Clinical

Insulin resistance causes steatosis in HCV infection

Last Updated: 2005-07-07 12:15:12 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Insulin resistance is a cause, not a consequence, of steatosis in patients with hepatitis C virus (HCV), according to a new report.

Dr. L. Serfaty of Hopital Saint-Antoine in Paris and colleagues conclude in the July issue of Gut that insulin resistance promotes liver fibrosis by inducing steatosis among patients with non-genotype-3 HCV. "Metformin or peroxisome proliferator activated receptor gamma agonists could be interesting therapeutic options for improving steatosis and fibrosis in HCV infected patients with insulin resistance," they write.

While insulin resistance, type II diabetes and steatosis and hepatic fibrosis are more common among HCV-infected patients, the researchers note, the relationship among these factors is not clear.

To investigate, they studied 141 patients with non-cirrhotic HCV infection, comparing the 28 with HCV genotype 3, which is known to promote steatosis, to those with other HCV genotypes. Non-genotype 3 patients were classified as "genotype 1," although the group included other genotypes.

Thirty percent of genotype 1 patients had fatty liver, defined as steatosis affecting more than 10% of hepatocytes, while nearly 60% of genotype 3 patients did. Genotype 1 patients with steatosis were older and had a higher average BMI than those without fatty liver.

Insulin resistance was worse in genotype 1 patients with fatty liver compared to genotype 3 patients with steatosis and with all patients without fatty liver, the researchers found. Multivariate analysis identified insulin resistance as the only factor independently associated with steatosis in genotype 1 patients. While insulin resistance was more common among genotype 1 patients with fibrosis, the researchers found, the relationship was no longer significant after they adjusted for steatosis. The only factors significantly associated with insulin resistance in the genotype 1 patients were age and degree of steatosis.

Among patients with genotype 3, the only variable related to steatosis was viral load. Steatosis also was associated with more severe fibrosis.

"Increased circulating insulin is a risk factor for fibrosis in genotype 1 infected patients with chronic hepatitis C through insulin resistance induced steatosis," the researchers conclude. "Accordingly, it may be speculated that intervention strategies to reduce insulin resistance associated with steatosis should target these patients."

In an editorial accompanying the study, Dr. A.M. Diehl and colleagues from Duke University Medical Center in Durham, North Carolina, say the findings underscore the importance of weight loss and related lifestyle changes in the treatment of patients with HCV. "Similarly, new therapeutic approaches exploiting the interaction between HCV and lipid metabolism are eagerly awaited," they conclude.

Gut 2005;54:903-906;1003-1008.