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ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 10
Oct.  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(10): 2320-2323

Association of inosine triphosphate pyrophosphatase gene polymorphisms with ribavirin combined with direct-acting antiviral agent in treatment of hepatitis C patients with hemolytic anemia

DOI: 10.3969/j.issn.1001-5256.2021.10.012
  • 1.

    Department of Infectious Diseases, Hebei Petrochina Central Hospital, Langfang, Hebei 065000, China

  • 2.

    Department of Hepatitis C & Toxic Liver Diseases, Beijing YouAn Hospital, Capital Medical University, Beijing 100071, China

Research funding:

The Research and Cultivation Program of the Municipal Hospital of Beijing (PX2018058);

Young and Middle-aged Talent Incubation Project in the Hospital of Beijing YouAn Hospital, Capital Medical University (YNKTTS20180114);

The Planned Project of Langfang Science and Technology (2019013010)

  • Received Date: 2021-03-18
  • Accepted Date: 2021-04-12
  • Published Date: 2021-10-20
    Abstract
  •   Objective  To investigate the influencing factors for ribavirin (RBV)-induced hemolytic anemia in the treatment of chronic hepatitis C, and to provide a reference for the early prediction of ribavirin-related hemolytic anemia in clinical practice.  Methods  A total of 49 patients with chronic hepatitis C who attended or were hospitalized in Hebei Petrochina Central Hospital from January 2018 to July 2019 and received antiviral therapy with direct-acting antiviral agent (DAA) and RBV were enrolled, with a major allele of C allele and a minor allele of A allele at the rs1127354 locus of the inosine triphosphate pyrophosphatase (ITPA) gene, and the patients with AA and AC genotypes were compared with those with CC genotype. During treatment, RBV was reduced to 600 mg when hemoglobin (Hb) level was < 100 g/L and was withdrawn when Hb level was < 85 g/L. Routine blood test, liver function, liver stiffness measurement, HCV RNA, HCV genotype, and ITPA genotype were measured before antiviral therapy, and the routine blood test was performed at weeks 2, 4, 8, and 12 of treatment. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups.  Results  A total of 49 patients were enrolled in this study, among whom 22 had chronic hepatitis C and 27 had liver cirrhosis, with a sustained virologic response (SVR) rate of 95.9%. The dose of RBV was reduced in 3 patients (2 in the AA/AC group and 1 in the CC group) due to anemia, and RBV was withdrawn in 3 patients (1 in the AA/AC group and 2 in the CC group); all these 6 patients had liver cirrhosis and finally achieved SVR. During the anti-HCV therapy with DAA+RBV, there was relatively mild RBV-related hemolysis, and the maximum reduction in Hb from baseline was compared between the patients with AA/AC genotype at ITPA rs1127354 and those with CC genotype, which showed no significant difference between the two groups (Z=-0.18, P=0.87).  Conclusion  During the treatment with RBV+DAA, RBV is withdrawn or reduced for liver cirrhosis patients due to anemia, and no obvious statistical relation is observed between ITPA genotype and the maximum reduction in Hb from baseline. Therefore, detection of ITPA genotype before the application of RBV does not improve safety during treatment, and it is not recommended to perform conventional detection of ITPA gene polymorphisms.

     

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    • References(15)
  • [1]
    LAVANCHY D. The global burden of hepatitis C[J]. Liver Int, 2009, 29 Suppl 1: 74-81. DOI: 10.1111/j.1478-3231.2008.01934.x.
    [2]
    BUNCHORNTAVAKUL C, MANEERATTANAPORN M, CHAVALITDHAMRONG D. Management of patients with hepatitis C infection and renal disease[J]. World J Hepatol, 2015, 7(2): 213-225.
    [3]
    Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for hepatitis C: A 2015 update[J]. J Clin Hepatol, 2015, 31(12): 1961-1979. DOI: 10.3969/j.issn.1001-5256.2015.12.003.

