Insulin Resistance Predicts Rapid Virologic Response to Peginterferon/Ribavirin Combination Therapy in Hepatitis C Genotype 4 Patients

Khattab, Mahmoud A.; Eslam, Mohammed; Sharwae, Mohammed Ahmed; Shatat, Mohammed; Ali, Ahmed; Hamdy, Lamia

doi:10.1038/ajg.2010.110

Cited by 74 publications

(67 citation statements)

References 24 publications

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“…29,30 Insulin resistance and baseline HCV viral loads have also been noted to predict RVR in patients with HCV-4 infection. 31 Mangia et al 32 showed that a high dose of ribavirin and low pretreatment HCV viral loads with an HCV-2 infection were independent factors predicting RVR in patients with HCV-2/HCV-3 infection. 32 However, little is known about the general relevance of host genetics to the early phases of viral kinetics in the treatment of HCV infection.…”

Section: Discussionmentioning

confidence: 99%

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

et al. 2011

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Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r 2 5 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P 5 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) 5 4.27, 95% confidence interval (CI) 5 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR 5 0.28, 95% CI 5 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR 5 3.10, 95% CI 5 1.34-7.21, P 5 0.008), and the pretreatment level of aspartate aminotransferase (OR 5 0.996, 95% CI 5 0.99-1.00, P 5 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI 5 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. Conclusion: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients. (HEPATOLOGY 2011;53:7-13)

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Section: Discussionmentioning

confidence: 99%

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

et al. 2011

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“…The association between chronic HCV infection and increased prevalence of IR and type 2 diabetes mellitus (DM) was extensively reported [4]. IR was reported to accelerate fibrosis in chronic HCV-infected patients [5,6], which may lead to increased risk of cirrhosis and hepatocellular carcinoma [7] and has been associated with reduced rate of sustained virological response (SVR) in response to pegylated interferon (IFN)-α and ribavirin therapy [8]. …”

Section: Introductionmentioning

confidence: 99%

Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs

Sagheer

Soliman

Ahmad

et al. 2018

Libyan Journal of Medicine

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Chronic hepatitis C virus (HCV) infection is associated with altered metabolism, including dyslipidemia and insulin resistance. These contribute to disease progression and influences the response to therapy. To investigate the relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4 patients were included; they were divided into four groups according to the severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered as a control group. Lipid profile changes and IR were analyzed at baseline and after the end of treatment, and any effect of these changes on the response to treatment was studied. Before treatment, the levels of serum triglycerides were significantly higher in patients than in the control, and the levels of fasting insulin showed a progressive increase with advancing stage of fibrosis. At the end of treatment, there were a significant reduction in serum triglycerides, FBS, fasting insulin, and homeostasis model for the assessment of IR (P < 0.001), and a significant elevation of serum cholesterol and low-density lipoprotein (LDL)-c, high-density lipoprotein (HDL)-c, and LDL/HDL ratio (P = 0.001). An end-of-treatment response (week 12) was achieved in (99%) of the treated cases with 99% sustained viral response for 12 weeks post-treatment (week 24). Significant lipid profile changes were detected at the end of treatment. Serum lipid levels and IR are no longer predictors of response to DAAs. Follow-up of the lipid profile is warranted to avoid any possible remote effect of atherosclerotic heart disease.

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“…There was a statistically significant difference comparing the HOMA-IR of patients achieving complete early virological response, partial early virological response and non-response (P = 0.006). Likewise, Khattab et al found a highly and significant relationship between insulin resistance and treatment response (P < 0.001) (25). Similarly, Moucari et al concluded from their study that HO-MA-IR score < 2 was associated with early virological response (P < 0.001) and also remained an independent predictor of sustained virological response by multiple logistic regression analysis (P = 0.03) (23).…”

Section: Discussionmentioning

confidence: 89%

“…End-of-treatment response was defined as serum HCV-RNA below the limit of detection at the end of treatment. We considered non-responders to be: patients with no or minimal change in their HCV-RNA titres (< 2 log10 drop at week 12 as compared with baseline); those with viral load drop > 2 log10 at week 12 as compared with baseline and who still had positive HCV-RNA at week 24; those who became HCV-RNA positive after negativization before the end of treatment (breakthrough response); and those who became HCV-RNA positive after negativization at the end of treatment (25).…”

Section: Virological Assessmentsmentioning

confidence: 99%

Study of prevalence and effects of insulin resistance in patients with chronic hepatitis C genotype 4

Alazawy

et al. 2015

Easter Mediterr Health J

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There is strong epidemiological evidence linking hepatitis C virus (HCV) infection and diabetes. Our aim was to evaluate the prevalence of insulin resistance in Egyptian patients with chronic HCV genotype 4 infection, to assess factors associated with insulin resistance and to test the impact of insulin resistance on outcomes of treatment with pegylated interferon/ribavirin. Insulin resistance [homeostasis model assessmentinsulin resistance (HOMA-IR) score > 3.0] was detected in 31 of 100 nondiabetic patients. The relationship between elevated HOMA-IR and baseline viral load and degree of fibrosis was statistically significant (r = 0.218 and r = 0.223). Follow-up of patients with complete early virological response until the end of treatment showed a statistically significant decrease in HOMA-IR score. Out of 29 liver tissue sections examined, 14 had a low level of expression of insulin receptor type 1 by immunohistochemical studies. This study confirms that insulin resistance affects treatment outcome, and thus HOMA-IR testing before initiation of therapy may be a cost-effective tool. ‫عليهم‬ ‫وتأثرياهتا‬

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Insulin Resistance Predicts Rapid Virologic Response to Peginterferon/Ribavirin Combination Therapy in Hepatitis C Genotype 4 Patients

Abstract: IR is a major determinant of both RVR and SVR in genotype 4 CHC patients. HOMA-IR would seem to be a useful tool for predicting the response to therapy.

Cited by 74 publications

References 24 publications

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs

Study of prevalence and effects of insulin resistance in patients with chronic hepatitis C genotype 4

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