title: Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients.
abstract: OBJECTIVE
  The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients.
  
  
  METHODS
  A total of 303 treatment-naïve Asian-region patients with CHC genotype 2/3 were enrolled in a multicenter phase 3 study of albinterferon alfa-2b plus ribavirin for 24 weeks. IR was defined as Homeostasis Model for Assessment of IR (HOMA-IR) > 2. Baseline liver biopsy was evaluated by a single expert histopathologist. Post hoc subgroup logistic regression modeling selected for independent variables associated with significant fibrosis (METAVIR stage F2-F4).
  
  
  RESULTS
  Insulin resistance was available in 263 non-diabetic Asian-region patients (hepatitis C virus-2 [HCV-2] = 171, HCV-3 = 92), and 433 non-Asian region patients (407 "Caucasian"); METAVIR fibrosis prevalence F0-F1 (minimal fibrosis)= 201 (77%) and F2-F4 (significant fibrosis) = 59 (23%), and steatosis prevalence of grade 0 = 169 (65%), grade 1 = 64 (25%), grade 2/3 = 27 (10%). Median HOMA-IR was 1.8 (interquartile range: 1.2-2.7); 100 (38%) patients had HOMA-IR > 2. Factors independently associated with significant fibrosis included HOMA-IR (odds ratio [OR]= 8.42), necro-inflammatory grade (OR = 3.17), age (OR = 1.07) and serum total cholesterol levels (OR = 0.008). This was similar to non-Asian region patients, but steatosis was not associated with significant fibrosis in either cohort.
  
  
  CONCLUSIONS
  In this subgroup study of Asian-region HCV genotype 2 or 3 patients, insulin resistance, along with age, cholesterol levels and necro-inflammation, but not steatosis may be associated with significant hepatic fibrosis.
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA. keyur.patel@duke.edu
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.forename: Chuan-Mo
authors.initials: CM
authors.lastname: Lee
authors.forename: Chen-Yuan
authors.initials: CY
authors.lastname: Peng
authors.forename: Ganesananthan
authors.initials: G
authors.lastname: Shanmuganathan
authors.forename: Satawat
authors.initials: S
authors.lastname: Thongsawat
authors.forename: Tawesak
authors.initials: T
authors.lastname: Tanwandee
authors.forename: Varocha
authors.initials: V
authors.lastname: Mahachai
authors.forename: Chutima
authors.initials: C
authors.lastname: Pramoolsinsap
authors.forename: Mong
authors.initials: M
authors.lastname: Cho
authors.forename: Kwang Hyup
authors.initials: KH
authors.lastname: Han
authors.forename: Samir R
authors.initials: SR
authors.lastname: Shah
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Clark
authors.forename: Erik
authors.initials: E
authors.lastname: Pulkstenis
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
mesh_terms: D000328:Adult; D000418:Albumins / Q000627:therapeutic use; D044466:Asian People; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D014943:Global Health; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000208:ethnology / Q000209:etiology* / Q000378:metabolism; D009017:Morbidity; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D000418:Albumins; D016898:Interferon-alpha; C531108:albinterferon alfa-2b