Gastroenterology

Gastroenterology

Volume 128, Issue 3, March 2005, Pages 636-641
Gastroenterology

Clinical-liver, pancreas, and biliary tract
Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients

https://doi.org/10.1053/j.gastro.2004.12.049Get rights and content

Background & Aims: We evaluated the effect of insulin resistance and viral factors on sustained virological response in patients with chronic hepatitis C treated with peginterferon plus ribavirin. Methods: Patients (n = 159; 94 men; age, 41.7 ± 11.1 years) with chronic hepatitis C (genotype 1, n = 113; non-1 genotype, n = 46) received treatment with interferon plus ribavirin. Serum levels of leptin and insulin were measured, and the insulin resistance index (HOMA-IR: homeostasis model of assessment) and body mass index were calculated. Results: A sustained virological response was associated with lower age, insulin resistance index, body mass index, and γ-glutamyltranspeptidase and serum leptin levels. There was no association with viral load, sex, type of interferon, or cholesterol levels. A sustained virological response was achieved in 43.4% (46/113) of genotype 1 and 89% (32/36) of genotype 2 and 3 (P = .0001) patients. Necroinflammatory activity and steatosis were not associated with the sustained virological response rate. Multivariate regression analysis indicated that the independent variables related to sustained virological response were genotype (odds ratio, 3.57; 95% confidence interval, 1.49–8.3; P = .001), insulin resistance index (odds ratio, 1.82; 95% confidence interval, 1.08–3.06; P = .012), and fibrosis (odds ratio, 1.36; 95% confidence interval, 1.01–1.84; P = .029). A sustained virological response in patients with genotype 1 and insulin resistance (HOMA-IR > 2) occurred in 23 of 70 (32.8%; 95% confidence interval, 21.9%–43.9%) patients, vs. 26 of 43 (60.5%; 95% confidence interval, 45.9%–75.1%) genotype 1 patients without insulin resistance (P = .007; odds ratio, 3.12, 95% confidence interval, 1.42–6.89). Conclusions: Insulin resistance, fibrosis, and genotype are independent predictors of the response to antiviral therapy in chronic hepatitis C patients treated with peginterferon plus ribavirin.

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Patient population

Consecutive patients from 5 Spanish hospitals were recruited and treated according to standard daily clinical practice. Patients (n = 159; 94 men [59.1%] and 65 women [41.9%]; mean age, 41.7 ± 11.1 years; range, 22–67 years) with biopsy-proven chronic hepatitis C, showing HCV RNA-positive and altered alanine aminotransferase levels, were treated with peginterferon plus ribavirin (alfa-2a, n = 85; alfa-2b, n = 74). Genotype distributions were as follows: genotype 1, n = 113; genotype 2, n = 7;

Factors associated with sustained virological response

Patients with SVR were younger (39.7 ± 10.4 years vs. 44.5 ± 10.9 years; P = .006), had a lower HOMA-IR (2.36 ± 1.85 vs. 3.76 ± 3.22; P = .001), had a lower BMI (25.4 ± 3.65 kg/m2 vs. 27.1 ± 4.89 kg/m2; P = .027), had lower γ-glutamyltranspeptidase levels (46.8 ± 49.5 U/L vs. 106.7 ± 107.2 U/L; P = .001), and had lower serum leptin levels in men (5.1 ± 3.97 ng/mL vs. 12.4 ± 13.7 ng/mL; P = .048) and in women (13.3 ± 10.5 ng/mL vs. 20.5 ± 13.5 ng/mL; P = .016). There was no association with sex

Discussion

Insulin resistance, advanced fibrosis, and genotype 1 are independent predictors of a poor response to antiviral therapy in chronic hepatitis C. It is interesting to note that insulin resistance seems to be a common denominator among groups of poor-response patients, such as those with cirrhosis4 or a high BMI,13 African Americans,14 and those with HIV/HCV co-infection.15 Whether insulin resistance is a marker for patients who are very difficult to treat or whether it plays a role in interferon

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This study was funded, in part, by grants from Consejería de Salud de la Junta de Andalucía (43/03 and PAI-532) and the Spanish Ministry of Health (G03/155-2002 and C03/02-2002).

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