Оценка эффективности и безопасности лечения пациентов с хроническим гепатитом С и циррозом печени и полиморфизмом UGT1A1*28 схемами с включением лекарственных средств прямого противовирусного действия и рибавирина

Главная

Статья в Elpub

РУС ENG

Рецепт. 2020; : 299-312

Оценка эффективности и безопасности лечения пациентов с хроническим гепатитом С и циррозом печени и полиморфизмом UGT1A1*28 схемами с включением лекарственных средств прямого противовирусного действия и рибавирина

Лукашик С. П., Карпов И. А., Синявская М. В., Даниленко Н. Г., Анисько Л. А., Давыденко О. Г., Красько О. В.

https://doi.org/10.34883/PI.2020.2.2.038

Аннотация

Цель. Оценить эффективность и безопасность лекарственных средств прямого противовирусного действия (ЛС ППД) в комбинации с рибавирином у пациентов с хроническим гепатитом С (ХГС) и циррозом (ВГС-ЦП), имеющих полиморфизм UGT1A1*28. Материалы и методы. Проведено клиническое открытое нерандомизированное ретроспективное обсервационное когортное исследование эффективности и безопасности ЛС ППД с включением 32 пациентов. Результаты. УВО12 достигнут у 100% пациентов с ХГС и ВГС-ЦП. НВО достигнут у 87,5%: с (ТА)7/ (А)7 генотипом – 100%, с (ТА)6/(ТА)7 – 92%, с (ТА)6/(ТА)6 – 75%. Частота НВО у пациентов с ХГС была 69%, с ВГС-ЦП – 100% и зависела от ответа на предшествующее лечение схемами с включением ИФН: у пациентов, ранее не достигших вирусологического ответа при назначении им ЛС ППД, частота НВО была ниже (р<0,001). НВО не зависел от (ТА)7/(А)7, (ТА)6/(ТА)7 или (ТА)6/ (ТА)6 (р=0,478) и длительности противовирусного лечения (12 или 24 недели) (р=0,273). Повышение общего билирубина до 1-й или 2-й степени не было связано с генотипами (ТА)6/(ТА)7, (ТА)7/(ТА)7 или (ТА)6/(ТА)6 (р=0,62), клиническим диагнозом (ХГС или ВГС-ЦП) (р=0,883), длительностью лечения (р=0,880), наличием предшествующего лечения схемами с включением ИФН и рибавирина (р=0,550) и не требовало отмены лечения. Лечение характеризовалось отсутствием повышения АЛТ у 97%, АСТ – у 100% и ЩФ – у 91%. Выводы. Лечение ЛС ППД в комбинации с рибавирином пациентов с хроническим гепатитом С и полиморфизмом UGT1A1*28 является эффективным и безопасным.

Список литературы

1. Petruzziello A., Loquercio G., Sabatino R. et al. (2019) Prevalence of Hepatitis C virus genotypes in nine selected European countries: A systematic review. J. Clin. Lab. Anal., vol. 33, no 5, pp. e22876.

2. Hanafiah K.M., Groeger J., Flaxman A.D. et al. (2013) Global epidemiology of hepatitis C virus infection: New estimates of age-specific antibody to HCV seroprevalence. Hepatology., vol. 57, no 4, pp. 1333–1342.

3. Leroy V., Dumortier J., Coilly A. et al. (2015) Efficacy of Sofosbuvir and Daclatasvir in Patients With Fibrosing Cholestatic Hepatitis C After Liver Transplantation. Clin. Gastroenterol. Hepatol., vol.13, no 11, pp. 1993–2001.

4. Reddy K.R., Bourlière M., Sulkowski M. et al. (2015) Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis. Hepatology., vol. 62, no1, pp. 79–86.

5. Saxena V., Koraishy F.M., Sise M.E. et al. (2016) Safety and efficacy of sofosbuvir-containing regimens in hepatitis C-infected patients with impaired renal function. Liver Int., vol. 36, no 6, pp. 807–16.

6. Caudle K.E., Klein T.E., Hoffman J.M. et al. (2014) Incorporation of Pharmacogenomics Into Routine Clinical Practice: The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline Development Process. Curr Drug Metab., vol. 15, no 2, pp. 209–17.

7. Swen J.J., Nijenhuis M., de Boer A. et al. (2011) Pharmacogenetics: From Bench to Byte – An Update of Guidelines. Clin Pharmacol Ther., vol. 89, no 5, pp. 662–673.

8. Torres A .К., Escartín N., Monzó C. et al. (2017) Genetic susceptibility to Gilbert’s syndrome in a valencian population; efficacy of the fasting test. Rev Clin Esp., vol. 217, no 1, pp. 1–6.

9. Köhle C., Möhrle B., Münzel P.A., et al. (2003) Frequent co-occurrence of the TATA box mutation associated with Gilbert’s syndrome (UGT1A1*28) with other polymorphisms of the UDP-glucuronosyltransferase-1 locus (UGT1A6*2 and UGT1A7*3) in Caucasians and Egyptians. Biochem. Pharmacol., vol. 65, no 9, pp. 1521–1527.

10. Balram C., Sabapathy K., Fei G. et al. (2002) Genetic polymorphisms of UDP-glucuronosyltransferase in Asians: UGT1A1*28 is a common allele in Indians. Pharmacogenetics, vol. 12, no1, pp. 81–83.

11. Beutler E., Gelbart T., Demina A. (1998) Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc. Natl. Acad. Sci. U.S.A., vol 95, no 14, pp. 8170–8174.

