Problems of VirologyProblems of VirologyВопросы вирусологии0507-40882411-2097Central Research Institute for Epidemiology12087ArticlesСтатьиRetherapy with lamivudine in HBeAg-negative chronic hepatitis B patients unresponsive to interferon/peginterferon treatmentПовторная терапия ламивудином у пациентов с HBeAg-негативным хроническим гепатитом В, не ответивших на лечение интерфероном/ пегинтерфероном15062011563NO3 (2011)№3 (2011)374009062023Copyright ©; 2011, Fedorchenko S.V., Martynovich T.L., Yanchenko V.I., Klimenko Z.B., Lyashok O.V., Fedorchenko S.V., Martynovich T.L., Yanchenko V.I., Klimenko Z.B., Lyashok O.V.Copyright ©; 2011, Федорченко С.В., Мартынович Т.Л., Янченко В.И., Клименко Ж.Б., Ляшок О.В., Fedorchenko S.V., Martynovich T.L., Yanchenko V.I., Klimenko Z.B., Lyashok O.V.2011Fedorchenko S.V., Martynovich T.L., Yanchenko V.I., Klimenko Z.B., Lyashok O.V., Fedorchenko S.V., Martynovich T.L., Yanchenko V.I., Klimenko Z.B., Lyashok O.V.Федорченко С.В., Мартынович Т.Л., Янченко В.И., Клименко Ж.Б., Ляшок О.В., Fedorchenko S.V., Martynovich T.L., Yanchenko V.I., Klimenko Z.B., Lyashok O.V.https://creativecommons.org/licenses/by/4.0https://virusjour.crie.ru/jour/article/view/12087

The paper gives data on retherapy with lamivudine in seven HBeAg-negative chronic hepatitis B patients previously unresponsive to interferon-α and peginterferon-α2b therapy (6 unresponsive patients and 1 with recurrence). Prior to lamivudine therapy, hepatic biopsy and HBV genotyping were carried out and the baseline level of viremia and the presence of YMDD mutations were determined in all the patients. Its therapeutic efficiency was based on viremia level and AlAT activity at 6, 12, 18, and 24 weeks of treatment. Six of the 7 patients, including 2 receiving peginterferon-α2a, achieved a virological response. Trends in viremia within the first 12 weeks of treatment were a major factor to assess the virological response. Positive predictors during retreatment with lamivudine are discussed.

Представлены данные о повторной терапии ламивудином 7 пациентов с HBeAg-негативным хроническим гепатитом В, ранее не давших ответа на терапию ИФН-α2b и пегинтерфероном-α2b (6 пациентов с отсутствием ответа и 1 с рецидивом). До начала терапии ламивудином всем пациентам проводили биопсию печени, генотипирование HBV, определение стартового уровня виремии и наличия YMDD-мутаций. Оценка эффективности терапии основывалась на уровне виремии и активности АлАТ на 6, 12, 18 и 24-й неделях лечения. Вирусологический ответ был достигнут у 6 из 7 пациентов, в том числе у двух, получавших пегинтерферон-α2a. Основным фактором в оценке вирусологического ответа была динамика виремии в течение первых 12 нед лечения. Обсуждены вопросы, касающиеся положительных предикт-факторов при повторной терапии ламивудином.

