Baclofen Benefits Cirrhosis, Alcohol-Associated Hepatitis Outcomes in AUD

Christopher Oldroyd, MBBS

Credit: LinkedIn

Just one available pharmaceutical intervention designated for alcohol use disorder (AUD) was associated with significant clinical trial-supported benefit for the specific treatment of patients with cirrhosis or alcohol-associated hepatitis, according to a new literature review.¹

In a systematic review conducted by a team of UK-based investigators, baclofen, a skeletal muscle relaxant associated with spasm and pain relief, was the lone intervention among psychological, pharmacological, education-based and lifestyle-based modalities that provided a statistically significant impact on outcomes associated with benefit for cirrhosis in patients with AUD.

In what investigators stated is a review of the “broadest possible range of interventions for AUD in patients with cirrhosis and alcohol-associated hepatitis,” the findings elucidate both current limitations with available interventions against a growing health concern in hepatology, as well as future opportunities to expand the AUD treatment market and refine patient-level education on disease management.

Led by Christopher Oldroyd, MBBS, an NIHR Doctoral Fellow at Cambridge University Hospitals NHS Foundation Trust, the investigative team sought to systematically review interventions for AUD specific to patients with cirrhosis or alcohol-associated hepatitis.

Numerous reports this year alone have elucidated a rapidly growing prevalence of alcohol-associated hepatitis and other chronic liver diseases driven by increased alcohol use among Americans; one such report from the Mayo Clinic showed rates of disease increased by more than 70% among persons of lower socioeconomic status from 2015 – 2019.² Another report this month showed annual alcohol-associated hepatitis hospitalizations increased by approximately 16% during the COVID-19 pandemic.³

Oldroyd and colleagues stressed the importance of health care professionals identifying and having access to evidence-based interventions for managing cirrhosis in patients with AUD—especially given that the effort to reduce alcohol intake in patients with cirrhosis presents “unique challenges.”

“Approved drug treatments for AUD are either contraindicated in cirrhosis (disulfiram, naltrexone and nalmefene) or lack an evidence base for safety, dosing and effectiveness (acamprosate, baclofen),” investigators wrote. “These challenges create reluctance among prescribers and low uptake of treatments.”

The team analyzed literature from 5 databases from their inception through November 2022 to identify clinical trials that included outcomes for abstinence, hepatic decompensation and mortality in patients with AUD. Both randomized and non-randomized trials were included in the analysis; meta-analyses were conducted where possible.

The final analysis included 23 studies that met inclusion criteria; 6 trials were randomized and 17 were nonrandomized. A total of 104,298 trial participants were identified. Mean/median ages for the trials in the analysis ranged from 44 – 65 years old; three-fourths (75%) were male.

Among the interventions assessed in trials were baclofen; fecal microbiota transplant (FMT); acamprosate; naltrexone; text-message interventions; psychological therapy; motivational therapy; and educational sessions, among others.

In univariate analysis of randomized trials, baclofen was the lone intervention to provide a statistically significant impact on the primary outcomes; abstinence rates were approximately 6-fold improved with treated patients versus control (odds ratio [OR], 6.3; 95% CI, 2.4 – 16.1). In multivariate models of analysis—which included just 2 randomized trials—only baclofen again provided statistically significant impact in reduced rates of alcohol lapse (hazard ratio [HR], 0.2; 95% CI, 0.1 – 0.9) and relapse (HR, 0.4; 95% CI, 0.2 – 0.8).

In a trio of non-randomized trials, hepatic decompensation episodes were significantly reduced per multivariate analyses when participants received psychological therapy, use of any pharmacotherapy, and use of any treatment for AUD.

“Although baclofen was the only intervention with RCT evidence for significant benefit in patients with cirrhosis, (non-randomized studies of interventions) also point to both pharmaceutical and non-pharmaceutical interventions improving clinical outcomes, in particular rates of hepatic decompensation,” the team concluded. “In parallel with establishing which therapies are beneficial in this patient group, it is also important to improve access to and uptake of effective interventions and to recognize patient preferences.”

References

1. ^{Oldroyd C, Greenham O, Martin G, Allison M, Notley C. Systematic review: Interventions for alcohol use disorder in patients with cirrhosis or alcohol-associated hepatitis [published online ahead of print, 2023 Aug 21]. Aliment Pharmacol Ther. 2023;10.1111/apt.17665. doi:10.1111/apt.17665}
2. ^{Kunzmann K. Alcohol-Associated Hepatitis Rapidly Increasing in the US. HCPLive. Published July 18, 2023. https://www.hcplive.com/view/alcohol-associated-hepatitis-rapidly-increasing-us}
3. ^{Kunzmann K. Alcohol-Associated Hepatitis Hospitalizations Increased During COVID-19. HCPLive. Published August 10, 2023. https://www.hcplive.com/view/alcohol-associated-hepatitis-hospitalizations-increased-covid-19}