title: The development of hepatocarcinoma after long-term antivirus treatment of Chinese patients with chronic hepatitis B virus infection: Incidence, long-term outcomes and predictive factors.
abstract: BACKGROUND
  Patients with chronic hepatitis B virus (HBV) infection are at high risk for progressing to decompensated cirrhosis and hepatocellular carcinoma (HCC). Although long-term treatment with nucleos(t)ide analogues (NAs) benefits patients with chronic hepatitis B (CHB), many develop HCC. Therefore, the clinical outcomes of patients CHB who undergo long-term treatment with NAs remain to be identified. The aim of this study therefore was to evaluate the risk and predictors of patients with CHB who develop hepatitis B-induced HCC.
  
  
  METHODS
  We investigated 1200 patients with CHB who were treated with NAs for at least four years and evaluated the association of the variables ALT, HBsAg, HBV DNA, age and platelet count with the occurrence of HCC. We used multivariable analysis to identify independent risk factors for the development of HCC.
  
  
  RESULTS
  HCC developed in 153 NA-treated patients. Serum HBV DNA levels of 18.17% (218/1200) patients were>2000IU/mL. The median level of liver stiffness measurement (LSM) of all patients was 8.3±6.7kPa vs. 19.8±10.1kPa in patients with HCC. Advanced age, lower platelet counts, positive HBV DNA load, lower ALB concentration and relatively advanced liver disease were associated with an increased risk of developing HCC. Further, TGF-β and IFN-γ levels were higher and lower in patients with HCC or CHB, respectively.
  
  
  CONCLUSIONS
  Hepato-carcinogenesis occurred more frequently in patients with a positive HBV DNA load and relatively advanced liver disease. Therefore, it is important to administer antiviral therapy to patients with CHB before they develop HBV-related cirrhosis.
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China; Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Li
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Hu
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Gu
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Yan-Min
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Qing-Lei
authors.initials: QL
authors.lastname: Zeng
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China. Electronic address: yanjingya666@163.com.
authors.forename: Jing-Ya
authors.initials: JY
authors.lastname: Yan
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Zu-Jiang
authors.initials: ZJ
authors.lastname: Yu
authors.affiliation: Department of infectious disease, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China; Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China; Department of Oncology, the First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China; School of Life Sciences, Zhengzhou University, 450052 Zhengzhou, Henan, China; Key Laboratory of Clinical-Medicine, the First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D044466:Asian People / Q000706:statistics & numerical data*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000175:diagnosis / Q000208:ethnology* / Q000209:etiology*; D002681:China / Q000453:epidemiology; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000208:ethnology*; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000139:chemically induced / Q000175:diagnosis / Q000208:ethnology* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000998:Antiviral Agents