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A hepatitis B vaccination (HepB) series with an initial dose of hepatitis B immune globulin (HBIG) is the recommended prophylaxis for infants born to mothers with chronic hepatitis B virus (HBV) infection and for HBV-exposed persons without known protection. The HepB and HBIG are administered at different sites (limbs). Instances of HepB and HBIG administered at the same site are documented but the impact on immune responses to HepB remains unanswered. Newborn and adult BALB/c mice received one dose of HepB at time zero alone or with HBIG in the same or different sites, followed by 2 additional doses of HepB at 3 and 10 weeks (newborn mice) or 4 and 16 weeks (adult mice). To study memory responses mice were given a 4th, booster, dose of HepB at 26 weeks and B cells analyzed. Administration of HepB with HBIG resulted in reduced responses to HepB following the first 2 doses, regardless of site, compared to mice that received HepB only. Lower levels of antibody to HBV surface antigen (anti-HBs) were observed at the end of the 3-dose series (p < 0.0001) in all groups of newborn mice that received HepB and HBIG. In adult mice, this difference was only seen when HepB and HBIG were delivered at the same site. However, following a HepB booster at 26 weeks, HBsAg-specific B-cell expansion and memory phenotype were not impacted by initial HBIG administration Administration of HBIG with HepB can delay and reduce responses to HepB in mice. Our findings suggest that the initial circulating levels of HBIG could prevent infection despite an impaired response to vaccine and support the current recommendation of assessing seroprotection after series completion for infants born to HBV carrier mothers, including in cases where vaccine and HBIG are administered incorrectly at the same site. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the efficacy and safety of pharmacologic interventions to prevent vertical transmission of the hepatitis B virus.Data Sources: Medline, Cochrane, and Scopus databases were searched up to October 28, 2020.Study Eligibility Criteria: All randomized controlled trials reporting vertical hepatitis B virus transmission with pharmacologic intervention were included.Methods: Risk of bias was assessed using the Cochrane Risk-of-Bias tool, version 2. Treatment efficacy was estimated using stratified network meta-analysis on the basis of maternal hepatitis B envelope antigen status.Results: Nineteen studies were included for mothers positive for hepatitis B surface and envelope antigens. Pooling indicated that a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants significantly reduced transmission risk compared with vaccination alone, with a risk ratio of 0.52 (95% confidence interval; 0.30-0.91). Only the addition of maternal tenofovir disoproxil fumarate, but not telbivudine, lamivudine, or maternal hepatitis B immunoglobulin further reduced transmission risk compared with a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants, with a pooled risk ratio of 0.10 (0.03-0.35). Twelve studies conducted in mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelope antigen status provided limited evidence to suggest that maternal hepatitis B immunoglobulin combined with hepatitis B vaccination and immunoglobulin in infants was the likely best treatment, but this failed to reach statistical significance compared with a combination of hepatitis B vaccination and immunoglobulin in infants. Similarly, infant hepatitis B immunoglobulin, added to vaccination, likely provides additional benefit but failed to reach statistical significance.Conclusion: A combination of hepatitis B vaccination and immunoglobulin in infants is the cornerstone for prevention of vertical transmission for mothers positive for both hepatitis B surface and envelope antigens. The addition of maternal tenofovir to this infant combination regimen was considered the likely most effective treatment. For infants of mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelop antigen status, no additional agents provided further benefit beyond hepatitis B vaccination alone. [ABSTRACT FROM AUTHOR]

