Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center Study

Donghee Kim, Nia Adeniji, Nyann Latt, Sonal Kumar, Patricia P Bloom, Elizabeth S Aby, Ponni Perumalswami, Marina Roytman, Michael Li, Alexander S Vogel, Andreea M Catana, Kara Wegermann, Rotonya M Carr, Costica Aloman, Vincent L Chen, Atoosa Rabiee, Brett Sadowski, Veronica Nguyen, Winston Dunn, Kenneth D Chavin, Kali Zhou, Blanca Lizaola-Mayo, Akshata Moghe, José Debes, Tzu-Hao Lee, Andrea D Branch, Kathleen Viveiros, Walter Chan, David M Chascsa, Paul Kwo, Renumathy Dhanasekaran, Donghee Kim, Nia Adeniji, Nyann Latt, Sonal Kumar, Patricia P Bloom, Elizabeth S Aby, Ponni Perumalswami, Marina Roytman, Michael Li, Alexander S Vogel, Andreea M Catana, Kara Wegermann, Rotonya M Carr, Costica Aloman, Vincent L Chen, Atoosa Rabiee, Brett Sadowski, Veronica Nguyen, Winston Dunn, Kenneth D Chavin, Kali Zhou, Blanca Lizaola-Mayo, Akshata Moghe, José Debes, Tzu-Hao Lee, Andrea D Branch, Kathleen Viveiros, Walter Chan, David M Chascsa, Paul Kwo, Renumathy Dhanasekaran

Abstract

Background & aims: Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19).

Methods: We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD.

Results: Of the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19.

Conclusions: The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. Clinicaltrials.gov number NCT04439084.

Keywords: Alcohol; COVID-19; Cirrhosis; Mortality.

Copyright © 2021 AGA Institute. All rights reserved.

Figures

Figure 1
Figure 1
Liver-specific factors predicting overall survival in patients with chronic liver disease and COVID-19. (A) Overall survival from time of diagnosis of COVID-19 in patients with alcohol-related liver disease (ALD) compared with other liver disease etiologies. (B) Overall survival in patients with liver disease stratified into those with no cirrhosis vs compensated cirrhosis vs decompensated cirrhosis. Significant and hazard ratios are derived from comparison of decompensated cirrhosis vs no cirrhosis. (C) Overall survival from time of diagnosis of COVID-19 in patients with underlying hepatocellular carcinoma (HCC). COVID-19, coronavirus disease 2019.
Supplementary Figure 1
Supplementary Figure 1
Patient study cohort. The flowchart shows how the study cohort was selected. CLD, chronic liver disease; COVID-19, coronavirus disease 2019.
Supplementary Figure 2
Supplementary Figure 2
Age at time of diagnosis of COVID-19 in patients with CLD stratified by overall mortality. Histogram shows distribution of age (years) in the entire patient cohort compared with deceased patients. CLD, chronic liver disease; COVID-19, coronavirus disease 2019.
Supplementary Figure 3
Supplementary Figure 3
Patient demographics stratified by clinical outcomes. (A) Clinical outcomes of patients with CLD and COVID-19 stratified by race and ethnicity. (B) Clinical outcomes of patients with CLD and COVID-19 stratified by sex. CLD, chronic liver disease; COVID-19, coronavirus disease 2019; ICU, intensive care unit; ns, not significant.
Supplementary Figure 4
Supplementary Figure 4
Comorbidities in patients with CLD and COVID-19. (A) Clinical severity of patients with CLD and COVID-19 CLD stratified by comorbidities that affect cardiovascular health. (B) Clinical severity of patients with CLD and COVID-19 stratified by comorbidities that affect pulmonary health. Graph shows the percentage of patients with a specific comorbidity who had these outcomes. Significance determined by comparing clinical outcomes in patients with (shown) vs those without (not shown) the specific comorbidity. CAD, coronary artery disease; CHF, congestive heart failure; CLD, chronic liver disease; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; DM, diabetes mellitus; HLD, hyperlipidemia; HTN, hypertension; ICU, intensive care unit; OSA, obstructive sleep apnea. ∗indicates a significantly higher proportion. ∗P < .05; ∗∗P < 0.01; ∗∗∗P < .001; ∗∗∗∗P < .0001; ∗∗∗∗∗P < .00001.
Supplementary Figure 5
Supplementary Figure 5
Etiology of CLD among patients with COVID-19. (A) Prevalence of different etiologies of CLD in patients with COVID-19. (B) Stage of CLD in patients with COVID-19. AIH, autoimmune hepatitis; ALD, alcohol-related liver disease; CC, cholangiocarcinoma; CLD, chronic liver disease; COVID-19, coronavirus disease 2019; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis.
Supplementary Figure 6
Supplementary Figure 6
Etiology of CLD and severity of COVID-19. Comparing the proportion of patients with different etiologies of CLD requiring hospitalization, ICU admission, mechanical ventilation, vasopressors or mortality. ALD, alcohol-related liver disease; CLD, chronic liver disease; COVID-19, coronavirus disease 2019; HBV, hepatitis B virus; HCV, hepatitis C virus; ICU, intensive care unit; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis. ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001; ∗∗∗∗∗P < .00001.
Supplementary Figure 7
Supplementary Figure 7
Indications for testing and risk factors for COVID-19 and in patients with CLD. (A) Indications of COVID-19 testing in patients with CLD. (B) Risk factors for acquiring COVID-19 in patients with CLD. CLD, chronic liver disease; COVID-19, coronavirus disease 2019.
Supplementary Figure 8
Supplementary Figure 8
Presenting symptoms of COVID-19 among patients with CLD. (A) Tiled heatmap of symptoms of COVID-19 stratified by severity of COVID-19. Each vertical bar represents a single patient. (B) Frequency of different COVID-19 symptoms in patients with CLD. CLD, chronic liver disease; COVID-19, coronavirus disease 2019.
Supplementary Figure 9
Supplementary Figure 9
Liver tests during COVID-19. ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, international normalized ratio.
Supplementary Figure 10
Supplementary Figure 10
Treatment for COVID-19 among patients with CLD. (A) Frequency of COVID-19 treatments in patients with CLD. (B) Tiled heatmap of treatment of COVID-19 stratified by severity of disease. Each horizontal bar represents a single patient. CLD, chronic liver disease; COVID-19, coronavirus disease 2019; HCQ, hydroxychloroquine.

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Source: PubMed

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