IL28B polymorphisms predict the virological response to standard therapy in patients with chronic hepatitis C virus genotype 4 infection
Genome-wide association studies have recently revealed that several single-nucleotide polymorphisms (SNPs) in the interleukin (IL) 28B genes can predict the sustained virological response (SVR) to pegylated interferon-α2a/b plus ribavirin in hepatitis C virus (HCV)-genotype 1 patients. However, data for patients infected with HCV genotype 4 (HCV-G4) are limited.
We analyzed the association of IL28B SNPs (hematological, biochemical, virological, and pathological factors) with SVR in the HCV-G4 monoinfected cohort of patients.
Patients and methods
One hundred twenty-nine treatment-naïve HCV-G4 patients undergoing treatment were recruited from three tertiary care centers in Saudi Arabia. Five IL28B SNPs (rs12979860, rs12980275, rs8105790, rs8099917, and rs72486680) were identified by polymerase chain reaction and DNA sequencing. SVR was statistically correlated with various clinical, histopathological, virological, and genetic parameters.
SVR was significantly associated with the CC and AA alleles of rs12979860 (p = 0.008) and rs12980275 (p = 0.004), respectively. Moreover, albumin levels (p = 0.002) and platelet count (p = 0.039) showed significant differences in the SVR and No SVR groups. On multivariate analysis, the CC allele of rs12979860 (OR, 2.89; 95 % CI 1.6–6.2, p = 0.006) and albumin levels (OR, 1.2; 95 % CI 1.1–1.4, p = 0.001) independently predicted SVR.
IL28B polymorphism (CC allele of rs12979860) predicts the sustained response to antiviral therapy in HCV-G4.
- Hepatitis C. Fact Sheet No. 164. Revised October 2000, WHO 2000, 3 p. Available at http://www.who.int/mediacentre/factsheets/fs164/en/. Accessed 12 Dec 2011.
- Khattab, MA, Ferenci, P, Hadziyannis, SJ (2011) Management of hepatitis C virus genotype 4: Recommendations of an international expert panel. J Hepatol 54: pp. 1250-1262 CrossRef
- Hadziyannis, SJ, Sette, H, Morgan, TR (2004) Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 140: pp. 346-355 CrossRef
- Zeuzem, S, Berg, T, Moeller, B, Hinrichsen, H (2009) Expert opinion on the treatment of patients with chronic hepatitis C. J Viral Hep 16: pp. 75-90 CrossRef
- Lange, CM, Zeuzem, S (2011) IL28B single nucleotide polymorphisms in the treatment of hepatitis C. J Hepatol 55: pp. 692-701 CrossRef
- Pagliaccetti, NE, Robek, MD (2010) Interferon-lambda in the immune response to hepatitis B virus and hepatitis C virus. J Interferon Cytokine Res 30: pp. 585-590 CrossRef
- Hou, W, Wang, X, Ye, L (2009) Lambda interferon inhibits human immunodeficiency virus type 1 infection of macrophages. J Virol 83: pp. 3834-3842 CrossRef
- Ge, D, Fellay, J, Thompson, AJ (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461: pp. 399-401 CrossRef
- Tanaka, Y, Nishida, N, Sugiyama, M (2009) Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 41: pp. 1105-1109 CrossRef
- Suppiah, V, Moldovan, M, Ahlenstiel, G (2009) IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 41: pp. 1100-1104 CrossRef
- Rauch A, Kutalik Z, Descombes P et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 2010 138(4):1338–1345, 1345.e1–1345.e7.
- Thomas, DL, Thio, CL, Martin, MP (2009) Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461: pp. 798-801 CrossRef
- McCarthy, JJ, Li, JH, Thompson, A (2010) Replicated association between an IL28B gene variant and a sustained response to pegylated interferon and ribavirin. Gastroenterology 138: pp. 2307-2314 CrossRef
- Clark, PJ, Thompson, AJ, McHutchison, JG (2011) IL28B genomic-based treatment paradigms for patients with chronic hepatitis C infection: the future of personalized HCV therapies. Am J Gastroenterol 106: pp. 38-45 CrossRef
- Moghaddam, A, Melum, E, Reinton, N (2011) IL28B genetic variation and treatment response in patients with hepatitis C virus genotype 3 infection. Hepatology 53: pp. 746-754 CrossRef
- Yu, ML, Huang, CF, Huang, JF (2011) Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients. Hepatology 53: pp. 7-13 CrossRef
- Asselah, T, Muynck, S, Broet, P (2012) (2012) IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C. J Hepatol 56: pp. 527-532 CrossRef
- Scherzer, TM, Stattermayer, AF, Strasser, M (2011) Impact of IL28B on treatment outcome in hepatitis C virus G1/4 patients receiving response-guided therapy with peginterferon alpha-2a (40KD)/ribavirin. Hepatology 54: pp. 1518-1526 CrossRef
- Nicola, S, Aghemo, A, Rumi, MG (2012) Interleukin 28B polymorphism predicts pegylated interferon plus ribavirin treatment outcome in chronic hepatitis C genotype 4. Hepatology 55: pp. 336-342 CrossRef
- IL28B polymorphisms predict the virological response to standard therapy in patients with chronic hepatitis C virus genotype 4 infection
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Volume 7, Issue 2 , pp 533-538
- Cover Date
- Print ISSN
- Online ISSN
- Springer India
- Additional Links
- Hepatitis C
- Genotype 4
- Sustained virological response
- Single nucleotide polymorphism
- Industry Sectors
- Ayman A. Abdo (1) (2)
- Mohammed N. Al-Ahdal (3)
- Saira S. Khalid (2)
- Ahmed Helmy (2) (4)
- Faisal M. Sanai (2) (5)
- Khalid Alswat (1) (2)
- Waleed Al-hamoudi (1) (2)
- Safiyya M. Ali (2)
- Hamad I. Al-Ashgar (6)
- Abdallah Al-Mdani (7)
- Ali Albenmousa (7)
- Faleh Z. Al Faleh (1)
- Mashael Al-Anazi (3)
- Nisreen Khalaf (3)
- Ahmed Al-Qahtani (2) (3)
- Author Affiliations
- 1. Division of Gastroenterology, Department of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
- 2. Liver Disease Research Centre, King Saud University, Riyadh, Kingdom of Saudi Arabia
- 3. Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354 (MBC-03), Riyadh, 11211, Kingdom of Saudi Arabia
- 4. Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University Hospitals, Assiut, Egypt
- 5. Department of Hepatobiliary Sciences and Liver Transplantation, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia
- 6. Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
- 7. Department of Gastroenterology, Riyadh Military Hospital, Riyadh, Kingdom of Saudi Arabia