Insulin Resistance Linked to Poor Hepatitis C Treatment Response in HIV/HCV Coinfected Patients

		SUMMARY: HIV/HCV coinfected people with insulin resistance have higher hepatitis C viral load on average and are significantly less likely to achieved sustained virological response to treatment with pegylated interferon plus ribavirin, according to a study presented last month at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010) in Boston.

By Liz Highleyman

Prior research has shown that HIV positive people coinfected with hepatitis C tend to experience more rapid liver disease progression and are less likely to respond to interferon-based therapy compared to individuals with chronic hepatitis C alone.

Insulin resistance -- a precursor to diabetes -- is also a predictor of poorer treatment response in patients with HCV alone, but this association has not been extensively evaluated in people with HIV/HCV coinfection.

In a prospective observational study, Paola Nasta and colleagues from the University of Brescia in Italy looked at the correlation between HCV RNA viral load, hepatitis C treatment response, and insulin resistance in 107 HIV/HCV coinfected patients.

Most participants (about 85%) were men and the average age was about 43 years. Half had hard-to-treat HCV genotypes 1 or 4, and nearly 60% had advanced liver fibrosis (Metavir stage F3-F4). Almost all patients (93%) were taking combination antiretroviral therapy (ART).

Participants received a hepatitis C treatment regimen consisting of 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day weight-adjusted ribavirin. HCV viral load was measured at baseline and then every 3 months. The researchers assessed sustained virological response (SVR), or continued undetectable HCV RNA 24 weeks after finishing therapy.

Insulin resistance was evaluated using the HOMA-IR (homeostasis model of assessment-insulin resistance) method, which is calculated based on fasting insulin level. At baseline, the average HOMA-IR score was 3.2; a score > 3.0 is typically considered the threshold for insulin resistance.

Results

	" Overall, 44% of treated patients achieved SVR.
	In a multivariate analysis, the following 3 factors were significant independent predictors of sustained response:
	HCV genotypes 1 or 4 (vs 2 or 3): adjusted odds ratio 0.10, or 90% less likely to achieve SVR; Baseline HCV RNA < 400.000 IU/mL: adjusted odds ratio 3.08, or about 3 times more likely to respond; HOMA-IR < 3.0: adjusted odds ratio 3.5, or 3.5-fold more likely to respond.
	Advanced liver fibrosis, blood lipid levels, and HIV viral load did not significantly affect likelihood of SVR.
	Lower HOMA-IR was also significantly associated with lower HCV viral load:
	HCV RNA < 6 log: median HOMA-IR score 2.9; HCV RNA >6 log: median HOMA-IR score 3.3.

These findings led the investigators to conclude, "A linear relationship was detected between HOMA-IR and hepatitis C viral load in HIV/HCV coinfected [patients] regardless viral genotype."

"This result could contribute to explain[ing] the role of insulin-resistance on the anti-HCV treatment outcome in HIV/HCV coinfected persons," they suggested.

University of Brescia, Brescia, Italy.

10/5/10

Reference
P Nasta, F Gatti, and F Borghi. Insulin Resistance is Associated with Hepatitis C Viremia and Reduces the Success of Peginterferon alfa2a Plus Ribavirin in HIV/HCV Co-Infected Patients. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. Abstract H-1683.