Abnormal liver function tests in COVID‐19 patients: relevance and potential pathogenesis

Bertolini, Anna; van de Peppel, Ivo P.; Bodewes, Frank A.J.A.; Moshage, Han; Fantin, Alberto; Farinati, Fabio; Fiorotto, Romina; Jonker, Johan W.; Strazzabosco, Mario; Verkade, Henkjan J.; Peserico, Giulia

Abnormal liver function tests (LFTs) are reported frequently in hospitalized coronavirus disease 2019 (COVID‐19) patients. A review of the literature shows that 46% of admitted COVID‐19 patients had elevated plasma aspartate aminotransferase (AST) and 35% had elevated alanine aminotransferase (ALT) levels on admission. Elevations of both AST and ALT are mostly below 5 times the upper reference limit and are associated with severe disease and increased inflammatory markers. AST and ALT elevations are more frequent in US patients compared to Chinese patients. Mild elevations in gamma‐glutamyltransferase (GGT), alkaline phosphatase (ALP) and total bilirubin are also reported, although less frequently. Significant impairment of liver function or overt liver failure as the cause of death in COVID‐19 rarely occur. There is no direct evidence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) hepatic infection, although a subset of hepatocytes and cholangiocytes express the host receptor utilized for cellular entry by SARS‐CoV‐2. The presence of pre‐existing liver disease in patients with elevated LFTs on admission has not been comprehensively assessed in most studies but is unlikely to account for all abnormalities in LFTs. Although abnormal LFTs are already frequently present upon admission before the start of treatment, drug‐induced liver injury should be taken into consideration, especially after the use of acetaminophen, lopinavir/ritonavir and remdesivir, which are potentially hepatotoxic. In conclusion, these initial observations suggest that the prevalence of abnormal LFTs is high in COVID‐19 patients, but that the clinical relevance is limited and that treatment is not required. The mechanisms underlying abnormal LFTs in COVID‐19 are likely multifactorial and related to a hyper‐inflammatory status and thrombotic microangiopathy that are observed in severe COVID‐19 disease.