Standard hepatitis C therapy improves insulin resistance in HIV/hepatitis C co-infected patients

Treatment with pegylated interferon and ribavirin is associated with lasting improvements in insulin resistance among HIV-positive people co-infected with hepatitis C, investigators report in the online edition of Clinical Infectious Diseases.

Hepatitis C therapy was also associated with transient falls in levels of cholesterol.

“Our data demonstrate that treatment with pegylated interferon and ribavirin can significantly affect lipid profile and that there may be a modest improvement in insulin resistance,” comment the authors. However, they are unclear about the significance of their findings and call for further research.

Standard therapy for hepatitis C consists of pegylated interferon and ribavirin. A successful response to this treatment has been associated with increases in lipid levels in hepatitis C-monoinfected individuals.

Infection with hepatitis C has also been associated with the development of diabetes. Insulin resistance (which occurs when the impact of insulin secretion on blood sugar levels is diminished) is a precursor to the development of type 2 diabetes. There is some evidence that successful treatment of of hepatitis C monoinfection is associated with a reduced risk of diabetes and impaired fasting glucose.

However, the impact of treatment on lipid levels and insulin resistance in HIV/hepatitis C-co-infected patients is unknown.

US investigators therefore designed a prospective study involving 182 co-infected patients.Their primary aim was to evaluate the effect of a prolonged course of pegylated interferon and ribavirin on fibrosis progression in prior non-responders to this regimen.

Their secondary aim was to evaluate the impact of hepatitis C therapy on total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and insulin resistance (HOMA-IR above 2.5).

The participants had a median age of 48 years, most (81%) were men and they were of mixed ethnicity. Median baseline hepatitis C viral load was 6.6 log₁₀. The majority of patients (82%) had genotype-1 infection. HIV therapy was widely used (84%). Approximately three-quarters of patients had an undetectable HIV viral load and median CD4 cell count was 508 cells/mm³.

Baseline lipid profiles were as follows:

• Total cholesterol, 171 mg/dl.

• HDL cholesterol, 42 mg/dl.

• Triglycerides, 139 mg/dl.

• LDL cholesterol, 95 mg/dl (among the 92% of patients with triglycerides below 400 mg/dl).

The median HOMA-IR was 3.3 and 62% of participants were classified as having insulin resistance.

There was a significant relationship between hepatitis C viral load and triglyceride levels (p < 0.0001).

A quarter of participants achieved a sustained virological response. Higher LDL cholesterol was associated with an increased chance of achieving a therapeutic response (OR = 1.17 each 10 mg/dl increase; 95% CI, 1.03-1.32).

An early virological response to treatment (undetectable or 2 log₁₀ reduction in hepatitis C viral load at week twelve) was achieved by 57% of patients. These individuals received an extended course of treatment with pegylated interferon and ribavirin lasting 72 weeks.

Significant falls in total cholesterol, HDL cholesterol and LDL cholesterol were observed by week 16 of treatment (all p < 0.001) and these persisted through to week 64 (p < 0.001). However, each of these measurements had returned to near their baseline levels 24 weeks after the completion of treatment.

Triglyceride levels had increased significantly by week 16 (+ 30 mg/dl, p < 0.001) and there was a further modest increase by week 64 (+ 23 mg/dl, p = 0.07). However, within six months of the end of therapy, triglycerides had returned to baseline levels.

“The significance and mechanism of these changes is not clear,” comment the investigators. However, they note that some research suggests that hepatitis C “may alter the expression profile of lipid metabolism-associated genes”.

Modest improvements were seen in HOMA-IR values at weeks 16 and 24. Six months after the completion of treatment, there was an overall significant decline in HOMA-IR (- 0.7; p = 0.02).

“Values of HOMA-IR showed a gradual modest decline while on treatment which persisted at 24 weeks after completion of treatment, suggesting an added benefit of therapy in…co-infected persons,” write the researchers. “Whether this improvement eventually translates into a decrease in incidence of overt diabetes mellitus, or improvement in glycemic controls in those who are already diabetic, requires further investigation.”