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Weight-Related Factors Tied to Outcomes of Chronic Hepatitis C

NEW YORK (Reuters Health) Aug 05 - A number of weight-related factors, including insulin resistance, histological features of fatty liver disease, and weight change are linked to greater disease progression in patients with chronic hepatitis C, according to researchers. The findings suggest that counseling patients to lose weight could make a difference in outcomes.

"With the limited efficacy of current therapy for chronic hepatitis C, modifiable risk factors for liver disease progression are important to identify," Dr. James E. Everhart, of the National Institutes of Health, Bethesda , Maryland , and colleagues write in the August issue of Gastroenterology.

The researchers used data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Patients were evaluated for predefined progression of liver disease unrelated to hepatocellular carcinoma. Clinical outcomes were assessed over 3.5 years for all patients.

For patients with bridging fibrosis, progression to cirrhosis was the main outcome measure, whereas for those with cirrhosis, the main outcome was a composite of death from liver disease or hepatic decompensation.

Of 1050 patients, results were analyzed for 985. Sixty-four patients with fibrosis who had no subsequent biopsy or any clinical outcome after excluding hepatocellular cancer and non-liver-related death were not included. In addition, one patient with unknown cause of death was excluded from the analysis.

The patients had a mean age of 50.2 years, 71% were men, and 18% were black. The median body mass index was high (29.2) at baseline. Other weight-related conditions at study entry included diabetes (24.9%), high median waist circumference, and insulin resistance (as measured with the updated homeostasis model assessment of insulin resistance-HOMA2-IR).

The investigators report that HOMA2-IR was the non-invasive measure most strongly associated with the outcomes studied (HR = 1.26 per quartile increase). In patients with bridging fibrosis, steatosis was associated with an increased rate of the main outcome, whereas in those with cirrhosis, the opposite was true.

Other factors directly linked to clinical endpoints included Mallory bodies on biopsy (HR 1.59) and weight change of at least 5% in the first year after randomization (HR 1.25 per category increase in weight).

"For patients resistant to or unable to take antiviral therapy for hepatitis C, body weight appears to be a significant modifiable risk factor for disease progression," Dr. Everhart and colleagues conclude. "In the absence of a long-term trial of weight loss and liver disease outcomes, the results of this study may provide the strongest evidence for a clinical benefit of weight loss among overweight or obese persons with chronic hepatitis C."

Gastroenterol 2009;137:549-557.

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