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Liver grafts from anti-hepatitis B core positive donors: A systematic review

Open AccessPublished:November 19, 2009DOI:https://doi.org/10.1016/j.jhep.2009.11.009

      Background & Aims

      Although hepatitis B virus (HBV) transmission after liver transplantation of grafts from HBsAg-negative, anti-HBc positive donors is well established, the growing organ shortage favours the use of such marginal grafts. We systematically evaluated the risk of HBV infection after liver transplantation with such grafts and the effect of anti-HBV prophylaxis.

      Methods

      We performed a literature review over the last 15 years identifying 39 studies including 903 recipients of anti-HBc positive liver grafts.

      Results

      Recurrent HBV infection developed in 11% of HBsAg-positive liver transplant recipients of anti-HBc positive grafts, while survival was similar (67–100%) to HBsAg-positive recipients of anti-HBc negative grafts. De novo HBV infection developed in 19% of HBsAg-negative recipients being less frequent in anti-HBc/anti-HBs positive than HBV naive cases without prophylaxis (15% vs 48%, p < 0.001). Anti-HBV prophylaxis reduced de novo infection rates in both anti-HBc/anti-HBs positive (3%) and HBV naive recipients (12%). De novo infection rates were 19%, 2.6% and 2.8% in HBsAg-negative recipients under hepatitis B immunoglobulin, lamivudine and their combination, respectively.

      Conclusions

      Liver grafts from anti-HBc positive donors can be safely used, preferentially in HBsAg-positive or anti-HBc/anti-HBs positive recipients. HBsAg-negative recipients should receive prophylaxis with lamivudine, while both anti-HBc and anti-HBs positive recipients may need no prophylaxis at all.

      Abbreviations:

      HBV (hepatitis B virus), LT (liver transplantation), anti-HBc (HBV core antigen), HBsAg (hepatitis B surface antigen), cccDNA (covalently closed circular DNA), HBIG (hepatitis B immunoglobulin), LAM (lamivudine)

      Keywords

      Introduction

      Despite the recent advances in liver transplantation (LT), there is a growing gap between the availability of donors and recipients on the waiting list. One of the current efforts to overcome the organ shortage is based on the use of grafts that are from donors with antibodies against the HBV core antigen (anti-HBc), but hepatitis B surface antigen (HBsAg) negative; the so called “anti-HBc positive donors” [
      • Nadig S.N.
      • Bratton C.F.
      • Karp S.J.
      Marginal donors in liver transplantation: expanding the donor pool.
      ]. These grafts are rather common in countries with high or even intermediate prevalence of HBV infection, such as Asia and the Mediterranean basin. However, anti-HBc positive liver donors frequently have occult HBV infection, i.e. persistent liver and/or serum HBV DNA without serologic evidence of active HBV infection (negative HBsAg with or without positive anti-HBs). Indeed, several studies in HBsAg-negative subjects have shown that there is often the detection in the liver of covalently closed circular DNA (cccDNA) and pregenomic RNA, which is a marker of ongoing viral replication [
      • Marusawa H.
      • Uemoto S.
      • Hijikata M.
      • Ueda Y.
      • Tanaka K.
      • Shimotohno K.
      • et al.
      Latent hepatitis B virus infection in healthy individuals with antibodies to hepatitis B core antigen.
      ,
      • Mason A.
      • Xu L.
      • Guo L.
      • Kuhns M.
      • Perrillo R.
      Molecular basis for persistent hepatitis B virus infection in the liver after clearance of serum hepatitis B surface antigen.
      ], and that may significantly increase with the use of post-LT immunosuppression and in particular with corticosteroids [
      • Scullard G.
      • Smith C.
      • Merigan T.
      • Robinson W.
      • Gregory P.
      Effects of immunosuppressive therapy on viral markers in chronic active hepatitis B.
      ]. The liver grafts from anti-HBc positive donors are currently the main sources of de novo HBV infection after LT [
      • Rokuhara A.
      • Tanaka E.
      • Yagi S.
      • Mizokami M.
      • Hasshikura Y.
      • Kawasaki S.
      • et al.
      De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome.
      ,
      • Jilg W.
      • Sieger E.
      • Zachoval R.
      • Schatzl H.
      Individuals with antibodies against hepatitis B core antigen as the only serological marker for hepatitis B infection: high percentage of carriers of hepatitis B and C virus.
      ], which is usually defined by the development of positive HBsAg and/or detectable serum or liver HBV DNA in previously HBsAg recipients or even development of positive anti-HBc in previously HBV naive recipients. However, the literature documenting the risk of de novo HBV infection and the effects on the graft is scanty and conflicting.
      The lack of definite data explains the wide variation in current clinical practice. In a survey in the USA in 2001, almost half of liver transplant physicians reported that they did not use anti-HBc positive donors in HBV naive recipients [
      • Burton J.
      • Shaw-Stiffel T.
      Use of hepatitis B core antibody positive donors in recipients without evidence of hepatitis B infection: a survey of current practice in the United States.
      ]. In a more recent international survey, the responders documented using prophylaxis with a nucleos(t)ide analogue (mostly lamivudine, but also entecavir and adefovir) in the majority of LT recipients of anti-HBc positive grafts, and 61% also used hepatitis B immunoglobulin (HBIG) (69% in US and 46% in non-US centres, p=0.03) [
      • Perrillo R.
      Hepatitis B virus prevention strategies for antibody to hepatitis B core antigen-positive liver donation: a survey of North American, European, and Asian-Pacific transplant programs.
      ].
      In this review, we systematically evaluated all the available data in order to quantify the impact of using liver grafts from anti-HBc positive donors and identify the optimal post-LT prophylaxis. We selected two types of recipients: (a) HBsAg-positive recipients and (b) HBsAg-negative recipients. In particular, we documented the rates of de novo HBV infection with or without anti-HBV prophylaxis relative to the donor–recipient HBV serological status, as well as data on the outcome of de novo post-LT HBV infection. Our search was based on Medline/PubMed from January 1994 to December 2008 using the search terms “hepatitis B core antibody” and “liver transplantation”, in papers published in English. We also conducted a manual search of the reference lists in the review articles. In total, 133 articles were identified. Two authors (E.C., G.V.P.) reviewed the abstracts of these articles to identify potentially relevant articles. In total, 39 original articles evaluated the rate of de novo HBV infection from anti-HBc positive donors, were included in the final analysis. Data abstraction was done by one author (E.C.) and any conflicts in data abstraction were arbitrated by discussion with the senior authors (G.V.P., A.K.B.).

      Prevalence of anti-HBc positive liver donors

      The rate of anti-HBc positivity in liver donors varies substantially in different countries reflecting the local prevalence of HBV infection. Thus, the prevalence of anti-HBc is lower in developed countries ranging from 3% to 15% [
      • Dickson R.C.
      • Everhart J.E.
      • Lake J.R.
      • Wei Y.
      • Seaberg E.C.
      • Wiesner R.H.
      • et al.
      Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.
      ,
      • Prieto M.
      • Gomez M.D.
      • Berenguer M.
      • Cordoba J.
      • Rayon J.M.
      • Pastor M.
      • et al.
      De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population.
      ,
      • Manzarbeitia C.
      • Reich D.J.
      • Ortiz J.A.
      • Rothstein K.D.
      • Araya V.R.
      • Munoz S.J.
      Safe use of livers from donors with positive hepatitis B core antibody.
      ,
      • Douglas D.
      • Rakela J.
      • Wright T.
      • Krom R.A.
      • Wiesner R.H.
      The clinical course of transplantation-associated de novo hepatitis B infection in the liver transplant recipient.
      ,
      • Shinji U.
      • Kohachiro S.
      • Hiroyuki M.
      • Yukihiro I.
      • Katsuhiro A.
      • Hiroto E.
      • et al.
      Transmission of hepatitis B virus from hepatitis B core antibody-positive donors in living related liver transplants.
      ], but it may exceed 50% in highly endemic areas [
      • Lee K.
      • Wai C.
      • Lim S.
      • Manjit K.
      • Lee H.L.
      • Da Costa M.
      • et al.
      Risk for de novo hepatitis B from antibody to hepatitis B core antigen-positive donors in liver transplantation in Singapore.
      ,
      • Lo C.
      • Fan S.
      • Liu C.
      • Yong B.H.
      • Wong Y.
      • Ng I.O.
      • et al.
      Safety and outcome of hepatitis B core antibody-positive donors in right-lobe living donor liver transplantation.
      ,
      • Chen Y.S.
      • Wang C.C.
      • deVilla V.H.
      • Wang S.H.
      • Cheng Y.F.
      • Huang T.L.
      • et al.
      Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors.
      ] (Table 1). The prevalence of anti-HBc may also vary in different areas of the same country and in specific ethnic populations (e.g. it is estimated that 25% of non-Hispanic black Americans in the USA are anti-HBc positive) [
      • McQuillan G.
      • Coleman P.
      • Kruszon-Moran D.
      • Moyer L.
      • Lambert S.
      • Margolis H.
      Prevalence of hepatitis B virus infection in the United States: The National Health and Nutrition Examination Survey, 1976 through 1994.
      ], and it is usually higher in older age individuals, who are currently increasingly used as liver donors [
      • Prieto M.
      • Gomez M.D.
      • Berenguer M.
      • Cordoba J.
      • Rayon J.M.
      • Pastor M.
      • et al.
      De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population.
      ]. The latter could partly explain the increasing number of anti-HBc positive cadaveric livers transplanted in the USA (from 3.9% in 1998 to 4.9% in 2002) [
      • Fontana R.J.
      • Merion R.M.
      Are we ready for marginal hepatitis B core antibody-positive living liver donors?.
      ].
      Table 1Published studies on the prevalence of anti-HBc positivity among liver donors in different countries.
      First author, year [Ref.]Donors, n/N anti-HBc
      CountryPositive/totalPrevalence (%)
      Wachs (1995)
      • Wachs M.E.
      • Amend W.J.
      • Ascher N.L.
      • Bretan P.N.
      • Emond J.
      • Lake J.R.
      • et al.
      The risk of transmission of hepatitis B from HBsAg(−), HBcAb(+), HBIgM(−) organ donors.
      USA25/11902
      Douglas (1997)
      • Douglas D.
      • Rakela J.
      • Wright T.
      • Krom R.A.
      • Wiesner R.H.
      The clinical course of transplantation-associated de novo hepatitis B infection in the liver transplant recipient.
      USA3/3323
      Dodson (1997)
      • Dodson S.F.
      • Issa S.
      • Araya V.
      • Gayowski T.
      • Pinna A.
      • Eghtesad B.
      • et al.
      Infectivity of hepatic allografts with antibodies to hepatitis B virus.
      USA70/25783
      Shinji (1998)
      • Shinji U.
      • Kohachiro S.
      • Hiroyuki M.
      • Yukihiro I.
      • Katsuhiro A.
      • Hiroto E.
      • et al.
      Transmission of hepatitis B virus from hepatitis B core antibody-positive donors in living related liver transplants.
      Japan16/1719
      Yu (2001)
      • Yu A.S.
      • Vierling J.M.
      • Colquhoun S.D.
      • Arnaout W.S.
      • Chan C.K.
      • Khanafshar E.
      • et al.
      Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy.
      USA15/1699
      Nery (2001)
      • Nery J.R.
      • Gedaly R.
      • Vianna R.
      • Berho M.
      • Weppler D.
      • Levi D.M.
      • et al.
      Are liver grafts from hepatitis B surface antigen negative/anti-hepatitis B core antibody positive donors suitable for transplantation?.
      USA48/7246
      Prieto (2001)
      • Prieto M.
      • Gomez M.D.
      • Berenguer M.
      • Cordoba J.
      • Rayon J.M.
      • Pastor M.
      • et al.
      De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population.
      Spain33/26812
      Lee (2001)
      • Lee K.
      • Wai C.
      • Lim S.
      • Manjit K.
      • Lee H.L.
      • Da Costa M.
      • et al.
      Risk for de novo hepatitis B from antibody to hepatitis B core antigen-positive donors in liver transplantation in Singapore.
      China16/3053
      Roque-Alfonso (2002)
      • Roque-Afonso A.M.
      • Feray C.
      • Samuel D.
      • Simoneau D.
      • Roche B.
      • Emile J.F.
      • et al.
      Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.
      France22/3157
      Chen (2002)
      • Chen Y.S.
      • Wang C.C.
      • deVilla V.H.
      • Wang S.H.
      • Cheng Y.F.
      • Huang T.L.
      • et al.
      Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors.
      Taiwan24/4257
      Lo (2003)
      • Lo C.
      • Fan S.
      • Liu C.
      • Yong B.H.
      • Wong Y.
      • Ng I.O.
      • et al.
      Safety and outcome of hepatitis B core antibody-positive donors in right-lobe living donor liver transplantation.
      China28/5155

