Hepatology International

, Volume 8, Issue 1, pp 64–71 | Cite as

Nucleoside analogs prevent disease progression in HBV-related acute-on-chronic liver failure: validation of the TPPM model

  • Junshuai Wang
  • Ke Ma
  • Meifang Han
  • Wei Guo
  • Jiaquan Huang
  • Daofeng Yang
  • Xiping Zhao
  • Jiangxin Song
  • Deying Tian
  • Junying Qi
  • Yuancheng Huang
  • Qin Ning
Original Article



This study aimed to evaluate the efficacy and safety of entecavir, lamivudine and telbivudine for treating patients with HBV-ACLF and to validate the Tongji prognostic predictor model (TPPM) in these patients.


In this retrospective study, we enrolled 283 patients with HBV-ACLF (100 treated with entecavir, 98 treated with lamivudine and 85 treated with telbivudine). There were no significant differences in baseline clinical and virological characteristics among patients treated with entecavir, telbivudine or lamivudine.


There were no significant differences in the 4- and 12-week survival rates of entecavir-, telbivudine- and lamivudine-treated patients (79.00, 81.18 and 86.73 %, respectively, at 4 weeks; 67.00, 65.88 and 73.47 %, respectively, at 12 weeks). Patients in all three groups achieved an improvement in the model for end-stage liver disease (MELD) score. Using the Hosmer-Lemeshow test, the validation of the TPPM score for HBV-ACLF demonstrated a good degree of fit with disease prognosis. Based on this unique group of patients, the TPPM score with an AUC of 0.787 was superior to the MELD score, which had an AUC of 0.736 in the prediction of 12-week mortality. The TPPM had an AUC of 0.733, and the MELD score had an AUC of 0.672 in the prediction of 4-week mortality. Using a cutoff value of 0.22 for 12-week mortality prediction by the TPPM, the positive predictive value was 49.66 %, with a negative predictive value of 89.55 %.


Treatment with nucleoside analogs including entecavir, lamivudine and telbivudine prevented disease progression and increased the survival of patients with HBV-ACLF. Validation of the established TPPM scoring system in this study confirmed its superior predictive value for HBV-ACLF patients when compared with the MELD system.


