Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation

HYPOTHESIS: Hepatic allografts from donors positive for antibody to hepatitis B core antigen (anti-HBc) frequently transmit hepatitis B virus (HBV) infection to recipients. Therefore, most transplantation centers will not use these organs for orthotopic liver transplantation (OLT). Although it is expensive and not always efficacious, hepatitis B immune globulin (HBIG) has been used routinely for indefinite periods to prevent HBV infection in liver allograft recipients. We assessed the effectiveness of long-term use of a nucleoside analog, lamivudine, in preventing HBV transmission by anti-HBc-positive allografts. DESIGN: Retrospective study. SETTING: A tertiary care center. PATIENTS: Twelve patients received hepatic allografts from anti-HBc-positive donors at Loyola University Medical Center, Chicago, between February 23, 1998, and March 13, 2001. INTERVENTION: All patients received 10 000 U/d of intravenous HBIG for 7 days. In addition, they received 300 mg/d of lamivudine in divided doses. Their liver biopsy specimens were tested for HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAb). Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody (HBsAb). MAIN OUTCOME MEASURE: The incidence of HBV infection in recipients who received HBcAb-positive donor livers and lamivudine prophylaxis. RESULTS: All recipients were anti-HBc negative before OLT. Five of the recipients had HBsAb titers greater than 150 U at the time of OLT. Three of the donor livers were HBV DNA positive and 2 were hepatitis B core antigen positive at the time of OLT. Donor serum was HBcAb positive in all 12 donors. None of the recipients have become infected with HBV with a follow-up of 2 to 38 months. CONCLUSION: Perioperative use of HBIG combined with long-term use of lamivudine can prevent HBV infection in recipients who receive hepatic allografts from HBcAb-positive donors.     

Lamivudine monoprophylaxis for de novo HBV infection in HBsAg-negative recipients with HBcAb-positive liver grafts

We followed the efficacy of long-term lamivudine monotherapy in preventing development of de novo hepatitis B (DNHB) in a large cohort of hepatitis B surface antigen (HBsAg)-negative recipients with grafts from hepatitis B core antibody (HBcAb)-positive donors. Recipients were observed over a long follow-up. Between July 1999 and December 2008, 45 patients (median age 54, range 19-67) who were HBsAg negative before transplantation were included in the study of monoprophylaxis with lamivudine starting on post-operative day 1, and continuing for life. Mean follow-up: 37.9 months; median 32.1 months (range 2.4-117). No suspension of therapy was reported during the study. Post-transplantation, no DNHB was observed in follow-up: all 45 HBsAg-negative recipients remained HBsAg and HBV DNA negative. Thirty-four of these HBsAg-negative recipients were alive at conclusion of the study. A total of 11 patients died, five of HCV recurrence, two of hepatocellular carcinoma (HCC) recurrence, two of disseminated KSV infection, and two of multiorgan failure because of early graft dysfunction. Patient and graft survival of HBsAg-negative recipients with HBcAb-positive donor grafts (45 cases) were not significantly different from those of the HBsAg-negative recipients with HBcAb-negative donor grafts (302 cases). In our experience, lamivudine monoprophylaxis provided complete protection against HBV reactivation and showed long-term efficacy.     

