Skip to main content

Advertisement

SpringerLink
Log in

Entecavir treatment prevents disease progression in hepatitis B virus-related acute-on-chronic liver failure: establishment of a novel logistical regression model

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Background

Hepatitis B-related acute-on-chronic liver failure (ACLF) has a poor prognosis with very high mortality. Unfortunately, most prognostic predictive models of liver failure are complicated and offer suboptimal sensitivity. Experience in entecavir (ETV)-treated patients with hepatitis B virus (HBV)-ACLF is limited.

Aims

This study was designed to evaluate the efficacy and safety of ETV in patients with HBV-ACLF and to develop a novel model (Tongji prognostic predictor model, TPPM) for prognostic prediction of HBV-ACLF patients.

Method

In this retrospective study, 248 patients with HBV-ACLF were enrolled. There were no significant differences in baseline clinical and virologic characteristics between patients treated with and without ETV.

Results

The 1- and 3-month survival rates of patients in the ETV-treated group (n = 124) were 72.58 and 61.29%, respectively, significantly higher than that in NA-free group (n = 124), which were 53.23 and 45.97%, respectively. By Hosmor and Lemeshow test, TPPM for HBV-ACLF had a very good degree of fit with disease prognosis. Based on this unique group of patients, the TPPM scoring offered a better prediction value in both specificity and sensitivity for 3-month mortality of patients with HBV-ACLF compared with MELD scoring system with statistically significant difference. In the patients with HBV-ACLF, using a cutoff of 0.22 for 3-month predicted mortality by TPPM, the positive predictive value was 93.6% and negative predictive value 91.3%.

Conclusion

ETV treatment prevented disease progression and increased the survival of patients with HBV-ACLF. The established TPPM scoring system offers superior predictor value in both specificity and sensitivity for HBV-ACLF patients when compared with MELD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Lee WM. Hepatitis B virus infection. N Engl J Med 1997;337:1733–1745.

    Article  PubMed  CAS  Google Scholar 

  2. Poland GA, Jacobson RM. Clinical practice: prevention of hepatitis B with the hepatitis B vaccine. N Engl J Med 2004;351:2832–2838.

    Article  PubMed  CAS  Google Scholar 

  3. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2001;34:1225–1241.

    Article  PubMed  CAS  Google Scholar 

  4. Morens DM, Folkers GK, Fauci AS. The challenge of emerging and re-emerging infectious diseases. Nature. 2004;430:242–9.

    Article  PubMed  CAS  Google Scholar 

  5. Ganem D, Prince AM. Hepatitis B virus infection-natural history and clinical consequences. N Engl J Med. 2004;350:1118–1129.

    Article  PubMed  CAS  Google Scholar 

  6. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–2576.

    Article  PubMed  CAS  Google Scholar 

  7. Fattovich G. Progression of hepatitis B and C of hepatocellular carcinoma in Western countries. Hepatogastroenterology. 1998;45:1206–1213.

    PubMed  Google Scholar 

  8. Lok AS. Natural history and control of perinatally acquired hepatitis B virus infection. Dig Dis. 1992;10:46–52.

    Article  PubMed  CAS  Google Scholar 

  9. Ke WM, Ye YN, Huang S. Discriminant function for prognostic indexes and probability of death in chronic severe hepatitis B. J Gastroenterol 2003;38:861–864.

    Article  PubMed  Google Scholar 

  10. Zou Z, Chen J, Xin S, et al. Features of chronic severe hepatitis in 520 cases with chronic severe hepatitis. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2002;16:246–248.

    PubMed  Google Scholar 

  11. Wang Y, Chen Y, Gu C, et al. Reevaluation of the nomenclature and diagnostic criteria in 477 patients with severe hepatitis. Zhonghua Gan Zang Bing Za Zhi 2000;8:261–263.

