindicated in combination or coadministration with a wide variety of other agents:

• Coadministration with simvastatin or lovastatin [statins – risk of increased blood levels with atazanavir].
• Combination with the anti-TB antibiotic rifampicin.
• Combination with the PDE5 inhibitor sildenafil when used for the treatment of pulmonary arterial hypertension only.
• Coadministration with substrates of the CYP3A4 isoform of cytochrome P450 that have narrow therapeutic windows (eg, quetiapine, lurasidone, alfuzosin, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, triazolam, oral midazolam, lomitapide, and ergot alkaloids).
• Coadministration with grazoprevir-containing products, including elbasvir/grazoprevir fixed dose combination (hepatitis C drug combination; atazanavir increases its blood levels).
• Coadministration with glecaprevir/pibrentasvir fixed dose combination (hepatitis C drug combination; increased hepatotoxicity due to increased bilirubin concentration).
• Coadministration with products containing St. John’s wort (Hypericum perforatum).

The EMA said detailed recommendations for the use of atazanavir will be described in the updated SmPC, which will be published in the revised European public assessment report after a decision on this change to the marketing authorization has been granted by the European Commission.

A version of this article appeared on Medscape.com.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) this week recommended new contraindications on the coadministration of the protease inhibitor atazanavir (Reyataz, Bristol-Myers Squibb) with antineoplastic agents encorafenib and ivosidenib (atazanavir may significantly increase blood levels and thus side effects), and with the anticonvulsants carbamazepine, phenobarbital, and phenytoin (which may decrease serum levels of atazanavir). 

The new rules alter sections 4.3 and 4.5 of the summary of product characteristics (SmPC) to reclassify drug–drug interactions with the new contraindications.

Atazanavir is an orally administered drug, used in combination with low-dose ritonavir (Norvir) to boost its pharmacokinetics. It is indicated for the treatment of HIV-1 infected adults and pediatric patients 3 months of age and older in combination with other antiretroviral medicinal products. A combination preparation boosted with cobicistat (Evotaz) is also available.

The drug is an azapeptide HIV-1 protease inhibitor (PI) that selectively inhibits the virus-specific processing of viral Gag-Pol proteins in HIV-1 infected cells, thus preventing formation of mature virions and infection of other cells. This prevents the virus from multiplying and slows the spread of infection. Based on available virological and clinical data from adult patients, no benefit is expected in patients with HIV strains resistant to multiple protease inhibitors (four or more PI mutations).

Therapy with atazanavir is intended to be initiated by a physician experienced in the management of HIV infection, with the choice of atazanavir in treatment-experienced adult and pediatric patients based on individual viral resistance testing and the patient’s treatment history. The standard dose is 300 mg atazanavir taken with 100 mg ritonavir once daily with food.

Atazanavir is already contraindicated in combination or coadministration with a wide variety of other agents:

• Coadministration with simvastatin or lovastatin [statins – risk of increased blood levels with atazanavir].
• Combination with the anti-TB antibiotic rifampicin.
• Combination with the PDE5 inhibitor sildenafil when used for the treatment of pulmonary arterial hypertension only.
• Coadministration with substrates of the CYP3A4 isoform of cytochrome P450 that have narrow therapeutic windows (eg, quetiapine, lurasidone, alfuzosin, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, triazolam, oral midazolam, lomitapide, and ergot alkaloids).
• Coadministration with grazoprevir-containing products, including elbasvir/grazoprevir fixed dose combination (hepatitis C drug combination; atazanavir increases its blood levels).
• Coadministration with glecaprevir/pibrentasvir fixed dose combination (hepatitis C drug combination; increased hepatotoxicity due to increased bilirubin concentration).
• Coadministration with products containing St. John’s wort (Hypericum perforatum).

The EMA said detailed recommendations for the use of atazanavir will be described in the updated SmPC, which will be published in the revised European public assessment report after a decision on this change to the marketing authorization has been granted by the European Commission.

A version of this article appeared on Medscape.com.