Prevention of hepatitis B virus (HBV) transmission from infected mothers to their newborns is critical to HBV control and eventual eradication. Mother-to-child perinatal transmission causes the highest chronic carrier rate (>85%) with a high rate of subsequent chronic liver disease and hepatocellular carcinoma. This risk is reduced by 90% with HBV vaccine given along with hepatitis B immune globulin (HBIG) starting at birth. New analyses of our data from US trials of HBIG and HBV vaccine in high-risk infants revealed better efficacy with yeast-recombinant vaccine than plasma-derived vaccine, especially in preventing late onset infections, with evidence that vaccine prevented transmission of maternal HBV infection with the glycine to arginine mutation in surface antigen codon 145 (sG145R). Most late infections with sG145R were in vaccine non-responders, suggesting escape from HBIG rather than from vaccine-induced antibody. Our findings also help explain survey results from Taiwan following universal childhood immunization implemented in the mid-1980s. We conclude that current vaccines will remain effective against surface antigen mutants. Anti-viral drugs in high-risk pregnant women, in combination with newborn HBIG and vaccine, show promise for eliminating residual breakthrough neonatal infections, critical to meeting WHO 2030 goals and for eradicating HBV.

Background: The long‐term administration of nucleotide analogues (NAs) and hepatitis B immune globulin (HBIG) comprises standard prophylaxis for patients with hepatitis B virus (HBV)‐related liver diseases to prevent HBV reinfection after liver transplantation (LT). However, prolonging the prophylaxis strategy involves safety issues, such as the development of escape mutations and/or emerging resistant strains, and is also associated with high costs; further, it remains unclear how long prophylactic treatment should be continued. Method: Liver transplantation recipients responding to hepatitis B vaccination due to HBV‐related liver diseases were retrospectively analysed after stopping HBIG and/or NAs, administered to prevent HBV reinfection, after long‐term follow‐up. The safety and effectiveness of the strategy were then evaluated for these responders. Result: Seventy‐eight responders were enrolled. All responders discontinued HBIG, among which 36 stopped both HBIG and NAs. During follow‐up, four recipients experienced HBV reinfection, which was associated with HBV escape mutations, after the withdrawal of both HBIG and NAs. No death or graft loss occurred in recipients during the follow‐up period. Conclusion: A careful withdrawal of HBIG and/or NAs is feasible and safe for responders to hepatitis B vaccination receiving transplants for HBV‐related liver diseases. [ABSTRACT FROM AUTHOR]

The effect of hepatitis B immune globulin (HBIG) combined with hepatitis B vaccine on blocking hepatitis B virus (HBV) transmission between mother and infant and its effect on immune cells were studied. Ninety newborn infants confirmed to be HBV surface antigen (HBsAg)-positive were divided equally into three groups. Group A newborns received the hepatitis B vaccine at 0, 1 and 6 months after birth (10 µg/time). Group B newborns received an intramuscular injection of 100 IU HBIG 2 h after birth before the same treatment as group A. Mothers of group C newborns received three gluteus maxinus injections of 200 IU HBIG. The newborns in group C got the same treatment as group B. The blocking effect of HBV transmission between mother and infant was evaluated, and cell immune function was assessed. There were significant differences in comparison of blocking success rates between group A and B, and between group A and C as well (p<0.05). At the end of 12 months follow-up, the CD4+ level and CD4+/CD8+ ratio in group C were higher thanthose in group A and B (p<0.05). In addition, the level of CD8+ T lymphocyte in group C was lower than those in group A and B (p<0.05). In comparison of levels of CD4+T lymphocyte at the end of 12 months follow-up and 24 h after birth, the differences were significant (p<0.05) in both group B and C. The differences of IFN-γ levels between groups B/C and group A were significant (p<0.05). For those newborn infants born to mothers who were positive for both HBsAg and HBeAg, HBIG intervention for mothers during late pregnancy, together with combined treatment of HBIG and hepatitis B vaccine for infants, gave better blocking result of HBV transmission. [ABSTRACT FROM AUTHOR]

