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.)     

Liver Transplantation from Donors Aged 80 Years and Over: Pushing the Limit

Older donors are a growing part of the total donor pool but no definite consensus exists on the limit of age for their acceptance. From November 1998 to January 2003, in a retrospective case-control multicenter study, we compared the outcome of 30 orthotopic liver transplantations (OLTs) with octogenarian donors and of 60 chronologically correlated OLTs performed with donors <40 years. The percentage of refusal was greater among older than younger donors (48.2 vs. 14.3%; p < 0.001). Cold ischemia was significantly shorter in the older than younger groups. Recipients with hepatocarcinoma and older age received octogenarian grafts more frequently. No differences were seen in post-operative complications and 6-month graft and patient survival. However, long-term survival was lower in patients transplanted with octogenarian donors (p = 0.04). Interestingly, the mortality related to hepatitis C recurrence was greater in patients with octogenarian donors. Accordingly, the long-term survival of HCV-positive patients who received older grafts was lower than those receiving younger grafts (p = 0.05). Octogenarian livers can be used safely but a careful donor evaluation and a short cold ischemia are required to prevent additional risk factors. However, hepatitis C recurrence is associated with a greater mortality in patients who received octogenarian grafts raising concerns whether to allocate these livers to HCV-positive recipients.     

Impact of anti-hepatitis Bc-positive grafts on the outcome of liver transplantation for HBV-related cirrhosis

BACKGROUND: The present scarcity of organ donors requires consideration of grafts from sources not previously used. Several studies have addressed the use of grafts from donors who have antibodies to the hepatitis B core antigen (anti-HBc+). The aim of this study was to evaluate the impact of the use of anti-HBc+ grafts in patients transplanted for hepatitis B virus (HBV)-related cirrhosis. METHODS: Recipients of first hepatic transplants from donors with antibodies to HBV were identified retrospectively. All patients who had serology suggestive of active HBV and were negative for hepatitis C and D were included in the analysis. The Kaplan-Meier method was used to assess the actuarial recurrence-free survival on patients with graft survival longer than 1.5 months. The stepwise Cox regression model was used to identify independent predictors of HBV recurrence. RESULTS: One thousand seven hundred seventeen first liver transplants were performed at the Thomas E. Starzl Transplantation Institute from September 1, 1990, to December 31, 1999. HBV was the cause of cirrhosis in 112 patients (6.5%). Thirty-three patients had coexistent viral infection (23 HCV and 10 HDV). Fourteen donors (17.2%) were positive for HBV markers, with nine anti-HBc+ and with five both anti-HBc+ and anti-HB surface-positive; of these, 13 anti-HBc+ organ recipients had long-term survival. Nine (69.2%) of these cases were reinfected versus 20 (35.7%) in the group that received grafts from HBV- donors (P<0.05, Fisher's exact test). The mean time to reinfection was shorter in the anti-HBc+ group (2.9 yr vs. 6.4 yr, P<0.005). There were no statistical differences in graft or patient survival between the two groups. HBV prophylaxis with combined lamivudine and hepatitis B immunoglobulin (HBIG) significantly reduced the reinfection rate (P<0.03). Hepatitis Be (Hbe) antigen-positive recipients trended to faster reinfection (not significant). Cox regression analysis revealed that both anti-HBc graft donor status (RR, 2.796; P=0.020) and combination of lamivudine/HBIG (RR, 0.249; P=0.021) are independently associated with reinfection. CONCLUSIONS: The use of anti-HBc+ liver grafts does not affect graft or patient survival. However, patients who receive these organs are 2.5 times more likely to develop HBV recurrence. Lamivudine and HBIG combination decreases HBV recurrence 4-fold.     

