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Journal of Gastroenterology
Published in: Journal of Gastroenterology 6/2017

01-06-2017 | Original Article—Liver, Pancreas, and Biliary Tract

ITPA polymorphism effects on decrease of hemoglobin during sofosbuvir and ribavirin combination treatment for chronic hepatitis C

Authors: Kei Morio, Michio Imamura, Yoshiiku Kawakami, Takashi Nakahara, Yuko Nagaoki, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Hiroshi Aikata, Clair Nelson Hayes, Grace Naswa Makokha, Hidenori Ochi, Hajime Amano, Keiko Arataki, Takashi Moriya, Hiroyuki Ito, Keiji Tsuji, Hiroshi Kohno, Koji Waki, Toru Tamura, Toshio Nakamura, Kazuaki Chayama, Hiroshima Liver Study Group

Published in: Journal of Gastroenterology | Issue 6/2017

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Abstract

Background

Polymorphisms in the inosine triphosphatase (ITPA) gene is associated with anemia induced by peg-interferon (PEG-IFN) plus ribavirin (RBV) treatment for patients with chronic hepatitis C virus (HCV) infection. However, the effect of ITPA polymorphism on sofosbuvir plus RBV treatment is unknown.

Methods

Two hundred and forty-four patients with chronic HCV genotype 2 infection without decompensated liver cirrhosis were treated with sofosbuvir plus RBV for 12 weeks. The effects of ITPA polymorphism on hemoglobin levels and RBV dose reduction and treatment response were analyzed. ITPA (rs1127354) was genotyped using the Invader assay. Multivariate regression analysis was performed to identify factors associated with sustained virological response (SVR).

Results

Overall, SVR12 was achieved in 231 (94.7%) patients, based on intention to treat analysis. During the therapy, reduction of hemoglobin levels was significantly greater in ITPA genotype CC patients than CA/AA patients. Therefore, the cumulative proportion of patients with RBV dose reduction was significantly higher and total dose of RBV was significantly lower in patients with CC genotype compared to CA/AA genotypes. SVR12 rates were similar between ITPA genotypes CC and CA/AA (94.7 and 94.4%, respectively, P = 0.933). Multivariate logistic regression analysis identified FIB4 index <3.25 (odds ratio [OR], 9.388 for ≥3.25; P = 0.005) and low body weight (OR, 1.059, for high body weight; P = 0.017) as independent predictors for SVR12.

Conclusions

ITPA polymorphism influences hemoglobin levels and incidence of RBV dose reduction during sofosbuvir plus RBV therapy. However, ITPA genotype CC patients can expect a curative effect equivalent to CA/AA patients for chronic HCV genotype 2 infection.

