Impact of IL28B gene variants (rs12979860) in peg-IFN therapy against Chronic Hepatitis B Pakistani patients

Irfan Kalam, Sajjad Ullah, Qaisar Ali, Arshad Jamal, Ahmad Bilal Waqar

Abstract


Background: Genome wide association studies elucidate that IL28B rs12979860 genetic polymorphism has a substantial role as a pretreatment predictor during PEG-IFN therapy in Hepatitis C virus (HCV) infection, however its role in chronic hepatitis B (CHB) is ambiguous.

Methods: In this study, we have investigated the role of IL28B variant rs12979860 for chronic hepatitis B (CHB) infection. 200 CHB patients were treated for 24 weeks, then we carried out our study on these patients. Moreover, all patients were investigated for IL28B rs12979860 genotypes CC, CT, TT through RT-PCR. Based on our preliminary results we categorized these patients into two groups i.e. Responder ¢R (n = 104) and Non-responder¢NR (n = 96).

Results: The proportion of IL28B CC, CT, TT genotypes were in both responder and non-responder groups as (72.1%, 25.0%, 2.9% vs 53.1%, 40.6%, 6.2% respectively; P = 0.02). In this study CC was the most frequent genotype, which has significant outcome in PEG-IFN therapy in both R and NR groups (72.1% vs 53.1%) (P = 0.03), while CT and TT were found as (25.0% vs 40.6%) (P = 0.1, 2.09% vs 6.2%) (P = 0.3) respectively.

Conclusion: Current study clearly demonstrates that IL28B rs12979860 polymorphism is a pretreatment predictor during PEG-IFN therapy in CHB infection, and patients with favorable genotype of rs12979860 (CC) may clear the virus than the non-favorable genotypes (CT, TT) in Pakistani population. 


Full Text:

PDF

References


Idrees M, Khan S, Riazuddin S. Common genotypes of hepatitis B virus. Journal of the College of Physicians and Surgeons–Pakistan: JCPSP, (2004); 14(6): 344-347.

Zhu R, Zhang H-P, Yu H, Li H, Ling Y-Q, et al. Hepatitis B virus mutations associated with in situ expression of hepatitis B core antigen, viral load and prognosis in chronic hepatitis B patients. Pathology-Research and Practice, (2008); 204(10): 731-742.

Ali L, Idrees M, Ali M, Rehman I-u, Hussain A, et al. An overview of treatment response rates to various anti-viral drugs in Pakistani Hepatitis B Virus infected patients. Virology journal, (2011); 8(1): 20.

Li G, Li W, Guo F, Xu S, Zhao N, et al. A novel real-time PCR assay for determination of viral loads in person infected with hepatitis B virus. Journal of virological methods, (2010); 165(1): 9-14.

Paraskevis D, Haida C, Tassopoulos N, Raptopoulou M, Tsantoulas D, et al. Development and assessment of a novel real-time PCR assay for quantitation of HBV DNA. Journal of virological methods, (2002); 103(2): 201-212.

Alam MM, Zaidi SZ, Malik SA, Naeem A, Shaukat S, et al. Serology based disease status of Pakistani population infected with Hepatitis B virus. BMC infectious diseases, (2007); 7(1): 64.

Noorali S, Hakim ST, McLean D, Kazmi SU, Bagasra O. Prevalence of Hepatitis B virus genotype D in females in Karachi, Pakistan. The Journal of Infection in Developing Countries, (2008); 2(05): 373-378.

Hakim S, Kazmi S, Bagasra O. Seroprevalence of hepatitis B and C genotypes among young apparently healthy females of Karachi-Pakistan. Libyan Journal of Medicine, (2008); 3(2): 66-70.

Ali M, Idrees M, Ali L, Hussain A, Rehman IU, et al. Hepatitis B virus in Pakistan: a systematic review of prevalence, risk factors, awareness status and genotypes. Virology journal, (2011); 8(1): 102.

Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology, (2009); 50(3): 661-662.

Ali Q, Jamal A, Imran M, Ullah S, Kalam I, et al. Correlation of IL28B rs12979860 genotype and gender with spontaneous clearance of HCV infection: a Pakistani cross-section study. Personalized medicine, (2018); 15(6).

Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. Journal of hepatology, (2006); 45(4): 529-538.

Hadziyannis SJ, Papatheodoridis GV. Hepatitis B e antigen-negative chronic hepatitis B: natural history and treatment; 2006. Copyright© 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. pp. 130-141.

Saeed MA, Ahmed N, Ali Q. Frequency of Autoantibodies to Thyroid Peroxidase (TPO) in Patients with Type 1 Diabetes Mellitus. International Journal of Applied Biology and Forensics (2018); 2(1): 171-174.

Lee WM. Hepatitis B virus infection. New England Journal of Medicine, (1997); 337(24): 1733-1745.

Di Marco V, Iacono OL, Cammà C, Vaccaro A, Giunta M, et al. The long‐term course of chronic hepatitis B. Hepatology, (1999); 30(1): 257-264.

Fattovich G. Natural course and prognosis of chronic hepatitis type B. Viral Hepatitis Reviews, (1996); 2: 263-276.

Liaw YF, Tai DI, Chu CM, Chen TJ. The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology, (1988); 8(3): 493-496.

McMahon BJ, Alberts SR, Wainwright RB, Bulkow L, Lanier AP. Hepatitis B–related sequelae: prospective study in 1400 hepatitis B surface antigen–positive Alaska native carriers. Archives of Internal Medicine, (1990); 150(5): 1051-1054.

Liver EAFTSOT. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. Journal of hepatology, (2012); 57(1): 167-185.

Ali Q, Kalam I, Ullah S, Jamal A, Imran M, et al. Predictive value of IL-28B rs12979860 variants for peg-IFN, sofosbuvir plus ribavirin treatment of HCV infection in Pakistani population. Personalized medicine, (2018); 15(6): 12.

Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, et al. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nature immunology, (2003); 4(1): 63-68.

Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, et al. IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nature immunology, (2003); 4(1): 69-77.

Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, et al. IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy. Nature genetics, (2009); 41(10): 1100-1104.

Martin MP, Qi Y, Goedert JJ, Hussain SK, Kirk GD, et al. IL28B polymorphism does not determine outcomes of hepatitis B virus or HIV infection. Journal of Infectious Diseases, (2010); 202(11): 1749-1753.

Sonneveld MJ, Wong VWS, Woltman AM, Wong GL, Cakaloglu Y, et al. Polymorphisms near IL28B and serologic response to peginterferon in HBeAg-positive patients with chronic hepatitis B. Gastroenterology, (2012); 142(3): 513-520. e511.

Kamatani Y, Wattanapokayakit S, Ochi H, Kawaguchi T, Takahashi A, et al. A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nature genetics, (2009); 41(5): 591-595.

Guo Y, Guo H, Zhang L, Xie H, Zhao X, et al. Genomic analysis of anti-hepatitis B virus (HBV) activity by small interfering RNA and lamivudine in stable HBV-producing cells. Journal of virology, (2005); 79(22): 14392-14403.

Mbarek H, Ochi H, Urabe Y, Kumar V, Kubo M, et al. A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population. Human molecular genetics, (2011); 20(19): 3884-3892.

Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature, (2009); 461(7265): 798.

Hamdan HZ, Ziad AHM, Ali SK, Adam I. Epidemiology of urinary tract infections and antibiotics sensitivity among pregnant women at Khartoum North Hospital. Annals of clinical microbiology and antimicrobials, (2011); 10(1): 2.

Jaroszewicz J. Praktyczne zastosowanie ilościowego oznaczania stężeń antygenu HBs. Medical Science Review-Hepatologia, 1(11): 33-36.

Papatheodoridis GV. Why do I treat HBeAg‐negative chronic hepatitis B patients with nucleos (t) ide analogues? Liver International, (2013); 33(s1): 151-156.

Perillo R. Benefits and risks of interferon therapy for hepatitis G. Hepatology, (2009); 49(5 Suppl): 103-111.

Lampertico P, Viganò M, Colombo M. Why do I treat HBeAg‐negative chronic hepatitis B patients with pegylated interferon? Liver International, (2013); 33(s1): 157-163.

Ono-Nita SK, Kato N, Shiratori Y, Omata M. Current options for the therapy of chronic hepatitis B infection. Current infectious disease reports, (2001); 3(2): 137-142.

Liaw Y-F, Lin S-M, Chen T-J, Chien R-N, Sheen I-S, et al. Beneficial effect of prednisolone withdrawal followed by human lymphoblastoid interferon on the treatment of chronic type B hepatitis in Asians: a randomized controlled trial. Journal of hepatology, (1994); 20(2): 175-180.

Lok AS, Wu P-C, Lai C-L, Lau JY, Leung EK, et al. A controlled trial of interferon with or without prednisone priming for chronic hepatitis B. Gastroenterology, (1992); 102(6): 2091-2097.

Sung J, Tsoi K, Wong V, Li K, Chan H. Meta‐analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Alimentary pharmacology & therapeutics, (2008); 28(9): 1067-1077.

van Zonneveld M, Honkoop P, Hansen BE, Niesters HG, Murad SD, et al. Long‐term follow‐up of alpha‐interferon treatment of patients with chronic hepatitis B. Hepatology, (2004); 39(3): 804-810.

Cooksley WG, Piratvisuth T, Lee SD, Mahachai V, Chao YC, et al. Peginterferon α‐2a (40 kDa): an advance in the treatment of hepatitis B e antigen‐positive chronic hepatitis B. Journal of viral hepatitis, (2003); 10(4): 298-305.

Chan HLY, Leung NWY, Hui AY, Wong VWS, Liew CT, et al. A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-α2b and lamivudine with lamivudine alone. Annals of internal medicine, (2005); 142(4): 240-250.

Janssen HL, van Zonneveld M, Senturk H, Zeuzem S, Akarca US, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. The Lancet, (2005); 365(9454): 123-129.

Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. New England Journal of Medicine, (2005); 352(26): 2682-2695.

Lacey L. Review of economic benefits of treating chronic hepatitis B with lamivudine. Journal of gastroenterology and hepatology, (2004); 19(S1): 10-12.

Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. Journal of viral hepatitis, (2004); 11(2): 97-107.

for Research EO, Liver EAFTSOT. EASL–EORTC clinical practice guidelines: management of hepatocellular carcinoma. Journal of hepatology, (2012); 56(4): 908-943.

Liver EAFTSOT. EASL Clinical Practice Guidelines: management of chronic hepatitis B. Journal of hepatology, (2009); 50(2): 227-242.

Skorka C, Grigorescu-Sido P, Manasia R, Lazăr C, Crişan M. EVOLUŢIA HEPATITEI CRONICE VIRALE B LA COPIL SUB TRATAMENT CU INTERFERON. Clujul Medical, 852.

Liaw YF, Jia JD, Chan H, Han K, Tanwandee T, et al. Shorter durations and lower doses of peginterferon alfa‐2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C. Hepatology, (2011); 54(5): 1591-1599.

Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, et al. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nature immunology, (2003); 4(1): 63-68.

Marcello T, Grakoui A, Barba–Spaeth G, Machlin ES, Kotenko SV, et al. Interferons α and λ inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology, (2006); 131(6): 1887-1898.

Urban TJ, Thompson AJ, Bradrick SS, Fellay J, Schuppan D, et al. IL28B genotype is associated with differential expression of intrahepatic interferon‐stimulated genes in patients with chronic hepatitis C. Hepatology, (2010); 52(6): 1888-1896.

Honda M, Sakai A, Yamashita T, Nakamoto Y, Mizukoshi E, et al. Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C. Gastroenterology, (2010); 139(2): 499-509.

Ge D, Fellay J, Thompson A, Simon J, Shianna K. rban 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); 461(7262): 399-401.

Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, et al. Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C. Nature genetics, (2009); 41(10): 1105-1109.

Rauch A, Kutalik Z, Descombes P, Cai T, Di Iulio J, 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. e1337.

Ank N, West H, Bartholdy C, Eriksson K, Thomsen AR, et al. Lambda interferon (IFN-λ), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. Journal of virology, (2006); 80(9): 4501-4509.

Lampertico P, Viganò M, Cheroni C, Facchetti F, Invernizzi F, et al. IL28B polymorphisms predict interferon‐related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen–negative patients with chronic hepatitis B. Hepatology, (2013); 57(3): 890-896.

Galmozzi E, Viganò M, Lampertico P. do interferon lambda 3 polymorphisms predict the outcome of interferon therapy in hepatitis B infection? Authors' reply. Alimentary pharmacology & therapeutics, (2014); 39(10): 1251-1252.

Mangia A, Santoro R, Mottola L, Fasano M, Minerva N, et al. 1331 lack of association between il28b variants and hbsag clearance after interferon treatment. Journal of hepatology, (2011); 54S525.

Li W, Jiang Y, Jin Q, Shi X, Jin J, et al. Expression and gene polymorphisms of interleukin 28B and hepatitis B virus infection in a Chinese Han population. Liver International, (2011); 31(8): 1118-1126.

Boglione L, Cusato J, Allegra S, Esposito I, Patti F, et al. Role of IL28-B polymorphisms in the treatment of chronic hepatitis B HBeAg-negative patients with peginterferon. Antiviral research, (2014); 10235-43.

Shi X, Chi X, Pan Y, Gao Y, Li W, et al. IL28B is associated with outcomes of chronic HBV infection. Yonsei medical journal, (2015); 56(3): 625-633.

Domagalski K, Pawłowska M, Zaleśna A, Tyczyno M, Skorupa-Kłaput M, et al. The relationship between IL-28B polymorphisms and the response to peginterferon alfa-2a monotherapy in anti-HBe-positive patients with chronic HBV infection. European journal of clinical microbiology & infectious diseases, (2014); 33(11): 2025-2033.




DOI: http://dx.doi.org/10.62940/als.v6i1.566

Refbacks

  • There are currently no refbacks.