成都某院乙型肝炎患者的免疫特点分析

目的分析成都某院乙型肝炎患者的免疫特点。 方法将329例乙型肝炎患者分为急性乙型肝炎组、慢性乙型肝炎组、乙型肝炎肝硬化组及乙型慢加急性肝功能衰竭组,比较各组患者的免疫球蛋白、补体和T淋巴细胞亚群等免疫指标的差异。 结果急性乙型肝炎组与慢性乙型肝炎组相比,各项免疫指标差异均无统计学意义（P均> 0.05）。乙型肝炎肝硬化组患者的IgG、IgA和IgM水平分别为（18.12 ± 5.70）g/L、（3.63 ± 0.94）g/L和（4.39 ± 0.82）g/L,显著高于其余3组;而该组患者CD3⁺ T、CD4⁺ T和CD8⁺ T细胞计数分别为（583.10 ± 276.35）个/μl、（339.13 ± 131.55）个/μl和（205.23 ± 41.22）个/μl,显著低于其余3组（P均< 0.05）。乙型慢加急性肝功能衰竭组患者的补体C3和C4水平分别是（0.39 ± 0.27）g/L和（0.08 ± 0.07）g/L,显著低于其余3组（P均< 0.05）。随着肝功能损害程度的加重,慢性乙型肝炎患者的ALT、AST、TBil和IgG水平均逐渐升高,而补体C3、C4、CD3⁺ T和CD4⁺ T细胞计数则逐渐下降（P均< 0.05）。 结论乙型肝炎患者的免疫状态与疾病进展及病情严重程度有一定相关性,肝硬化及肝功能衰竭患者体内存在免疫球蛋白升高、补体下降及T细胞损耗等免疫紊乱的情况。     

Successful hepatitis B vaccination in liver transplant recipients with donor-specific hyporesponsiveness

Currently, patients are prescribed lifelong treatment with hepatitis B immunoglobulin (HBIg) after liver transplantation (LT) for hepatitis B virus (HBV)-related diseases in order to prevent reinfection with HBV. Active immunization with an HBV vaccine would be a preferable alternative; however, the immunosuppressive environment in LT recipients is believed to elicit a poor response to vaccination. Minimizing the exposure of the HBV-infected LT recipients to immunosuppressants would be beneficial in inducing adaptive immunity against HBV by vaccination. In this study, in addition to efforts to minimize immunosuppression, prophylaxis with HBV vaccination combined with continuous HBIg administration was performed in 17 LT recipients who had undergone transplantation attributable to HBV-related diseases. During the observation period, the overall response rate to HBV vaccination was 64.7%. The immune status of the recipients was evaluated by a mixed lymphocyte reaction assay in response to allostimulation. Patients showing a donor-specific hyporesponse with a well-maintained response to the third-party stimulus always achieved a sustained immune response to the vaccine, whereas patients showing a hyporesponse to both the donor and the third-party stimulus were unable to do so. Thus, inducing an anti-donor-specific immunosuppressive status by minimizing immunosuppression should enable post-transplant HBV vaccination to be a promising prophylactic strategy.     

Transfer of humoral and cellular hepatitis B immunity by allogeneic hematopoietic cell transplantation

BACKGROUND: Previous data indicate that a transfer of specific humoral and cellular immunity by way of allogeneic hematopoietic cell transplantation (HCT) should, in principle, be possible. METHODS: In the HCT setting with a follow-up of up to 55 months, we studied the transfer of hepatitis B virus (HBV) specific immunity from electively immunized donors into HLA compatible recipients suffering from chronic myeloid leukemia (CML). After excluding preexisting HBV specific immunity in donor-recipient pairs, 27 prospective donors were vaccinated against HBV. In addition, on an average of 22 months postHCT, 8 of the 19 recipients were immunized once for HBV. RESULTS: Donor vaccination resulted in detectable hepatitis B surface (HBs) antibodies in 85% of donors and specific cellular in vitro responses in 77%. Two weeks postHCT, 86 and 67% of the recipients displayed positive humoral and cellular HBV reactions, respectively, which then decreased. Afterwards, HBV immunity reappeared in 83% of the recipients without revaccination. Following a single vaccination in recipients, seven of eight displayed a typical memory response. An HBV specific response was already detectable 1 week after vaccination, approximately 1,300-fold (humoral) and 60-fold (cellular) higher than observed in the corresponding donors after a single immunization. CONCLUSIONS: The "spontaneous" recurrence of HBV immunity and the memory response in recipients give evidence for an elective immune transfer (e.g., for viral antigens) by way of allogeneic HCT.     

