Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Am J Gastroenterol. 2021 Nov 1;116(11):2258-2269. doi: 10.14309/ajg.0000000000001347.
To estimate the annual incidence of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH) with advanced liver fibrosis, to determine the risk factors for the development of HCC, and to evaluate the chemoprotective effect of statin use stratified by fibrosis stage.
We conducted a retrospective study at 2 US tertiary academic centers, including patients with NASH-related advanced liver fibrosis (bridging fibrosis [F3] and cirrhosis [F4]) followed between July 2002 and June 2016. Patients were followed from the date of diagnosis to the time of last abdominal imaging, liver transplantation, or HCC diagnosis. Multivariable Cox regression analysis was performed to evaluate the risk factors associated with HCC development, stratified by fibrosis stage.
A total of 1,072 patients were included: 122 patients with F3 fibrosis and 950 patients with cirrhosis. No HCC was observed during 602 person-year follow-up among F3 patients. Among patients with cirrhosis, HCC developed in 82 patients with the annual incidence rate of 1.90 per 100 person-years (95% confidence interval [CI], 1.53-2.35). Multivariable analysis in patients with cirrhosis demonstrated that HCC development was associated with male sex (hazard ratio [HR] 4.06, 95% CI, 2.54-6.51, P < 0.001), older age (HR, 1.05, 95% CI, 1.03-1.08, P < 0.001), and CTP score (HR, 1.38, 95% CI, 1.18-1.60, P < 0.001). Statin use was associated with a lower risk of developing HCC (HR, 0.40, 95% CI, 0.24-0.67, P = 0.001). Each 365 increment in cumulative defined daily dose of statin use reduced HCC risk by 23.6%.
Our findings suggest that patients with NASH and bridging fibrosis have a low risk of HCC. Dose-dependent statin use reduced HCC risk significantly in patients with NASH cirrhosis.
评估非酒精性脂肪性肝炎（NASH）合并晚期肝纤维化患者的肝细胞癌（HCC）年发病率，确定 HCC 发展的危险因素，并评估按纤维化阶段分层的他汀类药物使用的化学预防作用。
我们在美国 2 家三级学术中心进行了一项回顾性研究，纳入了 2002 年 7 月至 2016 年 6 月期间 NASH 相关晚期肝纤维化（桥接纤维化 [F3] 和肝硬化 [F4]）的患者。患者从诊断之日起随访至最后一次腹部影像学检查、肝移植或 HCC 诊断的时间。多变量 Cox 回归分析评估了按纤维化阶段分层的与 HCC 发展相关的危险因素。
共纳入 1072 例患者：122 例 F3 纤维化患者和 950 例肝硬化患者。F3 患者的 602 人年随访期间未观察到 HCC。在肝硬化患者中，82 例患者发生 HCC，年发病率为 1.90/100 人年（95%置信区间 [CI]，1.53-2.35）。肝硬化患者的多变量分析显示，HCC 发生与男性（危险比 [HR] 4.06，95%CI，2.54-6.51，P<0.001）、年龄较大（HR，1.05，95%CI，1.03-1.08，P<0.001）和 CTP 评分（HR，1.38，95%CI，1.18-1.60，P<0.001）相关。他汀类药物的使用与 HCC 发生风险较低相关（HR，0.40，95%CI，0.24-0.67，P=0.001）。累积他汀类药物使用的每日定义剂量每增加 365 个，HCC 风险降低 23.6%。
我们的研究结果表明，NASH 合并桥接纤维化患者 HCC 风险较低。NASH 肝硬化患者中，他汀类药物的剂量依赖性使用显著降低了 HCC 风险。
