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.     

Hepatitis B core antibody positive donors as a safe and effective therapeutic option to increase available organs for lung transplantation

BACKGROUND: The use of hepatitis B core antibody (HBcAb+) and hepatitis C antibody (HCV Ab+) positive donors represents one strategy to increase available donor organs, but this remains controversial because of concern for viral transmission to recipients. We hypothesized that isolated HBcAb+ donors represent minimal risk of viral transmission in vaccinated lung transplant (LTx) recipients. METHODS: A retrospective study was performed of LTx recipients who received HBcAb+ or HCV Ab+ pulmonary allografts. We analyzed liver function studies, viral hepatitis screening tests, quantitative polymerase chain reaction for hepatitis B viral DNA (HBV DNA) and hepatitis C viral RNA (HCV RNA), freedom from bronchiolitis obliterans syndrome, acute rejection, and survival. RESULTS: Between April 1992 and August 2003, 456 LTx operations were performed. Twenty-nine patients (HB group) received HBcAb+ allograft transplants with a median posttransplant follow-up of 24.5 months. Three critically ill patients (HC group) received HCV Ab+ allografts with a median follow-up of 21.5 months. One-year survival for the HB group is 83% versus 82% for all patients who received non-HB organs (P=0.36). No patient in the HB group developed clinical liver disease because of viral hepatitis, and all patients alive (n=21) at follow-up are, to date, HBV DNA and/or HBcAb negative. All patients in the HC group tested HCV RNA positive; one patient died of liver failure at 22 months. CONCLUSIONS: Risk of viral transmission with HCV Ab+ allografts seems high after LTx. However, the use of HBcAb+ pulmonary allografts in recipients with prior hepatitis B vaccination seems to be a safe and effective strategy to increase organ availability.     

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.     

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.     

Prevention of de novo hepatitis B with adefovir dipivoxil in recipients of liver grafts from hepatitis B core antibody-positive donors

Lamivudine has been shown to prevent de novo hepatitis B virus (HBV) infections in liver transplantation (LT) patients receiving hepatitis B core antibody-positive (HBcAb(+)) grafts, but it may produce long-term resistance. Adefovir dipivoxil (ADV) might be effective in preventing de novo hepatitis and resistance. A single-center, prospective trial was conducted with 16 adults (10 men and 6 women, mean age = 54 ± 11 years) who underwent LT with HBcAb(+) grafts between September 2007 and October 2009. After LT, patients were given ADV [10 mg daily (adjusted for renal function)]. No hepatitis B immune globulin was administered. At LT, all graft recipients were hepatitis B surface antigen-negative (HBsAg(-)), 38% were surface antibody-positive (HBsAb(+)), and 50% were HBcAb(+). The median follow-up after LT was 1.8 years (range = 1.0-2.6 years). All recipients had undetectable HBV DNA (<40 IU/mL) after LT until the end of follow-up. One recipient (6%) who was HBsAb(-) and HBcAb(-) before LT became HBsAg(+) after 52 weeks. One recipient was switched from ADV to entecavir for chronic renal insufficiency, and 19% of the patients had renal dose adjustments. There was a nonsignificant trend of increasing creatinine levels over time (1.2 mg/dL at LT, 1.3 mg/dL 1 year after LT, and 2.0 mg/dL 2 years after LT, P = 0.27). A comparison with a control cohort of LT recipients with hepatitis C virus who did not receive ADV showed no difference in the creatinine levels at LT or 1 year after LT. In conclusion, ADV prophylaxis prevents HBV replication in recipients of HBcAb(+) livers but does not fully protect recipients from de novo HBV. Long-term follow-up is needed to better determine the risk of de novo infection.     

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 naı&#x0308;ve to HBV and receive an HBcAb-positive donor. (Liver Transpl 2002;8:556-561.)     

