El-Serag Hashem B, Thrift Aaron P, Duong Hao, Ning Jing, Khaderi Saira, Singal Amit G, Asrani Sumeet K, Marrero Jorge A, Powell Hannah, Rizwan Kinza, Najjar Omar, Amos Christopher I, Luster Michelle, Al-Sarraj Abeer, Salem Emad, Scheurer Michael E, Chhatwal Jagpreet, Kaochar Salma, Kanwal Fasiha
Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Hepatol Commun. 2024 Oct 10;8(11). doi: 10.1097/HC9.0000000000000545. eCollection 2024 Nov 1.
Previous studies have reported higher circulating bile acid levels in patients with HCC compared to healthy controls. However, the association between prediagnostic bile acid levels and HCC risk among patients with cirrhosis is unclear.
We measured total BA (TBA) concentration in serum samples collected from a prospective cohort of patients with cirrhosis who were followed until the development of HCC, death, or last study date. Competing risk proportional hazard-adjusted models were used to estimate the association between tertiles of serum TBA levels and the risk of developing HCC. We quantified the incremental predictive value of serum bile acid when added to a previously validated clinical model.
We analyzed data from 940 patients with cirrhosis, of whom 68 patients progressed to HCC during 3406 person-years of follow-up. Higher baseline serum TBA level was significantly associated with an increased risk of developing HCC with an adjusted HR of 3.69 (95% CI = 1.85-7.37) for the highest versus lowest tertile. TBA levels significantly increased predictive ability for progression to HCC at 2 years of follow-up; the c statistic increased from 0.74 to 0.80 (p < 0.001). There was evidence for a significant interaction between TBA level and hepatitis C (p = 0.04).
In a large prospective cohort study, the prediagnostic serum level of TBAs was associated with a significant increase in the risk of developing HCC among patients with multi-etiology cirrhosis. The TBA-associated risk was additive to that of established demographic and clinical predictors.
既往研究报道，与健康对照相比，肝癌患者的循环胆汁酸水平更高。然而，肝硬化患者诊断前胆汁酸水平与肝癌风险之间的关联尚不清楚。
我们测量了来自肝硬化前瞻性队列患者的血清样本中的总胆汁酸（TBA）浓度，这些患者随访至肝癌发生、死亡或最后研究日期。采用竞争风险比例风险调整模型来估计血清TBA水平三分位数与发生肝癌风险之间的关联。我们在先前验证的临床模型中加入血清胆汁酸，以量化其增量预测价值。
我们分析了940例肝硬化患者的数据，其中68例在3406人年的随访期间进展为肝癌。基线血清TBA水平较高与发生肝癌的风险增加显著相关，最高三分位数与最低三分位数相比，调整后的风险比为3.69（95%置信区间=1.85-7.37）。TBA水平显著提高了随访2年时进展为肝癌的预测能力；c统计量从0.74增加到0.80（p<0.001）。有证据表明TBA水平与丙型肝炎之间存在显著交互作用（p=0.04）。
在一项大型前瞻性队列研究中，多病因肝硬化患者诊断前血清TBA水平与发生肝癌的风险显著增加相关。TBA相关风险是已确定的人口统计学和临床预测因素风险之外的附加风险。