Hepatitis B surface antigen (HBsAg) quantification has recently been introduced to guide treatment in chronic hepatitis B virus (HBV) patients. No information is currently available on use of HBsAg levels to guide HBV immune globulin (HBIG) administration after liver transplantation (LT). We performed a retrospective analysis of a prospectively collected database. Patients were included if: adults (≥18 years); recipients of a primary liver graft; HBsAg-positive and HBV DNA-negative at transplantation; hepatitis C and/or HIV-negative; not transplanted for fulminant hepatic failure; on nucleoside analogues. All patients were administered 30,000 IU HBIG, perioperatively, and hepatitis B surface antibody (HBsAb) was tested at day 7, 14, 28, and monthly thereafter. A further 30,000 HBIG were administered if HBsAb 100 IU/mL on day 7. The primary endpoint was the efficacy of HBIG as a percentage of patients achieving HBsAg

Prevention of hepatitis B virus (HBV) transmission from infected mothers to their newborns is critical to HBV control and eventual eradication. Mother-to-child perinatal transmission causes the highest chronic carrier rate (>85%) with a high rate of subsequent chronic liver disease and hepatocellular carcinoma. This risk is reduced by 90% with HBV vaccine given along with hepatitis B immune globulin (HBIG) starting at birth. New analyses of our data from US trials of HBIG and HBV vaccine in high-risk infants revealed better efficacy with yeast-recombinant vaccine than plasma-derived vaccine, especially in preventing late onset infections, with evidence that vaccine prevented transmission of maternal HBV infection with the glycine to arginine mutation in surface antigen codon 145 (sG145R). Most late infections with sG145R were in vaccine non-responders, suggesting escape from HBIG rather than from vaccine-induced antibody. Our findings also help explain survey results from Taiwan following universal childhood immunization implemented in the mid-1980s. We conclude that current vaccines will remain effective against surface antigen mutants. Anti-viral drugs in high-risk pregnant women, in combination with newborn HBIG and vaccine, show promise for eliminating residual breakthrough neonatal infections, critical to meeting WHO 2030 goals and for eradicating HBV. [ABSTRACT FROM AUTHOR]

Background: Post-transplant hepatitis B virus (HBV) reinfection is one of the major problems facing patients who undergo HBV-related liver transplantation (LT). We analyzed the clinical impact of serum hepatitis B core-related antigen (HBcrAg) on HBV reinfection in post-LT patients with HBV-related liver diseases.Methods: Serum hepatitis B surface antigen (HBsAg), HBV DNA, and HBcrAg were measured over time in 32 post-LT patients. Twenty-one out of 32 patients had HCC at LT. The effects of HBcrAg, hepatocellular carcinoma (HCC) recurrence, and HBs gene mutation on HBV reinfection and withdrawal from hepatitis B immune globulin (HBIG) were analyzed.Results: Sixteen out of 32 patients (50 %) were positive for HBcrAg even though only six patients were thought to have experienced HBV reinfection based on reappearance of either HBV DNA or HBsAg during a median follow-up time of 75 months. Three of these six patients who became re-infected with HBV experienced HCC recurrence after LT. The HBV DNA reappearance rate was significantly higher in patients with HCC recurrence after LT (p < 0.001). Two HBV re-infected patients without HCC recurrence had HBs gene mutations G145R and G145A, respectively. Anti-HBs antibody development rate by HB vaccination was similar between HBcrAg-positive and negative patients (p = 0.325).Conclusions: HBV reinfection is more common than is usually considered based on conventional measurement of HBsAg and HBV DNA. HCC recurrence and mutations in the HBV S gene were associated with HBV reinfection after LT. [ABSTRACT FROM AUTHOR]

