Active vaccination has been utilized to prevent de novo hepatitis B virus infection (DNHB) in anti-HBc (+) grafts after liver transplantation. However, the long-term efficacy of active vaccination and graft/patient outcomes of anti-HBc (+) grafts have yet to be comprehensively investigated.

Among 204 pediatric patients enrolled in the study, 82 recipients received anti-HBc (+) grafts. For DNHB prevention, active vaccination was repeatedly administered prior to transplant. Antiviral therapy was given to patients with pretransplant anti-HBs <1000 IU/ml (nonrobust response) for 2 years and discontinued when post-transplant patients achieved anti-HBs >1000 IU/ml, while antiviral therapy was not given in patients with an anti-HBs titer over 1000 IU/ml. The primary outcome was to investigate the long-term efficacy of active vaccination, while the secondary outcomes included the graft and patient survival rates.

Among the 82 anti-HBc (+) transplant patients, 68% of recipients achieved a robust immune response, thus not requiring antiviral therapy. Two patients (2.4%) developed DNHB infection, one of which was due to an escape mutant. With a median follow-up of 150 months, the overall 10-year patient and graft survival rates were significantly worse in recipients of anti-HBc (+) grafts than those of anti-HBc (-) grafts (85.2 vs 93.4%, P =0.026; 85.1 vs 93.4%, P =0.034, respectively). Additionally, the 10-year patient and graft outcomes of the anti-HBc (+) graft recipients were significantly worse than those of the anti-HBc (-) graft recipients after excluding early mortality and nongraft mortality values (90.8 vs 96.6%, P =0.036; 93.0 vs 98.3%, P =0.011, respectively).

Our long-term follow-up study demonstrates that active vaccination is a simple, cost-effective strategy against DNHB infection in anti-HBc (+) graft patients, whereby the need for life-long antiviral therapy is removed. Notably, both the anti-HBc (+) grafts and patients exhibited inferior long-term survival rates, although the exact mechanisms remain unclear.

Viral hepatitis infections are a great burden in children who have received liver transplant. Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term. Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection, rendering the condition difficult to manage. Prevention strategies using vaccinations are agreeable to patients, safe, cost-effective and practical. Hence, strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant. Although a vaccine has been developed to prevent hepatitis C and E viruses, its use is not licensed worldwide. Consequently, eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy. Good hygiene and sanitation are also important to prevent hepatitis A and E infections. Donor blood products and liver grafts should be screened for hepatitis B, C and E in children who are undergoing liver transplantation. Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E. Moreover, novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.

This study aimed to explore the prevention and treatment of new hepatitis B in children after liver transplantation with livers positive for HBcAg and to examine the treatment of new hepatitis B.

A total of 22 children who received livers positive for HBcAg between January 2013 and December 2015 were retrospectively analyzed. After their operations, the children were given lamivudine for anti-hepatitis B virus (HBV) treatment, a hepatitis B vaccine or intermittent supplements of hepatitis B immunoglobulins to prevent recurrence of the infection, and entecavir for anti-hepatitis B treatment. The children were categorized into two groups: one group of children stopped taking lamivudine one year after operation (n=7) by themselves, while the other group did not (n=15).

Of the seven children who stopped lamivudine anti-HBV treatment, six developed hepatitis B at 24.33±13.95 months after operation. Of these children, five were treated with entecavir, resulting in their HBV DNA decreasing to undetectable levels (<50 IU/mL). HBsAg turned negative in four of these patients, but in one patient it did not. The other patient with new hepatitis B continued to use lamivudine, resulting in their HBV DNA decreasing to normal levels (<50 IU/mL) but without their HBsAg turning negative. No new cases of hepatitis B were found in the 15 children who did not stop anti-HBV treatment.

The long-term prophylactic therapy of nucleoside analogues combined with hepatitis B immunoglobulins should be used for a long time after liver transplantation with a liver positive for HBcAg. Discontinuation of nucleoside analogues is associated with a higher risk of the new onset of hepatitis B. Entecavir has a significant effect on the treatment of postoperative new hepatitis B in children.

Liver transplantation (LT) remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply. The advent of highly effective anti-viral treatments has reduced the number of patients undergoing LT for hepatitis C (HCV) and hepatitis B (HBV) related liver disease and yet the number of patients waiting for LT continues to increase, driven by an increase in the patients listed with a diagnosis of cirrhosis due to non-alcoholic steatohepatitis and alcohol-related liver disease. In addition, human immunodeficiency virus (HIV) infection, which was previously a contra-indication for LT, is no longer a fatal disease due to the effectiveness of HIV therapy and patients with HIV and liver disease are now developing indications for LT. The rising demand for LT is projected to increase further in the future, thus driving the need to investigate potential means of expanding the pool of potential donors. One mechanism for doing so is utilizing organs from donors that previously would have been discarded or used only in exceptional circumstances such as HCV-positive, HBV-positive, and HIV-positive donors. The advent of highly effective anti-viral therapy has meant that these organs can now be used with excellent outcomes in HCV, HBV or HIV infected recipients and in some cases uninfected recipients.

