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This study aimed to investigate the associations between hepatitis virus infection and inpatient outcomes of acute pancreatitis (AP). In this population-based, retrospective study, hospitalized patients with AP were identified in the 2005 to 2018 United States Nationwide Inpatient Sample database. Univariate and multivariable regression analyses were conducted to evaluate the associations between hepatitis virus infection, death/discharge against medical advice (DAMA), prolonged length of stay (LOS), and occurrence of life-threatening complications including ischemia/infarction of the intestine, portal vein thrombosis, acute organ failure, systemic inflammatory response syndrome, and hypovolemic shock. A total of 775,416 patients hospitalized for AP comprised the analytic cohort. Amongst, 26,407 subjects (3.4%) had been diagnosed hepatitis virus infection, whereas 749,009 (96.6%) had not. Mean age of the subjects was 51.4 years. After adjusting for relevant confounders, hepatitis virus infection was significantly and independently associated with increased odds of death/DAMA (aOR = 1.33, 95% CI = 1.26-1.40), prolonged LOS (aOR = 1.12, 95%CI = 1.09-1.16), and acute organ failure (aOR = 1.06, 95% CI = 1.01-1.12). In patients with AP, hepatitis virus infection is an independent predictor of worse inpatient outcomes in terms of more death/DAMA, prolonged LOS, and life-threatening complications. The findings may help risk stratification and the development of proper strategies for managing patients suffered from AP., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)