title: Influence of insulin resistance on the development of hepatocellular carcinoma after antiviral treatment for non-cirrhotic patients with chronic hepatitis C.
abstract: BACKGROUND
  Insulin resistance is considered to be an important factor in the progression of fibrosis and the enhancement of the risk of hepatocellular carcinoma (HCC) for chronic hepatitis C patients. The aim of this study was to assess the effect of insulin resistance on the development of HCC by non-cirrhotic chronic hepatitis C patients treated with pegylated interferon alpha-2b (PEG-IFNα2b) and ribavirin.
  
  
  METHODS
  This retrospective study consisted of 474 Japanese non-cirrhotic patients with chronic hepatitis C. The cumulative incidence of HCC was estimated using the Kaplan-Meier method, according to insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR) and treatment outcome.
  
  
  RESULTS
  The overall sustained virological response (SVR) rate was 45.1 % (214/474, genotype 1: 35.4 % [129/364] and genotype 2: 77.3 % [85/110]). Twenty-one (4.4 %) patients developed HCC during the follow-up period. The 5-year cumulative incidence of HCC of the SVR group (2.6 %) was significantly lower than that of the non-SVR group (9.7 %) (log-rank test: P = 0.025). In multivariable logistic regression analysis, HOMA-IR (≥2.5) (hazard ratio [HR] 12.8, P = 0.0006), fibrosis status (F3) (HR 8.85, P < 0.0001), and post-treatment alanine aminotransferase (ALT) level (≥40 U/L) (HR 4.33, P = 0.036) were independently correlated to the development of HCC. Receiver operating characteristic analysis to determine the optimal threshold value of HOMA-IR for predicting the development of HCC in the non-SVR group showed that the areas under the curve was high (0.80, cutoff value: 3.0). Only three patients (1.4 %) who achieved SVR developed HCC. Two of them had severe insulin resistance and did not show improvement in HOMA-IR after achieving SVR.
  
  
  CONCLUSIONS
  Insulin resistance has a strong impact on the development of HCC by non-cirrhotic patients who have PEG-IFNα2b and ribavirin treatment failure.
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka, 812-8582 Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka, 812-8582 Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ogawa
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka, 812-8582 Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka, 812-8582 Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Murata
authors.affiliation: Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
keywords: HOMA-IR; Hepatocellular carcinoma; Insulin resistance; Non-cirrhosis; Pegylated interferon; Ribavirin