gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLCgastro-j-1218Research ArticleГЕПАТОЛОГИЯHEPATOLOGYОтдаленные результаты противовирусной терапии у больных хроническим гепатитом С, достигших стойкого вирусологического ответаLong-term results of antiviral therapy in patients with chronic hepatitis C with sustained virologic responseИгнатоваТ. М.IgnatovaT. M.ЛопаткинаТ. Н.LopatkinaT. N.ЧулановВ. П.ChulanovV. P.ГайдашеваЕ. В.GaydashevaYe. V.БацкихС. Н.BatskikhS. N.МихайловскаяГ. В.MikhaylovskayaG. V.АбдурахмановД. Т.AbdurakhmanovD. T.КарповС. Ю.KarpovS. Yu.НикулкинаЕ. Н.NikulkinaYe. N.ЧерноваО. А.ChernovaO. A.ФГБУ «Научно-исследовательский институт ревматологии» РАМНРоссияFederal State Budget Institution Institute of Rheumatology of Russian Academy of Medical ScienceRussian FederationГБОУ ВПО ПМГМУ им. И.М. Сеченова Минздрава РоссииРоссияState educational government-financed institution of higher professional education «Sechenov First Moscow state medical university», Ministry of Healthcare of the Russian FederationRussian FederationФБУН «Центральный научно-исследовательский институт эпидемиологии» РоспотребнадзораРоссияFederal Budget scientific Institution «Central research institute of epidemiology» of The Federal service on customers' rights protection and human well-being surveillanceRussian FederationГБОУ ВПО ПМГМУ им. И.М. Сеченова Минздрава РоссииРоссияState educational government-financed institution of higher professional education «Sechenov First Moscow state medical university», Ministry of Healthcare of the Russian FederationRussian FederationФБУН «Центральный научно-исследовательский институт эпидемиологии» РоспотребнадзораРоссияFederal Budget scientific Institution «Central research institute of epidemiology» of The Federal service on customers' rights protection and human well-being surveillanceRussian Federation2013220920132343036Copyright © Игнатова Т.М., Лопаткина Т.Н., Чуланов В.П., Гайдашева Е.В., Бацких С.Н., Михайловская Г.В., Абдурахманов Д.Т., Карпов С.Ю., Никулкина Е.Н., Чернова О.А., 20132013Игнатова Т.М., Лопаткина Т.Н., Чуланов В.П., Гайдашева Е.В., Бацких С.Н., Михайловская Г.В., Абдурахманов Д.Т., Карпов С.Ю., Никулкина Е.Н., Чернова О.А.Ignatova T.M., Lopatkina T.N., Chulanov V.P., Gaydasheva Y.V., Batskikh S.N., Mikhaylovskaya G.V., Abdurakhmanov D.T., Karpov S.Y., Nikulkina Y.N., Chernova O.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/1218

Цель исследования. Оценить частоту поздних рецидивов и клинические исходы у больных хроническим гепатитом С (ХГС) со стойким вирусологическим ответом (СВО) в результате противовирусной терапии (ПВТ).Материал и методы. Обследовано 208 больных ХГС, в том числе 12 на стадии цирроза печени (ЦП), достигших СВО. Длительность наблюдения составила в среднем 56,1±35,4 мес. Проводилось стандартное клинико-лабораторное обследование и определение РНК HCV. У 114 больных РНК HCV и ДНК HBV в сыворотке крови и периферических мононуклеарных клетках крови исследовались методом полимеразной цепной реакции (ПЦР) с гибридизационно-флуоресцентной детекцией в режиме «реального времени» (чувствительность 10 МЕ/мл для HCV и 5 МЕ/мл для HBV).Результаты. У 3 (1,5%) больных наблюдались поздние (в сроки более 6 мес после ПВТ) рецидивы HCV-инфекции. Применение ультрачувствительного метода ПЦР позволило в 2 случаях констатировать рецидив за полгода до его явных клинико-лабораторных признаков. Сведений о латентном течении HCV-инфекции не получено ни в одном случае, в том числе у пациентов с рецидивом криоглобулинемического синдрома. Основной причиной повышения активности аланинаминотрансферазы был неалкогольный стеатогепатит. У одной больной ЦП зарегистрировано формирование варикозно-расширенных вен пищевода. Не было наблюдений декомпенсации ЦП, гепатоцеллюлярной карциномы и смерти от заболевания печени.Заключение. У пациентов, достигших СВО в результате ПВТ, поздние рецидивы HCV-инфекции редки и у большинства не отмечается прогрессирования болезни. Наблюдались рецидивы криоглобулинемического синдрома, но данных о наличии латентной HCV-инфекции не получено. Для определения СВО целесообразно применение высокочувствительных методов ПЦР.

