Interferon lambda 3 rs12979860 polymorphism in patients with haemophilia and HCV infection: a predictor of spontaneous viral clearance and sustained virological response

2014 ◽  
Vol 111 (06) ◽  
pp. 1067-1076 ◽  
Author(s):  
Silvia Linari ◽  
Alessio Aghemo ◽  
Dario Bartolozzi ◽  
Elena Santagostino ◽  
Maria Rumi ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Antiviral Therapy ◽  
Sustained Virological Response ◽  
Virological Response ◽  
Response Rates ◽  
Viral Clearance ◽  
Hcv Infection ◽  
Spontaneous Viral Clearance ◽  
Interferon Lambda ◽  
Interferon Lambda 3

SummaryChronic hepatitis C is the main cause of morbidity and mortality in adult haemophilic patients who received non-virally inactivated plasma-derived clotting factor concentrates. Overall, spontaneous viral clearance rate is 10–25% and the only approach that can halt disease progression is hepatitis C virus (HCV) eradication by means of antiviral therapy. In non-haemophilic patients a single nucleotide polymorphism located upstream the gene of interferon lambda 3 (IFNλ3) has been associated with both spontaneous viral clearance and sustained virological response after antiviral treatment. The aim of this study was to assess whether the rs12979860 polymorphism was a predictor of spontaneous viral clearance and of sustained virological response after antiviral therapy in a large cohort of haemophilic patients with HCV infection. The rs12979860 polymorphism, defined as CC genotype or T allele, was tested in a cohort of 342 haemophilic patients and evaluated as predictor of spontaneous clearance or response to antiviral therapy. By multivariate regression analysis the IFNλ3 CC genotype was an independent predictor of spontaneous viral clearance (odds ratio: 3.7, 95% confidence interval: 2.0–6.8). Sustained virological response rates were doubled in patients with the CC genotype than in those with the T allele (78% vs 44%; p<0.001), especially in patients with HCV type 1 (67% vs 32%; p<0.001) and higher sustained response rates were observed in patients with the CC genotype who did not achieve rapid virological response (61% vs 30% in T allele patients; p=0.006).

scholarly journals IL-28B - Predictor of Sustained Virological Response for IFN-based Regimens in Chronic Hepatitis C and Criteria for Optimizing DAAs Indication

2019 ◽  
Vol 70 (11) ◽  
pp. 3964-3966
Author(s):  
Ioan Sergiu Micu ◽  
Marilena Musat ◽  
Yousef Al Hamidi ◽  
Andrada Dumitru ◽  
Anca Rogoveanu ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Treatment Response ◽  
Sustained Virological Response ◽  
Chronic Hepatitis C ◽  
Virological Response ◽  
Antiviral Treatment ◽  
Sustained Viral Response ◽  
Response Rates ◽  
Viral Response

Chronic viral infections affecting the liver represents a global burden for medical comunities. More than 170 million individuals are infected chronically with hepatitis C virus (HCV), this accounting about 2�3% of the world�s population. Despite numerous progresses aquired in viral pahogenesis and treatment, chronic hepatitis C management is influenced by a multitude of factors. Interleukin IL-28 beta subunit (IL28B) demonstrated to be involved in both sustained virological response (SVR) to treatment, but even with spontaneous viral clearance without any therapy. In the era of direct antiviral agents (DAAs) we aimed to find out what was the real influence of IL28B phenotypes over the response to Peg-IFN and Ribavirin treatment in patients with chronic hepatitis C, many of theses being non-responders or relapsers, and as consequence, to optimize the referal of patients to more expensive and efficient treatments. In a retrospectively manner, we analyzed the IL28B phenotype and its influence over the rapid viral response (RVR), early viral response (EVR) and sustained viral response (SVR), in 250 patients HCV treated patients. We made correlations between the treatment response rates and the IL28B polymorphism.TT phenotype was correlated negatively with all parameters studied, while CC phenotype was correlated with the best response rates. We concluded that IL28B phenotypes interfere with the EVR and SVR rates, IL28B phenotype being an independent prognostic factor for antiviral treatment response in our patient groups, and according to this characteristics, we created the premise to optimize the patients referal to expensive therapies as DAAs.

scholarly journals Antidepressant Prophylaxis Reduces Depression Risk but Does Not Improve Sustained Virological Response in Hepatitis C Patients Receiving Interferon Without Depression at Baseline: A Systematic Review and Meta-Analysis