In a previous study, we observed immunoprophylaxis failure due to occult hepatitis B virus (HBV) infection (OBI) despite the presence of adequate levels of anti-HBs in 21 (28%) of 75 children born to HBsAg-positive mothers. The aim of the study was to explore the maintenance of this cryptic condition in this population. Of 21 OBI-positive children, 17 were enrolled. HBV serological profiles were determined by enzyme-linked immunosorbent assay. Highly sensitive real-time and standard PCR followed by direct sequencing were applied in positive cases. The mean age (±SD) of studied patients was 6.57 ± 2.75 years. All children still were negative for HBsAg. All but one (94%) were negative for HBV DNA. Only two children were positive for anti-HBc. The results of the most recent anti-HBs titration showed that 4 (23.5%) and 13 (76.5%) had low (<10 IU/mL) and adequate (>10 IU/mL) levels of anti-HBs, respectively. The only still OBI-positive patient had an HBV DNA level of 50 copy/mL, carried the G145R mutation when tested in 2009 and again in 2013 in the 'a' determinant region of the surface protein. Further follow-up showed that after 18 months, he was negative for HBV DNA. In high-risk children, the initial HBV DNA positivity early in the life (vertical infection) does not necessarily indicate a prolonged persistence of HBV DNA (occult infection). Adequate levels of anti-HBs after vaccine and hepatitis B immune globulin immunoprophylaxis following birth could eventually clear the virus as time goes by. Periodic monitoring of these children at certain time intervals is highly recommended. [ABSTRACT FROM AUTHOR]

Aim The feasibility of vaccination in liver transplant recipients is highly controversial, and the present study aimed to investigate the efficacy of a 1-year extended, monthly vaccine prophylaxis protocol of a second-generation recombinant vaccine for transplant recipients. Methods The recombinant hepatitis B vaccine (10 µg) was administrated s.c. every month for 12 months as the vaccination protocol to 39 liver transplant recipients in stable condition, including those with hepatitis B-related chronic liver disease ( n = 30), those with acute hepatitis B liver failure (hepatitis B surface antibody [HBsAb], n = 4), and those with hepatitis B core antibody positive grafts ( n = 5). A fixed dose of hepatitis B immune globulin (HBIG) was administrated during the study based on the monoprophylaxis approach, and the increase in the hepatitis B surface antibody titer was measured to evaluate the efficacy of the vaccination. Results The vaccination protocol was initiated a mean of 54 months (range, 13-124) after liver transplantation, and all patients tolerated the vaccination well without adverse effects. The overall hepatitis B virus (HBV) recurrence rate was 5% (2/39) based on hepatitis B surface antigen positivity, and 2% (1/39) based on HBV DNA detectability. Six (15%) patients showed a good response to vaccination with an increase in the HBsAb titer greater than 100 IU/L at the end of vaccination, but only three (8%) maintained an adequate HBsAb level to spare HBIG during the 2-year observation period. Conclusion While a few patients demonstrated an adequate response to vaccination, the clinical indication for the HBV vaccination for liver transplant recipients is currently minimal. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B immune globulin (HBIg) in combination with a nucleos(t)ide analog is the mainstay of prophylactic regimen to prevent recurrence of hepatitis B following orthotopic liver transplantation (OLT). HBIg therapy is costly and inconvenient for the patients. There is a growing experience converting HBIg/nucleos(t)ide to combination nucleotide/nucleoside analogs from. Methods: Twenty-six patients that underwent OLT between March 2001 and July 2011 who had received at least 12 months of HBIg and single nucleos(t)ide were enrolled. HBsAg and HBV DNA were undetectable, and anti-HBs were detectable at the time of switch. HBV DNA and HBsAg were measured every 3 months following discontinuation of HBIg and addition of nucleos(t)ide. Results: Patients included 23 Asians/3 Caucasian, 21 males/5 females. Mean time of conversion from HBIg/nucleos(t)ide to nucleoside/nucleotide combination was 77.5 (range 11-132) months after OLT. Mean duration of follow-up after conversion was 31.9 (range 14-70) months. All patients had undetectable HBV DNA, and 24 patients remained HBsAg negative during follow-up. Two patients recurred 7 and 9 months later, respectively, with detectable HBsAg. Both patients continued to have undetectable HBV DNA and normal ALT. HBsAg was neutralized by reinfusion of HBIg. Conclusion: Nucleoside/nucleotide combination is an effective alternative to HBIg/nucleos(t)ide to prevent recurrence of hepatitis B after OLT. [ABSTRACT FROM AUTHOR]