Aim of investigation

Aim of investigation. To estimate frequency of late relapses and clinical outcomes in patients with chronic hepatitis C (CHC) with sustained virologic response (SVO) achievement at antiviral therapy (AVT).

Material and methods

Material and methods. Overall 208 patients with CHC, including 12 at the stage of liver cirrhosis (LC), who achieved SVO were investigated. Mean duration of the follow-up was 56,1±35,4 months. Standard clinical and laboratory investigation and evaluation of RNA HCV was carried out. In 114 patients RNA HCV and DNA HBV in blood serum and peripheral mononuclear blood cells were studied by polymerase chain reaction (PCR) with fluorescent hybridization detection in «real time» mode (sensitivity of 10 IU/ml for HCV and 5 IU/ml for HBV).

Results

Results. In 3 (1,5%) patients late (i.e. over 6 months after AVT) relapses of HCV-infection were observed. Application of ultraresponsive PCR method allowed to reveal relapse half a year prior to its clinical and laboratory manifestation in 2 cases. No data on latent HCVinfection was obtained not in a single case, including patients with relapse of cryoglobulinemia syndrome. A principal cause of elevation of alanine transaminase activity was non-alcoholic steatohepatitis. In one LC patient development of esophageal varicose veins was detected. There were no cases of decompensation of LC, hepatocellular carcinoma and death due to liver disease.

Conclusion

Conclusion. At patients who have achieved SVO as a result of AVT, late relapses of HCV-infection are rare and in the majority no disease progression was found. Relapses of cryoglobulinemia syndrome were observed, but data on presence of latent HCV-infection were not received. Highly sensitive PCR methods are rational for assessment of SVO.