Low-dose intramuscular hepatitis B immune globulin and lamivudine for long-term prophylaxis of hepatitis B recurrence after liver transplantation

The combination of lamivudine and hepatitis B immunoglobulins (HBIg) to prevent recurrence of HBV hepatitis has significantly improved the survival of patients transplanted for HBV-related end-stage liver disease. Generally, HBIg are administered intravenously. We evaluated the efficacy, tolerability, and cost savings of long-term intramuscular HBIg and lamivudine in 28 patients (23 men and 5 women), who received liver transplants for acute or chronic HBV-related liver disease. Twelve patients started lamivudine before and 16 at the time of liver transplantation. HBIg were administered intravenously during the first week (50 to 70,000 IU) and intramuscularly thereafter (1200 IU every 3 to 6 weeks) to maintain an HbsAb titer >100 IU/L. Mean follow-up was 20 +/- 13 months. Only one patient experienced HBV recurrence (9 months after transplantation). This patient had failed to follow the scheduled prophylaxis. Cumulative survival at 3 years was 83%. Intramuscular HBIg were well tolerated in all cases. Cost analysis comparing intramuscular vs intravenous HBIg administration showed that 39,490 Euros were saved per patient per year. These preliminary results show that low-dose intramuscular HBIg and lamivudine are efficacious and cost-effective for long-term prophylaxis of hepatitis B recurrence after liver transplantation.     

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.     

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.     

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.     

Adherence to Lamivudine after an early withdrawal of hepatitis B immune globulin plays an important role in the long-term prevention of hepatitis B virus recurrence

Lamivudine combined with hepatitis B immune globulin (HBIg) is the standard of care for preventing the recurrence hepatitis B virus after liver transplant. To determine the risk of hepatitis B virus (HBV) recurrence after early withdrawal of HBIg in patients receiving lamivudine maintenance therapy, 20 patients receiving a course of HBIg and lamivudine after transplantation and long-term maintenance therapy with lamivudine and 9 patients receiving HBIg and lamivudine indefinitely were analyzed. The survival rate was 90% after a mean follow-up of 83 months. The HBV recurrence rate was 14% with a mean period of 91 months free from HBV recurrence. Both groups had similar HBV recurrence rates, 15% for the combination and 11% for lamivudine alone. Four patients, 3 of whom were noncompliant with therapy, experienced posttransplant HBV recurrence. Patients who adhere to long-term prophylaxis with lamivudine after early withdrawal of HBIg have a low risk of HBV recurrence, similar to those who receive combination prophylaxis.     

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.     

Use of liver grafts from donors positive for antihepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine

BACKGROUND: The increasing demand for transplantation has resulted in a trend toward using virologically compromised donors. We reviewed our experience with liver grafts from hepatitis-B surface antigen (HBsAg)(-), antibody to core antigen (anti-HBc)(+) donors. METHODS: Sixty-two liver transplants using HBsAg(-), anti-HBc(+) donors were studied. The decision to use prophylaxis was based on the presence or absence of donor and recipient risk factors for posttransplant hepatitis-B virus (HBV) transmission or reinfection. If the donor or recipient showed positive HBVDNA, hepatitis-B immunoglobulin (HBIg) and lamivudine were used. If both donor and recipient HBVDNA were negative, a choice between lamivudine and no prophylaxis was made on the basis of presence or absence of HBsAg and antibody to the surface antigen (anti-HBs) in the recipient. RESULTS: No death or graft loss could be ascribed to HBV. Mild HBV infection occurred in two patients who were not taking the recommended prophylaxis. Among the other 60 patients, 1 showed positive e antigen (HBeAg) early after transplantation, and 2 (1 with recurrent cancer, 1 with HIV infection) showed HBsAg(+). None of the three patients had any other evidence of HBV infection. Forty-seven patients underwent liver biopsies. Changes consistent with hepatitis were observed in 26, and 24 had HCV infection; immunostains for HBV antigens were negative in all cases, and 7 showed positive HBVDNA. CONCLUSIONS: A selective protocol based on donor and recipient risk factors for post-liver transplant HBV infection can prevent hepatitis-B infection and avoid unnecessary administration of antiviral prophylaxis in recipients of HBsAg(-), anti-HBc(+) liver allografts.     

