The effect of SARS-CoV-2 infection on the liver function tests: a systematic review and meta-analysis of observational studies.

Introduction: SARS-CoV-2 infection has been associated with respiratory distress syndrome and hepatic injury. The mechanism of liver injury is not fully understood and may be a combined effect of viral hepatitis, systemic inflammation, gut barrier disruption, microbiome alterations or drug toxicity.

Aim: We carried out a systematic review and meta-analysis to determine whether SARS-CoV-2 infection affects the level of liver-produced molecules: alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGTP), bilirubin, total protein, albumin, and prothrombin (with INR).

Methods: Ten authors independently searched PubMed and Embase from their inception until 04/03/2021 for observational studies to evaluate whether SARS CoV-2 infection influences the level of liver-produced molecules. This early search aimed to capture changes associated with the initial variants of SARS-CoV-2 before widespread vaccination efforts. Full-text studies in adult humans in which the aim was liver damage were included. Eligible studies included adult populations with more than 30 subjects, and the analysis adhered to PRISMA guidelines. Data extraction involved a thorough process to ensure accuracy, with inconsistencies resolved by senior clinicians. Statistical analysis was conducted using random effects meta-analysis of outcomes for which ≥ 2 studies contributed data, and the risk of bias was assessed using the New Ottawa Scale. The study protocol was registered in the PROSPERO database (CRD42021242958).

Results: The initial search yielded 3180 hits. 2644 studies were excluded as duplicates and/or after evaluation on the title/abstract level. No additional articles were identified via hand search. There were 536 full-text articles reviewed. Overall, the search strategy yielded 252 studies that were included in the meta-analysis.

Conclusions: The overall mean liver parameter values were not altered compared to physiological values, except for GGTP, lactate dehydrogenase activity, and INR values. In the case of AST, ALT and albumin levels, mean point estimates were close to limit values of standards. SARS-CoV-2 infection triggers gut barrier defects, which results in transient elevation of liver enzymes and clotting times.