12. Ando Y., Chida M., Nakayama K. et al. (1998) The UGT1A1*28 allele is relatively rare in a Japanese population. Pharmacogenetics., vol. 8, no 4, pp. 357–360.

13. Bosma P.J., Chowdhury J.R., Bakker C. et al. (1995) The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N. Engl. J. Med., vol. 333, no 18, pp. 1171–1175.

14. Melnikova L.I., Ilchenko L.Yu., Dunaeva E.A. et al. (2019) Diagnosis of gilbert’s syndrome via pyrosequencing in clinical practice. Arhiv vnutrennej mediciny, vol. 9, no 6, pp. 475–482.

15. Il’chenko L.J., Drozdov V.N., Shuljap’ev I.S. et al. (2006) Sindrom Gilbert’s syndrome: a clinical genetic study. Terapevticheskij arhiv., vol. 78, no2, pp. 48–52.

16. Nambu M., Namihisa T. (1996) Hepatic transport of serum bilirubin, bromsulfophthalein, and indocyanine green in patients with congenital non- hemolytic hyperbilirubinemia and patients with constitutional indocyanine green excretory defect. J. Gastroenterol., vol. 31, no 2, pp. 228–236.

17. Martin J.F., Vierling J.M., Wolkoff A.W. et al. (1976) Abnormal hepatic transport of indocyanine green in Gilbert’s syndrome. Gastroenterology., vol. 70, no 3, pp. 385–391.

18. Ha V.H., Jupp J., Tsang R.Y. (2017) Oncology Drug Dosing in Gilbert Syndrome Associated with UGT1A1: A Summary of the Literature. Pharmacotherapy., vol. 37, no 8, pp. 956–972.

19. Lankisch T.O., Vogel A., Eilermann S. et al. (2005) Identification and characterization of a functional TATA box polymorphism of the UDP glucuronosyltransferase 1A7 gene. Mol. Pharmacol., vol. 67, no 5, pp. 1732–1739.

20. Kirby B.J., Symonds W.Т., Kearney B.P. et al. (2015) Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of the Hepatitis C Virus NS5B Polymerase Inhibitor Sofosbuvir. Clin Pharmacokinet., vol. 54, no 7, pp. 677–690.

21. Garimella T., You X., Wang R. et al. (2016) A Review of Daclatasvir Drug–Drug Interaction. Adv Ther., vol. 33, no 11, pp. 1867–1884.

22. Mogalian E., Stamm L.M., Osinusi A. et al. (2018) Drug-Drug Interaction Studies Between Hepatitis C Virus Antivirals Sofosbuvir/Velpatasvir and Boosted and Unboosted Human Immunodeficiency Virus Antiretroviral Regimens in Healthy Volunteers. Clin Infect Dis., vol 67, no 6, pp. 934–940.

23. German P., Mathias A., Brainard D.M. et al. (2018) Drug–Drug Interaction Profile of the Fixed-Dose Combination Tablet Regimen Ledipasvir/ Sofosbuvir. Clinical pharmacokinetics., vol 57, no 11, pp. 1369–1383.

24. Garrison K.L., German P., Mogalian E. et al. (2018) The Drug-Drug Interaction Potential of Antiviral Agents for the Treatment of Chronic Hepatitis C Infection. Drug Metab. Dispos., vol 46, no 8, pp. 1212–1225.

25. R Core Team. The R Project for Statistical Computing. Available at: https://www.r-project.org/. Accessed 09.02.2020.

Recipe. 2020; : 299-312

The Evaluation of the Efficacy and Safety of Patients with Chronic Hepatitis C and Cirrhosis with Polymorphism UGT1A1*28 Treatment with Direct Antiviral Drugs and Ribavirin

Lukashyk S., Karpov I., Siniauskaya M., Danilenko N., Anisko L., Davydenko O., Krasko O.

https://doi.org/10.34883/PI.2020.2.2.038

Abstract

Purpose. To evaluate the efficacy and safety of drugs with direct antiviral effect (DAA) with ribavirin in patients with chronic hepatitis C (CHC) and cirrhosis (HCV-CL) with UGT1A1 * 28 polymorphism. Materials and methods. An open-label, non-randomized, observational study to assess efficacy and safety of DAA in patients (n=32) with CHC and HCV-CL and UGT1A1*28 polymorphism was performed. Results. SVR12 was achieved in 100% of patients with CHC and HCV-CL. IVR achieved in 87,5%: with (TA)7/(A)7 genotype – 100%, with (TA)6/(TA)7 – 92%, with (TA)6/(TA)6 – 75% . The frequency of IVR in patients with CHC was 69%, with HCV-CL – 100% and depended on the response to previous treatment with IFN-included regimens: the frequency of IVR was lower in patients who had not previously achieved a virological response when they were prescribed DAA drugs (p<0,001). IVR did not depend on (TA)7/(A)7, (TA)6/(A)7 or (TA)6/(A)6 (p=0,478) and duration of antiviral treatment (12 or 24 weeks) (p=0,273). An increase in total bilirubin to 1 or 2 degrees was not associated with the genotypes (TA)7/(A)7, (TA)6/(A)7 or (TA)6/(A)6 (p=0,62), clinical diagnosis (CHC or HCV-CL) (p=0,883), duration of treatment (p=0,880), the presence of previous treatment with regimens with IFN and ribavirin (p=0,550) and did not require withdrawal of treatment. Treatment was characterized by the absence of an increase in ALT in 97%, AST in 100% and alkaline phosphatase in 91%. Conclusion. The treatment with DAA with ribavirin was shown to be effective and safe in patients with chronic HCV infection and UGT1A1*28 polymorphism.

References