Probiotics appear to be beneficial for patients with cirrhosis, showing a reversal of hepatic encephalopathy (HE), improvement in liver function measures, and regulation of gut dysbiosis, according to a systematic review and meta-analysis.

They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.

“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.

“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”

The study was published online in Frontiers in Medicine .
 

Analyzing Probiotic Trials

The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.

The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.

Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.

In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.

Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.

Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).

Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.

“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
 

Considering Variables

The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.

“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.

“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”

Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.

“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”

However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.

“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.

The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.

A version of this article appeared on Medscape.com .

Probiotics appear to be beneficial for patients with cirrhosis, showing a reversal of hepatic encephalopathy (HE), improvement in liver function measures, and regulation of gut dysbiosis, according to a systematic review and meta-analysis.

They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.

“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.

“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”

The study was published online in Frontiers in Medicine .
 

Analyzing Probiotic Trials

The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.

The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.

Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.

In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.

Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.

Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).

Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.

“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
 

Considering Variables

The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.

“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.

“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”

Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.

“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”

However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.

“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.

The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.

A version of this article appeared on Medscape.com .

Probiotics appear to be beneficial for patients with cirrhosis, showing a reversal of hepatic encephalopathy (HE), improvement in liver function measures, and regulation of gut dysbiosis, according to a systematic review and meta-analysis.

They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.

“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.

“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”

The study was published online in Frontiers in Medicine .
 

Analyzing Probiotic Trials

The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.

The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.

Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.

In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.

Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.

Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).

Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.

“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
 

Considering Variables

The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.

“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.

“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”

Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.

“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”

However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.

“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.

The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.

A version of this article appeared on Medscape.com .

TOPLINE:

Metabolic dysfunction-associated steatotic liver disease (MASLD) co-occurring with HIV infection does not appear to increase the risk for cirrhosis or hepatocellular carcinoma (HCC) compared with MASLD alone. However, the incidence of major adverse cardiovascular events (MACE) is significantly increased among patients with MASLD and HIV, a large study suggested.

METHODOLOGY:

• MASLD is highly prevalent in people living with HIV, but the impact of HIV on liver and cardiovascular disease (CVD) outcomes in people with MASLD remains unclear.
• To investigate, researchers created a propensity score-matched cohort of veterans with noncirrhotic MASLD, with and without HIV (920 patients in each group).
• They evaluated the incidence of cirrhosis, HCC, and MACE, as well as overall survival, among the two groups. They also assessed these outcomes in MASLD patients with HIV on the basis of whether they were on antiretroviral therapy (ART).

TAKEAWAY:

• During a median follow-up of 10.4 years in the MASLD with HIV group and 11.8 years in the MASLD-only group, the overall incidence of cirrhosis and HCC was similar in MASLD with vs without HIV (cirrhosis: 0.97 vs 1.06 per 100 person-years, P = .54; HCC: 0.26 vs 0.17 per 100,000 person-years, P = .23), regardless of ART use.

• In contrast, the incidence of MACE was significantly higher in MASLD with vs without HIV (5.18 vs 4.48 per 100 person-years, P = .03). The incidence also was higher in patients with MASLD and HIV who were not on ART compared with those on ART (5.83 vs 4.7 per 100 person-years, P = .07).

• Compared with MASLD without HIV, the overall 5-year survival was significantly lower in MASLD with HIV (91.3% vs 85.7%). In MASLD with HIV, receipt of ART was associated with a significantly higher 5-year survival than no ART (87.4% vs 81.6%).

IN PRACTICE:

“Ensuring timely and appropriate initiation of HIV treatment is critical in patients with MASLD who have concurrent HIV infection, as well as optimizing metabolic comorbidities that may also contribute to increased risks of CVD and increased mortality,” the authors wrote.

SOURCE:

The study, led by Robert J. Wong, MD, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study cohort consisted predominantly of older men, which may limit generalizability to women and younger populations. Metabolic comorbidities are more common in veterans compared with the general population, potentially affecting the generalizability of the CVD risk findings.

