title: Sustained virological response prevents the development of insulin resistance in patients with chronic hepatitis C.
abstract: Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), which is a condition known to influence the progression of liver fibrosis and the response to pegylated interferon (PEG-IFN)/ribavirin (RBV) therapy. We aimed to assess whether a sustained virological response (SVR) after antiviral therapy prevents the development of IR in the long term. Members of the Milan Safety Tolerability study cohort, who received PEG-IFNα2a/RBV or PEG-IFNα2b/RBV, underwent a homeostasis model assessment (HOMA) at the baseline and 24 months after treatment completion. For all patients (n = 431), a liver biopsy sample was scored for grading, staging (Ishak), and steatosis. At the baseline, IR (HOMA value > 2) was detected in 48 patients (12%), and it was associated with body weight (P = 0.03), an HCV load < 0.6 × 10(6) IU/L (P = 0.006), fibrosis staging ≥ 4 (P = 0.01), and moderate to severe steatosis (P = 0.03). IR did not influence the rates of end-of-treatment response (75% versus 69%, P = 0.4), SVR (63% versus 60%, P = 0.8), or relapse (19% versus 24%, P = 0.5). After treatment, IR developed in 49 of the 384 nondiabetic patients (14%). Although the mean baseline and posttreatment HOMA values were similar in SVR patients (1.11 ± 0.8 versus 1.18 ± 1.1, P = 0.25), patients experiencing treatment failure showed a significant increase in the mean HOMA value at the follow-up visit (1.20 ± 0.85 versus 1.49 ± 1.3, P = 0.007), and there was an increased rate of de novo IR in non-SVR patients versus SVR patients (17% versus 7%, P = 0.007). According to a logistic regression analysis, treatment failure (odds ratio = 2.81, 95% confidence interval = 1.39-5.67, P = 0.004) and a 10% body mass index increase (odds ratio = 6.42, 95% confidence interval = 1.69-24.3, P = 0.006) were significantly associated with the development of de novo IR.
  
  
  CONCLUSIONS
  In nondiabetic patients with chronic HCV, the achievement of SVR with PEG-IFN and RBV prevents the development of de novo IR.
authors.affiliation: First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Italy. alessio.aghemo@policlinico.mi.it
authors.forename: Alessio
authors.initials: A
authors.lastname: Aghemo
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Prati
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Rumi
authors.forename: Roberta
authors.initials: R
authors.lastname: Soffredini
authors.forename: Roberta
authors.initials: R
authors.lastname: D'Ambrosio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Orsi
authors.forename: Stella
authors.initials: S
authors.lastname: De Nicola
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Degasperi
authors.forename: Valeria
authors.initials: V
authors.lastname: Grancini
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D016001:Confidence Intervals; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a