Outcomes of liver transplantation in simultaneously hepatitis B surface antigen and hepatitis C virus RNA positive recipients: the deleterious effect of donor hepatitis B core antibody positivity

Background

Recent data from Italian studies have shown excellent results of liver transplantation (LT) in hepatitis B virus (HBV)-infected patients with grafts from hepatitis B core antibody (HBcAb)—positive donors, whereas such grafts in hepatitis C virus (HCV)-infected recipients have displayed poorer outcomes. We investigated the results of LT with HBcAb-positive grafts in patients with ongoing HBV and HCV coinfections.

Methods

From August 1999 to December 2009, we performed 27 adult primary LTs from deceased heart-beating donors into recipients showing hepatitis B surface antigen (HBsAg)- and HCV-RNA-positivity simultaneously: 12 patients received a graft from an HBsAg-negative HBcAb-positive donor (core+D group) and 15 from an HBcAb-negative donor (core−D group). Immunosuppression included a calcineurin inhibitor, antimetabolite and steroids which were suspended at 6 months. Anti-HBV prophylaxis was always perfomed with anti-HBs immunoglobulins and nucleos(t)idic analogues.

Results

The groups were similar regarding variables of donor, recipient, donor-recipient match, LT procedure, and acute rejection treatment. Median follow-up for surviving grafts was 67 months (range, 16-141). Among all patients, HCV-RNA remained positive after LT. The prevalence of histologically proven recurrent HCV hepatitis was similar in the 2 groups: 83% core+D vs 73% core−D. No recurrent HBV hepatitis occurred during the follow-up. Graft survival at 5 years was significantly lower in the core+D group (core+D 48% vs core−D 87%; P = .018), in which a significantly higher prevalence of graft loss was caused by HCV recurrence (core+D 5/12, 42% vs core−D 1/15, 7%; P = .03). All of the 5 core+D patients who lost their grafts due to HCV recurrence did not receive anti-HCV therapy (4 owing to an aggressive disease and 1 because of patient refusal).

Conclusions

Outcomes of LT in patients with ongoing HBV and HCV coinfection are adversely affected by donor HBcAb positivity, an effect that is mainly mediated by the dismal course of HCV recurrence after LT.     

肝移植术后预防乙型肝炎病毒再感染281例的分析

目的分析乙型肝炎病毒(HBV)相关性肝病肝移植术后HBV再感染的原因及防治经验。方法回顾性分析281例HBV相关性肝病,移植前后给予抗病毒药物拉米夫定 人乙肝免疫球蛋白(HBIg)预防HBV再感染,其中9例为拉米夫定 阿德夫韦 HBIg,观察临床表现、血清HBV标志物、HBV DNA及肝活检免疫组织化学检测等指标。结果用拉米夫定 HBIg预防的272例中,有7例再感染,血清HBsAg、HBeAb和HBcAb阳性,肝活检免疫组织化学检测有HBsAg表达,其中2例血清HBV DNA阳性,4例经治疗后HBsAg又转阴。用拉米夫定 阿德夫韦 HBIg预防的9例中,血清学和肝活检免疫组织化学检测无HBsAg表达。结论拉米夫定 HBIg或拉米夫定 阿德夫韦 HBIg联合应用,可以有效预防HBV相关性肝病肝移植后HBV的再感染。     

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.     

