•  
  •  
 

Abstract

Introduction. Chronic hepatitis B (CHB) is endemic in Indonesia, where it is usually treated with pegylated interferon and nucleoside/nucleotide analogs (NA). The aim of this study was to determine the efficacy of treating CHB infection among Indonesian patients with NA (lamivudine, telbivudine, and tenofovir) for a 3-year period.Methods. We retrospectively reviewed the records of patients with CHB infection attending the Hepatology Clinic Cipto Mangunkusumo during 2010-2013 period. Subjects with inclusion criteria were all patients aged above 18 years treated with NA for at least three years. The degree of liver stiffness, hepatitis B virus deoxyribonucleic acid (HBV-DNA), alanine aminotransferase (ALT) levels, and hepatitis B antigen (HBeAg) were assessed before and after 3-years therapy.Results. A total of 62 subjects were included in the study. Forty-eight patients (77%) were treated with telbivudine, 9 (15%) with tenofovir, and 5 (8%) with lamivudine. At baseline prior to the onset of therapy, 52 patients (84%) had a positive HBeAg test, 15 patients (24%) had F3 liver disease (advance fibrosis), and 36 (58%) had liver cirrhosis using transient elastography. At the end of the 3 year study period, median of liver stiffness significantly decline from baseline (14.5 (3.3 – 59.3) kPa to 6.7 (3.3 – 37.2) kPa, p = 0.001), HBV DNA load significantly decline (1.31 x 107 (2.0x106 – 1.0x108) copies/mL to 0 (0 – 1.7 x 107) copies/mL, p = 0.001), alanine aminotransferase (ALT) levels significantly decline (58 (11– 404) U/L to 27 (8-291) U/L, p = 0.001). Nevertheless, there were five patients (8%) who still had F3 liver disease, and 20 patients (32.3%) had F4 liver disease, 21 (34%) had detectable HBV-DNA, 17 (27%) had not achieved ALT normalization. From 52 patients with positive HBeAg 140| Jurnal Penyakit Dalam Indonesia | Vol. 8, No. 3 | September 2021Andri S. Sulaiman, Irsan Hasan, C.R.A. Lesmana, Chyntia O.M. Jasirwan, Saut Horas H. Nababan, Kemal F. Kalista, Gita Aprilicia, Rino A. Ganibaseline, there were 20 patients (39%) who had seroconversion to negative HBeAg after three year period.Conclusion. NA therapy resulted in a reduction level of fibrosis in CHB induced liver disease.

References

1. Poh Z, Goh BB, Chang PE, Tan CK. Rates of cirrhosis and hepatocellular carcinoma in chronic hepatitis B and the role of surveillance: a 10-year follow-up of 673 patients. Eur J Gastroenterol Hepatol. 2015;27(6):638–43. 2. World Health Organization (WHO). Factsheet hepatitis B [Internet]. Geneva: WHO; 2021 [accessed September 2021]. Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-b3. MacLachlan JH, Cowie BC. Hepatitis B virus epidemiology. Cold Spring Harb Perspect Med. 2015;5:1-134. Peng CY, Chien RN, Liaw YF. Hepatitis B virus-related decompensated liver cirrhosis: benefits of antiviral therapy. J Hepatol. 2012 Aug;57(2):442-50. 5. Yang HC, Kao JH. Persistence of hepatitis B virus covalently closed circular DNA in hepatocytes: molecular mechanisms and clinical significance. Emerg Microbes Infect. 2014;3:1-7.6. Lai CL, Gane E, Liaw YF, Hsu CW, Thongswat S, Wang Y, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med. 2007;357:2576-88.7. Marcellin P, Lau GKK, Bonino F, Farci P, Hadziyannis S, Jin R, et al. Peginterferon Alfa-2a, lamivudine alone, and two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004;351:1206-17.8. European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-98. 9. Pol S, Lampertico P. First-line treatment of chronic hepatitis B with entecavir or tenofovir in real life settings: from clinical trials to clinical practice. J Viral Hepat. 2012;19:377-8610. Ridruejo E. Treatment of chronic hepatitis B in clinical practice with entecavir or tenofovir. World J Gastroenterol. 2014;20(23):7169-80.11. Buti M, Tsai N, Petersen J, Flisiak R, Gurel S, Kratsev Z, et al. Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection. Dig Dis Sci. 2015;60:1457-64.12. You H, Jia J. Telbivudine treatment in chronic hepatitis B: experience from China. J Viral Hepat. 2013;20:3-8.13. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1-98. 14. Taylor BC, Yuan JM, Shamliyan TA, Shaukat A, Kane RL, Wilt TJ. Clinical outcomes in adults with chronic hepatitis B in association with patient and viral characteristics: a systematic review of evidence. Hepatology. 2009;49(5):85-95.15. Andersen ES, Weiland O, Leutscher P, Krarup H, Westin J, Moessner B, et al. Low liver stiffness among cirrhotic patients with hepatitis B after prolonged treatment with nucleoside analogues. Scand J Gastroenterol. 2011;46(6):760-6.16. Fung J, Lai CL, Wong KH, Seto WK, Hung I, Yuen MF. Significant changes in liver stiffmess measurements in patients with chronic hepatitis B: 3-year follow-up study. J Viral Hepat. 2011;18:200-5.17. Mokdad AA, Lopez AD, Shahraz S, Lozano R, Mokdad AH, Stanaway J, et al. Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. BMC Medicine. 2014;12(145):1-24.18. Xu HW, Lu SN, Hung CH, Chang KC, Hu TH, Wang JH. Liver stiffness measurement in cirrhotic patient – implications of disease activity and treatment efficacy. Kaohsiung J Med Sci. 2012;28(12):641-8.19. Yo IK, Kwoon OS, Park JW, Lee JJ, Lee JH, Won IS, et al. The factors associated with longitudinal changes in liver stiffness in patients with chronic hepatitis B. Clin Mol Hepatol. 2015;21:32-40.20. Chan HLY, Wong GLH, Choi PCL, Chan AWH, Chim AML, Yiu KKL, et al. Alanine aminotransferae-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B. J Viral Hepat. 2009;16(1):36-44.21. Kitrinos KM, Corsa A, Liu Y, Flaherty J, Snow-Lampart A, Marcellin P, et al. No detectable resistance to tenofovir disoproxil fumarate after 6 years of therapy in patients with chronic hepatitis B. Hepatology. 2014;59(2):434-42.22. Lok AS, Zoulim F, Locarnini S, Bartholomeusz A, Ghany MG, Pawlotsky JM, et al. Antiviral drug-resistant HBV: standardization of nomenclature and assays and recommendations for management. Hepatology. 2007;46(1):254-65.23. Gane EJ, Wang Y, Liaw YF, Hou J, Thongsawat S, Wan M, et al. Efficacy and safety of prolonged 3-year telbivudine treatment in patientes with chronic hepatitis B. Liver Int. 2011;31(5):676-84.24. Marcellin P, Heathcote J, Buti M, Gane E, de Man RA, Kratsev Z, at al. Tenofovir disproxil fumarate versus adefovir diproxil for chronic hepatitis B. N Engl J Med. 2008;359:2442-55.25. World Health Organization (WHO). Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. Geneva: WHO; 2015.26. Van Bömmel F, de Man RA, Wedemeyer H, Deterding K, Petersen J, Buggisch P, et al. Long-term efficacy of tenofovir monotherapy for hepatitis B virus-monoinfected patients after failure of nucleoside/nucleotide analogues. Hepatology. 2010;51(1):73-80.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.