Декомпенсация заболевания, ассоциированная с безинтерфероновой противовирусной терапией, у пациентов с циррозом печени в исходе хронического гепатита С

1. Jessica K. Dyson, John Hutchinson, Laura Harrison, Olorunda Rotimi, Dina Tiniakos, Graham R. Foster, Mark A. Aldersley, Stuart McPherson. Liver toxicity associated with sofosbuvir, an NS5A inhibitor and ribavirin use. J Hepatology. 2016;64:234-8. https://doi.org/10.1016/ j.jhep.2015.07.041 
2. Jonathan G. Stine, Nicolas Intagliata, Neeral L. Shah, Curtis K. Argo, Stephen H. Caldwell, James H. Lewis, Patrick G. Northup. Hepatic decompensation likely attributable to simeprevir in patients with advanced cirrhosis. Digestive Disease and Sciences. 2015;60:1031-5. https://doi.org/10.1007/s10620-014-3422-x 
3. Martin-Walter Welker, Stefan Luhne, Christian M. Lange, Johannes Vermehren, Harald Farnik, Eva Herrmann, Tania Welzel, Stefan Zeuzem, Christoph Sarrazin. Lactic acidosis in patients with hepatitis C virus cirrhosis and combined ribavirin/ sofosbuvir treatment. J Hepatology. 2016;64:790-9. https://doi.org/10.1016/j.jhep.2015.11.034 
4. Fred Poordad, David R. Nelson, Jordan J. Feld, Michael W. Fried, Heiner Wedemeyer, Lois Larsen, Daniel E. Cohen, Eric Cohen, Niloufar Mobashery, Fernando Tatsch, Graham R. Foster. Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis – A pooled analysis. J Hepatology. 2017;67:700-7.      https://doi.org/10.1016/j.jhep.2017.06.011
5. Bart J. Veldt, E. Jenny Heathcote, Heiner Wedemeyer, Juerg Reichen, W.     Peter Hofmann, Stefan Zeuzem, Michael P. Manns, Bettina E. Hansen, Solko W. Schalm, Harry L.A. Janssen. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med. 2007;147(10):677-84. https://doi.org/10.7326/0003-4819-147-10-200711200-00003 
6. Adriaan J. van der Meer, Bart J. Veldt, Jordan J. Feld, Heiner Wedemeyer, Jean-François Dufour, Frank Lammert, Andres Duarte-Rojo, E. Jenny Heathcote, Michael P. Manns, Lorenz Kuske, Stefan Zeuzem, W. Peter Hofmann, Robert J. de Knegt, Bettina E. Hansen, Harry L. A. Janssen. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308(24):2584-93. https://doi.org/ 10.1001/jama.2012.144878 
7. Rebecca L. Morgan, Brittney Baack, Bryce D. Smith, Anthony Yartel, Marc Pitasi, Yngve Falck-Ytter. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013;158(5 Pt 1):329-37. https://doi.org/10.7326/0003-4819-158-5-201303050-00005 
8. Heiner Wedemeyer, Jens Reimer, Petra Sandow, Dietrich Hueppe, Thomas Lutz, Kurt Gruengreiff, Joerg Goelz, Stefan Christensen, Heike Pfeiffer-Vornkahl, UlrichAlshuth, Michael P. Mann. Long-term Outcome of Chronic Hepatitis C (CHC) Virus Infection in a Real-World Setting: The German LOTOS Study. Liver International. 2017;37:1468-75. https://doi.org/10.1111/liv.13399 
9. Jay H. Hoofnagle. Hepatic decompensation during direct-acting antiviral therapy of chronic hepatitis C. J Hepatology. 2016;646:763-5. https://doi.org/10.1016/j.jhep.2016.01.007 
10. Welker MW, Luhne S, Lange CM, Farnik H, Herrmann E, Welzel T, Zeuzem S, Christoph S. Lactic acidosis in patients with hepatitis C virus cirrhosis and combined ribavirin/ sofosbuvir treatment. J Hepatology. 2016;64:790-9. https://doi.org/10.1016/j.jhep.2015.11.034 