DISCLOSURES:

The study was supported by an investigator-initiated research grant from Theratechnologies. Wong has received funding for his institution from Gilead Sciences, Exact Sciences, and Durect Corporation and has served as a consultant for Gilead Sciences.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Metabolic dysfunction-associated steatotic liver disease (MASLD) co-occurring with HIV infection does not appear to increase the risk for cirrhosis or hepatocellular carcinoma (HCC) compared with MASLD alone. However, the incidence of major adverse cardiovascular events (MACE) is significantly increased among patients with MASLD and HIV, a large study suggested.

METHODOLOGY:

• MASLD is highly prevalent in people living with HIV, but the impact of HIV on liver and cardiovascular disease (CVD) outcomes in people with MASLD remains unclear.
• To investigate, researchers created a propensity score-matched cohort of veterans with noncirrhotic MASLD, with and without HIV (920 patients in each group).
• They evaluated the incidence of cirrhosis, HCC, and MACE, as well as overall survival, among the two groups. They also assessed these outcomes in MASLD patients with HIV on the basis of whether they were on antiretroviral therapy (ART).

TAKEAWAY:

• During a median follow-up of 10.4 years in the MASLD with HIV group and 11.8 years in the MASLD-only group, the overall incidence of cirrhosis and HCC was similar in MASLD with vs without HIV (cirrhosis: 0.97 vs 1.06 per 100 person-years, P = .54; HCC: 0.26 vs 0.17 per 100,000 person-years, P = .23), regardless of ART use.

• In contrast, the incidence of MACE was significantly higher in MASLD with vs without HIV (5.18 vs 4.48 per 100 person-years, P = .03). The incidence also was higher in patients with MASLD and HIV who were not on ART compared with those on ART (5.83 vs 4.7 per 100 person-years, P = .07).

• Compared with MASLD without HIV, the overall 5-year survival was significantly lower in MASLD with HIV (91.3% vs 85.7%). In MASLD with HIV, receipt of ART was associated with a significantly higher 5-year survival than no ART (87.4% vs 81.6%).

IN PRACTICE:

“Ensuring timely and appropriate initiation of HIV treatment is critical in patients with MASLD who have concurrent HIV infection, as well as optimizing metabolic comorbidities that may also contribute to increased risks of CVD and increased mortality,” the authors wrote.

SOURCE:

The study, led by Robert J. Wong, MD, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study cohort consisted predominantly of older men, which may limit generalizability to women and younger populations. Metabolic comorbidities are more common in veterans compared with the general population, potentially affecting the generalizability of the CVD risk findings.

DISCLOSURES:

The study was supported by an investigator-initiated research grant from Theratechnologies. Wong has received funding for his institution from Gilead Sciences, Exact Sciences, and Durect Corporation and has served as a consultant for Gilead Sciences.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Metabolic dysfunction-associated steatotic liver disease (MASLD) co-occurring with HIV infection does not appear to increase the risk for cirrhosis or hepatocellular carcinoma (HCC) compared with MASLD alone. However, the incidence of major adverse cardiovascular events (MACE) is significantly increased among patients with MASLD and HIV, a large study suggested.

METHODOLOGY:

• MASLD is highly prevalent in people living with HIV, but the impact of HIV on liver and cardiovascular disease (CVD) outcomes in people with MASLD remains unclear.
• To investigate, researchers created a propensity score-matched cohort of veterans with noncirrhotic MASLD, with and without HIV (920 patients in each group).
• They evaluated the incidence of cirrhosis, HCC, and MACE, as well as overall survival, among the two groups. They also assessed these outcomes in MASLD patients with HIV on the basis of whether they were on antiretroviral therapy (ART).

TAKEAWAY:

• During a median follow-up of 10.4 years in the MASLD with HIV group and 11.8 years in the MASLD-only group, the overall incidence of cirrhosis and HCC was similar in MASLD with vs without HIV (cirrhosis: 0.97 vs 1.06 per 100 person-years, P = .54; HCC: 0.26 vs 0.17 per 100,000 person-years, P = .23), regardless of ART use.