      Liver grafts from anti-HBc positive donors to HBsAg-positive recipients

      Nine studies [
      • Manzarbeitia C.
      • Reich D.J.
      • Ortiz J.A.
      • Rothstein K.D.
      • Araya V.R.
      • Munoz S.J.
      Safe use of livers from donors with positive hepatitis B core antibody.
      ,
      • Yu A.S.
      • Vierling J.M.
      • Colquhoun S.D.
      • Arnaout W.S.
      • Chan C.K.
      • Khanafshar E.
      • et al.
      Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy.
      ,
      • Joya-Vazquez F.S.
      • Dodson F.S.
      • Dvorchik I.
      • Gray E.
      • Chesky A.
      • Demetris A.J.
      • et al.
      Impact of anti-hepatitis Bc-positive grafts on the outcome of liver transplantation for HBV-related cirrhosis.
      ,
      • Roque-Afonso A.M.
      • Feray C.
      • Samuel D.
      • Simoneau D.
      • Roche B.
      • Emile J.F.
      • et al.
      Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.
      ,
      • Nery J.R.
      • Nery-Avila C.
      • Reddy K.R.
      • Cirocco R.
      • Weppler D.
      • Levi D.M.
      • et al.
      Use of liver grafts from donors positive for anti-hepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.
      ,
      • Montalti R.
      • Nardo B.
      • Bertelli R.
      • Beltempo P.
      • Puviani L.
      • Vivarelli M.
      • et al.
      Donor pool expansion in liver transplantation.
      ,
      • Donataccio D.
      • Roggen F.
      • De Reyck C.
      • Verbaandert C.
      • Bodeus M.
      • Lerut J.
      Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool.
      ,
      • Prakoso E.
      • Strasser S.I.
      • Koorey D.J.
      • Verran D.
      • McCaughan G.W.
      Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.
      ,
      • Celebi Kodak A.
      • Karasu Z.
      • Kilic M.
      • Ozacar T.
      • Tekin F.
      • Gunsar F.
      • et al.
      Living donor liver transplantation from hepatitis B core antibody positive donors.
      ] evaluated the recurrence of HBV infection in HBsAg-positive recipients of anti-HBc positive liver grafts (Table 2). During a median follow-up of 27 (19–42) months, post-transplant HBV infection was observed in 12 (10.5%) of 115 recipients, while median survival ranged from 67% to 100%. In the 12 cases with post-transplant HBV infection, the prophylaxis was: three with HBIG, three with lamivudine and six with HBIG and lamivudine (HBIG had been discontinued in one at HBV recurrence). In one retrospective cohort study [
      • Joya-Vazquez F.S.
      • Dodson F.S.
      • Dvorchik I.
      • Gray E.
      • Chesky A.
      • Demetris A.J.
      • et al.
      Impact of anti-hepatitis Bc-positive grafts on the outcome of liver transplantation for HBV-related cirrhosis.
      ], recipients of anti-HBc positive grafts (n = 14.5 with detectable serum HBV DNA at LT) were compared to recipients of anti-HBc negative grafts (n = 65). The 14 recipients of anti-HBc positive grafts developed HBV recurrence more frequently (69.2% vs 35.7%, p= 0.034) and earlier after LT (2.9 vs 6.4 years, p< 0.005). However, the patient and graft survival was not different between the two groups: 60-month survival: 67% vs 68%. In multivariate analysis, HBV recurrence was independently associated with anti-HBc donor status (RR: 2.796, p=0.02) and the use of combined HBIG and lamivudine prophylaxis (RR: 0.249, p=0.021), but not the recipients’ pre-transplant HBeAg status [
      • Joya-Vazquez F.S.
      • Dodson F.S.
      • Dvorchik I.
      • Gray E.
      • Chesky A.
      • Demetris A.J.
      • et al.
      Impact of anti-hepatitis Bc-positive grafts on the outcome of liver transplantation for HBV-related cirrhosis.
      ].
      Table 2Published studies of liver transplantation using anti-HBc positive donors in HBsAg-positive recipients.
      First author, year [Ref.]HBsAg positiveFollow-up (months)HBV recurrence, n (%)Survival (%)
      Recipients, nAnti-HBV prophylaxis
      Yu (2001)
      • Yu A.S.
      • Vierling J.M.
      • Colquhoun S.D.
      • Arnaout W.S.
      • Chan C.K.
      • Khanafshar E.
      • et al.
      Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy.
      6HBIG200100
      Manzabeita (2002)
      • Manzarbeitia C.
      • Reich D.J.
      • Ortiz J.A.
      • Rothstein K.D.
      • Araya V.R.
      • Munoz S.J.
      Safe use of livers from donors with positive hepatitis B core antibody.
      3HBIG + LAM261 (33)67
      Joya-Varquez (2002)
      • Joya-Vazquez F.S.
      • Dodson F.S.
      • Dvorchik I.
      • Gray E.
      • Chesky A.
      • Demetris A.J.
      • et al.
      Impact of anti-hepatitis Bc-positive grafts on the outcome of liver transplantation for HBV-related cirrhosis.
      14HBIG: 5, LAM: 3, HBIG + LAM: 5429
      2/5 patients under HBIG, 3/3 patients under LAM and 4/5 patients under HBIG+LAM.
      (69)
      Roque-Afonso (2002)
      • Roque-Afonso A.M.
      • Feray C.
      • Samuel D.
      • Simoneau D.
      • Roche B.
      • Emile J.F.
      • et al.
      Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.
      4HBIG19075
      Nery (2003)
      • Nery J.R.
      • Nery-Avila C.
      • Reddy K.R.
      • Cirocco R.
      • Weppler D.
      • Levi D.M.
      • et al.
      Use of liver grafts from donors positive for anti-hepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.
      17LAM: 12, HBIG + LAM: 5290
      Montalti (2004)
      • Montalti R.
      • Nardo B.
      • Bertelli R.
      • Beltempo P.
      • Puviani L.
      • Vivarelli M.
      • et al.
      Donor pool expansion in liver transplantation.
      26HBIG ± LAMNA0
      Donataccio (2006)
      • Donataccio D.
      • Roggen F.
      • De Reyck C.
      • Verbaandert C.
      • Bodeus M.
      • Lerut J.
      Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool.
      4HBIG: 3, HBIG + LAM: 1381
      1/3 patients under HBIG.
      (25)
      100
      Pracoso (2006)
      • Prakoso E.
      • Strasser S.I.
      • Koorey D.J.
      • Verran D.
      • McCaughan G.W.
      Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.
      5HBIG + LAM29067
      Celebi-Kobak (2007)
      • Celebi Kodak A.
      • Karasu Z.
      • Kilic M.
      • Ozacar T.
      • Tekin F.
      • Gunsar F.
      • et al.
      Living donor liver transplantation from hepatitis B core antibody positive donors.
      36HBIG + LAM191 (3)92
      HBIG, hepatitis B immunoglobulin; LAM, lamivudine; NA, not available.
      a 2/5 patients under HBIG, 3/3 patients under LAM and 4/5 patients under HBIG + LAM.
      b 1/3 patients under HBIG.

