Supplementary Material for: Risk of Hepatocellular Carcinoma by Steatotic Liver Disease and Its Newly Proposed Sub-Classification

Introduction: Steatotic liver disease (SLD) is a new overarching term proposed to replace non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction associated fatty liver disease (MAFLD). Subclassification includes metabolic dysfunction associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and cryptogenic SLD. This study aimed to investigate whether SLD and its subclassification could stratify hepatocellular carcinoma (HCC) risk. Methods: A cohort of 85,119 adults without viral hepatitis or heavy alcohol intake were analyzed for the risk of HCC according to SLD and its subclassification. Fibrosis-4 index (FIB-4) was used to estimate degree of liver fibrosis. Results: During a median follow-up of 11.9 years, HCC was diagnosed in 123 individuals. The incidence rate of HCC per 1,000 person-years was higher in individuals with SLD than in those without SLD (0.197 vs. 0.071, p < 0.001), with an adjusted hazard ratio of 2.02 (95% confidence interval: 1.40-2.92). The HCC incidence rate per 1,000 person-years was 0, 0.180, and 0.648 for cryptogenic SLD, MASLD, and MetALD, respectively. When participants with SLD was further stratified by FIB-4 index, the HCC incidence rate per 1,000 person-years was 0.074 for SLD with FIB-4 < 1.3 and 0.673 for SLD with FIB-4 ≥ 1.3. Of note, HCC risk was substantially high (HCC incidence rate: 1.847 per 1,000 person-years) for MetALD with FIB-4 ≥ 1.3. Conclusions: HCC risk was different by SLD and its subclassification. The utilization of SLD and its subclassification can aid in stratifying HCC risk and facilitate the identification of individuals requiring interventions to mitigate the risk of HCC.

引言：脂肪性肝病（Steatotic Liver Disease, SLD）是一项新近提出的统称术语，用于替代非酒精性脂肪性肝病（Non-Alcoholic Fatty Liver Disease, NAFLD）与代谢功能异常相关性脂肪性肝病（Metabolic Dysfunction Associated Fatty Liver Disease, MAFLD）。该疾病的亚分类包括代谢功能异常相关性脂肪性肝病（Metabolic Dysfunction Associated Steatotic Liver Disease, MASLD）、伴饮酒量增加的MASLD（MetALD）以及隐源性脂肪性肝病（cryptogenic SLD）。本研究旨在探讨脂肪性肝病及其亚分类能否对肝细胞癌（Hepatocellular Carcinoma, HCC）发病风险进行分层。方法：本研究纳入85119名无病毒性肝炎或重度饮酒史的成人队列，依据脂肪性肝病及其亚分类分析肝细胞癌发病风险。采用肝纤维化4指数（Fibrosis-4 Index, FIB-4）评估肝纤维化程度。结果：中位随访11.9年期间，共123名受试者被确诊为肝细胞癌。脂肪性肝病受试者的每1000人年肝细胞癌发病率高于无脂肪性肝病受试者（0.197 vs 0.071，p<0.001），校正后的危险比为2.02（95%置信区间：1.40~2.92）。隐源性脂肪性肝病、MASLD及MetALD受试者的每1000人年肝细胞癌发病率分别为0、0.180及0.648。当依据FIB-4指数对脂肪性肝病受试者进一步分层时，FIB-4<1.3的脂肪性肝病受试者每1000人年肝细胞癌发病率为0.074，FIB-4≥1.3者则为0.673。值得注意的是，伴FIB-4≥1.3的MetALD受试者肝细胞癌风险极高，每1000人年发病率达1.847。结论：脂肪性肝病及其亚分类对应的肝细胞癌发病风险存在差异。采用脂肪性肝病及其亚分类可有助于肝细胞癌风险分层，助力识别需采取干预措施以降低肝细胞癌发病风险的人群。