Temporal Trends and Regional Variations in Hepatocellular Carcinoma Etiology:  A Multinational Study Across Asia

Background: Hepatocellular carcinoma (HCC) remains a major health burden in Asia. Advances in antiviral therapies are reshaping the etiological landscape of HCC. This study evaluated temporal shifts in HCC etiology across Asian countries and their clinical implications. Methods: This multinational study analyzed 6,261 newly diagnosed HCC patients registered in the APASL Hepatology/Oncology Consortium (A-HOC) from 19 centers across seven Asian countries and regions between 2013 and 2023. Data on demographics, tumor characteristics, etiology, and treatment patterns were collected. Etiologies included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), metabolic dysfunction-associated fatty liver disease (MAFLD), MAFLD plus excess alcoholic intake (MAFLD + eAL), autoimmune liver disease, cryptogenic, and others. Temporal trends and regional variations were assessed. Results: In many countries, HBV remained predominant (43.3% to 69.5%) and relatively stable throughout the period, while HCV showed only modest reductions. In Japan, HCV was the leading cause of HCC (33.1%), with a significant decline over time, accompanied by a rise in MAFLD-related HCC. ALD-related HCC increased in South Korea, and MAFLD-related HCC rose in Turkey. Tumor size and stage at diagnosis varied by etiology and region, affecting treatment strategies. Early-stage diagnosis was more frequent in Japan and Taiwan, whereas advanced-stage HCC was common in China and Indonesia. Conclusions: Distinct regional patterns and temporal changes in HCC etiology across Asia highlight the need for tailored prevention and surveillance measures. The growing burden of MAFLD-related HCC emphasizes its emerging role in liver cancer development, particularly in regions with declining viral hepatitis.