Liver injury could be associated with severe disease in COVID-19 patients: a meta-analysis.

Abstract

This letter is to compare liver injury in severe vs. nonsevere or dead vs. surviving patients and investigate whether liver injury can help predict clinical severity and mortality in patients with coronavirus disease 2019 (COVID-19). An extensive electronic search of PubMed, Embase and the Cochrane Library was conducted without date (until 5 May 2020). Two authors independently screened articles, assessed qualities and performed data extraction. Any discrepancies during these steps were regularly resolved by consulting with a third reviewer. Dichotomous variables were estimated with odd risks (OR) and 95% credible interval (CI). Continuous data (using mean and SD) were compared and mean difference was calculated with 95% CI and P value (<0.05 was considered statistically significant). Random-effects model was used if I2 > 50%. The publication bias was evaluated by the visual inspection of funnel plot. Our meta-analysis was carried out using Review Manager software version 5.3. Thirty-six studies were enrolled in our analysis. All studies originated from China and involved 7083 confirmed COVID-19 patients in total. The incidence of patients with chronic liver disease prior to the diagnosis of COVID-19 was not significantly associated with an enhanced risk of severe COVID-19 (OR: 1.36; 95% CI, 0.89–2.07; P = 0.16). The total bilirubin was found to be obviously elevated in COVID-19 patients with severe group (mean difference: 1.68; 95% CI, 1.17–2.19; P < 0.0001) and mortality group (mean difference: 3.90, 95% CI, 2.63–5.18; P < 0.0001). Albumin was significantly lower in COVID-19 patients with severe group (mean difference: –4.48, 95% CI, –6.51 to –2.44; P < 0.0001) and mortality group (mean difference: –4.80, 95% CI, –5.94 to –3.67; P < 0.0001). Our study revealed that increasing mean lactate dehydrogenase (LDH) was significantly associated with an increased likelihood of severity (mean difference: 122.66; 95% CI, 86.50–158.81; P < 0.0001) and death (mean difference: 246.30; 95% CI, 176.78–315.82; P < 0.0001). A more substantial rise in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed in severe cases [ALT: mean difference = 5.73; 95% CI (4.32–7.14); AST: mean difference = 9.41; 95% CI (6.51–12.31); P < 0.0001] and in the nonsurvivors [ALT: mean difference = 5.64; 95% CI (0.52–10.75); P = 0.03; AST: mean difference = 12.93; 95% CI (4.95–20.91); P = 0.002]. Based on visual inspection of funnel plots, no evidence of publication bias was found. More details of our meta-analysis are demonstrated in Fig. 1.Fig. 1.: Meta-analysis results of outcomes: (a) the incidence of COVID-19 patients with chronic liver disease; (b) total bilirubin; (c) albumin; (d) ALT; (e) AST; and (f) LDH. ALT, alanine aminotransferase; AST, aspartate aminotransferase; COVID-19, coronavirus disease 2019; LDH, lactate dehydrogenase.This meta-analysis provides evidence that liver injury, including total bilirubin, albumin, ALT, AST and LDH, could be associated with a more severe form of COVID-19, which can guide the clinicians in recognizing critically ill patients earlier and faster. The mechanisms of COVID-19-associated liver injury might be due to the damage to bile duct cells, immune-related injury, drug-induced injury or direct viral infection of hepatocytes [1–4]. Our results are consistent with previous studies [1,5]. There are limitations to this study. First, most of the included studies are retrospective and lack a prospective design. Second, all included studies are from China and the results of this meta-analysis may not be applicable to other regions of the world. Acknowledgements The National Natural Science Foundation of China (No. 81370494 and No. 31471330) funded this manuscript. Conflicts of interest There are no conflicts of interest.