Increased risk of hepatic outcomes after SARS-CoV-2 infection in individuals with pre-existing chronic liver disease

Viral infections can accelerate chronic liver disease (CLD) progression, yet whether SARS-CoV-2 infection drives worse long-term hepatic outcomes in patients with pre-existing CLD remains unknown. This retrospective cohort study investigated whether SARS-CoV-2 infection was associated with mortality, hepatic decompensation, and abnormal fibrosis-related laboratory markers in patients with pre-existing CLD up to 4.5 years post-infection. Adults with pre-existing CLD in the Montefiore Health System in the Bronx, NY (February 2020-August 2024) were stratified by COVID-19 hospitalization status and 1:1 propensity-score matched to uninfected controls, with associations estimated using Cox proportional hazards and logistic regression models. Among 37,559 adults with pre-existing CLD, 6,178 tested positive for SARS-CoV-2 (2,182 was hospitalized for COVID-19). Compared with matched controls, hospitalized COVID-19 patients showed higher mortality (HR = 2.92, 95% CI 2.00-4.27, p < 0.005) and higher odds of abnormal Fibrosis 4 score (FIB4, OR = 1.37, 1.21–1.56), aspartate aminotransferase (AST, OR = 1.60, 1.04–2.47), and platelet count (PLT, OR = 1.40, 1.02–1.92) within the first year, with FIB4 remaining abnormal beyond one year (OR = 1.20, 1.06–1.37, p = 0.006). In contrast, non-hospitalized COVID-19 patients did not show increased mortality but showed lower odds of hepatic decompensation, and lower odds of abnormal aminotransferases within the first year and beyond ( p < 0.005). These paradoxically favorable associations likely reflect selection bias, as non-hospitalized COVID-19 patients represent a healthier subgroup while controls are enriched for sicker patients. A sensitivity analysis in a matched cohort with FIB4 staging confirmed overall findings. Severe, hospitalized COVID-19 is a clinically actionable risk marker in patients with pre-existing CLD, warranting structured hepatic surveillance, whereas patients with mild infection can be reassured.