хронический гепатит Сотдаленные результаты леченияэрадикация HCVпоздний рецидивлатентная HCV-инфекцияchronic hepatitis Clong-term treatment resultsHCV eradicationlate relapselatent HCVinfectionReferencesИгнатова Т.М., Милованова С.Ю., Чернова О.А., Байжанова Ж.Ж. В-лимфома у больной хроническим гепатитом С и смешанной криоглобулинемией 2-го типа // Тер. арх. – 2011. – № 4. – С. 69–71.Игнатова Т.М., Милованова С.Ю., Чернова О.А., Байжанова Ж.Ж. В-лимфома у больной хроническим гепатитом С и смешанной криоглобулинемией 2-го типа // Тер. арх. – 2011. – № 4. – С. 69–71.Игнатова Т.М., Чернова О.А., Гайдашева Е.В. Успешное лечение ритуксимабом HCV-криоглобулинемического васкулита с тяжелым язвенно-некротическим поражением кожи // Клин. мед. – 2012. – № 5. – С. 64–66.Игнатова Т.М., Чернова О.А., Гайдашева Е.В. Успешное лечение ритуксимабом HCV-криоглобулинемического васкулита с тяжелым язвенно-некротическим поражением кожи // Клин. мед. – 2012. – № 5. – С. 64–66.Ондос Ш.А., Маевская М.В., Павлов Ч.С., Ивашкин В.Т. Комбинированное противовирусное лечение пегилированным интерфероном-α-2а и рибавирином больных хроническим гепатитом С, принимающих умеренные дозы алкоголя // Рос. журн. гастроэнтерол. гепатол. колопроктол. – 2008. – Т. 18, № 2. – С. 35–41.Ондос Ш.А., Маевская М.В., Павлов Ч.С., Ивашкин В.Т. Комбинированное противовирусное лечение пегилированным интерфероном-α-2а и рибавирином больных хроническим гепатитом С, принимающих умеренные дозы алкоголя // Рос. журн. гастроэнтерол. гепатол. колопроктол. – 2008. – Т. 18, № 2. – С. 35–41.Alberti A. Impact of sustained virological response on the long-term outcome of hepatitis C // Liver Int. – 2011. – Vol. 31. – P. 18–22.Alberti A. Impact of sustained virological response on the long-term outcome of hepatitis C // Liver Int. – 2011. – Vol. 31. – P. 18–22.Bate J.P., Colman A.J., Frost P.J. et al. High prevalence of late relapse and reinfection in prisoners treated for chronic hepatitis C // J. Gastroenterol. Hepatol. –2010. – Vol. 25, N 7. – P. 1276–1280.Bate J.P., Colman A.J., Frost P.J. et al. High prevalence of late relapse and reinfection in prisoners treated for chronic hepatitis C // J. Gastroenterol. Hepatol. –2010. – Vol. 25, N 7. – P. 1276–1280.Carreno V. Occult hepatitis C virus infection: a new form of hepatitis C // World J. Gastroenterol. – 2006.– Vol. 12. – P. 6922–6925.Carreno V. Occult hepatitis C virus infection: a new form of hepatitis C // World J. Gastroenterol. – 2006.– Vol. 12. – P. 6922–6925.Carreno V., Bartalome J., Castillo I., Quiroga J.A. New perspectives in occult hepatitis C virus infection // World J. Gastroenterol. – 2012. – Vol. 18. – P. 2887–2894.Carreno V., Bartalome J., Castillo I., Quiroga J.A. New perspectives in occult hepatitis C virus infection // World J. Gastroenterol. – 2012. – Vol. 18. – P. 2887–2894.Castillo I., Bartolome J., Quiroga J.A. et al. Diagnosis of occult hepatitis C without the need for a liver biopsy // J. Med. Virol. – 2010. – Vol. 82. – P. 1554–1559.Castillo I., Bartolome J., Quiroga J.A. et al. Diagnosis of occult hepatitis C without the need for a liver biopsy // J. Med. Virol. – 2010. – Vol. 82. – P. 1554–1559.Chavalitdhamrong D., Tanwandee T. Long-term outcomes of chronic hepatitis C patients with sustained virological response at 6 months after the end of treatment // World J. Gastroenterol. – 2006. – Vol. 12. – P. 5532–5535.Chavalitdhamrong D., Tanwandee T. Long-term outcomes of chronic hepatitis C patients with sustained virological response at 6 months after the end of treatment // World J. Gastroenterol. – 2006. – Vol. 12. – P. 5532–5535.Ciancio A., Smedile A., Giordanino C. et al. Longterm follow-up of previous hepatitis C virus positive nonresponders to interferon monotherapy successfully retreated with combination therapy: are they really cured? // Am. J. Gastroenterol. – 2006. – Vol. 101. – P. 1811–1816.Ciancio A., Smedile A., Giordanino C. et al. Longterm follow-up of previous hepatitis C virus positive nonresponders to interferon monotherapy successfully retreated with combination therapy: are they really cured? // Am. J. Gastroenterol. – 2006. – Vol. 101. – P. 1811–1816.Coppola N., Pisaturo