병원약사회지 (Journal of Korean Society of Health-System Pharmacists)

  • 제35권4호
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  • Pages.453-462
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  • 2018
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  • 1226-640X(pISSN)
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  • 2466-2143(eISSN)
한국병원약사회 (The Korean Society of Health-System Pharmacists)
권호 표지
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고령의 만성 C형 간염 환자에서 Daclatasvir와 Asunaprevir 병용 요법의 유효성 및 안전성 평가

Efficacy and Safety of Daclatasvir and Asunaprevir Combination Therapy in Elderly Chronic Hepatitis C Patients

  • 박유경 (가톨릭대학교 서울성모병원 약제부) ;
  • 신수진 (가톨릭대학교 서울성모병원 약제부) ;
  • 최유옥 (가톨릭대학교 서울성모병원 약제부) ;
  • 최혜정 (가톨릭대학교 성바오로병원 약제팀) ;
  • 강진숙 (가톨릭대학교 서울성모병원 약제부) ;
  • 황보신이 (가톨릭대학교 서울성모병원 약제부)
  • Park, You Kyung (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Shin, Su Jin (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Choi, You Ock (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Choi, Hye Jung (Department of Pharmacy, St. Paul's Hospital, The Catholic University of Korea) ;
  • Kang, Jin Suk (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Hwangbo, Shin-Yi (Department of Pharmacy, Seoul St. Mary's Hospital, The Catholic University of Korea)
  • 투고 : 2018.04.03
  • 심사 : 2018.09.14
  • 발행 : 2018.12.31
⟨ 이전 논문 다음 논문 ⟩

초록

Background : The prevalence of chronic hepatitis C virus (HCV) tends to be higher in the elderly. Pegylated interferon and ribavirin therapy (Peg-IFN/RBV) was recommended as the first-line treatment in the past decades, but this regimen showed unsatisfactory results in terms of safety and efficacy especially in elderly patients. Recently, it was demonstrated that dual therapy with daclatasvir and asunaprevir was well tolerated and led to high sustained virological response (SVR) rates, irrespective of age. We conducted a study to evaluate the efficacy and safety of daclatasvir plus asunaprevir by involving elderly patients aged above 65 years. Methods : We retrospectively analyzed clinical data from chronic hepatitis C virus (HCV) genotype 1b patients treated with daclatasvir plus asunaprevir from September 2015 to December 2016 at Seoul St. Mary's hospital. The patients were divided into two groups as elderly patients (older than 65 years) and non-elderly patients (younger than 65 years) and compared the efficacy and safety. Results : A total of 112 patients were treated with daclatasvir plus asunaprevir for chronic hepatitis C. Among them, 101 patients completed the whole treatment, and in 88 patients the amount of HCV RNA was measured after 12 weeks of treatment. There was no significant difference in SVR at 12 weeks between both the groups (p=0.68). Typically, 91.4%(32/35) of elderly patients and 94.3%(50/53) of non-elderly patients achieved SVR12. Common adverse events included elevation in transaminase level, headache, and gastrointestinal disorders. There was no statistical difference in the symptoms between the two groups. Conclusions : The combination therapy with daclatasvir plus asunaprevir exhibited similar rates of SVR12 in HCV elderly patients without leading to further adverse events compared to non-elderly patients. Therefore, it is proposed that daclatasvir plus asunaprevir therapy could be considered as an effective and safe treatment, even in patients aged over 65 years.