    中华医学会肝病学分会, 中华医学会感染病学分会. 丙型肝炎防治指南(2015年更新版)[J]. 临床肝胆病杂志, 2015, 31(12): 1961-1979. DOI: 10.3969/j.issn.1001-5256.2015.12.003.
    [4]
    RAO HY, WEI L. EASL recommendations on treatment of Hepatitis C 2015[J]. J Clin Hepatol, 2015, 31(7): 1008-1017. DOI: 10.3969/j.issn.1001-5256.2015.07.004.

    饶慧瑛, 魏来. 2015年欧洲肝病学会丙型肝炎治疗推荐意见[J]. 临床肝胆病杂志, 2015, 31(7): 1008-1017. DOI: 10.3969/j.issn.1001-5256.2015.07.004.
    [5]
    XU JF, ZHANG XH, LIU YL, et al. Influencing factors for hemolytic anemia in patients with chronic hepatitis C treated by ribavirin combined with pegylated interferon-α[J]. J Clin Hepatol, 2019, 35(2): 319-322. DOI: 10.3969/j.issn.1001-5256.2019.02.015.

    徐金凤, 张晓慧, 柳雅立, 等. 利巴韦林联合聚乙二醇干扰素α治疗慢性丙型肝炎发生相关溶血性贫血的影响因素分析[J]. 临床肝胆病杂志, 2019, 35(2): 319-322. DOI: 10.3969/j.issn.1001-5256.2019.02.015.
    [6]
    CHENG YQ, ZHAO P, WANG XF. Research advances in the anti-HCV mechanism of ribavirin[J]. Foreign Med Sci(Epidemiol Loimol), 2003, 30(3): 156-160. https://www.cnki.com.cn/Article/CJFDTOTAL-GWLX200303010.htm

    程勇前, 赵平, 王晓峰. 利巴韦林抗HCV作用机制研究进展[J]. 国外医学(流行病学传染病学分册), 2003, 30(3): 156-160. https://www.cnki.com.cn/Article/CJFDTOTAL-GWLX200303010.htm
    [7]
    FELLAY J, THOMPSON AJ, GE D, et al. ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C[J]. Nature, 2010, 464(7287): 405-408. DOI: 10.1038/nature08825.
    [8]
    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[J]. Gastroenterology, 2010, 139(4): 1190-1197. DOI: 10.1053/j.gastro.2010.06.071.
    [9]
    MATSUURA K, TANAKA Y, WATANABE T, et al. ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type[J]. J Viral Hepat, 2014, 21(7): 466-474. DOI: 10.1111/jvh.12171.
    [10]
    RAU M, STICKEL F, RUSSMANN S, et al. Impact of genetic SLC28 transporter and ITPA variants on ribavirin serum level, hemoglobin drop and therapeutic response in patients with HCV infection[J]. J Hepatol, 2013, 58(4): 669-675. DOI: 10.1016/j.jhep.2012.11.027.
    [11]
    CLARK PJ, AGHEMO A, DEGASPERI E, et al. Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy[J]. J Viral Hepat, 2013, 20(12): 858-866. DOI: 10.1111/jvh.12113.
    [12]
    MURAKAWA M, ASAHINA Y, NAGATA H, et al. ITPA gene variation and ribavirin-induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin[J]. Hepatol Res, 2017, 47(11): 1212-1218. DOI: 10.1111/hepr.12867.URABEA.
    [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[J]. Hepatology, 2011, 53(2): 415-421. DOI: 10.1002/hep.24058.
    [14]
    MORIO K, IMAMURA M, KAWAKAMI Y, et al. ITPA polymorphism effects on decrease of hemoglobin during sofosbuvir and ribavirin combination treatment for chronic hepatitis C[J]. J Gastroenterol, 2017, 52(6): 746-753. DOI: 10.1007/s00535-016-1279-9.
    [15]
    URABE A, SAKAMORI R, TAHATA Y, et al. Predictive factors of anemia during sofosbuvir and ribavirin therapy for genotype 2 chronic hepatitis C patients[J]. Hepatol Res, 2019, 49(8): 853-859. DOI: 10.1111/hepr.13354.
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