Hepatitis B Prophylaxis after Liver Transplantation in Korea: Analysis of the KOTRY Database

Background Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population. Methods Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis. Results The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence. Conclusion Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.

[1]  G. Song,et al.  Determination of Hepatitis B Immunoglobulin Infusion Interval Using Pharmacokinetic Half-life Simulation for Posttransplant Hepatitis B Prophylaxis , 2019, Journal of Korean medical science.

[2]  H. Wang,et al.  A Multicenter Phase III Study to Evaluate the Efficacy and Safety of Hepabulin, a New Hepatitis B Immunoglobulin, in Liver Transplantation Recipients with Hepatitis B , 2017, Annals of transplantation.

[3]  M. Yuen,et al.  Long‐term outcomes of entecavir monotherapy for chronic hepatitis B after liver transplantation: Results up to 8 years , 2017, Hepatology.

[4]  K. Radhakrishnan,et al.  Short Course of Postoperative Hepatitis B Immunoglobulin Plus Antivirals Prevents Reinfection of Liver Transplant Recipients , 2017, Transplantation.

[5]  F. Nevens,et al.  Rational Basis for Optimizing Short and Long-term Hepatitis B Virus Prophylaxis Post Liver Transplantation: Role of Hepatitis B Immune Globulin , 2015, Transplantation.

[6]  G. Song,et al.  Correlation between risk of hepatitis B virus recurrence and tissue expression of covalently closed circular DNA in living donor liver transplant recipients treated with high-dose hepatitis B immunoglobulin. , 2014, Transplantation proceedings.

[7]  Xiaoshun He,et al.  Is Hepatitis B Immunoglobulin Necessary in Prophylaxis of Hepatitis B Recurrence after Liver Transplantation? A Meta-Analysis , 2014, PloS one.

[8]  H. Yim,et al.  KASL Clinical Practice Guidelines: Management of chronic hepatitis B , 2012, Clinical and molecular hepatology.

[9]  H. Lee,et al.  Posttransplantation prophylaxis with primary high‐dose hepatitis B immunoglobulin monotherapy and complementary preemptive antiviral add‐on , 2011, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[10]  W. Kim,et al.  High Viremia, Prolonged Lamivudine Therapy and Recurrent Hepatocellular Carcinoma Predict Posttransplant Hepatitis B Recurrence † , 2010, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[11]  Jörg Petersen,et al.  EASL Clinical Practice Guidelines: management of chronic hepatitis B. , 2009, Journal of hepatology.

[12]  G. Song,et al.  Prevention of hepatitis B recurrence after living donor liver transplantation: Primary high‐dose hepatitis B immunoglobulin monotherapy and rescue antiviral therapy , 2008, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[13]  D. Samuel,et al.  Management of the hepatitis B virus in the liver transplantation setting: A European and an American perspective , 2005, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[14]  S. Cotler,et al.  Management of hepatitis B in liver transplant patients. , 2005, Journal of clinical gastroenterology.

[15]  D. Samuel,et al.  Evolving strategies to prevent HBV recurrence , 2004, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[16]  T. Berg,et al.  Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high‐dose hepatitis B immune globulin after liver transplantation , 1998, Hepatology.

[17]  A. Lok,et al.  Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis , 1998, Hepatology.