Progressive cholestasis and associated sclerosing cholangitis are frequent complications of COVID ‐19 in chronic liver disease patients

Cholestasis is associated with disease severity and worse outcome in coronavirus disease of 2019 (COVID-19). Cases of secondary sclerosing cholangitis (SSC) after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have been described.Hospitalized patients with COVID-19 between 03/2020 and 07/2021 were included. Patients were stratified as having (i) no chronic liver disease (CLD), (ii) non-advanced (non-ACLD), or (iii) advanced chronic liver disease (ACLD). CLD patients with non-COVID-19 pneumonia were matched to CLD patients with COVID-19 as a control cohort. Liver chemistries before (Pre), at first, second and third blood withdrawal after SARS-CoV-2 infection (T1-T3) and at last available time point (last) were recorded.496 patients were included. 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 CLD patients (24.6% vs. 10.6%; p=0.001). After SARS-CoV-2 infection, CLD patients exhibited progressive cholestasis with persistently increasing levels of alkaline phosphatase (ALP; Pre: 91.0 vs. T1: 121.0 vs. last: 175.0U/L; p<0.001) and gamma-glutamyl transferase (GGT; Pre: 95.0 vs. T1: 135.0 vs. last: 202.0U/L; p=0.001). 23.1% of CLD patients (n=15/65) developed cholestatic liver failure (cholestasis plus bilirubin ≥6mg/dL) during COVID-19 and 15.4% of patients (n=10/65) developed SSC. SSC was significantly more frequent among CLD patients with COVID-19 than in CLD patients with non-COVID-19 pneumonia (p=0.040). COVID-19-associated SSC occurred predominantly in NAFLD/NASH patients with metabolic risk factors. 26.3% (n=5/19) of ACLD patients experienced hepatic decompensation after SARS-CoV-2 infection.About 20% of CLD patients develop progressive cholestasis after SARS-CoV-2 infection. NAFLD/NASH patients with metabolic risk factors are at particular risk for developing cholestatic liver failure and/or SSC after COVID-19.