Global burden of cirrhosis and other chronic liver diseases caused by specific etiologies from 1990 to 2021.

Background: The global burden of cirrhosis and chronic liver diseases has remained substantial and continues to evolve in response to shifting etiological patterns. While viral hepatitis and alcohol use have historically dominated, non-alcoholic fatty liver disease (NAFLD) is emerging as a major contributor worldwide. A comprehensive understanding of these trends across regions and sociodemographic levels is essential for targeted public health interventions.

Methods: We analyzed data on cirrhosis and chronic liver diseases from 1990 to 2021 using estimates from the Global Burden of Disease (GBD) study. Age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and disability-adjusted life years rate (ASDR) were assessed globally and across sociodemographic index (SDI) levels. Estimated annual percentage change (EAPC) was calculated to quantify temporal trends.

Results: From 1990 to 2021, NAFLD-related cirrhosis was the only etiology with a significantly increasing ASIR (EAPC = 0.73; 95% CI: 0.69-0.77), while viral and alcohol-related cirrhosis showed stable or declining trends. In 2021, NAFLD became the leading global cause of incident cirrhosis. Although high-SDI countries demonstrated effective control of HBV and HCV-related mortality, NAFLD remains a major and growing challenge. The ASMR of NAFLD-related cirrhosis showed a fluctuating pattern overall but increased notably in several low- to middle-SDI countries, particularly in Eastern Europe (e.g., EAPC in ASMR = 3.8). HCV-related ASIRs were concentrated in Central Asia, especially in Mongolia, Turkmenistan, and Uzbekistan. HBV-related ASMR declined rapidly in countries with SDI below 0.65, then plateaued.

Conclusions: Cirrhosis and chronic liver diseases remain a major global health challenge. NAFLD has emerged as the predominant cause of incident cirrhosis, affecting both high-income and lower-SDI countries, signaling a critical shift toward metabolic etiologies. These findings call for urgent, region-specific strategies that integrate prevention, early detection, and management of both infectious and metabolic liver disease risk factors.