Safe use of livers from donors with positive hepatitis B core antibody

Thirty-five patients received liver transplants using liver donors who had positive test results for the hepatitis B core antibody (HBcAb). In the same time frame, 195 patients received HBcAb-negative liver donors. Mean follow up for patients receiving HBcAb-positive donors was 25 months. All patients receiving HBcAb-positive donors were monitored for recurrence of hepatitis B (HBV) with HBV DNA assays. There was no de novo HBV in recipients of HBcAb-negative grafts. In the group of patients receiving HBcAb-positive donors, 4 of 35 patients died within 3 months after transplant with no evidence of HBV recurrence at time of death. Four patients were transplanted for HBV-related disease and were postoperatively placed on lamivudine and hepatitis B immune globulin (HBIG). HBV recurrence was seen in one of these patients. Of the remaining 27 patients, three of three mismatched patients (HBcAb-positive donor to HBcAb-negative recipient) developed de novo HBV (100%). Of 24 matched patients (HBcAb-positive donor to HBcAb-positive recipient), only two (7%) developed recurrent HBV allograft reinfection. All de novo and recurrent HBV infections were successfully managed with HBIG and lamivudine therapy. Survival for this subgroup of patients receiving HBcAb-positive donors for non-HBV–related liver disease was 100%. We conclude that the judicious use of HBcAb-positive donors is reasonably safe and associated with low morbidity and mortality, with the appropriate follow-up protocols. Additionally, lamivudine use can be reserved for those cases with de novo or recurrent HBV in the liver allograft, or, selectively, as prophylaxis in those recipients patients who are naı̈ve to HBV and receive an HBcAb-positive donor. (Liver Transpl 2002;8:556-561.)     

Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors

Exclusion of liver grafts from hepatitis B core antibody (anti-HBc) positive donors to prevent de novo hepatitis B virus (HBV) infection after liver transplantation is not feasible in areas highly endemic for HBV virus like Taiwan, where approximately 80% of adults are anti-HBc(+). The efficacy of lamivudine monotherapy to prevent de novo HBV infection after living donor liver transplantation (LDLT) using grafts from anti-HBc(+) donors remains to be elucidated. From June 1994 to August 2000, LDLT was performed in 42 recipients. Twenty-four of the 42 donors were anti-HBc(+) (57%). Pre-transplant HBV vaccination was given to all recipients irrespective of anti-HBc status at monthly intervals for 3 months. Until December 1997, eight recipients received liver grafts from anti-HBc(+) donors without prophylaxis. Since January 1998, prophylaxis with lamivudine monotherapy was given to 16 recipients receiving liver grafts from anti-HBc(+) donors. De novo HBV infection occurred in three of the eight recipients (37.5%) who did not receive prophylaxis, while none of the 16 recipients given lamivudine developed de novo HBV infection after a mean follow-up of 25 months. Two of the three recipients with de novo HBV infection were anti-HBs(-) and one recipient was anti-HBs(+). Lamivudine was well tolerated, and no side effects were noted. These results suggest that lamivudine monotherapy for recipients receiving anti-HBc(+) liver grafts is a simple, relatively inexpensive and effective prophylactic regimen for prevention of de novo HBV infection. The additive protection provided by vaccine-induced or natural immunity is uncertain.     

Safety of using hepatitis B virus core antibody or surface antigen-positive donors in kidney or pancreas transplantation

Hepatitis B virus core antibody (HBcAb) or surface antigen (HBsAg)-positive organ donors have the potential to transmit infection to transplant recipients. We investigated the safety of using HBcAb(+) or HBsAg(+) donors in kidney or pancreas transplant recipients with 1 yr lamivudine prophylaxis. While HBsAb(-) recipients of HBcAb(+) donors received prophylaxis, HBsAb(+) recipients did not. HBsAg(+) organs were only used in patients who were both HBcAb and HBsAb(+). Forty-six patients received HBcAb(+) and four received HBsAg(+) organs (47 kidney, two pancreas, and one kidney/pancreas). All but one recipient were HBsAg(-), 25 were HBsAb(+), and 19 HBcAb(+). During a median 36 months of follow-up (range 6-66 months), with 43 of a total 50 patients having at least 1 yr follow-up and were off lamivudine, and none of the patients developed hepatitis B viremia or seroconversion to HBsAg or HBsAb(+). These results suggest that HBcAb(+) or HBsAg(+) organs can be used safely in selected recipients with lamivudine prophylaxis without requiring hepatitis B immunglobulin.     