Liver transplant centres throughout the USA face a huge shortage of liver organs for their wait-listed patients. Various types of innovations are being considered for expansion of this donor pool. Organs that were previously deemed to be high risk are now being considered for transplantation. For the last 25 years, hepatitis B core antibody (anti-HBc+) organs have been used for liver transplantation. While the initial transplantations did reveal a high incidence of de novo hepatitis (DNH) in the recipients, the medical knowledge and experience have evolved and this risk has been markedly decreased. In this paper, medical literature evaluating the safety of such organ transplants has been reviewed. There is strong evidence to suggest that using anti-HBc+ organs with appropriate prophylaxis after transplant is a safe practice with good patient and graft survivals. In the second half of the paper, we discuss whether it is ethical to use anti-HBc+ organs. We argue that the use of such organs is in compliance with the principles of medical ethics and that society at large benefits from the use of these organs. Hence, we recommend that the use of such organs is both safe and ethical and this practice should be continued in the future.

Taiwan has a high prevalence of hepatitis B and C viral infections, and consequently a high burden of chronic liver diseases. Liver transplantation (LT) began in Taiwan in 1984, and living donor liver transplantation (LDLT) in 1994. Education and collaboration between physicians on a national and international scale were important factors in the development of transplantation in East Asia. Technical innovations in donor hepatectomy, vascular and biliary reconstruction, and interventional radiology, perioperative management of transplant patients and development of associated specialties have enabled achievement of excellent results after both adult and pediatric LDLT. The establishment of rigorous protocols to withstand strict medico-legal scrutiny, combined with technical excellence has contributed to excellent surgical outcomes. The socioeconomic development of Taiwan and the first nationwide hepatitis B vaccination program in the world have also contributed to the decrease in disease burden and improvement of quality of healthcare. This article examines the factors enabling the development of LT in Taiwan, the innovations that have contributed to excellent outcomes, and indicates the future prospects of LDLT in Taiwan.

Occult hepatitis B virus infection (OBI) in patients undergoing liver transplantation (LT) is a suspected source of de novo hepatitis B virus (HBV) infection after LT. This study aimed to investigate the prevalence of OBI in liver transplant recipients with alcoholic cirrhosis and demonstrate the association between OBI and de novo HBV infection after LT in these patients.

Forty-three patients with alcoholic cirrhosis who were negative for HBsAg before LT were recruited in this retrospective study. DNA was extracted from paraffin-embedded native liver tissues and quantified for HBV DNA by real-time PCR. Correlation between de novo HBV infection after LT (positive HBsAg and/or detectable HBV DNA in serum) and detection of intrahepatic HBV DNA before LT was analysed.

Detectable HBV DNA in the explanted liver was found in 41.9% (18/43) of the patients and was thus defined as OBI, which was correlated with the presence of serum hepatitis B core antibody (P = 0.008). De novo HBV infection occurred in 18.6% (8/43) of the recipients at a median of 10 months after LT. The rate of de novo HBV infection was 38.9% (7/18) in patients with OBI, compared with 4% (1/25) in patients without OBI (P = 0.004). Furthermore, de novo HBV infection was inversely correlated with the presence of hepatitis B surface antibody in recipients with OBI (P = 0.026).

With a prevalence of 41.9% in liver transplant recipients with alcoholic cirrhosis, OBI in the native liver can predict de novo HBV infection after LT.

The use of serum anti-hepatitis B core antibody (HBc)-positive/hepatitis B surface antigen (HBsAg)-negative liver donors for patients with hepatitis B virus (HBV)-related liver disease (HBRLD) is a promising means of expanding the organ donor pool and does not increase the risk of HBV recurrence. However, whether such donors will compromise the histology of the liver grafts is unclear.

Among 84 patients who underwent transplantation for HBRLD and who did not have post-transplant HBV recurrence (non-detectable serum HBsAg and HBV DNA), 19 underwent liver biopsy (eight received anti-HBc-positive/HBsAg-negative liver grafts; 11 received anti-HBc-negative liver grafts) and were included in the study. Intrahepatic total HBV DNA and covalently closed circular DNA (cccDNA) were detected using real-time polymerase chain reaction; histological characteristics were evaluated with the Batts-Ludwig semi-quantitative scoring system.

Of the 19 recipients, nine (47.4%) were positive for intrahepatic HBV DNA; 82.5% (7/8) received grafts from anti-HBc-positive donors and 18.2% (2/11) received grafts from anti-HBc-negative donors (P=0.003). HBV cccDNA was not detectable in the liver grafts of the 19 recipients. Ten patients had mild inflammation and minimal fibrosis in the portal area: four of the eight in the anti-HBc-positive group and six of the 11 in the anti-HBc-negative group (P>0.05).

