Liver Disease and Coronavirus Disease 2019: From Pathogenesis to Clinical Care.

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that emerged in late 2019, is posing an unprecedented challenge to global health. Coronavirus disease 2019 (COVID-19), the clinical disease caused by SARS-CoV-2, has a variable presentation ranging from asymptomatic infection to life-threatening acute respiratory distress syndrome and multiorgan failure. Liver involvement is common during COVID-19 and exhibits a spectrum of clinical manifestations from asymptomatic elevations of liver function tests to hepatic decompensation. The presence of abnormal liver tests has been associated with a more severe presentation of COVID-19 disease and overall mortality. Although SARS-CoV-2 RNA has been detected in the liver of patients with COVID-19, it remains unclear whether SARS-CoV-2 productively infects and replicates in liver cells and has a direct liver-pathogenic effect. The cause of liver injury in COVID-19 can be attributed to multiple factors, including virus-induced systemic inflammation, hypoxia, hepatic congestion, and drug-induced liver disease. Among patients with cirrhosis, COVID-19 has been associated with hepatic decompensation and liver-related mortality. Additionally, COVID-19's impact on health care resources can adversely affect delivery of care and outcomes of patients with chronic liver disease. Understanding the underlying mechanisms of liver injury during COVID-19 will be important in the management of patients with COVID-19, especially those with advanced liver disease. This review summarizes our current knowledge of SARS-CoV-2 virus-host interactions in the liver as well the clinical impact of liver disease in COVID-19.

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.

Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study.

BACKGROUND & AIMS: Chronic liver disease (CLD) and cirrhosis are associated with immune dysregulation, leading to concerns that affected patients may be at risk of adverse outcomes following SARS-CoV-2 infection. We aimed to determine the impact of COVID-19 on patients with pre-existing liver disease, which currently remains ill-defined. METHODS: Between 25th March and 8th July 2020, data on 745 patients with CLD and SARS-CoV-2 (including 386 with and 359 without cirrhosis) were collected by 2 international registries and compared to data on non-CLD patients with SARS-CoV-2 from a UK hospital network. RESULTS: Mortality was 32% in patients with cirrhosis compared to 8% in those without (p <0.001). Mortality in patients with cirrhosis increased according to Child-Pugh class (A [19%], B [35%], C [51%]) and the main cause of death was from respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (odds ratio [OR] 1.02; 1.01-1.04), Child-Pugh A (OR 1.90; 1.03-3.52), B (OR 4.14; 2.4-7.65), or C (OR 9.32; 4.80-18.08) cirrhosis and alcohol-related liver disease (OR 1.79; 1.03-3.13). Compared to patients without CLD (n = 620), propensity-score-matched analysis revealed significant increases in mortality in those with Child-Pugh B (+20.0% [8.8%-31.3%]) and C (+38.1% [27.1%-49.2%]) cirrhosis. Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of whom 21% had no respiratory symptoms. Half of those with hepatic decompensation had acute-on-chronic liver failure. CONCLUSIONS: In the largest such cohort to date, we demonstrate that baseline liver disease stage and alcohol-related liver disease are independent risk factors for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic. LAY SUMMARY: This international registry study demonstrates that patients with cirrhosis are at increased risk of death from COVID-19. Mortality from COVID-19 was particularly high among patients with more advanced cirrhosis and those with alcohol-related liver disease.

Effect of COVID-19 on patients with compensated chronic liver diseases.

BACKGROUND AND AIM: Cytokine storm has been reported in patients with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We examine the incidence of acute on chronic liver failure (ACLF) in COVID-19 patients with pre-existing compensated chronic liver disease (CLD). METHODS: From 20 Jan 2020 to 7 Feb 2020, we studied 140 consecutive COVID-19 patients admitted to either Fuyang Second People's Hospital (FYSPH), Anhui or the Fifth Medical Center of Chinese PLA General Hospital (PLAGH) in Beijing, China. Pre-existing CLD includes those with liver cirrhosis assessed by APRI/FIB-4 score and /or ultrasound; NAFLD as identified by either ultrasound or hepatic steatosis index with significant liver fibrosis and chronic hepatitis B (CHB) or hepatitis C (CHC) infection. The diagnosis, grading of severity and clinical management of COVID-19 patients complied to the guideline and clinical protocol issued by the China National Health Commission. All patients had liver function test at least twice weekly till discharge with full recovery or death. RESULTS: In total, 3 had liver cirrhosis, 6 patients had CHB, 13 had NAFLD with significant liver fibrosis (one also had CHB). On admission, none had liver decompensation. COVID-19 disease progression was significantly less frequent in non-CLD patients (10/118 8.5%) than CLD patients (13/22 59.1%, p < 0.001). One patient with CLD had acute-on-chronic liver failure (ACLF). CONCLUSION: Disease progression is significantly higher in those COVID-19 patients with CLD as compared to those with no CLD. ACLF can also occur in patient with pre-existing compensated CLD who had severe COVID-19.