HBV-ACLF Antiviral therapy Nucleoside analogs MELD TPPM 


  1. 1.
    Lai CL, Yuen MF. The natural history and treatment of chronic hepatitis B: a critical evaluation of standard treatment criteria and end points. Ann Intern Med 2007;147:58–61PubMedCrossRefGoogle Scholar
  2. 2.
    Liaw YF. Hepatitis B virus replication and liver disease progression: the impact of antiviral therapy. Antivir Ther 2006;11:669–679PubMedGoogle Scholar
  3. 3.
    Laleman W, Verbeke L, Meersseman P, Wauters J, van Pelt J, Cassiman D, et al. Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions. Expert Rev Gastroenterol Hepatol 2011;5:523–537 quiz 537PubMedCrossRefGoogle Scholar
  4. 4.
    Jalan R, Williams R. Acute-on-chronic liver failure: pathophysiological basis of therapeutic options. Blood Purif 2002;20:252–261PubMedCrossRefGoogle Scholar
  5. 5.
    Graziadei IW. The clinical challenges of acute on chronic liver failure. Liver Int 2011;31(Suppl 3):24–26PubMedCrossRefGoogle Scholar
  6. 6.
    Wong GL, Wong VW, Choi PC, Chan AW, Chim AM, Yiu KK, et al. Increased liver stiffness measurement by transient elastography in severe acute exacerbation of chronic hepatitis B. J Gastroenterol Hepatol 2009;24:1002–1007PubMedCrossRefGoogle Scholar
  7. 7.
    Olson JC, Kamath PS. Acute-on-chronic liver failure: concept, natural history, and prognosis. Curr Opin Crit Care 2011;17:165–169PubMedCrossRefGoogle Scholar
  8. 8.
    Jindal A, Kumar M, Sarin SK. Management of acute hepatitis B and reactivation of hepatitis B. Liver Int 2013;33(Suppl 1):164–175PubMedCrossRefGoogle Scholar
  9. 9.
    Ma K, Guo W, Han M, Chen G, Chen T, Wu Z, et al. Entecavir treatment prevents disease progression in hepatitis B virus-related acute-on-chronic liver failure: establishment of a novel logistical regression model. Hepatol Int 2012;6:735–743CrossRefGoogle Scholar
  10. 10.
    Garg H, Sarin SK, Kumar M, Garg V, Sharma BC, Kumar A. Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure. Hepatology 2011;53:774–780PubMedCrossRefGoogle Scholar
  11. 11.
    Seto WK, Lai CL, Yuen MF. Acute-on-chronic liver failure in chronic hepatitis B. J Gastroenterol Hepatol 2012;27:662–669PubMedCrossRefGoogle Scholar
  12. 12.
    Sarin SK, Kumar A, Almeida JA, Chawla YK, Fan ST, Garg H, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 2009;3:269–282PubMedCrossRefGoogle Scholar
  13. 13.
    Chen T, He Y, Liu X, Yan Z, Wang K, Liu H, et al. Nucleoside analogues improve the short-term and long-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure. Clin Exp Med 2012;12:159–164PubMedCrossRefGoogle Scholar
  14. 14.
    Cui YL, Yan F, Wang YB, Song XQ, Liu L, Lei XZ, et al. Nucleoside analogue can improve the long-term prognosis of patients with hepatitis B virus infection-associated acute on chronic liver failure. Dig Dis Sci 2010;55:2373–2380PubMedCrossRefGoogle Scholar
  15. 15.
    Sun LJ, Yu JW, Zhao YH, Kang P, Li SC. Influential factors of prognosis in lamivudine treatment for patients with acute-on-chronic hepatitis B liver failure. J Gastroenterol Hepatol 2010;25:583–590PubMedCrossRefGoogle Scholar
  16. 16.
    Liver Failure and Artificial Liver Group CSoID, Chinese Medical Association, Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology. Diagnostic and treatment guidelines for liver failure. Chin J Hepatol 2006;14:643–646Google Scholar
  17. 17.
    Freeman RB Jr. Model for end-stage liver disease (MELD) for liver allocation: a 5-year score card. Hepatology 2008;47:1052–1057PubMedCrossRefGoogle Scholar
  18. 18.
    Mao W, Ye B, Lin S, Fu Y, Chen Y. Prediction value of model for end-stage liver disease scoring system on prognosis in the acute on chronic liver failure patients with plasma exchange treatment. ASAIO J 2010;56:475–478PubMedCrossRefGoogle Scholar
  19. 19.
    Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis 2003;23:47–58PubMedCrossRefGoogle Scholar
  20. 20.
    Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007;45:507–539PubMedCrossRefGoogle Scholar
  21. 21.
    Hoofnagle JH, Doo E, Liang TJ, Fleischer R, Lok AS. Management of hepatitis B: summary of a clinical research workshop. Hepatology. 2007;45:1056–75PubMedCrossRefGoogle Scholar
  22. 22.
    Lee WM. Hepatitis B virus infection. N Engl J Med 1997;337:1733–1745PubMedCrossRefGoogle Scholar
  23. 23.