Anti-HBc-positive/HBsAg-negative donors for HBRLD pose a higher risk of occult HBV infection post-liver transplant but do not cause liver damage. Thus, anti-HBc-positive grafts may be considered an effective and safe means of expanding the pool of liver donors for patients with HBRLD.

The greatest challenge facing liver transplantation today is the shortage of donor livers. Demand far exceeds supply, and this deficit has driven expansion of what is considered an acceptable organ. The evolving standard has not come without costs, however, as each new frontier of expanded donor quality (i.e., advancing donor age, donation after cardiac death, and split liver) may have traded wait-list for post-transplant morbidity and mortality. This article delineates the nature and severity of risk associated with specific deceased donor liver characteristics and recommends strategies to maximally mitigate these risks.

Although there are many reports on donor safety, there are few concerning aborted donations. We sought to analyze the "no go" donor hepatectomies in our liver transplantation center over 10 years' experience.

Among 290 living donors brought to the operating room for liver graft harvest from March 2002 to April 2012, we examined the reasons to abandon the procedure, comparing their data with those of successful donors.

The donor operation was aborted in 5 cases various for reasons. The main reason for the abandonment of the operation process was poor liver quality: in single cases there was: poor liver quality due to a massive cirrhotic nodule observed by laparoscopy; serious steatosis of the liver, indicated by an intraoperative biopsy; and an unsuitable biliary anatomy, including 4 branches with 2 small ones. In another case, a biliary duct variation in the intraoperative cholangiogram showed a narrow crotch of the left and right ducts. In the 5th case, the donor would have been left with only a small remaining left lobe (<30%) if the right lobe had been harvested. All 5 donors proceeded to accept a right lobe hepatectomy. Comparison with the 285 successful donors showed no significant differences in preoperative demographic data. All 5 donors recovered without complication and were in good condition over long-term follow-up.

A low rate of "no go" donor hepatectomy can be achieved. There was no short- or long-term harm to the living donor owing to abandonment of the procedure.

The aim of this study was to analyze the incidence and risk factors of de novo hepatitis B virus (HBV) infection from hepatitis B core antibody (anti-HBc)-positive donors in pediatric living donor liver transplantation (LDLT).

We retrospectively analyzed 46 recipients without pre-liver transplantation (LT) HBV infection evidence who underwent LDLT from October 2006 to May 2011 in our center. HBV markers, including hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), anti-HBc, hepatitis B e antigen (HBeAg) and antibody (anti-HBe) were determined in both donors and recipients before LT and in recipients after LT. HBV DNA titer was measured if the recipients were strongly suspected of de novo HBV infection.

Without prophylaxis, de novo HBV infection occurred in 11 of 46 recipients (23.9%) 6-36 months after LT. All 11 patients received grafts from anti-HBc-positive donors. The donors' baseline status and the characteristics of recipients at the time of transplantation were not associated with the acquisition of de novo hepatitis B infection. The overall 2-year survival rate of patients from anti-HBc-positive donors was 84.2%. Two de novo HBV-infected patients who had YMDD mutation were given adefovir combined with lamivudine, and their liver function gradually improved during the follow-up period.

Anti-HBc-positive donors can significantly increase the incidence of de novo HBV infection in HBsAg-negative recipients. Administration with adefovir in patients who are resistant to lamivudine seems to be an effective and safe way for de novo HBV infection.

Lamivudine (LAM) has been shown to prevent de novo hepatitis B virus (HBV) infection in recipients of hepatitis B core antibody (HBcAb)-positive liver transplants (LT) but primarily in small studies with limited follow-up.

We conducted a retrospective cohort study of HBcAb+ graft recipients at our institution from October 1999 to August 2008.

One hundred nineteen recipients without prior HBV were identified (median age, 54 years; 70% male), of which 62 received LAM. The median follow-up was 2.6 years overall and 5.3 years in the LAM group. Among LAM recipients, 44% were HBV naïve (HBsAb-/HBcAb-) at LT, of which 6% developed HBsAb+ and 3% developed HBcAb+ after LT. Eight percent developed de novo HBV: two recipients became hepatitis B surface antigen positive at 70 and 23 months and three experienced breakthrough with HBV DNA more than 2000 IU at 1 to 9 months after LT. Sixty percent (3 of 5) were HBV naïve. Four (6%) other recipients also had transiently detectable HBV less than 2000 IU, which did not require any changes to their prophylaxis regimen. When compared with recipients who received other nucleos(t)ide analogues, there was no difference in de novo rates: LAM 8% (5 of 62), adefovir 15% (5 of 33), tenofovir 0% (0 of 3), entecavir 0% (0 of 1), and 5% (1 of 20) for those not given prophylaxis (P=0.59).

LAM monoprophylaxis was effective in preventing de novo HBV in the vast majority of recipients over long-term follow-up. Adefovir had a higher rate of de novo infections numerically, whereas tenofovir and entecavir had no cases and may be more effective, but this was limited by a small sample size.

