Impact of Interleukin 28B (rs12979860) Genotype on Virological Responses Chronic Hepatitis C Treatment
Impact of Interleukin 28B (rs12979860) Genotype on Virological Responses Chronic Hepatitis C Treatment
Objective:

 Pegulated Interferon α2 plus ribavirin is a treatment of choice in patients with chronic
 hepatitis C infection. This study was conducted to find out the frequency of different IL-28B
 (rs12979860) genotypes in patients with chronic hepatitis C (HCV genotype type 2 & 3)
 infection treated with Pegulated Interferon α2 plus ribavirin and to evaluate the role of
 IL-28B genotypes in achieving Sustained Virological Response (SVR).

 Methods:

 In this non-randomized observational study, ninety eight (98) patients with diagnosis of
 chronic hepatitis C were included. In all patients, Peg-IFN plus Ribavirin were given in
 standard doses for 24 weeks. End treatment response, sustained virological response, and
 relapse rate were the primary endpoints of this study. Analysis of IL28B (rs12979860)
 polymorphism (CC, CT and TT) was performed by PCR-RFLP protocol.
INTRODUCTION:

 Hepatitis C virus (HCV) is a major health problem that effects nearly 170 million people
 worldwide [1, 2]. According to a report, about 64-103 million people are suffering from
 chronic HCV infection [3] and this chronic infection results in liver scarring,
 hepatocellular carcinoma or end-stage liver disease in about forty thousand (40,000) patients
 every year [4, 5]. According to WHO, liver disease initiated by chronic hepatitis C infection
 is responsible for more than 35 thousand deaths and 3 to 4 million people are infected every
 year[3, 6]. Hepatitis C Virus has been classified into seven genotypes and several subtypes,
 which are associated with distinct forms of geographic dispersal [7, 8]. The success of HCV
 treatment is affected by many viral, treatment or host factors.

 Pegulated Interferon α2 plus ribavirin is a treatment of choice in patients with chronic
 hepatitis C infection. Sustained virological response (SVR) rate with this treatment in HCV-2
 & 3 has been reported to be 58-84% in previously untreated patients [9]. SVR can be affected
 by liver cirrhosis, hepatocellular carcinoma, ethnicity, age, gender and obesity. [10, 11] It
 has been clarified by some studies that interleukin-28B has an important role in the
 treatment success of HCV infection and IL-28B CC genotype is associated with 2 folds higher
 sustained virological response (SVR) as compared to CT and TT genotype [12-14]. The aim of
 present study was to find out the frequency of different IL28B (rs12979860) genotypes in
 patients with chronic hepatitis C (genotype type 2 or 3) infection treated with Pegulated
 Interferon α2 plus ribavirin and to evaluate the role of IL-28B genotypes in achieving
 Sustained Virological Response (SVR).

 METHODS:

 This non-randomized observational study was conducted in Sheikh Zayed Medical
 College/Hospital Rahim Yaar Khan. A total of ninety eight (98) patients with diagnosis of
 chronic hepatitis C genotype 2 or 3 were involved in this study. The duration of study was
 from January 2015 to January 2016. People living in Rahim Yaar Khan City belongs to different
 ethinic backgrounds because this city is located at the junction of three provinces of
 Pakistan (total provinces are four), so people residing here represent the whole Pakistani
 population living in different provinces. Institutional ethical approval was taken before
 starting this research work. A written informed consent was taken from every patient before
 including him/her in this study.

 The diagnosis of chronic hepatitis C was made through liver enzyme levels, HCV-RNA positivity
 and anti-HCV antibody test. Patients with other chronic liver disorders, with positive
 hepatitis B virus (HBV), and human immunodeficiency virus (HIV) infection were excluded from
 this study.

 Treatment Protocol and Detection of IL28B Polymorphism:

 In all patients Pegulated Interferon α2 (pegIFN) plus Ribavirin were given in standard doses.
 PegINF was given in a dose of 180 μg/week and ribavirin 1200 mg/day to every patient for the
 period of 24 weeks for HCV genotype 2 & 3.

 PCR analysis was done in every patient before starting the treatment, after 24 weeks of
 treatment (to see end treatment response) and 48 weeks (to evaluate SVR and relapse rate) of
 treatment. Analysis of IL28B (rs12979860) polymorphism (CC, CT and TT) was performed by PCR
 restriction fragment length polymorphism (RFLP) assay protocol. Pyrosequencing method was
 used to determine HCV genotypes.

 Data analysis was done using SPSS V17 software. Mean and standard deviation were used for the
 presentation of quantitative variables. Frequency and percentages were used to present
 qualitative data. Chi-square test/Fisher Exact test was used to compare qualitative data.
 P-value <0.05 was taken as significant.
Inclusion Criteria:

 -  patients with diagnosis of chronic hepatitis C genotype 2 or 3

 Exclusion Criteria:

 -  Patients with hepatitis genotype I and IV