title: Peginterferon Is Superior to Nucleos(t)ide Analogues for Prevention of Hepatocellular Carcinoma in Chronic Hepatitis B.
abstract: BACKGROUND
  Clinical factors associated with hepatocellular carcinoma (HCC) have been extensively studied in antiviral treatment-naive patients with chronic hepatitis B virus (HBV) infection but not in treatment-experienced patients. Owing to the wide availability of antiviral agents that effectively suppress HBV replication, we investigated HCC risk factors in treatment-experienced patients.
  
  
  METHODS
  In a cohort of 330 patients who underwent pretherapeutic liver biopsy, we analyzed the HCC incidence in relationship to clinical parameters. Ultra-deep sequencing of the viral genome was performed on 11 entecavir-treated and pegylated interferon (peginterferon)-treated patients.
  
  
  RESULTS
  Initial univariate/multivariate explorations indicated that cirrhosis and antiviral treatment were independently associated with HCC occurrence. The peginterferon-experienced patients had a lower HCC incidence than the nucleos(t)ide analogue-treated patients (P = .011). The peginterferon and entecavir monotherapy groups also differed in HCC incidence (P = .018). Results of analysis of baseline-matched subgroups concurred with cohort analysis (P = .009 for comparison of peginterferon-experienced vs nucleotide analogue-treated patients; P = .022 for comparison of peginterferon- vs entecavir-treated patients). Viral loads of entecavir-treated patients were constantly suppressed to levels lower than those of peginterferon-treated patients (P < .001). Oncogenic surface antigen truncation mutations were detected in entecavir-treated patients with HCC but not in peginterferon-treated patients (P = .015).
  
  
  CONCLUSIONS
  Treatment by peginterferon was associated with a lower HCC incidence than nucleos(t)ide-analogue treatment in chronic HBV infection.
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Kung-Hao
authors.initials: KH
authors.lastname: Liang
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital.
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Hsu
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Chang
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lai
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009705:Nucleosides / Q000627:therapeutic use*; D009711:Nucleotides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009705:Nucleosides; D009711:Nucleotides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a
keywords: HBV mutations; cohort analysis; pretreatment histology; ultra-deep sequencing