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.

Donor liver allografts with positive serology for hepatitis B core antibody [HBc (+)] have been increasingly used for liver transplantation. However, the optimal prophylactic regimen to prevent development of de novo hepatitis B has not been determined. To evaluate this, we screened United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) registry data for adult recipients of HBc (+) organs who were HBsAg (-), and evaluated the effects of using prophylactic anti-viral therapies (HBIG and lamivudine) on patient and graft survival. Out of a total cohort of 958 patients transplanted since 2004, 61 received HBIG alone, 116 received lamivudine alone, 66 both, 509 neither and 206 were missing this information. Based on several multivariable Cox regression models, patients receiving HBIG therapy-only were observed to have a statistically significant (approximately 70%) reduction in risk of mortality compared with patients receiving lamivudine-only therapy [HR=0.29, 95% CI (0.10, 0.86), P=0.026], and a nonstatistically significant reduction in risk of graft failure. However, no graft failures were attributed to de novo hepatitis B, suggesting that any improved graft/patient survival possibly associated with HBIG therapy occurs independently of de novo hepatitis B virus (HBV) reduction. While this study cannot prove that HBIG therapy is protective for graft and patient survival after liver transplantation, these findings do highlight the need to further examine and study prophylactic use in recipients of HBc (+) donors.

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.

Use of grafts from hepatitis B (HBV) core antibody (HBcAb(+)) individuals is a routine transplant practice. Herein, we have reported the results of 20 HBV-negative patients transplanted with a HBcAb-positive liver grafts in order to access the efficacy of HBV prophylaxis using immunoglobulin (IE) and antiviral drugs.

From January 2004 to December 2009, we performed 168 liver transplantations including 38 HBcAb-positive grafts (22.6%) in 18 cases of HBV-positive recipients and 20 HBV-negative recipients. Histological data obtained from these last 20 grafts during retrieval showed an Ishak 1 score in three and no fibrosis in the other cases. HBV prophylaxis included infusion of 10,000 UI IG during the anhepatic phase and every 24 hours for the first 7 days irrespective of the antibody titer as well as lamivudin (100 mg) administered daily. Once discharged, outpatient management provided modulated IG infusions according to when the antibody titer was lower than 400 UI.

No patient displayed an HBV infection. The overall survival was 80%. Two patients died within the first month after transplantation due to septic complications; one patient succumbed at 24 months after transplantation because of a lymphoproliferative malignancy and another died due to an aggressive hepatitis C virus recurrence at 6 months post transplant.

By using appropriate anti-HBV prophylaxis, HBcAb-positive grafts can be used safely for HBcAb-negative recipients.

After liver transplant (LT) from Anti-HBc+/HBsAg- donors into HBsAg- recipients, transmission of hepatitis B virus (HBV) may occur (de novo HBV infection). This study analyzes the incidence of de novo HBV infection in HBsAg- recipients of Anti-HBc+/HBsAg- LT with respect to: (i) the recipients' HBV serology and (ii) the type of preventive therapy adopted.

A systematic review of the literature using the electronic database Medline.

Five hundred and fifty-two LT in 36 articles were selected. Lamivudine, Hepatitis B immune globulin (HBIG), revaccination, and combined therapies were employed in multiple strategies as preventive interventions. Naïve recipients had a high risk of de novo HBV infection, with smaller incidences when HBIG and lamivudine were used, either alone or in association. Vaccinated recipients or those with isolated hepatitis B core antibodies (Anti-HBc) and previous HBV infection had lower risks of viral transmission, additionally reduced by any prophylaxis adoption.

LT from Anti-HBc+/HBsAg- donors into HBsAg- recipients is apparently safe, as long as the recipient is vaccinated or presents an isolated Anti-HBc or previous HBV infection and some prophylaxis is employed. Currently lamivudine seems the best alternative; other nucleoside analogs and revaccination strategies should be considered in future studies. Follow-up and preventive therapies should be maintained for five yr or preferably throughout the recipients' life span.

SkagenMany 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.

Liver grafts from donors positive for antibody to hepatitis B core antigen (anti-HBc) may be used for transplantation in patients with hepatitis B virus (HBV)-related liver disease, and an occult HBV infection may develop from either source. Liver biopsy was performed for 31 patients who remained seronegative for hepatitis B surface antigen for a median of 44.5 months (range = 13.6-126.4 months) and received nucleoside analogue prophylaxis post-transplant. Nineteen of these recipients (61%) had received anti-HBc-positive grafts. Intrahepatic total HBV DNA and covalently closed circular DNA (cccDNA) levels were quantified, and the sequence was analyzed. Intrahepatic total HBV DNA and cccDNA were detectable in 26 (84%) and 16 (52%) of the 31 recipients, respectively, and they were more common when the donor was positive for anti-HBc (95% versus 67%, P = 0.038). The intrahepatic HBV DNA level correlated with the recipient pretransplant serum HBV DNA level (P = 0.06), and the intrahepatic HBV cccDNA level correlated with the donor intrahepatic HBV cccDNA level (P = 0.06). A phylogenetic analysis of the isolated HBV DNA sequence revealed HBV infections of both donor and recipient origins. In conclusion, an occult HBV infection after liver transplantation can originate from both the donor and recipient despite prolonged nucleoside analogue prophylaxis. The presence of intrahepatic HBV cccDNA is attributable more to the persistence of preexisting intrahepatic HBV cccDNA from a donor with previous exposure.

