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

Jinfeng XU; Lixia QIU; Haibin YU; Yirong LIU; Jing ZHANG; Yali LIU; Wei LIN

doi:10.3969/j.issn.1001-5256.2021.10.012

Volume 37 Issue 10

Oct. 2021

Turn off MathJax

Article Contents

Abstract

References

Article Navigation > Journal of Clinical Hepatology > 2021 > 37(10): 2320-2323

PDF( 1925 KB)

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

Jinfeng XU¹,
Lixia QIU²,
Haibin YU²,
Yirong LIU²,
Jing ZHANG²,
Yali LIU^{2
,
,},
Wei LIN^{2
,
,}

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

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 100 g/L and was withdrawn when Hb level was 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.
- Hepatitis C, Chronic,
- Anemia, Hemolytic,
- Ribavirin,
- Risk Factors

FullText(HTML)

References(15)

References

[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.

Relative Articles

[1]	Wei ZHANG, Song ZHAI, Hong DU, Fuchun JING, Limei WANG, Ye ZHANG, Bibo KANG, Jiuping WANG, Shuangsuo DANG, Jianqi LIAN, Hong JIANG. Efficacy and safety of the 12-week sofosbuvir-coblopasvir regimen in treatment of chronic hepatitis C[J]. Journal of Clinical Hepatology, 2023, 39(3): 539-545. doi: 10.3969/j.issn.1001-5256.2023.03.009
[2]	Siqin LIU, Xiaomei WANG, Xia LI, Luwen LIANG, Ke WANG, Rui WANG. Covert hepatic encephalopathy in liver cirrhosis: Risk factors and prognosis[J]. Journal of Clinical Hepatology, 2022, 38(2): 359-364. doi: 10.3969/j.issn.1001-5256.2022.02.020
[3]	Wanshu LIU, Lijun SHEN, Qinghui ZHAI, Shaojie XIN, Shaoli YOU. Risk factors for acute variceal bleeding in acute-on-chronic liver failure and its influence on prognosis[J]. Journal of Clinical Hepatology, 2022, 38(11): 2532-2536. doi: 10.3969/j.issn.1001-5256.2022.11.018
[4]	Tao WANG, Fenghui LI, Jing LIANG, Huiling XIANG, Fang LIU, Hongmin LYU, Baoxin QIAN, Jiajun TIAN. Clinical effect of direct-acting antiviral agents in treatment of chronic hepatitis C patients with thrombocytopenia[J]. Journal of Clinical Hepatology, 2022, 38(1): 91-96. doi: 10.3969/j.issn.1001-5256.2022.01.014
[5]	Lamei LI, Qi ZHU, Lin CHEN, Xinle YANG, Fang XU, Yanjun CAI, Junqi NIU, Wanyu LI. A case of acute hepatitis A with thrombocytopenia and hemolytic anemia[J]. Journal of Clinical Hepatology, 2021, 37(4): 902-904. doi: 10.3969/j.issn.1001-5256.2021.04.035
[6]	Ruan FangMing, Li BiMin. Risk factors for the formation of portal vein thrombosis in patients with liver cirrhosis[J]. Journal of Clinical Hepatology, 2020, 36(1): 182-185. doi: 10.3969/j.issn.1001-5256.2020.01.043
[7]	Yao ChengZi, Feng Gong, Yu WenSi, Du Huan, Mi Man. Risk factors for the development and progression of nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2020, 36(2): 433-436. doi: 10.3969/j.issn.1001-5256.2020.02.044
[8]	Lyu Jing, Dong SiSi, Gu HongTu, Zhao ZhangQing, Liu ChengHai. TCM syndrome characteristics of portal vein thrombosis in patients with liver cirrhosis and related risk factors[J]. Journal of Clinical Hepatology, 2019, 35(10): 2210-2213. doi: 10.3969/j.issn.1001-5256.2019.10.016
[9]	Bai Xue, Ma ZuoHong, Hao ZhiQiang, Fu XiBo, Jiao Ao, Shang Hai, Hua XiangDong. Research advances in the risk factors for microvascular invasion in hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2019, 35(11): 2578-2581. doi: 10.3969/j.issn.1001-5256.2019.11.042