11. Scheiner B, Lindner G, Reiberger T, Schneeweiss B, Trauner M, Zauner C, Funk GC. Acid-base disorders in liver disease. J Hepatology. 2017;67:1062-73. https://doi.org/10.1016/j.jhep.2017.06.023 
12. Vanwolleghem T, Meuleman P, Libbrecht L, Roskams T, De Vos R, Leroux-Roels G. Ultra-Rapid Cardiotoxicity of the Hepatitis C Virus Protease Inhibitor BILN 2061 in the Urokinase-Type Plasminogen Activator Mouse. Gastroenterology. 2007;133(4):1144-55.  https://doi.org/ 10.1053/j.gastro.2007.07.007 
13. Sheridan C. Calamitous HCV trial casts shadow over nucleoside drugs. Nature Biotechnology. 2012;30:1015-6.  https://doi.org/10.1038/ nbt1112-1015 
14. Arnold JJ, Sharma SD, Feng JY, Ray AS, Smidansky ED, Kireeva ML, Cho A, Perry J, Vela JE, Park Y, Xu Y, Tian Y, Babusis D, Barauskus O, Peterson BR, Gnatt A, Kashlev M, Zhong W, Cameron CE. Sensitivity of Mitochondrial Transcription and Resistance of RNA Polymerase II Dependant Nuclear Transcription to Antiviral Ribonucleosides. PLoS Pathogens. 2012;8(11):e1003030. https://doi.org/10.1371/ journal.ppat.1003030 
15. McKenzie R, Fried MW, Sallie R, Conjeevaram H, Di Bisceglie AM, Park Y, Savarese B, Kleiner D, Tsokos M, Luciano C, Pruett T, Stotka JL, Straus SE, Hoofnagle JH. Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. N Engl J Med. 1995;333:1099-105. https://doi.org/10.1056/nejm199510263331702 
16. Tujios S, Fontana RJ. Mechanisms of drug-induced liver injury: from bedside to bench. Nature Reviews Gastroenterology & Hepatology. 2011 Apr;8(4):202-11.  https://doi.org/10.1038/nrgastro.2011.22 
17. Xu D, Nishimura T, Nishimura S, Zhang H, Zheng M, Guo YY, Masek M, Michie SA, Glenn J, Peltz G. Fialuridine induces acute liver failure in chimeric TK-NOG mice:a model for detecting hepatic drug toxicity prior to human testing. PLoS Med. 2014;11:31001628.  https://doi.org/10.1371/journal.pmed.1001628 
18. Coats SJ, Garnier-Amblard EC, Amblard F, Ehteshami M, Amiralaei S, Zhang H, Zhou L, Boucle SRL, Lu X, Bondada L, Shelton JR, Li H, Liu P, Li C, Cho JH, Chavre SN, Zhou S, Mathew J, Schinazi RF. Chutes and ladders in hepatitis C nucleoside drug development. Antiviral Res. 2014;102:119-47.  https://doi.org/10.1016/ ­j.antiviral.2013.11.008 
19. Renet S, Chaumais MC, Antonini T, Zhao A, Thomas L, Savoure A, Samuel D, Duclos-Vallée JC, Algalarrondo V. Extreme bradycardia after first doses of sofosbuvir and daclatasvir in patients receiving amiodarone: 2 cases including a rechallenge. Gastroenterology. 2015;149(6):1378-80. https://doi.org/10.1053/j.gastro.2015.07.051 
20. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatology. 2017;66:153-94. https://doi.org/10.1016/j.jhep.2016.09.001 
21. AASLD/IDSA HCV Guidance Panel Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;4(62)3:932-54. https://doi.org/10.1002/hep.27950 
22. Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD. IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in eff ector T cell generation and trafficking. J Immunol. 2002;168:3195-204.  https://doi.org/10.4049/ ­jimmunol.168.7.3195 
23. Edward J Gane, Stuart K Roberts, Catherine AM Stedman, Peter W Angus, Brett Ritchie, Rob Elston, David Ipe, Peter N Morcos, Linda Baher, Isabel Najera, Tom Chu, Uri Lopatin, M Michelle Berrey, William Bradford, Mark Laughlin, Nancy S Shulman, Patrick F Smith. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet. 2010;376:1467-75.  https://doi.org/10.1016/ s0140-6736(10)61384-0 