• In contrast, the incidence of MACE was significantly higher in MASLD with vs without HIV (5.18 vs 4.48 per 100 person-years, P = .03). The incidence also was higher in patients with MASLD and HIV who were not on ART compared with those on ART (5.83 vs 4.7 per 100 person-years, P = .07).

• Compared with MASLD without HIV, the overall 5-year survival was significantly lower in MASLD with HIV (91.3% vs 85.7%). In MASLD with HIV, receipt of ART was associated with a significantly higher 5-year survival than no ART (87.4% vs 81.6%).

IN PRACTICE:

“Ensuring timely and appropriate initiation of HIV treatment is critical in patients with MASLD who have concurrent HIV infection, as well as optimizing metabolic comorbidities that may also contribute to increased risks of CVD and increased mortality,” the authors wrote.

SOURCE:

The study, led by Robert J. Wong, MD, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study cohort consisted predominantly of older men, which may limit generalizability to women and younger populations. Metabolic comorbidities are more common in veterans compared with the general population, potentially affecting the generalizability of the CVD risk findings.

DISCLOSURES:

The study was supported by an investigator-initiated research grant from Theratechnologies. Wong has received funding for his institution from Gilead Sciences, Exact Sciences, and Durect Corporation and has served as a consultant for Gilead Sciences.
 

A version of this article appeared on Medscape.com.

People with opioid use disorder (OUD) who have hepatitis C virus (HCV) were twice as likely to be treated and cured of HCV if they received facilitated telemedicine treatment within their opioid treatment program than if they were referred for off-site treatment, the results of a new study showed.

In addition, among cured patients, illicit drug use fell significantly, and there were few reinfections, reported the researchers, led by Andrew Talal, MD, MPH, with the University at Buffalo, State University of New York, Buffalo.

The study was published online in JAMA.

HCV is a major public health concern, especially among people with OUD. Geographic and logistical barriers often prevent this underserved population from accessing treatment; however, telemedicine has the potential to overcome these obstacles.

In a prospective cluster randomized clinical trial, Dr. Talal and colleagues assessed the impact of embedding facilitated telemedicine for HCV care into 12 opioid treatment programs in New York State.

They studied 602 HCV-infected adults (61% male; 51% White) with OUD. Of these, 290 (mean age, 47.1 years) were enrolled in facilitated telemedicine programs onsite, and 312 (mean age, 48.9 years) received an off-site referral (usual care).

Telemedicine participants had an initial telemedicine encounter facilitated by study case managers onsite who also administered a blood test. The telemedicine clinician subsequently evaluated participants and ordered direct-acting antiviral (DAA) medication that was delivered to the opioid treatment program monthly (as refills required) and dispensed along with methadone.

In the telemedicine group, 268 of 290 individuals (92.4%) initiated HCV treatment compared with 126 of 312 (40.4%) in the referral group.

Participants in the telemedicine group were also seen sooner and started treatment faster.

The interval between screening and initial appointments was 14 days with telemedicine vs 18 days with a referral (P = .04). The time between the initial visit and DAA initiation was 49.9 days with telemedicine vs 123.5 days with a referral (P < .001).

Intention-to-treat analysis showed significantly higher HCV cure rates with telemedicine than with referral (90.3% vs 39.4%, respectively). Similarly, the observed cure rates were also higher in the telemedicine group (84.8% vs 34.0%).

Sustained virologic response was durable, with only 13 reinfections (incidence, 2.5 per 100 person-years) occurring during the 2-year follow-up period, the researchers reported.

In addition, illicit drug use decreased significantly among cured patients in both the telemedicine group (P < .001) and the referral group (P = .001). Adults in both groups rated healthcare delivery satisfaction as high or very high.

“Our study demonstrates how telemedicine successfully integrates medical and behavioral treatment,” Dr. Talal said in a statement.

The intervention “builds patient-clinician trust across the screen, and significant decreases in substance use were observed in cured participants with minimal HCV reinfections,” the study team wrote.

Support for this research was provided by the Patient-Centered Outcomes Research Institute and by the Troup Fund of the Kaleida Health Foundation.

A version of this article appeared on Medscape.com .

