TY - JOUR
T1 - Effect of varenicline on major adverse liver outcomes in alcohol-associated liver disease
T2 - An exploratory analysis
AU - Danpanichkul, Pojsakorn
AU - Pang, Yanfang
AU - Kim, Donghee
AU - Suenghataiphorn, Thanathip
AU - Ko, Donghyun
AU - Ibrahim, Andrew F.
AU - Prasitsumrit, Vitchapong
AU - Duangsonk, Kwanjit
AU - Noureddin, Mazen
AU - Wijarnpreecha, Karn
AU - Liangpunsakul, Suthat
N1 - Publisher Copyright:
© 2025 The Author(s). Alcohol, Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.
PY - 2025
Y1 - 2025
N2 - Background: Varenicline, a partial agonist of the α4β2 nicotinic acetylcholine receptor, is effective for smoking cessation and has shown promise in treating alcohol use disorder (AUD). However, its impact on patients with concurrent alcohol-associated liver disease (ALD) remains understudied. We aimed to evaluate the association between varenicline use and long-term clinical outcomes in this population. Methods: We conducted a retrospective cohort study using the TriNetX federated network of deidentified electronic health records. Adults with diagnoses of both ALD and AUD were included. Patients prescribed varenicline were compared to those receiving FDA-approved AUD pharmacotherapies (acamprosate or naltrexone), using 1:1 propensity score matching based on demographics, comorbidities, medications, and laboratory values. The primary outcome was major adverse liver outcomes (MALO); secondary outcomes included all-cause mortality and other liver-related complications. Hazard ratios (HRs) were estimated using Cox proportional hazards models over a five-year follow-up period. Results: A total of 1278 patients were included after matching. Varenicline use was associated with lower all-cause mortality (14.4% vs. 17.4%; HR 0.75, 95% CI 0.57–0.99) and a significantly reduced risk of hepatic encephalopathy (3.5% vs. 6.7%; HR 0.47, 95% CI 0.28–0.79). Although overall MALO rates were similar between groups (17.3% vs. 17.6%; HR 0.89, 95% CI 0.66–1.20), subgroup analyses revealed reduced MALO incidence among females and all-cause mortality among individuals aged ≥65 years. Conclusion: In this real-world cohort study, varenicline use was associated with improved survival and a lower risk of hepatic encephalopathy compared to standard AUD pharmacotherapies in patients with co-occurring ALD and AUD. These findings support further investigation of varenicline as a potential therapeutic option, ideally through randomized controlled trials.
AB - Background: Varenicline, a partial agonist of the α4β2 nicotinic acetylcholine receptor, is effective for smoking cessation and has shown promise in treating alcohol use disorder (AUD). However, its impact on patients with concurrent alcohol-associated liver disease (ALD) remains understudied. We aimed to evaluate the association between varenicline use and long-term clinical outcomes in this population. Methods: We conducted a retrospective cohort study using the TriNetX federated network of deidentified electronic health records. Adults with diagnoses of both ALD and AUD were included. Patients prescribed varenicline were compared to those receiving FDA-approved AUD pharmacotherapies (acamprosate or naltrexone), using 1:1 propensity score matching based on demographics, comorbidities, medications, and laboratory values. The primary outcome was major adverse liver outcomes (MALO); secondary outcomes included all-cause mortality and other liver-related complications. Hazard ratios (HRs) were estimated using Cox proportional hazards models over a five-year follow-up period. Results: A total of 1278 patients were included after matching. Varenicline use was associated with lower all-cause mortality (14.4% vs. 17.4%; HR 0.75, 95% CI 0.57–0.99) and a significantly reduced risk of hepatic encephalopathy (3.5% vs. 6.7%; HR 0.47, 95% CI 0.28–0.79). Although overall MALO rates were similar between groups (17.3% vs. 17.6%; HR 0.89, 95% CI 0.66–1.20), subgroup analyses revealed reduced MALO incidence among females and all-cause mortality among individuals aged ≥65 years. Conclusion: In this real-world cohort study, varenicline use was associated with improved survival and a lower risk of hepatic encephalopathy compared to standard AUD pharmacotherapies in patients with co-occurring ALD and AUD. These findings support further investigation of varenicline as a potential therapeutic option, ideally through randomized controlled trials.
KW - addiction
KW - alcohol-related liver disease
KW - liver disease
KW - public health
KW - substance use disorder
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U2 - 10.1111/acer.70160
DO - 10.1111/acer.70160
M3 - Article
AN - SCOPUS:105016108076
SN - 2993-7175
JO - Alcohol, Clinical and Experimental Research
JF - Alcohol, Clinical and Experimental Research
ER -