24. Meike H. van der Ree, Femke Stelma, Sophie B. Willemse, Anthony Brown, Leo Swadling, Marc van der Valk, Marjan J. Sinnige, Ad C. van Nuenen, J. Marleen L. de Vree, Paul Klenerman, Eleanor Barnes, Neeltje A. Kootstra, Hendrik W. Reesink.   Immune responses in DAA treated chronic hepatitis C patients with and without prior RG-101 dosing. Antiviral Research. 2017;146:139-45.  https://doi.org/10.1016 j.antiviral.2017.08.016 
25. Eric G. Meissner, David Wu, Anu Osinusi, Dimitra Bon, Kimmo Virtaneva, Dan Sturdevant, Steve Porcella, Honghui Wang, Eva Herrmann, John McHutchison, Anthony F. Suffredini, Michael Polis, Stephen Hewitt, Ludmila Prokunina-Olsson, Henry Masur, Anthony S. Fauci, Shyamasundaran Kottilil. Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome. J Clinical. 2014;124:3352-63. https://doi.org/10.1172/jci75938 
26. Jens M. Werner, Akinbami Adenugba, Ulrike Protzer. Immune Reconstitution After HCV Clearance With Direct Antiviral Agents: Potential Consequences for Patients With HCC? Transplantation. 2017;101(5):904-9. https://doi.org/10.1097/tp.0000000000001606 
27. Oldford SA, Arseneault K, Barrett L. Early Immune Changes during HCV DAA Therapy in an Incarcerated Population. J Hepatology. 2016;64:525-26. https://doi.org/10.1016/s0168-8278(16)00926-0 

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1. Jessica K. Dyson, John Hutchinson, Laura Harrison, Olorunda Rotimi, Dina Tiniakos, Graham R. Foster, Mark A. Aldersley, Stuart McPherson. Liver toxicity associated with sofosbuvir, an NS5A inhibitor and ribavirin use. J Hepatology. 2016;64:234-8. https://doi.org/10.1016/ j.jhep.2015.07.041 
2. Jonathan G. Stine, Nicolas Intagliata, Neeral L. Shah, Curtis K. Argo, Stephen H. Caldwell, James H. Lewis, Patrick G. Northup. Hepatic decompensation likely attributable to simeprevir in patients with advanced cirrhosis. Digestive Disease and Sciences. 2015;60:1031-5. https://doi.org/10.1007/s10620-014-3422-x 
3. Martin-Walter Welker, Stefan Luhne, Christian M. Lange, Johannes Vermehren, Harald Farnik, Eva Herrmann, Tania Welzel, Stefan Zeuzem, Christoph Sarrazin. Lactic acidosis in patients with hepatitis C virus cirrhosis and combined ribavirin/ sofosbuvir treatment. J Hepatology. 2016;64:790-9. https://doi.org/10.1016/j.jhep.2015.11.034 
4. Fred Poordad, David R. Nelson, Jordan J. Feld, Michael W. Fried, Heiner Wedemeyer, Lois Larsen, Daniel E. Cohen, Eric Cohen, Niloufar Mobashery, Fernando Tatsch, Graham R. Foster. Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis – A pooled analysis. J Hepatology. 2017;67:700-7.      https://doi.org/10.1016/j.jhep.2017.06.011
5. Bart J. Veldt, E. Jenny Heathcote, Heiner Wedemeyer, Juerg Reichen, W.     Peter Hofmann, Stefan Zeuzem, Michael P. Manns, Bettina E. Hansen, Solko W. Schalm, Harry L.A. Janssen. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med. 2007;147(10):677-84. https://doi.org/10.7326/0003-4819-147-10-200711200-00003 
