Weight-Related Effects on Disease Progression in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial

BACKGROUND & AIMS: 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 >= 5% in the first year after randomization (HR, 1.25 per category increase in weight, 95% Cl, 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.