Risk factors and outcomes for acute-on-chronic liver failure in COVID-19: a large multi-center observational cohort study.

OBJECTIVE: Coronavirus disease 2019 [COVID-19] infection in patients with chronic liver disease [CLD] may precipitate acute-on-chronic liver failure [ACLF]. In a large multi-center cohort of COVID-19-infected patients, we aim to analyze (1) the outcomes of patients with underlying CLD [with and without cirrhosis] and (2) the development and impact of ACLF on in-hospital mortality. DESIGN: We identified 192 adults with CLD from among 10,859 patients with confirmed COVID-19 infection (admitted to any of 12 hospitals in a New York health care system between March 1, 2020 and April 27, 2020). ACLF was defined using the EASL-CLIF Consortium definition. Patient follow-up was through April 30, 2020, or until the date of discharge, transfer, or death. RESULTS: Of the 84 patients with cirrhosis, 32 [38%] developed ACLF, with respiratory failure [39%] and renal failure [26%] being the most common. Hispanic/Latino ethnicity was particularly at higher risk of in-hospital mortality [adjusted HR 4.92, 95% 1.27-19.09, p < 0.02] in cirrhosis despite having lower risk of development of ACLF [HR 0.26, 95% CI 0.08-0.89, p = 0.03]. Hypertension on admission predicted development of ACLF [HR 3.46, 95% CI 1.12-10.75, p = 0.03]. In-hospital mortality was not different between CLD patients with or without cirrhosis [p = 0.24] but was higher in those with cirrhosis who developed ACLF [adjusted HR 9.06, 95% CI 2.63-31.12, p < 0.001] with a trend for increased mortality by grade of ACLF [p = 0.002]. There was no difference in in-hospital mortality between the CLD cohort compared to matched control without CLD (log rank, p = 0.98) and between the cirrhosis cohort compared to matched control without cirrhosis (log rank, p = 0.51). CONCLUSION: Development of ACLF is the main driver of increased in-hospital mortality in hospitalized patients with COVID-19 infection and cirrhosis.

Severity of liver test abnormalities in coronavirus disease 2019 depends on comorbidities and predicts early in-hospital mortality.

BACKGROUND AND AIMS: Liver chemistry abnormalities (LCA) are common in patients with coronavirus disease 2019 (COVID-19), but their causes and clinical impact have not been adequately studied. We assessed the associations between LCA and clinical characteristics, inflammatory serum markers, in-hospital mortality. METHODS: Ten thousand eight hundred fifty-six adult patients with COVID-19 hospitalized in 13 hospitals in New York (1 March to 27 April 2020) were analyzed retrospectively. Abnormalities of liver chemistries [aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, or total bilirubin] were defined as absent, mild-moderate (at least one value up to four times elevated), or severe. RESULTS: LCA were mild-moderate in 63.9% and severe in 7.6% at admission. Risk factors for severe LCA were male sex and chronic liver disease. Conversely, hypertension and diabetes mellitus were less likely associated with severe LCA. AST elevation correlated weakly to modestly with inflammatory markers. On adjusted analysis, in-hospital mortality was 1.56 times and 1.87 times increased in patients with mild-to-moderate and severe LCA, respectively. Diabetes, hypertension, male sex, and age greater than 60 years was associated with incremental risk of mortality with increase severity of LCA, especially in the first week of hospitalization. HTN was not associated with increased in-hospital mortality unless LCA was present. CONCLUSION: Increasing severity of LCA on hospital admission predicts early in-hospital mortality in COVID-19 patients. Mortality associated with the known risk factors, hypertension, diabetes, male sex, and old age was accentuated in the presence of LCA. AST correlated modestly with inflammatory markers.

Post-COVID-19 Cholangiopathy: A Novel Entity.

INTRODUCTION: Liver chemistry abnormalities are a frequent manifestation of coronavirus disease 2019 (COVID-19) but are usually transient and resolve with disease resolution. METHODS: We describe the clinical course and histologic features of 3 adults who developed prolonged and severe cholestasis during recovery from critical cardiopulmonary COVID-19. RESULTS: These patients had clinical and histologic features similar to secondary sclerosing cholangitis of the critically ill patient, but with unique histologic features including severe cholangiocyte injury and intrahepatic microangiopathy suggestive of direct hepatic injury from COVID-19. DISCUSSION: We believe that these cases constitute a novel severe post-COVID-19 cholangiopathy with potential for long-term hepatic morbidity.