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

BACKGROUND: Liver transplantation from hepatitis B core-antibody (HBcAb)-positive donors to hepatitis B surface-antigen (HBsAg)-negative recipients has been associated with a risk of hepatitis B virus (HBV) infection in the absence of antiviral prophylaxis. The aim of this study is to assess the efficacy of long-term lamivudine monotherapy to prevent development of HBV infection in HBsAg-negative recipients of liver allografts from HBcAb-positive donors. METHODS: From 315 cadaveric adult liver transplantations performed at our unit between July 1999 and March 2005, 18 recipients (5.7%) received liver allografts from HBcAb-positive donors, 13 of whom were HBsAg-negative pre-transplantation. The recipients consisted of four females and 14 males, age range 28-65 yr (median 49.5 yr). Post-transplantation, HBsAg-negative recipients were administered lamivudine 100 mg daily long term. HBsAg-positive recipients were administered low-dose hepatitis B immunoglobulin (HBIg) and lamivudine according to our usual protocol. Standard post-transplantation immunosuppression was given. Recipients were followed up regularly (range 2-69 months, median 21 months) for development of de novo HBV infection. RESULTS: Ten HBsAg-negative recipients received long-term lamivudine. One patient (HBcAb and HBsAb positive pre-transplant) did not receive lamivudine and, in two patients, lamivudine was discontinued following urgent re-transplantation for primary graft non-function. All 13 of the HBsAg-negative recipients were still alive, with no evidence of HBV infection at the end of follow-up. CONCLUSION: Long-term lamivudine monotherapy was effective in preventing development of HBV infection in HBsAg-negative liver transplant recipients 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.     

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.     

Poor survival after liver retransplantation: Is hepatitis C to blame?

Data from 1990 to 1996 suggest that the prevalence of hepatitis C virus (HCV) infection in repeated orthotopic liver transplantation (re-OLT) is increasing, and patient survival may be worse. Aims of the study are to: (1) assess the prevalence of HCV in re-OLT, (2) compare survival between primary OLT and re-OLT for HCV versus non-HCV diseases, and (3) evaluate Model for End-Stage Liver Disease (MELD) scores in re-OLT. The United Network for Organ Sharing database for adult patients undergoing primary OLT or re-OLT from January 1996 to June 2002 was analyzed. Patients with malignancy or those who underwent re-OLT within 30 days of primary OLT were excluded. A total of 22,120 primary OLTs and 2,129 re-OLTs were performed. HCV was noted in 9,564 primary OLTs (43.2%) and 899 re-OLTs (42.2%). Overall 1, 3, and 5-year patient survival rates were 86%, 79%, and 73% for primary OLT, but 67%, 56%, and 52% for re-OLT (P < .001). Survival rates of patients with HCV at 1, 3, and 5 years were 86%, 76%, and 68% for primary OLT and 61%, 50%, and 45% for re-OLT (P < .001). Survival was less for patients with HCV compared with those with autoimmune hepatitis (AIH) and hepatitis B for re-OLT (P < .01). However, survival after re-OLT was no different for those with HCV than for those with all other causes. MELD scores between 11 and 20 were the most common for re-OLT. A marked decreased in survival was noted in all patients who underwent re-OLT with MELD scores greater than 25. HCV prevalence in OLT has reached a plateau in recent years. Survival after re-OLT is inferior to that for primary OLT, but re-OLT survival appears to have improved. Survival after re-OLT is lower in patients with HCV compared with those with AIH and hepatitis B, but no different than for those with most other liver diseases. Survival appeared worse in patients who underwent re-OLT with a MELD score greater than 25. (Liver Transpl 2003;9:1019-1024.)     

Morbidity and mortality in liver retransplantation

INTRODUCTION: The incidence of orthotopic liver retransplantation (re-OLT) ranges from 6% to 11%. The most frequent causes of early re-OLT are allograft failure, uncontrolled acute rejection, and vascular complications. MATERIALS AND METHODS: A retrospective study of 512 orthotopic liver transplants (OLTs) in 482 patients over 15 years. RESULTS: The incidence of re-OLT was 6.6%, with a higher percentage of men requiring re-OLT than first-time OLT (75.0% vs 63.0%, P < .05). The reasons for re-OLT were thrombosis 21.7%, aneurysm 6.5%, stenosis 3.2%, primary nonfunction (PNF) 21.7%, and chronic rejection or recurrence of the initial disease 40.4%. Complications included PNF (22.0%), acute renal failure (65.6%), postoperative infection (87.5%), and adult respiratory distress syndrome (9.4%; P < .05). No differences were seen in the incidence of septicemia or postoperative hemorrhage. The average survival was much lower in re-OLT (21.8 days) compared with OLT (194.5 days; P < .05). The mortality rates in re-OLT were 100% for primary biliary cirrhosis, 85.7% for HCV, 50% for alcoholic cirrhosis, and 20% for HBV. A direct association between the Model for End-stage Liver Disease (MELD) score and the number of complications was present. DISCUSSION: There was a greater requirement for re-OLT in men and those patients transplanted due to hepatitis B virus cirrhosis and fulminant hepatitis (P < .05). The re-OLT patients had no greater incidence of sepsis compared with the OLT patients, although they did have a greater incidence of primary graft dysfunction, acute renal failure, adult respiratory distress syndrome, and postoperative infection (P < .05). The MELD was a good parameter for predicting graft evolution. Re-OLT in patients with primary biliary cirrhosis and hepatitis C virus was associated with a high degree of mortality.     

