Real-World Virologic Response Rates and Prediction of Outcomes with Peginterferon Alfa-2a/Ribavirin in Hungarian HCV Genotype 1 Patients

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Hepatitis C-vírussal fertôzött cirrhosisos betegek kezelésével nyert hazai real-life tapasztalatok a két pegilált interferonnal

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Ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin in HCV genotype 1 infected patients who failed previous protease inhibitor therapy

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IL28B and IL10R -1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort.

BACKGROUND: Previous studies have shown that single nucleotide polymorphisms (SNP) in IL28B and IL10R are associated with sustained virological response (SVR) in chronic hepatitis C patients treated with pegilated interferon plus ribavirin (P/R). The present study extends our earlier investigations on a large East-Central European cohort. The allele frequencies of IL28B and IL10R in genotype 1 HCV infection were compared with that of healthy controls for the purpose of examining the relationship between the polymorphisms and the SVR to P/R treatment. METHODS: A total of 748 chronic HCV1 infected patients (365 male, 383 female; 18-82 years) and 105 voluntary blood donors as controls were enrolled. Four hundred and twenty HCV patients were treated with P/R for 24-72 weeks, out of them 195 (46.4%) achieved SVR. The IL28 rs12979860 SNP was determined using Custom Taqman SNP Genotyping Assays. The IL10R -1087 (also known as IL10R -1082 (rs1800896) promoter region SNP was determined by RT-PCR and restriction fragment length polymorphism analysis. RESULTS: The IL28B CC genotype occurred with lower frequency in HCV patients than in controls (26.1% vs 51.4%, p<0.001). P/R treated patients with the IL28B CC genotype achieved higher SVR rate, as compared to patients with CT (58.6% vs 40.8%, p=0.002). The prevalence of IL10R -1087 GG genotype was lower in patients than in controls (31.8 % vs 52.2%, p<0.001). Among patients achieving SVR, the IL10R -1087 GG genotype occurred with higher frequency than the AA (32.0% vs 17.4%, p=0.013). The IL28B T allele plus IL10R A allele combination was found with higher prevalence in patients than in controls (52% vs 20.7%, p<0.001). The IL28B CC plus IL10R A allele combination occurred with higher frequency among patients with SVR than in non-responders (21.3% vs 12.8%, p=0.026). Both the IL28B CC plus IL10R GG and the IL28B CC plus IL10R A allele combinations occurred with lower frequency in patients than in controls. CONCLUSIONS: In our HCV1 patients, both the IL28B CC and IL10R GG genotypes are associated with clearance of HCV. Moreover, distinct IL28B and IL10R allele combinations appear to be protective against chronic HCV1 infection and predictors of response to P/R therapy

Mit várhatunk az 1-es genotípusú hepatitis C-vírus-fertőzöttek új, hármas kombinációs antivirális kezelésétől? | What is expected from the novel triple combination antiviral treatment of patients infected with hepatitis C virus genotype 1?

Bevezetés: 2011 májusától az 1-es genotípusú hepatitis C-vírussal fertőzöttek standard kezelése a proteázgátló/ribavirin/peginterferon kombináció. Célkitűzés: A szerzők hepatológiai centrumukban retrospektív felmérést végeztek az új kezelésre váró betegekről annak becslésére, hogy az új kezelés milyen arányban hozhat tartós vírusválaszt. Módszer: 2004. január és 2012. szeptember között 269, krónikus hepatitis C-vírus-fertőzöttet kezeltek peginterferon/ribavirin terápiával. 142 beteg nem ért el tartós vírusválaszt, de közülük csak 93-nál jön szóba hármas kombinációs antivirális kezelés. Ez utóbbi betegcsoportban meghatározták a megelőző sikertelen kezelésre adott vírusválaszt, a fibrosis mértékét és 49 betegnél az interleukin-28B genotípust. Eredmények: A megelőző kettős kezelésre adott vírusválasz alapján 25 visszaeső, 26 részlegesen reagáló, hat áttörés és 36 nullreagáló volt a 93 beteg között. A betegek 29%-ának enyhe-mérsékelt és 71%-ának már súlyos fibrosisa van. 49-ből csak nyolc betegnek van interleukin-28B CC genotípusa. Következtetés: Főleg a visszaesőknek, de a részlegesen reagálóknak is jó esélye van a tartós vírusválasz elérésére, amelyet a fibrosis foka is befolyásolhat. Orv. Hetil., 2013, 154, 257–261. | Introduction: Since May 2011, protease inhibitor/ribavirin/peginterferon combination has become the standard treatment for both treatment-naive and treatment-experienced patients infected with hepatitis C virus genotype 1. In Hungary, due to limited resources, the therapy of treatment-experienced patients might only be financed in the near future. Aim: The aim of this retrospective study was to find out characteristics of the patient group waiting for new triple combination in a single hepatology centre in Hungary, and to estimate the possible rate of their sustained virologic response. Method: Between January 2004 and September 2012, 269 patients with chronic hepatitis C virus infection were treated with peginterferon/ribavirin therapy. 142 patients failed to achieve sustained virologic response, but out of them, 93 individuals are the possible candidates for the triple antiviral treatment. In the latter group, the previous virologic response to dual therapy was determined. To register fibrosis scores, findings of liver biopsy and/or fibroelastography were also collected. Interleukin28B genotypes of 49 patients were determined. Results: Among the 93 treatment-experienced patients, 25 relapsed, 26 responded partially , 6 broke through, and 36 null-responders were found. 29% of patients had mild or moderate fibrosis and 71% of those already had severe fibrosis. Of the 49 patients with known interleukin28B genotype only 8 patients had the CC genotype. Conclusions: About half of the patients (mostly relapsers, and some partial responders as well) have a good chance of achieving sustained virologic response, which may be influenced by the fibrosis score. Orv. Hetil., 2013, 154, 257–261

Predictive value of FIB-4 and APRI versus METAVIR on sustained virologic response in genotype 1 hepatitis C patients

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