[10]	Xu JinFeng, Zhang XiaoHui, Liu YaLi, Zhang Jing. Influencing factors for hemolytic anemia in patients with chronic hepatitis C treated by ribavirin combined with pegylated interferon-α[J]. Journal of Clinical Hepatology, 2019, 35(2): 319-322. doi: 10.3969/j.issn.1001-5256.2019.02.015
[11]	Wang XianPeng, Meng XianZhi. Risk factors for gallstones complicated by acute biliary pancreatitis[J]. Journal of Clinical Hepatology, 2018, 34(8): 1728-1732. doi: 10.3969/j.issn.1001-5256.2018.08.027
[12]	Chang XiuJuan, Lu YinYing, Rong GuangHua, Liu Ze, Chen Yan, Xu GuiLin, Gao XuDong, Lou Min, Wang ChunPing, Yang YongPing, Ceng Zhen. Risk factors for vascular invasion of primary liver cancer[J]. Journal of Clinical Hepatology, 2018, 34(5): 1038-1041. doi: 10.3969/j.issn.1001-5256.2018.05.022
[13]	Hu WeiLin. Risk factors for hypertriglyceridemia-induced acute pancreatitis[J]. Journal of Clinical Hepatology, 2017, 33(8): 1518-1521. doi: 10.3969/j.issn.1001-5256.2017.08.022
[14]	Wang FengJiao, Liu MingJiang, Wu RuiHong, Niu JunQi. A multivariate logistic regression analysis of short-term prognosis of patients with hepatic encephalopathy[J]. Journal of Clinical Hepatology, 2017, 33(4): 711-714. doi: 10.3969/j.issn.1001-5256.2017.04.022
[15]	Zhou RenHua, Li Peng, Zhang YanTing, Yang Hua, Yang ShaoQi. Clinical manifestations of portal vein thrombosis and related risk factors in patients with liver cirrhosis[J]. Journal of Clinical Hepatology, 2016, 32(2): 275-278. doi: 10.3969/j.issn.1001-5256.2016.02.015
[16]	Zhang YueRong, Zhou Ning, Li XiangLin, Wu LiYang, Wei ShiFang, Zhang YaoDi, Zhang YuePing. Causes and countermeasures for relapse after drug withdrawal in patients with chronic hepatitis C[J]. Journal of Clinical Hepatology, 2015, 31(9): 1434-1438. doi: 10.3969/j.issn.1001-5256.2015.09.017
[17]	Chen BiHua, Zhang Wei, Wu Pei, Huang Ying. Research advances in risk factors for primary biliary cirrhosis[J]. Journal of Clinical Hepatology, 2015, 31(12): 2088-2092. doi: 10.3969/j.issn.1001-5256.2015.12.024
[18]	Cai ShaoPing, Zhang WenJin, He WeiPing, Fan ZhenPing, Ji YingJie. Efficacy and safety of interferon plus ribavirin in elderly patients with chronic hepatitis C: report of 4 cases[J]. Journal of Clinical Hepatology, 2014, 30(1): 69-71. doi: 10.3969/j.issn.1001-5256.2014.01.019
[19]	Zhang YiNing, Du HongWei, Liu YanJun, Wang ChaoXia. The diagnosis and risk factors for evaluation of nonalcoholic fatty liver disease in children and adolescents[J]. Journal of Clinical Hepatology, 2011, 27(7): 690-693.
[20]	Zheng YingYing, Fan XiaoHong, Wang LiFen, Tian Di, Huo Na, Lu HaiYing, Wu ChiHong, Xu XiaoYuan, Wei Lai. Efficacy and side effects of PEG-IFNα-2a plus ribavirin on elderly patients with chronic hepatitis C[J]. Journal of Clinical Hepatology, 2011, 27(8): 821-823.

Supplements(0)

Cited By

Cited by

Periodical cited type(1)

郑玲玲，孟银梅，刘南南，叶小欣，马珺珺，李铭，李卫. 阜阳市丙型病毒性肝炎流行病学特点及疾病进展影响因素. 实用临床医药杂志. 2022(12): 61-64 .

Other cited types(0)

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(1) / Tables(3)

Get Citation

PDF

XML

Article Metrics

Article views (525) PDF downloads(32)

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