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HCC, Decompensation, Alcohol, Tied to
Death in Liver Patients With COVID-19
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AASLD The Liver Meeting Digital Experience, November 13-16, 2020
Mark Mascolini
Hepatocellular carcinoma (HCC), decompensated cirrhosis, and alcoholic liver disease all independently boosted odds of all-cause mortality 3-fold or more in people with chronic liver disease (CLD) who got COVID-19 [1]. In an 867-person study available as a journal preproof [2] shortly before the AASLD Liver Meeting, researchers from 23 US centers found that alcoholic liver disease raised odds of COVID-19 death more than 3-fold in this CLD population.
Because CLD afflicts many people across the world in the face of the COVID-19 pandemic, US researchers conducted the COLD study with three aims: (1) to determine independent predictors of all-cause mortality in people with CLD and COVID-19, (2) to determine independent predictors of COVID-19-related mortality in people with CLD, and (3) to assess the risk of severe COVID-19 (hospital admission, intensive care unit [ICU] admission, mechanical ventilation, or use of vasopressors, which treat severely low blood pressure) in people with CLD.
The study involved US adults with CLD and lab-confirmed COVID-19 identified in electronic medical records at 23 centers across the United States from March through May 2020. The research group formed on April 14, 2020 and began patient accrual immediately (ClinicalTrials.gov identifier NCT04439084). Researchers excluded people with liver transplantation. They used Cox proportional hazards analyses to identify independent predictors of outcomes.
Among 867 participants, median age stood at 59 years and 54.5% were men. Similar proportions were non-Hispanic white (30.9%), non-Hispanic black (30.8%), and Hispanic (25.3%). Asians made up 5% of the group.
Over half of these people, 61%, got admitted to the hospital, 23% needed ICU support, and 18% needed mechanical ventilation. Overall mortality stood at 14% and COVID-19 mortality at 12%.
ICU admission, need for mechanical ventilation, vasopressor therapy, and deaths did not differ by race/ethnicity. Hispanics and non-Hispanic Asians got admitted to the hospital more often than non-Hispanic blacks or whites (about 70% versus 55%). Hospital admission proved significantly more frequent in men than women, but the other 4 indicators of severe COVID-19 did not differ by gender.
Rates of gastrointestinal (GI) symptoms did not differ between people who survived and those who died. But 3 symptoms proved significantly more frequent in people with severe COVID-19 versus nonsevere COVID-19: diarrhea (30.7% vs 18.9%, P = 0.001), nausea/vomiting (28.5% vs 18%, P = 0.002), and anorexia (29.8% vs 14.5%, P < 0.001). Anosmia (no sense of smell) was less frequent in people with severe COVID-19 (11.1% vs 19.5%, P = 0.010).
The multivariate model to predict all-cause mortality adjusted for age, sex, race/ethnicity, CLD cause, cirrhosis, hepatic decompensation, HCC, several nonliver comorbidities, smoking status, and alcohol consumption. Eight demographic, behavioral, liver-specific factors, or nonliver comorbidities independently raised the risk of all-cause mortality: HCC (odds ratio [OR] about 6), COPD (OR about 4), alcoholic liver disease (OR about 3), decompensated cirrhosis (OR about 3), current smoking (OR about 3), diabetes (OR about 2), hypertension (OR about 2), and older age.
People with decompensated cirrhosis did significantly worse than those with compensated cirrhosis or noncirrhotic CLD in all 5 measures of severe COVID-19: hospital admission, ICU admission, mechanical ventilation, vasopressor use, and death (for death, hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.01 to 3.21, P < 0.045).
Participants with alcoholic liver disease did significantly worse than those with other liver disease in all 4 indicators of severe COVID-19 and had significantly higher COVID-related mortality (HR 3.24, 95% CI 1.64 to 6.41, P = 0.001). Among all CLD patients, one third actively used alcohol.
People with HCC had more than a 3-fold higher death risk than those without HCC (HR 3.31, 95% CI 1.53, to 7.16, P = 0.002). In this study group 52.4% with HCC died. But HCC was not significantly more frequent in people admitted to the hospital, admitted to the ICU, needing mechanical ventilation, or needing vasopressors.
The researchers believe their findings can help prioritize people with CLD for future COVID-19 vaccination and for inclusion in prospective COVID-19 studies and treatment trials. They stressed that liver-specific drivers of mortality in people with COVID-19 were alcoholic liver disease, HCC, and decompensated cirrhosis. Because of the higher COVID-19-specific death risk with alcoholic liver disease, the investigators urged clinicians to strongly discourage excess alcohol use during the pandemic. The researchers also think clinicians should use telemedicine when possible during the pandemic to help contain the coronavirus.
References
1. Adeniji N, Kim D, Latt NL, et al. Predictors of outcomes of COVID-19 in patients with chronic liver disease: US multi-center study. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 9.
2. Kim D, Adeniji N, Latt NL, et al. Predictors of outcomes of COVID-19 in patients with chronic liver disease: US multi-center study. Clin Gastroenterol Hepatol. September 2020. DOI: https://doi.org/10.1016/j.cgh.2020.09.027
Predictors of Outcomes of COVID-19 in Patients with Chronic Liver Disease: US Multi-center Study - (11/05/20)
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. In oil she said they had higher risk for only hospitalization.
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.
Another subgroup that was found in our study to be at significantly high risk for mortality was that of patients with HCC. The all-cause mortality rate in this subgroup was 52.4% (n = 11), almost 7-fold higher than in patients without HCC, however the number of patients is small. Patients with cancer, in general, have worse clinical outcomes after COVID-19 14,26. Patients with HCC may be uniquely susceptible to COVID-19 related complications due to a constellation of active malignancy, presence of cirrhosis, as well as the presence of an active underlying liver disease that led to that cirrhosis, all resulting in compromised immune function, which may be further complicated by HCC-directed treatment.
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