A new scheme with infusion of hepatitis B immunoglobulin combined with entecavir for prophylaxis of hepatitis B virus recurrence among liver transplant recipients

Objective Liver transplantation significantly increases recurrence of hepatitis B virus (HBV) among high-risk patients. Hepatitis B immunoglobulin (HBIG) and antiviral nucleotide analogues are effective prophylaxis reagents in preventing HBV recurrence. However, HBV recurrence still occurs with these treatments. Methods To explore a more cost-effective prophylaxis protocol in patients after liver transplantation, we treated patients with an initial high dose of 10 000 IU HBIG during the anhepatic phase and a second high dose of HBIG at an optimal time point during surgery. The patients were treated with the traditional European protocol as a control, in which one dose of 10 000 IU HBIG was infused during the anhepatic phase and multiple doses of 10 000 IU HBIG were administered daily for 1 week after liver transplantation. Results There were two mortalities among 50 patients treated with the new protocol and nine mortalities among 52 patients treated with the European protocol within 3 years after liver transplantation. The new prophylaxis method markedly improved the 3-year survival without HBV recurrence in 50 treated patients. However, there were five recurrences in 52 patients treated with the European protocol. High-risk factors such as HBV DNA+, positive hepatitis B e antigen, and hepatocellular carcinoma were all detected among five patients with HBV recurrence. The suppressed HBV recurrence was associated with significantly lower serum alanine aminotransferase and aspartate aminotransferase in the new protocol-treated patients tested at 1 month and 1 week after liver surgery compared with those treated with the European protocol. Conclusion Infusion of two high doses of HBIG during surgery in combination with entecavir significantly prevented HBV recurrence and improved the 3-year survival after liver transplantation.

[1]  A. Takaki,et al.  Safe and cost-effective control of post-transplantation recurrence of hepatitis B , 2014, Hepatology research : the official journal of the Japan Society of Hepatology.

[2]  D. Samuel,et al.  Prevention of Hepatitis B Virus Reinfection in Liver Transplant Recipients , 2014, Intervirology.

[3]  Sheng-Nan Lu,et al.  Entecavir vs. lamivudine in chronic hepatitis B patients with severe acute exacerbation and hepatic decompensation. , 2014, Journal of hepatology.

[4]  Chao-Long Chen,et al.  Section 14. Combination of Entecavir Plus Low-Dose On-Demand Hepatitis B Immunoglobulin is Effective With Very Low Hepatitis B Recurrence After Liver Transplantation , 2014, Transplantation.

[5]  T. Cherian,et al.  Anti-HBs response to hepatitis B immunoglobulin prophylaxis in liver transplant recipients , 2014, Indian Journal of Gastroenterology.

[6]  Hanwei Li,et al.  A clinical‐pathological analysis of hepatitis B virus recurrence after liver transplantation in Chinese patients , 2014, Journal of gastroenterology and hepatology.

[7]  Ji‐yao Wang Clinical utility of entecavir for chronic hepatitis B in Chinese patients , 2013, Drug design, development and therapy.

[8]  S. Kim,et al.  Clinical outcomes and risk factors of hepatitis B virus recurrence in patients who received prophylaxis with entecavir and hepatitis B immunoglobulin following liver transplantation. , 2013, Transplantation proceedings.

[9]  B. van Hoek,et al.  Nucleoside plus nucleotide analogs and cessation of hepatitis B immunoglobulin after liver transplantation in chronic hepatitis B is safe and effective. , 2013, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[10]  J. Yang,et al.  Hepatitis B prophylaxis using lamivudine and individualized low-dose hepatitis B immunoglobulin in living donor liver transplantation. , 2013, Transplantation proceedings.

[11]  O. Shibolet,et al.  Immunosuppression and HBV Reactivation , 2013, Seminars in Liver Disease.

[12]  Jung-Hwan Yoon,et al.  Post-transplantation sequential entecavir monotherapy following 1-year combination therapy with hepatitis B immunoglobulin , 2013, Journal of Gastroenterology.

[13]  S. Kong,et al.  Outcome of Various Treatments for Posttransplant Hepatitis B Virus Recurrence , 2013, World Journal of Surgery.

[14]  A. Mehrabi,et al.  The role of HBIg as hepatitis B reinfection prophylaxis following liver transplantation , 2012, Langenbeck's Archives of Surgery.

[15]  M. Rizzetto,et al.  Lactic acidosis during Entecavir treatment in decompensated hepatitis B virus-related cirrhosis. , 2011, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[16]  C. Coffin,et al.  Hepatitis B immunoglobulin for prevention of hepatitis B virus infection and recurrence after liver transplantation , 2011, Expert review of clinical immunology.

[17]  H. Shiraha,et al.  Serum hepatitis B virus DNA before liver transplantation correlates with HBV reinfection rate even under successful low-dose hepatitis B immunoglobulin prophylaxis , 2011, Hepatology international.

[18]  Q. Xia,et al.  The role of entecavir in preventing hepatitis B recurrence after liver transplantation , 2009, Journal of digestive diseases.

[19]  P. Angus,et al.  Post-liver transplant hepatitis B prophylaxis: the role of oral nucleos(t)ide analogues , 2009, Current opinion in organ transplantation.

[20]  A. Marzano The prevention of viral recurrence in the long term. , 2009, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[21]  X. Teng,et al.  Prevalence of occult hepatitis B virus infection among hepatopathy patients and healthy people in China. , 2009, The Journal of infection.

[22]  Karen G. Smith,et al.  Hepatitis B immunoglobulin and Lamivudine improve hepatitis B-related outcomes after liver transplantation: meta-analysis. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[23]  J. Pascasio,et al.  Prevalence of hepatitis A and B markers and vaccine indication in cirrhotic patients evaluated for liver transplantation in Spain. , 2008, Transplantation proceedings.

[24]  M. Manns,et al.  HBsAg level at time of liver transplantation determines HBsAg decrease and anti-HBs increase and affects HBV DNA decrease during early immunoglobulin administration. , 2007, Journal of hepatology.

[25]  Jun Li,et al.  [Clinical characteristies and distribution of hepatitis B virus genotype and sub-genotype]. , 2007, Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi.

[26]  Guihua Chen,et al.  [Prevention and treatment of hepatitis B virus reinfection after liver transplantation]. , 2006, Zhonghua wai ke za zhi [Chinese journal of surgery].

[27]  J. Lee,et al.  Is lamivudine with 1-week HBlg as effective as long-term high-dose HBlg in HBV prophylaxis after liver transplantation? , 2002, Transplantation proceedings.