Trends and Outcomes of Alcoholic Acute Pancreatitis in Patients with Alcohol Use Disorder Treated with Naltrexone in the United States: Before and After the COVID-19 Pandemic.

Background: The role of naltrexone in improving acute alcoholic pancreatitis (AAP) outcomes in alcohol use disorder (AUD) patients, remains unclear.

Aim: We aimed to assess the temporal trends in AAP incidence and the impact of naltrexone use on clinical outcomes in AUD patients.

Methods: We conducted a retrospective cohort study using de-identified patient data from the TriNetX database, including all adults (≥ 18 years) diagnosed with AUD. AAP patients were then identified and stratified by naltrexone exposure. The incidence and prevalence of AAP in AUD patients were assessed pre-(March 2015-2019) and post-COVID-19(March 2020-2025). Propensity score matching (PSM) (1:1) was performed to adjust for confounders. Univariate Cox proportional hazards model was used to assess the outcomes including mortality, chronic pancreatitis, alcoholic hepatitis, cirrhosis, hospital readmission, and emergency department (ED) visits at 1, 6, and 12 months. Standardized mean differences < 0.1 ensured well-matched cohorts.

Results: Among 1,331,338 AUD adults, 33,561 (2.52%) developed AAP. The incidence of AAPs increased significantly following the COVID-19 pandemic, with the largest relative rise among younger adults (18-34 years), women, and racial minorities. Of those with AAP, 1,871(5.6%) received naltrexone. Following PSM, naltrexone use was associated with significantly lower odds of mortality at one (OR 0.274, p < 0.0001) and six months (OR 0.571, p = 0.005). Reduced odds were also observed for alcoholic hepatitis at one month and hospital readmissions across all time points. Surprisingly, naltrexone use was associated with increased odds of ED visits.

Conclusions: The incidence of AAP has increased since COVID-19 onset. Naltrexone may improve short-term outcomes in patients with AUD and AAP.