Hope for treating alcohol-related liver disease

Health and Wellness 28. mar 2023 2 min Post doc, PhD, MD Mads Bastrup Israelsen Written by Kristian Sjøgren

Millions of people worldwide have alcohol-related liver disease from long-term excessive alcohol consumption, and many die from this. Until now, there was no optimal treatment. However, this may change after a trial with rifaximin-a, an antibiotic that has shown promising results. A researcher involved in the study says that the antibiotic may also be used for other liver diseases.

The trial results shocked the researchers.

“Our results are amazing because treatment with rifaximin-α convincingly reduced scarring of the liver among people with alcohol-related liver disease. If we can confirm our findings in a larger study, we could potentially treat millions of people who have no treatment options today,” explains Mads Israelsen, Postdoctoral Fellow at the Centre for Liver Research, Odense University Hospital.

The research has been published in The Lancet Gastroenterology and Hepatology.

Potential remedy against travellers’ diarrhoea

People with excessive alcohol consumption may develop alcohol-related liver disease. Alcohol damages the liver partly because the alcohol degrades the gut barrier, thereby enabling bacterial products to move from the gut to the liver. Over time, this leads to the formation of scar tissue in the liver and can develop into cirrhosis if nothing is done.

Cirrhosis is associated with extremely poor life expectancy of less than 18 months.

Few people with alcohol-related liver disease realise they have it, since it is only noticeable when the liver is very damaged. Millions of people have it, but diagnosis requires a fibrosis scan or a blood test currently only available in a few hospitals.

“Our aim was identifying a way to stop the damage to the liver before these people develop cirrhosis. We tried rifaximin-α, with the idea that it will promote gut-barrier repair so that fewer harmful bacterial products penetrate the gut wall and damage the liver,” says Mads Israelsen.

Rifaximin-α is already used to treat recurrent hepatic encephalopathy, which is directly related to a compromised gut barrier. It is also used for travellers’ diarrhoea.

136 participants

In a randomised placebo-controlled Phase 2 trial, the researchers randomised 136 people with alcohol-related liver disease for treatment with rifaximin-α or placebo for 18 months.

The participants had a history of excessive alcohol consumption, averaging four drinks per day, and had all been diagnosed with asymptomatic alcohol-related liver disease.

The participants averaged 60 years old, and 84% were men.

The researchers examined scar tissue formation in the liver by taking a liver biopsy before the trial started and after it ended. The participants were also advised not to drink excessively during the 18-month trial.

Fifty-four people in the rifaximin-α group and 54 in the placebo group completed the trial.

Impressive results

Treatment with rifaximin-α slowed the progression of alcohol-related liver disease.

After 18 months, liver disease worsened among 23 people in the placebo group versus only 13 people in the active treatment group.

“Alcohol-related liver disease is the second largest cause of death among people of working age in Europe, so we are pleased that this drug appears to stop progression among many people. This may benefit not only people with alcohol-related liver disease but also society in general,” explains Mads Israelsen.

In the study, the researchers also examined the subgroup of people with metabolic syndrome, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Treatment with rifaximin-α worked at least as well among these people.

Mads Israelsen sees huge potential in investigating the effectiveness of rifaximin-α in large randomised multicentre Phase 3 studies on not only alcohol-related liver disease but also NAFLD and NASH. Initially, however, the focus is on alcohol-related liver disease.

“Alcohol-related liver disease is often stigmatising because many people think that these people can just stop drinking alcohol. However, similar to chronic obstructive pulmonary disease among people who continue to smoke and type 2 diabetes among people with overweight, we should help these people who are not successful in quitting alcohol despite disease,” concludes Mads Israelsen.

Post doc researcher and clinical hepatologist with a PhD in alcohol-related liver disease (2020). His main research interests are alcohol-related live...

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