Living donor liver transplantation from hepatitis B core antibody positive donors

Liver allografts from donors previously exposed to hepatitis B virus (HBV) carry the risk of transmission of HBV infection to immunosuppressed recipients. However, exclusion of donor candidates with the serologic evidence of resolved hepatitis B-HBV surface antigen (HbsAg) negative and HBV core antibody (anti-HBc) positive-is not feasible in countries endemic for HBV. AIM: Our aim was to assess the safety of living donor liver transplantation from anti-HBc positive donors. MATERIALS AND METHODS: In our institution, 152 transplants were performed between June 1999 and April 2004. Fifty-six (37%) of the living donors were anti-HBc positive. Twenty of these liver grafts were transplanted to HbsAg-negative recipients. We excluded four HBsAg negative recipients who died because of early complications after transplantation. Lamivudine (100 mg/day) was given for prophylaxis of de novo HBV infection. RESULTS: The mean follow-up time for 16 HBsAg-negative recipients was 21.7 (7-48) months. None of them experienced de novo HBV infection. CONCLUSION: The use of liver allografts from anti-HBc-positive living donors is reasonably safe in HBsAg-negative recipients under lamivudine prophylaxis.     

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

INTRODUCTION: With the shortage of donor organs, increasing number of hepatitis B core antibody (HBcAb)-positive [HBcAb(+)] liver allografts are being used for liver transplantation (LTx) in patients who are HBcab-negative [HBsAb(-)]. This study was aimed at assessing outcomes for hepatitis C virus (HCV)-positive [HCV(+)] and HCV-negative [HCV(-)] patients who received HBcAb(+) liver grafts from deceased donors and also received a short course of hepatitis B immunoglobulin (HBIg) with long-term lamivudine therapy after LTx. MATERIALS AND METHODS: From February 1995 through February 2003, 28 patients (mean age 53.8 +/- 10.2 years, 19 men and nine women, 16 HCV[-]; 12 HCV[+]) received HbcAb(+) liver allografts. All recipients received a short course of HBIg prophylaxis (10,000 units/day for 4 days) and long-term lamivudine 100 mg/d after LTx in addition to a tacrolimus-based immunosuppressive regimen. RESULTS: Seven (25%) of the 28 recipients died during follow-up and three recipients required retransplantation. Three recipients (10.7%) developed HBV infection during follow-up, one of whom died 36 months after LTx and the other two had YMDD mutant HBV. The overall 6-year actuarial patient survival after transplantation was 74.4% and those for HCV(-) and HCV(+) recipients were 81.3% and 66.6%, respectively (P = .46). The overall 6-year actuarial graft survival was 63.9% and those for HCV(+) and HCV(-) recipients were 68.8% and 57.1%, respectively (P = .6). CONCLUSION: We conclude that HBcAb(+) liver grafts can be used for both HCV(+) patients and HCV(-) patients who are critically ill, have early hepatocellular carcinoma, or have been exposed to HBV in the past. A short course of HBIg-lamivudine combination therapy provides effective prophylaxis against HBV infection in 89% of recipients of HBcAb(+) grafts.     

Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti-HBc positive donors.

BACKGROUND: The shortage of donor organs occasionally mandates the use of hepatic allografts from anti-HBc+ donors in recipients who are susceptible to de novo hepatitis B virus (HBV) infection. The efficacy of hepatitis B immune globulin and lamivudine to prevent de novo HBV infection in anti-HBs negative recipients of allografts from anti-HBc+ donors has not been investigated. METHODS: After liver transplantation with an allograft from a donor positive for anti-HBc, recipients who were anti-HBs-, HbsAg- received hepatitis B immune globulin (HBIG) 10,000 IU i.v. daily for 7 days and monthly for 6 months. After 6 months, 1000 IU of HBIG was given IM. every 2 weeks for 18 months. Patients transplanted after 4/1/97 were given lamivudine 150 mg daily starting postoperative day 1. RESULTS: Between 8/14/96 and 6/10/98, 264 orthotopic liver transplants were performed and 16 anti-HBs-, HbsAg- patients received an hepatic allograft from a donor positive for anti-HBc. HBIG mono-therapy was administered to one patient. HBIG and lamivudine combination therapy was administered to 15 patients. Of the 16 patients, 8 were positive only for anti-HBc before transplant, and 8 were naive (anti-HBs-, anti-HBc-). The single patient who received HBIG monotherapy became HbsAg+ at 6 months. All patients receiving combination therapy with HBIG and lamivudine have remained HbsAg-. The average follow-up is 459 days (range 170-754). Two patients died from unrelated causes. CONCLUSIONS: Combination therapy with HBIG and lamivudine may prevent de novo HBV infection in anti-HBs-, HbsAg- recipients of hepatic allografts from anti-HBc+ donors.     

