Diabetes Mellitus Is Associated with Impaired Response to Antiviral Therapy in Chronic Hepatitis C Infection

Avera Center for Liver Disease, Transplant Institute, Sanford School of Medicine, University of South Dakota, 1001 East 21st Street, Suite 303, Sioux Falls, South Dakota 57105, USA.
Digestive Diseases and Sciences (Impact Factor: 2.61). 12/2009; 54(12):2699-705. DOI: 10.1007/s10620-008-0683-2
Source: PubMed


Insulin resistance may promote hepatic fibrosis in chronic hepatitis C (HCV) and has emerged as a cofactor in failure to achieve sustained viral response (SVR). AIMS: (1) To assess the association of diabetes mellitus (DM) in HCV patients to the severity of hepatic fibrosis and to the response to antiviral treatment. (2) To assess the safety of pegylated interferon and ribavirin combination therapy (Peg IFN/RBV) in diabetic HCV patients. Methods HCV diabetics (n=61) were identified. A 2:1 matching control group was used to identify independent factors of advanced fibrosis and treatment failure. RESULTS: Compared to HCV non-diabetics, HCV diabetics were more likely to have steatosis (P<0.0001) and advanced fibrosis (P=0.003). Patients' age, Caucasian ethnicity, obesity, and histologic activity index were independently associated with advanced fibrosis (P<0.05). Only 23% of HCV diabetics achieved SVR compared to 46% of HCV non-diabetics (P=0.003). DM, genotype 1, high baseline viral load, and African- American ethnicity were independently associated with less SVR (P<0.05). Significant adverse events were more common in HCV diabetics compared to HCV non-diabetics (P=0.001). Side effects did not increase in patients receiving PEG IFN/RBV and insulin sensitizers. Conclusion DM was associated with impaired virologic response to PEG IFN/RBV in HCV patients. Adverse events during therapy were more frequent in diabetic compared to non-diabetic HCV patients.

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    • "Insulin resistance and diabetes are major disease modifiers in chronic hepatitis C (CHC).1 There is evidence for a role of insulin resistance, the best predictor of type 2 diabetes mellitus, in failure to achieve sustained viral response (SVR) in patients with CHC.1-3 Also, insulin resistance has been associated with fibrosis progression, development of steatosis and greater risk of developing hepatocellular carcinoma in those infected with CHC.4,5 In several prospective studies of CHC patients, higher fasting insulin levels and higher homeostasis model assessment of insulin resistance levels (HOMA-IR) were all independently associated with a poor viral response to therapy even in patients traditionally considered as those who responded very well to treatment.3 Likewise it has been shown that patients who have previously failed anti-viral therapy have greater insulin resistance.2 "
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    ABSTRACT: BACKGROUND Evidence indicates that insulin resistance results in poor sustained viral response (SVR) in patients with chronic hepatitis C (CHC). Metformin is an oral hypoglycemic agent which improves insulin resistance. METHODS We sought to determine if the addition of metformin to the treatment regimen could improve SVR in treatment-naïve CHC patients in a randomized, double-blind, placebo-controlled trial. We randomized 140 consecutive CHC patients to receive either metformin 500 mg three times a day or placebo in addition to pegylated interferon (PEG-IFN) and ribavirin (RBV). Only treatment-naïve subjects aged between 15 and 65 years of age were included. SVR was defined as no detectable HCV RNA six months after the end of treatment.Subjects who received at least one dose of PEG-IFN were included in the finala nalysis. RESULTS The SVR rate in the metformin group was 75% versus 79% in controls (intention-to-treat) which was not significantly different. Also, the difference between the placebo and metformin group was not significant in subsets of different genotypes or those with homeostasis model assessment of insulin resistance (HOMA-IR) levels greater than 2 or body mass index greater than 25. The most common complaint was gastrointestinal discomfort (13% in metformin group versus 4% in controls; p=0.002) that lead to discontinuation of metformin in 8 participants. CONCLUSION Although triple therapy with metformin, PEG-IFN and RBV is relatively well tolerated, the addition of metformin did not significantly improve viral response in CHC patients.
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