    Wang J, Wang M, Huang Y. Acute liver failure resulting from discontinuation of nucleoside analogues in chronic hepatitis B patients: a report of two cases. Scand J Infect Dis 2013;45:158–160PubMedCrossRefGoogle Scholar
  24. 24.
    Zheng Y, Huang Z, Chen X, Tian Y, Tang J, Zhang Y, et al. Effects of telbivudine treatment on the circulating CD4(+) T-cell subpopulations in chronic hepatitis B patients. Mediators Inflamm 2012;2012:789859PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Zhao S, Tang L, Fan X, Chen L, Zhou R, Dai X. Comparison of the efficacy of lamivudine and telbivudine in the treatment of chronic hepatitis B: a systematic review. Virol J 2010;7:211PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Hadziyannis SJ, Vassilopoulos D. Telbivudine in the treatment of chronic hepatitis B. Expert Rev Gastroenterol Hepatol 2008;2:13–22PubMedCrossRefGoogle Scholar
  27. 27.
    Matthews SJ. Entecavir for the treatment of chronic hepatitis B virus infection. Clin Ther 2006;28:184–203PubMedCrossRefGoogle Scholar
  28. 28.
    Yao G, Chen C, Lu W, Ren H, Tan D, Wang Y, et al. Virologic, serologic, and biochemical outcomes through 2 years of treatment with entecavir and lamivudine in nucleoside-naive Chinese patients with chronic hepatitis B: a randomized, multicenter study. Hepatol Int 2008;2:486–493PubMedCrossRefGoogle Scholar
  29. 29.
    Lange CM, Bojunga J, Hofmann WP, Wunder K, Mihm U, Zeuzem S, et al. Severe lactic acidosis during treatment of chronic hepatitis B with entecavir in patients with impaired liver function. Hepatology 2009;50:2001–2006PubMedCrossRefGoogle Scholar
  30. 30.
    Wong VW, Wong GL, Yiu KK, Chim AM, Chu SH, Chan HY, et al. Entecavir treatment in patients with severe acute exacerbation of chronic hepatitis B. J Hepatol 2011;54:236–242PubMedCrossRefGoogle Scholar
  31. 31.
    Lai CL, Yuen MF. Chronic hepatitis B—new goals, new treatment. N Engl J Med 2008;359:2488–2491PubMedCrossRefGoogle Scholar
  32. 32.
    Dienstag JL, Wei LJ, Xu D, Kreter B. Cross-study analysis of the relative efficacies of oral antiviral therapies for chronic hepatitis B infection in nucleoside-naive patients. Clin Drug Investig 2007;27:35–49PubMedCrossRefGoogle Scholar
  33. 33.
    Lim SG, Wai CT, Rajnakova A, Kajiji T, Guan R. Fatal hepatitis B reactivation following discontinuation of nucleoside analogues for chronic hepatitis B. Gut 2002;51:597–599PubMedCrossRefGoogle Scholar
  34. 34.
    Marsden PA, Ning Q, Fung LS, Luo X, Chen Y, Mendicino M, et al. The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis. J Clin Invest 2003;112:58–66PubMedCentralPubMedGoogle Scholar
  35. 35.
    Zhu CL, Yan WM, Zhu F, Zhu YF, Xi D, Tian DY, et al. Fibrinogen-like protein 2 fibroleukin expression and its correlation with disease progression in murine hepatitis virus type 3-induced fulminant hepatitis and in patients with severe viral hepatitis B. World J Gastroenterol 2005;11:6936–6940PubMedGoogle Scholar
  36. 36.
    Zou Y, Chen T, Han M, Wang H, Yan W, Song G, et al. Increased killing of liver NK cells by Fas/Fas ligand and NKG2D/NKG2D ligand contributes to hepatocyte necrosis in virus-induced liver failure. J Immunol 2010;184:466–475PubMedCrossRefGoogle Scholar
  37. 37.
    Kumar A, Mishra SR, Sharma P, Sharma BC, Sarin SK. Clinical, laboratory, and hemodynamic parameters in portal hypertensive gastropathy: a study of 254 cirrhotics. J Clin Gastroenterol 2010;44:294–300PubMedCrossRefGoogle Scholar
  38. 38.
    Yang WB, Chen EQ, Bi HX, Bai L, Chen XB, Feng P, et al. Different models in predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure. Ann Hepatol 2012;11:311–319PubMedGoogle Scholar
  39. 39.
    Lv XH, Liu HB, Wang Y, Wang BY, Song M, Sun MJ. Validation of model for end-stage liver disease score to serum sodium ratio index as a prognostic predictor in patients with cirrhosis. J Gastroenterol Hepatol 2009;24:1547–1553PubMedCrossRefGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2013

Authors and Affiliations

  • Junshuai Wang
    • 1
  • Ke Ma
    • 1
  • Meifang Han
    • 1
  • Wei Guo
    • 1
  • Jiaquan Huang
    • 1
  • Daofeng Yang
    • 1
  • Xiping Zhao
    • 1
  • Jiangxin Song
    • 1
  • Deying Tian
    • 1
  • Junying Qi
    • 1
  • Yuancheng Huang
    • 1
  • Qin Ning
    • 1
  1. 1.Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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