Case Report of Lamivudine-Resistant Hepatitis B Virus Infection Post Liver Transplantation from a Hepatitis B Core Antibody Donor

The use of allografts from donors with hepatitis B core antibody in liver transplantation (LT) is associated with the risk of de novo hepatitis B virus (HBV) infection. Prophylaxis using hepatitis B Immune globulin (HBIg) and lamivudine alone or in combination has been reported. Yet, there are no standardized regimens and long-term efficacy is not known. We report a case of a patient who underwent LT for alcoholic liver disease who received an allograft from a donor with Hepatitis B core antibody. The patient had no previous exposure to HBV, was vaccinated against HBV, and had demonstrated Hepatitis B surface antibody present in serum before and 6 months after transplantation. Prophylaxis with short-term HBIg (1 week) and indefinite lamivudine was given. De novo HBV infection developed more than 3 years after LT with a lamivudine-resistant polymerase mutant containing the rtM204I and rtl180L/M mutations. We reviewed the risk of de novo post-LT HBV infection in recipients of livers from hepatitis B core antibody positive donors. High risk were HBV naïve recipients, moderate risk recipients had isolated hepatitis B surface antibody (anti-HBs) or hepatitis B core antibody (anti-HBc), while low-risk recipients had both anti-HBs and anti-HBc. We reviewed prophylaxis protocols reported in the literature and made recommendations for management.     

Dual hepatitis virus infections in liver transplant: case report and a review of the literature

Abstract: Background: Liver transplantation (LT) using grafts from anti‐HBVcore antibody‐positive (anti‐HBVcAB+) donors carry risk for development of hepatitis B virus (HBV) infection. The long‐term course of hepatitis C virus (HCV) patients receiving anti‐HBVcAB+ grafts is poorly understood. Patients and methods: A patient with chronic hepatitis C received an anti‐HBVc+ graft and developed de novo hepatitis B after four months. We describe the 14 HCV patients who received antiHBVc+ grafts and the condition of disease. Results: Hepatitis B was treated successfully with lamivudine. One year later, breakthrough infection developed with a lamivudine‐resistant mutant. Addition of adefovir led to HBV surface antigen to surface antibody seroconversion after two yr, which was maintained long term. Antiviral therapy was discontinued. Liver biopsy revealed minimal histologic changes up to eight yr post‐LT. Survival of 14 recipients of antiHBVc+ allografts and 180 recipients of antiHBVc‐negative grafts was equal (minimum follow up of five yr). Liver biopsies at four yr showed grade 0/1 and stage 0/1 in >70%; only two patients showed bridging fibrosis. A literature review of dual hepatitis virus infection revealed an overall milder course of hepatitis post‐LT. Conclusion: The outcome of HCV patients receiving anti‐HBc+ grafts is good and may be associated with a milder course of recurrent HCV.     

Beneficial Effects of Short-Term Lamivudine Treatment for de novo Hepatitis B Virus Reactivation After Liver Transplantation

Clearance of hepatitis B surface antigen (HBsAg) by lamivudine is achieved in only a small proportion of patients with chronic hepatitis B virus (HBV) infection. We investigated the effect of lamivudine on de novo HBV reactivation after living-donor liver transplantation when the number of HBV was expected to be very small. Thirty-eight HBV-naive recipients who received liver grafts from antibodies to core antigen-positive donors receiving hepatitis B immunoglobulin (HBIG) were studied. HBsAg appeared in nine cases (23.7 %) despite receiving HBIG for 12-71 months (mean: 35.1 months) after transplantation. Lamivudine treatment was started in six recipients during the acute phase of HBV reactivation. Five of the six recipients achieved complete clearance of HBsAg in sera at a median of 4.6 months (ranging from 21 to 330 days) after lamivudine administration. Although lamivudine was stopped in four cases, all remained negative for HBsAg. Our findings suggested that short-term lamivudine treatment during acute phase of HBV reactivation could achieve complete clearance of HBsAg in a significant number of liver transplant recipients.     