Antiviral treatment of hepatitis B virus (HBV) cirrhosis using entecavir or tenofovir suppresses replication of HBV and can reverse liver insufficiency in some cases, which might imply delisting. After liver transplantation, combination HBV prophylaxis with low-dose hepatitis B immune globulin and antivirals effectively prevents HBV recurrence in >90 % of transplant recipients. Some forms of prevention of HBV recurrence should be continued indefinitely post-transplant, but in patients with a low risk of recurrence (i.e., HBV DNA levels undetectable pre-transplant), discontinuation of hepatitis B immune globulin (HBIG) is possible if patients are treated with long-term nucleos(t)ide(s) analogue(s) therapy. A more cautious approach is necessary for patients with high pre-transplant HBV replication, patients with HIV or hepatitis D virus coinfection or preexisting HBV drug resistance, those with a high risk of hepatocellular carcinoma recurrence, and those at risk of noncompliance with antiviral therapy. In this group, HBIG-free prophylaxis cannot be recommended. [ABSTRACT FROM AUTHOR]

Antiviral therapy using newer nucleos(t)ide analogues with lower resistance rates such as entecavir or tenofovir could suppress hepatitis B virus (HBV) replication, improve liver function, delay or obviate the need for liver transplantation in some patients, and reduce the risk of HBV recurrence. The combination of long-term antiviral and low-dose hepatitis B immune globulin (HBIG) can effectively prevent HBV recurrence in more than 90% of transplant recipients. Some form of HBV prophylaxis needs be continued indefinitely after transplantation. However, in patients with a low risk of HBV recurrence (i.e. HBV DNA levels undetectable before transplantation), it is possible to discontinue HBIG and maintain long-term antiviral therapy. A more cautious approach to prophylaxis regimen is necessary for those patients with high pretransplant HBV DNA levels, those with limited antiviral options if HBV recurrence occurs (i.e. HIV or HDV coinfection, preexisting drug resistance), those with a high risk of hepatocellular carcinoma recurrence, and those with a risk of noncompliance to antiviral therapy. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In patients infected with chronic hepatitis B virus ( HBV) that goes untreated, therapeutic options are limited once the disease decompensates, and orthotopic liver transplantation is often the only treatment available to save the patient's life. After liver transplantation, combined therapy with hepatitis B immune globulin ( HBIG) and a nucleos(t)ide analog is the standard of practice for the prevention of HBV recurrence. Historically, nucleos(t)ide analogs such as lamivudine and adefovir have been used with low-dose HBIG for the prevention of HBV recurrence after liver transplantation. However, these analogs are ineffective when used alone due the emergence of resistance mutations. Newer nucleos(t)ide analogs such as tenofovir disoproxil fumarate have demonstrated higher resistance thresholds and effective viral suppression when paired with low-dose HBIG. In this case series, we evaluated the safety and efficacy of switching four patients from low-dose HBIG plus nucleos(t)ide analog therapy for the prevention of HBV recurrence to a combination tenofovir-emtricitabine regimen. At the end of follow-up, all patients remained hepatitis B surface antigen negative and had HBV DNA levels of less than 10 IU/ml. Additionally, no tenofovir-associated nephrotoxicity was observed among the four patients. Tenofovir-emtricitabine monotherapy in lieu of HBIG plus nucleos(t)ide analog therapy demonstrated prevention of HBV recurrence without tenofovir-associated nephrotoxicity after 9 months of follow-up in all four patients and up to 15 months in one patient. [ABSTRACT FROM AUTHOR]

