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Nucleoside analogues improve the short-term and long-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure

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Abstract

Hepatitis B virus (HBV) infection is a major public health problem, and HBV-related acute-on-chronic liver failure (ACLF) has an extremely poor prognosis. There is no standard approach for managing ACLF. Nucleos(t)ide analogue has been proven effective in suppressing viral replication, improving histology and biochemical, and decreasing the inflammatory response in patients with chronic hepatitis B. This study was designed to evaluate the short-term and long-term efficacy of nucleoside analogue treatment of patients with HBV-related ACLF. One hundred and six consecutive subjects were recruited from 2,308 patients with elevated alanine aminotransferase activity. Forty-two patients were treated with 0.5 mg entecavir (ETV) daily (ETV group); 30 patients received 100 mg lamivudine (LAM) daily (LAM group); 34 patients did not take any nucleos(t)ide analogues (non-NAs group). All eligible patients were given standard medical treatment. All the patients were followed up until death or until October 2010. The HBV DNA levels and the short-term and long-term efficacy of the drugs were evaluated. After 3 weeks of nucleoside analogue treatment and/or supportive therapy, HBV DNA levels were decreased when compared with the baseline level in the ETV group (7.04 ± 1.58 log10 IU/mL vs. 4.03 ± 2.04 log10 IU/mL, P = 0.001), the LAM group (7.25 ± 0.89 log10 IU/mL vs. 4.33 ± 2.48 log10 IU/mL, P = 0.01), and the non-NAs group (5.73 ± 0.96 log10 IU/mL vs. 4.21 ± 1.47 log10 IU/mL, P = 0.01). The ETV and LAM groups showed a similar accumulative mortality in the first 3 months of treatment (33.3% vs. 40%, χ2 = 0.568, P = 0.374). The non-NAs group had a significantly high mortality, compared with the ETV group (64.7% vs. 33.3%, χ2 = 7.163, P = 0.007), the LAM group (64.7% vs. 40%, χ2 = 3.906, P = 0.042), and the nucleoside analogue group (ETV group + LAM group) (64.7% vs. 36.2%, χ2 = 7.443, P = 0.006). All the 56 patients survived were followed up to October 2010. The median follow-up period was 7.3 months. Recurrence was observed in a total of 6 patients (10.72%), of whom 4 patients (33.33%) were from the non-NAs group, 2 (11.11%) from the LAM group after cessation LAM therapy by patients himself, and 0 from the ETV group (P = 0.003). Nucleoside analogue may improve the short-term and long-term prognosis of patients with HBV-related ACLF.

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References

  1. Stravitz RT, Kramer DJ (2009) Management of acute liver failure. Nat Rev Gastroenterol Hepatol 6:542–553

    Article  PubMed  Google Scholar 

  2. Sarin SK, Kumar A, Almeida JA, Chawla YK, Fan ST, Garg H, de Silva HJ, Hamid SS, Jalan R, Komolmit P, Lau GK, Liu Q, Madan K, Mohamed R, Ning Q, Rahman S, Rastogi A, Riordan SM, Sakhuja P, Samuel D, Shah S, Sharma BC, Sharma P, Takikawa Y, Thapa BR, Wai CT, Yuen MF (2009) Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hep Int 3:269–282

    Article  Google Scholar 

  3. [Anon], Liver EAS (2009) EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 50:227–242

    Google Scholar 

  4. Lok ASF, McMahon BJ (2009) Chronic hepatitis b: update 2009. Hepatology 50:661–662

    Article  PubMed  Google Scholar 

  5. Polson J, Lee WM (2005) AASLD position paper: the management of acute liver failure. Hepatology 41:1179–1197

    Article  PubMed  Google Scholar 

  6. Cui YL, Yan F, Wang YB, Song XQ, Liu L, Lei XZ, Zheng MH, Tang H, Feng P (2010) Nucleoside analogue can improve the long-term prognosis of patients with hepatitis B virus infection-associated acute on chronic liver failure. Dig Dis Sci 55:2373–2380

    Article  PubMed  CAS  Google Scholar 

  7. Chen J, Han JH, Liu C, Yu RH, Li FZ, Li QF, Gong GZ (2009) Short-term entecavir therapy of chronic severe hepatitis B. Hepatobiliary Pancreat Dis Int 8:261–266

    PubMed  CAS  Google Scholar 

  8. Biggins SW, Kim WR, Terrault NA, Saab S, Balan V, Schiano T, Benson J, Therneau T, Kremers W, Wiesner R, Kamath P, Klintmalm G (2006) Evidence-based incorporation of serum sodium concentration into MELD. Gastroenterology 130:1652–1660

    Article  PubMed  Google Scholar 

  9. Sun LJ, Yu JW, Zhao YH, Kang P, Li SC (2010) Influential factors of prognosis in lamivudine treatment for patients with acute-on-chronic hepatitis B liver failure. J Gastroenterol Hepatol 25:583–590

