Liver injury with COVID-19: laboratory and histopathological outcome—systematic review and meta-analysis

Abstract

Background The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been predominantly linked to respiratory distress syndrome, but hepatic injury has also been reported. The mechanism of liver injury is poorly understood. This review aimed to systematically review the current data through laboratory tests and liver tissue pathology to ascertain the correlation of liver involvement in SARS-CoV-2 infection patients. Methods The PubMed, Scopus, Science Direct, and Web of Science databases were searched systematically. We included peer-reviewed published papers available online as clinical cases, cohort studies, and retrospective studies, for both in vitro and in vivo human studies. Independent extraction of the data was done by two independent authors. Results A total of 15 articles were finally included in the systematic review process and meta-analysis after exclusion of studies that did not meet the eligibility criteria, summarized in a PRISMA flow diagram. The meta-analysis showed that patients with underlying abnormal liver function and/or histopathological finding had a statistically significant 8.08 times higher odds of severe COVID-19 outcomes when data from the individual studies were pooled (OR 8.08; 95% CI,3.43, 19.03; p = 0.00001). Five of these studies showed histopathological changes on autopsy from cases with severe COVID-19, and in four of these five studies, the histopathology was associated with a history of abnormal liver function after affection with COVID-19. Short conclusion The study observed that the severity of COVID-19 was associated with more patients with aberrant liver function tests.

Heterogeneity and Risk of Bias in Studies Examining Risk Factors for Severe Illness and Death in COVID-19: A Systematic Review and Meta-Analysis

“…This systematic review has several strengths. Unlike previous meta-analyses on related topics [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], this study: (i) involves a comprehensive analysis of a large number of studies that are based in different countries in the world; (ii) includes many articles that were published in 2021, after the introduction of the Delta strain; (iii) analyzes only peer-reviewed data; (iv) assesses the extensive analysis of the source of the heterogeneity and bias in the studies; and (v) compares the risk of admission to the ICU vs. no admission among hospitalized COVID-19 patients, and is stratified on the basis of comorbidities and demographic status.…”

“…However, the associations with other comorbidities have been less clear, such as with cancer, chronic liver disease, diabetes, and kidney disease. While several meta-analyses studies report an increased risk of death in COVID-19 patients with diabetes [ 5 , 11 , 19 ], cancer [ 20 , 21 , 22 ], liver disease [ 23 , 24 , 25 ], and kidney disease [ 26 , 27 , 28 , 29 ], some report the lack of correlation between these comorbidities and the disease progression or the clinical outcomes of COVID-19 patients [ 30 , 31 , 32 ].…”

From Cytokine Storm to Cytokine Breeze: Did Lessons Learned from Immunopathogenesis Improve Immunomodulatory Treatment of Moderate-to-Severe COVID-19?

“…They concluded that COVID-19 infection was not associated with a specific histopathological pattern of the liver [ 62 ]. In any case, one recently published meta-analysis demonstrated that the severity of COVID-19 was associated with aberrant liver function tests [ 63 ]. Interesting findings regarding the temporal evolution of COVID-19-associated cardiopathy were reported by Haslbauer et al [ 64 ].…”

COVID-19 associated liver injury: A general review with special consideration of pregnancy and obstetric outcomes

“…However, patients infected with SARS-CoV-2 often suffer other devastating end-organ injuries[ 10 ], suggesting the virus causes systemic infection and inflammation. These observations have prompted interest in the extra-pulmonary manifestations of COVID-19[ 11 ], including those in the heart[ 12 , 13 ], intestines[ 14 , 15 ], kidney[ 16 ], reproductive system[ 17 , 18 ], and the liver, where the effect of SARS-CoV-2 is poorly understood[ 19 , 20 ].…”

“…COVID-19 associated liver injury (COVALI) is a clinical entity encompassing any abnormal liver function test present in individuals positive for SARS-CoV-2[ 20 ]. Currently there are no specific or unique diagnostic criteria for COVALI relative to other causes of transaminitis[ 21 ] which complicates the process of synthesizing evidence from clinical studies.…”