COVID-19-Induced Hepatic Injury: A Systematic Review and Meta-Analysis

Abstract

Background The current pandemic of the novel coronavirus disease (COVID-19) is a global health challenge. Pulmonary dysfunction is the main outcome of COVID-19 infection. In critically ill patients, however, liver complications have also been reported. Thus, we conducted a systematic review and meta-analysis to draw generalized conclusions regarding impaired liver biochemistry and its potential relationship with COVID-19 disease severity. Materials and Methods We searched the PubMed, Scopus, and Web of Science databases for all the related literature published up to June 20, 2020. The data were analyzed using R statistical software. A random-effects model was employed for pooling the data. The risk of bias and quality of included studies was assessed using the modified Newcastle-Ottawa Scale (NOS) for cohort studies. Results The present meta-analysis comprises 10 retrospective and two prospective studies (6,976 COVID-19 patients). The serum analysis revealed significantly higher levels of alanine aminotransferases and aspartate aminotransferases and significantly lower albumin levels. Moreover, insignificant increases in serum levels of total bilirubin were observed. Upon subgroup analysis of six studies (severe cases, n=131; non-severe cases, n=334) stratified on the basis of disease severity, we found that these abnormalities were relatively higher in severe cases of COVID-19

Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications

“…A significant association between liver dysfunction and mortality of COVID-19 patients has been also reported [ 41 , 42 ], which may relate to direct viral infection (still questionable due to relatively low ACE2 expression levels in the liver [ 17 ]); to indirect damage because of drug-induced liver injury or because of COVID-19-triggered systemic inflammation [ 43 ]. Analyses of severe COVID-19-induced biochemical alterations in the liver have shown the elevation of liver enzymes, such as alanine aminotransferases and aspartate aminotransferases, and significantly lower albumin levels [ 43 , 44 ] and thus, liver markers should be monitored continuously during COVID-19 evolvement. ACE2 and TMPRSS2 are highly expressed in gallbladder [ 17 ], whereas regarding pancreas ACE2 is expressed in exocrine tissue microvasculature and in a subset of pancreatic ducts with TMPRSS2 expression being restricted to ductal cells [ 45 , 46 ].…”

COVID-19 and liver dysfunction: Epidemiology, association and potential mechanisms

“…The levels of AST, ALT, TBIL, globulin, GGT, ALP, and PT increased, while levels of ALB decreased among COVID-19 patients with liver injury during COVID-19 progression. The proportion of increased AST was 15%–34% [ 7 , 29 , 30 , 35 , 37 , 63 , 67 , 70 , 71 , 72 , 73 , 74 , 75 ]. Labenz et al [72] reported that the mean AST value was 33 U/L among COVID-19 patients, and Bansal et al [76] reported that the mean AST value was 27.28 IU/L among COVID-19 patients.…”

“…Labenz et al [72] reported that the mean AST value was 33 U/L among COVID-19 patients, and Bansal et al [76] reported that the mean AST value was 27.28 IU/L among COVID-19 patients. The proportion of increased ALT was 15%–28% [ 7 , 29 , 30 , 35 , 37 , 63 , 67 , 70 , 71 , 72 , 73 , 74 , 75 ].…”

Special Considerations in the Management of Autoimmune Hepatitis in COVID-19 Hotspots: A Review

“…Liver abnormalities noted to be present in patients having COVID-19 include transaminitis, hyperbilirubinemia and hypoalbuminemia. [8][9][10][11] These abnormalities are thought to occur by one or more of the following several mechanisms (Fig. 1): direct cytopathy; 12 immune-mediated; 13 3. hypoxia-related; 14 drug-induced; 14 and, microvascular thrombosis.…”