      Liver grafts from anti-HBc positive donors to HBsAg-negative recipients–risk of de novo HBV infection

      We identified 38 relevant studies published as full papers [
      • Rokuhara A.
      • Tanaka E.
      • Yagi S.
      • Mizokami M.
      • Hasshikura Y.
      • Kawasaki S.
      • et al.
      De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome.
      ,
      • Dickson R.C.
      • Everhart J.E.
      • Lake J.R.
      • Wei Y.
      • Seaberg E.C.
      • Wiesner R.H.
      • et al.
      Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.
      ,
      • Prieto M.
      • Gomez M.D.
      • Berenguer M.
      • Cordoba J.
      • Rayon J.M.
      • Pastor M.
      • et al.
      De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population.
      ,
      • Manzarbeitia C.
      • Reich D.J.
      • Ortiz J.A.
      • Rothstein K.D.
      • Araya V.R.
      • Munoz S.J.
      Safe use of livers from donors with positive hepatitis B core antibody.
      ,
      • Douglas D.
      • Rakela J.
      • Wright T.
      • Krom R.A.
      • Wiesner R.H.
      The clinical course of transplantation-associated de novo hepatitis B infection in the liver transplant recipient.
      ,
      • Shinji U.
      • Kohachiro S.
      • Hiroyuki M.
      • Yukihiro I.
      • Katsuhiro A.
      • Hiroto E.
      • et al.
      Transmission of hepatitis B virus from hepatitis B core antibody-positive donors in living related liver transplants.
      ,
      • Chen Y.S.
      • Wang C.C.
      • deVilla V.H.
      • Wang S.H.
      • Cheng Y.F.
      • Huang T.L.
      • et al.
      Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors.
      ,
      • Yu A.S.
      • Vierling J.M.
      • Colquhoun S.D.
      • Arnaout W.S.
      • Chan C.K.
      • Khanafshar E.
      • et al.
      Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy.
      ,
      • Roque-Afonso A.M.
      • Feray C.
      • Samuel D.
      • Simoneau D.
      • Roche B.
      • Emile J.F.
      • et al.
      Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.
      ,
      • Nery J.R.
      • Nery-Avila C.
      • Reddy K.R.
      • Cirocco R.
      • Weppler D.
      • Levi D.M.
      • et al.
      Use of liver grafts from donors positive for anti-hepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.
      ,
      • Montalti R.
      • Nardo B.
      • Bertelli R.
      • Beltempo P.
      • Puviani L.
      • Vivarelli M.
      • et al.
      Donor pool expansion in liver transplantation.
      ,
      • Donataccio D.
      • Roggen F.
      • De Reyck C.
      • Verbaandert C.
      • Bodeus M.
      • Lerut J.
      Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool.
      ,
      • Prakoso E.
      • Strasser S.I.
      • Koorey D.J.
      • Verran D.
      • McCaughan G.W.
      Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.
      ,
      • Celebi Kodak A.
      • Karasu Z.
      • Kilic M.
      • Ozacar T.
      • Tekin F.
      • Gunsar F.
      • et al.
      Living donor liver transplantation from hepatitis B core antibody positive donors.
      ,
      • De Feo T.
      • Poli F.
      • Mozzi F.
      • Moretti M.P.
      • Scalamogna M.
      Collaborative Kidney Liver and Heart North Italy Transplant Program Study Groups
      Risk of transmission of hepatitis B virus from anti-HBC positive cadaveric organ donors: a collaborative study.
      ,
      • Suehiro T.
      • Shimada M.
      • Kishikawa K.
      • Shimura T.
      • Soejima Y.
      • Yoshizumi T.
      • et al.
      Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.
      ,
      • Dodson S.F.
      • Issa S.
      • Araya V.
      • Gayowski T.
      • Pinna A.
      • Eghtesad B.
      • et al.
      Infectivity of hepatic allografts with antibodies to hepatitis B virus.
      ,
      • Crespo J.
      • Fabrega E.
      • Casafont F.
      • Rivero M.
      • Heras G.
      • de la Pepa J.
      • et al.
      Severe clinical course of de novo hepatitis B infection after liver transplantation.
      ,
      • Holt C.D.
      • Thomas R.
      • van Thiel D.H.
      • Brems J.J.
      Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation.
      ,
      • Loss Jr., G.
      • Mason A.
      • Nair S.
      • Blazek J.
      • Farr G.
      • Guo L.
      • et al.
      Does lamivudine prophylaxis eradicate persistent HBV DNA from allografts derived from anti-HBc-positive donors?.
      ,
      • Takemura N.
      • Sugawara Y.
      • Tamura S.
      • Makuuchi M.
      Liver transplantation using hepatitis B core antibody-positive grafts: review and university of Tokyo experience.
      ,
      • Fabrega E.
      • Garcia-Suarez C.
      • Guerra A.
      • Orive A.
      • Casafont F.
      • Crespo J.
      • et al.
      Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach.
      ,
      • Dodson F.
      • Bonham C.
      • Geller D.
      • Cacciarelli T.V.
      • Rakela J.
      • Fung J.J.
      Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti-HBc positive donors.
      ,
      • Barcena R.
      • Moraleda G.
      • Moreno J.
      • Dolore Martin M.
      • de Vicente E.
      • Nupo J.
      • et al.
      Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers.
      ,
      • Barcena Marugan R.
      • Garcia-Hoz F.
      • Vazquez Romero M.
      • Nash R.
      • Mateos M.
      • Gonzalez Alonso R.
      • et al.
      Prevention of de novo hepatitis B infection in liver allograft recipients with previous hepatitis B infection or hepatitis B vaccination.
      ,
      • Villamil I.
      • Gonzalez-Quintela A.
      • Aquilera A.
      • Tome S.
      • Otero E.
      • Castroagudin F.J.
      • et al.
      Truly de novo HBV infection after liver transplantation.
      ,
      • Castells L.
      • Vargas V.
      • Rodrygez F.
      • Allende H.
      • Jardy R.
      • Margarit C.
      • et al.
      Transmission of hepatitis B virus by transplantation of livers from donors positive for antibody to hepatitis B core antigen.
      ,
      • Nery J.R.
      • Gedaly R.
      • Vianna R.
      • Berho M.
      • Weppler D.
      • Levi D.M.
      • et al.
      Are liver grafts from hepatitis B surface antigen negative/anti-hepatitis B core antibody positive donors suitable for transplantation?.
      ,
      • Chazouilleres O.
      • Mamish D.
      • Kim M.
      • Carey K.
      • Ferrell L.
      • Roberts J.
      • et al.
      “Occult” hepatitis B virus as source of infection in liver transplant recipients.
      ,
      • Wachs M.E.
      • Amend W.J.
      • Ascher N.L.
      • Bretan P.N.
      • Emond J.
      • Lake J.R.
      • et al.
      The risk of transmission of hepatitis B from HBsAg(−), HBcAb(+), HBIgM(−) organ donors.
      ,
      • Jain A.
      • Orloff M.
      • Abt P.
      • Kashyap R.
      • Mohanka R.
      • Lansing K.
      • et al.
      Use of hepatitis B core antibody positive liver allograft in hepatitis C virus-positive and -negative recipients with use of short course of hepatitis B immunoglobulin and lamivudine.
      ,
      • Lin C.C.
      • Chen C.L.
      • Concejero A.
      • Wang C.C.
      • Wang S.H.
      • Liu Y.W.
      • et al.
      Active immunization to prevent de novo hepatitis B virus infection in pediatric live donor liver recipients.
      ,
      • Kwon C.
      • Suh K.
      • Yi N.
      • Chang S.
      • Cho Y.
      • Lee H.
      • et al.
      Long-term protection against hepatitis B in pediatric liver recipients can be achieved effectively with vaccination after transplantation.
      ,
      • Hwang S.
      • Moon D.B.
      • Lee S.G.
      • Park K.M.
      • Kim K.H.
      • Ahn C.S.
      • et al.
      Safety of anti-hepatitis B core antibody-positive donors for living-donor liver transplantation.
      ,
      • Umeda M.
      • Marusawa H.
      • Ueda M.
      • Takada Y.
      • Egawa H.
      • Uemoto S.
      • et al.
      Beneficial effects of short-term lamivudine treatment for de novo hepatitis B virus reactivation after liver transplantation.
      ,
      • Soejima Y.
      • Ikegami T.
      • Taketomi A.
      • Yoshizumi T.
      • Uchiyama H.
      • Harada N.
      • et al.
      Hepatitis B vaccination after living donor liver transplantation.
      ,
      • Park J.B.
      • Kwon C.H.
      • Lee K.W.
      • Choi G.S.
      • Kim D.J.
      • Seo J.M.
      • et al.
      Hepatitis B virus vaccine switch program for prevention of de novo hepatitis B virus infection in pediatric patients.
      ,
      • Lee K.
      • Lee D.
      • Lee H.
      Prevention of de novo hepatitis B infection from HbcAb-positive donors in living donor liver transplantation.
      ] (Table 3). Nine did not have sufficient data regarding the serological HBV status in donors and/or recipients [
      • Douglas D.
      • Rakela J.
      • Wright T.
      • Krom R.A.
      • Wiesner R.H.
      The clinical course of transplantation-associated de novo hepatitis B infection in the liver transplant recipient.
      ,
      • Shinji U.
      • Kohachiro S.
      • Hiroyuki M.
      • Yukihiro I.
      • Katsuhiro A.
      • Hiroto E.
      • et al.
      Transmission of hepatitis B virus from hepatitis B core antibody-positive donors in living related liver transplants.
      ,
      • Montalti R.
      • Nardo B.
      • Bertelli R.
      • Beltempo P.
      • Puviani L.
      • Vivarelli M.
      • et al.
      Donor pool expansion in liver transplantation.
      ,
      • Holt C.D.
      • Thomas R.
      • van Thiel D.H.
      • Brems J.J.
      Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation.
      ,
      • Castells L.
      • Vargas V.
      • Rodrygez F.
      • Allende H.
      • Jardy R.
      • Margarit C.
      • et al.
      Transmission of hepatitis B virus by transplantation of livers from donors positive for antibody to hepatitis B core antigen.
      ,
      • Jain A.
      • Orloff M.
      • Abt P.
      • Kashyap R.
      • Mohanka R.
      • Lansing K.
      • et al.
      Use of hepatitis B core antibody positive liver allograft in hepatitis C virus-positive and -negative recipients with use of short course of hepatitis B immunoglobulin and lamivudine.