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

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.

A retrospective study of HBsAg-negative patients receiving liver transplantation (LT) from anti-HBc-positive donors during a 10-year period.

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.

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.

A variety of prophylactic strategies are used to prevent the risk of hepatitis B virus (HBV) transmission from antibody to hepatitis B core antigen (anti-HBc)-positive donors. The mechanisms underlying the failure of HBV immunoglobulin monoprophylaxis have been poorly evaluated. Seventy-seven anti-HBc-positive grafts were used in 21 hepatitis B surface antigen (HBsAg)-positive recipients and 56 HBsAg-negative recipients. HBsAg-positive recipients received prophylaxis comprising hepatitis B immunoglobulins (HBIG) and antiviral agents, 45 HBsAg-negative recipients received a modified HBIG regimen, and 11 HBsAg-negative recipients received no prophylaxis. Both donors and recipients were screened for HBsAg, antibody to HBsAg (anti-HBs) and anti-HBc in their sera and for HBV DNA in both their sera and liver. S gene mutations were investigated after HBV reinfection. HBV infection occurred in 15 HBsAg-negative recipients (19.4%) at a median interval of 16 months (range = 6-67 months) post-transplant and in none of the HBsAg-positive recipients. HBV infections were observed in 31.6% of HBV-naive recipients and 7.7% of HBV-immune recipients receiving HBIG prophylaxis versus 100% of HBV-naive recipients (P = 0.0068) and 33% of HBV-immune recipients (P = 0.08) with no such prophylaxis. S gene mutations were identified in 9 recipients. In conclusion, priority should be given to using anti-HBc positive grafts for HBsAg-positive or HBV-immune recipients. Our study has confirmed the high risk of HBV transmission to naive recipients. HBIG monoprophylaxis was associated with a significant risk of de novo HBV infection and HBV escape mutations. In these patients, we therefore recommend prophylaxis with lamivudine or new nucleos(t)ides analogues. The potential benefits of HBIG prophylaxis combined with antiviral drugs require further evaluations. Long-term prophylaxis is needed because of the long interval of de novo HBV infection post-transplant in some patients.

Orthotopic liver transplantation (OLT) recipients without hepatitis B virus (HBV) infection who receive liver grafts from antibody to hepatitis B core antigen-positive [HBcAb(+)], hepatitis B surface antigen-negative [HBsAg(-)] donors have an increased risk of developing de novo hepatitis B infection. We compared the 2 most commonly employed prophylactic regimens-lamivudine (LAM) monotherapy and hepatitis B immunoglobulin (HBIG)+LAM combination therapy-to determine the relative efficacies of these 2 protocols in preventing de novo hepatitis B infection. A comprehensive search of the Cochrane Database of Systematic Reviews, MEDLINE (1966 to June 2009), and bibliographies of retrieved trials was conducted. Eligible studies included OLT recipients who received HBcAb(+) liver grafts and were treated prophylactically with either LAM monotherapy or HBIG+LAM combination therapy. 13 studies were identified as meeting the eligibility criteria. The rates of de novo hepatitis B infection, mortality, and mortality due to de novo hepatitis B infection were assessed. The incidence of de novo hepatitis B infection was 2.7% (n = 73) in patients receiving LAM-only prophylaxis versus 3.6% (n = 110) in patients receiving HBIG+LAM combination therapy. In the HBIG+LAM group, the dose and duration of HBIG therapy were highly variable. The median follow-up time for the LAM monotherapy group was 25.4 months with a range of 14.78 to 27.6 months, whereas the median follow-up time for the LAM+HBIG group was 31.1 months with a range of 15.3 to 38.5 months. The risk of developing de novo hepatitis B infection based on the pretransplant recipient HBV serology in each treatment group could not be calculated because of incomplete data and the limited number of de novo hepatitis B infection cases in the series reviewed. In conclusion, on the basis of these findings, we conclude that published studies have not shown HBIG+LAM combination therapy to be more effective than LAM-only treatment. Nucleoside analogue monotherapy should therefore be considered when one is treating HBV(-) patients who have received liver allografts from HBcAb(+) donors.

Although hepatitis B virus (HBV) transmission after liver transplantation of grafts from HBsAg-negative, anti-HBc positive donors is well established, the growing organ shortage favours the use of such marginal grafts. We systematically evaluated the risk of HBV infection after liver transplantation with such grafts and the effect of anti-HBV prophylaxis.

We performed a literature review over the last 15 years identifying 39 studies including 903 recipients of anti-HBc positive liver grafts.

Recurrent HBV infection developed in 11% of HBsAg-positive liver transplant recipients of anti-HBc positive grafts, while survival was similar (67-100%) to HBsAg-positive recipients of anti-HBc negative grafts. De novo HBV infection developed in 19% of HBsAg-negative recipients being less frequent in anti-HBc/anti-HBs positive than HBV naive cases without prophylaxis (15% vs 48%, p<0.001). Anti-HBV prophylaxis reduced de novo infection rates in both anti-HBc/anti-HBs positive (3%) and HBV naive recipients (12%). De novo infection rates were 19%, 2.6% and 2.8% in HBsAg-negative recipients under hepatitis B immunoglobulin, lamivudine and their combination, respectively.

Liver grafts from anti-HBc positive donors can be safely used, preferentially in HBsAg-positive or anti-HBc/anti-HBs positive recipients. HBsAg-negative recipients should receive prophylaxis with lamivudine, while both anti-HBc and anti-HBs positive recipients may need no prophylaxis at all.

The characteristics of hepatitis B virus (HBV) in vaccinated children who acquire de novo HBV infections after orthotopic liver transplantation (OLT) remain largely unknown. The aim of this study was to explore HBV mutants in pediatric OLT recipients with de novo HBV infections. In all, 50 recipients underwent OLT between December 1997 and October 2005, and they were regularly checked for HBV serum markers from November 2005 to April 2009. Before OLT, all were hepatitis B surface antigen (HBsAg)-negative and under the coverage of the universal infant HBV vaccination program. Those who became HBsAg-positive after OLT were diagnosed with de novo HBV infection. HBV viral loads and full-length genome sequencing were determined when the diagnosis of de novo HBV infection was established. Nine patients (9/50, 18%) acquired de novo HBV infections after OLT. None had graft loss or fulminant hepatitis. Five cleared HBsAg, and 4 of the 5 even recovered with antibody to hepatitis B surface antigen (anti-HBs) formation. The other 4 were persistently HBsAg-positive. Mutations in the major S gene (681 base pairs) were discovered in 8 (88.9%) of the de novo HBV-infected children. Six of them harbored mutations within the "a" determinant region (codons 124-147), whereas the other 2 had mutations outside this region. These 2 cleared HBsAg and recovered with anti-HBs formation. HBV DNA levels were not different between those who cleared HBsAg and those who did not. In conclusion, surface mutants are frequent among pediatric liver transplant recipients with de novo HBV infections, but their clinical relevance requires further study.

Prophylactic therapy is generally used to prevent reactivated hepatitis B after transplantation of an antibody to hepatitis B core antigen (anti-HBc)-positive liver. To gain insight into current practice, a questionnaire was e-mailed to 89 liver transplant physicians in the United States, Europe, and Asia/Australia and 4 hepatitis B experts. Addressees were asked if they prefer lamivudine or other nucleoside analogs and whether these drugs are used indefinitely. They were also questioned about the use of hepatitis B immune globulin (HBIg), the preferred duration of its administration, and whether treatment strategies differ according to the knowledge of the serologic status of the recipient. Responses were obtained from 78 physicians. All transplant physicians reported the use of nucleoside analog therapy, and 65% prefer lamivudine (58% versus 81% for US and non-US physicians, P = 0.05). Sixty-one percent use HBIg (38% always, 23% sometimes). HBIg was used more frequently in the United States than other parts of the world (69% versus 46%, P = 0.03). Eighty-one percent of transplant physicians use nucleoside analog therapy for an indefinite period, but the duration of HBIg treatment varies widely. Although some centers omit nucleoside analog or HBIg therapy in antibody to hepatitis B surface antigen-positive recipients, 90% will not omit these agents if the recipient is positive for anti-HBc alone. In conclusion, nucleoside analog therapy is nearly always used for anti-HBc-positive livers, and most transplant physicians treat for an indefinite period. Lamivudine continues to be preferred as first-line therapy. Many programs also use HBIg, but there is wide variation in the way this is administered. Further study is needed to determine the most cost-beneficial regimen.

De novo hepatitis B virus (HBV) infection is defined as infection occurring in HBV surface antigen (HBsAg)-negative patients who become HbsAg positive after organ transplantation. We assessed the incidence and risk factors of de novo HBV infection in pediatric liver transplant recipients.

From 1996 to 2006, 71 Taiwanese children with non-HBV-related liver diseases underwent orthotopic liver transplantation (OLT) at the National Taiwan University Hospital. All of the surviving recipients were tested regularly for liver function, serum levels of immunosuppressant, HBsAg, titers of antibodies to hepatitis B surface antigen (anti-HBs), antibodies to hepatitis B core antigen (anti-HBc), and antibodies to hepatitis C virus (anti-HCV). HBV vaccination histories and the anti-HBs titers before OLT were recorded. No regular prophylaxis was given.

Fifty-nine patients (33 girls and 26 boys) were followed up for a median of 4.4 years (range 1.0-10.0). Of those, 36 (61.0%) received allografts from anti-HBc-positive and HBsAg-negative donors. De novo HBV infection was found in 9 (15.3%) patients after OLT, 8 of whom received allografts from HBsAg-negative and anti-HBc-positive donors. Forty-eight (81.4%) patients received 3 or more doses of HBV vaccine before OLT. Pre-OLT anti-HBs titers were available for 49 recipients. Of the 9 de novo HBV-infected recipients, 8 had anti-HBs titers <200 mIU/mL. No graft loss or fulminant hepatitis was noted.

In the absence of adequate prophylaxis, the incidence of de novo HBV infection in pediatric OLT recipients is 15.3%. An anti-HBs titer of >200 mIU/mL before OLT may be sufficient to prevent de novo HBV infection in HBsAg-negative recipients.

Routine versus selective predonation liver biopsy (LBx) remains controversial for assuring the safety of right hepatic lobe live donor (RHLD). Between December 1999 and March 2007, 403 potential RHLD were evaluated; 142 donated. Indications for selective LBx were: abnormal liver function tests or imaging studies, body mass index (BMI) >28, history of substance abuse or family history of immune mediated liver disease. All donors had a LBx at the time of surgery. Of 403 potential RLD, 149(36.9%) were accepted as donors, 25(6.3%) had their recipient receive a deceased donor graft, 94(23.4%) were rejected, 52(12.9%) stopped the evaluation process, 76(18.8%) withdrew from the process and 7(1.7%) are currently completing evaluation. Eighty-seven (21.5%) met criteria and were biopsied. Seventy-three (83.9%) had either normal (n = 24) or macrosteatosis <10% (n = 49); 51 of these donated. Abnormal LBx eliminated 15 potential donors. No significant abnormalities were found in donation biopsies of donors not meeting algorithm criteria. Three of 87 (3.4%) had complications requiring overnight admission (2 for pain, 1 for bleeding; transfusion not required). Use of this algorithm resulted in 78% of potential donors avoiding biopsy and potential complications. No significant liver pathology was identified in donors not meeting criteria for evaluation LBx. Routine predonation LBx is unnecessary in potential RHLD.

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.

Liver transplantation using a graft from a donor with a positive hepatitis B surface antigen (HBsAg) has been contraindicated owing to the extremely high risk for recurrent disease leading to graft loss. However, the severe shortage of donors often forces the transplant community to utilize suboptimal donors, especially in the setting of living donor liver transplantation (LDLT).

Here, we report a case of successful LDLT for a patient with hepatitis B-related cirrhosis utilizing a graft from an HBsAg-positive 'healthy carrier' donor using a combination prophylaxis of lamivudine and adefovir dipivoxil.

To date, the patient has been doing well with normal liver function tests and liver histological findings at 4 years after the transplantation and the donor has also been doing well.

Although virological recurrence appears to be universal despite prophylaxis, re-evaluation of the use of a graft from a healthy HBsAg-positive donor is warranted in this era of combination prophylaxis.

Hepatitis B surface antigen-negative and hepatitis B core antibody-positive grafts were considered unsuitable for transplantation. The number of potential recipients for liver transplantation now exceeds that of potential donor organs, which has led us to reevaluate the feasibility of these grafts. Several strategies involving prophylactic administration of hepatitis B immunoglobulin and/or lamivudine to transplant recipients have been proposed. At the University of Tokyo, we have continued to use hepatitis B immunoglobulin monoprophylaxis with zero recurrence. In this article we report our experience with the use of hepatitis B surface antigen-negative/hepatitis B core antibody-positive grafts with hepatitis B immunoglobulin monotherapy. We conducted a review of the literature regarding the feasibility of these grafts to reconfirm optimal prophylactic strategies for preventing de novo hepatitis B virus infection in transplant recipients.

The efficacy of hepatitis B vaccination after living donor liver transplantation (LDLT) in patients transplanted anti-HBc-positive grafts or in patients who underwent LDLT for fulminant hepatitis B remains unknown.

A total of 11 recipients who underwent LDLT between October 1996 and October 2002 prospectively received hepatitis B vaccination three times within 6 months, starting a few weeks after the cessation of hepatitis B immunoglobulin (HBIG) prophylaxis. Serial quantification of the hepatitis B surface antibody (HBsAb) was performed.

At the last follow-up, six out of 11 patients (54.5%) had seroconversion and were free from HBIG thereafter. Four out of those six responders had a peak HBsAb level of more than 1000 IU/L, while the other two patients had peak HbsAb levels below 1000 IU/L. Five patients never responded to the treatment and were back to HBIG prophylaxis. The average age of the six responders was 25.5 years, which was significantly younger than that of non-responders (44.4 years, P<0.05). None had side effects or hepatitis B infection during the study period.