Liver transplantation using donors older than 80 years: a single-center experience

AIM: The shortage of organs for orthotopic liver transplantation (OLT) has forced transplantation centers to expand the donor pool by using donors traditionally labeled as "extended criteria donors." One such example is OLT using a donor with advanced age. MATERIALS AND METHODS: We retrospectively evaluated 10 patients who received a liver graft from cadaveric donors older than 80 years. We analyzed pretransplantation donor and recipient characteristics, as well as the evolution of the recipients. RESULTS: All 10 donors were older than 80 years (median age, 83.5; range, 80-93). No steatosis (>30%) was accepted in the older donor group. Medium follow-up was 19.5 months. The most frequent cause for OLT was hepatitis C virus (HCV) cirrhosis (8/10 patients). We had 1 case of primary nonfunction, 1 patient died immediately after surgery because of extrahepatic complications (cardiac arrest), and 2 other patients had a severe HCV recurrence and died after 1 and 2 years from OLT, respectively. Five patients had HCV recurrence and biliary complications were present in 60% of the patients. No cases of acute or chronic rejection were described. Overall survival rates after 1 and 3 years were 80% and 40%, respectively. CONCLUSIONS: Old donor age is not an absolute contraindication to OLT. Liver grafts from donors older than 80 years can be used knowing that there is a high risk of postoperative complications. Furthermore, the increased risk of developing severe HCV recurrence, related to older donor age, suggests that such livers should be used in HCV-negative recipients.     

Liver transplantation using non-heart-beating donors: Belgian experience

Mortality on liver transplantation (OLT) waiting lists has increased dramatically. Until recently, non-heart-beating donors (NHBD) were not considered suitable for OLT, because of a higher risk of primary graft nonfunction (PNF) and biliary strictures. However, recent experimental/clinical evidence has indicated that NHBD-OLT is feasible when the period of warm ischemia is short. PURPOSE: To characterize the results of NHBD-OLT in Belgium, a survey was sent to all Belgian OLT centers. RESULTS: Between January 2003 and November 2005, 16 livers originating from NHBD were procured and transplanted. The mean donor age was 48.8 years, including 9 males and 7 females with mean time of stop-therapy to cardiac arrest being 18 minutes and from cardiac arrest to liver cold perfusion, 10.5 minutes. Mean recipient age was 52.2 years including 12 males and 4 females. Mean cold ischemia time was 7 hours 15 minutes. No PNF requiring re-OLT was observed. Mean post-OLT peak transaminase was 2209 IU/L, which was higher among imported versus locally procured grafts. Biliary complications occurred in 6 patients requiring re-OLT (n = 2), endoscopic treatment (n = 2), surgical treatment (n = 1), or left untreated (n = 1). These tended to be more frequent after prolonged warm ischemia. Graft and patient survivals were 62.5% and 81.3%, respectively, with a follow-up of 3 to 36 months. CONCLUSION: This survey showed acceptable graft/patient survivals after NHBD-LT. The NHBD-liver grafts suffered a high rate of ischemic injury and biliary complications and therefore should be used carefully, namely with no additional donor risk factors, lower risk recipients, and short cold/warm ischemia.     

Influence of donor histology on outcome in patients undergoing transplantation for hepatitis C