      ,
      • Kwon C.
      • Suh K.
      • Yi N.
      • Chang S.
      • Cho Y.
      • Lee H.
      • et al.
      Long-term protection against hepatitis B in pediatric liver recipients can be achieved effectively with vaccination after transplantation.
      ,
      • Park J.B.
      • Kwon C.H.
      • Lee K.W.
      • Choi G.S.
      • Kim D.J.
      • Seo J.M.
      • et al.
      Hepatitis B virus vaccine switch program for prevention of de novo hepatitis B virus infection in pediatric patients.
      ,
      • Lee K.
      • Lee D.
      • Lee H.
      Prevention of de novo hepatitis B infection from HbcAb-positive donors in living donor liver transplantation.
      ]. Four centres published two studies: one in Spain [
      • Barcena R.
      • Moraleda G.
      • Moreno J.
      • Dolore Martin M.
      • de Vicente E.
      • Nupo J.
      • et al.
      Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers.
      ,
      • Barcena Marugan R.
      • Garcia-Hoz F.
      • Vazquez Romero M.
      • Nash R.
      • Mateos M.
      • Gonzalez Alonso R.
      • et al.
      Prevention of de novo hepatitis B infection in liver allograft recipients with previous hepatitis B infection or hepatitis B vaccination.
      ] and three in the USA [
      • Nery J.R.
      • Nery-Avila C.
      • Reddy K.R.
      • Cirocco R.
      • Weppler D.
      • Levi D.M.
      • et al.
      Use of liver grafts from donors positive for anti-hepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.
      ,
      • Dodson S.F.
      • Issa S.
      • Araya V.
      • Gayowski T.
      • Pinna A.
      • Eghtesad B.
      • et al.
      Infectivity of hepatic allografts with antibodies to hepatitis B virus.
      ,
      • Crespo J.
      • Fabrega E.
      • Casafont F.
      • Rivero M.
      • Heras G.
      • de la Pepa J.
      • et al.
      Severe clinical course of de novo hepatitis B infection after liver transplantation.
      ,
      • Fabrega E.
      • Garcia-Suarez C.
      • Guerra A.
      • Orive A.
      • Casafont F.
      • Crespo J.
      • et al.
      Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach.
      ,
      • Dodson F.
      • Bonham C.
      • Geller D.
      • Cacciarelli T.V.
      • Rakela J.
      • Fung J.J.
      Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti-HBc positive donors.
      ,
      • Nery J.R.
      • Gedaly R.
      • Vianna R.
      • Berho M.
      • Weppler D.
      • Levi D.M.
      • et al.
      Are liver grafts from hepatitis B surface antigen negative/anti-hepatitis B core antibody positive donors suitable for transplantation?.
      ] with two of these reports having overlap in study periods [
      • Dodson S.F.
      • Issa S.
      • Araya V.
      • Gayowski T.
      • Pinna A.
      • Eghtesad B.
      • et al.
      Infectivity of hepatic allografts with antibodies to hepatitis B virus.
      ,
      • Dodson F.
      • Bonham C.
      • Geller D.
      • Cacciarelli T.V.
      • Rakela J.
      • Fung J.J.
      Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti-HBc positive donors.
      ]. The indication for LT was recorded in 21 studies [
      • Prieto M.
      • Gomez M.D.
      • Berenguer M.
      • Cordoba J.
      • Rayon J.M.
      • Pastor M.
      • et al.
      De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population.
      ,
      • Yu A.S.
      • Vierling J.M.
      • Colquhoun S.D.
      • Arnaout W.S.
      • Chan C.K.
      • Khanafshar E.
      • et al.
      Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy.
      ,
      • Roque-Afonso A.M.
      • Feray C.
      • Samuel D.
      • Simoneau D.
      • Roche B.
      • Emile J.F.
      • et al.
      Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.
      ,
      • Nery J.R.
      • Nery-Avila C.
      • Reddy K.R.
      • Cirocco R.
      • Weppler D.
      • Levi D.M.
      • et al.
      Use of liver grafts from donors positive for anti-hepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.
      ,
      • Montalti R.
      • Nardo B.
      • Bertelli R.
      • Beltempo P.
      • Puviani L.
      • Vivarelli M.
      • et al.
      Donor pool expansion in liver transplantation.
      ,
      • Prakoso E.
      • Strasser S.I.
      • Koorey D.J.
      • Verran D.
      • McCaughan G.W.
      Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.
      ,
      • Celebi Kodak A.
      • Karasu Z.
      • Kilic M.
      • Ozacar T.
      • Tekin F.
      • Gunsar F.
      • et al.
      Living donor liver transplantation from hepatitis B core antibody positive donors.
      ,
      • Suehiro T.
      • Shimada M.
      • Kishikawa K.
      • Shimura T.
      • Soejima Y.
      • Yoshizumi T.
      • et al.
      Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.
      ,
      • Crespo J.
      • Fabrega E.
      • Casafont F.
      • Rivero M.
      • Heras G.
      • de la Pepa J.
      • et al.
      Severe clinical course of de novo hepatitis B infection after liver transplantation.
      ,
      • Holt C.D.
      • Thomas R.
      • van Thiel D.H.
      • Brems J.J.
      Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation.
      ,
      • Barcena R.
      • Moraleda G.
      • Moreno J.
      • Dolore Martin M.
      • de Vicente E.
      • Nupo J.
      • et al.
      Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers.
      ,
      • Barcena Marugan R.
      • Garcia-Hoz F.
      • Vazquez Romero M.
      • Nash R.
      • Mateos M.
      • Gonzalez Alonso R.
      • et al.
      Prevention of de novo hepatitis B infection in liver allograft recipients with previous hepatitis B infection or hepatitis B vaccination.
      ,
      • Castells L.
      • Vargas V.
      • Rodrygez F.
      • Allende H.
      • Jardy R.
      • Margarit C.
      • et al.
      Transmission of hepatitis B virus by transplantation of livers from donors positive for antibody to hepatitis B core antigen.
      ,
      • Chazouilleres O.
      • Mamish D.
      • Kim M.
      • Carey K.
      • Ferrell L.
      • Roberts J.
      • et al.
      “Occult” hepatitis B virus as source of infection in liver transplant recipients.
      ,
      • Wachs M.E.
      • Amend W.J.
      • Ascher N.L.
      • Bretan P.N.
      • Emond J.
      • Lake J.R.
      • et al.
      The risk of transmission of hepatitis B from HBsAg(−), HBcAb(+), HBIgM(−) organ donors.
      ,
      • Jain A.
      • Orloff M.
      • Abt P.
      • Kashyap R.
      • Mohanka R.
      • Lansing K.
      • et al.
      Use of hepatitis B core antibody positive liver allograft in hepatitis C virus-positive and -negative recipients with use of short course of hepatitis B immunoglobulin and lamivudine.
      ,
      • Lin C.C.
      • Chen C.L.
      • Concejero A.
      • Wang C.C.
      • Wang S.H.
      • Liu Y.W.
      • et al.
      Active immunization to prevent de novo hepatitis B virus infection in pediatric live donor liver recipients.
      ,
      • Kwon C.
      • Suh K.
      • Yi N.
      • Chang S.
      • Cho Y.
      • Lee H.
      • et al.
      Long-term protection against hepatitis B in pediatric liver recipients can be achieved effectively with vaccination after transplantation.
      ,
      • Umeda M.
      • Marusawa H.
      • Ueda M.
      • Takada Y.
      • Egawa H.
      • Uemoto S.
      • et al.
      Beneficial effects of short-term lamivudine treatment for de novo hepatitis B virus reactivation after liver transplantation.
      ,
      • Park J.B.
      • Kwon C.H.
      • Lee K.W.
      • Choi G.S.
      • Kim D.J.
      • Seo J.M.
      • et al.
      Hepatitis B virus vaccine switch program for prevention of de novo hepatitis B virus infection in pediatric patients.
      ,
      • Lee K.
      • Lee D.
      • Lee H.
      Prevention of de novo hepatitis B infection from HbcAb-positive donors in living donor liver transplantation.
      ]: HCV cirrhosis was the most common (25%), followed by alcoholic cirrhosis and cholestatic liver diseases. The cohort size ranged from 6 to 91 patients with only two studies reporting >50 patients [
      • Celebi Kodak A.
      • Karasu Z.
      • Kilic M.
      • Ozacar T.
      • Tekin F.
      • Gunsar F.
      • et al.
      Living donor liver transplantation from hepatitis B core antibody positive donors.
      ,
      • Barcena Marugan R.
      • Garcia-Hoz F.
      • Vazquez Romero M.
      • Nash R.
      • Mateos M.
      • Gonzalez Alonso R.
      • et al.
      Prevention of de novo hepatitis B infection in liver allograft recipients with previous hepatitis B infection or hepatitis B vaccination.
      ]. The total number of patients that could be evaluated was 788.
      Table 3Published studies
      Twenty-two studies with <10 patients each (n=13) [5,19,25,30,34,36,38,40–42,44,46,48] or insufficient data (n=9) on the serological HBV status of donors and/or recipients [12,13,23,31,39,43,45,49,50] are not included. De novo HBV infection developed in: (a) 15/57 HBV naive recipients [5,19,25,30,34,38,40–42,48] under no anti-HBV prophylaxis or LAM±HBIG±vaccination, (b) 2/51 anti-HBc positive recipients [anti-HBs negative (1/9), anti-HBs positive (1/20), anti-HBs unknown (0/22)] [5,19,25,36,38,40,44,46] under no anti-HBV prophylaxis or HBIG±LAM±vaccination and (d) 1/25 only anti-HBs positive recipients under LAM plus vaccination [44]. De novo HBV infection also developed in (a) 15/20 anti-HBc positive recipients (unknown anti-HBs status) under no anti-HBV prophylaxis (15/16) [13] or HBIG+LAM (0/1) [31] or HBIG plus vaccination (0/3) [49], (b) 0/11 anti-HBs positive recipients under HBIG plus vaccination [49] and (c) 14/95 recipients with unknown anti-HBs/anti-HBc status under HBIG±LAM or no prophylaxis (9/67) [12,23,39,43] or HBIG±vaccination (2/25) [45,50] or vaccination alone (3/3) [50].
      with liver transplantation using anti-HBc positive donors in HBsAg-negative recipients.
      Thirty one recipients (from seven studies [11,16,21,22,24,36,37]) with successful pre-LT vaccination and no post-LT prophylaxis were not included; three (9.6%) of them developed de novo HBV infection. In addition, 34 recipients (from seven studies [19,24–26,31,33,34]) with successful pre-LT vaccination and HBIG and/or lamivudine post-LT prophylaxis were not included; none of them developed de novo HBV infection.