No hepatitis recurrence using combination prophylaxis in HBV-positive liver transplant recipients with YMDD mutants

Recurrence of hepatitis B impairs the outcome of liver transplantation (OLT). In serum hepatitis B virus (HBV)-DNA-positive recipients, prophylaxis using lamivudine and immunoglobulins (HBIg) reduces the risk of recurrence, but it is undefined whether this regimen also protects candidates with YMDD mutants. Seventeen OLT viraemic candidates received pre-emptive lamivudine followed by post-OLT prophylaxis with lamivudine and HBIg. Both sera and liver biopsies were prospectively collected and high-sensitive polymerase chain reaction (PCR) assay was applied for HBV-DNA detection. Finally, the presence of YMDD mutants was explored in all PCR-positive samples. All patients remained hepatitis B recurrence-free after a mean follow up of 32 months. By PCR, serum HBV-DNA was detectable in 64.3% of cases at OLT-baseline, in 64.7% under combined prophylaxis and in 58.8% in patients (70.5% of the total) with a minimum follow up of 24 months. At OLT-baseline, YMDD mutants were found in 44.4% of patients. After OLT, mutants were present in 50% of patients but only in 16.6% of cases in the long period. Although 41% of the native livers and 42.8% of the analysed grafts harboured HBV-DNA, YMDD mutants were detected in 57% of the native positive livers. YMDD mutants were largely detected both at OLT-baseline and post-OLT, but their presence decreased over time. Regardless of the presence of YMDD mutants, no hepatitis B recurrence was observed in our OLT recipients using pre-emptive lamivudine followed by continuous prophylaxis with lamivudine and HBIg.     

Role of lamivudine in the posttransplant prophylaxis of chronic hepatitis B virus and hepatitis delta virus coinfection

BACKGROUND: Posttransplant combined lamivudine (LAM) and immunoglobulin (HBIg) prophylaxis is the gold standard in the case of single hepatitis B virus (HBV), but is still not recommended in the case of patients coinfected with hepatitis delta virus (HDV). METHODS: We compared two consecutive groups of chronic HDV carriers who survived >6 months after liver transplantation of the risk of recurrence, survival and HBIg requirements: 21 received passive prophylaxis (HBIg group) and 25 were treated with combined prophylaxis (LAM+HBIg group). The immunoprophylaxis schedule was the same in both groups: intramuscular HBIg targeted to maintain anti-HBs levels of >500 IU/L during the first 6 posttransplant months and >200 IU/L thereafter. RESULTS: The mean length of follow-up in the two groups was significantly different (133 vs. 40 months; P<0.001). None of the patients in either group developed recurrent hepatitis, and the 3-year actuarial survival rate was 100% in both groups. During the first 6 months, HBIg requirement was 38% lower in the LAM+HBIg group although similar anti-HBs target levels were maintained, leading to significantly lower costs (5,000 Euros in the first year and 500 Euros in the second). CONCLUSIONS: This is the first study of large and homogeneous cohort of long-term HDV coinfected liver transplant survivors showing the absence of HBV recurrence under combined prophylaxis. Although retrospective, our results suggest that combined anti-HBV prophylaxis should also be preferred to single immunoprophylaxis in patients with HDV coinfection because it allows significant cost savings in the first two posttransplant years.     

Management of hepatitis B virus infection in liver transplant recipients: prospects and challenges

Although survival of liver transplantation for patients with hepatitis B infection is comparable to uninfected transplant recipients, prevention of hepatitis B virus (HBV) reinfection remains an important goal. In this article, several aspects of the hepatitis B reinfection and its management will be examined. Approximately 50% of the treatment failures that occur with hepatitis B immune globulin (HBIg) prophylaxis are due to mutations in the 'a' determinant of the HBV. In patients without mutations, failure of HBIg therapy may relate to the frequency and dose of HBIg, the type and amount of immunosuppression, and the pre-transplant replication status. Antiviral therapy with lamivudine and famciclovir has been used successfully to treat patients who have failed HBIg treatment and as monotherapies for liver transplant recipients. Combining antiviral and immunomodulatory therapies appears efficacious, at least in the short term. New developments related to immunotherapy predict three potential trends in future use: 1) i.v. formulated HBIg, 2) monoclonal antibodies, or 3) hepatitis B immune plasma. In conclusion, there are an increasing number of therapeutic options for the management of patients undergoing liver transplantation for hepatitis B infection. Continued improvement in patient outcomes requires further understanding of each therapeutic agent and the specific patient characteristics that may influence efficacy.