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

NCT ID: NCT03090035

Last Updated: 2017-04-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

98 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-01

Study Completion Date

2014-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hepatitis C Hepatitis C Relapse

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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chronic hepatitis C genotype 2 or 3

In all patients Pegylated Interferon α2 (pegIFN) plus Ribavirin were given in standard doses. Peg-INF 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

Group Type EXPERIMENTAL

Pegylated Interferon α2

Intervention Type DRUG

Peg-INF was given in a dose of 180 μg/week

Ribavirin

Intervention Type DRUG

ribavirin 1200 mg/day to every patient for the period of 24 weeks for HCV genotype 2 \& 3

Interventions

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Pegylated Interferon α2

Peg-INF was given in a dose of 180 μg/week

Intervention Type DRUG

Ribavirin

ribavirin 1200 mg/day to every patient for the period of 24 weeks for HCV genotype 2 \& 3

Intervention Type DRUG

Other Intervention Names

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Unipg Ribavil

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* Patients with hepatitis genotype I and IV
Minimum Eligible Age

20 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sheikh Zayed Medical College

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Muhammad ZM Babar, FCPS

Role: PRINCIPAL_INVESTIGATOR

Sheikh Zayed Medical College/Hospital

Locations

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Muhammad Zafar Majeed Babar

Sadiqabad, Punjab Province, Pakistan

Site Status

Countries

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Pakistan

References

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Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis. 2005 Sep;5(9):558-67. doi: 10.1016/S1473-3099(05)70216-4.

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Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014 Nov;61(1 Suppl):S45-57. doi: 10.1016/j.jhep.2014.07.027. Epub 2014 Jul 30.

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Wise M, Bialek S, Finelli L, Bell BP, Sorvillo F. Changing trends in hepatitis C-related mortality in the United States, 1995-2004. Hepatology. 2008 Apr;47(4):1128-35. doi: 10.1002/hep.22165.

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Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009 Apr;49(4):1335-74. doi: 10.1002/hep.22759. No abstract available.

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Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci. 2006;3(2):47-52. doi: 10.7150/ijms.3.47. Epub 2006 Apr 1.

Reference Type RESULT
PMID: 16614742 (View on PubMed)

Argentini C, Genovese D, Dettori S, Rapicetta M. HCV genetic variability: from quasispecies evolution to genotype classification. Future Microbiol. 2009 Apr;4(3):359-73. doi: 10.2217/fmb.09.8.

Reference Type RESULT
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Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, Simmonds P. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology. 2014 Jan;59(1):318-27. doi: 10.1002/hep.26744.

Reference Type RESULT
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Yee BE, Nguyen NH, Zhang B, Lin D, Vutien P, Wong CR, Lutchman GA, Nguyen MH. Sustained virological response and its treatment predictors in hepatitis C virus genotype 4 compared to genotypes 1, 2, and 3: a meta-analysis. BMJ Open Gastroenterol. 2015 Jul 9;2(1):e000049. doi: 10.1136/bmjgast-2015-000049. eCollection 2015.

Reference Type RESULT
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Chen TY, Hsieh YS, Wu TT, Yang SF, Wu CJ, Tsay GJ, Chiou HL. Impact of serum levels and gene polymorphism of cytokines on chronic hepatitis C infection. Transl Res. 2007 Aug;150(2):116-21. doi: 10.1016/j.trsl.2007.01.007. Epub 2007 May 23.

Reference Type RESULT
PMID: 17656331 (View on PubMed)

Younossi ZM, McCullough AJ. Metabolic syndrome, non-alcoholic fatty liver disease and hepatitis C virus: impact on disease progression and treatment response. Liver Int. 2009 Mar;29 Suppl 2:3-12. doi: 10.1111/j.1478-3231.2008.01949.x.

Reference Type RESULT
PMID: 19187068 (View on PubMed)

Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009 Sep 17;461(7262):399-401. doi: 10.1038/nature08309. Epub 2009 Aug 16.

Reference Type RESULT
PMID: 19684573 (View on PubMed)

Grebely J, Petoumenos K, Hellard M, Matthews GV, Suppiah V, Applegate T, Yeung B, Marks P, Rawlinson W, Lloyd AR, Booth D, Kaldor JM, George J, Dore GJ; ATAHC Study Group. Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection. Hepatology. 2010 Oct;52(4):1216-24. doi: 10.1002/hep.23850.

Reference Type RESULT
PMID: 20803561 (View on PubMed)

Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009 Oct;41(10):1105-9. doi: 10.1038/ng.449. Epub 2009 Sep 13.

Reference Type RESULT
PMID: 19749757 (View on PubMed)

Other Identifiers

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sheikhZMC

Identifier Type: -

Identifier Source: org_study_id

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