Liver and Bile
Hepatology. 2022;76(6):1563–75
Progressive cholestasis and associated sclerosing cholangitis are frequent complications of COVID-19 in patients with chronic liver disease
Background and aims: Cholestasis is associated with disease severity and worse outcome in COVID-19. Cases of secondary sclerosing cholangitis (SSC) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been described.
Approach and results: Hospitalized patients with COVID-19 between March 2020 and July 2021 were included. Patients were stratified as having (i) no chronic liver disease (CLD), (ii) non-advanced CLD (non-ACLD), or (iii) advanced CLD (ACLD). Patients with CLD and non-COVID-19 pneumonia were matched to patients with CLD and COVID-19 as a control cohort. Liver chemistries before (Pre) and at first, second, and third blood withdrawal after SARS-CoV-2 infection (T1–T3) and at last available time point (last) were recorded. A total of 496 patients were included. In total, 13.1% (n = 65) had CLD (non-ACLD: 70.8%; ACLD: 29.2%); the predominant etiology was non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH, 60.0%). COVID-19-related liver injury was more common among patients with CLD (24.6% vs. 10.6%; p = 0.001). After SARS-CoV-2 infection, patients with CLD exhibited progressive cholestasis with persistently increasing levels of alkaline phosphatase (Pre: 91.0 vs. T1: 121.0 vs. last: 175.0 U/l; p < 0.001) and gamma-glutamyl transferase (Pre: 95.0 vs. T1: 135.0 vs. last: 202.0 U/l; p = 0.001). A total of 23.1% of patients with CLD (15/65) developed cholestatic liver failure (cholestasis plus bilirubin ≥ 6 mg/dl) during COVID-19, and 15.4% of patients (10/65) developed SSC. SSC was significantly more frequent among patients with CLD and COVID-19 than in patients with CLD and non-COVID-19 pneumonia (p = 0.040). COVID-19-associated SSC occurred predominantly in patients with NAFLD/NASH and metabolic risk factors. A total of 26.3% of patients (5/19) with ACLD experienced hepatic decompensation after SARS-CoV-2 infection.
Conclusions: About 20% of patients with chronic liver disease develop progressive cholestasis after SARS-CoV-2 infection. Patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and metabolic risk factors are at particular risk for developing cholestatic liver failure and/or secondary sclerosing cholangitis after COVID-19.