Failure of reactivation of hepatitis B after liver transplantation in hepatitis B surface antigen-negative, core antibody-positive recipients

BACKGROUND: Hepatitis B virus (HBV) infection after liver transplantation may occur in patients previously not exposed to the virus, but who receive an organ from a surface antigen (HBsAg)-negative, core antibody (HBcAb)-positive donor. The risk of HBV reactivation after liver transplantation in recipients that are HBsAg negative and HBcAb positive requires definition, because reactivation in kidney and bone marrow transplant patients has occurred. PATIENTS AND METHODS: A total of 409 HBsAg-negative patients underwent transplantation between April 1994 and June 1999. Pretransplantation sera were tested subsequently for HBcAb and HBsAb and posttransplantation sera for HBsAg. RESULTS: Of the 55 recipients who were positive for HBcAb, 48, who were immunosuppressed predominantly using tacrolimus, showed no evidence of HBV reactivation as shown by the absence of HBsAg (mean follow up 21.3+/-13.5 months). The remaining seven died within 6 months. CONCLUSIONS: In our experience, HBV reactivation did not occur in HBsAg-negative, HBcAb-positive recipients after liver transplantation, most of whom were immunosuppressed with tacrolimus. We would not, therefore, currently recommend HBV prophylaxis in these patients.     

Risk of de novo hepatitis in liver recipients from hepatitis-B core antibody-positive grafts - a systematic analysis

Skagen CL, Jou JH, Said A. Risk of de novo hepatitis in liver recipients from hepatitis‐B core antibody‐positive grafts – a systematic analysis.
Clin Transplant 2011: 25: E243–E249. © 2011 John Wiley & Sons A/S. Abstract: Many transplant programs utilize liver grafts from hepatitis‐B core antibody (HBcAb)‐positive and hepatitis‐B surface antigen (HBsAg)‐negative donors. However, there is risk for de novo hepatitis B (DNH) in recipients of these grafts. We reviewed 26 studies reporting the rates of DNH in recipients receiving HBcAb‐positive liver grafts. Four hundred and sixty‐two donor–recipient pairs were included to evaluate the risk of DNH stratified by the recipient’s immune status to hepatitis B and type of prophylactic therapy given, if any. The rate of DNH was highest (58%) in the stratum of hepatitis‐B (HBV) naïve recipients who did not receive prophylaxis. In HBV naïve recipients, prophylactic therapy (lamivudine and/or hepatitis‐B immunoglobulin – HBIG) reduced DNH to 11% (odds ratio [OR] = 11.1, 95% CI 4.98–25, p < 0.0001 for DNH without prophylaxis). Recipients with hepatitis‐B surface antibody (HBsAb) positivity had DNH rates of 18% without prophylaxis and 0% with prophylaxis (OR = 9.2, 95% CI 1.1–83.3, p = 0.039). Recipients with both HBsAb and HBcAb positivity had DNH rates of 4% without prophylaxis and 3% with prophylaxis (p = 1.00), while recipients with HBcAb positivity alone had DNH rates of 14% without prophylaxis and 3% with prophylaxis (p = 0.21). There was no significant difference between the types of HBV prophylaxis received whether lamivudine, HBIG or both. However, in the subgroup who received HBIG alone, rates of DNH were higher after cessation of HBIG prophylaxis compared to DNH rates with indefinite HBIG (p = 0.0002). In summary, the risk of DNH is highest for HBV naïve liver recipients from HBcAb‐positive donors. Recipients who are HBV naïve as well as those recipients with isolated HBsAb positivity derive significant benefit from HBV prophylaxis after transplantation with a HBcAb‐positive graft. The ideal prophylactic regimen for prevention of DNH is unclear, but based on our analysis of the literature, antivirals alone may suffice. More data are needed with the newer antivirals for hepatitis B.     