    PubMed  CAS  Google Scholar 

  12. Sarin SK, Kumar A, Almeida JA, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL). Hepatol Int 2009;3:269–282.

    Article  PubMed  Google Scholar 

  13. Jalan R, Williams R. Acute-on-chronic liver failure: patho-physiological basis of therapeutic options. Blood Purif 2002;20:252–261.

    Article  PubMed  Google Scholar 

  14. Wu Z, Han M, Chen T, et al. Acute liver failure: mechanisms of immune-mediated liver injury. Liver International. 2010;30:782–794.

    Article  PubMed  CAS  Google Scholar 

  15. Marsden PA, Ning Q, Fung LS, et al. The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis. J Clin Invest 2003;112:58–66.

    PubMed  CAS  Google Scholar 

  16. Zou Y, Chen T, Han M, 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;184:466–475.

    Article  PubMed  CAS  Google Scholar 

  17. Sen S, Mohensi S, Sjodin L, et al. Baseline SOFA score and its lack of early improvement accurately predicts mortality in patients with acute-on-chronic liver failure. Hepatology. 2004;40:489A.

    Article  Google Scholar 

  18. Stauber R, Stadlbauer V, Struber G, et al. Evaluation of four prognostic scores in patients with acute-on-chronic liver failure. J Hepatol 2006;44:S69–70.

    Article  Google Scholar 

  19. Yao FY, Bass NM. Lamivudine treatment in patients with severely decompensated cirrhosis due to replicating hepatitis B infection. J Hepatol 2000;33:301–307.

    Article  PubMed  CAS  Google Scholar 

  20. Tillmann HL, Hadem J, Leifeld L, et al. Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience. J Viral Hepat 2006;13:256–263.

    Article  PubMed  CAS  Google Scholar 

  21. Dai CY, Yu ML, Hsieh MY, et al. Early response to lamivudine therapy in clinically noncirrhotic chronic hepatitis B patients with decompensation. Liver Int 2007;27:1364–1370.

    Article  PubMed  CAS  Google Scholar 

  22. Chan HL. Antiviral therapy for acute-on-chronic liver failure in chronic hepatitis B: is it too late? Dig Dis Sci 2010;55:2126–2128.

    Article  PubMed  Google Scholar 

  23. Cui YL, Yan F, Wang YB, 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;55:2373–2380.

    Article  PubMed  CAS  Google Scholar 

  24. Chen J, Han JH, Liu C, et al. Short-term entecavir therapy of chronic severe hepatitis B. Hepatobiliary Pancreat Dis Int 2009;8:261–266.

    PubMed  CAS  Google Scholar 

  25. Chan HL, Tsang SW, Hui Y, et al. The role of Lamivudine and predictors of mortality in severe flare-up of chronic hepatitis B with jaundice. J Viral Hepatitis 2002;9:424–428.

    Article  Google Scholar 

  26. Tsubota A, Arase Y, Suzuki Y, et al. Lamivudine monotherapy for spontaneous severe acute exacerbation of chronic hepatitis B. J Gastroenterol Hepatol 2005;20:426–432.

    Article  PubMed  CAS  Google Scholar 

  27. Lai CL, Shouval D, Lok AS, et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2006;354:1011–1020.

    Article  PubMed  CAS  Google Scholar 

  28. Child CG, Turcotte JG. Surgery and portal hypertension. In: Child CG, editor. The Liver and Portal Hypertension. Philadelphia: W.B Saunders Co; 1964. p. 1–85.

    Google Scholar 

  29. Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60:646–649.

    Article  PubMed  CAS  Google Scholar 

  30. Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001;33:464–470.

    Article  PubMed  CAS  Google Scholar 

  31. Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124:91–96.

    Article  PubMed  Google Scholar 

  32. Yu JW, Wang GQ, Zhao YH, et al. The MELD scoring system for predicting prognosis in patients with severe hepatitis after plasma exchange treatment. Hepatobiliary Pancreat Dis Int. 2007;6:492–496.

