It is well known that liver inflammation facilitates the progression of fibrosis and the occurrence of hepatocellular carcinoma (HCC) in people with chronic hepatitis C, although the factors associated with hepatic inflammation are not fully understood.

A study presented at the recent Digestive Disease Week 2006 conference in Los Angeles suggests that insulin resistance may be one such factor.

In this study, 72 patients with chronic hepatitis C (44 men, 28 women; mean age 56) underwent liver biopsy and administration of a 75-gram oral glucose tolerance test to determine whether they had normal glucose tolerance, impaired glucose tolerance, or diabetes mellitus. Insulin sensitivity was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR) and the insulin sensitivity index (ISI composite).

The researchers also assessed other factors, including body mass index (BMI), HCV core antigen level, HCV genotype, serum adiponectin level, histological fibrosis stage, and steatosis grade, and their association with histological evidence of inflammation and serum levels of alanine aminotransferase (ALT), a marker for liver inflammation.

Results

Serum ALT was correlated with HOMA-IR (R = 0.464; P < 0.0001) and ISI composite (R = -0.352; P = 0.002) scores.

ALT level was not correlated with age, BMI, adiponectin level, or HCV core antigen level.

There was no difference in ALT levels related to gender, glucose tolerance, HCV genotype, histological fibrosis stage, or grade of steatosis.

In a logistic regression analysis, insulin resistance assessed by HOMA-IR was the only factor associated with an ALT level greater than 80 IU/L (OR 3.12; P = 0.024).

There was a significant difference in ALT levels between patients with HOMA-IR scores greater than 2 and those with scores less than 2 (63.9 +/- 34.0 vs 97.2 +/-59.2, respectively; P = 0.002).

ISI composite score was the only factor associated with histological inflammation grade greater than A2 (OR 0.064; P = 0.022).

83.8% of patients with ISI composite scores less than 8 had histological inflammation grades greater than A2, compared with 25% of those with ISI scores greater than 8.

Conclusion

The researchers concluded that inflammatory activity in patients with chronic hepatitis C is strongly related to insulin resistance. These data suggest that improving insulin sensitivity might lead to decreased liver inflammation, and ultimately reduced fibrosis progression.

First-line treatment for insulin resistance is diet modification, increased exercise, and weight loss. If lifestyle modification is insufficient, various medications may be used, including metformin (Glucophage) and the thiazolidinediones, e.g., rosiglitazone (Avandia) and pioglitazone (Actos).

6/27/06

Reference
K Ario, T Mizuta, Y Eguchi, and others. Insulin resistance influences hepatic inflammation in patients with chronic hepatitis C. Abstract 553. Digestive Disease Week 2006. May 20-25, 2006. Los Angeles, CA.