키워드

과제정보

연구 과제 주관 기관 : 한국보건산업진흥원

참고문헌

  1. C형간염 진료가이드라인, 2015 대한간학회
  2. Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci. 2006;3(2):47-52.
  3. Shiratori Y, Ito Y, Yokosuka O et al. 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(2):105-114. https://doi.org/10.7326/0003-4819-142-2-200501180-00009
  4. Bruno S, Stroffolini T, Colombo M et al. 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(3):579-587. https://doi.org/10.1002/hep.21492
  5. Mohd Hanafiah K, Groeger J, Flaxman AD et al. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013;57(4):1333-1342. https://doi.org/10.1002/hep.26141
  6. Jeong SH, Jang ES, Choi HY et al. Current status of hepatitis C virus infection and countermeasures in South Korea. Epidemiology and health. 2017;39:e201701.
  7. 2016 국민건강통계, 국민건강영양조사(2016), 보건복지부 질병관리본부 발행
  8. Asahina Y, Tsuchiya K, Tamaki N et al. Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. Hepatology. 2010;52(2):518-527 https://doi.org/10.1002/hep.23691
  9. Nudo CG, Wong P, Hilzenrat N et al. Elderly patients are at greater risk of cytopenia during antiviral therapy for hepatitis C. Can J Gastroenterol. 2006;20(9):589 -592. https://doi.org/10.1155/2006/357259
  10. Manns Michael, Pol Stanislas, Jacobson et al. : All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet. 2014;384(9954):1597-1605. https://doi.org/10.1016/S0140-6736(14)61059-X
  11. Jensen D, Sherman KE, Hezode C et al. HALLMARK-QUAD Study Team. : Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders. J Hepatol. 2015;63(1):30-37. https://doi.org/10.1016/j.jhep.2015.02.018
  12. Kao JH, Lee YJ, Heo J et al. All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection: a sub-analysis in Asian patients from the HALLMARK DUAL study. Liver Int 2016;36(10):1433-1441. https://doi.org/10.1111/liv.13128
  13. Tarao K, Tanaka K, Nozaki A et al. Efficacy and safety of dual therapy with daclatasvir and asunaprevir in elderly patients. World journal of hepatology. 2017;9(11):544-550. https://doi.org/10.4254/wjh.v9.i11.544
  14. McPhee F, Suzuki Y, Toyota J et al. High sustained virologic response to daclatasvir plus asunaprevir in elderly and cirrhotic patients with hepatitis C virus genotype 1b without baseline NS5A polymorphisms. Adv Ther. 2015;32(7):637-649. https://doi.org/10.1007/s12325-015-0221-5
  15. Hernandez D, Yu F, Huang X Kirov S et al. Impact of pre-existing NS5A-L31 or -Y93H minor variants on response rates in patients infected with HCV genotype-1b treated with daclatasvir/asunaprevir. Adv Ther. 2016;33(7):1169-1179. https://doi.org/10.1007/s12325-016-0354-1
  16. Pawlotsky JM. Hepatitis C virus resistance to direct-acting antiviral drugs in interferon-free regimens. Gastroenterology. 2016 Jul;151(1):70-86 https://doi.org/10.1053/j.gastro.2016.04.003
  17. C형 간염 바이러스, NS5A L31/Y93 유전자, 돌연변이[염기서열검사] =Hepatitis C virus, NS5A L31/Y93 gene, mutation[sequencing]/ 편집: 한국보건의료연구원, 보건복지부; 신의료기술평가위원회, 2017
  18. C형간염 진료가이드라인, 2017 대한간학회
  19. AASLD-IDSA HCV Guidance: Recommendations for testing, managing, and treating Hepatitis C [updated 2017 Sep 21]. Available from: https://www.hcvguidelines.org/
  20. Cho BW, Kim SB, Song IH et al. Efficacy and safety of daclatasvir plus asunaprevir for Korean patients with HCV genotype Ib infection: a retrospective multi-institutional study. Clin Mol Hepatol. 2017;23(1):51-56. https://doi.org/10.3350/cmh.2016.0053
  21. Kumada H, Suzuki Y, Ikeda K et al. Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Hepatology (Baltimore, Md). 2014;59(6):2083-2091. https://doi.org/10.1002/hep.27113
  22. 순베프라캡슐: 식품의약품안전처 허가사항
  23. Akuta N, Sezaki H, Suzuki F et al. Relationships between serum asunaprevir concentration and alanine aminotransferase elevation during daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Journal of medical virology. 2016;88(3):506-511. https://doi.org/10.1002/jmv.24360
  24. Ji F, Wei B, Yeo YH et al. Systematic review with meta-analysis: effectiveness and tolerability of interferon-free direct-acting antiviral regimens for chronic hepatitis C genotype 1 in routine clinical practice in Asia. Aliment Pharmacol Ther. 2018;47(5):550-562. https://doi.org/10.1111/apt.14507