Coronavirus Disease (COVID-19) and the Liver: A comprehensive systematic review and meta-analysis (preprint)

ABSTRACT

Background: Liver function derangements have been reported in coronavirus disease (COVID-19) but reported rates are variable. Methods: We searched Pubmed and Embase with terms COVID and SARS-COV-2 from December 1, 2019 till April 5, 2020. We estimated overall prevalence, stratified prevalence based on severity, estimated risk ratio (RR) and estimated standardized mean difference (SMD) of liver function parameters in severe as compared to nonsevere COVID. Random effect method utilizing inverse variance approach was used for pooling the data. Results: In all, 128 studies were included. The most frequent abnormalities were hypoalbuminemia [61.27% (48.24 - 72.87)], elevations of gamma-glutamyl transferase (GGT) [27.94%(18.22 -40.27)], alanine aminotransferase (ALT) [23.28%(19.92 - 27.01)] and aspartate aminotransferase (AST) [23.41%(18.84 - 28.70)]. Further the relative risk of these abnormalities was higher in the patients with severe COVID-19 when compared to non-severe disease [Hypoalbuminemia - 2.65(1.38 - 5.07); GGT - 2.31(1.6 - 3.33); ALT - 1.76(1.44 - 2.15); AST 2.30(1.82 - 2.90)]. The SMD of hypoalbuminemia, GGT, ALT and AST elevation in severe as compared to nonsevere were -1.05(-1.27 - -0.83), 0.76(0.40 - 1.12), 0.42(0.27 - 0.56) and 0.69 (0.52 - 0.86) respectively. The pooled prevalence and RR of chronic liver disease as a comorbidity was 2.64% (1.73- 4) and 1.69(1.05-2.73) respectively. Conclusion: The most frequent abnormality in liver functions was hypoalbuminemia followed by derangements in gamma-glutamyl transferase and aminotransferases and these abnormalities were more frequent in severe disease.  The systematic review was, however, limited by heterogeneity in definitions of severity and liver function derangements.