Natural leukocyte interferon alfa for the treatment of chronic viral hepatitis in heart transplant recipients

BACKGROUND: A more rapid and aggressive course of hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related infection in organ transplant recipients has been described. Interferon alfa is the most accepted drug for treating HBV and HCV chronic infections. However, the use of interferon alfa-N3 has been contraindicated in heart transplant (HTx) recipients because of the hypothesized greater risk of triggering acute cellular rejection. The aim of this clinical pilot study was to evaluate tolerability, safety, and efficacy of natural leukocyte interferon alfa in the treatment of chronic HBV and HCV in HTx recipients. METHODS: Seven HTx recipients were enrolled in the study: two with HBV, four with HCV, and one with combined HBV-HCV chronic infection. The patients had a mean follow-up after heart transplantation of 8.5+/-3 years, before starting interferon alfa-N3 treatment at a dose of 6 MU three times per week, intramuscularly for 12 months. RESULTS: All patients completed the treatment with no major side effects. No unexpected episodes of acute cellular rejection were observed during the treatment. Mean aminotransferase serum levels were significantly lower than before transplantation at 3 (P<0.03), 6 (P<0.02), and 12 (P<0.02) months of treatment and at the 12-month follow-up (P<0.02). A complete and sustained response was achieved in all subjects with HBV-related chronic hepatitis, whereas sustained virologic response was observed in one of four HCV patients. CONCLUSIONS: The preliminary data emerging from our study indicate that natural leukocyte interferon alfa-N3 can be safely administered in HTx recipients with chronic HBV or HCV viral hepatitis. Further studies with larger numbers of patients are needed to assess the efficacy of interferon alfa-N3 on HCV virologic response.     

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.     

Solid Organ Transplantation From Hepatitis B Virus–Positive Donors: Consensus Guidelines for Recipient Management

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non‐liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti‐HBc+) donors. Organs from anti‐HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non‐liver recipients but is not recommended in immune non‐liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost‐effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.     

Erythropoietin Use and Immunogenicity of Hepatitis B Virus Vaccine in Chronic Kidney Disease Patients: A Meta-Analysis

Background: It is known that the immunogenicity of hepatitis B virus (HBV) vaccine is lower in uremic patients than healthy subjects. Numerous inherited or acquired factors have been implicated in this lowered response, and the high frequency of recombinant human erythropoietin use among patients on maintenance dialysis has been suggested to play a pivotal role. However, the impact of therapy with recombinant erythropoietin on the immune response to HBV vaccine in patients with chronic kidney disease (CKD) is not appropriately detailed. Aim: To evaluate the influence of human recombinant erythropoietin therapy on the immunological response to HBV vaccine in CKD patients by performing a systematic review of the literature with a meta-analysis of clinical studies. Methods: We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The end-point of interest was the rate of patients showing seroprotective anti-hepatitis B titers at completion of a hepatitis B vaccine schedule among human erythropoietin users versus those who did not receive the drug in a CKD population. Results: We identified 11 studies involving 862 unique patients with CKD. Aggregation of study results did not show a significant increase in response rates among erythropoietin user versus non-user patients (pooled odds ratio = 1.431; 95% CI 0.954; 2.146), according to a random-effects model. No heterogeneity was found, the p value was 0.1 for our test of study heterogeneity (Q = 14.147). Stratified analysis in various subgroups of interest did not significantly change these findings. Conclusions: Our meta-analysis showed no link between immunological response to HBV vaccine and therapy with human recombinant erythropoietin among individuals on long-term dialysis. We suggest the use of recombinant vaccine towards hepatitis B in patients on regular dialysis irrespective of erythropoietin treatment.     

