Tseng Tai-Chung, Liu Chun-Jen, Su Tung-Hung, Yang Wan-Ting, Chen Chi-Ling, Yang Hung-Chih, Wang Chia-Chi, Kuo Stephanie Fang-Tzu, Liu Chen-Hua, Chen Pei-Jer, Chen Ding-Shinn, Kao Jia-Horng
Department of Internal Medicine, National Taiwan University Hospital Jinshan Branch, New Taipei City, Taiwan.
Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Am J Gastroenterol. 2017 Oct;112(10):1564-1574. doi: 10.1038/ajg.2017.254. Epub 2017 Aug 29.
Several viral and host risk factors have been used to predict risks of hepatocellular carcinoma (HCC) in patients with chronic infection of hepatitis B virus (HBV). However, little is known whether fibrosis-4 (FIB-4) index, a liver fibrosis biomarker, helps identify non-cirrhotic patients with the lowest HCC risk.
A total of 2075 treatment-naive Taiwanese patients with chronic HBV infection were followed for an average period of 16.02 years. None of them had liver cirrhosis at baseline. We explored whether a low FIB-4 index complements the favourable predictors to defines patients with the lowest HCC risk. The finding was validated in 532 non-cirrhotic patients receiving long-term nucleos(t)ide analogue (NUC) treatment with suppressed viral replication.
A total of 137 treatment-naive and 10 NUC-treated patients developed HCC, respectively. We found that HCC risk started to increase when baseline FIB-4 index >1.29 in the treatment-naive cohort. Patients with FIB-4 >1.29, compared to those with FIB-4 <1.29, were associated with a higher risk of HCC with hazards ratio of 5.56 (95% confidence interval: 3.93-7.86). More importantly, among patients with low viral load (HBV DNA level <2,000 IU/ml), baseline FIB-4 index helped stratify different HCC risks such that none of 326 HBeAg-negative patients with FIB-4 index <1.29, ALT level <40 U/l, and HBsAg level <1,000 IU/ml developed HCC. In addition, the patients with the FIB-4 index <1.29 consistently had the lowest HCC risks in the validation cohort receiving long-term NUC treatment.
In non-cirrhotic patients with chronic HBV infection, FIB-4 index <1.29 complements the existing clinical profile to define patients with the lowest HCC risk.
多种病毒和宿主风险因素已被用于预测慢性乙型肝炎病毒（HBV）感染患者发生肝细胞癌（HCC）的风险。然而，对于肝纤维化生物标志物纤维化-4（FIB-4）指数是否有助于识别HCC风险最低的非肝硬化患者，人们所知甚少。
对总共2075例未接受过治疗的台湾慢性HBV感染患者进行了平均16.02年的随访。他们在基线时均无肝硬化。我们探讨了低FIB-4指数是否能补充有利的预测指标，以确定HCC风险最低的患者。这一发现随后在532例接受长期核苷（酸）类似物（NUC）治疗且病毒复制受到抑制的非肝硬化患者中得到了验证。
分别有137例未接受过治疗的患者和10例接受NUC治疗的患者发生了HCC。我们发现，在未接受过治疗的队列中，当基线FIB-4指数>1.29时，HCC风险开始增加。与FIB-4<1.29的患者相比，FIB-4>1.29的患者发生HCC的风险更高，风险比为5.56（95%置信区间：3.93 - 7.86）。更重要的是，在病毒载量较低（HBV DNA水平<2000 IU/ml）的患者中，基线FIB-4指数有助于区分不同的HCC风险，以至于326例FIB-4指数<1.29、ALT水平<40 U/l且HBsAg水平<1000 IU/ml的HBeAg阴性患者均未发生HCC。此外，在接受长期NUC治疗的验证队列中，FIB-4指数<1.29的患者HCC风险始终最低。
在慢性HBV感染的非肝硬化患者中，FIB-4指数<1.29可补充现有的临床特征，以确定HCC风险最低的患者。