M., Guastafiero S. et al. Absence of occult hepatitis C virus infection in patients under immunosuppressive therapy for oncohematological diseases // Hepatology. – 2011 – Vol. 54. – P. 1487–1489.Coppola N., Pisaturo M., Guastafiero S. et al. Absence of occult hepatitis C virus infection in patients under immunosuppressive therapy for oncohematological diseases // Hepatology. – 2011 – Vol. 54. – P. 1487–1489.D'Ambrosio R., Aghemo A., Rumi M.G. et al. The course of esophageal varices in patients with hepatitis C cirrhosis responding to interferon/ribavirin therapy // Antivir. Ther. – 2011. – Vol. 16. – P. 677–684.D'Ambrosio R., Aghemo A., Rumi M.G. et al. The course of esophageal varices in patients with hepatitis C cirrhosis responding to interferon/ribavirin therapy // Antivir. Ther. – 2011. – Vol. 16. – P. 677–684.European Association for the Study of the Liver. Clinical practice Guidelines: management of hepatitis C virus infection // J. Hepatol. – 2011. – Vol. 55. – P. 245–264.European Association for the Study of the Liver. Clinical practice Guidelines: management of hepatitis C virus infection // J. Hepatol. – 2011. – Vol. 55. – P. 245–264.Ferreira S.C., Carneiro M.V., Souza F.F. et al. Longterm follow-up of patients with chronic hepatitis C with sustained virologic response to interferon // Braz. J. Infect. Dis. – 2010. – Vol. 14. – P. 330–334.Ferreira S.C., Carneiro M.V., Souza F.F. et al. Longterm follow-up of patients with chronic hepatitis C with sustained virologic response to interferon // Braz. J. Infect. Dis. – 2010. – Vol. 14. – P. 330–334.Formann E., Steindl-Munda P., Hofer H. et al. Long-term follow-up of chronic hepatitis C patients with sustained virological response to various forms of interferon-based anti-viral therapy // Aliment. Pharmacol. Ther. – 2006. – Vol. 23. – P. 507–511.Formann E., Steindl-Munda P., Hofer H. et al. Long-term follow-up of chronic hepatitis C patients with sustained virological response to various forms of interferon-based anti-viral therapy // Aliment. Pharmacol. Ther. – 2006. – Vol. 23. – P. 507–511.George S.L., Bacon B.R., Brunt E.M. et al. Clinical, virologic, histologic and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients // Hepatology. – 2009. – Vol. 49. – P. 729–738.George S.L., Bacon B.R., Brunt E.M. et al. Clinical, virologic, histologic and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients // Hepatology. – 2009. – Vol. 49. – P. 729–738.Giannini C., Petrarca A., Monti M. et al. Association between persistent lymphatic infection by hepatitis C virus after antiviral treatment and mixed cryoglobulinemia // Blood. – 2008. – Vol. 111. – P. 2943–2945.Giannini C., Petrarca A., Monti M. et al. Association between persistent lymphatic infection by hepatitis C virus after antiviral treatment and mixed cryoglobulinemia // Blood. – 2008. – Vol. 111. – P. 2943–2945.Halfon P., Bourliere M., Ouzan D. et al. Occult hepatitis C virus infection revisited with ultrasensitive real-time PCR assay // J. Clin. Microbiol. – 2008. – Vol. 46. – P. 2106–2108.Halfon P., Bourliere M., Ouzan D. et al. Occult hepatitis C virus infection revisited with ultrasensitive real-time PCR assay // J. Clin. Microbiol. – 2008. – Vol. 46. – P. 2106–2108.Landau D.A., Saadoun D., Halfon P. et al. Relapse of hepatitis C virus-associated mixed cryoglobulinemia vasculitis in patients with sustained viral response // Arthritis Rheumatism. – 2008. – Vol. 58. – P. 604–611.Landau D.A., Saadoun D., Halfon P. et al. Relapse of hepatitis C virus-associated mixed cryoglobulinemia vasculitis in patients with sustained viral response // Arthritis Rheumatism. – 2008. – Vol. 58. – P. 604–611.Manns M., Lindsay K.L., Gordon S.C. et al. Sustained virologic response after peginterferon alfa-2b and ribavirin treatment predicts long-term clearance of HCV at 5-year follow-up [Abstract] // J. Hepatol. – 2008. – Vol. 48 (suppl. 2). – P. 300.Manns M., Lindsay K.L., Gordon S.C. et al. Sustained virologic response after peginterferon alfa-2b and ribavirin treatment predicts long-term clearance of HCV at 5-year follow-up [Abstract] // J. Hepatol. – 2008. – Vol. 48 (suppl. 