Prevalence of Hepatitis A and B Markers and Vaccine Indication in Cirrhotic Patients Evaluated for Liver Transplantation in Spain

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is generally recommended for patients with chronic liver disease and those evaluated for liver transplantation in the absence of immunity. HAV and HBV infections after liver transplantation are frequent and associated with a worse prognosis. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV and HBV is substantial, and that new vaccination strategies are needed. The aim of this study was to determine the level of immunity from hepatitis A and B infections and the need for HBV and HAV vaccination among cirrhotic patients evaluated for liver transplantation. We studied HBV and HAV serological markers (HbsAg, anti-HBc, anti-HBs, IgG anti-HAV) in 451 cirrhotic patients evaluated for liver transplantation to investigate the association with gender, age, and etiology of cirrhosis. Negative HBV markers were observed in 57% of patients with 43% displaying one positive HBV marker: HBsAg (+), 9.5%; anti-HBc (+)/anti-HBs (−), 11.5%; anti-HBc (−)/anti-HBs(+), 4.2%; anti-HBc(+)/anti-HBs(+), 17.7%. HBV vaccine indication established in 68.5% of patients was greater among women and hepatitis C virus-negative patients. No differences were observed in age or cause of cirrhosis. HAV vaccination indicated in 6.7% of patients (IgG anti-HVA-negative) was greater among patients with negative HBV markers (9.3% vs 3.3%, P = .018) and younger patients (25.3% of patients ≤45 years). In conclusion, there are frequent indication, for HBV vaccine among cirrhotic patients evaluated for liver transplantation, as is time for HAV vaccine, especially among patients younger than 45 years of age.     

Frequent detection of hepatitis B core antibodies in heart transplant recipients without preceding hepatitis B infection

It is unclear whether heart donors positive for hepatitis B core antibodies (anti-HBc) can transfer hepatitis B virus (HBV) infection to immunosuppressed heart recipients, or whether passive transfer of anti-HBc simulates a hepatitis B infection. Therefore, we performed a case-controlled study in 46 heart recipients who all tested negative for hepatitis B antigen (HbsAg), antiHBc, and hepatitis B surface antibodies before heart transplantation. Twenty-three patients (group 1) received hearts from anti-HBc-positive donors, while 23 other patients (group 2) received hearts from anti-HBc-negative donors. After heart transplantation, anti-HBc were present in 65.0% of blood samples among group 1 and 47.8% of the blood samples among group 2 (P > .05). HbsAg was undetectable in blood samples of all patients of both study groups. The immunoglobulin preparation that we regularly use for immune suppression immediately after heart transplantation contained a relatively high concentration of anti-Hbc antibodies. The nearly identical presence of anti-HBc in both study groups indicated that passive transfer via immunoglobulin preparations rather than HBV infection is the cause for the anti-HBc detected in heart recipients. Since only a small volume of blood is transferred with the donor heart, it seems to be rather unlikely that the donor heart might be the source of anti-HBc. In summary, we observed no evidence for HBV infection in those heart recipients who received organs from anti-HBc-positive donors. Moreover, our data demonstrated that the presence of anti-HBc in heart recipients frequently occurs but does not necessarily indicate a preceding HBV infection.     

