Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.

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

Liver transplantation for acute and chronic viral hepatitis

Summary. Hepatotrophic viruses are responsible for a substantial proportion of cases of both end-stage chronic liver disease and of acute liver failure which are treated by liver transplantation. We review here current practice in transplantation for viral-induced liver disease addressing, in particular, the selection of patients for transplantation and the increasingly recognized problem of recurrent disease in liver grafts.     

Laparoscopic and robotic donor pancreatectomy for living donor pancreas and pancreas–kidney transplantation

Pancreas transplantation is a widely accepted procedure that can efficiently restore euglycemia and prevent progression of complications. In most instances, the limiting factor for deceased donor organ transplantation is the availability and quality of the available organs. Living donor pancreas transplant was introduced at the University of Minnesota in 1979. Because of the potential risks for the donor and the technical challenges in the recipient operation, this procedure has not become very popular since then. In 1999, in the attempt to decrease the morbidity associated with open distal pancreatectomy, the first laparoscopic donor distal pancreatectomy with hand-assisted technique was performed at the same institution. In 2000, the FDA approved the robotic surgical system Da Vinci for general use. Since then, the system has been extensively used at our institution to perform living donor nephrectomy. The only case reported worldwide of robotic distal pancreatectomy and nephrectomy for living donor pancreas–kidney transplantation was successfully performed by our team in 2006 at the University of Illinois at Chicago and proved as a promising technique. The application of minimally invasive techniques has allowed an increased acceptance of the procedure among potential donors and may, therefore, increase the number of donors for this life-saving transplant. The initial results are encouraging and clearly prove feasibility.     

Efficacy and safety of prophylaxis with entecavir and hepatitis B immunoglobulin in preventing hepatitis B recurrence after living‐donor liver transplantation

Aim: Hepatitis B recurrence after liver transplantation can be reduced to less than 10% by combination therapy with lamivudine (LAM) and hepatitis B immunoglobulin (HBIG). The aim of this study was to evaluate the efficacy and safety of prophylaxis with entecavir (ETV), which has higher efficacy and lower resistance rates than LAM, combined with HBIG in preventing hepatitis B recurrence after living‐donor liver transplantation (LDLT). Methods: Twenty‐six patients who received ETV plus HBIG (ETV group) after LDLT for hepatitis B virus (HBV)‐related end‐stage liver disease were analyzed by comparing with 63 control patients who had received LAM plus HBIG (LAM group). Results: The survival rates of the patients treated with ETV plus HBIG was 73% after both 1 and 3 years, and there was no statistical difference between the patients in the ETV group and LAM group. No HBV recurrence was detected during the median follow‐up period of 25.1 months in the ETV group, whereas the HBV recurrence rate was 4% at 3 years and 6% at 5 years in the LAM group. No patients had adverse effects related to ETV administration. Conclusion: ETV combined with HBIG provides effective and safe prophylaxis in preventing hepatitis B recurrence after LDLT.     

Successful living donor liver transplantation using a graft from a hepatitis B surface antigen-positive donor.

BACKGROUND/AIMS: 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). METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.     

Utilization of hepatitis B core antibody-positive donor liver grafts

Background

The inclusion of hepatitis B core antibody-positive (HBcAb+) liver donors is a strategy utilized to increase organ availability. This study examined HBcAb+ transplantation practices to identify specific factors influencing outcomes.

Methods

Twenty-five HBcAb+ liver transplants were identified retrospectively among 868 adult transplants performed between 1 January 1997 and 31 December 2009. Twelve (48%) recipients had hepatitis C and five (20%) had hepatitis B. Patient and donor demographics, preoperative morbidity, transplant data and outcomes were examined. Statistical analysis was completed using Student''s t-test or the Kaplan–Meier method. A P-value of <0.05 was considered significant.

