Hospital Admissions for Hepatitis A and E in Spain: Nationwide Trends and In-Hospital Outcomes.

The prognosis of acute hepatitis A virus (HAV) and hepatitis E virus (HEV) in patients with immunosuppression (IS) or chronic liver disease (CLD) remains unclear. We aimed to identify predictors of severe outcomes in these patients. Using the Spanish National Hospital Discharge Database, we identified all admissions for acute HAV or HEV (January 2016-December 2023). Primary outcomes were intensive care unit (ICU) admission, acute or subacute hepatic failure, and in-hospital mortality. Multivariable logistic regression estimated associations between IS causes, CLD etiologies, and outcomes, adjusting for age, sex, and extrahepatic manifestations. Among 6477 unique admissions, 5306 had HAV (81.9%) and 1191 had HEV (18.4%), including 20 dual HAV/HEV coinfections counted in both virus-specific groups. HEV admissions increased whereas HAV admissions declined over time. HAV admissions were younger (39.5 vs. 59.8 years) and had higher HIV coinfection rates (6.8% vs. 1.3%), but lower rates of IS (20.0% vs. 45.7%) and underlying CLD (12.4% vs. 32.7%) (p < 0.001). HAV admissions had lower rates of acute or subacute hepatic failure (2.4% vs. 4.5%) and mortality (1.4% vs. 3.1%). All admissions with coded acute or subacute hepatic failure had pre-existing CLD. Multivariable analysis identified CLD as the principal mortality determinant (HAV: OR 2.8, 95% CI: 1.7-4.6; HEV: OR 5.2, 95% CI: 2.5-10.9). Alcoholic liver disease predicted both acute or subacute hepatic failure and mortality in both viruses; autoimmune hepatitis predicted hepatic failure only, and chronic hepatic insufficiency predicted ICU admission in both viruses, acute or subacute hepatic failure in HAV, and mortality in HEV. Despite increased mortality, IS did not predict acute or subacute hepatic failure. Severe outcomes in admissions with HAV and HEV infections are mostly driven by baseline hepatic reserve regardless of viral type. Thus, risk stratification should prioritize pre-existing liver dysfunction, the major risk determinant for acute or subacute hepatic failure.