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

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. Keywords: hepatitis C virus, IL-28 beta subunit,viral treatment

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

Revista de Chimie ◽

10.37358/rc.19.11.7682 ◽

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.

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Abbott RealTime Hepatitis C Virus (HCV) and Roche Cobas AmpliPrep/Cobas TaqMan HCV Assays for Prediction of Sustained Virological Response to Pegylated Interferon and Ribavirin in Chronic Hepatitis C Patients

Journal of Clinical Microbiology ◽

10.1128/jcm.01753-08 ◽

2008 ◽

Vol 47 (2) ◽

pp. 385-389 ◽

Cited By ~ 21

Author(s):

K. Matsuura ◽

Y. Tanaka ◽

I. Hasegawa ◽

T. Ohno ◽

H. Tokuda ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Sustained Virological Response ◽

Chronic Hepatitis C ◽

Virological Response ◽

Pegylated Interferon ◽

Cobas Taqman ◽

Chronic Hepatitis C Patients ◽

Roche Cobas

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IL28B CC genotype: a protective factor and predictor of the response to interferon treatment in chronic hepatitis C virus infection

Orvosi Hetilap ◽

10.1556/oh.2013.29680 ◽

2013 ◽

Vol 154 (32) ◽

pp. 1261-1268 ◽

Cited By ~ 5

Author(s):

Alajos Pár ◽

Gabriella Pár ◽

István Tornai ◽

Ferenc Szalay ◽

Dalma Várszegi ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Sustained Virological Response ◽

Chronic Hepatitis C ◽

Virological Response ◽

Pegylated Interferon ◽

Hepatitis C Virus Infection ◽

Pegylated Interferon Plus Ribavirin ◽

Chronic Hepatitis C Virus

Introduction: In chronic hepatitis C-virus infection the possible role of gene variants encoding cytokines has become the focus of interest. Aim: The aim of the study was to investigate the effect of IL28B polymorphisms on the outcome of chronic hepatitis C-virus genotype 1 infection in the Hungarian population. In addition, the association between IL28B genotypes and the Th1/Th2 cytokine production of activated peripheral blood monocytes and lymphocytes was evaluated. Method: Total of 748 chronic hepatitis C-virus genotype 1 positive patients (365 males and 383 females, aged between 18 and 82 years; mean age, 54±10 years) were enrolled, of which 420 patients were treated with pegylated interferon plus ribavirin for 24–72 weeks. Of the 420 patients, 195 patients (46.4%) achieved sustained virological response. The IL28B rs12979860 polymorphism was determined using Custom Taqman SNP Genotyping Assays (Applied Biosystems, Life Technologies, Foster, CA, USA). For cytokine studies, tumour necrosis factor-α, interleukin-2, interferon-γ, interleukin-2 and interleukin-4 production by LPS-stimulated monocytes and PMA-ionomycine activated lymphocytes were measured from the supernatant of the cells obtained from 40 hepatitis C-virus infected patients, using FACS-CBA Becton Dickinson test. The cytokine levels were compared in patients with different (CC, CT, TT) IL28B genotypes. Results: The IL28B rs12979860 CC genotype occurred in lower frequency in hepatitis C-virus infected patients than in healthy controls (26.1% vs 51.4%, OR 0.333, p<0.001). Patients carried the T allele with higher frequency than controls (73.9%, vs 48.6%, OR 3.003, p<0.001). Pegylated interferon plus ribavirin treated patients with the IL28B CC genotype achieved higher sustained virological response rate than those with the CT genotype (58.6% vs 40.8%, OR 2.057, p = 0.002), and those who carried the T allele (41.8%, OR1.976, p = 0.002). LPS-induced TLR-4 activation of monocytes resulted in higher tumour necrosis factor-α production in patients with the IL28B CC genotype compared to non-CC individuals (p<0.01). Similarly, increased tumour necrosis factor-α, interleukin-2 and interferon-γ production by lymphocytes was found in the IL28B CC carriers (p<0.01) Conclusions: The IL28B CC genotype exerts protective effect against chronic hepatitis C-virus infection and may be a pretreatment predictor of sustained virological response during interferon-based antiviral therapy. The IL28B CC polymorphism is associated with increased Th1 cytokine production of activated peripheral blood monocytes and lymphocytes, which may play a role in interferon-induced rapid immune control and sustained virological response of pegylated interferon plus ribavirin treated patients. Orv. Hetil., 2013, 154, 1261–1268.

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