title: Interferon-associated hepatic steatosis is related to discrepancies in biochemical and virological responses of chronic hepatitis C to IFN-based therapy.
abstract: OBJECTIVE
  A discrepancy in virological and biochemical responses may occur throughout interferon-based therapy for hepatitis C virus (HCV). We aimed to explore the risk, associated factors, potential mechanisms, and impact on the treatment outcome of the discrepancy.
  
  
  METHODS
  Consecutive 496, chronic HCV-infected patients receiving interferon/ribavirin or peginterferon/ribavirin for 24 weeks with a 24-week follow-up period were enrolled. Of 433 patients with pretreatment liver biopsy, 46 received serial liver biopsies at the end of treatment and end of follow-up to explore the corresponding change in liver histopathology. A virological/biochemical discrepancy was defined as persistently elevated alanine aminotransferase levels throughout the treatment period, despite the seronegativity for HCV RNA at least at the end of treatment. The sustained virological response (SVR) was defined as seronegativity for HCV RNA 6 months after the end of treatment.
  
  
  RESULTS
  Virological/biochemical discrepancy was observed in 28.7 % (137/478) patients. The SVR rate was comparable between patients with (75.2 %, 103/137) and without discrepancy (81.2 %, 277/341, p = 0.14). For patients with discrepancy and SVR, 78 (75.7 %) had a subsequent normalization of alanine aminotransferase. Hepatic steatosis, advanced fibrosis, obesity, older age, peginterferon preparation, and low viral load were independently predictive of a virological/biochemical discrepancy. Serial liver histology showed that significant transient aggravation of hepatic steatosis during interferon-based therapy was observed among patients with a virological/biochemical discrepancy (difference 0.64 ± 0.93, p = 0.022), but not among those without it (difference 0.09 ± 0.69, p = 0.447).
  
  
  CONCLUSIONS
  A virological/biochemical discrepancy no longer exists after treatment cessation in most patients, and had little impact on the HCV treatment outcome. Treatment-related hepatic steatosis might play an important role in the pathogenesis of the discrepancy.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Internal Medicine, Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.
authors.forename: Jee-Fu
authors.initials: JF
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung, 807, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung, 807, Taiwan.
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Yeh
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung, 807, Taiwan.|Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Jeng-Fu
authors.initials: JF
authors.lastname: Yang
authors.affiliation: Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung, 807, Taiwan.
authors.forename: Ming-Yen
authors.initials: MY
authors.lastname: Hsieh
authors.affiliation: Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.
authors.forename: Nai-Jen
authors.initials: NJ
authors.lastname: Hou
authors.affiliation: Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung, 807, Taiwan.
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung, 807, Taiwan.
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung, 807, Taiwan.
authors.forename: Ming-Yuh
authors.initials: MY
authors.lastname: Hsieh
authors.affiliation: Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung, 807, Taiwan.
authors.forename: Liang-Yen
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung, 807, Taiwan.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung, 807, Taiwan.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.affiliation: Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. fish6069@gmail.com.|Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan. fish6069@gmail.com.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd, Kaohsiung, 807, Taiwan. fish6069@gmail.com.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
keywords: Alanine aminotransferase; Discrepancy; HCV; Steatosis; Sustained virological response