BACKGROUND: Risk factors for graft loss and recipient death in liver transplantation for hepatitis C virus (HCV) have been extensively investigated. Donor age was defined as one of the most important predictors of outcome in these patients; however, the mechanism leading to more severe recurrent hepatitis has not yet been investigated. METHOD: In a retrospective analysis, histological findings of 79 donor liver grafts were assessed according to criteria inflammation, fibrosis, fatty degeneration, and necrosis. These findings were correlated with the histological and clinical course of HCV-positive liver graft recipients. RESULTS: The overall 1-, 5- and 10-year graft survival figures were 85%, 77%, and 60%, respectively. We could not identify any correlation between outcome, fat content, and necrosis in the donor liver. However, stage 3 and 4 fibrosis 1 year after liver transplantation was significantly increased in the group of patients receiving a graft from a donor with portal inflammation (P<0.05). Additionally, the occurrence of intrahepatic inflammation was significantly increased in older donors (P<0.05) and donors with prolonged intensive care hospitalization (P<0.05). CONCLUSION: A number of risk factors for detrimental outcome in HCV-positive patients after liver transplantation have been identified. In particular, older donor age significantly impaired outcome in recent analysis, but due to donor shortage it is not possible to provide young grafts for all HCV-positive patients. Our data show that donor histology is helpful in identifying patients with more severe recurrent hepatitis prior to transplantation, and that especially in older donors, prolonged intensive care hospitalization should be avoided.     

Donors positive for hepatitis B core antibodies in nonliver transplantations

We reviewed available, particularly epidemiological data regarding transplantation of organs from donors positive for hepatitis B core antibodies (HBcAb) to evaluate the possibility of transmitting the disease. For nonhepatic organs, the risk is low: higher for lung but lower for kidneys and heart, according to the quantity of lymphoid tissue. The use of such organs is increasing owing to the worldwide organ shortage. Unfortunately, even if the use of HBcAb-positive donors does not seem to affect patient or graft survival, the United Network for Organ Sharing and United States Renal Data System registries do not have data on hepatitis B incidence after transplantation. Cohort data suggest that the use of such donors is safe if one follows suggested guidelines. In particular, recipients with no evidence of HBsAb should receive prophylaxis with either lamivudine or HB immunoglobulin. Our data show a 15%-20% incidence of HBcAb-positive donors, as in other European countries. The 1-year graft outcomes are good, with a 3% seroconversion rate to HB surface antigen.     

Use of kidney donors with hepatitis B, hepatitis C, or brain tumor: a single-center experience

Introduction

With the rapid increase in the number of patients on the waiting lists, the idea of using organs from donors who were previously classified as “marginal” has emerged. The aim of this study was to evaluate the clinical outcomes of the patients who received kidneys from donors with hepatitis B, hepatitis C, or brain tumors.

Patients and Method

Between 2003 and 2010, 27 transplantations were performed from donors with hepatitis B, hepatitis C or brain tumors between 2003 and 2010. Demographic and clinical characteristics of donors and recipients were retrospectively collected from medical files.

Results

Fifteen patients received kidneys from donors with hepatitis B: 9 from deceased donors having a positive hepatitis B surface antigen (HBsAg) and six from living donors with positive HBsAg having negative results of qualitative hepatitis B DNA analysis. Two of the fifteen recipients were previously diagnosed with chronic active mild hepatitis B infection. The remaining 13, who were HBsAg (−)/anti-HBs(+) at the time of transplantation, underwent hepatitis B immune globulin and lamivudine therapy. Median follow up time was 40 ± 35 months. One patient developed decompensated liver disease owing to noncompliance to lamivudine therapy. Five patients who received grafts from anti-HCV(+) deceased donors were anti-HCV(+) at the time of transplantation with alanine aminotransferase (ALT) levels <40 U/L. All grafts remained functional at a median of 70 months. Seven subjects received grafts from deceased donors with brain tumors, none of whom had a history of a craniotomy or a ventriculoperitoneal shunt. All recipients had serious vascular access problems. No graft loss or de novo malignancies was observed among these patients after a median follow-up of 69 ± 26 months.

Conclusion

With appropriate patient selection, the donated organ pool can be expanded by addition of donors with hepatitis or brain tumors.     

Predictability and Survival in Liver Replantransplantation: Monocentric Experience