    Article  PubMed  CAS  Google Scholar 

  10. Hsu CY, Lin HC, Huang YH, Su CW, Lee FY, Huo TI, Lee PC, Lee JY, Lee SD (2010) Comparison of the model for end-stage liver disease (MELD), MELD-Na and MELDNa for outcome prediction in patients with acute decompensated hepatitis. Dig Liver Dis 42:137–142

    Article  PubMed  CAS  Google Scholar 

  11. Wong VWS, Wong GLH, Yiu KKL, Chim AML, Chu SHT, Chan HY, Sung JJY, Chan HLY (2011) Entecavir treatment in patients with severe acute exacerbation of chronic hepatitis B. J Hepatol 54:236–242

    Article  PubMed  CAS  Google Scholar 

  12. Zhang Z, Zou ZS, Fu JL, Cai L, Jin L, Liu YJ, Wang FS (2008) Severe dendritic cell perturbation is actively involved in the pathogenesis of acute-on-chronic hepatitis B liver failure. J Hepatol 49:396–406

    Article  PubMed  CAS  Google Scholar 

  13. Williams CD, Bajt ML, Farhood A, Jaeschke H (2010) Acetaminophen-induced hepatic neutrophil accumulation and inflammatory liver injury in CD18-deficient mice. Liver Int 30:1280–1292

    Article  PubMed  CAS  Google Scholar 

  14. Manizate F, Fiel MI, Schwartz ME, Labow DM, Roayaie S, Dieterich D, Luan W, Hiotis SP (2010) Intrahepatic Cccdna burden and severity of hepatic fibrosis in patients with Hbv-associated Hcc. J Hepatol 52:S220

    Google Scholar 

  15. Zoulim F, Locarnini S (2009) Hepatitis B virus resistance to nucleos(t)ide analogues. Gastroenterology 137:1593–1608

    Article  PubMed  CAS  Google Scholar 

  16. Vallet-Pichard A, Mallet V, Costentin CE, Pol S (2009) Treatment of HBV-related cirrhosis. Expert Rev Anti Infect Ther 7:527–535

    Article  PubMed  CAS  Google Scholar 

  17. Chan AC, Fan ST, Lo CM, Liu CL, Chan SC, Ng KK, Yong BH, Chiu A, Lam BK (2009) Liver transplantation for acute-on-chronic liver failure. Hep Int 3:571–581

    Article  Google Scholar 

  18. Chan PC, Chen HL, Kong MS, Huang FC, Lee HC, Lin CC, Liu CC, Lee IH, Wu TC, Wu SF, Ni YH, Hsu HY, Chang MH (2005) Factors affecting the mortality of pediatric fulminant hepatic failure in relation to hepatitis B virus infection. J Gastroenterol Hepatol 20:1223–1227

    Article  PubMed  Google Scholar 

  19. Schiff E, Simsek H, Lee WM, Chao YC, Sette H Jr, Janssen HL, Han SH, Goodman Z, Yang J, Brett-Smith H, Tamez R (2008) Efficacy and safety of entecavir in patients with chronic hepatitis B and advanced hepatic fibrosis or cirrhosis. Am J Gastroenterol 103:2776–2783

    Article  PubMed  CAS  Google Scholar 

  20. Ghany MG, Doo EC (2009) Antiviral resistance and hepatitis B therapy. Hepatology 49:S174–S184

    Article  PubMed  CAS  Google Scholar 

  21. Bartholomeusz A, Locarnini S (2006) Hepatitis B virus mutations associated with antiviral therapy. J Med Virol 78:S52–S55

    Article  PubMed  CAS  Google Scholar 

  22. Doo E, Liang TJ (2001) Molecular anatomy and pathophysiologic implications of drug resistance in hepatitis B virus infection. Gastroenterology 120:1000–1008

    Article  PubMed  CAS  Google Scholar 

  23. Barile M, Valenti D, Passarella S, Quagliariello E (1997) 3′-Azido-3′-deoxythymidine uptake into isolated rat liver mitochondria and impairment of ADP/ATP translocator. Biochem Pharmacol 53:913–920

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  25. Katoonizadeh A, Laleman W, Verslype C, Wilmer A, Maleux G, Roskams T, Nevens F (2010) Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study. Gut 59:1561–1569

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Major National Science and Technology Projects for Infectious Diseases (11th Five Year, China) (2008ZX10002-007) and the National Natural Science Fund of China (Project Number 30700712).

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Authors and Affiliations

  1. Department of Infectious Diseases, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi Province, China

    Tianyan Chen, Yingli He, Xiaojing Liu, Shuling Zhang & Yingren Zhao

  2. Hepatitis Institution, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi Province, China

    Zhi Yan, Ke Wang & Hongli Liu

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  1. Tianyan Chen
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  2. Yingli He
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  3. Xiaojing Liu
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  6. Hongli Liu
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  7. Shuling Zhang
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Correspondence to Yingli He or Yingren Zhao.

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Chen, T., He, Y., Liu, X. 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 12, 159–164 (2012). https://doi.org/10.1007/s10238-011-0160-7

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  • DOI: https://doi.org/10.1007/s10238-011-0160-7

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