Insulin resistance and geographical origin: major predictors of liver fibrosis and response to peginterferon and ribavirin in HCV-4

Moucari, Rami; Ripault, Marie–Pierre; Martinot–Peignoux, Michelle; Voitot, Hélène; Cardoso, Abel Silveira; Stern, Christiane; Boyer, Nathalie; Maylin, Sarah; Nicolas–Chanoine, Marie–Hélène; Vidaud, Michel; Valla, Dominique; Bédossa, Pierre; Marcellin, Patrick

doi:10.1136/gut.2009.185074

Cited by 67 publications

(69 citation statements)

References 33 publications

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“…Mutations in the NS5A region, particularly in patients with more than 6 aa mutations in the Interferon RBV resistance determining region (IRRDR) are highly associated with good response to PEGIFN and RBV combination therapy, while a less diverse (≤ 5) IRRDR sequence is associated with nonresponse [144146] . Another predictor of response to PEGIFN/RBV therapy was found to be insulin resistance, which impairs response rates to PEG IFN/RBV therapy in HCV GT4 patients, and patients with Homeostasis Model Assessment for Insulin Resistance scores > 2 had lower SVR rates than those with scores < 2 (36% vs 72%) [147] . AbuMouch et al [148] found that adding vitaminD to the standard of care with PEGIFN/RBV therapy for HCVGT1 infected patients increases SVR rates from 42% to 82%.…”

Section: Background In Hcv Treatmentmentioning

confidence: 99%

Hepatitis C genotype 4: The past, present, and future

Abdel-Ghaffar

Sira

Naghi

2015

WJH

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Hepatitis C virus (HCV) genotype (GT) 4 represents 12%-15% (15-18 million) of total global HCV infection. It is prevalent in Northern and Equatorial Africa and the Middle East, and is also present in some countries in Europe. GT-4 (and subtype 4a in particular) dominates the HCV epidemic in Egypt. In underdeveloped countries, risk factors associated with HCV infection may be due to unsafe medical practices or other factors such as familial transmission, mother's HCV status, or illiteracy. HCV prevention and control programs should include health education, increased community awareness towards the disease, controlling infection distribution in healthcare centers, proper sterilization of medical and dental instruments, and ensuring safe supply of blood and blood-products. Response rates to a 48-wk combined pegylated-interferon (PEG-IFN) and ribavirin (RBV) treatment range from 40%-69%, and HCV-GT-4 has been considered better than GT-1 but worse than GT-2 and GT-3 in treatment with PEG-IFN/RBV. However, with the introduction of the HCV-GT-1 effective protease inhibitors boceprevir and telaprevir in 2011, HCV-GT-4 became the "most difficult (GT) to treat". Recently, the direct-acting antivirals (DAAs) with pan-genotypic activities simeprevir, sofosbuvir, and daclatasvir have been recommended in triple regimens with PEG-IFN/RBV for the treatment of HCV-GT-4. An IFN-free regimen will be available for treatment of all genotypes of HCV in the near future. To date, several DAAs have been developed and are currently being evaluated in various combinations in clinical trials. As new regimens and new agents are being approved by the Food and Drug Administration, we can expect the guidelines for HCV treatment to be changed. The availability of shorter, simpler, and more tolerable treatment regimens can reduce the morbidity and mortality associated with HCV infection. With such a large number of therapeutic agents available, we can end up with a range of choices that we can select from to treat patients.

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Section: Background In Hcv Treatmentmentioning

confidence: 99%

Hepatitis C genotype 4: The past, present, and future

Abdel-Ghaffar

Sira

Naghi

2015

WJH

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“…SOCS-7 mRNA expression is independent of signal transducer and activator of transcription 3 and is modulated by peroxisome proliferator-activated receptor gamma activity (Figure 1) [52,55] . HCV genotype 4 is the most common variant in the Middle East and Africa and is increasing in prevalence in Western countries [56] . Infection with HCV genotype 4 is associated with a high prevalence of hepatic steatosis and obesity; however, the impact of adiponectin on insulin resistance remains controversial [57,58] and specific mechanisms of insulin resistance in HCV genotype 4 infection also remain unclear.…”

Section: Pathogenesis Of Insulin Resistance In Patients With Chronic mentioning

confidence: 99%

Insulin resistance and chronic liver disease

Kawaguchi

Taniguchi²,

Itou³

et al. 2011

WJH

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Increased insulin resistance is frequently associated with chronic liver disease and is a pathophysiological feature of hepatogenous diabetes. Distinctive factors including hepatic parenchymal cell damage, portalsystemic shunting and hepatitis C virus are responsible for the development of hepatogenous insulin resistance/ diabetes. Although it remains unclear whether insulin secretion from pancreatic beta cells is impaired as it is in type 2 diabetes, retinopathic and cardiovascular risk is low and major causes of death in cirrhotic patients with diabetes are liver failure, hepatocellular carcinoma and gastrointestinal hemorrhage. Hemoglobin A1c is an inaccurate marker for the assessment and management of hepatogenous diabetes. Moreover, exogenous insulin or sulfonylureas may be harmful because these agents may promote hepatocarcinogenesis. Thus, pathogenesis, cause of death, assessment and therapeutic strategy for hepatogenous insulin resistance/diabetes differ from those for lifestyle-related type 2 diabetes. In this article, we review features of insulin resistance in relationship to chronic liver disease. We also discuss the impact of anti-diabetic agents on interferon treatment and hepatocarcinogenesis.

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“…Besides presence of advanced fibrosis, treatment outcome in genotype 4 has been associated with insulin resistance, hepatic steatosis and adiponectin changes, as in other genotypes [27][28][29][30][31][32]. Even though neither insulin resistance nor adiponectin levels were addressed in our study, indirect evidence, estimated by histologic presence of hepatic steatosis and measurement of BMI, showed that these factors were probably not related to genotype's 4 worse prognosis.…”

Section: Discussionmentioning

confidence: 45%