Studies on the integration of hepatitis B virus DNA sequence in human sperm chromosomes

Aim: To study the integration of hepatitis B virus (HBV) DNA into sperm chromosomes in hepatitis B patients and the features of its integration. Methods: Sperm chromosomes of 14 subjects (5 healthy controls and 9 HB patients, including 1 acute hepatitis B, 2 chronic active hepatitis B, 4 chronic persistent hepatitis B, 2 HBsAg chronic carriers with no clinical symptoms) were prepared using interspecific in vitro fertilization between zona-free hamster oocytes and human spermatozoa. Fluorescence in situ hybridization (FISH) to sperm chromosome spreads was carried out with biotin-labeled full length HBV DNA probe to detect the specific HBV DNA sequences in the sperm chromosomes. Results: Specific fluorescent signal spots for HBV DNA were seen in sperm chromosomes of one patient with chronic persistent hepatitis B. In 9(9/42) sperm chromosome complements containing fluorescent signal spots, one presented 5 obvious FISH spots and the others 2 to 4 signals. The fluorescence intensity showed significant diffe     

Favourable outcome of adefovir-dipivoxil treatment in acute de novo hepatitis B after liver transplantation

Adefovir-dipivoxil has been shown to be effective against lamivudine-resistant mutants in immunocompetent patients and in a small number of liver transplant recipients with recurrent hepatitis B virus (HBV) infection. The therapeutic role of adefovir-dipivoxil in acute de novo HBV infection after transplantation is uncertain. We describe a case of acute de novo HBV infection that occurred after liver transplantation and that was treated with lamivudine followed (when viral escape mutants emerged) by adefovir-dipivoxil rescue. Treatment outcome was excellent, with complete viral clearance and development of a protective titer of antibodies to anti-hepatitis B surface antigen. Because the donor was vaccinated against HBV, it is conceivable that clearance of HBV infection in the recipient might have been favored by adoptive transfer of immunity to HBV. The immune status of the donor might be a factor to consider when determining the treatment options for de novo hepatitis B.     

Immunogenicity of hepatitis B vaccine in renal transplant recipients

To evaluate the immunogenicity of hepatitis B vaccine in renal transplant recipients, we administered three 40-microgram doses of vaccine to 17 patients who had previously undergone transplantation and were on immunosuppressive therapy. Life-table analysis revealed a cumulative antibody response rate of only 17.6% at 12 months, and the three responders had low titers of antibody to hepatitis B surface antigen. There were no serious adverse effects and no episodes of graft rejection in responders or nonresponders. In addition, the ratio of helper/inducer (T4) to suppressor/cytotoxic (T8) T cells in vaccinees bore no relationship to the immunogenicity of the vaccine. These data indicate that hepatitis B vaccine is weakly immunogenic in renal transplant recipients and illustrate the need for vaccination prior to transplantation for maximal protection against hepatitis B virus infection.     

拉米呋定与乙肝疫苗预防HBcAb阳性供肝儿童肝移植术后新发乙肝病毒感染效果的对照研究

目的 比较拉米呋定与乙肝疫苗方案预防乙型肝炎核心抗体(hepatitis B core antibody,HBcAb)阳性供肝儿童肝移植术后新发乙型肝炎病毒(hepatitis B virus,HBV)感染效果.方法 对天津市第一中心医院自2013年5月—2019年6月251例接受HBcAb阳性供肝儿童肝移植的资料进行...     

Relationship of hepatitis B or C virus prevalences, risk factors, and outcomes in renal transplant recipients: analysis of German data