2). – P. 300.Maylin S., Martinot-Peignoux M., Moucari R. et al. Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C // Gastroenterology. – 2008. – Vol. 135. – P. 821–829.Maylin S., Martinot-Peignoux M., Moucari R. et al. Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C // Gastroenterology. – 2008. – Vol. 135. – P. 821–829.McHutchison J.G., Shiffman M.L., Gordon S.C. et al. Sustained virologic response (SVR) to interferon-alpha-2b +/– ribavirin therapy at 6 months reliably predicts longterm clearance of HCV at 5-year follow-up [Abstract] // J. Hepatol. – 2006. – Vol. 44 (suppl. 2). – P. 275.McHutchison J.G., Shiffman M.L., Gordon S.C. et al. Sustained virologic response (SVR) to interferon-alpha-2b +/– ribavirin therapy at 6 months reliably predicts longterm clearance of HCV at 5-year follow-up [Abstract] // J. Hepatol. – 2006. – Vol. 44 (suppl. 2). – P. 275.Moreno M., Perez-Alvarez R., Rodrigo L. et al. Longterm evolution of liver histopatology in patients with chronic hepatitis C and sustained response // Rev. Esp. Enferm. Dig. – 2005. – Vol. 97. – P. 860–869.Moreno M., Perez-Alvarez R., Rodrigo L. et al. Longterm evolution of liver histopatology in patients with chronic hepatitis C and sustained response // Rev. Esp. Enferm. Dig. – 2005. – Vol. 97. – P. 860–869.Nagaoki Y., Aikata H., Kobayashi T. et al. Risk factors for the exacerbation of esophageal varices or portosystemic encephalopathy after sustained virological response with IFN therapy for HCV-related compensated cirrhosis // J. Gastroenterol. – 2012. – Vol. 47. – P. 847–855.Nagaoki Y., Aikata H., Kobayashi T. et al. Risk factors for the exacerbation of esophageal varices or portosystemic encephalopathy after sustained virological response with IFN therapy for HCV-related compensated cirrhosis // J. Gastroenterol. – 2012. – Vol. 47. – P. 847–855.Nicot F., Kamar N., Mariame B. et al. No evidence of occult hepatitis C virus (HCV) infection in serum of HCV antibody-positive HCVRNA-negative kidney-transplant patients // Transplant. Int. – 2010. – Vol. 23. – P. 594–601.Nicot F., Kamar N., Mariame B. et al. No evidence of occult hepatitis C virus (HCV) infection in serum of HCV antibody-positive HCVRNA-negative kidney-transplant patients // Transplant. Int. – 2010. – Vol. 23. – P. 594–601.Pham T.N., Coffin C.S., Churchill N.D. et al. Hepatitis C virus persistence after sustained virological response to antiviral therapy in patients with or without past exposure to hepatitis B virus // J. Vral. Hepat. – 2012. – Vol. 19. – P. 103–111.Pham T.N., Coffin C.S., Churchill N.D. et al. Hepatitis C virus persistence after sustained virological response to antiviral therapy in patients with or without past exposure to hepatitis B virus // J. Vral. Hepat. – 2012. – Vol. 19. – P. 103–111.Swain M.G., Lai M.Y., Shiffman M.L. et al. A sustained virological response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin // Gastroenterology. – 2010. – Vol. 139. – P.1593–1601.Swain M.G., Lai M.Y., Shiffman M.L. et al. A sustained virological response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin // Gastroenterology. – 2010. – Vol. 139. – P.1593–1601.Trapero-Marugan M., Mendoza J., Chaparro M. et al. Long-term outcome of chronic hepatitis C patients with sustained virological response to peginterferon plus ribavirin // World J. Gastroenterol. – 2011. – Vol. 17. – P. 493–498.Trapero-Marugan M., Mendoza J., Chaparro M. et al. Long-term outcome of chronic hepatitis C patients with sustained virological response to peginterferon plus ribavirin // World J. Gastroenterol. – 2011. – Vol. 17. – P. 493–498.Veldt B.J., Saracco G., Boyer N. et al. Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy // Gut. – 2004. – Vol. 53. – P. 1504–1508.Veldt B.J., Saracco G., Boyer N. et al. Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy // Gut. – 2004. – Vol. 53. – P. 1504–1508.Welker M.W., Zeuzem S. Occult hepatitis C: how convincing are the current data? // Hepatology. – 2009.– Vol. 49. – P. 665–675.Welker M.W., Zeuzem S. Occult hepatitis C: how convincing are the current data? // Hepatology. – 2009.– Vol. 49. – P. 665–675.

The authors declare that there are no conflicts of interest present.