Kidney transplantation from hepatitis B virus core antibody-positive donors: prophylaxis with hepatitis B immunoglobulin

Objective

Hepatitis B virus core antibody (HBcAb)-positive organ donors have the potential to transmit infection to transplant recipients.

Patients and Methods

We investigated the use of a single dose of 2000 IU of hepatitis B immunoglobulin in 18 patients among a population of 54 kidney transplant recipients from HBcAb-positive deceased donors.

Results

Twelve recipients were HBcAb-positive before transplantation. Among the other 42 patients, 5 (11.9%) seroconverted from HBcAb-negative to HBcAb-positive, whereas one HBcAb-positive recipient became hepatitis B virus surface antigen-positive with clinical signs of active hepatitis 6 years after transplantation. In the 18 patients who underwent prophylaxis, we did not find any seroconversion or hepatitis B virus (HBV) transmission. Graft and patient survival of HBcAb-positive kidney transplants did not differ significantly with a matched population of HBcAb-negative transplantation.

Conclusion

These results suggest that kidney transplantation from HBcAb-positive donors is safe with a low rate of HBV transmission. A prophylaxis with a single shot of hepatitis B immunoglobulin may be effective in reducing the risk of HBV seroconversion or reactivation and may be suggested in all naïve or HBcAb-positive transplant recipients.     

Kidney Transplantation from Hepatitis B Surface Antigen Positive Donors into Hepatitis B Surface Antibody Positive Recipients: A Prospective Nonrandomized Controlled Study from a Single Center

The number of patients on renal transplant waiting list is increasing rapidly in many countries, exacerbating the shortage of organs. We conducted a study to evaluate the safety and efficacy of deceased-donor kidney transplantation from hepatitis B surface antigen (HBsAg)-positive (+) donors into hepatitis B surface antibody (anti-HBs)-positive (+) recipients. Sixty-five patients received grafts from HBsAg(+) donors, and 308 subjects received grafts from HBsAg-negative(−) donors. Posttransplantation, recipients with HBsAg(−) grafts or HBsAg(+) grafts received 400 U of hepatitis B immunoglobulin once and twice, respectively. The seven recipients who received grafts from hepatitis B virus (HBV) DNA(+) donors were treated with hepatitis B immunoglobulin 400 U weekly for 3 months and lamivudine 100 mg daily for 6 months. All patients were monitored for liver function and hepatitis B viral status. The follow-up period was 38.7 ± 15.4 months. Although two recipients developed de novo HBV infection, neither patient developed severe liver dysfunction nor died. The incidence of liver injury (39/65 vs. 207/308, chi-square test, p > 0.05) and survival (log-rank test, p > 0.05) did not differ between the groups. We conclude that anti-HBs(+) recipients receiving HBsAg(+) grafts did as well as those receiving HBsAg(−) grafts.     

Occult hepatitis B virus infection in liver transplant recipients with recurrent hepatitis C: relationship with donor age and fibrosis progression

Abstract:  Liver transplantation (OLT) recipients who receive a graft from donors positive for hepatitis B virus (HBV) anti-core antibodies may develop overt " de novo " HBV infection. The study was undertaken to explore how often HBV infection may remain occult after OLT for hepatitis C, and whether it may represent a factor of graft fibrosis progression. We studied 30 consecutive patients transplanted for hepatitis C liver disease. Specimens from the native liver and from the graft were searched for occult HBV infection (O-HBV). In the native liver, 8/30 patients had detectable O-HBV; during the follow-up, O-HBV infection was demonstrated in 14 graft specimens. Graft O-HBV was associated with older donor age (≥50 yr; 8/9 vs. 6/21, p < 0.005). Recipients with graft O-HBV and no O-HBV in the native liver who received their grafts from donors aged >40 yr had faster fibrosis progression than recipients with no post-transplant O-HBV, whose grafts came from donors aged >40 yr and recipients whose grafts came from donors aged ≤40 yr (4/7 vs. 1/7 vs. 2/16, p < 0.05). In OLT recipients, O-HBV is more likely to occur when grafts are obtained from aged donors and may affect the rate of fibrosis progression because of recurrent hepatitis C.     

