Significant Liver Injury During Hospitalization for COVID-19 Is Not Associated With Liver Insufficiency or Death.

BACKGROUND & AIMS: Coronavirus-19 disease (COVID-19) is associated with hepatocellular liver injury of uncertain significance. We aimed to determine whether development of significant liver injury during hospitalization is related to concomitant medications or processes common in COVID-19 (eg, ischemia, hyperinflammatory, or hypercoagulable states), and whether it can result in liver failure and death. METHODS: There were 834 consecutive patients hospitalized with COVID-19 who were included. Clinical, medication, and laboratory data were obtained at admission and throughout hospitalization using an identified database. Significant liver injury was defined as an aspartate aminotransferase (AST) level 5 or more times the upper limit of normal; ischemia was defined as vasopressor use for a minimum of 2 consecutive days; hyperinflammatory state was defined as high-sensitivity C-reactive protein value of 100 mg/L or more, and hypercoagulability was defined as D-dimer 5 mg/L or more at any time during hospitalization. RESULTS: A total of 105 (12.6%) patients developed significant liver injury. Compared with patients without significant liver injury, ischemia (odds ratio [OR], 4.3; range, 2.5-7.4; P < .0001) and tocilizumab use (OR, 3.6; range, 1.9-7.0; P = .0001) were independent predictors of significant liver injury. Although AST correlated closely with alanine aminotransferase (R = 0.89) throughout hospitalization, AST did not correlate with the international normalized ratio (R = 0.10) or with bilirubin level (R = 0.09). Death during hospitalization occurred in 136 (16.3%) patients. Multivariate logistic regression showed that significant liver injury was not associated with death (OR, 1.4; range, 0.8-2.6; P = .2), while ischemic (OR, 2.4; range, 1.4-4.0; P = .001), hypercoagulable (OR, 1.7; range, 1.1-2.6; P = .02), and hyperinflammatory (OR, 1.9; range, 1.2-3.1; P = .02) disease states were significant predictors of death. CONCLUSIONS: Liver test abnormalities known to be associated with COVID-19 are secondary to other insults, mostly ischemia or drug-induced liver injury, and do not lead to liver insufficiency or death.

Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort.

OBJECTIVE: Comorbid conditions are associated with poor prognosis in COVID-19. Registry data show that patients with cirrhosis may be at high risk. However, outcome comparisons among patients with cirrhosis+COVID-19 versus patients with COVID-19 alone and cirrhosis alone are lacking. The aim of this study was to perform these comparisons. DESIGN: A multicentre study of inpatients with cirrhosis+COVID-19 compared with age/gender-matched patients with COVID-19 alone and cirrhosis alone was performed. COVID-19 and cirrhosis characteristics, development of organ failures and acute-on-chronic liver failure (ACLF) and mortality (inpatient death+hospice) were compared. RESULTS: 37 patients with cirrhosis+COVID-19 were matched with 108 patients with COVID-19 and 127 patients with cirrhosis from seven sites. Race/ethnicity were similar. Patients with cirrhosis+COVID-19 had higher mortality compared with patients with COVID-19 (30% vs 13%, p=0.03) but not between patients with cirrhosis+COVID-19 and patients with cirrhosis (30% vs 20%, p=0.16). Patients with cirrhosis+COVID-19 versus patients with COVID-19 alone had equivalent respiratory symptoms, chest findings and rates of intensive care unit transfer and ventilation. However, patients with cirrhosis+COVID-19 had worse Charlson Comorbidity Index (CCI 6.5±3.1 vs 3.3±2.5, p<0.001), lower presenting GI symptoms and higher lactate. Patients with cirrhosis alone had higher cirrhosis-related complications, maximum model for end-stage liver disease (MELD) score and lower BiPAP/ventilation requirement compared with patients with cirrhosis+COVID-19, but CCI and ACLF rates were similar. In the entire group, CCI (OR 1.23, 95% CI 1.11 to 1.37, p<0.0001) was the only variable predictive of mortality on multivariable regression. CONCLUSIONS: In this multicentre North American contemporaneously enrolled study, age/gender-matched patients with cirrhosis+COVID-19 had similar mortality compared with patients with cirrhosis alone but higher than patients with COVID-19 alone. CCI was the only independent mortality predictor in the entire matched cohort.

Clinical Research in Hepatology in the COVID-19 Pandemic and Post-Pandemic Era: Challenges and the Need for Innovation.

The severe acute respiratory syndrome coronavirus 2 pandemic has drastically altered all facets of clinical care and research. Clinical research in hepatology has had a rich tradition in several domains, including the discovery and therapeutic development for diseases such as hepatitis B and C and studying the natural history of many forms of chronic liver disease. National Institutes of Health, foundation, and industry funding have provided important opportunities to advance the academic careers of young investigators while they strived to make contributions to the field. Instantaneously, however, all nonessential research activities were halted when the pandemic started, forcing those involved in clinical research to rethink their research strategy, including a shift to coronavirus disease 2019 research while endeavoring to maintain their preexisting agenda. Strategies to maintain the integrity of ongoing studies, including patient follow-up, safety assessments, and continuation of investigational products, have included a shift to telemedicine, remote safety laboratory monitoring, and shipping of investigational products to study subjects. As a revamp of research is being planned, unique issues that face the research community include maintenance of infrastructure, funding, completion of studies in the predetermined time frame, and the need to reprogram career path timelines. Real-world databases, biomarker and long-term follow up studies, and research involving special groups (children, the homeless, and other marginalized populations) are likely to face unique challenges. The implementation of telemedicine has been dramatically accelerated and will serve as a backbone for the future of clinical research. As we move forward, innovation in clinical trial design will be essential for conducting optimized clinical research.