Serum lipids in European chronic HCV genotype 1 patients during and after treatment with pegylated interferon-alfa-2a and ribavirin

Lange, CM; Wagner, M. von; Bojunga, Jörg; Berg, Thomas; Farnik, Harald; Hassler, Angela; Sarrazin, Christoph; Herrmann, Evelyn; Zeuzem, Stefan

doi:10.1055/s-0030-1263882

Cited by 8 publications

(11 citation statements)

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“…35 Such therapy also has an effect on the lipid and metabolic profile, with lipid levels significantly increasing from baseline. 36 Interestingly, when we calculated event rates separately for cardiac, cerebrovascular, and peripheral events, SVR was not associated with a significant decrease in any event rates, but treatment with DAA regimens was associated with a significant decrease compared with untreated and PEG-and RBVtreated persons. This suggests that treatment regimen might be a more important driver in decreasing risk than attainment of an SVR.…”

Section: March 2019mentioning

confidence: 86%

Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events

et al. 2019

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is associated with an increased risk of cardiovascular disease (CVD) events. It is not clear whether treatment with directacting antiviral (DAA) agents affects risk of CVD. METHODS:We searched the Electronically Retrieved Cohort of HCV-Infected Veterans database for patients with chronic HCV infection (n ¼ 242,680) and identified patients who had been treated with a pegylated interferon and ribavirin regimen (n ¼ 4436) or a DAA-containing regimen (n ¼ 12,667). Treated patients were matched for age, race, sex, and baseline values with patients who had never received treatment for HCV infection (controls). All subjects were free of any CVD event diagnosis of HCV infection at baseline. The primary outcome was incident CVD events, identified by International Classification of Diseases, Ninth Edition, Clinical Modification or International Classification of Diseases, Tenth Edition code, in the different groups and in patients with vs without a sustained virologic response to therapy. RESULTS: There were 1239 (7.2%) incident CVD events in the treated groups and 2361 (13.8%) events in the control group. Incidence rates were 30.9 per 1000 patient-years (95% CI 29.6-32.1) in the control group and 20.3 per 1000 patientyears (95% CI 19.2-21.5) in the treated groups (P < .0001). Treatment with pegylated interferon and ribavirin (hazard ratio 0.78; 95% CI 0.71-0.85) or a DAA regimen (hazard ratio 0.57; 95% CI 0.51-0.65) was associated with a significantly lower risk of a CVD event compared with no treatment (controls). Incidence rates for CVD events were 23.5 per 1000 patient-years (95% CI 21.8-25.3) in the group treated with the pegylated interferon and ribavirin regimen, 16.3 per 1000 patient-years (95% CI 14.7-18.0) in the group treated with a DAA regimen, and 30.4 (95% CI 29.2-31.7) in the control group. A sustained virologic response was associated with a lower risk of incident CVD events (hazard ratio 0.87; 95% CI 0.77-0.98). CONCLUSIONS: In an analysis of a cohort of HCV-infected veterans, treatment of HCV infection was associated with a significant decrease in risk of CVD events. Patients treated with a DAA regimen and patients who achieved sustained virologic responses had the lowest risk for CVD events.

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Section: March 2019mentioning

confidence: 86%

Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events

et al. 2019

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“…The present, to our knowledge, largest, most comprehensive study, which was restricted to adherent patients who had received the recommended dose of PEG‐IFN‐α and ribavirin during the first 12 weeks of therapy, had the power to clearly demonstrate that serum ferritin is an independent predictor of treatment failure, even though serum ferritin was also independently associated with advanced liver fibrosis and steatosis. This observation indicates that serum ferritin is a promising candidate to be included in the panel of predictors of response to IFN‐α‐based therapy 12, 26, 38‐42. This may be especially relevant in patients infected with HCV genotype 3, in whom the utility of IL28B genotyping is limited, even though a substantial number of patients cannot be cured with PEG‐IFN‐α and ribavirin alone 43, 44.…”

