Haoliang Wang

Scientific Reports 6: Article number: 35050; published online: 12 October 2016; updated: 19 December 2016

To investigate the association between long-term changes of serum total bile acid and hepatocellular carcinoma in chronic hepatitis B patients, we did a retrospective cohort study of 2262 chronic hepatitis B patients with regular antiviral treatment using data from the Hepatitis Biobank at Southwest Hospital Program from 2004 to 2014. Patients in the study were classified into 3 groups according to persistence of elevated serum total bile acid during follow-up: none-low, medium, and high persistence of elevated serum total bile acid. The association between persistence of elevated serum total bile acid and hepatocellular carcinoma was estimated using Cox proportional hazard models and Kaplan-Meier analysis including information about patients' demographic and clinical characteristics. There were 62 hepatocellular carcinoma cases during a total follow-up of 14756.5 person-years in the retrospective study. Compared to patients with none-low persistence of elevated total bile acid, the multivariate adjusted hazard ratios (95% confidence interval) were 2.37 (1.16-4.84), and 2.57 (1.28-5.16) for patients with medium, and high persistence of elevated total bile acid. Our findings identified persistence of elevated serum total bile acid as an independent risk factor of hepatocellular carcinoma in chronic hepatitis B patients.

Prognosis of hepatocellular carcinoma (HCC) remains unsatisfying due to a lack of early detecting methods. Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) has been proved to be an efficient biomarker for HCC. However, the predicting efficacy of PIVKA-II has barely been reported. In the Hepatitis Biobank of Southwest Hospital (HBS) cohort at Southwest Hospital, we did a two-stage nested case-control study. Totally, 45 HCC cases versus 138 matched controls were enrolled to compare levels of α-fetoprotein (AFP) and PIVKA-II in sequential sera at -12, -9, -6, -3 and 0 months before imaging diagnosis. Levels of both PIVKA-II and AFP in HCC cases elevated significantly at all time points compared with controls. In validation stage, the sensitivity and specificity of PIVKA-II at baseline were 58.3% and 92.6%, and AFP were 75.0% and 91.7%. AFP-/PIVKA-II+ patients covered 27.4%, 29.4% and 19.6% at M-12, M-6 and M-0, respectively, while AFP+/PIVKA-II- patients covered 25.5%, 19.6% and 17.7%, respectively. Both PIVKA-II and AFP have the potential for HCC prediction, while PIVKA-II has a better positive rate than AFP before diagnosis.