    PubMed  Google Scholar 

  33. Freeman RB Jr, Wiesner RH, Harper A, et al. The new liver allocation system: moving toward evidence-based transplantation policy. Liver Transpl 2002;8:851–858.

    Article  PubMed  Google Scholar 

  34. Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, 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;14:643–646.

    Google Scholar 

  35. Forman LM, Lucey MR. Predicting the prognosis of chronic liver disease: an evolution from child to MELD. Hepatology. 2001;33:473–475.

    Article  PubMed  CAS  Google Scholar 

  36. Kao JH, Chen DS. Global control of hepatitis B virus infection. Lancet Infect Dis. 2002;2:395–403.

    Article  PubMed  Google Scholar 

  37. Zhu C, Sun Y, Luo X, et al. Novel mfgl2 antisense plasmid inhibits murine fgl2 expression and ameliorates murine hepatitis virus type 3-induced fulminant hepatitis in BALB/cJ mice. Hum Gene Ther 2006;17:589–600.

    Article  PubMed  CAS  Google Scholar 

  38. Zhu CL, Yan WM, Zhu F, 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;11:6936–6940.

    PubMed  CAS  Google Scholar 

  39. Han M, Yan W, Guo W, et al. Hepatitis B virus-induced hFGL2 transcription is dependent on c-Ets-2 and MAPK signal pathway. J Biol Chem 2008;283:32715–32729.

    Article  PubMed  CAS  Google Scholar 

  40. Armbrust T, Kreissig M, Tron K, et al. Modulation of fibronectin gene expression in inflammatory mononuclear phagocytes of rat liver after acute liver injury. J Hepatol 2004;40:638–645.

    Article  PubMed  CAS  Google Scholar 

  41. Sanchez MJ, Buti M, Homs M, et al. Successful use of entecavir for a severe case of reactivation of hepatitis B virus following polychemotherapy containing rituximab. J Hepatol 2009;51:1091–1096.

    Article  PubMed  CAS  Google Scholar 

  42. Jochum C, Gieseler RK, Gawlista I, et al. Hepatitis B-associated acute liver failure: Immediate treatment with entecavir inhibits hepatitis B virus replication and potentially its sequelae. Digestion. 2009;80:235–240.

    Article  PubMed  CAS  Google Scholar 

  43. Tsang SW, Chan HL, Leung NW, et al. Lamivudine treatment for fulminant hepatic failure due to acute exacerbation of chronic hepatitis B infection. Aliment Pharm Therapeut 2001;15:1737–1744.

    Article  CAS  Google Scholar 

  44. Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33:464–470.

    Article  PubMed  CAS  Google Scholar 

  45. Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124:91–96.

    Article  PubMed  Google Scholar 

  46. Malinchoc M, Kamath PS, Gordon FD, et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. 2000;31:864–871.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Supported by research grants from National Natural Science Foundation of China (81030007, 30972606), Changjiang Scholars and Innovative Research Team in University (IRT1131) and National key Basic Research Program of China (2007CB512900).

Author information

Authors and Affiliations

  1. Department of Infectious Disease, Tongji Hospital, Tongji Medical College, University of Science and Technology, No 1095, Jiefang Avenue, 430030, Wuhan, China

    Ke Ma, Wei Guo, Meifang Han, Guang Chen, Tao Chen, Zenguang Wu, Daofeng Yang, Jiaquan Huang, Yuancheng Huang, Xiping Zhao, Deying Tian, Jianxin Song, Junying Qi & Qin Ning

Authors
  1. Ke Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Meifang Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zenguang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daofeng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jiaquan Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuancheng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xiping Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Deying Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jianxin Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Junying Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Qin Ning
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qin Ning.

Additional information

K. Ma and W. Guo contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 92 kb)

Supplementary material 2 (PDF 9339 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ma, K., Guo, W., Han, M. 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 6, 735–743 (2012). https://doi.org/10.1007/s12072-012-9344-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-012-9344-9

Keywords

Search

Navigation