Section: Discussionmentioning

confidence: 99%

Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy

et al. 2012

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Elevated serum ferritin levels may reflect a systemic inflammatory state as well as increased iron storage, both of which may contribute to an unfavorable outcome of chronic hepatitis C (CHC). We therefore performed a comprehensive analysis of the role of serum ferritin and its genetic determinants in the pathogenesis and treatment of CHC. To this end, serum ferritin levels at baseline of therapy with pegylated interferon-alpha and ribavirin or before biopsy were correlated with clinical and histological features of chronic hepatitis C virus (HCV) infection, including necroinflammatory activity (N 5 970), fibrosis (N 5 980), steatosis (N 5 886), and response to treatment (N 5 876). The association between high serum ferritin levels (>median) and the endpoints was assessed by logistic regression. Moreover, a candidate gene as well as a genome-wide association study of serum ferritin were performed. We found that serum ferritin ! the sex-specific median was one of the strongest pretreatment predictors of treatment failure (univariate P < 0.0001, odds ratio [OR] 5 0.45, 95% confidence interval [CI] 5 0.34-0.60). This association remained highly significant in a multivariate analysis (P 5 0.0002, OR 5 0.35, 95% CI 5 0.20-0.61), with an OR comparable to that of interleukin (IL)28B genotype. When patients with the unfavorable IL28B genotypes were stratified according to high versus low ferritin levels, SVR rates differed by >30% in both HCV genotype 1-and genotype 3-infected patients (P < 0.001). Serum ferritin levels were also independently associated with severe liver fibrosis (P < 0.0001, OR 5 2.67, 95% CI 5 1.68-4.25) and steatosis (P 5 0.002, OR 5 2.29, 95% CI 5 1.35-3.91), but not with necroinflammatory activity (P 5 0.3). Genetic variations had only a limited impact on serum ferritin levels. Conclusion: In patients with CHC, elevated serum ferritin levels are independently associated with advanced liver fibrosis, hepatic steatosis, and poor response to interferon-alpha-based therapy. (HEPATOLOGY 2012;55:1038-1047 C hronic hepatitis C (CHC) is one of the most significant infectious diseases by being a leading cause of liver-related morbidity and liver transplantation worldwide. 1,2 Triple therapy comprising the hepatitis C virus (HCV) nonstructural protein 3-4A protease inhibitors, telaprevir or boceprevir, in combination with pegylated interferon-alpha (PEG-IFN-a) and ribavirin is becoming the new standard treatment for patients infected with the difficult-tocure HCV genotype 1. 3 Recently completed phase III

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“…IL28B SNPs were shown to be the strongest pretreatment-predictor of treatment outcome in HCV genotype 1 patients. Nevertheless, it was estimated that IL28B variations account for ''only'' about 15% of inter-individual variability of SVR, a finding which supports the importance of additional predictors of treatment response, possibly including more recently established predictors such as vitamin D deficiency, interferon-c-inducible protein-10 (IP-10) serum levels, or steatosis/insulin resistance [1,2,43,[63][64][65][66][67]. In this context, models for the prediction of SVR which include a variety of parameters in combination with IL28B genotype might be of value, since they were shown to achieve higher accuracy in predicting treatment response compared to the IL28B genotype alone [63,[68][69][70].…”

Section: Il28b Snps and Treatment With Directly Acting Antiviral Agentsmentioning

confidence: 94%

“…In addition, good response IL28B SNPs were associated with a lower incidence of hepatic steatosis in patients with chronic hepatitis C [84]. Interferons were shown to decrease serum levels of cholesterol and other parameters of lipid metabolism [65]. The association of good-response IL28B variations with higher LDL and cholesterol serum levels may, therefore, reflect a lower pre-treatment IFN-(k) activity in these patients.…”

Section: Il28b Snps and The Natural Course Of Hepatitis Cmentioning

confidence: 99%

IL28B single nucleotide polymorphisms in the treatment of hepatitis C

Lange

Zeuzem

2011

Journal of Hepatology

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Recent genome-wide association studies (GWAS) have identified genetic variations near the IL28B gene which are strongly associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. Protective IL28B variations are strongly associated with on-treatment viral kinetics and approximately 2-fold increased sustained virologic response (SVR) rates in HCV genotype 1 and 4 patients. In HCV genotype 1 patients, IL28B variations were shown to be the strongest pre-treatment predictor of virologic response. In the treatment of HCV genotype 2 and 3 infected patients, IL28B variations play only a minor role. Preliminary data indicate that IL28B variations are also associated with treatment outcome of regimens, including directly acting antiviral (DAA) agents, though their impact seems to be attenuated compared to standard treatment. Here, we review these important findings and discuss possible implications for clinical decision making in the treatment of HCV infection.

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Serum lipids in European chronic HCV genotype 1 patients during and after treatment with pegylated interferon-alfa-2a and ribavirin

Cited by 8 publications

References 0 publications

Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events

Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events

Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy

IL28B single nucleotide polymorphisms in the treatment of hepatitis C

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