Patients who undergo liver transplantation (LT) for chronic hepatitis B virus (HBV) infection are at high risk of developing recurrent HBV in the absence of effective prophylaxis. Pre-LT management should focus on suppression of HBV DNA levels, which have been associated with HBV recurrence. Evidence linking hepatocellular carcinoma (HCC) recurrence to HBV recurrence has been less clear. Prophylaxis against recurrent HBV after LT with combination HBIG and antiviral therapy is the current standard of care and is effective in >90% of patients, but investigation is ongoing to determine the most cost-effective treatment regimens. While antiviral therapy with newer nucleos(t)ide analogues without HBIG is assumed to be effective, no recent studies have examined the long-term efficacy of salvage regimens for recurrent HBV. Large, prospective trials are urgently needed. Overall, LT for HBV is highly effective with appropriate pre- and post-LT antiviral therapy. [ABSTRACT FROM AUTHOR]

Livers from donors positive for antibody against anti-HBc can potentially transmit de novo hepatitis B (DNH) to their recipients. Despite a good outcome, prophylaxis is usually offered to such recipients. There is no consensus on the standard prophylactic regimen and hence prophylaxis varies among different transplant centres. Nonetheless, hepatitis B immune globulin (HBIG) is considered the mainstay of such prophylaxis, either alone or in combination with an oral antiviral treatment. We aim to provide a concise review of the current use of HBIG in prevention of DNH. We also address a few important questions regarding HBIG use. [ABSTRACT FROM AUTHOR]

Summary: Objective: To evaluate the compliance with the protocol for preventing perinatal hepatitis B infection in Italy, including HBsAg screening of pregnant women and immunization of newborns to infected mothers. Methods: Women consecutively delivering, over 6 months in 2008–2009, in public and private hospitals of 13 Italian regions were recruited. Data on socio-demographic characteristics, HBsAg prenatal screening and newborns immunization were collected. Results: 17,260 pregnant women were enrolled. Of them 16,858 (97.7%) attended prenatal screening. Delivering in a public hospital and in hospitals located in South Italy were both independent predictors of non-adherence to HBsAg screening. Foreign pregnant women were also less likely to be screened. Overall, HBsAg prevalence was 0.86%; it was 0.4% for Italian women and 2.5% for foreign women. Differences in prevalence by country of origin and education were statistically significant. Of 138 newborns from HBsAg positive mothers 131 received passive/active immunization; 7 newborns received just vaccine. Conclusion: In this study compliance with the protocol for preventing perinatal hepatitis B was very good. Further efforts are needed to improve adherence to prenatal screening in public hospitals, in hospital located in southern Italy and among foreign women. HBV spread in Italy is progressively declining, also involving immigrant population. [ABSTRACT FROM AUTHOR]

Background and aim: Transmission of hepatitis B virus (HBV) infection occurs in up to 87.5% of HBsAg-negative recipients of anti-HBc-positive donor livers in the absence of HBV prophylaxis. There is no standardized prophylactic regimen to prevent HBV infection in this setting. The aim of this study was to determine the long-term efficacy of nucleoside analogue to prevent HBV infection in this setting. Methods: A retrospective study of HBsAg-negative patients receiving liver transplantation (LT) from anti-HBc-positive donors during a 10-year period. Results: Twenty patients were studied, mean age was 50.2 ± 8.3 years, 40% were men, and 90% were Caucasian. The median MELD score at the time of LT was 18 (12-40). None of the patients received hepatitis B immune globulin. Eighteen patients received nucleoside analogue monotherapy: 10 received lamivudine and 8 received entecavir. None of these 18 patients developed HBV infection after a median follow up of 32 (1-75) months. One patient received a second course of hepatitis B vaccine 50 months after LT with anti-HBs titer above 1,000 mIU/mL. Lamivudine was discontinued and the patient remained HBsAg negative 18 months after withdrawal of lamivudine. Two patients who were anti-HBs positive before LT were not started on HBV prophylaxis after LT; both developed HBV infection after LT. Conclusions: Nucleoside monotherapy is sufficient in preventing HBV infection in HBsAg-negative recipients of anti-HBc-positive donor livers. HBV prophylaxis is necessary in anti-HBs-positive recipients of anti-HBc-positive donor livers. [ABSTRACT FROM AUTHOR]

