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IL-28B Genetic Analysis And HBV Disease Association Studies With Small Number Study Subjects; Should We Rely On Results?

Muhammad Sohail Afzal

Muhammad Sohail Afzal, Department of Life Sciences, School of Science, University of Management and Technology (UMT), Lahore, Pakistan

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http: //creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Muhammad Sohail Afzal, Department of Life Sciences, School of Science, University of Management and Technology (UMT), Lahore, Pakistan.
Email: sohail.ncvi@gmail.com
Telephone: +92-321-5244808

Received: October 20, 2016
Revised: December 24, 2017
Accepted: December 25, 2017
Published online: December 26, 2017

ABSTRACT

Hepatitis B Virus (HBV) is one of the leading cause of cirrhosis and hepatocellular carcinoma worldwide. The virus has 10 different genotypes and has a specific geographic distribution for each genotype. Viral genotypes and certain mutations in the viral genome are associated with differential clinical features and therapeutic response. It is also evident that during HBV infection certain host genetic factors play major role in determining the outcome of infection and also impact the outcomes of antiviral therapy. IL28B plays an important role in the outcome of HBV infection and it could inhibit the viral replication. There are some functional genetic variants in IL28B gene which regulate the expression of IL28B. These genetic variants played significant role in predicting the antiviral therapy response and disease progression. There are several case control studies across the globe which are investigating the role of these functional variants on disease progression and antiviral therapy outcomes. In current study the available data on the genetic analysis of IL28B variants and their impact on HBV disease progression or antiviral therapy response is analyzed. The results showed that most of the studies including only small number of study participants hence the low sample number impact the power of statistical analysis. It is proposed that in future the case control studies must be conducted on large scale so statistical results can be justified and will be of help in clinical settings.

Key words: IL-28B; HBV; Ethnicity; Genetic analysis; Case-control studies

© 2017 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Afzal MS. IL-28B Genetic Analysis And HBV Disease Association Studies With Small Number Study Subjects; Should We Rely On Results? Journal of Gastroenterology and Hepatology Research 2017; 6(6): 2502-2504 Available from: URL: http://www.ghrnet.org/index.php/joghr/article/view/2171

Dear Editor

The major recent breakthrough in genetics and hepatology is the role of variations found in the region of interleukin-28B (IL28B), the gene coding for the IL28B protein, also known as interferon (IFN)-λ3. The genetic variations in this region are highly predictive of pegylated INF alpha (Peg-IFN-α) and ribavirin (RBV) therapy response and viral clearance in different ethnic groups of chronic hepatitis C patients[1]. Recently there are growing numbers of studies on investigating the role of these genetic variations in different ethnic groups and Peg-IFN-α and RBV treatment response in hepatitis B patients.

A report published by Holmes et al (2013) showed that IL28B genotype (rs12979860) is not a useful predicting marker for treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferon-α. The study includes very small number of patients as well control subjects. Conclusion of the study based on 52 patients and 32 controls from Asian ethnicity; study groups were further divided into 4 different groups on ethnic basis. The study includes 8, 14, 22, 8 patients of Cambodian, Chinese, Vietnam and other ethnic background respectively. Similarly the control group from Cambodian, Chinese, Vietnam and other ethnicity includes 7, 9, 11 and 5 individuals respectively. The Caucasian and African study groups includes 7, 1 patients and 2, 2 healthy control respectively[2]. The results showed that CC IL28B genotype was the major prevalent genotype and was present in 85% patients and 83.3% healthy individuals followed by CT genotype which was present in 15% patients and 13.9% controls. Genotype TT prevalence was 0% in cases and 2.8% in controls; the very low prevalence was may be due to very small number of investigated individuals. On the basis of these results authors concluded that IL-28B polymorphism (rs12979860) has no association with pegylated interferon therapy outcomes in HBV patients with Asian ethnic background.

The findings of other reports analyzing the role of IL-28B polymorphic variants on HBV infection susceptibility and therapy outcomes from different groups are conflicting but were based on comparatively larger number of patients and controls (Table 1)[3-18]. A recent report by Chen et al[6] investigated the IL-28B Gene polymorphism association and the Progress of Hepatitis B Infection in Han Chinese. Irrespective of results; the study includes 3 patients and a healthy group of 406, 406, 393 and 244 individuals respectively. A summary of all available studies in PubMed investigating the role of IL-28B polymorphism with respect to HBV infection is given in Table 1. The main problem of case control studies for genetic analysis of host genetic markers is the number of individuals being analyzed. The studies based on small number of samples like 1, 2, 7, 8 individuals may showed statistically false positive or false negative association. Therefore care should be taken while concluding such kind of studies. It is highly recommended that this kind of investigation must include larger study groups and should be done on larger scale.

Table 1 Summary of studies investigating IL-28B polymorphic variants association with HBV disease susceptibility, progression and Interferon ribavirin therapy response.
YearEthnicitySettingsConclusion/Association with IL-28 PolymorphismReference
Patients (n)Control (n)
2013Italian101-Good predictor of Interferon ribavirin therapy response3
2013Taiwanese115-Positive association with disease susceptibility4
2013Hong Kong203203Positive association with disease susceptibility5
2012Chinese Han1205244Positive association with disease progression6
2012Chinese140150No association with HBV recurrence in the liver transplant recipients or the donors.7
2012Han Chinese28347Positive association with disease susceptibility and chronicity8
2012Spanish4949No association with disease susceptibility9
2012Taiwanese133-No association with disease progression and chronicity10
2012Chinese512-Positive association with Interferon ribavirin therapy response11
2012Chinese651226No association with disease susceptibility12
2012Not differentiated205-Positive association with Interferon ribavirin therapy response13
2012Netherlands95-No association with HBeAg seroconversion or HBsAg clearance14
2011Chinese Han 406203Preventive effect on disease progression15
2011Taiwanese115-No association with HBeAg seroconversion16
2011Italian292344Positive correlation with viral infection17
2011Chinese342144No correlation with the outcome of HBV infection18

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