Liver Cancer Etiology in Asian Subgroups and American Indian, Black, Latino, and White Populations.

Importance: Hepatocellular carcinoma (HCC) is a major public health issue in the US, linked to hepatitis C virus (HCV), hepatitis B virus (HBV), alcohol-related liver disease (ALD), and metabolic dysfunction-associated steatotic liver disease (MASLD). Monitoring HCC high-risk populations and trends across increasingly diverse groups is crucial for targeted prevention and intervention strategies. Objective: To evaluate incidence patterns and temporal trends in HCC incidence by etiology across sex, race and ethnicity, and detailed Asian subgroups in California, highlighting emerging metabolic risks and declining viral influences, to guide targeted prevention strategies. Design, Setting, and Participants: This population-based, retrospective cohort study used data from the California Cancer Registry linked to statewide hospital diagnostic records for etiology classification. All HCC cases diagnosed between 2010 and 2018 in California were included. Data were analyzed from March 28 to November 3, 2024. Exposure: Etiology of HCC, categorized as HCV, HBV, ALD, MASLD, or other causes. Main Outcomes and Measures: Age-adjusted incidence rates (AAIRs) of HCC, stratified by sex, race and ethnicity, and etiology. Trends were analyzed using Joinpoint regression. Results: From 2010 to 2018, 31 671 patients (23 558 [74.4%] male; median [IQR] age, 64 [15] years) were newly diagnosed with HCC in California, with 14 664 (46.3%) due to HCV, 7457 (23.5%) due to MASLD, 3941 (12.4%) due to ALD, and 3271 (10.3%) due to HBV. By 2017 to 2018, MASLD accounted for 27.4% of HCCs, surpassing HCV among women. HCV-related HCC rates per 100 000 population were highest among American Indian (men: 12.8; women: 3.6), Black (men: 10.8; women: 3.0), and US-born Latino (men: 15.7; women: 3.5) populations and specific Asian groups (particularly Cambodian [men: 15.5; women: 6.3] and Vietnamese [men: 13.7; women: 4.8]). Rates of MASLD-related HCC per 100 000 population were highest among American Indian (men: 4.2; women: 2.7), Asian and Pacific Islander (men: 3.9; women: 1.8), and Latino (men: 4.4; women: 2.9) populations. Rates of HBV-related HCC per 100 000 population remained high throughout the study period in some Asian and Pacific Islander subgroups (Cambodian [men: 18.3; women: 3.4], Chinese [men: 10.1; women: 2.6], Korean [men: 11.5; women: 2.8], Laotian [men: 25.0; women: 5.4], and Vietnamese [men: 16.6; women: 3.5]), but not all subgroups, and HBV-related HCC declined overall. During 2014 to 2018, the overall HCC incidence changed annually by -3.1% (95% CI -4.8% to -1.4%) in men and -3.2% (95% CI, -10.9% to -0.9%) in women, largely due to declines in HCV-related HCC. However, MASLD- and ALD-related HCC rates increased throughout 2010 to 2018 (MASLD: 1.9% [95% CI, 0.8% to 3.0%]; ALD: 1.9% [95% CI, 0.6% to 3.1%]). Conclusions and Relevance: This retrospective cohort study found that etiology of HCC was associated with detailed racial and ethnic groups, with notable variation across disaggregated Asian groups. Rates of MASLD-related and ALD-related HCC were increasing, posing new challenges for prevention. American Indian, Asian and Pacific Islander, and Latino populations were disproportionately affected by HCC, beyond viral causes. Targeted public health interventions addressing alcohol, viral, and metabolic risk factors are needed.