Drugs for alcohol addiction can thwart liver disease

According to a retrospective study, people taking medication for alcohol use disorder (AUD) were less likely to develop or experience progression of alcohol-related liver disease.

Among more than 9,500 patients with AUD, a multivariate analysis showed that those in medical addiction treatment had a 63% lower chance of being diagnosed with alcohol-related liver disease (adjusted odds ratio [aOR] 0.37, 95% CI 0.31-0.43), according to Jay Luther, MD, of Massachusetts General Hospital in Boston, and colleagues.

And AUD patients with cirrhosis on drug therapy had a 65% lower risk of hepatic decompensation (aOR 0.35, 95% CI 0.23-0.53), an association that “persisted” even though treatment was started after cirrhosis was diagnosed, the group reported in Open JAMA Network.

“The take-home message from this study may seem obvious, but its clinical and public health importance cannot be overstated,” wrote Lorenzo Leggio, MD, PhD, and Dr. Katherine Jung, PhD, both of the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, in an accompanying editorial.

Three drugs for AUD have been approved by the FDA (acamprosate, disulfiram, and naltrexone), but off-label use of other drugs is common.

“One of the most challenging aspects of treating patients with AUD is that many patients do not receive evidence-based treatments despite the availability of such treatments,” Leggio and Jung continued. “This lack of treatment is alarming and is one reason why the results of this study matter, now more than ever.”

With the COVID-19 pandemic, an increase in alcohol consumption has been reported, along with subsequent increases in alcohol-related liver disease and alcohol-related deaths.

For their study, Luther and colleagues looked at Mass General Brigham Biobank data on 9,635 AUD patients from 2010 to 2021, 11.8% of whom had alcohol-related liver disease (n=1,135) and 40.5% were receiving medical addiction therapy (n=3906). The mean follow-up was 9.2 years.

The definition of alcohol-related liver disease included a diagnosis of alcoholic hepatitis, cirrhosis of the liver, fibrosis, sclerosis, and liver failure, as well as other or unspecified cirrhosis. But patients with alcoholic fatty liver disease or unspecified alcoholic liver disease were excluded because “many patients with moderate and heavy alcohol consumption develop fatty liver disease, the clinical significance of which is unclear in with respect to liver-related morbidity and mortality,” the authors noted.

Several approved and off-label addiction drugs were analyzed – disulfiram, acamprosate, naltrexone, gabapentin, baclofen and topiramate – with at least three prescriptions used as the definition of AUD medical treatment.

Among other factors, analyzes were adjusted for demographics, homelessness, psychiatric disorders, and concurrent liver disease.

Several of the therapies were associated with a lower likelihood of being diagnosed with alcohol-related liver disease:

  • Gabapentin: aOR 0.36 (95% CI 0.30-0.43)
  • Topiramate: aOR 0.47 (95% CI 0.32-0.66)
  • Baclofen: aOR 0.57 (95% CI 0.36-0.88)
  • Naltrexone: ORa 0.67 (95% CI 0.46-0.95)

And several were associated with a lower likelihood of liver decompensation among the 406 patients with cirrhosis:

  • Naltrexone: ORa 0.27 (95% CI 0.10-0.64)
  • Gabapentin: aOR 0.36 (95% CI 0.23-0.56)

Acamprosate, on the other hand, was associated with an increased likelihood of being diagnosed with alcohol-related liver disease (aOR 2.59, 95% CI 1.84-3.61) and showed a trend to a higher likelihood of hepatic decompensation in people with cirrhosis (aOR 1.99, 95% CI 0.99-4.06).

“It is possible that, given the favorable hepatotoxic profile of acamprosate, it may be prescribed to patients who are judged to be more susceptible to developing liver disease or who show signs of mild alcohol-induced liver injury,” they wrote. noted Luther and his colleagues. “Also, in our practice, acamprosate is reserved for patients with more severe AUD.”

The average age in the entire study population was 55 years, 60% were male and 83% were Caucasian. The average body mass index was 29 and most patients had a history of psychiatric disorders (85%).

In the treatment group, initiation of medical treatment occurred an average of 1.65 years after an index diagnosis of AUD, and the average duration of treatment was 4 years.

“In patients who experienced a liver decompensation event despite receiving pharmacotherapy for AUD, the time to decompensation after diagnosis of cirrhosis was significantly longer compared to patients who did not receive pharmacotherapy. [~6 vs 2 years]“, note the editorialists.

Luther and coauthors acknowledged several limitations to the data, including the risk of unknown confounders, the lack of diversity in the study population, and the fact that the proportion receiving treatment for AUD was higher than observed in the previous reports.

  • Zaina Hamza is a writer for MedPage Today, covering gastroenterology and infectious diseases. She is based in Chicago.

Disclosures

This study was funded by the National Institutes of Health.

Luther and his co-authors reported no conflicts of interest.

Leggio reported dealings with the UK Medical Council on Alcohol and royalties from Routledge. No additional disclosures were reported.

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