People with opioid use disorder (OUD) who have hepatitis C virus (HCV) were twice as likely to be treated and cured of HCV if they received facilitated telemedicine treatment within their opioid treatment program than if they were referred for off-site treatment, the results of a new study showed.

In addition, among cured patients, illicit drug use fell significantly, and there were few reinfections, reported the researchers, led by Andrew Talal, MD, MPH, with the University at Buffalo, State University of New York, Buffalo.

The study was published online in JAMA.

HCV is a major public health concern, especially among people with OUD. Geographic and logistical barriers often prevent this underserved population from accessing treatment; however, telemedicine has the potential to overcome these obstacles.

In a prospective cluster randomized clinical trial, Dr. Talal and colleagues assessed the impact of embedding facilitated telemedicine for HCV care into 12 opioid treatment programs in New York State.

They studied 602 HCV-infected adults (61% male; 51% White) with OUD. Of these, 290 (mean age, 47.1 years) were enrolled in facilitated telemedicine programs onsite, and 312 (mean age, 48.9 years) received an off-site referral (usual care).

Telemedicine participants had an initial telemedicine encounter facilitated by study case managers onsite who also administered a blood test. The telemedicine clinician subsequently evaluated participants and ordered direct-acting antiviral (DAA) medication that was delivered to the opioid treatment program monthly (as refills required) and dispensed along with methadone.

In the telemedicine group, 268 of 290 individuals (92.4%) initiated HCV treatment compared with 126 of 312 (40.4%) in the referral group.

Participants in the telemedicine group were also seen sooner and started treatment faster.

The interval between screening and initial appointments was 14 days with telemedicine vs 18 days with a referral (P = .04). The time between the initial visit and DAA initiation was 49.9 days with telemedicine vs 123.5 days with a referral (P < .001).

Intention-to-treat analysis showed significantly higher HCV cure rates with telemedicine than with referral (90.3% vs 39.4%, respectively). Similarly, the observed cure rates were also higher in the telemedicine group (84.8% vs 34.0%).

Sustained virologic response was durable, with only 13 reinfections (incidence, 2.5 per 100 person-years) occurring during the 2-year follow-up period, the researchers reported.

In addition, illicit drug use decreased significantly among cured patients in both the telemedicine group (P < .001) and the referral group (P = .001). Adults in both groups rated healthcare delivery satisfaction as high or very high.

“Our study demonstrates how telemedicine successfully integrates medical and behavioral treatment,” Dr. Talal said in a statement.

The intervention “builds patient-clinician trust across the screen, and significant decreases in substance use were observed in cured participants with minimal HCV reinfections,” the study team wrote.

Support for this research was provided by the Patient-Centered Outcomes Research Institute and by the Troup Fund of the Kaleida Health Foundation.

A version of this article appeared on Medscape.com .

People with opioid use disorder (OUD) who have hepatitis C virus (HCV) were twice as likely to be treated and cured of HCV if they received facilitated telemedicine treatment within their opioid treatment program than if they were referred for off-site treatment, the results of a new study showed.

In addition, among cured patients, illicit drug use fell significantly, and there were few reinfections, reported the researchers, led by Andrew Talal, MD, MPH, with the University at Buffalo, State University of New York, Buffalo.

The study was published online in JAMA.

HCV is a major public health concern, especially among people with OUD. Geographic and logistical barriers often prevent this underserved population from accessing treatment; however, telemedicine has the potential to overcome these obstacles.

In a prospective cluster randomized clinical trial, Dr. Talal and colleagues assessed the impact of embedding facilitated telemedicine for HCV care into 12 opioid treatment programs in New York State.

They studied 602 HCV-infected adults (61% male; 51% White) with OUD. Of these, 290 (mean age, 47.1 years) were enrolled in facilitated telemedicine programs onsite, and 312 (mean age, 48.9 years) received an off-site referral (usual care).

Telemedicine participants had an initial telemedicine encounter facilitated by study case managers onsite who also administered a blood test. The telemedicine clinician subsequently evaluated participants and ordered direct-acting antiviral (DAA) medication that was delivered to the opioid treatment program monthly (as refills required) and dispensed along with methadone.