      First author, year [Ref.]Anti-HBc (+), anti-HBs (−) recipientsAnti-HBc (+), anti-HBs (+) recipientsHBV naive recipients
      Patients, NAnti-HBV prophylaxisFollow-up, monthsDe novo HBV, nPatients, NAnti-HBV prophylaxisFollow-up, monthsDe novo HBV, nPatients NAnti-HBV prophylaxisFollow-up, monthsDe novo HBV, n
      Dickson (1997)
      • Dickson R.C.
      • Everhart J.E.
      • Lake J.R.
      • Wei Y.
      • Seaberg E.C.
      • Wiesner R.H.
      • et al.
      Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.
      2None220None18None2215
      Dodson (1997)
      • Dodson S.F.
      • Issa S.
      • Araya V.
      • Gayowski T.
      • Pinna A.
      • Eghtesad B.
      • et al.
      Infectivity of hepatic allografts with antibodies to hepatitis B virus.
      15None562756025None5618
      Dodson (1999)
      • Dodson F.
      • Bonham C.
      • Geller D.
      • Cacciarelli T.V.
      • Rakela J.
      • Fung J.J.
      Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti-HBc positive donors.
      8HBIG + LAM460None8HBIG + LAM: 7, HBIG: 1461
      Prietro (2001)
      • Prieto M.
      • Gomez M.D.
      • Berenguer M.
      • Cordoba J.
      • Rayon J.M.
      • Pastor M.
      • et al.
      De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population.
      3None2902None29025None2915
      Manzabeita (2002)
      • Manzarbeitia C.
      • Reich D.J.
      • Ortiz J.A.
      • Rothstein K.D.
      • Araya V.R.
      • Munoz S.J.
      Safe use of livers from donors with positive hepatitis B core antibody.
      11None262132602HBIG262
      Roque-Afonso (2002)
      • Roque-Afonso A.M.
      • Feray C.
      • Samuel D.
      • Simoneau D.
      • Roche B.
      • Emile J.F.
      • et al.
      Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.
      4HBIG26012None: 4, HBIG: 8225
      Bacerna (2002)
      • Barcena Marugan R.
      • Garcia-Hoz F.
      • Vazquez Romero M.
      • Nash R.
      • Mateos M.
      • Gonzalez Alonso R.
      • et al.
      Prevention of de novo hepatitis B infection in liver allograft recipients with previous hepatitis B infection or hepatitis B vaccination.
      19NoneNA064NA10
      Chen (2002)
      • Chen Y.S.
      • Wang C.C.
      • deVilla V.H.
      • Wang S.H.
      • Cheng Y.F.
      • Huang T.L.
      • et al.
      Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors.
      2LAM: 1, none: 14003LAM: 2, none:140015LAM: 13, none: 2402
      Nery (2003)
      • Nery J.R.
      • Nery-Avila C.
      • Reddy K.R.
      • Cirocco R.
      • Weppler D.
      • Levi D.M.
      • et al.
      Use of liver grafts from donors positive for anti-hepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.
      13HBIG + LAM: 4, LAM: 922123HBIG + LAM: 6, none: 172108HBIG + LAM: 2, LAM: 6371
      Loss (2003)1
      • Loss Jr., G.
      • Mason A.
      • Nair S.
      • Blazek J.
      • Farr G.
      • Guo L.
      • et al.
      Does lamivudine prophylaxis eradicate persistent HBV DNA from allografts derived from anti-HBc-positive donors?.
      11HBIG (bolus) + LAM + Vaccination330
      Suehiro (2005)
      • Suehiro T.
      • Shimada M.
      • Kishikawa K.
      • Shimura T.
      • Soejima Y.
      • Yoshizumi T.
      • et al.
      Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.
      4HBIG + LAM3903NA39015HBIG + LAM390
      De Feo (2005)2
      • De Feo T.
      • Poli F.
      • Mozzi F.
      • Moretti M.P.
      • Scalamogna M.
      Collaborative Kidney Liver and Heart North Italy Transplant Program Study Groups
      Risk of transmission of hepatitis B virus from anti-HBC positive cadaveric organ donors: a collaborative study.
      NANoneNA0NANoneNA014NoneNA6
      Donataccio (2006)3
      • Donataccio D.
      • Roggen F.
      • De Reyck C.
      • Verbaandert C.
      • Bodeus M.
      • Lerut J.
      Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool.
      NAHBIGNANANAHBIGNANA11HBIG + LAM: 1,577
      Umeda (2006)
      • Umeda M.
      • Marusawa H.
      • Ueda M.
      • Takada Y.
      • Egawa H.
      • Uemoto S.
      • et al.
      Beneficial effects of short-term lamivudine treatment for de novo hepatitis B virus reactivation after liver transplantation.
      38HBIG429
      Celebi-Kobak (2007)
      • Celebi Kodak A.
      • Karasu Z.
      • Kilic M.
      • Ozacar T.
      • Tekin F.
      • Gunsar F.
      • et al.
      Living donor liver transplantation from hepatitis B core antibody positive donors.
      4LAM1703LAM2804LAM230
      Takemura (2007)
      • Takemura N.
      • Sugawara Y.
      • Tamura S.
      • Makuuchi M.
      Liver transplantation using hepatitis B core antibody-positive grafts: review and university of Tokyo experience.
      2LAM3105HBIG3119HBIG311
      HBIG, hepatitis B immunoglobulin; LAM, lamivudine; NA, not available.
      De novo HBV infection also developed in (a) 1/3 anti-HBs positive recipients under HBIG + LAM + vaccination1
      • Loss Jr., G.
      • Mason A.
      • Nair S.
      • Blazek J.
      • Farr G.
      • Guo L.
      • et al.
      Does lamivudine prophylaxis eradicate persistent HBV DNA from allografts derived from anti-HBc-positive donors?.
      ; (b) 0/35 anti-HBc positive and/or anti-HBs positive recipients under no anti-HBV prophylaxis2
      • De Feo T.
      • Poli F.
      • Mozzi F.
      • Moretti M.P.
      • Scalamogna M.
      Collaborative Kidney Liver and Heart North Italy Transplant Program Study Groups
      Risk of transmission of hepatitis B virus from anti-HBC positive cadaveric organ donors: a collaborative study.
      , (c) 0/1 anti-HBc positive recipient (unknown anti-HBs status) under HBIG during 11 months of follow-up3
      • Donataccio D.
      • Roggen F.
      • De Reyck C.
      • Verbaandert C.
      • Bodeus M.
      • Lerut J.
      Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool.
      .
      a Twenty-two studies with <10 patients each (n = 13)
      • Rokuhara A.
      • Tanaka E.
      • Yagi S.
      • Mizokami M.
      • Hasshikura Y.
      • Kawasaki S.
      • et al.
      De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome.
      ,
      • Yu A.S.
      • Vierling J.M.
      • Colquhoun S.D.
      • Arnaout W.S.
      • Chan C.K.
      • Khanafshar E.
      • et al.
      Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy.
      ,
      • Prakoso E.
      • Strasser S.I.
      • Koorey D.J.
      • Verran D.
      • McCaughan G.W.
      Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.
      ,
      • Crespo J.
      • Fabrega E.
      • Casafont F.
      • Rivero M.
      • Heras G.
      • de la Pepa J.
      • et al.
      Severe clinical course of de novo hepatitis B infection after liver transplantation.
      ,
      • Fabrega E.
      • Garcia-Suarez C.
      • Guerra A.
      • Orive A.
      • Casafont F.
      • Crespo J.
      • et al.
      Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach.
      ,
      • Barcena R.
      • Moraleda G.
      • Moreno J.
      • Dolore Martin M.
      • de Vicente E.
      • Nupo J.
      • et al.
      Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers.
      ,
      • Villamil I.
      • Gonzalez-Quintela A.
      • Aquilera A.
      • Tome S.
      • Otero E.
      • Castroagudin F.J.
      • et al.
      Truly de novo HBV infection after liver transplantation.
      ,
      • Nery J.R.
      • Gedaly R.
      • Vianna R.
      • Berho M.
      • Weppler D.
      • Levi D.M.
      • et al.
      Are liver grafts from hepatitis B surface antigen negative/anti-hepatitis B core antibody positive donors suitable for transplantation?.
      ,
      • Chazouilleres O.
      • Mamish D.
      • Kim M.
      • Carey K.
      • Ferrell L.
      • Roberts J.
      • et al.
      “Occult” hepatitis B virus as source of infection in liver transplant recipients.
      ,
      • Wachs M.E.
      • Amend W.J.
      • Ascher N.L.
      • Bretan P.N.
      • Emond J.
      • Lake J.R.
      • et al.
      The risk of transmission of hepatitis B from HBsAg(−), HBcAb(+), HBIgM(−) organ donors.
      ,
      • Lin C.C.
      • Chen C.L.
      • Concejero A.
      • Wang C.C.
      • Wang S.H.
      • Liu Y.W.
      • et al.
      Active immunization to prevent de novo hepatitis B virus infection in pediatric live donor liver recipients.
      ,
      • Hwang S.
      • Moon D.B.
      • Lee S.G.
      • Park K.M.
      • Kim K.H.
      • Ahn C.S.
      • et al.
      Safety of anti-hepatitis B core antibody-positive donors for living-donor liver transplantation.
      ,
      • Soejima Y.
      • Ikegami T.
      • Taketomi A.
      • Yoshizumi T.
      • Uchiyama H.
      • Harada N.
      • et al.
      Hepatitis B vaccination after living donor liver transplantation.
      or insufficient data (n = 9) on the serological HBV status of donors and/or recipients
      • Douglas D.
      • Rakela J.
      • Wright T.
      • Krom R.A.
      • Wiesner R.H.
      The clinical course of transplantation-associated de novo hepatitis B infection in the liver transplant recipient.
      ,
      • Shinji U.
      • Kohachiro S.
      • Hiroyuki M.
      • Yukihiro I.
      • Katsuhiro A.
      • Hiroto E.
      • et al.
      Transmission of hepatitis B virus from hepatitis B core antibody-positive donors in living related liver transplants.
      ,
      • Montalti R.
      • Nardo B.
      • Bertelli R.
      • Beltempo P.
      • Puviani L.
      • Vivarelli M.
      • et al.
      Donor pool expansion in liver transplantation.
      ,
      • Holt C.D.
      • Thomas R.
      • van Thiel D.H.
      • Brems J.J.
      Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation.
      ,
      • Castells L.
      • Vargas V.
      • Rodrygez F.
      • Allende H.
      • Jardy R.
      • Margarit C.
      • et al.
      Transmission of hepatitis B virus by transplantation of livers from donors positive for antibody to hepatitis B core antigen.
      ,
      • Jain A.
      • Orloff M.
      • Abt P.
      • Kashyap R.
