Departments of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Eur J Gastroenterol Hepatol. 2010 Dec;22(12):1495-502. doi: 10.1097/MEG.0b013e32834059e7.
The reported incidence of hepatocellular carcinoma (HCC) among patients with primary biliary cirrhosis (PBC) varies from 0.7-3.8%, whereas in cirrhotic patients the risk is considerably higher. Age, male sex, cirrhosis, and portal hypertension are reported risk factors. It has been suggested that ursodeoxycholic acid (UDCA) may protect against HCC. We aimed to define risk factors for the development of HCC at the time of PBC diagnosis and to identify, among patients treated with UDCA for a long term, a subgroup that could benefit from screening.
Prospective multicenter cohort study of patients with established PBC treated with 13-15 mg/kg/day UDCA. Age, sex, antimitochondrial antibodies, bilirubin, albumin, alkaline phosphatase, alanine aminotransferase, aspartate amino transferase, cirrhosis, portal hypertension, Mayo Risk Score, prognostic class (based on bilirubin and albumin levels), and response to UDCA (normalization of bilirubin and/or albumin levels) were analyzed as potential risk factors in Cox regression analysis.
Three hundred and seventy-five patients were included, median follow-up was 9.7 years. HCC occurred in nine patients, corresponding with an annual incidence of 0.2%. The factor significantly associated with the development of HCC was the response to UDCA (P<0.001). The risk for HCC was highest in the group of nonresponders to UDCA: the 10 years incidence of HCC was 9% and the 15 years incidence was 20%. The number needed to screen in this subgroup was 11.
In UDCA treated PBC patients the risk of HCC is relatively low. The main risk factor for HCC in this study was the absence of biochemical response to UDCA after 1-year treatment.
原发性胆汁性肝硬化（PBC）患者中肝细胞癌（HCC）的报告发病率为 0.7-3.8%，而在肝硬化患者中风险明显更高。年龄、男性、肝硬化和门静脉高压被认为是危险因素。有研究表明熊去氧胆酸（UDCA）可能具有预防 HCC 的作用。我们旨在确定 PBC 诊断时发生 HCC 的危险因素，并在长期接受 UDCA 治疗的患者中确定可能受益于筛查的亚组。
对接受 13-15mg/kg/天 UDCA 治疗的确诊 PBC 患者进行前瞻性多中心队列研究。年龄、性别、抗线粒体抗体、胆红素、白蛋白、碱性磷酸酶、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肝硬化、门静脉高压、Mayo 风险评分、预后分类（基于胆红素和白蛋白水平）和 UDCA 反应（胆红素和/或白蛋白水平正常化）被分析为 Cox 回归分析中的潜在危险因素。
共纳入 375 例患者，中位随访时间为 9.7 年。9 例患者发生 HCC，年发病率为 0.2%。与 HCC 发展显著相关的因素是 UDCA 的反应（P<0.001）。UDCA 无反应组 HCC 的发病风险最高：10 年 HCC 发病率为 9%，15 年 HCC 发病率为 20%。在该亚组中，需要筛查的人数为 11 人。
在接受 UDCA 治疗的 PBC 患者中，HCC 的风险相对较低。本研究中 HCC 的主要危险因素是治疗 1 年后 UDCA 生化反应缺失。