BACKGROUND: Chronic liver disease resulting from hepatitis B (HBV) and hepatitis C (HCV) virus infections is still a major concern in kidney recipients. Our aim was to evaluate the prevalences, risk factors, and impact of HBV and HCV infections in adult renal transplant recipients in Germany. MATERIALS AND METHODS: Data were collected on 1633 kidney recipients transplanted between 1989 and 2002 at the 21 German renal transplant centers participating in MOST, the prospective Multinational Observational Study in Transplantation. Subgroup analyses compared HBV- and HCV-positive patients vs those with HBV/HCV-negative serology at the time of transplantation. RESULTS: The prevalences of 4.4% (n = 72) for HBV and 5.8% (n = 94) for HCV showed a marked decline over the last 15 years. Retransplantations were significantly more common among HBV+ (29%) and HCV+ (36%) than HBV-/HCV- patients (12%). HCV+ patients experienced significantly longer dialysis times and received significantly more pretransplantation blood transfusions. Between all groups, no significant differences were observed in acute rejection rate at 12 months or in renal graft function up to 5 years posttransplantation (mean glomerular filtration rate: HBV+, 57.3 mL/min; HCV+, 58.5 mL/min; HBV-/HCV-, 59 mL/min). No progressive elevations in liver enzymes and bilirubin were noted during the 5-year observation period. CONCLUSIONS: HBV and HCV infections currently have a low prevalence among German kidney graft recipients. Long dialysis times, blood transfusions, and retransplantations were identified as risk factors for hepatitis infections. At 5 years posttransplantation, kidney and liver functions did not differ significantly between HBV+ and HCV+ vs HBV-/HCV- renal transplant recipients.     

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.     

Immunopathogenesis of hepatitis B virus recurrence after liver transplantation

BACKGROUND AND AIMS: Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation is associated with inflammatory graft changes, despite immunosuppression and donor/recipient HLA mismatch. We investigated whether immune mechanisms are involved in the pathogenesis of hepatitis B after liver transplantation. METHODS: The virus-specific T helper (Th) cell response, activation of Th1/Th2 subpopulations, donor/recipient HLA, and expression of tumor necrosis factor (TNF)-alpha/TNF receptors were determined in 28 patients who underwent transplantation for HBV-related cirrhosis (17 with HBV recurrence and 11 without recurrence) in comparison to 30 nontransplant patients with chronic hepatitis B. RESULTS: Orthotopic liver transplantation recipients with HBV recurrence showed significant hepatitis B core antigen-specific T-cell proliferation, comparable to nontransplant patients, which was not present in transplant recipients without recurrence. In addition, hepatic and serum interleukin (IL)-2, interferon-gamma, and TNF-alpha were enhanced, without changes in IL-4 and IL-10. Phenotypically, hepatic infiltrates in allografts with HBV recurrence were comprised of CD4+ lymphocytes and macrophages with a correlation between interferon-gamma- and TNF-alpha-producing cells and the degree of necroinflammatory activity. There was a marked up-regulation of both TNF-alpha receptors, significantly greater than in nontransplant patients. CONCLUSIONS: These findings suggest that despite immunosuppression, HLA class I-independent immune mechanisms have a significant pathogenic role in liver damage associated with HBV recurrence after liver transplantation.     

Significance of monocytic cytokines at single cell level for the immune responsiveness in renal transplant recipients

Cytokine dysregulation is an important factor underlying the immune unresponsiveness to hepatitis B vaccination (HBV) in renal transplant recipients. This study investigated the relationship between monocyte-derived interleukin-6 (IL-6) and interleukin-10 (IL-10) production and the immune responsiveness using flow cytometry (cytoflow) after whole blood culture. According to their previous response to hepatitis B vaccination, 40 renal transplant recipients were divided into two groups of 20 patients. The percentage of CD 14+ monocytes stained positive for intracellular IL-6 or IL-10 was measured using flow cytometry after 4 and 20 h of whole blood culture with lipopolysaccharide stimulation. The percentage of CD 14+/IL-6+ cells after incubation in vitro for 4 h was lower in the responders compared to the non-responders and controls (27.15+/-8.93 vs 35.47+/-9.95, P=NS; and 37.06+/-10.89, P<0.05 respectively). The staining intensity of IL-6 at 4 h for responders was also significantly reduced. At 20 h, there were a significantly higher percentage of CD 14+/IL-10+ positive cells in the responders compared to the non-responders (41.87+/-18.39 vs 27.55+/-17.25, P<0.05). These results indicate that alteration of intracellular cytokine profile in activated monocytes distinguishes the HBV vaccination responders from the non-responders among renal transplant recipients. The capacity to upregulate monocyte IL-10 production in this subset of patients may modulate the immune responsiveness and effectively assists in mounting a positive response to HBV vaccination.     

