Possibilities of modern pangenotypic antiviral drugs for the treatment of chronic hepatitis C in patients on hemodialysis

Patients receiving hemodialysis (HD) treatment are one of the most promising groups for implementing the WHO HCV Infection Elimination Program. Until recently an obstacle to its elimination was the lack of antiviral drugs for the treatment of chronic hepatitis C in HCV genotypes 2 and 3 patients with low glomerular filtration rate. New opportunities have emerged with the introduction into clinical practice of direct antiviral drugs combination - glecaprevir and pibrentasvir (GLE/PIB). Eighteen dialysis patients with HCV (average age 49.4±12.4 years, HD duration 100.9±70.1 months) were treated with GLE/PIB. Thirteen (72.2%) of them had genotype 3 HCV, 4 (22.2%) had genotype 2, (one with the recombinant 2k/1b subtype) and 1 (5.6%) had genotype 1b. A sustained virological response was achieved at 12 and 24 weeks in all patients with a limited number of adverse events. In 17 of 18 patients after completion of antiviral therapy, there was a positive dynamics of transient liver elastography indicators, expressed to a greater extent in patients with initially increased activity of alanine aminotransferase. Thus, the use of the GLE/PIB pangenotype combination proved to be highly effective and safe in hemodialysis patients with HCV 2 or 3 genotypes, including the 2K/1b chimeric variant. Further analysis on a larger sample of patients with a longer follow-up period is required to clarify the possibility and degree of reduction of fibrosis severity after decreased inflammation activity in the liver.

хронический гепатит С, препараты прямого противовирусного действия, гемодиализ, chronic hepatitis C, direct acting antiviral agents, hemodialysis

1. Glassock R., D. Warnock, P. Delanave. The global burden of chronic kidney disease: estimates, variability and pitfalls. Nat Rev Nephrol. 2017; 13(2): 104-114. http://dx.doi.org/10.1038/nrneph.2016.163.

2. Fabrizi F., Donato F., Messa P. Association between hepatitis C virus and chronic kidney disease: A systematic review and meta-analysis. Ann Hepatol. 2018; 17(3): 364-391 http://dx.doi.org/10.5604/01.3001.0011.7382.

3. Зубкин М.Л., Селиванов Н.А., Стаханова В.М. и соавт. Распространенность и особенности инфицирования вирусами гепатитов В и С в условиях лечения гемодиализом. Вопросы вирусологии. 2000; 45(1): 10-14.

4. Зубкин М.Л. HBV- и HCV-инфекции у больных, получающих лечение программным гемодиализом; алгоритм вакцинопрофилактики гепатита В при хронической почечной недостаточности. Автореф. Диссертации на соискание уч. степени докт. мед. наук. 2004. М. 42 с.

5. Ярош Л.В., Семененко Т.А., Никитина Г.Ю. и соавт. Распространенность маркеров инфицирования вирусами гепатитов В и С в отделениях гемодиализа. Нефрология и диализ. 2013; 15(4): 293-298.

6. Зубкин М.Л., Червинко В.И., Крюков Е.В. и соавт. Хроническая HCV-инфекция в условиях заместительной почечной терапии. Нефрология и диализ. 2016; 18(4): 374-386.

7. Акалаев Р.Н., Арипходжаева Г.З., Рашидова С.А. и соавт. Клинико-эпидемиологические и патогенетические особенности вирусного гепатита С в отделениях гемодиализа. Трансплантология. 2019; 11(4): 282-289. doi.org/10.23873/2074-0506-2019-11-4-282-289.

8. Jadoul M., Bieber B.A., Martin P., et al. Prevalence, incidence, and risk factors for hepatitis C virus infection in hemodialysis patients. Kidney Int. 2019; 95(4): 939-947. doi: 10.1016/j.kint.2018.11.038.

9. Fabrizi F., Lampertico P., Messa P. Direct-acting antiviral agents, hepatitis C and dialysis: an update. G Ital Nefrol. 2018; 35(5).

10. Amjad U., Ahmad S.Q, Mir S., Ayub M. Association of anti-HCV sero-prevalence with blood transfusion and practice of haemodialysis from multiple centres in patients on maintenance haemodialysis. Pak J Med Sci. 2020; 36(2): 286-289. doi: 10.12669/pjms.36.2.1343.

11. Furusyo N., Hayashi J., Ariyama I. et al. Maintenance hemodialysis decreases serum hepatitis C virus (HCV) RNA levels in hemodialysis patients with chronic HCV infection. Am J Gastroenterol. 2000; 95 (2): 490-449. doi: 10.1111/j.1572-0241.2000.01773.x.

12. Ishida H., Agishi T., Koyama I., et al. Hemodialysis paradox: survey on the incidence rate of hepatocellular carcinoma in antihepatitis virus C-antibody-positive chronic hemodialysis patients. Artif Organs. 2001; 25(1): 58-60. doi: 10.1046/j.1525-1594.2001.025001058.x.

13. Aslinia F.M., Wasan S.K., Mindikoglu A.L. et al. End-stage renal disease and African American race are independent predictors of mild liver fibrosis in patients with chronic hepatitis C infection. J Viral Hepat. 2012; 19(5): 371-376. doi: 10.1111/j.1365-2893.2011.01565.x.

14. Зубкин М.Л., Червинко В.И., Овчинников Ю.В., и соавт. Хроническая HCV-инфекция; взляд интерниста (II Часть). Терапевтический архив. 2016; 88(11): 141-151. doi: 10.17116/terarkh20168811138-148.

