Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy

作者: P. J. Clark , A. Aghemo , E. Degasperi , E. Galmozzi , T. J. Urban

DOI: 10.1111/JVH.12113

关键词:

摘要: Anaemia frequently complicates peginterferon/ribavirin therapy for chronic hepatitis C infection. Better prediction of anaemia, ribavirin dose reduction or erythropoietin (EPO) need, may enhance patient management. Inosine triphosphatase (ITPA) genetic variants are associated with ribavirin-induced anaemia and reduction; however, their impact in real-life clinic cohorts remains to be defined. We studied 193 patients infection mixed viral genotype (genotype 1/4 n = 123, 2/3, 70) treated peginterferon/ribavirin. Patients were genotyped ITPA polymorphisms rs1127354 rs7270101 using Taqman primers. Hardy-Weinberg equilibrium was present. Estimated deficiency graded on severity (0-3, no deficiency/mild/moderate/severe, 126/40/24/3, respectively). Multivariable models tested the association at 4 weeks treatment [including decline haemoglobin (g/dL); 3 g/dL]; EPO use explored sustained response (SVR) More severe less level (P < 0.001; R2 0.34), (OR 0.42; (95% CI 0.23-0.77); P 0.005) [OR 0.53; (0.30-0.94); 0.029]. SVR [OR: 1.70; (1.02-2.83); 0.041] independently clinical covariates (adjusted 0.31). In this cohort, helped predict risk on-treatment reduction, need support SVR. For HCV regimens including peginterferon/ribavirin, testing have utility.

参考文章(27)
Nezam H Afdhal, Douglas T Dieterich, Paul J Pockros, Eugene R Schiff, Mitchell L Shiffman, Mark S Sulkowski, Teresa Wright, Zobair Younossi, Betty L Goon, K Linda Tang, Peter J Bowers, Proactive Study Group, Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study. Gastroenterology. ,vol. 126, pp. 1302- 1311 ,(2004) , 10.1053/J.GASTRO.2004.01.027
Fumitaka Suzuki, Yoshiyuki Suzuki, Norio Akuta, Hitomi Sezaki, Miharu Hirakawa, Yusuke Kawamura, Tetsuya Hosaka, Masahiro Kobayashi, Satoshi Saito, Yasuji Arase, Kenji Ikeda, Mariko Kobayashi, Kazuaki Chayama, Naoyuki Kamatani, Yusuke Nakamura, Yuzo Miyakawa, Hiromitsu Kumada, Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir. Hepatology. ,vol. 53, pp. 415- 421 ,(2011) , 10.1002/HEP.24058
Douglas T Dieterich, Ronald Wasserman, Norbert Bräu, Tarek I Hassanein, Edmund J Bini, Peter J Bowers, Mark S Sulkowski, Once-weekly epoetin alfa improves anemia and facilitates maintenance of ribavirin dosing in hepatitis C virus-infected patients receiving ribavirin plus interferon alfa. The American Journal of Gastroenterology. ,vol. 98, pp. 2491- 2499 ,(2003) , 10.1016/J.AMJGASTROENTEROL.2003.08.006
John G McHutchison, Michael Manns, Keyur Patel, Thierry Poynard, Karen L Lindsay, Christian Trepo, Jules Dienstag, William M Lee, Carmen Mak, Jean–Jacques Garaud, Janice K Albrecht, International Hepatitis Interventional Therapy Group, Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C Gastroenterology. ,vol. 123, pp. 1061- 1069 ,(2002) , 10.1053/GAST.2002.35950
Christophe Hézode, Nicole Forestier, Geoffrey Dusheiko, Peter Ferenci, Stanislas Pol, Tobias Goeser, Jean-Pierre Bronowicki, Marc Bourlière, Shahin Gharakhanian, Leif Bengtsson, Lindsay McNair, Shelley George, Tara Kieffer, Ann Kwong, Robert S. Kauffman, John Alam, Jean-Michel Pawlotsky, Stefan Zeuzem, Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. The New England Journal of Medicine. ,vol. 360, pp. 1839- 1850 ,(2009) , 10.1056/NEJMOA0807650
M.S. Sulkowski, F. Poordad, M.P. Manns, J.-P. Bronowicki, K.R. Reddy, S.A. Harrison, N.H. Afdhal, N. Boparai, V. Sniukiene, M. Burroughs, J.K. Albrecht, C.A. Brass, I.M. Jacobson, 476 ANEMIA DURING TREATMENT WITH PEGINTERFERON ALFA-2B/ RIBAVIRIN WITH OR WITHOUT BOCEPREVIR IS ASSOCIATED WITH HIGHER SVR RATES: ANALYSIS OF PREVIOUSLY UNTREATED AND PREVIOUS-TREATMENT-FAILURE PATIENTS Journal of Hepatology. ,vol. 54, ,(2011) , 10.1016/S0168-8278(11)60478-9
M. S. Sulkowski, R. Wasserman, L. Brooks, L. Ball, R. Gish, Changes in haemoglobin during interferon alpha-2b plus ribavirin combination therapy for chronic hepatitis C virus infection. Journal of Viral Hepatitis. ,vol. 11, pp. 243- 250 ,(2004) , 10.1111/J.1365-2893.2004.00490.X
Alexander J. Thompson, Jacques Fellay, Keyur Patel, Hans L. Tillmann, Susanna Naggie, Dongliang Ge, Thomas J. Urban, Kevin V. Shianna, Andrew J. Muir, Michael W. Fried, Nezam H. Afdhal, David B. Goldstein, John G. McHutchison, Variants in the ITPA Gene Protect Against Ribavirin-Induced Hemolytic Anemia and Decrease the Need for Ribavirin Dose Reduction Gastroenterology. ,vol. 139, pp. 1181- 1189 ,(2010) , 10.1053/J.GASTRO.2010.06.016
Mitchell L Shiffman, Marc G Ghany, Timothy R Morgan, Elizabeth C Wright, Gregory T Everson, Karen L Lindsay, Anna SF Lok, Herbert L Bonkovsky, Adrian M Di Bisceglie, William M Lee, Jules L Dienstag, David R Gretch, HALT-C Trial Group, None, Impact of Reducing Peginterferon Alfa-2a and Ribavirin Dose During Retreatment in Patients With Chronic Hepatitis C Gastroenterology. ,vol. 132, pp. 103- 112 ,(2007) , 10.1053/J.GASTRO.2006.11.011
Nancy Reau, Stephanos J. Hadziyannis, Diethelm Messinger, Michael W. Fried, Donald M. Jensen, Early Predictors of Anemia in Patients with Hepatitis C Genotype 1 Treated with Peginterferon alfa-2a (40KD) plus Ribavirin The American Journal of Gastroenterology. ,vol. 103, pp. 1981- 1988 ,(2008) , 10.1111/J.1572-0241.2008.01957.X