Lamivudine or lamivudine combined with hepatitis B immunoglobulin in prophylaxis of hepatitis B recurrence after liver transplantation: a meta-analysis

There is a controversy over whether the different outcomes of prophylaxis of hepatitis B virus (HBV) recurrence are attributable to different treatments. A systematic review and a meta-analysis were conducted to evaluate lamivudine monotherapy and combined therapy of lamivudine and hepatitis B immunoglobulin (HBIG) in HBV infected liver recipients. A fixed effects model was used for statistical pooling of relative risks (RR) for the different outcomes. Six articles (551 patients) fulfilled the inclusion criteria. Statistically significant differences were observed between lamivudine monotherapy and lamivudine + HBIG therapy in hepatitis B recurrence [ P  < 0.0001; RR = 0.38; 95% CI (0.25, 0.58)], YMDD mutant [ P  = 0.002; RR = 0.40; 95% CI (0.23, 0.72)] and hepatitis B recurrence in HBV-DNA positive patients before orthotopic liver transplantation [ P  < 0.00001; RR = 0.31; 95% CI (0.21, 0.45)]. No significant differences were observed in patient survival [ P  = 0.59; RR = 1.02; 95% CI (0.95, 1.09)], graft survival [ P  = 0.56; RR = 1.02; 95% CI (0.95, 1.09)] and diseases leading to death between the two groups [HBV recurrence leading to death: P  = 0.05; RR = 0.47; 95% CI (0.22, 1.02); hepatocellular carcinoma recurrence leading to death: P  = 0.13; RR = 0.34; 95% CI (0.09, 1.36)]. In conclusion, combination of lamivudine and HBIG can effectively decrease the recurrence rate of HBV and the incidence of YMDD mutant, but it can not improve patient survival and graft survival significantly. Well-designed large-sample trials are needed to evaluate the efficiency of combined therapy of lamivudine and HBIG in prophylaxis of HBV recurrence in liver graft recipients.     

Transplantation of hepatitis B surface antigen-positive livers into hepatitis B virus-positive recipients and the role of hepatitis delta coinfection.

The scarcity of liver donors requires consideration of grafts from sources not previously used. Allografts from hepatitis B surface antigen (HBsAg)-carriers without a significant liver disease have been proposed for liver transplant recipients with hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC). Combination prophylaxis schemes against HBV post-liver transplantation (LT) recurrence are currently available; the efficacy of those schemes in HBV-related cirrhosis and HCC must be assessed. This report describes the allocation of HBsAg-positive grafts in three HBsAg-positive recipients, with HBV-related cirrhosis and evolving HCC lesions, two of them with hepatitis Delta virus (HDV) coinfection. Patients were administered anti-hepatitis B immunoglobulins (HBIGs) and lamivudine in order to prevent HBV recurrence. In spite of anti-HBV prophylaxis, HBV infection did persist after LT in all patients (no serum clearance of HBsAg). HBV replication assessed by serum HBV deoxyribonucleic acid (DNA) presence was detected in the first month after LT in the 3 recipients. A prompt HDV reinfection with a clinical and histological pattern of hepatitis was observed in the 2 HBV / HDV coinfected recipients. In 1 of them, an evolving chronic hepatitis required a second LT. The non-HDV-infected patient showed an uneventful follow-up, but the lack of the neutralizing effect of HBIGs and the high risk of escape mutants forced the addition of adefovir-dipivoxil to lamivudine, in order to prevent viral variants and hepatitis recurrence. In conclusion, allografts from HBsAg-positive donors in HBsAg-positive recipients are associated with the persistence of the HBsAg after LT due to the failure of HBIG prophylaxis, even if lamivudine does inhibit virion production. This condition favors HDV replication and HDV hepatitis recurrence in coinfected patients. The allocation of HBsAg-positive grafts in HBsAg-positive recipients could be justified only in recipients without HDV coinfection and a combined prophylaxis with lamivudine and adefovir-dipivoxil is currently the best way to manage escape mutants in these recipients.     