Results

There was no difference in age, body mass index or comorbidities between HBcAb+ liver recipients and control subjects. Model for End-stage Liver Disease (MELD) scores of >30 were significantly more frequent in HBcAb+ liver recipients (32% vs. 15%; P = 0.04). All patients received immunoglobulin and longterm antiviral therapy as prophylaxis against graft hepatitis B resurgence. No patients who received HBcAb+ livers developed hepatitis B infection on follow-up. Overall survival at 30 days, 1 year and 5 years in HBcAb+ liver recipients was 92%, 74% and 74%, respectively, compared with 96%, 89% and 76%, respectively, in the control group (P = not significant, log-rank test). All except one of the deaths in the HBcAb+ liver recipient group occurred within 90 days postoperatively and in patients with MELD scores >30.

Conclusions

The practice of transplanting HBcAb+ grafts incurs low risk for infection using current methods of prophylaxis. The highest mortality risk was in the early postoperative period, specifically in patients with very high MELD scores. This probably reflects the practice of using positive serology grafts in emergent situations.     

Transmission of viral hepatitis by blood and blood derivatives: current risks, past heritage

For more than 40 years in the history of transfusion medicine, transmission of viral hepatitis from infected donors to recipients has been a frequent and serious adverse effect of the administration of blood components and plasma derivatives. This epidemic is now over, at least in developed and resource-rich countries. Hence, the attention of clinicians and investigators now focuses mainly on the measures to reduce the residual risk, on the possible emergence of novel or undiscovered agents causing post-transfusion hepatitis, and on the long-term outcome of patients who became infected more than ten years ago. The present article reviews these issues.     

Liver transplantation in viral hepatitis: Prevention of recurrence

Of patients undergoing OLT, 10–30% have HBV and HCV infection, respectively. Outcome depends on the prevention of allograft reinfection. The advent of long-term hepatitis B immunoglobulin administration and the introduction of antiviral agents were a major breakthrough in the management of these patients. Today, survival after OLT is similar to that in patients receiving transplants for HBsAg-negative liver disease, and the risk of HBV recurrence is <10%. New antiviral drugs, such as entecavir and tenofovir, as mono or combination therapy will be additional antiviral alternatives pre- and post-transplantation. Several issues warrant further study: testing of prophylactic protocols that utilize lower or shorter HBIG doses in combination with antiviral agents, and evaluation of new antiviral combinations which have low rates of drug resistance. Conversely, HCV reinfection occurs almost invariably, and it significantly impairs patient and graft survival. Factors that may influence progression of HCV graft injury remain unclear. Chronic HCV infection develops in 75–90% of patients, and 5–30% progress to cirrhosis within 5 years. Pre-transplantation and prophylactic post-transplantation antiviral treatment is limited by low applicability and poor tolerance. Treatment of established graft lesions with (peg)interferon and ribavirin combination therapy achieved sustained virological response in 30–45% of patients.     

Direct‐acting antivirals and hepatitis B virus (HBV) reactivation in co‐infected HBV/HCV kidney‐transplant recipients

Direct‐acting agents (DAAs) are highly efficient at treating hepatitis C virus (HCV) infections after kidney transplantation. Although drug agencies have recently warned of the risk of hepatitis B virus (HBV) reactivation after patients have received DAAs, reports have discrepant results in HBsAg‐positive and HBsAg‐negative patients. We report on 3 cases of HBV reactivation that were detected after achieving a DAA‐associated sustained virological response in 3 kidney‐transplant recipients initially HBsAg‐negative. In the first case, retrospective virological analysis revealed that HBsAgs had become positive and HBV DNA was detectable before initiating DAA therapy. In the second and third cases, HBV reactivation occurred 2 months and more than 1 year after stopping anti‐HCV therapy. These cases underline the discrepancies and highlight the need for comprehensive information before making definitive conclusions regarding the causal link between DAAs and HBV reactivation.     

Older donor allografts are associated with poor patient survival after living donor liver transplantation for hepatitis B virus-related liver diseases.

