Pauline Chen

A 10-year Experience of Liver Transplantation for Hepatitis C: Analysis of Factors Determining Outcome in Over 500 Patients

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 HCV-positive 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. ConclusionThe earlier the recurrence of HCV, the greater the impact on patient and graft survival. The use of HCV-positive donors may accelerate HCV recurrence, and they should be used judiciously. Patient survival at the time of transplantation is predicted by donor gender, UNOS status, serum creatinine, and recipient age. Graft survival is affected by donor gender, warm ischemia time, and pretransplant patient condition. The authors’ current survival prognostic models require further multicenter validation.

Pretransplant Model to Predict Posttransplant Survival in Liver Transplant Patients

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) + 1.085 (log10 recipient creatinine) + 0.289 (donor female gender) + 0.675 urgent UNOS - 1.612 (log10 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 = 0.0084 donor age + 0.019 recipient age + 0.816 log creatinine + 0.0044 warm ischemia (in minutes) + 0.659 (if second transplant) + 0.10 log bilirubin + 0.0087 PT + 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.

Predictors of Survival After In Vivo Split Liver Transplantation: Analysis of 110 Consecutive Patients

ObjectiveTo determine the factors that influence patient survival after in vivo split liver transplantation (SLT). Summary Background DataSplit liver transplantation is effective in expanding the donor pool, and its use reduces the number of deaths in patients awaiting orthotopic liver transplantation. Early SLTs were associated with poor outcomes, and acceptance of the technique has been slow. A better understanding of the factors that influence patient and graft survival would be useful in widening the application of SLT. MethodsDuring a 3.5-year period, 55 right and 55 left lateral in vivo split grafts were transplanted in 102 pediatric and adult recipients. The authors’ in vivo split technique has been previously described. Median follow-up was 14.5 months. Recipient, donor, and surgical variables were analyzed for their effect on patient survival after SLT. ResultsOverall survival rates of patients who received an SLT were not significantly different from those of patients who received whole organ transplants. Survival of left lateral segment recipients, at median follow-up time, was 76% versus 80% in patients receiving a trisegment. Fifty of 102 patients (49%) were high-risk urgent recipients (United Network for Organ Sharing [UNOS] status 1 and 2A) and 52 (51%) were nonurgent recipients (UNOS status 2B, 3). High-risk recipients had a survival rate significantly lower than that of nonurgent recipients. By univariate comparison, two variables—UNOS status and number of transplants per patient—were significantly associated with an increased risk of death. Preoperative recipient mechanical ventilation, preoperative prothrombin time, donor sodium level, donor length of hospital stay, and warm ischemia time approached significance. The type of graft (right vs. left) did not reduce the survival rate after transplantation. Multivariate logistic regression analysis identified UNOS status and length of donor hospital stay as independent predictors of survival. ConclusionsPatient survival of in vivo SLT is not significantly different from that of whole-organ orthotopic liver transplantation. The variables affecting outcome of in vivo SLT are similar to those in whole-organ transplantation. in vivo SLT should be widely applied to expand a severely depleted donor pool.

Predictors of survival after liver transplantation for hepatocellular carcinoma associated with hepatitis C

The efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This study examines the variables that may determine the outcome of OLT for HCC in HCV patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these patients, 67 with concurrent HCC were included in the study. Univariate and multivariate analyses considered the following variables: gender, pTNM stage, tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant chemotherapy, preoperative chemoembolization, alpha‐fetoprotein (AFP) tumor marker, lobar distribution, and histological grade. Overall OLT survival of HCV patients diagnosed with concomitant HCC was significantly lower when compared to patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55% versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients with stage I HCC was significantly better than patients with stage II, III, or IV (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence included transplanted liver (5), lung (5), and bone (1). Twenty‐four of 67 patients (36%) died during the follow‐up time. Causes of deaths included recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV or HCC. Both univariate and multivariate analysis demonstrated that pTNM status (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM staging (P = .038) increased risk of recurrence. Multivariate analysis showed that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of death after OLT in HCC recipients. In conclusion, this study demonstrates the effectiveness of OLT for patients with HCC in a large cohort of chronic HCV patients. Advanced tumor stage, and particularly vascular invasion, are poor prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant chemotherapy, and preoperative chemoembolization were associated with positive outcomes for patients who underwent OLT for concomitant HCV and HCC. (Liver Transpl 2004;10:1478–1486.)

Early graft function after pediatric liver transplantation: Comparison between in situ split liver grafts and living-related liver grafts

Background. The systematic application of living-related and cadaveric, in situ split-liver transplantation has helped to alleviate the critical shortage of suitable-sized, pediatric donors. Undoubtedly, both techniques are beneficial and advantageous; however, the superiority of either graft source has not been demonstrated directly. Because of the potential living-donor risks, we reserve the living donor as the last graft option for pediatric recipients awaiting liver transplantation. Inasmuch as no direct comparison between these two graft types has been performed, we sought to perform a comparative analysis of the functional outcomes of left lateral segmental grafts procured from these donor sources to determine whether differences do exist. Methods. A retrospective analysis of all liver transplants performed at a single institution between February 1984 and January 1999 was undertaken. Only pediatric (<18 years) recipients of left lateral segmental grafts procured from either living-related (LRD) or cadaveric, in situ split-liver (SLD) donors were included. A detailed analysis of preoperative, intraoperative, and postoperative variables was undertaken. Survival was estimated using the Kaplan-Meier method, and comparison of variables between groups was undertaken using the t test of Wilcoxon rank sum test. Results. There were no significant differences in the preoperative variables between the 39 recipients of SLD grafts and 34 recipients of LRD grafts. The donors did differ significantly in mean age, ABO blood group matching, and preoperative liver function testing. Postoperative liver function testing revealed significant early differences in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, prothrombin time, and alkaline phosphatase, with grafts from LRD performing better than those from SLD. SLD grafts also had significantly longer ischemia times and a higher incidence of graft loss owing to primary nonfunction and technical complications (9 vs. 2, P <0.05). However, six of these graft losses in the SLD group were because of technical or immunologic causes, which, theoretically, should not differ between the two groups. Furthermore, these graft losses did not negatively impact early patient survival as most patients were successfully rescued with retransplantation (30-day actuarial survival, 97.1% SLD vs. 94.1% LRD, P =0.745). In the surviving grafts, the early differences in liver function variables normalized. Conclusions. Inherent differences in both donor sources exist and account for differences seen in preoperative and intraoperative variables. Segmental grafts from LRD clearly performed better in the first week after transplantation as demonstrated by lower liver function variables and less graft loss to primary nonfunction. However, the intermediate function (7–30 days) of both grafts did not differ, and the early graft losses did not translate into patient death. Although minimal living-donor morbidity was seen in this series, the use of this donor type still carries a finite risk. We therefore will continue to use SLD as the primary graft source for pediatric patients awaiting liver transplantation.

A Cost-effectiveness Analysis of Biliary Anastomosis With or Without T-tube after Orthotopic Liver Transplantation

Biliary reconstruction continues to be a major source of morbidity following orthotopic liver transplantation. We wished to determine if choledochocholedochostomy without a T‐tube was associated with fewer biliary complications and was less costly than choledochocholedochostomy with a T‐tube.