Prophylaxis against de novo hepatitis B for liver transplantation utilizing hep B core (+) donors: does hepatitis B immunoglobulin provide a survival advantage?

Abstract

Summary Donor liver allografts with positive serology for hepatitis B core antibody [HBc (+)] have been increasingly used for liver transplantation. However, the optimal prophylactic regimen to prevent development of de novo hepatitis B has not been determined. To evaluate this, we screened United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) registry data for adult recipients of HBc (+) organs who were HBsAg (−), and evaluated the effects of using prophylactic anti‐viral therapies (HBIG and lamivudine) on patient and graft survival. Out of a total cohort of 958 patients transplanted since 2004, 61 received HBIG alone, 116 received lamivudine alone, 66 both, 509 neither and 206 were missing this information. Based on several multivariable Cox regression models, patients receiving HBIG therapy‐only were observed to have a statistically significant (approximately 70%) reduction in risk of mortality compared with patients receiving lamivudine‐only therapy [HR = 0.29, 95% CI (0.10, 0.86), P = 0.026], and a nonstatistically significant reduction in risk of graft failure. However, no graft failures were attributed to de novo hepatitis B, suggesting that any improved graft/patient survival possibly associated with HBIG therapy occurs independently of de novo hepatitis B virus (HBV) reduction. While this study cannot prove that HBIG therapy is protective for graft and patient survival after liver transplantation, these findings do highlight the need to further examine and study prophylactic use in recipients of HBc (+) donors.

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

“…Brock et al [94] HBc+/HBsAg-(n = 958) HBIg alone: n = 61 70% reduction in risk of mortality by HBIg prophylaxis; HBIg + Lam: n = 66…”

“…However, sample size was rather small and analysis was mixed up with data of other subpopulations [102] . Brock et al [94] have specifically addressed this issue in 958 HBsAg-negative liver recipients who received HBc+ liver allografts. Evaluating the UNOS STAR registry data n = 116 Significant reduction (P < 0.05) of acute and chronic rejection rate (1.7%) compared to other indications like PBC (6.1%), PSC (13%), AIC (17%), and HCV (9.2%), without increased risk of bacterial infection; significantly lower risk (P < 0.05) of death or retransplantation from rejection or either sepsis or de novo malignancy (3.5%) compared to patients with alcoholic cirrhosis (19%) Couto et al [81] n = 12…”

“…No allograft failures in this series were attributed to de novo hepatitis B infection. Therefore, the authors drew the conclusion that patient and graft survival benefits were rather resulting from anti-inflammatory and immunomodulatory properties than from antiviral efficacies of HBIg treatment [94] . To further expand the available donor pool, the focus recently shifted towards a greater use of HBsAg-positive liver grafts from donors with overt HBV infection, but with normal graft morphology and liver function.…”

“…In the absence of antiviral prophylaxis, incidences of viral reactivation up to 13% [85][86][87] and de novo HBV infection rates up to 100% [88][89][90][91][92][93][94][95] have been reported. There is currently no standard recommendation for antiviral prophylaxis in this special transplant matching, mainly since well designed studies are lacking.…”

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]…”