Liver transplantation with allografts from hepatitis B core antibody-positive donors: A new approach

Abstract

The enduring shortfall of organ donors has inspired the widespread utilization of hepatic allografts from donors with hepatitis B core antibodies in spite of the potential risk of transmitting hepatitis B virus (HBV) infection to the recipient. Here we report a protocol of naive recipients receiving livers from hepatitis B core antibody-positive donors. From November, 1999 to March, 2002, 77 liver transplantations were performed in 73 patients at our institution, 7 of whom received livers from hepatitis B core antibody-positive donors. All recipients received 10,000 U/d of intravenous HBIg for 7 days and 100 mg /d of lamivudine until we could obtain the HBV-DNA from the donor samples (serum and liver tissue). If the results of the HBV-DNA from the donor samples were positive, the patient would continue with prophylaxis and if they were negative we would finish the combined prophylaxis. After transplantation, HBV serologic markers and HBV-DNA by polymerase chain reaction (PCR) in serum and lymphocytes were tested in the recipients on the seventh, fifteenth, thirtieth, and ninetieth days as well as every 3 months after transplantation. All seven donor organs were negative for HBV-DNA in serum and liver tissue. Thus, we stopped the combined prophylaxis in all recipients (range, 7 to 10 days). None of the 7 patients developed de novo HBV infection over the 3-year study period (range, 9 to 36 months). Our approach is reasonably safe, and it appears to be very effective in the prevention of de novo HBV infection after liver transplantation. (Liver Transpl 2003;9:916-920.) D e novo hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) has been reported in recipients negative for hepatitis B surface antigen (HBsAg) from hepatitis B core antibody (anti-HBc)-positive donors. Several studies have reported a 16.6% to 95% increased incidence for HBV infection in these patients. 1-12 As a result, many centers do not use antiHBc-positive donors for recipients without previous HBV infection. 11 These results were derived mostly from studies performed in geographic regions with a low prevalence (3% to 5%) of anti-HBc-positive liver donors. However, in a recent study, anti-HBc positivity was found in 10% of the Spanish adults in the 26 to 65 age range and in 27% of donors older than 60. 2 For this reason, the prevalence of anti-HBc positivity in Spanish liver donors and, thus, the incidence of de novo HBV infection after liver transplantation would be greater in our area than in areas of lower prevalence.In an attempt to prevent transmission of HBV infection to recipients from donors positive for anti-HBc, polyclonal hepatitis B immunoglobulin (HBIg) has been administered to the recipients almost universally. Many centers use HBIg either continuously or for an indefinite amount of time, usually 2 or more years after OLT. 10 Recent studies have suggested that lamivudine, a nucleoside analog that inhibits HBV replication, can be used in addition to or as an alternative to HBIg in such cases. [13][14][15] However, thi...

Current use of hepatitis B immune globulin for prevention of de novo hepatitis B in recipients receiving anti-HBc-positive livers

“…With HBIG monotherapy prophylaxis, DNH occurred from 11.1 to 100% in naïve recipients (Table 3) [18,20,21,24,27,29,33,34,36,38,39,41,44]. Overall, HBIG monotherapy decreases DNH occurrence rate from 65.2 to 28% in this high-risk population.…”

“…Furthermore, prophylactic protocols may vary even within a center based on donor and recipient HBV serologic status. Table 2 summarizes published prophylactic protocols involving HBIG use at different transplant programs [15,18,20,21,24,26,27,29,[33][34][35][36][37][38][39][40][41][42][43]. There are a number of important questions that remain to be answered regarding prevention of DNH in anti-HBc-positive donor LT. We will address the following four questions.…”

“…Both articles suggest HBIG 10,000 IU IV during anhepatic phase and then daily 9 7 days, followed by HBIG 10,000 IU IV monthly 9 6 months, then HBIG 1,000 IU IM every 2 weeks 9 18 months plus LAM 150 mg daily lifelong Loss [35] HBIG 10,000 IU IV during anhepatic phase plus LAM 150 mg daily lifelong* Manzarbeitia [21] HBIG 10,000 IU IV monthly 9 6 months to maintain anti-HBs [100 IU/L Roque-Afonso [20] HBIG 5,000 IU IV daily 9 7 days, followed by booster to maintain anti-HBs [100 IU/L Holt [36] HBIG 10,000 IU IV daily 9 7 days plus LAM 150 mg b.i.d. 9 2 years Chang [37] HBIG 100 IU/Kg IV intraoperatively and then daily 9 3 days, followed by booster to maintain anti-HBs [20 IU/L plus vaccination based on anti-HBs titer Fabrega [38] HBIG 10,000 IU IV during anhepatic phase and then daily 9 7 days plus LAM 100 mg daily ¥ Nery [29] HBIG 10,000 IU IV intraoperatively and then daily 9 7 days, weekly 9 1 month, and monthly 9 6 months and/or LAM 150 mg daily lifelong } Lee [15] HBIG (100 IU/Kg for children and 10,000 IU for adults) IV daily 9 7 days, followed by booster to maintain antiHBs [ 200 IU/L Suehiro [39] HBIG 10,000 IU IV during anhepatic phase and then 2,000 IU IV daily 9 7 days, followed by 2,000 IU IV every 2 months to maintain anti-HBs [ 100 IU/L plus LAM 100 mg daily Donataccio [24] HBIG 10,000 IU IV during anhepatic phase and then daily that current available studies do not support prophylactic use of the combination therapy over LAM monotherapy in HBV DNA negative patients receiving anti-HBcpositive liver grafts. LAM monotherapy has the same efficacy as the combination therapy at far less cost [47,48].…”

Controversies Regarding the Hepatitis B Immune Globulin Prophylaxis (HBIG) for Liver Transplantation Recipients

“…Angus/2008 [32] Avolio/2008 [106] Angus/2000 [51] Anselmo/2002 [33] Anderson/2007 [107] Alonso/2003 [108] Brock/2011 [109] Buti/2003 [110] Ben-Ari/2004 [111] Chun/2010 [112] Dadson/2000 [113] Dehghani/2013 [114] Dickson/2006 [59] Dumortier/2003 [115] Degertekin/2010 [116] Di Paolo/2004 [117] Faust/2003 [118] Freshwater/2008 [99] Fabrega/2003 [119] Feretti/2004 [120] Filipponi/2010 [121] Gane/2013 [55] Han/2000 [35] Han/2003 [122] Honaker/2002 [123] Iacob/2008 [124] Jiang/2010 [125] Jain/2005 [126] Jiao/2007 [127] Karademir/2006 [128] Kwon/2006 [129] Lee/2000 [130] Lee/2004 [131] Lu/2004 [85] Lu/2008 [39] Loss/2003 [132]…”

Donor Safety in Live-Related Liver Transplantation

“…Recipients of grafts from such donors may require lifelong lamivudine treatment [20]. However, there are suggestions that recipients with hepatitis B surface antibody positivity and donors with hepatitis B DNA negativity may have their lamivudine terminated after transplant [21].…”