Abstract
BACKGROUND: Current trends in complications and mortality among individuals with chronic liver disease and cirrhosis are largely unknown. OBJECTIVE: To explore changes in mortality trends among patients with cirrhosis and chronic liver disease based on etiology in the Veneto Region (Italy), to differentiate mortality between liver-related and non-liver-related causes before and during the COVID-19 pandemic, and to determine trends in the development of cirrhosis complications. METHODS: Three subsequent population-based cohorts of individuals with chronic liver disease/cirrhosis were identified in Veneto (North-eastern Italy, 4.9 million residents): the first enrolled before introduction of direct-acting antivirals (DAA); the second corresponding to full availability of DAA treatment; and the last enrolled at the beginning of the pandemic. Risks of liver decompensation and death-liver and non-liver related-were recorded for each cohort during a 3-year follow-up. Changes in the risk of death across cohorts were measured by risk ratios (RR) obtained through Poisson regression models with robust error variance. RESULTS: Across the cohorts spanning over 10 years, we found that the number of individuals with CLD and cirrhosis remained stable at about 40,000 and 10,000, respectively. The 3-year risk of ascites, hepatic encephalopathy, and hepatocellular carcinoma decreased across the study period, largely due to individuals with HCV-related liver disease. The overall 3-year mortality risk declined by 14% (liver cirrhosis, subjects enrolled in 2020 vs. 2013: RR = 0.86, 95% CI 0.83-0.89), especially among those with viral etiology. In contrast, mortality due to alcohol-related chronic liver disease/cirrhosis was stable or increasing during the COVID-19 pandemic, especially for non-liver causes of death. CONCLUSIONS: Despite increased awareness and proactive enrollment into patient care, chronic liver disease and cirrhosis remain significant health-challenges. The reduction in HCV-related mortality underscores the impact of antiviral treatments, while the persistently high mortality risk of alcohol-related disease highlights the need for targeted interventions.