6. Adriaan J. van der Meer, Bart J. Veldt, Jordan J. Feld, Heiner Wedemeyer, Jean-François Dufour, Frank Lammert, Andres Duarte-Rojo, E. Jenny Heathcote, Michael P. Manns, Lorenz Kuske, Stefan Zeuzem, W. Peter Hofmann, Robert J. de Knegt, Bettina E. Hansen, Harry L. A. Janssen. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308(24):2584-93. https://doi.org/ 10.1001/jama.2012.144878 
7. Rebecca L. Morgan, Brittney Baack, Bryce D. Smith, Anthony Yartel, Marc Pitasi, Yngve Falck-Ytter. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013;158(5 Pt 1):329-37. https://doi.org/10.7326/0003-4819-158-5-201303050-00005 
8. Heiner Wedemeyer, Jens Reimer, Petra Sandow, Dietrich Hueppe, Thomas Lutz, Kurt Gruengreiff, Joerg Goelz, Stefan Christensen, Heike Pfeiffer-Vornkahl, UlrichAlshuth, Michael P. Mann. Long-term Outcome of Chronic Hepatitis C (CHC) Virus Infection in a Real-World Setting: The German LOTOS Study. Liver International. 2017;37:1468-75. https://doi.org/10.1111/liv.13399 
9. Jay H. Hoofnagle. Hepatic decompensation during direct-acting antiviral therapy of chronic hepatitis C. J Hepatology. 2016;646:763-5. https://doi.org/10.1016/j.jhep.2016.01.007 
10. Welker MW, Luhne S, Lange CM, Farnik H, Herrmann E, Welzel T, Zeuzem S, Christoph S. Lactic acidosis in patients with hepatitis C virus cirrhosis and combined ribavirin/ sofosbuvir treatment. J Hepatology. 2016;64:790-9. https://doi.org/10.1016/j.jhep.2015.11.034 
11. Scheiner B, Lindner G, Reiberger T, Schneeweiss B, Trauner M, Zauner C, Funk GC. Acid-base disorders in liver disease. J Hepatology. 2017;67:1062-73. https://doi.org/10.1016/j.jhep.2017.06.023 
12. Vanwolleghem T, Meuleman P, Libbrecht L, Roskams T, De Vos R, Leroux-Roels G. Ultra-Rapid Cardiotoxicity of the Hepatitis C Virus Protease Inhibitor BILN 2061 in the Urokinase-Type Plasminogen Activator Mouse. Gastroenterology. 2007;133(4):1144-55.  https://doi.org/ 10.1053/j.gastro.2007.07.007 
13. Sheridan C. Calamitous HCV trial casts shadow over nucleoside drugs. Nature Biotechnology. 2012;30:1015-6.  https://doi.org/10.1038/ nbt1112-1015 
14. Arnold JJ, Sharma SD, Feng JY, Ray AS, Smidansky ED, Kireeva ML, Cho A, Perry J, Vela JE, Park Y, Xu Y, Tian Y, Babusis D, Barauskus O, Peterson BR, Gnatt A, Kashlev M, Zhong W, Cameron CE. Sensitivity of Mitochondrial Transcription and Resistance of RNA Polymerase II Dependant Nuclear Transcription to Antiviral Ribonucleosides. PLoS Pathogens. 2012;8(11):e1003030. https://doi.org/10.1371/ journal.ppat.1003030 
15. McKenzie R, Fried MW, Sallie R, Conjeevaram H, Di Bisceglie AM, Park Y, Savarese B, Kleiner D, Tsokos M, Luciano C, Pruett T, Stotka JL, Straus SE, Hoofnagle JH. Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. N Engl J Med. 1995;333:1099-105. https://doi.org/10.1056/nejm199510263331702 
16. Tujios S, Fontana RJ. Mechanisms of drug-induced liver injury: from bedside to bench. Nature Reviews Gastroenterology & Hepatology. 2011 Apr;8(4):202-11.  https://doi.org/10.1038/nrgastro.2011.22 
17. Xu D, Nishimura T, Nishimura S, Zhang H, Zheng M, Guo YY, Masek M, Michie SA, Glenn J, Peltz G. Fialuridine induces acute liver failure in chimeric TK-NOG mice:a model for detecting hepatic drug toxicity prior to human testing. PLoS Med. 2014;11:31001628.  https://doi.org/10.1371/journal.pmed.1001628 
