Increasing incidence and changing trends in etiology & survival rates in HCC in a European cohort.
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BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) represents a major global health burden. While incidence rates are declining in some regions, they are rising in the Netherlands, traditionally a low-endemic country for HCC. Despite these trends, comprehensive data on longitudinal changes in etiology, tumor characteristics, and overall survival remain scarce. METHODS: Consecutive patients registered in the Netherlands Cancer Registry (NCR) with newly diagnosed HCC were included (2014-2022). Average annual percentage change (AAPC) was calculated to assess trends in age-adjusted incidence rates. Cox regression analyses were performed to determine risk factors for overall mortality. RESULTS: Between January 2014 and December 2022, 6,526 patients were diagnosed with HCC in the Netherlands. The age-adjusted incidence rate of HCC rose from 3.5 to 4.1 per 100,000 person-years, reflecting an AAPC of 2.3% (95% CI: 0.9-3.7). While alcohol-related liver disease (ALD) was the most common etiology of HCC, metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC had the highest AAPC at 8.3% (95% CI: 2.9-13.7). 1-, 3- and 5-year survival rates were 46.5, 26.1 and 18.8%, respectively. ALD-related HCC was associated with worse overall survival probability than MASLD-related HCC (HR: 1.21 (95% CI: 1.08-1.35)). Curative-intent treatment allocation had the most profound effect on overall survival probability (HR: 0.17 (95% CI: 0.15-0.19)), followed by other tumor-directed treatment (HR: 0.37 (95% CI: 0.34-0.40)), and the presence of distant metastases (HR: 1.99 (95% CI: 1.83-2.15)). CONCLUSION: This comprehensive nationwide cohort study demonstrates a sustained increase in HCC incidence rates in the Netherlands, with a significant rise in MASLD-related HCC. Overall survival remains poor. These findings underscore the need for increased clinical awareness and further investigation into surveillance strategies. IMPACT & IMPLICATIONS: Hepatocellular carcinoma (HCC) represents a major global health problem. However, comprehensive data on longitudinal changes from nationwide cohorts remain limited. This study demonstrates that the incidence rate of HCC is increasing in the Netherlands. Furthermore, it identifies treatment allocation, the presence of distant metastases, Child-Pugh C, and multifocal disease as key predictors of overall mortality. Overall survival remains poor, particularly among patients with no registered risk factor for chronic liver disease or those with unknown cirrhotic status. These findings underscore the need for increased clinical awareness and early diagnostic evaluation of underlying liver disease to facilitate timely detection, appropriate management, and improved clinical outcomes.