      • Mohanka R.
      • Lansing K.
      • et al.
      Use of hepatitis B core antibody positive liver allograft in hepatitis C virus-positive and -negative recipients with use of short course of hepatitis B immunoglobulin and lamivudine.
      ,
      • Kwon C.
      • Suh K.
      • Yi N.
      • Chang S.
      • Cho Y.
      • Lee H.
      • et al.
      Long-term protection against hepatitis B in pediatric liver recipients can be achieved effectively with vaccination after transplantation.
      ,
      • Park J.B.
      • Kwon C.H.
      • Lee K.W.
      • Choi G.S.
      • Kim D.J.
      • Seo J.M.
      • et al.
      Hepatitis B virus vaccine switch program for prevention of de novo hepatitis B virus infection in pediatric patients.
      ,
      • Lee K.
      • Lee D.
      • Lee H.
      Prevention of de novo hepatitis B infection from HbcAb-positive donors in living donor liver transplantation.
      are not included. De novo HBV infection developed in: (a) 15/57 HBV naive recipients
      • Rokuhara A.
      • Tanaka E.
      • Yagi S.
      • Mizokami M.
      • Hasshikura Y.
      • Kawasaki S.
      • et al.
      De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome.
      ,
      • Yu A.S.
      • Vierling J.M.
      • Colquhoun S.D.
      • Arnaout W.S.
      • Chan C.K.
      • Khanafshar E.
      • et al.
      Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy.
      ,
      • Prakoso E.
      • Strasser S.I.
      • Koorey D.J.
      • Verran D.
      • McCaughan G.W.
      Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.
      ,
      • Crespo J.
      • Fabrega E.
      • Casafont F.
      • Rivero M.
      • Heras G.
      • de la Pepa J.
      • et al.
      Severe clinical course of de novo hepatitis B infection after liver transplantation.
      ,
      • Fabrega E.
      • Garcia-Suarez C.
      • Guerra A.
      • Orive A.
      • Casafont F.
      • Crespo J.
      • et al.
      Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach.
      ,
      • Villamil I.
      • Gonzalez-Quintela A.
      • Aquilera A.
      • Tome S.
      • Otero E.
      • Castroagudin F.J.
      • et al.
      Truly de novo HBV infection after liver transplantation.
      ,
      • Nery J.R.
      • Gedaly R.
      • Vianna R.
      • Berho M.
      • Weppler D.
      • Levi D.M.
      • et al.
      Are liver grafts from hepatitis B surface antigen negative/anti-hepatitis B core antibody positive donors suitable for transplantation?.
      ,
      • Chazouilleres O.
      • Mamish D.
      • Kim M.
      • Carey K.
      • Ferrell L.
      • Roberts J.
      • et al.
      “Occult” hepatitis B virus as source of infection in liver transplant recipients.
      ,
      • Wachs M.E.
      • Amend W.J.
      • Ascher N.L.
      • Bretan P.N.
      • Emond J.
      • Lake J.R.
      • et al.
      The risk of transmission of hepatitis B from HBsAg(−), HBcAb(+), HBIgM(−) organ donors.
      ,
      • Soejima Y.
      • Ikegami T.
      • Taketomi A.
      • Yoshizumi T.
      • Uchiyama H.
      • Harada N.
      • et al.
      Hepatitis B vaccination after living donor liver transplantation.
      under no anti-HBV prophylaxis or LAM ± HBIG ± vaccination, (b) 2/51 anti-HBc positive recipients [anti-HBs negative (1/9), anti-HBs positive (1/20), anti-HBs unknown (0/22)]
      • Rokuhara A.
      • Tanaka E.
      • Yagi S.
      • Mizokami M.
      • Hasshikura Y.
      • Kawasaki S.
      • et al.
      De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome.
      ,
      • Yu A.S.
      • Vierling J.M.
      • Colquhoun S.D.
      • Arnaout W.S.
      • Chan C.K.
      • Khanafshar E.
      • et al.
      Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy.
      ,
      • Prakoso E.
      • Strasser S.I.
      • Koorey D.J.
      • Verran D.
      • McCaughan G.W.
      Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.
      ,
      • Barcena R.
      • Moraleda G.
      • Moreno J.
      • Dolore Martin M.
      • de Vicente E.
      • Nupo J.
      • et al.
      Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers.
      ,
      • Villamil I.
      • Gonzalez-Quintela A.
      • Aquilera A.
      • Tome S.
      • Otero E.
      • Castroagudin F.J.
      • et al.
      Truly de novo HBV infection after liver transplantation.
      ,
      • Nery J.R.
      • Gedaly R.
      • Vianna R.
      • Berho M.
      • Weppler D.
      • Levi D.M.
      • et al.
      Are liver grafts from hepatitis B surface antigen negative/anti-hepatitis B core antibody positive donors suitable for transplantation?.
      ,
      • Lin C.C.
      • Chen C.L.
      • Concejero A.
      • Wang C.C.
      • Wang S.H.
      • Liu Y.W.
      • et al.
      Active immunization to prevent de novo hepatitis B virus infection in pediatric live donor liver recipients.
      ,
      • Hwang S.
      • Moon D.B.
      • Lee S.G.
      • Park K.M.
      • Kim K.H.
      • Ahn C.S.
      • et al.
      Safety of anti-hepatitis B core antibody-positive donors for living-donor liver transplantation.
      under no anti-HBV prophylaxis or HBIG ± LAM ± vaccination and (d) 1/25 only anti-HBs positive recipients under LAM plus vaccination
      • Lin C.C.
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      Active immunization to prevent de novo hepatitis B virus infection in pediatric live donor liver recipients.
      . De novo HBV infection also developed in (a) 15/20 anti-HBc positive recipients (unknown anti-HBs status) under no anti-HBV prophylaxis (15/16)
      • Shinji U.
      • Kohachiro S.
      • Hiroyuki M.
      • Yukihiro I.
      • Katsuhiro A.
      • Hiroto E.
      • et al.
      Transmission of hepatitis B virus from hepatitis B core antibody-positive donors in living related liver transplants.
      or HBIG + LAM (0/1)
      • Holt C.D.
      • Thomas R.
      • van Thiel D.H.
      • Brems J.J.
      Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation.
      or HBIG plus vaccination (0/3)
      • Park J.B.
      • Kwon C.H.
      • Lee K.W.
      • Choi G.S.
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      • Seo J.M.
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      Hepatitis B virus vaccine switch program for prevention of de novo hepatitis B virus infection in pediatric patients.
      , (b) 0/11 anti-HBs positive recipients under HBIG plus vaccination
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      • Choi G.S.
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      Hepatitis B virus vaccine switch program for prevention of de novo hepatitis B virus infection in pediatric patients.
      and (c) 14/95 recipients with unknown anti-HBs/anti-HBc status under HBIG ± LAM or no prophylaxis (9/67)
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      • Wiesner R.H.
      The clinical course of transplantation-associated de novo hepatitis B infection in the liver transplant recipient.
      ,
      • Montalti R.
      • Nardo B.
      • Bertelli R.
      • Beltempo P.
      • Puviani L.
      • Vivarelli M.
      • et al.
      Donor pool expansion in liver transplantation.
      ,
      • Castells L.
      • Vargas V.
      • Rodrygez F.
      • Allende H.
      • Jardy R.
      • Margarit C.
      • et al.
      Transmission of hepatitis B virus by transplantation of livers from donors positive for antibody to hepatitis B core antigen.
      ,
      • Jain A.
      • Orloff M.
      • Abt P.
      • Kashyap R.
      • Mohanka R.
      • Lansing K.
      • et al.
      Use of hepatitis B core antibody positive liver allograft in hepatitis C virus-positive and -negative recipients with use of short course of hepatitis B immunoglobulin and lamivudine.
      or HBIG ± vaccination (2/25)
      • Kwon C.
      • Suh K.
      • Yi N.
      • Chang S.
      • Cho Y.
      • Lee H.
      • et al.
      Long-term protection against hepatitis B in pediatric liver recipients can be achieved effectively with vaccination after transplantation.
      ,
      • Lee K.
      • Lee D.
      • Lee H.
      Prevention of de novo hepatitis B infection from HbcAb-positive donors in living donor liver transplantation.
      or vaccination alone (3/3)
      • Lee K.
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      Prevention of de novo hepatitis B infection from HbcAb-positive donors in living donor liver transplantation.
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      b Thirty one recipients (from seven studies
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      Use of liver grafts from donors positive for anti-hepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.
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      Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool.
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      • Barcena R.
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      Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.
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      ) with successful pre-LT vaccination and HBIG and/or lamivudine post-LT prophylaxis were not included; none of them developed de novo HBV infection.
      The diagnosis of de novo HBV infection was based on the detection of HBsAg in previously HBsAg-negative recipients with or without compatible biochemical or histological findings in 14 studies [
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      • de la Pepa J.
      • et al.
      Severe clinical course of de novo hepatitis B infection after liver transplantation.
      ,
      • Holt C.D.
      • Thomas R.
      • van Thiel D.H.
      • Brems J.J.
      Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation.
      ,
      • Loss Jr., G.
      • Mason A.
      • Nair S.
      • Blazek J.
      • Farr G.
      • Guo L.
      • et al.
      Does lamivudine prophylaxis eradicate persistent HBV DNA from allografts derived from anti-HBc-positive donors?.
      ,
      • Fabrega E.
      • Garcia-Suarez C.
      • Guerra A.
      • Orive A.
      • Casafont F.
      • Crespo J.
      • et al.
      Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach.
      ,
      • Barcena R.
      • Moraleda G.