18. Coats SJ, Garnier-Amblard EC, Amblard F, Ehteshami M, Amiralaei S, Zhang H, Zhou L, Boucle SRL, Lu X, Bondada L, Shelton JR, Li H, Liu P, Li C, Cho JH, Chavre SN, Zhou S, Mathew J, Schinazi RF. Chutes and ladders in hepatitis C nucleoside drug development. Antiviral Res. 2014;102:119-47.  https://doi.org/10.1016/ ­j.antiviral.2013.11.008 
19. Renet S, Chaumais MC, Antonini T, Zhao A, Thomas L, Savoure A, Samuel D, Duclos-Vallée JC, Algalarrondo V. Extreme bradycardia after first doses of sofosbuvir and daclatasvir in patients receiving amiodarone: 2 cases including a rechallenge. Gastroenterology. 2015;149(6):1378-80. https://doi.org/10.1053/j.gastro.2015.07.051 
20. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatology. 2017;66:153-94. https://doi.org/10.1016/j.jhep.2016.09.001 
21. AASLD/IDSA HCV Guidance Panel Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;4(62)3:932-54. https://doi.org/10.1002/hep.27950 
22. Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD. IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in eff ector T cell generation and trafficking. J Immunol. 2002;168:3195-204.  https://doi.org/10.4049/ ­jimmunol.168.7.3195 
23. Edward J Gane, Stuart K Roberts, Catherine AM Stedman, Peter W Angus, Brett Ritchie, Rob Elston, David Ipe, Peter N Morcos, Linda Baher, Isabel Najera, Tom Chu, Uri Lopatin, M Michelle Berrey, William Bradford, Mark Laughlin, Nancy S Shulman, Patrick F Smith. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet. 2010;376:1467-75.  https://doi.org/10.1016/ s0140-6736(10)61384-0 
24. Meike H. van der Ree, Femke Stelma, Sophie B. Willemse, Anthony Brown, Leo Swadling, Marc van der Valk, Marjan J. Sinnige, Ad C. van Nuenen, J. Marleen L. de Vree, Paul Klenerman, Eleanor Barnes, Neeltje A. Kootstra, Hendrik W. Reesink.   Immune responses in DAA treated chronic hepatitis C patients with and without prior RG-101 dosing. Antiviral Research. 2017;146:139-45.  https://doi.org/10.1016 j.antiviral.2017.08.016 
25. Eric G. Meissner, David Wu, Anu Osinusi, Dimitra Bon, Kimmo Virtaneva, Dan Sturdevant, Steve Porcella, Honghui Wang, Eva Herrmann, John McHutchison, Anthony F. Suffredini, Michael Polis, Stephen Hewitt, Ludmila Prokunina-Olsson, Henry Masur, Anthony S. Fauci, Shyamasundaran Kottilil. Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome. J Clinical. 2014;124:3352-63. https://doi.org/10.1172/jci75938 
26. Jens M. Werner, Akinbami Adenugba, Ulrike Protzer. Immune Reconstitution After HCV Clearance With Direct Antiviral Agents: Potential Consequences for Patients With HCC? Transplantation. 2017;101(5):904-9. https://doi.org/10.1097/tp.0000000000001606 
27. Oldford SA, Arseneault K, Barrett L. Early Immune Changes during HCV DAA Therapy in an Incarcerated Population. J Hepatology. 2016;64:525-26. https://doi.org/10.1016/s0168-8278(16)00926-0 

С.Н. Бацких, Е.В. Винницкая, Ю.Г. Сандлер, Т.Ю. Хайменова 

ГБУЗ «Московский клинический научно-практический центр имени А.С. Логинова» Департамента здравоохранения города Москвы, Москва, Россия 

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S.N. Batskikh, E.V. Vinnitskaya, Yu.G. Sandler, T.Yu. Кhaimenova

A.S. Loginov Moscow Clinical Scientific and Practical Center, Moscow City Department of Health, Moscow, Russia