Medication for Drinking Addiction May Thwart Liver Disease

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

Among over 9,500 patients with AUD, multivariable analysis showed that those on medical addiction therapy had a 63% lower likelihood of an alcohol-related liver disease diagnosis (adjusted odds ratio [aOR] 0.37, 95% CI 0.31-0.43), according to Jay Luther, MD, of the Massachusetts General Hospital in Boston, and colleagues.

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

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

Three medications 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 in 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 a reason that the results of this study are important, now more than ever.”

With the COVID-19 pandemic, a surge in alcohol consumption has been reported, along with subsequent increases in alcohol-linked liver disease and drinking addiction-related deaths.

For their study, Luther and colleagues examined Mass General Brigham Biobank data on 9,635 AUD patients from 2010 to 2021, of whom 11.8% had an alcohol-related liver disease (n=1,135) and 40.5% received medical addiction therapy (n=3,906). Average follow-up was 9.2 years.

The definition for alcohol-related liver disease included a diagnosis of alcoholic hepatitis, liver cirrhosis, fibrosis, sclerosis, and hepatic failure, as well as other or unspecified cirrhosis. But excluded were patients with alcoholic fatty liver or an unspecified alcoholic liver disease, as “many patients with moderate and high alcohol use develop hepatic steatosis, which has unclear clinical significance regarding liver-related morbidity and mortality,” the authors noted.

Several approved and off-label addiction medications were analysed — disulfiram, acamprosate, naltrexone, gabapentin, baclofen, and topiramate — with at least three prescriptions used as the definition for medical AUD treatment.

Among other factors, analyses adjusted for demographics, homelessness, psychiatric disorders, and concurrent liver diseases.

Several of the therapies were linked with lower odds of an alcohol-related liver disease diagnosis:

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

Acamprosate, meanwhile, was associated with an increased likelihood of an alcohol-related liver disease diagnosis (aOR 2.59, 95% CI 1.84-3.61), and showed a trend toward higher odds of liver decompensation in those with cirrhosis (aOR 1.99, 95% CI 0.99-4.06).

“It is possible that, given the favorable hepatotoxic profile of acamprosate, it is prescribed to patients who are deemed more likely to develop liver disease or have evidence of mild hepatic injury from alcohol,” noted Luther and colleagues. “Furthermore, in our practice, acamprosate is reserved for use in patients with more severe AUD.”

Mean age in the full study population was 55 years, 60% were men, and 83% were white. Average body mass index was 29, and most patients had a history of a psychiatric disorder (85%).

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

“In patients who experienced a hepatic decompensating event despite having received pharmacotherapy for AUD, the time to decompensation after cirrhosis diagnosis was significantly longer compared with patients who did not receive pharmacotherapy [~6 vs 2 years],” the editorialists noted.

Luther and coauthors acknowledged several limitations to the data, including the chance of unknown confounders, lack of diversity in the study population, and that the proportion receiving treatment for AUD was higher than what has been observed in prior reports.