Use of hepatitis B core antibody-positive donor kidneys in hepatitis B surface antibody-positive and -negative recipients

INTRODUCTION: The rate of hepatitis B virus transmission via organs from with isolated hepatitis B virus core antibody-positive (HBcAb+) donors in kidney transplant recipients seems very low. PATIENTS AND METHODS: Over 4 years, we performed 36 transplants from Ig HBcAb+, hepatitis B surface antigen (HBsAg)-negative donors into recipients with a history of prior hepatitis B virus (HBV) infection or reported vaccination (28 patients) and in recipients who were not immunized and received a pretransplant prophylaxis with hepatitis B immunoglobulins. We examined the HBV-related outcomes in these 36 patients in comparison with 40 recipients of allografts from HBcAb- donors. RESULTS: No patient receiving an allograft from an HBcAb+ donor developed clinical HBV infection or HBSAg positivity. The rate of seroconversion was 14.2% in immunized patients, 12.5% in nonimmunized patients, and 0% in the control group. The 17.8% of immunized patients developed elevated transaminases after transplant, in comparison with 25% and 10% in the nonimmunized patients and the control group, respectively. Graft and patient survival was 93% and 93% for immunized patients, 100% and 100% for nonimmunized patients, and 98% and 95% for the control group, respectively. CONCLUSION: The use of anti-HBc antibody-positive kidneys was associated with no risk of transmission of HBV infection, without affecting graft and patient survival, and could be considered a safe way to expand the donor pool. Our preliminary results suggest that such kidneys could be safely transplanted even in not immunized patients who underwent a prophylaxis with hepatitis B immunoglobulins.     

Twenty-four year single-center experience of hepatitis B virus infection in heart transplantation

Objective

Hepatitis B virus (HBV) infection is hyperendemic in Taiwan. We have reported the outcome of (1) recipients with hepatitis B surface antigen (HBsAg)-positive; HBsAg-negative recipients who receive donor hearts from HBsAg-positive donors; and treatment with lamivudine of hepatitis B flare-ups after heart transplantation, using case numbers that range from 100 to 200.

Methods

From July 1987 to May 2011, all 412 orthotopic heart transplant recipients and donors underwent routine preoperative screening for hepatitis B virus markers and liver function parameters. Lamivudine was prescribed prophylactically for recipients with elevated serum enzyme levels or an HBV DNA virus load before transplantation, or when there was evidence of hepatitis B flare-up after transplantation. Postoperative HBV markers and liver function parameters were collected over a mean follow-up time of 7.8 years.

Results

Thirty-four recipients were HBsAg-positive before heart transplantation, and 23 experiencing HBV reactivation upon follow-up requiring lamivudine treatment. Clinical responses were achieved in all of them: 15 were complete and two, slow partial responses. Twenty-six recipients with an HBV naïve status at the time of heart transplantation, and three patients received donor hearts from an HBsAg-positive donor under perioperative hepatitis B immunoglobulin prophylaxis. HBV infection was successfully prevented in two patients, but the other one contracted HBV hepatitis, which was successfully treated with lamivudine.

Conclusions

HBV reactivation after the heart transplantation was common but usually well controlled with lamivudine treatment. Although posttransplantation liver function deteriorated for a period, there was no HBV infection-related morbidity or mortality. Perioperative hepatitis B immunoglobulin prophylaxis can successfully prevent HBV naïve recipients from infection in some cases, but HBsAg-positive donors should only be considered in high risk situations.