In the telemedicine group, 268 of 290 individuals (92.4%) initiated HCV treatment compared with 126 of 312 (40.4%) in the referral group.

Participants in the telemedicine group were also seen sooner and started treatment faster.

The interval between screening and initial appointments was 14 days with telemedicine vs 18 days with a referral (P = .04). The time between the initial visit and DAA initiation was 49.9 days with telemedicine vs 123.5 days with a referral (P < .001).

Intention-to-treat analysis showed significantly higher HCV cure rates with telemedicine than with referral (90.3% vs 39.4%, respectively). Similarly, the observed cure rates were also higher in the telemedicine group (84.8% vs 34.0%).

Sustained virologic response was durable, with only 13 reinfections (incidence, 2.5 per 100 person-years) occurring during the 2-year follow-up period, the researchers reported.

In addition, illicit drug use decreased significantly among cured patients in both the telemedicine group (P < .001) and the referral group (P = .001). Adults in both groups rated healthcare delivery satisfaction as high or very high.

“Our study demonstrates how telemedicine successfully integrates medical and behavioral treatment,” Dr. Talal said in a statement.

The intervention “builds patient-clinician trust across the screen, and significant decreases in substance use were observed in cured participants with minimal HCV reinfections,” the study team wrote.

Support for this research was provided by the Patient-Centered Outcomes Research Institute and by the Troup Fund of the Kaleida Health Foundation.

A version of this article appeared on Medscape.com .

The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.

Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
 

Ten-Year Results

This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.

A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.

Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.

For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.

Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
 

Efficacy and Duration

The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.

In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.

The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.

An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.

The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.

In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.

Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
 

Ten-Year Results

This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.

A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.

Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.

For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.

Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
 

Efficacy and Duration

The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.

In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.

The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.

An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.

The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.

In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.

Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
 

Ten-Year Results

This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.

A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.

Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.

For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.

Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
 

Efficacy and Duration

The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.

In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.

The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.

An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.

The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.

In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals), the first drug to treat patients with metabolic dysfunction–associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (consistent with stage F2 and F3 disease), along with diet and exercise. 

Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.

The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses. 

The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.) 

The results were published online February 6 in The New England Journal of Medicine. 

“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release. 

“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.

 

Addressing an Unmet Need 

MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication. 

In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo. 

Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.

Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.

Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo. 

The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo. 

Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo. 

The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.

Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.

Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals), the first drug to treat patients with metabolic dysfunction–associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (consistent with stage F2 and F3 disease), along with diet and exercise. 

Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.

The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses. 

The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.) 

The results were published online February 6 in The New England Journal of Medicine. 

“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release. 

“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.

 

Addressing an Unmet Need 

MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication. 

In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo. 

Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.

Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.

Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo. 

The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo. 

Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo. 

The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.

Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.

Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals), the first drug to treat patients with metabolic dysfunction–associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (consistent with stage F2 and F3 disease), along with diet and exercise. 

Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.

The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses. 

The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.) 

The results were published online February 6 in The New England Journal of Medicine. 

“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release. 

“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.

 

Addressing an Unmet Need 

MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication. 

In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo. 

Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.

Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints. 

At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.

Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo. 

The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo. 

Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo. 

The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.

Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.

Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.

A version of this article appeared on Medscape.com.

Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.

Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
 

‘A First’

SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.

The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.

Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.

The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.

A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.

In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.

Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.

The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.

Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.

The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.

All participants completed the full 24 weeks of therapy at the originally prescribed dose.
 

Potential Impact

“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”

“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.

The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.

Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
 

‘A First’

SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.

The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.

Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.

The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.

A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.

In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.

Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.

The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.

Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.

The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.

All participants completed the full 24 weeks of therapy at the originally prescribed dose.
 

Potential Impact

“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”

“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.

The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.

Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
 

‘A First’

SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.

The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.

Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.

The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.

A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.

In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.

Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.

The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.

Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.

The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.

All participants completed the full 24 weeks of therapy at the originally prescribed dose.
 