L.H. Katz, M. Paul, D.G. Guy, R. Tur-Kaspa. Prevention of recurrent hepatitis B virus infection after liver transplantation: hepatitis B immunoglobulin, antiviral drugs, or both? Systematic review and meta-analysis. Transpl Infect Dis 2009: 12: 292–308. All rights reserved Objectives. To evaluate antiviral prophylaxis against hepatitis B virus (HBV) following liver transplantation. Methods. Systematic review and meta-analysis. Clinical trials and comparative cohort studies comparing the use of hepatitis B immunoglobulin (HBIg), antivirals, or both following liver transplantation for HBV infection were included. The primary outcome was reappearance of hepatitis B surface antigen (HBsAg). Other outcomes included all-cause and HBV-related mortality, HB-related active liver disease, and reappearance of HBV DNA after transplantation. Relative risks (RR) with 95% confidence intervals (CIs) are reported. Results. Twenty studies (22 comparisons) were included. Ten studies compared HBIg to combination treatment, 9 compared antivirals to combination treatment, and 3 compared lamivudine (LAM) to HBIg. Combination treatment reduced HBsAg reappearance (RR 0.28; 95% CI 0.12–0.66), and was superior to HBIg alone in all other outcome measures. Combination treatment was significantly better than antivirals in preventing reappearance of HBsAg (RR 0.31; 95% CI 0.22–0.44), even when low-dose HBIg was given. No significant difference was found between HBIg and LAM monotherapy for all measured outcomes. Major limitations with regard to comparability of the study groups in non-randomized trials were revealed. Conclusions. Combination treatment with HBIg and LAM reduced HBV recurrence following liver transplantation, compared with HBIg or LAM alone, and reduced mortality compared with HBIg alone. [ABSTRACT FROM AUTHOR]

End-stage liver disease caused by the hepatitis B and C viruses (HBV and HCV) are major indications for liver transplantation. Outcome depends largely on the prevention of allograft reinfection. The advent of long-term hepatitis B immune globulin administration and the introduction of new antiviral agents were a major breakthrough in the management of these patients. Today, survival after orthotopic liver transplantation (OLT) is similar to that of patients transplanted for HBsAg-negative liver disease, and the risk of recurrence is below 10%. In contrast, HCV reinfection is almost constant and significantly impairs patient and graft survival. Factors that may influence disease severity and consequently progression of HCV graft injury remain unclear. Pre-transplantation and prophylactic post-transplantation antiviral treatments are limited by low applicability and poor tolerance. Treatment of established graft lesions with combination therapy gave promising results, with sustained virological response in 25–45% of patients, but indications, modality and duration of treatment should be assessed. [Copyright &y& Elsevier]

Background: Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors’ experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG. Method: Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients. Results: In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6–48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy. Conclusion: Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV. [ABSTRACT FROM AUTHOR]

Advances in hepatitis B virus (HBV) antiviral prophylaxis have dramatically improved graft and patient survival for patients undergoing liver transplantation for hepatitis B related end-stage liver disease. In particular, the availability of hepatitis B immune globulin (HBIg) in combination with nucleos(t)ide analogues such as lamivudine and adefovir, have transformed outcomes. The availability of newer antivirals such as adefovir, tenofovir and entecavir either as monotherapy or in combination offer an increasing number of antiviral options. Despite these advances, significant challenges remain. Factors that affect the efficacy of anti-viral therapy include detectable HBV viraemia at the time of transplant and emergence of HBV mutants (especially in patients with prior exposure to lamivudine). HBV prophylaxis protocols are expensive especially with use of high-dose HBIg and newer nucleos(t)ide analogues. This review summarizes current HBV prophylaxis protocols and management of recurrent disease post-transplantation. There is an increasing need for individualization of therapy based on prior drug exposures, level of HBV DNA at time of transplantation and type of prophylaxis used. [ABSTRACT FROM AUTHOR]