Positive association between severity of COVID-19 infection and liver damage: a systematic review and meta-analysis

Aim: The current study aimed to report a pooled analysis of the association of the circulating levels of liver enzymes and total bilirubin with severe and non-severe COVID-19. Background: The ongoing coronavirus outbreak is an important threat to health worldwide. Epidemiological data representing greater risk of liver failure in patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Methods: Electronic databases were comprehensively searched using Medline, ISI Web of Science, EMBASE, and the Cochrane Library up to July 2020. Outcomes from each relevant study were pooled using a random-effects model. Heterogeneity was analyzed by Q test and I2 statistics. Sensitivity analysis was also evaluated. Results: A total of 24 studies were included (4,246 patients) in this study. We found a significant association of COVID-19 severity with increased levels of ALT [SMD: 1.40 U/L; 95% CI (0.93, 1.88); P < 0.05, I2 = 96.5%, PHeterogenity = 0.000 ], AST [SMD: 2.11 U/L; 95% CI (1.40, 2.83); P < 0.05, I2 = 97.9%, PHeterogenity = 0.000], LDH [SMD: 3.88 U/L; 95% CI (2.70, 5); P < 0.05, I2 = 98.7%, PHeterogenity = 0.000] and TBil [SMD: 1.08 mol/L; 95% CI (0.44, 1.72); P = 0.001, I2 = 97.7, PHeterogenity = 0.000], whereas, ALP values [SMD: 0.31; 95% CI (-1.57, 2.20); P = 0.74] was not significant between severe and non-severe COVID-19 patients. Moreover, elevated liver enzymes were found more in males [OR: 1.52, (95% CI 1.26, 1.83), P < 0.05] with severe COVID-19 infection than in females. Conclusion: The alterations of liver function indexes caused by SARS-CoV-2 infection suggested a potential prognosis biomarker for screening of severe patients at early stages of the disease.