A meta-analysis of the impact of COVID-19 on liver dysfunction

Abstract

Background The novel coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to a worldwide pandemic. Except representative manifestation of pneumonia and acute respiratory symptoms, COVID-19 patients have also shown different levels of liver injury or liver dysfunction. The aim of our study was to explore the probable clinical severity and mortality of COVID-19 patients and their liver dysfunction. Method A combination of computer and manual retrieval was used to search in Medline through PubMed, EMBASE and Web of Science. Review Manager 5.3 software was used to examine the heterogeneity among the studies and to calculate the combined effect value (OR, 95CI). Subgroup analysis, sensitivity analysis, and publication bias test were also performed. Results We found a significant connection between liver dysfunction and mortality of COVID-19 patients with a pooled OR of 1.98 (95% CI 1.39–2.82; P = 0.0002). There was a significant association between AST and severity of COVID-19 with a pooled OR of 4.48 (95% CI 3.24–7.21; P < 0.001), and a pooled WMD of 3.35 (95% CI, 2.07 to 4.64; P < 0.001). In addition, there was a significant difference between TBIL and severity of COVID-19, with a pooled OR of 1.91 (95% CI 1.40–2.60; P < 0.001), and with a pooled WMD of 1.18 (95% CI, 0.78 to 1.58; P < 0.001). Conclusion The mortality and severity of COVID-19 patients are significantly associated with liver dysfunction. The non-survivors and severe COVID-19 patients have elevated serum AST levels than the survivors and non-severe COVID-19 patients. The results of this study form a basis for better clinical liver management of patients with COVID-19.

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

“…In support, intra-gastric inoculation of SARS-CoV-2 in a mouse model expressing human ACE2 caused productive infection and most interestingly led to pulmonary pathological changes [40]. A significant association between liver dysfunction and mortality of COVID-19 patients has been also reported [41,42], which may vasodilation, increased capillary permeability, apoptosis/necrosis of endothelial cells as well as 12. ARDS-induced "cytokine storm" and likely virus entry to the circulation which may then cause systemic failure due to broad organotropism in tissues expressing high levels of ACE2 (e.g., heart and kidneys) or the "cytokine storm"-related excessive inflammation, are indicated.…”

“…In support, intra-gastric inoculation of SARS-CoV-2 in a mouse model expressing human ACE2 caused productive infection and most interestingly led to pulmonary pathological changes [ 40 ]. 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.…”

Risk Factors and Prognosis in Patients with COVID-19 and Liver Injury: A Retrospective Analysis

“… 10 A meta-analysis proved that there was a relationship between liver injury and severity and mortality of patients with COVID-19. 11 However, Wang et al 9 reported there were no differences in ALT between survival and death, and argued that although liver injury was common in patients with infectious SARS-Cov-2, abnormal liver functioning may not a notable symptom of COVID-19 disease. Our study found that AST on admission and at its peak was higher in critical patients than the other two groups, suggesting that AST was associated with disease severity; however, ALT on admission showed no difference among the three groups.…”

Coronavirus Disease-2019 (COVID-19) and the Liver

“…26 The prevalence of aspartate aminotransferase (AST) elevation ranged between 4% to 53% in a Chinese cohort and up to 58% in a USA cohort. 23,25,26 Both enzymes were mildly elevated in terms of absolute numbers and less than 5-times the upper limit of normal (ULN) in the majority. Kulkarni et al 13 in their meta-analysis, placed the pooled incidence of AST and ALT elevation at 22.5% and 20.1%, respectively.…”

“…Alanine aminotransferase (ALT) elevations were seen in 4% to 33% of cases, according to China's initial reports, [23][24][25] and 39% of cases in a large study from New York, USA. 26 The prevalence of aspartate aminotransferase (AST) elevation ranged between 4% to 53% in a Chinese cohort and up to 58% in a USA cohort.…”