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.

ObjectiveTo develop a prognostic model that determines patient survival outcomes after orthotopic liver transplantation (OLT) using readily available pretransplant variables. Summary Background DataThe current liver organ allocation system strongly favors organ distribution to critically ill recipients who exhibit poor survival outcomes following OLT. A severely limited organ resource, increasing waiting list deaths, and rising numbers of critically ill recipients mandate an organ allocation system that balances disease severity with survival outcomes. Such goals can be realized only through the development of prognostic models that predict survival following OLT. MethodsVariables that may affect patient survival following OLT were analyzed in hepatitis C (HCV) recipients at the authors' center, since HCV is the most common indication for OLT. The resulting patient survival model was examined and refined in HCV and non-HCV patients in the United Network for Organ Sharing (UNOS) database. Kaplan-Meier methods, univariate comparisons, and multivariate Cox proportional hazard regression were employed for analyses. ResultsVariables identified by multivariate analysis as independent predictors for patient survival following primary transplantation of adult HCV recipients in the last 10 years at the authors' center were entered into a prognostic survival model to predict patient survival. Accordingly, mortality was predicted by 0.0293 (recipient age) ϩ 1.085 (log 10 recipient creatinine) ϩ 0.289 (donor female gender) ϩ 0.675 urgent UNOS -1.612 (log 10 recipient creatinine times urgent UNOS). The above variables, in addition to donor age, total bilirubin, prothrombin time (PT), retransplantation, and warm and cold ischemia times, were applied to the UNOS database. Of the 46,942 patients transplanted over the last 10 years, 25,772 patients had complete data sets. An eight-factor model that accurately predicted survival was derived. Accordingly, the mortality index posttransplantation ϭ 0.0084 donor age ϩ 0.019 recipient age ϩ 0.816 log creatinine ϩ 0.0044 warm ischemia (in minutes) ϩ 0.659 (if second transplant) ϩ 0.10 log bilirubin ϩ 0.0087 PT ϩ 0.01 cold ischemia (in hours). Thus, this model is applicable to first or second liver transplants. Patient survival rates based on model-predicted risk scores for death and observed posttransplant survival rates were similar. Additionally, the model accurately predicted survival outcomes for HCV and non-HCV patients. ConclusionsPosttransplant patient survival can be accurately predicted based on eight straightforward factors. The balanced application of a model for liver transplant survival estimate, in addition to disease severity, as estimated by the model for end-stage liver disease, would markedly improve survival outcomes and maximize patients' benefits following OLT.

No abstract

Orthotopic liver transplantation (OLT) for hepatitis B virus (HBV) infectionO rthotopic liver transplantation (OLT) for hepatitis B virus (HBV) is complicated by a high rate of graft reinfection by HBV in the absence of prophylaxis. The consequences vary, ranging from asymptomatic infection with minimal graft dysfunction to fibrosing cholestatic hepatitis, graft failure, and patient death. The introduction of passive immunoprophylaxis with hepatitis B immune globulin (HBIG) post-OLT provided an initial approach to prevent recurrent HBV. [1][2][3][4][5] Despite HBIG, HBV still recurs in approximately 15% to 36% of the patients. 4,6 More recently, the advent of lamivudine, an oral purine nucleoside analogue with antiviral activity against HBV, has provided an alternative strategy to prevent recurrent HBV. Prophylaxis with lamivudine monotherapy has been shown to prevent initial HBV recurrence post-OLT. 7-9 Unfortunately, the emergence of lamivudine-resistant mutants with allograft reinfection also limits the efficacy of lamivudine monotherapy as a strategy to prevent HBV recurrence. 7,10,11 In previous studies, combination lamivudine and HBIG prevented HBV recurrence in all patients with no evidence of the development of lamivudine-resistant escape mutants during long-term follow-up. [12][13][14] In the present study, with our expanded experience in a larger cohort of patients administered combination HBIG and lamivudine to prevent recurrent HBV post-OLT, we evaluate the efficacy and cost-effectiveness of this strategy to prevent HBV recurrence compared with standard HBIG monotherapy.

Cholangiocellular carcinoma (CCC) is a biliary malignancy that frequently presents in advanced unresectable stages. The role of liver transplantation (LT) as a surgical modality is unclear. The goal of this study is to evaluate outcomes of patients with CCC undergoing LT. A retrospective analysis of all patients undergoing LT was undertaken. Only those patients with the pathological diagnosis of CCC were included on the study. Patients were divided into two groups based on primary tumor location: extrahepatic (EH)-CCC and intrahepatic (IH)-CCC. The Kaplan-Meier method was used to calculate overall and recurrence-free survival. Log-rank analysis was used to determine the significance of prognostic variables. Twenty-five patients were identified: 9 patients with EH-CCC (5 patients, Klatskin-type; 2 patients, the middle third; and 2 patients, the distal third) and 16 patients with IH-CCC. Mean age was 47.1 ؎ 10.6 years. There were 14 men and 11 women. Tumor stage was local (stages I and II; n ‫؍‬ 9) or advanced (stages III and IV; n ‫؍‬ 16). Overall and disease-free survival rates were 71% and 67% at 1 year and 35% and 32% at 3 years, respectively. Analysis of variables showed statistically significant improved outcomes (P < .05) for the absence of contiguous organ invasion at LT, small tumor size, and single tumor foci. This study indicates that early survival after LT for CCC is acceptable. Three-year disease-free survival is achieved in approximately 30% of patients. These outcomes can be improved by applying strict selection criteria based on prognostic variables identified in this study. (Liver Transpl 2001;7:1023-1033.)