15. Fabrizi F., Martin P., Dixit V. et al. Meta-analysis: effect of hepatitis C virus infection on mortality in dialysis. Aliment Pharmacol Ther. 2004; 20(11-12):1271-1277. doi: 10.1111/j.1365-2036.2004.02290.

16. Scott D., Wong J.K.W., Spicer T.S. et al. Adverse impact of hepatitis C virus infection on renal replacement therapy and renal transplant patients in Australia and New Zealand. Transplantation. 2010; 90(11):1165-1171. doi: 10.1097/TP.0b013e3181f92548.

17. Gordon C.E., Balk E.M., Francis J.M. Summary of the 2018 Kidney Disease: Improving Global Outcomes (KDIGO) Guideline on hepatitis C in chronic kidney disease. Semin Dial. 2019; 32(2): 187-195. doi: 10.1111/sdi.12768.

18. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C infection. Geneva: World Health Organization. 2018.

19. Toyoda H., Kumada T., Tada T. et al. Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis. J Gastroenterol. 2016; 51(7): 741-747. doi: 10.1007/s00535-016-1174-4.

20. Roth D., Nelson D.R., Bruchfeld A. et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015; 386(10003): 1537-1545. doi: 10.1016/S0140-6736(15)00349-9.

21. Pockros P.J., Reddy K.R., Mantry P.S. et al. Efficacy of direct-acting antiviral combination for patients with hepatitis C virus genotype 1 infection and severe renal impairment or end-stage renal disease. Gastroenterology. 2016; 150(7): 1590-1598. doi: 10.1053/j.gastro.2016.02.078.

22. Ponziani F.R., Siciliano M., Lionetti R. et al. Effectiveness of paritaprevir/ritonavir/ombitasvir/dasabuvir in hemodialysis patients with hepatitis C virus infection and advanced liver fibrosis: case reports. Am J Kidney Dis. 2017; 70(2): 297-300. doi: 10.1053/j.ajkd.2017.01.037.

23. De Ledinghen V. and Vergniol J. Transient elastography (FibroScan). Gastroenterologie Clin Bio. 2008; 32, 58-67.doi.org/10.1016/S0399-8320(08)73994-0.

24. Gane Е., Lawitz E., Pugatch D. et al. Glecaprevir and pibrentasvir in patients with HCV and severe renal impairment. N Engl J Med. 2017; 377(15): 1448-1455. doi: 10.1056/NEJMoa1704053

25. Kumada H., Watanabe T., Suzuki F. et al. Efficacy and safety of glecaprevir/pibrentasvir in hcv-infected japanese patients with prior daa experience, severe renal impairment, or genotype 3 infection. J Gastroenterol. 2018; 53(4): 566-575. doi: 10.1007/s00535-017-1396-0.

26. Hotta N. Efficacy and safety of glecaprevir/pibrentasvir in combination therapy in chronic hemodialysis patients with genotype 2 hepatitis c virus infection. Open Journal of Gastroenterology. 2019; 9: 1-6. doi.org/10.4236/ojgas.2019.91001.

27. Tanaka Y., Masaki T., Uojima H. et al. Glecaprevir and pibrentasvir combination therapy for hepatitis C virus-infected Japanese patients on hemodialysis. Renal Replacement Therapy. 2018 4(51): 2-7. doi.org/10.1186/s41100-018-0193-4.

28. Zubkin M.L., Shchepetkova G.S., Balkarova O.V. et al. Successful Hepatitis C Virus Eradication in a Hemodialysis Patient With 2k/1b Chimera Genotype: A Case Report and Literature Review. Gastroenterology Res. 2019; 12(3): 176-180. doi: 10.14740/gr1171.

29. Kalinina O., Norder H., Mukomolov S., Magnius L.O. A natural intergenotypic recombinant of hepatitis C virus identified in St. Petersburg. J Virol 2002; 76(8): 4034-4043 doi: 10.1128 / JVI.76.8.4034-4043.2002.

30. Raghwani J., Thomas X.V., Koekkoek S.M. et al. Origin and evolution of the unique hepatitis C virus circulating recombinant form 2k/1b. J Virol. 2012; 86(4): 2212-2220. doi: 10.1128/JVI.06184-11.

31. Калинина О.В. Организация генома и географическое распределение природного межгенотипического рекомбинанта вируса гепатита С RF1_2k/1b. Инфекция и иммунитет. 2012; 4: 677-686. doi.org/10.15789/2220-7619-2012-4-677-686.

32. Карандашова И.В., Булатова К.В., Чуланов В.П. Распространенность рекомбинантной формы RF1_2k/1b вируса гепатита С в России. Молекулярная диагностика 2017. Cборник трудов IХ Всероссийской научно-практической конференции с международным участием. 2017; 1:56-57.

33. Susser S., Dietz J., Schlevogt B. et al. Origin, prevalence and response to therapy of hepatitis C virus genotype 2k/1b chimeras. J Hepatol. 2017; 67(4): 680-686. doi: 10.1016/j.jhep.2017.05.027.

34. Espinosa M., Martin-Malo A., Alvarez de Lara M.A. et al. High ALT levels predict viremia in anti-HCV-positive HD patients if a modified normal range of ALT is applied. Clin Nephrol. 2000. 54: 151-156.

35. Guh J.Y., Lai Y., Yang C.Y. et al. Impact of decreased serum transaminase levels on the evaluation of viral hepatitis in hemodialysis patients. Nephron. 1995. 69: 459-465. doi: 10.1159/000188520.