In conclusion, the use of this treatment modality could be used to reduce the cost of HBIG.

Liver allografts from donors previously exposed to hepatitis B virus (HBV) carry the risk of transmission of HBV infection to immunosuppressed recipients. However, exclusion of donor candidates with the serologic evidence of resolved hepatitis B-HBV surface antigen (HbsAg) negative and HBV core antibody (anti-HBc) positive-is not feasible in countries endemic for HBV.

Our aim was to assess the safety of living donor liver transplantation from anti-HBc positive donors.

In our institution, 152 transplants were performed between June 1999 and April 2004. Fifty-six (37%) of the living donors were anti-HBc positive. Twenty of these liver grafts were transplanted to HbsAg-negative recipients. We excluded four HBsAg negative recipients who died because of early complications after transplantation. Lamivudine (100 mg/day) was given for prophylaxis of de novo HBV infection.

The mean follow-up time for 16 HBsAg-negative recipients was 21.7 (7-48) months. None of them experienced de novo HBV infection.

The use of liver allografts from anti-HBc-positive living donors is reasonably safe in HBsAg-negative recipients under lamivudine prophylaxis.

Since the introduction of liver transplantation as a routine surgical procedure for the treatment of end-stage liver disease, there has been an increasing gap between the number of available grafts and the number of patients on the waiting list. This has led transplant centers to expand the donor pool by different means. One of them has been the introduction of living donor liver transplantation. Other strategies include using less than optimal allografts from deceased donors, the so-called marginal donors, which include the use of grafts from older subjects, livers with moderate amounts of steatosis, or from donors with markers of past or current infection with hepatitis viruses who have absent or minimal liver biochemical or histologic injury. In this review, we will focus on the current use of allografts from donors with antihepatitis B core antibody and/or antibodies against hepatitis C virus in cadaveric and living donor liver transplantation.

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.

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.

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.

Long-term lamivudine monotherapy was effective in preventing development of HBV infection in HBsAg-negative liver transplant recipients from HBcAb-positive donors.

Liver recipients who have antibodies to hepatitis B core antigen (anti-HBc) or received an anti-HBc positive liver graft are at risk of acquiring de novo hepatitis B infection so a life long prophylaxis is required. A post-transplant vaccination against hepatitis B virus (HBV) can offer a better alternative than either hepatitis B hyperimmune globulin (HBIG) or lamivudine. This study investigated the course of anti-HBs titer after vaccination and analyzed the factors that influence the response. Between October 1999 and February 2003, 37 pediatric patients were given a post-transplant vaccination when an anti-HBc positive graft was used, the recipient was anti-HBc positive, or when anti-HBs titer was below 20 IU/L irrespective of the serological status. Thirty-three patients responded to the vaccine and did not require further HBIG injections at a mean follow up of 33.6 months. Fifteen patients were good responder and only needed a single set of vaccines, and 18 were poor responder needing additional boosters. Two patients developed de novo hepatitis B infection and two required additional HBIG injections. Preoperative severity of liver disease, serological status of HBV of recipient or donor, use of HBIG or pulse steroid therapy, type of vaccines, and dose or time interval between doses had no influence on response rate. Recipients with a high preoperative anti-HB titer, small graft-recipient weight ratio (GRWR), greater catch up growth, heavier body weight, lower tacrolimus level at the time of vaccination, and longer time interval between transplant or steroid medication and vaccination yielded good response. If well tailored, post-transplant vaccination can be effective and offer patients prophylaxis against de novo hepatitis B infection for a prolonged period of time.

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.

Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors.

We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA.

All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months.

Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors.

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.

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.

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.

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.

After hematopoietic cell transplantation (HCT), hepatitis due to hepatitis B virus (HBV) rarely occurred beyond the initial 12 months after transplantation.

We investigated the cause of "late" hepatitis due to HBV infection in two recipients after allogeneic HCT.

Two male patients with acute myeloid leukemia and light chain myeloma, respectively, developed HBV-related hepatitis more than 2 years after HCT. All serum samples collected from the recipients, donors and their respective spouses were tested for HBV DNA by nested PCR, and if positive further quantified by Digene Hybrid Capture assay II. The HBV genotype was determined by PCR and sequencing.

Genotypic analysis suggested that the cause of "late" hepatitis was due to acute HBV infection transmitted from their respective spouse.

Our findings suggested that sexual precautions should be taken in these patients after HCT. Alternatively, or even additionally, active vaccination should be delivered to these patients once they have lost their HBV immunity.

Living donor liver transplantation (LDLT) has the capacity to reduce the current discrepancy between the number of patients on the transplant waiting list and the number of available organ donors. For pediatric patients, LDLT has clearly reduced the number of waiting list deaths, providing compelling evidence for an increase in LDLT programs. This review discusses many of the recent advances in LDLT.