      • Moreno J.
      • Dolore Martin M.
      • de Vicente E.
      • Nupo J.
      • et al.
      Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers.
      ,
      • Barcena Marugan R.
      • Garcia-Hoz F.
      • Vazquez Romero M.
      • Nash R.
      • Mateos M.
      • Gonzalez Alonso R.
      • et al.
      Prevention of de novo hepatitis B infection in liver allograft recipients with previous hepatitis B infection or hepatitis B vaccination.
      ,
      • Villamil I.
      • Gonzalez-Quintela A.
      • Aquilera A.
      • Tome S.
      • Otero E.
      • Castroagudin F.J.
      • et al.
      Truly de novo HBV infection after liver transplantation.
      ,
      • Castells L.
      • Vargas V.
      • Rodrygez F.
      • Allende H.
      • Jardy R.
      • Margarit C.
      • et al.
      Transmission of hepatitis B virus by transplantation of livers from donors positive for antibody to hepatitis B core antigen.
      ,
      • Nery J.R.
      • Gedaly R.
      • Vianna R.
      • Berho M.
      • Weppler D.
      • Levi D.M.
      • et al.
      Are liver grafts from hepatitis B surface antigen negative/anti-hepatitis B core antibody positive donors suitable for transplantation?.
      ,
      • Chazouilleres O.
      • Mamish D.
      • Kim M.
      • Carey K.
      • Ferrell L.
      • Roberts J.
      • et al.
      “Occult” hepatitis B virus as source of infection in liver transplant recipients.
      ,
      • Jain A.
      • Orloff M.
      • Abt P.
      • Kashyap R.
      • Mohanka R.
      • Lansing K.
      • et al.
      Use of hepatitis B core antibody positive liver allograft in hepatitis C virus-positive and -negative recipients with use of short course of hepatitis B immunoglobulin and lamivudine.
      ,
      • Soejima Y.
      • Ikegami T.
      • Taketomi A.
      • Yoshizumi T.
      • Uchiyama H.
      • Harada N.
      • et al.
      Hepatitis B vaccination after living donor liver transplantation.
      ]. The presence of HBV DNA was determined by a hybridization technique in three [
      • Prieto M.
      • Gomez M.D.
      • Berenguer M.
      • Cordoba J.
      • Rayon J.M.
      • Pastor M.
      • et al.
      De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population.
      ,
      • Chen Y.S.
      • Wang C.C.
      • deVilla V.H.
      • Wang S.H.
      • Cheng Y.F.
      • Huang T.L.
      • et al.
      Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors.
      ,
      • Barcena Marugan R.
      • Garcia-Hoz F.
      • Vazquez Romero M.
      • Nash R.
      • Mateos M.
      • Gonzalez Alonso R.
      • et al.
      Prevention of de novo hepatitis B infection in liver allograft recipients with previous hepatitis B infection or hepatitis B vaccination.
      ], branched-DNA assay in one [
      • Manzarbeitia C.
      • Reich D.J.
      • Ortiz J.A.
      • Rothstein K.D.
      • Araya V.R.
      • Munoz S.J.
      Safe use of livers from donors with positive hepatitis B core antibody.
      ] and polymerase chain reaction (PCR) assay in the remaining 20 studies [
      • Rokuhara A.
      • Tanaka E.
      • Yagi S.
      • Mizokami M.
      • Hasshikura Y.
      • Kawasaki S.
      • et al.
      De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome.
      ,
      • Dickson R.C.
      • Everhart J.E.
      • Lake J.R.
      • Wei Y.
      • Seaberg E.C.
      • Wiesner R.H.
      • et al.
      Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.
      ,
      • Shinji U.
      • Kohachiro S.
      • Hiroyuki M.
      • Yukihiro I.
      • Katsuhiro A.
      • Hiroto E.
      • et al.
      Transmission of hepatitis B virus from hepatitis B core antibody-positive donors in living related liver transplants.
      ,
      • Yu A.S.
      • Vierling J.M.
      • Colquhoun S.D.
      • Arnaout W.S.
      • Chan C.K.
      • Khanafshar E.
      • et al.
      Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy.
      ,
      • Roque-Afonso A.M.
      • Feray C.
      • Samuel D.
      • Simoneau D.
      • Roche B.
      • Emile J.F.
      • et al.
      Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.
      ,
      • Nery J.R.
      • Nery-Avila C.
      • Reddy K.R.
      • Cirocco R.
      • Weppler D.
      • Levi D.M.
      • et al.
      Use of liver grafts from donors positive for anti-hepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.
      ,
      • Prakoso E.
      • Strasser S.I.
      • Koorey D.J.
      • Verran D.
      • McCaughan G.W.
      Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.
      ,
      • Celebi Kodak A.
      • Karasu Z.
      • Kilic M.
      • Ozacar T.
      • Tekin F.
      • Gunsar F.
      • et al.
      Living donor liver transplantation from hepatitis B core antibody positive donors.
      ,
      • Suehiro T.
      • Shimada M.
      • Kishikawa K.
      • Shimura T.
      • Soejima Y.
      • Yoshizumi T.
      • et al.
      Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.
      ,
      • Crespo J.
      • Fabrega E.
      • Casafont F.
      • Rivero M.
      • Heras G.
      • de la Pepa J.
      • et al.
      Severe clinical course of de novo hepatitis B infection after liver transplantation.
      ,
      • Holt C.D.
      • Thomas R.
      • van Thiel D.H.
      • Brems J.J.
      Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation.
      ,
      • Loss Jr., G.
      • Mason A.
      • Nair S.
      • Blazek J.
      • Farr G.
      • Guo L.
      • et al.
      Does lamivudine prophylaxis eradicate persistent HBV DNA from allografts derived from anti-HBc-positive donors?.
      ,
      • Fabrega E.
      • Garcia-Suarez C.
      • Guerra A.
      • Orive A.
      • Casafont F.
      • Crespo J.
      • et al.
      Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach.
      ,
      • Barcena R.
      • Moraleda G.
      • Moreno J.
      • Dolore Martin M.
      • de Vicente E.
      • Nupo J.
      • et al.
      Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers.
      ,
      • Castells L.
      • Vargas V.
      • Rodrygez F.
      • Allende H.
      • Jardy R.
      • Margarit C.
      • et al.
      Transmission of hepatitis B virus by transplantation of livers from donors positive for antibody to hepatitis B core antigen.
      ,
      • Nery J.R.
      • Gedaly R.
      • Vianna R.
      • Berho M.
      • Weppler D.
      • Levi D.M.
      • et al.
      Are liver grafts from hepatitis B surface antigen negative/anti-hepatitis B core antibody positive donors suitable for transplantation?.
      ,
      • Chazouilleres O.
      • Mamish D.
      • Kim M.
      • Carey K.
      • Ferrell L.
      • Roberts J.
      • et al.
      “Occult” hepatitis B virus as source of infection in liver transplant recipients.
      ,
      • Umeda M.
      • Marusawa H.
      • Ueda M.
      • Takada Y.
      • Egawa H.
      • Uemoto S.
      • et al.
      Beneficial effects of short-term lamivudine treatment for de novo hepatitis B virus reactivation after liver transplantation.
      ,
      • Soejima Y.
      • Ikegami T.
      • Taketomi A.
      • Yoshizumi T.
      • Uchiyama H.
      • Harada N.
      • et al.
      Hepatitis B vaccination after living donor liver transplantation.
      ,
      • Park J.B.
      • Kwon C.H.
      • Lee K.W.
      • Choi G.S.
      • Kim D.J.
      • Seo J.M.
      • et al.
      Hepatitis B virus vaccine switch program for prevention of de novo hepatitis B virus infection in pediatric patients.
      ]. HBV DNA was evaluated in serum in 17 [
      • Dickson R.C.
      • Everhart J.E.
      • Lake J.R.
      • Wei Y.
      • Seaberg E.C.
      • Wiesner R.H.
      • et al.
      Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.
      ,
      • Prieto M.
      • Gomez M.D.
      • Berenguer M.
      • Cordoba J.
      • Rayon J.M.
      • Pastor M.
      • et al.
      De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population.
      ,
      • Manzarbeitia C.
      • Reich D.J.
      • Ortiz J.A.
      • Rothstein K.D.
      • Araya V.R.
      • Munoz S.J.
      Safe use of livers from donors with positive hepatitis B core antibody.
      ,
      • Chen Y.S.
      • Wang C.C.
      • deVilla V.H.
      • Wang S.H.
      • Cheng Y.F.
      • Huang T.L.
      • et al.
      Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors.
      ,
      • Nery J.R.
      • Nery-Avila C.
      • Reddy K.R.
      • Cirocco R.
      • Weppler D.
      • Levi D.M.
      • et al.
      Use of liver grafts from donors positive for anti-hepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.
      ,
      • Prakoso E.
      • Strasser S.I.
      • Koorey D.J.
      • Verran D.
      • McCaughan G.W.
      Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.
      ,
      • Celebi Kodak A.
      • Karasu Z.
      • Kilic M.
      • Ozacar T.
      • Tekin F.
      • Gunsar F.
      • et al.
      Living donor liver transplantation from hepatitis B core antibody positive donors.
      ,
      • Crespo J.
      • Fabrega E.
      • Casafont F.
      • Rivero M.
      • Heras G.
      • de la Pepa J.
      • et al.
      Severe clinical course of de novo hepatitis B infection after liver transplantation.
      ,
      • Barcena Marugan R.
      • Garcia-Hoz F.
      • Vazquez Romero M.
      • Nash R.
      • Mateos M.
      • Gonzalez Alonso R.
      • et al.
      Prevention of de novo hepatitis B infection in liver allograft recipients with previous hepatitis B infection or hepatitis B vaccination.
      ,
      • Castells L.
      • Vargas V.
      • Rodrygez F.
      • Allende H.
      • Jardy R.
      • Margarit C.
      • et al.
      Transmission of hepatitis B virus by transplantation of livers from donors positive for antibody to hepatitis B core antigen.
      ,
      • Nery J.R.
      • Gedaly R.
      • Vianna R.
      • Berho M.
      • Weppler D.
      • Levi D.M.
      • et al.
      Are liver grafts from hepatitis B surface antigen negative/anti-hepatitis B core antibody positive donors suitable for transplantation?.
      ,
      • Jain A.
      • Orloff M.
      • Abt P.
      • Kashyap R.
      • Mohanka R.
      • Lansing K.
      • et al.
