Abstract
Background
The mortality of acute-on-chronic hepatitis B liver failure (ACHBLF) from acute exacerbation of chronic hepatitis B is 30–70 % without liver transplant.
Methods
We conducted an open-label, prospective, 48-week study to evaluate the efficacy of entecavir (ETV) in ACHBLF with 110 patients who received either ETV or no treatment. Primary measurements were survival and improvement in disease severity scores.
Results
Of the 110 patients enrolled, 2 withdrew consent, 108 were treated with 53 ETV, and 55 were untreated. When compared to the patients in the untreated group at week 48, a lower cumulative mortality rate in ETV-treated patients was observed [54.7 % (29/53) vs. 78.2 % (43/55), p < 0.01). ETV treatment significantly improved disease severity scores including Child–Turcotte–Pugh (CTP), model for end-stage liver disease (MELD), and MELD sodium (MELD-Na). All ETV-treated subjects achieved an undetectable HBV DNA level (<500 copies/mL; 100 % vs. 7.9 %, p < 0.001). In univariate analysis, predictors of survival at week 48 included baseline age, total bilirubin, international normalized ratio of prothrombin time, albumin, cholesterol, receiving ETV therapy, CTP, MELD, MELD-Na, and sequential organ failure assessment (SOFA) scores. In multivariate analysis, baseline age, total bilirubin, untreated (with ETV), CTP, and SOFA scores were the independent risk factors for mortality.
Conclusions
Entecavir treatment for patients with ACHBLF significantly improves disease severity scores with a marked reduction in mortality and suppression in HBV DNA to undetectable levels at week 48. Patients’ age, total bilirubin, CTP, and SOFA scores at baseline are independent risk factors for higher mortality without liver transplantation.
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References
Bosch FX, Ribes J, Cleries R, Diaz M. Epidemiology of hepatocellular carcinoma. Clin Liver Dis 2005;9(2):191–211, v
Lee WM, Squires RH Jr, Nyberg SL, Doo E, Hoofnagle JH. Acute liver failure: summary of a workshop. Hepatology 2008;47(4):1401–15
Liu Q, Liu Z, Wang T, et al. Characteristics of acute and sub-acute liver failure in China: nomination, classification, and interval. J Gastroenterol Hepatol 2007;22(12):2101–216
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(1):269–82
Chuang CS, Tung SY, Lee IL, et al. Clinical features and outcome of chronic viral hepatitis with acute exacerbation in patients with concurrent infections of hepatitis B and C virus. Dig Dis Sci 2008;53(2):511–6
Wang YM, Tang YZ. Antiviral therapy for hepatitis B virus associated hepatic failure. Hepatobiliary Pancreat Dis Int 2009;8(1):17–24
Tsubota A, Arase Y, Suzuki Y, et al. Lamivudine monotherapy for spontaneous severe acute exacerbation of chronic hepatitis B. J Gastroenterol Hepatol 2005;20(3):426–32
Liaw YF, Sheen IS, Lee CM, et al. Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease. Hepatology 2011;53(1):62–72
Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004;351(15):1521–31
Chien RN, Lin CH, Liaw YF. The effect of lamivudine therapy in hepatic decompensation during acute exacerbation of chronic hepatitis B. J Hepatol 2003;38(3):322–7
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(4):256–63
Lu GF, Tang FA, Zheng PY, Yang PC, Qi YM. Entecavir up-regulates dendritic cell function in patients with chronic hepatitis B. World J Gastroenterol 2008;14(10):1617–21
Pan CQ, Tong M, Kowdley KV et al. High rates of viral suppression after long-term entecavir treatment of Asian patients with hepatitis B e antigen-positive chronic hepatitis B. Clin Gastroenterol Hepatol 2012;10(9):1047–1050, e1
Wong VW, Wong GL, Yiu KK, et al. Entecavir treatment in patients with severe acute exacerbation of chronic hepatitis B. J Hepatol 2011;54(2):236–42
Garg H, Sarin SK, Kumar M, et al. Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure. Hepatology 2011;53(3):774–80
Chan HL, Chim AM, Lau JT, et al. Evaluation of model for end-stage liver disease for prediction of mortality in decompensated chronic hepatitis B. Am J Gastroenterol 2006;101(7):1516–23
Wong VW, Chim AM, Wong GL, Sung JJ, Chan HL. Performance of the new MELD-Na score in predicting 3-month and 1-year mortality in Chinese patients with chronic hepatitis B. Liver Transpl 2007;13(9):1228–35
Acknowledgments
The research was funded by a grant from the Ministry of Science and Technology of China for the National Eleventh Five-Year Key Projects in Infectious Diseases—for the prevention and control of major infectious diseases, such as AIDS and viral hepatitis (grant no. 2008ZX10202) and research grants from Guangdong Province Government for the Science and Technology Projects (grant nos. 2007B060401001 and 2006B36005004).
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Calvin Q. Pan is a Co-First Author with Equal Contributions.
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Lin, B., Pan, C.Q., Xie, D. et al. Entecavir improves the outcome of acute-on-chronic liver failure due to the acute exacerbation of chronic hepatitis B. Hepatol Int 7, 460–467 (2013). https://doi.org/10.1007/s12072-012-9415-y
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DOI: https://doi.org/10.1007/s12072-012-9415-y