Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3

Thompson, Alexander; Patel, Keyur; Chuang, Wan‐Long; Lawitz, Eric; Rodrı́guez-Torres, Maribel; Rustgi, Vinod K.; Flisiak, Robert; Pianko, Stephen; Diago, M.; Arora, Sanjeev; Foster, Graham R.; Torbenson, Michael; Benhamou, Yves; Nelson, David R.; Sulkowski, Mark S.; Zeuzem, Stefan; Pulkstenis, Erik; Subramanian, G. Mani; McHutchison, John G.

doi:10.1136/gut.2010.236158

Cited by 81 publications

(80 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As expected, race was not a significant predictor of SVR after accounting for ribavirin AUC 0-7 and IL28B genotype in the model. Our finding that HOMA-IR and IL28B genotype had a significant effect on SVR is consistent with recent reports (29)(30)(31). Hepatic fibrosis showed a weak association with SVR in the univariate model, which may be explained by the majority of patients (85%) having mild to moderate Ishak scores.…”

Section: Discussionsupporting

confidence: 82%

Population Pharmacokinetics and Pharmacodynamics of Ribavirin in Patients with Chronic Hepatitis C Genotype 1 Infection

Jin

Fossler

McHutchison

et al. 2012

AAPS J

View full text Add to dashboard Cite

Abstract. We report a population pharmacokinetic (PK) and pharmacodynamic (PD) model of orally administered ribavirin in patients with chronic hepatitis C virus (HCV) infection enrolled in a multicenter clinical trial, including the estimation of covariate effects on ribavirin PK parameters and sustained viral response (SVR). Ribavirin concentrations obtained from 144 patients, consisting of n=71 African American (AA) and n=73 Caucasian Americans (CA), during 24 weeks of therapy were best described by a twocompartment model with first-order absorption and elimination parameterized in terms of apparent oral clearance (CL/F), apparent central volume (Vc/F), apparent peripheral volume (Vp/F), and apparent intercompartmental clearance (Q/F). The typical population parameters were CL/F (19.0 L/h), Vc/F (1,130 L), Vp/F (4,020 L), and Q/F (38.6). The Vp/F was approximately 50% greater in AA compared to CA. Significant covariates in the SVR model included IL-28B genotype, homeostasis model assessment of insulin resistance, and ribavirin exposure during the first week (AUC 0−7 ). The population PK and logistic regression models both described the observed ribavirin concentration data and SVR data well. These findings suggest that optimization of ribavirin plasma concentrations during the first week of ribavirin dosing is most critical in AA patients in order to increase the rate of SVR, especially those with the IL-28B TT genotype.

show abstract

Section: Discussionsupporting

confidence: 82%

Population Pharmacokinetics and Pharmacodynamics of Ribavirin in Patients with Chronic Hepatitis C Genotype 1 Infection

Jin

Fossler

McHutchison

et al. 2012

AAPS J

View full text Add to dashboard Cite

show abstract

“…A number of studies indicate that the eradication of HCV through interferon-based therapy leads to an improvement in insulin resistance and a reduction in the incidence of T2DM (28)(29)(30). The current study confirmed this significant drop in glycemic levels (both in terms of mean value and the percentage of patients with hyperglycemia) Hepat Mon.…”

Section: Discussionsupporting

confidence: 78%

Metabolic Syndrome and Genotype 1 Virus C Compensated Liver Cirrhosis in the Era of Directly Acting Antiviral Therapy

et al. 2017

View full text Add to dashboard Cite

Objectives: The current study aimed at evaluating the association between metabolic syndrome (MeS) in patients with hepatitis C virus (HCV) liver cirrhosis (compensated, genotype, 1b) and changes after sustained viral response (SVR) following a 12-week therapy with paritaprevir, ritonavir, ombitasvir, dasabuvir, and ribavirin (PrOD+R). Methods: The current multicenter retrospective study included 809 patients diagnosed with compensated HCV cirrhosis (child class A), all 1b genotype treated for 12 weeks with direct acting antiviral agents -PrOD+R -regimen (according to the protocol practiced in Romania) and achieved SVR. The parameters of MeS (according to the definition of the International Diabetes Federation) were collected from medical records before and 12 weeks after the treatment. The results were collected in a central database and analyzed with SPSS 18.0. Statistical analysis used both descriptive and analytical methods with a significance level of 95% (CI 95%). Results: Out of the 809 patients, 105 (13%) demonstrated 3 out of the 5 criteria for MeS. Based on the MeS criteria, the commonest parameters were abnormal glycaemia (54.1%), followed by visceral obesity (38.6%), raised triglycerides (26.1%), high blood pressure (12.1%), and a low high-density lipoprotein (HDL)-cholesterol (4.6%). The re-assessment of MeS parameters after SVR showed favourable changes, which were statistically significant: a siginficanttly lower serum triglyeride level (182.32 vs. 153.50 mg/dL, P = 0.001), lower systolic arterial blood pressure (130.57 vs. 124.85 mmHg; P = 0.001), lower diastolic arterial blood pressure (80.26 vs. 78.42 mmHg; P = 0.001) and lower glyceamic levels (130.06 vs. 120.71 mg/dL; P = 0.001), as well as a significant rise in HDL-cholesterol levels (48.61 vs. 50.50 mg/dL; P = 0.003). Abdominal circumference was the only parameter, which did not change after SVR. Following the changes sustained after SVR, 26.7% of the patients no longer fulfilled the minimum 3 criteria for MeS. No correlation was observed between the presence of MeS and the risk of severe adverse events, but it was noted that 37.5% of the patients who decompensated, 66.7% of the ones who developed hepatocarcinoma and 100% of the ones that died of abnormal glycaemic levels. Conclusions: Hyperglycemia, and not MeS, is associated with HCV compensated liver cirrhosis genotype 1b, and is a risk factor for severe adverse events. The attainment of SVR through PrOD+R regimen results in short-term improvements in MeS parameters.

show abstract

“…A significant improvement in IR was reported in patients who achieved SVR after treatment from HCV genotype 1 infection compared with those who did not [9,25]. Others [26–29] concluded that achieving viral clearance significantly reduces the risk for both type 2 DM and de novo IR in nondiabetic HCV patients. Similarly, in our study, patients who achieved SVR showed a significant improvement in fasting insulin and HOMA-IR.…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3

Cited by 81 publications

References 40 publications

Population Pharmacokinetics and Pharmacodynamics of Ribavirin in Patients with Chronic Hepatitis C Genotype 1 Infection

Population Pharmacokinetics and Pharmacodynamics of Ribavirin in Patients with Chronic Hepatitis C Genotype 1 Infection

Metabolic Syndrome and Genotype 1 Virus C Compensated Liver Cirrhosis in the Era of Directly Acting Antiviral Therapy

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

Contact Info

Product

Resources

About