Trends of Cirrhosis-related Mortality in the USA during the COVID-19 Pandemic

Abstract

Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavirus disease 2019 (COVID-19) pandemic. A nationwide dataset that includes more than 99% of the decedents in the U.S. between April 2012 and September 2021 was used. Projected age-standardized mortality during the pandemic were estimated according to prepandemic mortality rates, stratified by season. Excess deaths were determined by estimating the difference between observed and projected mortality rates. A temporal trend analysis of observed mortality rates was also performed in 0.83 million decedents with cirrhosis between April 2012 and September 2021 was included. Following an increasing trend of cirrhosis-related mortality before the pandemic, with a semiannual percentage change (SAPC) of 0.54% [95% confidence interval (CI): (0.0-1.0%), p=0.036], a precipitous increase with seasonal variation occurred during the pandemic (SAPC 5.35, 95% CI: 1.9-8.9, p=0.005). Significantly increased mortality rates were observed in those with alcohol-associated liver disease (ALD), with a SAPC of 8.44 (95% CI: 4.3-12.8, p=0.001) during the pandemic. All-cause mortality of nonalcoholic fatty liver disease rose steadily across the entire study period with a SAPC of 6.79 (95% CI: 6.3-7.3, p<0.001). The decreasing trend of HCV-related mortality was reversed during the pandemic, while there was no significant change in HBV-related deaths. While there was significant increase in COVID-19-related deaths, more than 55% of the excess deaths were the indirect impact of the pandemic. We observed an alarming increase in cirrhosis-related deaths during the pandemic especially for ALD, with evidence in both direct and indirect impact. Our findings have implications on formulating policies for patients with cirrhosis.

Keywords: Alcohol-associated liver disease; COVID-19; Cirrhosis mortality; Epidemiology; Nonalcoholic fatty liver disease.

Fig. 1. Age-standardized mortality rate (ASMR) for cirrhosis in the USA between 2012 and 2021.

(A) Temporal trend of ASMR between 2012 and 2021, divided by 6 months; (B) Overall cirrhosis: comparison between predicted and observed mortality rates in 4/2020–9/2020 (green cross vs. green dot), 10/2020–3/2021 (orange star vs. orange dot), and 4/2021–9/2021 (green cross vs. green dot); (C) ALD; (D) NAFLD; (E) Hepatitis C; (F) Hepatitis B; (G) Autoimmune liver disease. *Only one linear regression was fitted to the trends in (E) and (F) as there were no significant seasonal variations observed in these two panels. **R square for predictive models: (B) 4–9/2020: 0.935, 10/2020–3/2021: 0.858; (C) 4–9/2020: 0.987, 10/2020–3/2021: 0.966; (D) 4–9/2020: 0.988, 10/2020–3/2021: 0.993; (E) 0.971; (F) 0.802; (G) 4–9/2020: 0.046, 10/2020–3/2021: 0.043. ***The trend for hepatitis C in (E) started from 4/2015 to coincide with availability of new antivirals for HCV. CI, confidence interval; OLS, ordinary least squares.

Fig. 2. Trend of cause of death of people with cirrhosis.

(A) Between April and September and (B) between October and March of the following year. The trend was stratified by season to allow better visualization.