A 10-year experience of liver transplantation for hepatitis C: analysis of factors determining outcome in over 500 patients

Abstract

Objective: To 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 data: The 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.

Methods: The 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.

Results: Overall 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.

Conclusion: The 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.

Figure 1. Kaplan-Meier patient and graft survival curves after liver transplantation for hepatitis C.

Figure 2. Outcome of liver transplantation after histologic recurrence of hepatitis C.

Figure 3. Overall patient and graft survival estimates based on hepatitis C (HCV) status of donor.

Figure 4. (A) Overall hepatitis C (HCV) recurrence-free patient survival estimates. (B) Recurrence-free patient survival estimates according to donor status; 26 patients with unknown time to recurrence and donor status were omitted.

Figure 5. Patient and graft survival analysis based on time to hepatitis C (HCV) recurrence by histologic examination. Patients were classified into five subgroups: patients with recurrence within the first 12 months (▪), between 12 and 24 months (⋄), between 24 and 36 months (•), after 36 months (▴); or patients without evidence of histologic recurrence after 36 months (-).

Figure 6. Risk ratios for death and graft failure based on time of histologic hepatitis C (HCV) recurrence.