viral replicationnucleoside analoguespeginterferonhepatitis B virusвирусная репликациянуклеозидные аналогипегинтерферонвирус гепатита ВAluto N., Kumada H. Influense of hepatitis B virus genotypes on the response to antiviral therapies // J. Antimicrob. Chemother. - 2005. - Vol. 55. - P. 139-142.Alvarodo-Esquivel C., Carrera-Gracia M., Conde-Gonzales C. et al. Genotypic resistance to lamivudine among hepatitis B virus isolates in Mexico // J. Antimicrob. Chemother. - 2006. - Vol. 57, N 2. - P. 221-223.Born M. J., Hansen B. E., Bigot G. et al. ALT viral load decline during PEG-INF alpha-2a treatment for HBeAg-positive chronic hepatitis B // J. Clin. Virol. - 2008. - Vol. 42, N 2. - P. 160-164.Brunetto M. R., Oliveri F., Coco B. et al. The outcome of chronic anti-HBe-positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study // Hepatology. - 2002. - Vol. 36. - P. 263-270.Croagh C., Bell S., Kong Y. et al. Prevalence of significant fibrosis and correlations between histological inflammation and fibrosis scores and hepatitis B (HBV) DNA levels in chronic hepatitis B // 44th (Annual Meeting of the European Association for the Study of the Liver. Copenhagen, Denmark, 2009. April 22-26.6. Da Silva L. C., Fonseca L. E., Carrilho F. J. et al. Predictive factors for response to lamivudine in chronic hepatitis B // Rev. Inst. Med. Trop. S. Paulo. - 2000. - Vol. 42, N 4. - P. 189- 196.Erhardt A., Gobel T., Ludwing A. et al. Response to antiviral ment in patients infected with hepatitis B virus genotypes E- H // J. Med. Virol. - 2009. - Vol. 81, N 10. - P. 1716-1720.Gish R. G., Lau D. T., Schmid P., Perrillo R. A pilot study of extended duration-peginterferon alfa-2a for patients with hepatitis Be-antigen negativ chronic hepatitis B // Am. J. Gastroenterol. - 2007. - Vol. 102, N 12. - P. 2718-2723.Graham W., Cooksley E. The role of interferon therapy in hepatitis B // Medscape Gen. Med. - 2004. - Vol. 6, N 1. - P. 16-19.Hadzyannis S. J. Treatment options for chronic hepatitis B not responding to interferon // Hepatology. - 2003. - Vol. 38, N 6. - P. 853-855.Hartman C., Berkowitz D., Shouval D. et al. Lamivudine treatment for chronic hepatitis B infection in children unresponsive to interferon // Pediatr. infect. Dis. J. - 2003. - Vol. 22, N 3. - P. 224-228.Hui C. K., Lau G. K. Peginterferon alpha-2a (40 kDa) (Pegasys) for hepatitis B // Expert Rev. Anti Infect. Ther. - 2005. - Vol. 3, N 4. - P. 495-504.Karabay O., Tamer A., Tahtaci M. et al. Effectiveness of lamivudine and interferon-α combination therapy monotherapy for the treatment of HBeAg-negative chronic hepatitis B patients: arandomized clinical trial // J. Microbiol. Immunol. Infect. - 2005. - Vol. 38. - P. 262-266.Kurdas O., Guzelbulut F., Gokden Y. et al. Peginterferon are not satisfactory in genotype D chronic HBV infection // 60th Annual Meeting of the American Association for the Study Liver Diseases. Boston. October 30-November 1, 2009. - Abstr. 462.Lai L., Hui C., Leung N., Lau G. K. Pegylated interferon alpha-2a (40 kDa) in the treatment of chronic hepatitis B // Int. J. Nanomed. - 2006. - Vol. 1, N 3. - P. 255-262.Liaw Y. F., Sung J. Y., Chow W. C. et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease // N. Engl. J. Med. - 2004. - Vol. 351, N 15. - P. 1521-1531.Lui K., Hou W., Zumbica E., Ni Q. Clinical features of chronic hepatitis B patients with YMDD mutation after lamivudine therapy // J. Zheijang Univ. Sci. B. - 2005. - Vol. 6, N 12. - P. 1182-1187.Marcellin P., Lau G. K., Bonino F. et al. Peginterferon alpha-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B // N. Engl. J. Med. - 2004. - Vol. 351, N 27. - P. 2879.Schiff E. R., Dienstag J. L., Karayalcin S. et al. Lamivudine and 24 weeks of lamivudine interferon combination therapy for hepatitis Be-antigen positive chronic hepatitis B in interferon nonresponders // Hepatology. - 2003. - Vol. 38, N 6. - P. 813- 826.Tuncbilek S., Kose S., Elaldi A., Aman S. Lamivudine resistance in untreated chronic hepatitis B patients in Turkey // Turk. J. Gastroenterol. - 2008. - Vol. 19, N 2. - P. 99-103.Wong G. L., Wong V. W., Choi P. C. et al. Evaluation of alanine transaminase and hepatitis B virus DNA to predict liver cirrhosis in hepatitis HBe-antigen negative chronic hepatitis B using transrent elastography // Am. J. Gastroenterol. - 2008. - Vol. 103, N 12. - P. 3071-3081.Yang H. J., Jloeje U. H., Su J. Association between HBV replication and serum ALT changes is not dependent of HBV genotype and mutants // Digestive disease week. Chicago, May 30-June 4, 2009. - Abstr. W1800.