title: Weight-related effects on disease progression in the hepatitis C antiviral long-term treatment against cirrhosis trial.
abstract: OBJECTIVE
  With the limited efficacy of current therapy for chronic hepatitis C, modifiable risk factors for liver disease progression are important to identify. Because obesity is associated with liver disease, we examined the effects of weight-related conditions on disease outcomes in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial.
  
  
  METHODS
  Of 1050 patients, 985 could be evaluated for predefined progression of liver disease not related to hepatocellular carcinoma. Clinical outcomes were determined over 3.5 years for all patients and progression to cirrhosis on protocol biopsy among patients who had bridging fibrosis (56.5% of cohort) at entry.
  
  
  RESULTS
  At study entry, median body mass index was high (29.2 kg/m(2)) and accompanied by other weight-related conditions, including diabetes (24.9%), high median waist circumference, and insulin resistance (by updated homeostasis model assessment of insulin resistance; HOMA2-IR). Among noninvasive measures, HOMA2-IR was most strongly associated with outcomes with hazard ratio (HR) of 1.26 per quartile increase (95% CI, 1.09-1.45). Presence of steatosis on baseline biopsy was associated with an increased outcome rate among patients with bridging fibrosis (P < .0001) and a decreased rate among patients with cirrhosis (P = .006). Presence of Mallory bodies was associated with outcomes (HR, 1.59; 95% CI, 1.10-2.31) as was significant weight change of >or=5% in the first year after randomization (HR, 1.25 per category increase in weight, 95% CI, 1.01-1.55).
  
  
  CONCLUSIONS
  Insulin resistance, histologic features of fatty liver disease, and weight change were associated with outcomes of chronic hepatitis C. Improvement in these weight-related factors might modify disease progression.
authors.affiliation: Department of Health and Human Services, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-5450, USA. JE17g@nih.gov
authors.forename: James E
authors.initials: JE
authors.lastname: Everhart
authors.forename: Anna S
authors.initials: AS
authors.lastname: Lok
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.forename: Karen L
authors.initials: KL
authors.lastname: Lindsay
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Marc G
authors.initials: MG
authors.lastname: Ghany
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D001835:Body Weight; D016001:Confidence Intervals; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000473:pathology* / Q000517:prevention & control; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D011336:Probability; D018570:Risk Assessment; D012720:Severity of Illness Index; D017678:Sex Distribution; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents