Interleukin-28B gene non-TT allele strongly predicts treatment failure for genotype 1 infected chronic hepatitis C patients with advanced fibrosis: a case control study

BMC Infectious Diseases

Rong-Nan Chien²  Ching-Jung Liu²  Li-Wei Chen²  Cheng-Hung Chien²  Liang-Che Chang¹  Chih-Lang Lin²  Ching-Chih Hu² 

[1] Department of Pathology, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung 20401, Taiwan;Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung 20401, Taiwan

关键词: Sustained virologic response;    rs8099917;    Interleukin-28B;    Chronic hepatitis C;    Advanced fibrosis;   

Others  :  1173929
DOI  :  10.1186/s12879-015-0888-x

 received in 2014-11-29, accepted in 2015-03-12,  发布年份 2015

【 摘 要 】

Background

The role of single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B in predicting therapeutic response of pegylated interferon (peg-IFN) plus ribavirin (PR) for genotype 1 infected chronic hepatitis C patients with advanced fibrosis (AF) is limited. The aim of this study is to assess its role in predicting sustained virologic responses (SVR) to treatment.

Methods

Forty-two patients with biopsy proven hepatitis C virus (HCV) related AF (group A; Ishak fibrosis score, ≥4) and 126 sex- and HCV genotype-matched patients without AF (group B; Ishak fibrosis score, ≤3) were recruited into study. All patients received PR therapy for 24 weeks. Baseline and on-treatment clinical, virological and host factors were evaluated for treatment efficacy.

Results

The SVR rate was significantly lower in group A than group B patients with genotype 1 infection (24% vs. 53.3%; p = 0.011). However, it was similar in those with genotype non-1 infection (76.5% vs. 76.5%; p = 1.0). IL-28B rs8099917 genotype TT is the strongest predictor for SVR in genotype 1 infection. Patients who had TT genotype and achieved RVR in group A had similar SVR rates with those in group B (44.4% vs. 53.3%; p = 0.614). One third of patients in group A developed hematological adverse effects and had required modified doses during antiviral therapy.

Conclusions

In HCV genotype 1 infected AF receiving 24 weeks of PR treatment, patients with IL28B rs8099917 genotype TT, achieving RVR had similar SVR rate with those without AF. In contrast, patients with IL-28B rs8099917 non-TT genotype without achieving RVR are suggested to stop therapy.

【 授权许可】

   
2015 Hu et al.; licensee BioMed Central.

【 参考文献 】

• [1]Alter MJ: Epidemiology of hepatitis C virus infection. World J Gastroenterol 2007, 13:2436-2441.
• [2]Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, Nakanishi K, Fujimoto I, Inoue A, Yamazaki H, Kawashimaet T: Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 1993, 328:1797-1801.
• [3]Fassio E: Hepatitis C and hepatocellular carcinoma. Ann Hepatol 2010, 9(Suppl):119-122.
• [4]Colombo M, de Franchis R, Del Ninno E, Sangiovanni A, De Fazio C, Tommasini M, Donato MF, Piva A, Di Carlo V, Dioguardi N: Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med 1991, 325:675-680.
• [5]Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, Nevens F, Solinas A, Mura D, Brouwer JT, Thomas H, Njapoum C, Casarin C, Bonetti P, Fuschi P, Basho J, Tocco A, Bhalla A, Galassini R, Noventa F, Schalm SW, Realdi G: Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology 1997, 112:463-472.
• [6]Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnu L, Mazzella G, Ascione A, Santantonio T, Piccinino F, Andreone P, Mangia A, Gaeta GB, Persico M, Fagiuoli S, Almasio PL: Italian Association of the Study of the Liver Disease (AISF): Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology 2007, 45:579-587.
• [7]Shiratori Y, Ito Y, Yokosuka O, Imazeki F, Nakata R, Tanaka N, Arakawa Y, Hashimoto E, Hirota K, Yoshida H, Ohashi Y, Omata M: Tokyo-Chiba Hepatitis Research Group: Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival. Ann Intern Med 2005, 142:105-114.
• [8]Hung CH, Lee CM, Lu SN, Wang JH, Hu TH, Tung HD, Chen CH, Chen WJ, Changchien CS: Long-term effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis. J Viral Hepat 2006, 13:409-414.
• [9]Veldt BJ, Heathcote EJ, Wedemeyer H, Reichen J, Hofmann WP, Zeuzem S, Manns MP, Hansen BE, Schalm SW, Janssen HL: Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med 2007, 147:677-684.
• [10]Floreani A, Baldo V, Rizzotto ER, Carderi I, Baldovin T, Minola E: Pegylated interferon alpha-2b plus ribavirin for naive patients with HCV-related cirrhosis. J Clin Gastroenterol 2008, 42:734-737.
• [11]Bruno S, Crosignani A, Facciotto C, Rossi S, Roffi L, Redaelli A, de Franchis R, Almasio PL, Maisonneuve P: Sustained virologic response prevents the development of esophageal varices in compensated, Child-Pugh class A hepatitis C virus-induced cirrhosis. A 12-year prospective follow-up study. Hepatology 2010, 51:2069-2076.
• [12]Cardoso AC, Moucari R, Figueiredo-Mendes C, Ripault MP, Giuily N, Castelnau C, Boyer N, Asselah T, Martinot-Peignoux M, Maylin S, Carvalho-Filho RJ, Valla D, Bedossa P, Marcellin P: Impact of peginterferon and ribavirin therapy on hepatocellular carcinoma: incidence and survival in hepatitis C patients with advanced fibrosis. J Hepatol 2010, 52:652-657.
• [13]Wright TL: Treatment of patients with hepatitis C and cirrhosis. Hepatology 2002, 36(5 Suppl 1):S185-S194.
• [14]Strader DB, Wright T, Thomas DL, Seeff LB: Diagnosis, management, and treatment of hepatitis C. Hepatology 2004, 39:1147-1171.
• [15]Abergel A, Hezode C, Leroy V, Barange K, Bronowicki JP, Tran A, Alric L, Castera L, Bernard PH, Henquell C, Lafeuille H, Ughetto S, Darcha C, Chevallier M, Martineau N, Dubost S, Randl K, Dhumeaux D, Bommelaer G, Bonny C: French multicenter study group: Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis: a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b. J Viral Hepat 2006, 13:811-820.
• [16]Helbling B, Jochum W, Stamenic I, Knopfli M, Cerny A, Borovicka J, Gonvers JJ, Wilhelmi M, Dinges S, Müllhaupt B, Esteban A, Meyer-Wyss B, Renner EL: Swiss Association for the Study of the Liver (SASL): HCV-related advanced fibrosis/cirrhosis: randomized controlled trial of pegylated interferon alpha-2a and ribavirin. J Viral Hepat 2006, 13:762-769.
• [17]Cheng WS, Roberts SK, McCaughan G, Sievert W, Weltman M, Crawford D, Rawlinson W, Marks PS, Thommes J, Rizkalla B, Yoshihara M, Dore GJ: CHARIOT Study Group: Low virological response and high relapse rates in hepatitis C genotype 1 patients with advanced fibrosis despite adequate therapeutic dosing. J Hepatol 2010, 53:616-623.
• [18]McHutchison JG, Manns M, Patel K, Poynard T, Lindsay KL, Trepo C, Dienstag J, Lee WM, Mak C, Garaud JJ, Albrecht JK: International Hepatitis Interventional Therapy Group: Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology 2002, 123:1061-1069.
• [19]Sarrazin C, Susser S, Doehring A, Lange CM, Muller T, Schlecker C, Herrmann E, Lötsch J, Berg T: Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients. J Hepatol 2011, 54:415-421.
• [20]Mangia A, Mottola L, Santoro R: Interleukin 28B polymorphisms as predictor of response in hepatitis C virus genotype 2 and 3 infected patients. World J Gastroenterol 2013, 19:8924-8928.
• [21]Rangnekar AS, Fontana RJ: Meta-analysis: IL-28B genotype and sustained viral clearance in HCV genotype 1 patients. Aliment Pharmacol Ther 2012, 36:104-114.
• [22]Lin CY, Chen JY, Lin TN, Jeng WJ, Huang CH, Huang CW, Chang SW, Sheen IS: IL28B SNP rs12979860 is a critical predictor for on-treatment and sustained virologic response in patients with hepatitis C virus genotype-1 infection. PLoS One 2011, 6:e18322.
• [23]Ramos JA, Silva R, Hoffmann L, Ramos AL, Cabello PH, Urmenyi TP, Villella-Nogueira CA, Lewis-Ximenez L, Rondinelli E: Association of IL-10, IL-4, and IL-28B gene polymorphisms with spontaneous clearance of hepatitis C virus in a population from Rio de Janeiro. BMC Res Notes 2012, 5:508. BioMed Central Full Text
• [24]Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002, 347:975-982.
• [25]Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK: Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001, 358:958-965.
• [26]Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM: PEGASYS International Study Group: Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004, 140:346-355.
• [27]Roffi L, Colloredo G, Pioltelli P, Bellati G, Pozzpi M, Parravicini P, Bellia V, Del Poggio P, Fornaciari G, Ceriani R, Ramella G, Corradi C, Rossini A, Bruno S: Gruppo Epatologico Lombardo: Pegylated interferon-alpha2b plus ribavirin: an efficacious and well-tolerated treatment regimen for patients with hepatitis C virus related histologically proven cirrhosis. Antivir Ther 2008, 13:663-673.
• [28]Bruno S, Camma C, Di Marco V, Rumi M, Vinci M, Camozzi M, Rebucci C, Di Bona D, Colombo M, Craxì A, Mondelli MU, Pinzello G: Peginterferon alfa-2b plus ribavirin for naive patients with genotype 1 chronic hepatitis C: a randomized controlled trial. J Hepatol 2004, 41:474-481.
• [29]Yu ML, Dai CY, Lin ZY, Lee LP, Hou NJ, Hsieh MY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL: A randomized trial of 24- vs. 48-week courses of PEG interferon alpha-2b plus ribavirin for genotype-1b-infected chronic hepatitis C patients: a pilot study in Taiwan. Liver Int 2006, 26:73-81.
• [30]Kawaoka T, Hayes CN, Ohishi W, Ochi H, Maekawa T, Abe H, Tsuge M, Mitsui F, Hiraga N, Imamura M, Takahashi S, Kubo M, Tsunoda T, Nakamura Y, Kumada H, Chayama K: Predictive value of the IL28B polymorphism on the effect of interferon therapy in chronic hepatitis C patients with genotypes 2a and 2b. J Hepatol 2011, 54:408-414.
• [31]Shakado S, Sakisaka S, Okanoue T, Chayama K, Izumi N, Toyoda J, Tanaka E, Ido A, Takehara T, Yoshioka K, Hiasa Y, Nomura H, Seike M, Ueno Y, Kumada H: Interleukin 28B polymorphism predicts interferon plus ribavirin treatment outcome in patients with hepatitis C virus-related liver cirrhosis: A multicenter retrospective study in Japan. Hepatol Res 2014, 44:983-992.
• [32]Snoeck E, Wade JR, Duff F, Lamb M, Jorga K: Predicting sustained virological response and anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin. Br J Clin Pharmacol 2006, 62:699-709.
• [33]Kowdley KV: Hematologic side effects of interferon and ribavirin therapy. J Clin Gastroenterol 2005, 39(1 Suppl):S3-S8.
• [34]Hu CC, Weng CH, Lin CL, Tien HC, Kuo YL, Chien CH, Yen CL, Lin CY, Chien RN: Predictors of changes in hemoglobin levels in patients with chronic hepatitis C treated with ribavirin plus pegylated interferon-alpha. Ren Fail 2012, 34:429-434.
• [35]Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, Schultz M, Davis MN, Kayali Z, Reddy KR, Jacobson IM, Kowdley KV, Nyberg L, Subramanian GM, Hyland RH, Arterburn S, Jiang D, McNally J, Brainard D, Symonds WT, McHutchison JG, Sheikh AM, Younossi Z, Gane EJ: Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013, 368:1878-1887.
• [36]Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, Shiffman ML, Lawitz E, Everson G, Bennett M, Schiff E, Al-Assi MT, Subramanian GM, An D, Lin M, McNally J, Brainard D, Symonds WT, McHutchison JG, Patel K, Feld J, Pianko S, Nelson DR: POSITRON Study; FUSION Study: Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013, 368:1867-1877.