Potential Impact

“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”

“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.

The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A multicomponent strategy of nurse-led communication, home blood pressure monitoring, evidence-based treatment algorithms, and electronic health record tools improved systolic blood pressure (SBP) and non–high-density lipoprotein (non-HDL) cholesterol levels in people living with HIV.

METHODOLOGY:

• Investigators assessed if EXTRA-CVD, a nurse-led multicomponent intervention for preventing cardiovascular diseases (CVD), could effectively improve SBP and non-HDL cholesterol levels in people living with HIV whose viral replication has been controlled effectively using antiretroviral therapy.
• They recruited 297 individuals (median age, 59 years; 20.9% women) from three academic HIV clinics in the United States with an HIV-1 viral load < 200 copies/mL who were diagnosed with both hypertension and hypercholesterolemia.
• Participants were randomly assigned to either the EXTRA-CVD intervention group or a control group comprising individuals who received general prevention education.
• SBP (the primary outcome) was calculated as the mean of two SBP measurements obtained 1 minute apart, and non-HDL cholesterol (the secondary outcome) was calculated as total cholesterol minus HDL cholesterol.

TAKEAWAY:

• Participants in the intervention vs control group reported having significantly lower SBP as early as 4 months after the nurse-led strategy (mean difference, −6.4 mm Hg; P = .002), with the improvements sustaining until 12 months (mean difference, −4.2 mm Hg; P = .04).
• At 12 months, participants in the intervention group showed a 16.9-mg/dL (P < .001) reduction in non-HDL cholesterol levels compared with those in the control group.
• The nurse-led strategy led to a greater reduction in SBP in women with HIV vs men living with HIV (5.9 mm Hg greater SBP difference at 12 months), with the difference being clinically meaningful but not statistically significant.
• This nurse-led strategy did not increase the risk for adverse events in people living with HIV.

IN PRACTICE:

“Although the EXTRA-CVD intervention was limited to BP and cholesterol, nurse-led case management might be beneficial for a range of other primary care conditions in HIV clinics. If HIV clinics choose to implement EXTRA-CVD, they might consider adding staff trained in other chronic comorbidities and/or health promotion activities,” the authors noted.

SOURCE:

This study was led by Christopher T. Longenecker, MD, University of Washington School of Medicine, Seattle, and published online on March 5, 2024, in JAMA Network Open.

LIMITATIONS:

Because this trial was conducted at well-resourced, major academic HIV clinics, the results may not be applicable to other populations, such as smaller community-based clinics or HIV care outside the United States. The sensitivity analyses performed in this study may not have fully accounted for the bias introduced by the differential attrition in the intervention group.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health (NIH). The authors declared receiving grants and personal fees from or having other ties with the NIH and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

A multicomponent strategy of nurse-led communication, home blood pressure monitoring, evidence-based treatment algorithms, and electronic health record tools improved systolic blood pressure (SBP) and non–high-density lipoprotein (non-HDL) cholesterol levels in people living with HIV.

METHODOLOGY:

• Investigators assessed if EXTRA-CVD, a nurse-led multicomponent intervention for preventing cardiovascular diseases (CVD), could effectively improve SBP and non-HDL cholesterol levels in people living with HIV whose viral replication has been controlled effectively using antiretroviral therapy.
• They recruited 297 individuals (median age, 59 years; 20.9% women) from three academic HIV clinics in the United States with an HIV-1 viral load < 200 copies/mL who were diagnosed with both hypertension and hypercholesterolemia.
• Participants were randomly assigned to either the EXTRA-CVD intervention group or a control group comprising individuals who received general prevention education.
• SBP (the primary outcome) was calculated as the mean of two SBP measurements obtained 1 minute apart, and non-HDL cholesterol (the secondary outcome) was calculated as total cholesterol minus HDL cholesterol.