2013 ◽  
Vol 27 (10) ◽  
pp. 575-581 ◽  
Author(s):  
Awad Al-Omari ◽  
Juthaporn Cowan ◽  
Lucy Turner ◽  
Curtis Cooper
Keyword(s):  
Depressive Symptoms ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Sustained Virological Response ◽  
Risk Ratio ◽  
Virological Response ◽  
Randomized Clinical Trials ◽  
Rating Scale ◽  
Antiviral Treatment ◽  
Well Being

BACKGROUND: Depression complicates interferon-based hepatitis C virus (HCV) antiviral therapy in 10% to 40% of cases, and diminishes patient well-being and ability to complete a full course of therapy. As a consequence, the likelihood of achieving a sustained virological response (SVR [ie, permanent viral eradication]) is reduced.OBJECTIVE: To systematically review the evidence of whether preemptive antidepressant prophylaxis started before HCV antiviral initiation is beneficial.METHODS: Inclusion was restricted to randomized controlled trials in which prophylactic antidepressant therapy was started at least two weeks before the initiation of HCV antiviral treatment. Studies pertaining to patients with active or recent depressive symptoms before commencing HCV antiviral therapy were excluded. English language articles from 1946 to July 2012 were included. The MEDLINE, Embase and Cochrane Central databases were searched. Where possible, meta-analyses were conducted evaluating the effect of antidepressant prophylaxis on SVR and major depression as well as on Montgomery-Asberg Depression Rating Scale and Beck Depression Index scores at four, 12 and 24 weeks. The Cochrane Collaboration tool was used to assess bias risk.RESULTS: Six randomized clinical trials involving 522 patients met the inclusion criteria. Although the frequency of on-treatment clinical depression was decreased with antidepressant prophylaxis (risk ratio 0.60 [95% CI 0.38 to 0.93]; P=0.02; I2=24%), no benefit to SVR was identified (risk ratio 1.08 [95% CI 0.74 to 1.57]; P=0.69; I2=58%).CONCLUSION: This practice is not justified to improve SVR in populations free of active depressive symptoms leading up to HCV antiviral therapy.

scholarly journals Association of the Sialylation of Antibodies Specific to the HCV E2 Envelope Glycoprotein with Hepatic Fibrosis Progression and Antiviral Therapy Efficacy

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Oleg Kurtenkov ◽  
Jelena Jakovleva ◽  
Boris Sergejev ◽  
Julia Geller
Keyword(s):  
Antiviral Therapy ◽  
Sustained Virological Response ◽  
Hepatic Fibrosis ◽  
Virological Response ◽  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
Predictive Biomarkers ◽  
Hcv Infection ◽  
Hcv Genotype ◽  
Treatment Naïve

The E2 envelope glycoprotein of the hepatitis C virus (HCV) is a major target of broadly neutralizing antibodies that are closely related to a spontaneous cure of HCV infection. There is still no data about the diversity of E2-specific antibodies (Abs) glycosylation. The aim of this study was to analyze the level and sialylation of E2 IgG Abs, the relation of the respective changes to hepatic fibrosis (F) progression and their possible association with the efficacy of interferon-α-2a plus ribavirin (IFN-RBV) antiviral therapy. One hundred three HCV infected treatment-naive patients were examined using ELISA with E2 recombinant protein as antigen and sialic acid-specific Sambucus nigra agglutinin. The efficacy of the IFN-RBV treatment of patients with HCV dominant 1b and 3a genotypes (GT) was evaluated. A significant decrease of E2 Abs sialylation in the late stages of fibrosis was found irrespective of HCV genotype. On this basis, the F4 stage of fibrosis can be discriminated from its F0 or F1-3 stage by an about 75-79% accuracy. HCV infection of 1b genotype is associated with the production of lower sialylated E2 Abs, a higher frequency of F4 stage fibrosis, and a worse response to antiviral therapy. The increased SNA reactivity of E2 Abs was observed in patients with a sustained virological response (SVR). The proportion of SVR responders was significantly higher among patients with 3a genotype. However, for both dominant HCV genotypes (3a and 1b), an increased sialylation of E2 IgG was associated with a higher rate of patients with sustained virological response to antiviral therapy. Thus, the association of alterations of anti-E2 IgG Abs sialylation with hepatic fibrosis stage, HCV genotype, and the efficacy of antiviral therapy enables using these changes as novel noninvasive predictive biomarkers. The clinical potential of these findings is discussed.

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