Liver retransplantation is the only treatment for patients with hepatic graft failure. Due to the shortage of organs, it is essential to optimize its use. Between 1998–2010, our center performed retransplantations on 48 (12.8%) patients (re-OLT). The data are compared with those for a group of 374 patients who did not receive retransplantations (NO re-OLT). The re-OLT vs NO re-OLT groups did not significantly differ in mean age of recipients (47 vs 51 years), indications for transplantation (hepatitis C virus cirrhosis 54% vs 56%, alcoholic cirrhosis 25% vs 17%, hepatocellular carcinoma 14% vs 22%), mean Model for End-stage Liver Disease (25 vs 20), mean total cold ischemia time (385 vs 379 minutes), or mean age of donors (52 vs 49 years). The main causes of retransplantation were primary graft nonfunction (64%), arterial thrombosis (8%), biliary complications (6%), and hepatitis C virus recurrence (4%). The difference in overall patient survival was not statistically significant. The patient's survival at 1, 3, 5, and 10 years for RE-OLT vs NO-reOLT was 56% vs 63%, 53% vs 60%, 46% vs 57%, and 44% vs 53%, respectively. Multivariate analysis identified Model for End-stage Liver Disease ≥23 as a predictor factor of retransplantation (P = .04). Other variables predicting outcome included age of donors (≥65 years vs younger group), age of recipients (≥50 years vs younger group), cold ischemia (≥600 vs <600 minutes), and transplantation indications (hepatitis C virus, hepatitis B virus, alcohol, and others). The retransplantation performed between 8–15 days appeared to have worse results than those in other periods (0–7 days, 16–30 days, 1–6 months, >6 months). The incidence of re-OLT in the series (12.8%) was comparable to that in the literature, and primary graft nonfunction in the study represents the main cause of retransplantation. Our analysis showed that the indication of the first transplant and the age of the donor were not risk factors for re-OLT. Liver retransplantation is a concrete alternative lifesaver for patients with graft failure.     

Successful Use of Extended Criteria Donor Grafts With Low to Moderate Steatosis in Patients With Model for End-Stage Liver Disease Scores Below 27

Liver transplantation may be performed using extended criteria donor grafts (ECDg). The characteristics of ECDg include age >60 years, long intensive care unit (ICU) stay, history of malignancy or steatosis. Grafts are often discarded due to steatosis, which can be macrovesicular (MaS) or microvesicular (MiS). MaS is the variety most frequently involved with unfavorable outcomes due to primary nonfunction (PNF) or primary dysfunction (PDF). As of January 2000, all livers referred to our institution were considered potentially transplantable. Steatosis was defined as the presence of fat droplets in more than 5% of hepatocytes. We observed 35 steatotic grafts. Grafts were stratified according to MaS and MiS as follows: low steatosis (5%–15%), mild steatosis (16%–30%), moderate steatosis (31%–60%), or severe steatosis (>60%). Fifteen grafts with moderate (n = 2) or severe (n = 13) MaS were discarded. Twenty grafts were harvested: 18 of them were transplanted at our institution, the remaining 2, discarded by our donor team, were transplanted by other Italian centers. Low MaS was detected in 10 grafts (50%), mild MaS in 4 (20%), and moderate MaS in 2 (10%). Low MiS was detected in 8 grafts (40%), mild MiS in 5 (25%), and moderate MiS in 1 (5%). Steatotic grafts were transplanted only into recipients with model for end-stage liver disease (MELD) scores <27. The 6-month graft survival was 80%; the PNF rate was 10%; and the PDF rate was 15%. The careful use of ECDg with low to moderate steatosis is possible if particular care is taken to avoid additional risk factors related to the recipient.     

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.     

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.     

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.     

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.     

拉米夫定预防肝移植术后乙型肝炎病毒再感染的研究

目的 探讨和评价拉米夫定预防原位肝移植术后乙型肝炎病毒（HBV）再感染的效果。方法 41例患者，术前诊断为肝炎后肝硬化（失代偿期）者22例，慢性重型肝炎并肝炎后肝硬化（失代偿期）者12例，慢性重型肝炎者7例，其中HBVDNA阳性16例。41例患者均采用背驮式原位肝移植，术前15例给予拉米夫定治疗，术后41例患者均服用拉米夫定。结果 10例患者术后出现HBV再感染，其中9例为YMDD变异毒株感染，术后1、2年的HBV再感染率分别为9．8％（4／41）、24．4％（10／41）。术前血清HBVDNA阴性者术后HBV再感染率（12．0％，3／25）明显低于HBVDNA阳性者（43．8％，7／16）。术前长期服用（超过6个月）拉米夫定者和未服用拉米夫定者术后HBV再感染率分别为66．7％、23．1％，均明显高于术前短期（未超过6个月）服用拉米夫定者（0，P〈0．05）。结论 术前服用拉米夫定可降低乙型肝炎患者肝移植后HBV再感染率，但服药时间不宜超过6个月；长期、单一的应用拉米夫定易导致病毒变异而出现耐药毒株感染。