Laboratory effect of HBV infection in kidney transplant recipients and donors

Background

Viral infections are the most common cause of opportunistic infections after kidney transplantation. Among hepatotropic viruses that induce kidney graft failure and rejection, hepatitis B virus (HBV) has an important and critical role. Extrahepatic HBV-related disorders increase morbidity and mortality in kidney transplant recipients.

Objective

To analyze the molecular prevalence of HBV infection in kidney transplant recipients and donors before and after transplantation.

Patients and Methods

This cross-sectional study included 273 serum samples collected between 2005 and 2008 in 96 kidney transplant recipients and 59 donors. Detection of HBV DNA was via amplification of the S gene fragment of HBV genome using a qualitative simple polymerase chain reaction assay. Also analyzed were statistical relationships between HBV infection and laboratory and clinical demographic data in all kidney transplant donors and recipients.

Results

The HBV genome was detected in 102 of 273 serum samples. Molecular HBVinfection was demonstrated in 2 of 13 serum samples (15.4%) from recipients testedbefore transplantation. HBV DNA was detected in 42 of 96 patients (43.7%) after kidneytransplantation. The HBV genome was demonstrated in 21 of 59 donors (35.6%).Significant relationships were observed between HBV infections and hematologic andbiochemical indices after kidney transplantation.

Conclusion

Detection of a high molecular prevalence of HBV infection in kidneyrecipients enforces the importance of HBV infection in clinical outcome.     

Hepatitis B virus vaccine switch program for prevention of de novo hepatitis B virus infection in pediatric patients.

The principal objective of this study was to evaluate the feasibility of Hepatitis B virus (HBV) vaccine switch program after 1-year Hepatitis B immunoglobulin (HBIG) for the prevention of de novo HBV (DNHBV) infection in pediatric recipients of hepatitis B core antibody (anti-HBc)-positive grafts. In this study, we enrolled pediatric recipients (n = 14), who had undergone living donor liver transplantation with anti-HBc-positive grafts between July 2000 and July 2005 and were followed up for over 24 months after transplantation. HBIG was given daily during the first week and intermittently in order to maintain anti-hepatitis B surface antigen (anti-HBs) titers greater than 200 IU/l until 12 months post-transplantation. Then the HBV vaccine was given intermittently as a substitute for HBIG when anti-HBs titer fell below 200 IU/l. The median follow-up duration after vaccination was 26.5 months, and a median of 2.03 doses of vaccine per year was required for the maintenance of anti-HBs titers greater than at least 100 IU/l. Two of the patients did not start the HBV vaccine due to sustained high anti-HBs titer. Eleven completed the HBV switch, whereas 1 was ongoing. With the HBV vaccine switch program, anti-HBs titers greater than 100 IU/l could be maintained conveniently and effectively.     

Severe clinical course of de novo hepatitis B infection after liver transplantation.

The aim of this study is to determine the origin, clinical outcome, allograft histological characteristics, and virological outcome of de novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). We studied 136 hepatitis B surface antigen (HBsAg)-negative liver transplant recipients. HBV DNA was detected by dot-blot hybridization and polymerase chain reaction (PCR). The S gene was sequenced. Hepatitis C virus (HCV) RNA was assessed by PCR. The long-term clinical and histological outcome was determined. Six of 136 HBsAg-negative patients (4.4%) became HBsAg positive after transplantation. The source of HBV infection was reactivation of latent HBV infection in 2 patients and was not identified in 4 patients. Two donors had isolated core antibody. Two of these 6 patients developed acute liver failure related to hepatitis B. The 4 other patients had severe chronic hepatitis related to hepatitis B. All patients had high-level HBV replication. No significant mutations in the S gene were found. These data suggest that de novo hepatitis B infection is not a mild disease and might represent a significant cause of graft dysfunction. This is the first report of fulminant hepatitis caused by de novo hepatitis B infection after OLT.