Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 21, 2012; 18(47): 7003-7008
Published online Dec 21, 2012. doi: 10.3748/wjg.v18.i47.7003
Interleukin-28 and hepatitis C virus genotype-4: Treatment-induced clearance and liver fibrosis
Moutaz Derbala, Nasser Rizk, Fatima Shebl, Saad Alkaabi, Nazeeh Eldweik, Anil John, Manik Sharma, Rafie Yaqoob, Muneera Almohanadi, Mohammed Butt, Khaled Alejji
Moutaz Derbala, Saad Alkaabi, Nazeeh Eldweik, Anil John, Manik Sharma, Rafie Yaqoob, Muneera Almohanadi, Mohammed Butt, Khaled Alejji, Department of Gastroenterology and Hepatology, Hamad Hospital, Doha 3050, Qatar
Moutaz Derbala, Department of Gastroenterology and Hepatology, Weill Cornell Medical College, Doha 3050, Qatar
Nasser Rizk, Department of Health Sciences, Qatar University, Doha 2713, Qatar
Fatima Shebl, Chronic Disease Epidemiology Division, Yale School of Public Health, New Haven, CT 06520, United States
Author contributions: All authors contributed to the study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; statistical analysis.
Supported by Hamad Hospital-HMC and Qatar University-Health Sciences-Biomedical Labs and sponsored by HMC
Correspondence to: Moutaz Derbala, Professor and Con-sultant, Department of Gastroenterology and Hepatology, Hamad Hospital, Doha 3050, Qatar. mod2002@qatar-med.cornell.edu
Telephone: +97-4-44392532 Fax: +97-4-44392279
Received: March 12, 2012
Revised: May 31, 2012
Accepted: June 8, 2012
Published online: December 21, 2012
Abstract

AIM: To investigate the association between interleukin-28B (IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus (HCV) genotype 4.

METHODS: Two hundred and one HCV-genotype 4 patients were included. All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk. End of treatment response (ETR) was defined as loss of detectable serum HCV RNA at the end of treatment. Sustained viral response (SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up. Genotyping of IL28B rs12979860 was performed using the TaqMan assay. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95%CI.

RESULTS: The study included 201 HCV-genotype 4 patients. The majority of patients were men (89.6%), with a median age of 47 years, inter-quartile range (40-51). Approximately 62.5% of patients had ETR, and 49.6% had SVR. Individuals who achieved SVR were more likely to be younger (χ2 = 4.91, P = 0.027), and less likely to have fibrosis (χ2 = 15.54, P < 0.0001), or inflammation (χ2 = 7.58, P = 0.006). The genotype distribution of rs12979860 was 36.2%, 49.0% and 14.8% for genotypes CC, CT, and TT, respectively. In these participants, rs12979860 genotype distribution did not differ by gender (P = 0.466), pretreatment viral load (P = 0.600), inflammation (P = 0.435), or fibrosis (P = 0.291). The frequencies of IL28B rs12979860 genotypes were TT (14.8%), CT (49.0%), and CC (36.2%). Compared to rs12979860 genotype TT, aORs (95%CI) for ETR and SVR were: CC genotype, [17.55 (5.34-57.69) and 5.92 (2.09-16.76), respectively]; CT genotype, [5.15 (1.80-14.78) and 2.48 (0.94-6.52), respectively]. In the current study, the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC (17.4% and 23.3%, respectively) than individuals who had ETR or SVR (47.9% and 47.2%, respectively). Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype (aOR = 5.92; 95%CI: 2.09-16.76). Similarly, patients with CT genotype had SVR more often than patients with TT genotype (aOR = 2.48; 95%CI: 0.94-6.52). Carrying at least one copy of the C allele (genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT (aOR = 7.87; 95%CI: 2.84-21.82), and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT (aOR = 3.46; 95%CI: 1.37-8.74). In addition, data were consistent with a significant gene-dose relationship (aOR = 4.05/allele; 95%CI: 2.27-7.22). The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.

CONCLUSION: In HCV-genotype 4 patients, rs12979860 is a sensitive predictor of viral clearance, independent of viral load, age, gender or fibrosis, with no similar relation to severity of fibrosis.

Keywords: Genotype 4, Hepatic fibrosis, Hepatitis C virus, Interleukin-28B, rs12979860