Until recently, liver transplantation in patients with hepatitis B was associated with a high rate of graft loss and poor survival because of viral recurrence. 1-3 Favorable outcome following liver transplantation for hepatitis B virus (HBV)-related liver disease was made possible with long-term, high-dose, passive immunoprophylaxis using hepatitis B immune globulin (HBIG). 4,5 Hepatitis B still recurs, however, despite HBIG. Recurrence may be caused by saturation of the antibody binding capacity of HBIG by a high viral load, or by mutations in the hepatitis B surface antigen (HBsAg) molecule that render HBIG ineffective. 6,7 Overall recurrence rates with HBIG monotherapy vary from approximately 15% to 50%. 4,5,[8][9][10][11] Using a different dosing schedule, in early experience from our own institution HBV recurrence on HBIG was 44%. 12 The wide disparity in the data reflects differing patient populations, e.g., patients who are HBV-DNA-positive at the time of transplantation have higher rates of recurrence. Moreover, the different dosing regimens of HBIG are also likely to influence recurrence rates. 5,11,13 An alternative approach to preventing HBV recurrence became possible using the purine nucleoside analog reversetranscriptase inhibitor, lamivudine. Demonstration of its efficacy, in the nontransplantation setting, in suppressing HBV-DNA synthesis 14,15 led to studies using lamivudine following liver transplantation as prophylaxis against hepatitis B recurrence, 16,17 or as treatment of de novo or recurrent hepatitis B. 17,18 Although a DNA virus, HBV replicates via an RNA intermediate. As is seen in human immunodeficiency virus, 19 lamivudine escape mutations in the tyrosine, methionine, aspartate, aspartate (YMDD) locus of the HBV-DNA polymerase are increasingly being reported. [20][21][22][23] While prophylactic failures of HBIG have been treated successfully with lamivudine, there are no reports documenting successful treatment of patients with lamivudine-resistant HBV.Mechanistic evidence suggests that HBIG and lamivudine would be synergistic. By inhibiting viral replication with lamivudine, it would be less likely that the viral binding capacity of HBIG would be overwhelmed; furthermore, there would be little pressure to select for HBIG-resistant mutations in the HBsAg molecule. By providing humoral immunity, HBIG may limit viral spread, confining the virus to extraheAbbreviations: HBV, hepatitis B virus; HBIG, hepatitis B immune globulin; HBsAg, hepatitis B surface antigen; anti-HBs, antibodies against hepatitis B surface antigen; PCR, polymerase chain reaction; HCC, hepatocellular carcinoma; HBeAg, hepatitis B envelope antigen.From

Long-term benefits of OLT are greatest in pediatric and nonurgent patients. Multiple factors involving the recipient, etiology of liver disease, donor characteristics, operative variables, and surgical experience influence long-term survival outcomes. By balancing and matching these factors with a given recipient, optimum results can be achieved.

A roundtable meeting to discuss the use of therapeutic drug monitoring (TDM) to guide immunosuppression with mycophenolate mofetil was held in New York in December 2004. Existing recommendations for the initial months after transplantation were updated. After ensuring adequate levels of mycophenolic acid (MPA, the active metabolite of mycophenolate mofetil) immediately after transplantation, optimal efficacy may require only a few dose adjustments, because intrapatient variability in exposure seems low. Recommendations based on current knowledge were made for posttransplantation sampling time points and for target MPA concentrations. Algorithms for estimating MPA exposure using limited sampling strategies were presented, and a new assay for MPA discussed. It was agreed that because of interpatient variability and the influence of concomitant immunosuppressants, TDM might help optimize outcomes, especially in patients at higher risk of rejection. The value of TDM in the general transplant population will be assessed from large, ongoing, randomized studies.

ObjectiveTo determine the factors affecting the outcome of orthotopic liver transplantation (OLT) for end-stage liver disease caused by hepatitis C virus (HCV) and to identify models that predict patient and graft survival. Summary Background DataThe national epidemic of HCV infection has become the leading cause of hepatic failure that requires OLT. Rapidly increasing demands for OLT and depleted donor organ pools mandate appropriate selection of patients and donors. Such selection should be guided by a better understanding of the factors that influence the outcome of OLT. MethodsThe authors conducted a retrospective review of 510 patients who underwent OLT for HCV during the past decade. Seven donor, 10 recipient, and 2 operative variables that may affect outcome were dichotomized at the median for univariate screening. Factors that achieved a probability value less than 0.2 or that were thought to be relevant were entered into a stepdown Cox proportional hazard regression model. ResultsOverall patient and graft survival rates at 1, 5, and 10 years were 84%, 68%, and 60% and 73%, 56%, and 49%, respectively. Overall median time to HCV recurrence was 34 months after transplantation. Neither HCV recurrence nor HCV-positive donor status significantly decreased patient and graft survival rates by Kaplan-Meier analysis. However, use of HCVpositive donors reduced the median time of recurrence to 22.9 months compared with 35.7 months after transplantation of HCV-negative livers. Stratification of patients into five subgroups, based on time of recurrence, revealed that early HCV recurrence was associated with significantly increased rates of patient death and graft loss. Donor, recipient, and operative variables that may affect OLT outcome were analyzed. On univariate analysis, recipient age, serum creatinine, donor length of hospital stay, donor female gender, United Network for Organ Sharing (UNOS) status of recipient, and presence of hepatocellular cancer affected the outcome of OLT. Elevation of pretransplant HCV RNA was associated with an increased risk of graft loss. Of 15 variables considered by multivariate Cox regression analysis, recipient age, UNOS status, donor gender, and log creatinine were simultaneous significant predictors for patient survival. Simultaneously significant factors for graft failure included log creatinine, log alanine transaminase, log aspartate transaminase, UNOS status, donor gender, and warm ischemia time. These variables were therefore entered into prognostic models for patient and graft survival.

We report the largest single institution experience of LT for NASH. Over a 10-year period, the frequency of LT for NASH has increased 5-fold. Although outcomes are comparable with LT for other indications, health care resources are stressed significantly by this new and increasing group of transplant candidates.