The Topic of COVID-19–Related Liver Injury Needs More Rigorous Research
Authors: Xiu-He Lv, Jin-Lin Yang, Kai Deng
Journal: Clinical Gastroenterology and Hepatology (2020)

We read with great interest the study written by Fan et al.1Fan Z. et al.Clin Gastroenterol Hepatol. 2020; 18: 1561-1566Abstract Full Text Full Text PDF PubMed Scopus (551) Google Scholar The authors report the clinical features of COVID-19–related liver damage. Because liver injury in COVID-19 patients is common and occurs especially in severe cases, the results of this study therefore are important. However, we do have some concerns about it. First, Fan et al1Fan Z. et al.Clin Gastroenterol Hepatol. 2020; 18: 1561-1566Abstract Full Text Full Text PDF PubMed Scopus (551) Google Scholar defined liver injury as any one of 6 parameters more than the upper limit of normal value. We understand that guidance or consensus on classification of COVID-19–related liver injury is lacking. However, a mild abnormality of these parameters should be classified more accurately as a COVID-19–associated liver biochemistry abnormality, and be distinguished from COVID-19–related liver injury, because such exceptions can be observed in a variety of situations.2Bangash M. et al.Lancet Gastroenterol Hepatol. 2020; 5: 529-530Abstract Full Text Full Text PDF PubMed Scopus (323) Google Scholar Furthermore, according to the recommendations from the American College of Gastroenterology, only 4 parameters including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin are markers of liver injury, and the increases in these parameters suggest hepatocellular injury.3Kwo P.Y. et al.Am J Gastroenterol. 2017; 112: 18-35Crossref PubMed Scopus (623) Google Scholar Second, Fan et al1Fan Z. et al.Clin Gastroenterol Hepatol. 2020; 18: 1561-1566Abstract Full Text Full Text PDF PubMed Scopus (551) Google Scholar provided valuable comparisons between 2 groups. The results showed that significant differences were found for procalcitonin and C-reactive protein, but not for CD4+ T-cell counts, CD8+ T-cell counts, and CD3+ T-cell counts. However, why these markers were selected remains unclear. As mentioned by Fan et al,1Fan Z. et al.Clin Gastroenterol Hepatol. 2020; 18: 1561-1566Abstract Full Text Full Text PDF PubMed Scopus (551) Google Scholar laboratory examination was conducted every 3 days. It is not clear whether the results were calculated using the data on the day of admission or from data collected throughout the hospitalization, which may lead to bias. In the meantime, the normal baseline levels for each parameter were not given, so the readers cannot understand the meaning of these changes between groups compared with their baseline. Third, Fan et al1Fan Z. et al.Clin Gastroenterol Hepatol. 2020; 18: 1561-1566Abstract Full Text Full Text PDF PubMed Scopus (551) Google Scholar concluded that a significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir, recommending caution when using lopinavir/ritonavir. In a recently published randomized controlled trial,4Cao B. et al.N Engl J Med. 2020; 382: 1787-1799Crossref PubMed Scopus (3823) Google Scholar there were no significant differences in alanine aminotransferase, aspartate aminotransferase, and bilirubin between the lopinavir/ritonavir group and the standard care group, showing its safety. We believe the problem may arise from a retrospective design of this study, and the fact that more patients used lopinavir/ritonavir in the abnormal liver function group may be owing to confounding resulting from age, sex, and the severity of illness. We found that there were some studies published on the topic of COVID-19–related liver injury in recent weeks. However, current studies inevitably encounter the problem of bias owing to their retrospective design. They also have not yet addressed the causes and mechanisms of liver damage associated with COVID-19 clearly. As described in a correspondence,5Peyrin-Biroulet L. Clin Gastroenterol Hepatol 2020 Mar 30. pii: S1542-3565(20)30431-6. https://doi.org/10.1016/j.cgh.2020.03.054. Epub ahead of print.Google Scholar we hope more studies with rigorous design are conducted in the near future. Clinical Features of COVID-19-Related Liver Functional AbnormalityClinical Gastroenterology and HepatologyVol. 18Issue 7PreviewSome patients with SARS-CoV-2 infection have abnormal liver function. We aimed to clarify the features of COVID-19-related liver damage to provide references for clinical treatment. Full-Text PDF ReplyClinical Gastroenterology and HepatologyVol. 18Issue 12PreviewWe thank Chen and Zhou,1 Lv et al,2 and Ye and Song3 for the comments on our study. We did not apply the definition of drug-induced liver injury from the European Association for the Study of the Liver Clinical Practice Guidelines in our study because the exact mechanism of COVID-19-related liver damage is still unclear (eg, a drug, the virus itself, immune response, or a mixture). We defined COVID-19-related liver injury based on elevation in any 1 of the 5 (not 6) parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), and total bilirubin. Full-Text PDF Liver Function Should Be Monitored When Treating COVID-19 in Chronic HBV-Infected PatientsClinical Gastroenterology and HepatologyVol. 18Issue 13PreviewWe appreciate the comment by Lv et al on our article. In our study, we aimed to describe the characteristics of liver function and its relationship with severity of disease and prognosis of patients with severe acute respiratory syndrome–associated coronavirus 2 (SARS-CoV-2) and chronic hepatitis B virus (HBV) coinfection. Therefore, only patients with SARS-CoV-2 and chronic HBV coinfection were enrolled. Although we did not compare coronavirus disease 2019 (COVID-19) patients with HBV coinfection and patients with SARS-CoV-2 infection alone in our study, Chen et al1 found no significant differences in liver function parameters, discharge rate, length of stay, severity, and mortality between COVID-19 patients with and without HBV infection. Full-Text PDF