Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, United States of America.
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
PLoS Med. 2024 Oct 25;21(10):e1004479. doi: 10.1371/journal.pmed.1004479. eCollection 2024 Oct.
Detailed subgroup incidence rates for steatotic liver disease (SLD)-related hepatocellular carcinoma (HCC) are critical to inform practice and public health interventions but remain sparse. We aimed to fill in this gap.
In a retrospective cohort study of adults with SLD from the United States (US) Merative Marketscan Research Databases (1/2007 to 12/2021), we estimated HCC incidence stratified by sex, age, cirrhosis, diabetes mellitus (DM), and a combination of all these 4 factors. We excluded patients with significant alcohol use and chronic viral hepatitis. We analyzed data from 741,816 patients with SLD (mean age 51.5 ± 12.8 years, 46% male, 14.7% cirrhosis). During a 2,410,166 person-years (PY) follow-up, 1,740 patients developed HCC. The overall HCC incidence yielded 0.72 per 1,000 PY (95% confidence interval [CI, 0.68, 0.75]). The incidence was higher in males (0.95, 95% CI [0.89, 1.01]) compared to females (0.52, 95% CI [0.48, 0.56]) (p < 0.001). For those with cirrhosis, the incidence was significantly higher at 4.29 (95% CI [4.06, 4.51]) compared to those without cirrhosis (0.14, 95% CI [0.13, 0.16]) (p < 0.001). Additionally, the incidence was higher in patients with DM (1.19, 95% CI [1.12, 1.26]) compared to those without DM (0.41, 95% CI [0.38, 0.44]) (p < 0.001). Chronic kidney disease (CKD) was also associated with a higher HCC incidence of 2.20 (95% CI [2.00, 2.41]) compared to those without CKD (0.58, 95% CI [0.55, 0.62]) (p < 0.001). Similarly, individuals with cardiovascular disease (CVD) had a higher HCC incidence of 1.89 (95% CI [1.75, 2.03]) compared to those without CVD (0.51, 95% CI [0.48, 0.54]) (p < 0.001). Finally, the incidence of HCC was significantly higher in patients with non-liver cancer (3.90, 95% CI [3.67, 4.12]) compared to those without other cancers (0.29, 95% CI [0.26, 0.31]) (p < 0.001). On further stratification, HCC incidence incrementally rose by 10-year age intervals, male sex, cirrhosis, and DM, reaching 19.06 (95% CI [16.10, 22.01]) and 8.44 (95% CI [6.78, 10.10]) in males and females, respectively, but only 0.04 for non-diabetic, noncirrhotic aged <40 years patients in both sexes. The main limitation of this methodology is the potential misclassification of the International Classification of Diseases (ICD) codes inherent in claims database studies.
This nationwide study provided robust granular estimates for SLD-related HCC incidence stratified by several key risk factors. In addition to cirrhosis, future surveillance strategies, prevention, public health initiatives, and future research models should also take into account the impact of sex, age, and DM.
详细的脂肪性肝病（SLD）相关肝细胞癌（HCC）亚组发病率对于指导实践和公共卫生干预至关重要，但目前仍很少见。我们旨在填补这一空白。
在一项来自美国（US）Merative Marketscan Research Databases 的 SLD 成年人回顾性队列研究中（2007 年 1 月至 2021 年 12 月），我们按性别、年龄、肝硬化、糖尿病（DM）和这 4 个因素的组合对 HCC 发病率进行分层估计。我们排除了有大量饮酒和慢性病毒性肝炎的患者。我们分析了来自 741,816 例 SLD 患者的数据（平均年龄 51.5±12.8 岁，46%为男性，14.7%为肝硬化）。在 2,410,166 人年（PY）随访期间，1,740 例患者发生 HCC。总 HCC 发病率为 0.72/1,000 PY（95%置信区间[CI]，0.68，0.75）。男性（0.95，95%CI[0.89，1.01]）的发病率高于女性（0.52，95%CI[0.48，0.56]）（p<0.001）。对于肝硬化患者，发病率显著更高，为 4.29（95%CI[4.06，4.51]），而非肝硬化患者为 0.14（95%CI[0.13，0.16]）（p<0.001）。此外，DM 患者（1.19，95%CI[1.12，1.26]）的发病率高于非 DM 患者（0.41，95%CI[0.38，0.44]）（p<0.001）。慢性肾脏病（CKD）也与更高的 HCC 发病率相关，发病率为 2.20（95%CI[2.00，2.41]），而非 CKD 患者为 0.58（95%CI[0.55，0.62]）（p<0.001）。同样，患有心血管疾病（CVD）的个体 HCC 发病率也更高，为 1.89（95%CI[1.75，2.03]），而非 CVD 患者为 0.51（95%CI[0.48，0.54]）（p<0.001）。最后，非肝癌患者的 HCC 发病率（3.90，95%CI[3.67，4.12]）显著高于无其他癌症患者（0.29，95%CI[0.26，0.31]）（p<0.001）。进一步分层显示，HCC 发病率随年龄、男性、肝硬化和 DM 每增加 10 岁而递增，男性和女性的发病率分别达到 19.06（95%CI[16.10，22.01]）和 8.44（95%CI[6.78，10.10]），而在年龄<40 岁且非糖尿病、非肝硬化的患者中发病率仅为 0.04。这种方法的主要局限性是在索赔数据库研究中固有的国际疾病分类（ICD）代码潜在的错误分类。
这项全国性研究提供了基于几个关键危险因素的 SLD 相关 HCC 发病率的可靠详细估计。除了肝硬化之外，未来的监测策略、预防、公共卫生干预措施和未来的研究模型还应考虑到性别、年龄和 DM 的影响。