BACKGROUND AND AIMS: The significance of donor age in living donor liver transplantation (LDLT) for hepatitis B virus (HBV) infection has not been fully evaluated. METHODS: We analyzed the data of 136 patients who underwent LDLT for HBV-related liver diseases from January 1999 to April 2004. The recipients were divided into an older donor group (donor age > or = 40) and a younger donor group (donor age < 40). Posttransplant clinical outcomes and survival were compared between two groups, and predictors of survival after LDLT were evaluated. RESULTS: Baseline characteristics were not different between the two groups, except for more number of female donors and higher positive donor anti-HBc rate in the older group. The frequencies of acute rejection and early mortality after transplantation were similar in the two groups. The long-term survival rates for the older donor group were significantly lower than those of the younger donor group (1-, 3-, 5-year survival rate = 84%, 75%, 46% vs. 92%, 86%, and 83%, P = 0.03). Multivariate analysis showed that older donor age was the only independent risk factor associated with survival after LDLT (HR = 2.3; 95% CI = 1.1-5.6, P = 0.04). CONCLUSIONS: Our study suggests that older donor allografts would be associated with poor patient survival after LDLT for HBV-related liver diseases.     

No increased mortality from donor or recipient hepatitis B‐ and/or hepatitis C‐positive serostatus after related‐donor allogeneic hematopoietic cell transplantation

Limited data exist on allogeneic transplant outcomes in recipients receiving hematopoietic cells from donors with prior or current hepatitis B (HBV) or C virus (HCV) infection (seropositive donors), or for recipients with prior or current HBV or HCV infection (seropositive recipients). Transplant outcomes are reported for 416 recipients from 121 centers, who received a human leukocyte antigen‐identical related‐donor allogeneic transplant for hematologic malignancies between 1995 and 2003. Of these, 33 seronegative recipients received grafts from seropositive donors and 128 recipients were seropositive. The remaining 256 patients served as controls. With comparable median follow‐up (cases, 5.9 years; controls, 6.7 years), the incidence of treatment‐related mortality, survival, graft‐versus‐host disease, and hepatic toxicity, appears similar in all cohorts. The frequencies of hepatic toxicities as well as causes of death between cases and controls were similar. Prior exposure to HBV or HCV in either the donor or the recipient should not be considered an absolute contraindication to transplant.     

Hepatitis B reactivation after kidney transplantation in hepatitis B surface antigen‐negative,core antibody‐positive recipients

Nowadays, intensive immunosuppressive therapy including rituximab is commonly used prior to kidney transplantation (KT), raising concerns over hepatitis B virus (HBV) reactivation among hepatitis B surface antigen (HBsAg)‐negative and anti‐hepatitis B core (HBc)‐positive KT recipients. Recent practice guidelines suggested watchful monitoring or antiviral prophylaxis for the first 6‐12 months, the period of maximal immunosuppression. However, the actual risk for HBV reactivation, and whether short‐term antiviral therapy in the early period is necessary, remains unclear. A total of 449 HBsAg‐negative and anti‐HBc‐positive KT recipients were analysed for HBV reactivation. During a median follow‐up of 6.7 (interquartile range: 4.2‐9.4) years, HBV reactivation was observed in 9 patients (2.0%). The median time of HBV reactivation from KT was 2.8 years (range: 1.4‐11.5 years), with cumulative incidence rates of 0%, 1% and 2% for 1, 3 and 5 years, respectively. There were no severe adverse outcomes, including liver transplantation or mortality related to HBV reactivation. The risk of HBV reactivation was not high, even in anti‐HBs‐negative patients (n = 60, 4% at 5 years), ABO mismatch (n = 92, 4% at 5 years), use of rituximab (n = 66, 3% at 5 years) or plasmapheresis (n = 17, 7% at 5 years), and acute rejection (n = 169, 3% at 5 years). In conclusion, the HBV reactivation risk was not high and the time of detection was not clustered in the early post‐KT period. Our findings favour continued watchful monitoring over antiviral prophylaxis in the early period.