TAKEAWAY:

• Participants in the intervention vs control group reported having significantly lower SBP as early as 4 months after the nurse-led strategy (mean difference, −6.4 mm Hg; P = .002), with the improvements sustaining until 12 months (mean difference, −4.2 mm Hg; P = .04).
• At 12 months, participants in the intervention group showed a 16.9-mg/dL (P < .001) reduction in non-HDL cholesterol levels compared with those in the control group.
• The nurse-led strategy led to a greater reduction in SBP in women with HIV vs men living with HIV (5.9 mm Hg greater SBP difference at 12 months), with the difference being clinically meaningful but not statistically significant.
• This nurse-led strategy did not increase the risk for adverse events in people living with HIV.

IN PRACTICE:

“Although the EXTRA-CVD intervention was limited to BP and cholesterol, nurse-led case management might be beneficial for a range of other primary care conditions in HIV clinics. If HIV clinics choose to implement EXTRA-CVD, they might consider adding staff trained in other chronic comorbidities and/or health promotion activities,” the authors noted.

SOURCE:

This study was led by Christopher T. Longenecker, MD, University of Washington School of Medicine, Seattle, and published online on March 5, 2024, in JAMA Network Open.

LIMITATIONS:

Because this trial was conducted at well-resourced, major academic HIV clinics, the results may not be applicable to other populations, such as smaller community-based clinics or HIV care outside the United States. The sensitivity analyses performed in this study may not have fully accounted for the bias introduced by the differential attrition in the intervention group.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health (NIH). The authors declared receiving grants and personal fees from or having other ties with the NIH and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

A multicomponent strategy of nurse-led communication, home blood pressure monitoring, evidence-based treatment algorithms, and electronic health record tools improved systolic blood pressure (SBP) and non–high-density lipoprotein (non-HDL) cholesterol levels in people living with HIV.

METHODOLOGY:

• Investigators assessed if EXTRA-CVD, a nurse-led multicomponent intervention for preventing cardiovascular diseases (CVD), could effectively improve SBP and non-HDL cholesterol levels in people living with HIV whose viral replication has been controlled effectively using antiretroviral therapy.
• They recruited 297 individuals (median age, 59 years; 20.9% women) from three academic HIV clinics in the United States with an HIV-1 viral load < 200 copies/mL who were diagnosed with both hypertension and hypercholesterolemia.
• Participants were randomly assigned to either the EXTRA-CVD intervention group or a control group comprising individuals who received general prevention education.
• SBP (the primary outcome) was calculated as the mean of two SBP measurements obtained 1 minute apart, and non-HDL cholesterol (the secondary outcome) was calculated as total cholesterol minus HDL cholesterol.

TAKEAWAY:

• Participants in the intervention vs control group reported having significantly lower SBP as early as 4 months after the nurse-led strategy (mean difference, −6.4 mm Hg; P = .002), with the improvements sustaining until 12 months (mean difference, −4.2 mm Hg; P = .04).
• At 12 months, participants in the intervention group showed a 16.9-mg/dL (P < .001) reduction in non-HDL cholesterol levels compared with those in the control group.
• The nurse-led strategy led to a greater reduction in SBP in women with HIV vs men living with HIV (5.9 mm Hg greater SBP difference at 12 months), with the difference being clinically meaningful but not statistically significant.
• This nurse-led strategy did not increase the risk for adverse events in people living with HIV.

IN PRACTICE:

“Although the EXTRA-CVD intervention was limited to BP and cholesterol, nurse-led case management might be beneficial for a range of other primary care conditions in HIV clinics. If HIV clinics choose to implement EXTRA-CVD, they might consider adding staff trained in other chronic comorbidities and/or health promotion activities,” the authors noted.

SOURCE:

This study was led by Christopher T. Longenecker, MD, University of Washington School of Medicine, Seattle, and published online on March 5, 2024, in JAMA Network Open.

LIMITATIONS:

Because this trial was conducted at well-resourced, major academic HIV clinics, the results may not be applicable to other populations, such as smaller community-based clinics or HIV care outside the United States. The sensitivity analyses performed in this study may not have fully accounted for the bias introduced by the differential attrition in the intervention group.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health (NIH). The authors declared receiving grants and personal fees from or having other ties with the NIH and other sources.

A version of this article appeared on Medscape.com.