Literature
  1. Kiyosawa K, Sodeyama T, Tanaka E, et al. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology. 1990;12:671–5.View ArticlePubMed
  2. Niederau C, Lange S, Heintges T, et al. Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology. 1998;28:1687–95.View ArticlePubMed
  3. Shiffman ML, Suter F, Bacon BR, et al. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2007;357:124–34.View ArticlePubMed
  4. Sato K, Hashizume H, Yamazaki Y, et al. Response-guided peginterferon-alfa-2b plus ribavirin therapy for chronic hepatitis C patients with genotype 2 and high viral loads. Heptol Res. 2012;42:854–63.View Article
  5. Chayama K, Hayes CN, Ohishi W, Kawakami Y. Treatment of chronic hepatitis C virus infection in Japan: update on therapy and guidelines. J Gastroenterol. 2013;48:1–12.View ArticlePubMed
  6. DeClercq E. Current race in the development ofDAAs (direct- acting antivirals) against HCV. Biochem Pharmacol. 2014;89:441–52.View Article
  7. Lawitz E, Mangia S, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878–87.View ArticlePubMed
  8. Jacobson IM, Gordon SC, Kowdley KV, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368:1867–77.View ArticlePubMed
  9. Zeuzem S, Dusheiko GM, Salupere R, et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med. 2014;370:1993–2001.View ArticlePubMed
  10. Omata M, Nishiguchi S, Ueno Y, et al. Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open-label, phase 3 trial. J Viral Hepat. 2014;21:762–8.View ArticlePubMed
  11. Fellay J, Thompson AJ, Ge D, et al. ITPA gene variants protect against anemia in patients treated for chronic hepatitis C. Nature. 2010;464:405–8.View ArticlePubMed
  12. Ochi H, Maekawa T, Abe H, et al. ITPA polymorphism affects ribavirin-induced anemia and outcomes of therapy—a genome-wide study of Japanese HCV virus patients. Gastroenterology. 2010;139:1190–7.View ArticlePubMed
  13. Suzuki F, Suzuki Y, Akuta N, et al. Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir. Hepatology. 2011;53:415–21.View ArticlePubMed
  14. Akamatsu S, Hayes CN, Tsuge M, et al. Ribavirin dose reduction during telaprevir/ribavirin/peg-interferon therapy overcomes the effect of the ITPA gene polymorphism. J Viral Hepat. 2015;22:166–74.View ArticlePubMed
  15. Morio K, Imamura M, Kawakami Y, et al. Effects of ITPA polymorphism on decrease of hemoglobin during simeprevir, peg-interferon, and ribavirin combination treatment for chronic hepatitis C. Hepatol Res. 2016 (Epub ahead of print).
  16. Sterling RK, Lissen E, Clumeck N, APRICOT Clinical Investigators, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;2016(43):1317–25.View Article
  17. Kobayashi M, Suzuki F, Akuta N, et al. Association of two polymorphisms of the IL28B gene with viral factors and treatment response in 1,518 patients infected with hepatitis C virus. J Gastroenterol. 2012;47:596–605.View ArticlePubMed
  18. Zinsmeister AR, Connor JT. Ten common statistical errors and how to avoid them. Am J Gastroenterol. 2008;103:262–6.View ArticlePubMed
  19. Layer P, Zinsmeister AR, DiMagno EP. Effects of decreasing intraluminal amylase activity on starch digestion and postprandial gastrointestinal function in humans. Gastroenterology. 1986;91:41–8.View ArticlePubMed
  20. Rubin DB. Estimating causal effects from large data sets using propensity scores. Ann Intern Med. 1997;127:757–63.View ArticlePubMed
  21. D’Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81.View ArticlePubMed
  22. Hiramatsu N, Oze T, Yakushijin T, et al. Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin. J Viral Hepat. 2009;16:586–94.View ArticlePubMed
  23. Azakami T, Hayes CN, Sezaki H, et al. Common genetic polymorphism of ITPA gene affects ribavirin-induced anemia and effect of peg-interferon plus ribavirin therapy. J Med Virol. 2011;83:1048–57.View ArticlePubMed
  24. Lee SS, Bain VG, Peltekian K, et al. Treating chronic hepatitis C with pegylated interferon alfa-2a (40 KD) and ribavirin in clinical practice. Aliment Pharmacol Ther. 2006;3:397–408.View Article
  25. Ho SB, Monto A, Peyton A, et al. Efficacy of sofosbuvir plus ribavirin in veterans with hepatitis C virus genotype 2 infection, compensated cirrhosis, and multiple comorbidities. Clin Gastroenterol and Hepatol. 2016. doi:10.​1016/​j.​cgh.​2016.​05.​024 (Epub ahead of print).
  26. Backus LI, Belperio PS, Shahoumian TA, et al. Effectiveness of sofosbuvir-based regimens in genotype 1 and 2 hepatitis C virus infection in 4026 US Veterans. Aliment Pharmacol Ther. 2015;42:559–73.View ArticlePubMed
  27. Rower JE, Meissner EG, Jimmerson LC, et al. Serum and cellular ribavirin pharmacokinetic and concentration-effect analysis in HCV patients receiving sofosbuvir plus ribavirin. J Antimicrob Chemother. 2015;70:2322–9.View ArticlePubMedPubMed Central
Metadata
Title
ITPA polymorphism effects on decrease of hemoglobin during sofosbuvir and ribavirin combination treatment for chronic hepatitis C
Authors
Kei Morio
Michio Imamura
Yoshiiku Kawakami
Takashi Nakahara
Yuko Nagaoki
Tomokazu Kawaoka
Masataka Tsuge
Akira Hiramatsu
Hiroshi Aikata
Clair Nelson Hayes
Grace Naswa Makokha
Hidenori Ochi
Hajime Amano
Keiko Arataki
Takashi Moriya
Hiroyuki Ito
Keiji Tsuji
Hiroshi Kohno
Koji Waki
Toru Tamura
Toshio Nakamura
Kazuaki Chayama
Hiroshima Liver Study Group
Publication date
01-06-2017
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 6/2017
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-016-1279-9

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