      Use of hepatitis B core antibody positive liver allograft in hepatitis C virus-positive and -negative recipients with use of short course of hepatitis B immunoglobulin and lamivudine.
      ,
      • Lin C.C.
      • Chen C.L.
      • Concejero A.
      • Wang C.C.
      • Wang S.H.
      • Liu Y.W.
      • et al.
      Active immunization to prevent de novo hepatitis B virus infection in pediatric live donor liver recipients.
      ,
      • Kwon C.
      • Suh K.
      • Yi N.
      • Chang S.
      • Cho Y.
      • Lee H.
      • et al.
      Long-term protection against hepatitis B in pediatric liver recipients can be achieved effectively with vaccination after transplantation.
      ,
      • Umeda M.
      • Marusawa H.
      • Ueda M.
      • Takada Y.
      • Egawa H.
      • Uemoto S.
      • et al.
      Beneficial effects of short-term lamivudine treatment for de novo hepatitis B virus reactivation after liver transplantation.
      ,
      • Soejima Y.
      • Ikegami T.
      • Taketomi A.
      • Yoshizumi T.
      • Uchiyama H.
      • Harada N.
      • et al.
      Hepatitis B vaccination after living donor liver transplantation.
      ,
      • Park J.B.
      • Kwon C.H.
      • Lee K.W.
      • Choi G.S.
      • Kim D.J.
      • Seo J.M.
      • et al.
      Hepatitis B virus vaccine switch program for prevention of de novo hepatitis B virus infection in pediatric patients.
      ] and in both serum and liver tissue in nine studies [
      • Rokuhara A.
      • Tanaka E.
      • Yagi S.
      • Mizokami M.
      • Hasshikura Y.
      • Kawasaki S.
      • et al.
      De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome.
      ,
      • Shinji U.
      • Kohachiro S.
      • Hiroyuki M.
      • Yukihiro I.
      • Katsuhiro A.
      • Hiroto E.
      • et al.
      Transmission of hepatitis B virus from hepatitis B core antibody-positive donors in living related liver transplants.
      ,
      • Yu A.S.
      • Vierling J.M.
      • Colquhoun S.D.
      • Arnaout W.S.
      • Chan C.K.
      • Khanafshar E.
      • et al.
      Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy.
      ,
      • Roque-Afonso A.M.
      • Feray C.
      • Samuel D.
      • Simoneau D.
      • Roche B.
      • Emile J.F.
      • et al.
      Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.
      ,
      • Suehiro T.
      • Shimada M.
      • Kishikawa K.
      • Shimura T.
      • Soejima Y.
      • Yoshizumi T.
      • et al.
      Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.
      ,
      • Holt C.D.
      • Thomas R.
      • van Thiel D.H.
      • Brems J.J.
      Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation.
      ,
      • Loss Jr., G.
      • Mason A.
      • Nair S.
      • Blazek J.
      • Farr G.
      • Guo L.
      • et al.
      Does lamivudine prophylaxis eradicate persistent HBV DNA from allografts derived from anti-HBc-positive donors?.
      ,
      • Fabrega E.
      • Garcia-Suarez C.
      • Guerra A.
      • Orive A.
      • Casafont F.
      • Crespo J.
      • et al.
      Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach.
      ,
      • Chazouilleres O.
      • Mamish D.
      • Kim M.
      • Carey K.
      • Ferrell L.
      • Roberts J.
      • et al.
      “Occult” hepatitis B virus as source of infection in liver transplant recipients.
      ], while it was also evaluated in leukocytes in two studies [
      • Rokuhara A.
      • Tanaka E.
      • Yagi S.
      • Mizokami M.
      • Hasshikura Y.
      • Kawasaki S.
      • et al.
      De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome.
      ,
      • Fabrega E.
      • Garcia-Suarez C.
      • Guerra A.
      • Orive A.
      • Casafont F.
      • Crespo J.
      • et al.
      Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach.
      ]. In only one study, cccDNA was assessed in liver tissue [
      • Barcena R.
      • Moraleda G.
      • Moreno J.
      • Dolore Martin M.
      • de Vicente E.
      • Nupo J.
      • et al.
      Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers.
      ].
      The immunosuppressive therapy after LT was reported in detail for each patient in only one study [
      • Loss Jr., G.
      • Mason A.
      • Nair S.
      • Blazek J.
      • Farr G.
      • Guo L.
      • et al.
      Does lamivudine prophylaxis eradicate persistent HBV DNA from allografts derived from anti-HBc-positive donors?.
      ], while the immunosuppressive regimens with or without the number of patients in each regimen was reported in 19 studies [
      • Prieto M.
      • Gomez M.D.
      • Berenguer M.
      • Cordoba J.
      • Rayon J.M.
      • Pastor M.
      • et al.
      De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population.
      ,
      • Manzarbeitia C.
      • Reich D.J.
      • Ortiz J.A.
      • Rothstein K.D.
      • Araya V.R.
      • Munoz S.J.
      Safe use of livers from donors with positive hepatitis B core antibody.
      ,
      • Shinji U.
      • Kohachiro S.
      • Hiroyuki M.
      • Yukihiro I.
      • Katsuhiro A.
      • Hiroto E.
      • et al.
      Transmission of hepatitis B virus from hepatitis B core antibody-positive donors in living related liver transplants.
      ,
      • Chen Y.S.
      • Wang C.C.
      • deVilla V.H.
      • Wang S.H.
      • Cheng Y.F.
      • Huang T.L.
      • et al.
      Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors.
      ,
      • Yu A.S.
      • Vierling J.M.
      • Colquhoun S.D.
      • Arnaout W.S.
      • Chan C.K.
      • Khanafshar E.
      • et al.
      Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy.
      ,
      • Prakoso E.
      • Strasser S.I.
      • Koorey D.J.
      • Verran D.
      • McCaughan G.W.
      Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.
      ,
      • Suehiro T.
      • Shimada M.
      • Kishikawa K.
      • Shimura T.
      • Soejima Y.
      • Yoshizumi T.
      • et al.
      Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.
      ,
      • Crespo J.
      • Fabrega E.
      • Casafont F.
      • Rivero M.
      • Heras G.
      • de la Pepa J.
      • et al.
      Severe clinical course of de novo hepatitis B infection after liver transplantation.
      ,
      • Holt C.D.
      • Thomas R.
      • van Thiel D.H.
      • Brems J.J.
      Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation.
      ,
      • Takemura N.
      • Sugawara Y.
      • Tamura S.
      • Makuuchi M.
      Liver transplantation using hepatitis B core antibody-positive grafts: review and university of Tokyo experience.
      ,
      • Fabrega E.
      • Garcia-Suarez C.
      • Guerra A.
      • Orive A.
      • Casafont F.
      • Crespo J.
      • et al.
      Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach.
      ,
      • Barcena R.
      • Moraleda G.
      • Moreno J.
      • Dolore Martin M.
      • de Vicente E.
      • Nupo J.
      • et al.
      Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers.
      ,
      • Castells L.
      • Vargas V.
      • Rodrygez F.
      • Allende H.
      • Jardy R.
      • Margarit C.
      • et al.
      Transmission of hepatitis B virus by transplantation of livers from donors positive for antibody to hepatitis B core antigen.
      ,
      • Jain A.
      • Orloff M.
      • Abt P.
      • Kashyap R.
      • Mohanka R.
      • Lansing K.
      • et al.
      Use of hepatitis B core antibody positive liver allograft in hepatitis C virus-positive and -negative recipients with use of short course of hepatitis B immunoglobulin and lamivudine.
      ,
      • Lin C.C.
      • Chen C.L.
      • Concejero A.
      • Wang C.C.
      • Wang S.H.
      • Liu Y.W.
      • et al.
      Active immunization to prevent de novo hepatitis B virus infection in pediatric live donor liver recipients.
      ,
      • Kwon C.
      • Suh K.
      • Yi N.
      • Chang S.
      • Cho Y.
      • Lee H.
      • et al.
      Long-term protection against hepatitis B in pediatric liver recipients can be achieved effectively with vaccination after transplantation.
      ,
      • Umeda M.
      • Marusawa H.
      • Ueda M.
      • Takada Y.
      • Egawa H.
      • Uemoto S.
      • et al.
      Beneficial effects of short-term lamivudine treatment for de novo hepatitis B virus reactivation after liver transplantation.
      ,
      • Soejima Y.
      • Ikegami T.
      • Taketomi A.
      • Yoshizumi T.
      • Uchiyama H.
      • Harada N.
      • et al.
      Hepatitis B vaccination after living donor liver transplantation.
      ,
      • Park J.B.
      • Kwon C.H.
      • Lee K.W.
      • Choi G.S.
      • Kim D.J.
      • Seo J.M.
      • et al.
      Hepatitis B virus vaccine switch program for prevention of de novo hepatitis B virus infection in pediatric patients.
      ] and no information on the immunosuppression was provided in 18 studies [
      • Rokuhara A.
      • Tanaka E.
      • Yagi S.
      • Mizokami M.
      • Hasshikura Y.
      • Kawasaki S.
      • et al.
      De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome.
      ,
      • Dickson R.C.
      • Everhart J.E.
      • Lake J.R.
      • Wei Y.
      • Seaberg E.C.
      • Wiesner R.H.
      • et al.
      Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.
      ,
      • Douglas D.
      • Rakela J.
      • Wright T.
      • Krom R.A.
      • Wiesner R.H.
      The clinical course of transplantation-associated de novo hepatitis B infection in the liver transplant recipient.
      ,
      • Roque-Afonso A.M.
      • Feray C.
      • Samuel D.
      • Simoneau D.
      • Roche B.
      • Emile J.F.
      • et al.
      Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.
      ,
      • Nery J.R.
      • Nery-Avila C.
      • Reddy K.R.
      • Cirocco R.
      • Weppler D.
      • Levi D.M.
      • et al.
      Use of liver grafts from donors positive for anti-hepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.
      ,
      • Montalti R.
      • Nardo B.
      • Bertelli R.
      • Beltempo P.
      • Puviani L.
      • Vivarelli M.
      • et al.
      Donor pool expansion in liver transplantation.
      ,
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