Is recurrence of hepatitis C worse after living donor or deceased donor liver transplantation

Living donor liver transplantation (LDLT) has become one of the most exciting and controversial aspects of liver transplantation in recent years. It’s exciting because it offers an alternative to the deceased donor waiting lists with long waiting times, potential mortality, and impaired quality of life. It’s controversial because of the real risks in the donor and the potential for inferior outcomes in the recipient due to the use of a reduced sized graft. Initial concerns for the recipient focused on poor outcomes for patients with very advanced liver disease undergoing LDLT—i.e., prior United Network for Organ Sharing status 2A or high model for end-stage liver disease (MELD) cases. More recent research has focused on issues of relative rates and severity of recurrence of hepatitis C and hepatocellular carcinoma following LDLT and deceased donor liver transplantation (DDLT). Since hepatitis C (HCV) is the most common indication for liver transplantation in the United States, the issue of recurrent HCV in LDLT is of critical importance. Some early reports have shown earlier and more severe recurrence of hepatitis C following LDLT compared to deceased donor controls.1–3 Our group showed that though the overall recurrence rate was not different between living donor and deceased donor recipients, severe recurrence including cholestaticHCVoccurredmore frequently in our living donor recipients.4 Most of these studies were limited by the lack of long-term outcome or protocol biopsies. Recently, Russo et al. analyzed the Scientific Registry of Transplant Recipients (SRTR) registry and demonstrated that patient and graft survival were similar for HCV patients undergoing living donor or deceased donor transplant.5 However, since it was a database study, they could not examine the severity of histologic recurrence in the 2 groups, only the rates of graft failure. In this issue of Liver Transplantation, Shiffman et al. present a comparison between recipients of living donor and deceased donor transplants for chronic HCV with up to 4 years of follow-up using protocol biopsies to reliably grade the severity of graft recurrence.6 Similar to the data of Russo et al., they show no difference in either graft or patient survival. More importantly, there was no difference seen in either hepatic inflammation or fibrosis between the 2 groups during follow-up. In contrast to prior studies, there is actually a trend toward less fibrosis in living donor liver transplant recipients in the later years, with stabilization of the fibrosis progression in these grafts. This is very important data and the most rigorous single-center report to date. The strengths of the Shiffman et al. data include the relatively long follow-up in their cohort and, most importantly, the fact that they did annual protocol biopsies regardless of the presence of liver function test abnormalities. Many of the prior studies can be critiqued by the absence of protocol biopsies, which are necessary for a truly unbiased comparison of histology between living donor and deceased donor HCV-positive recipients. In the absence of protocol biopsies, biopsy rates in the two groups may be systematically different due to higher levels of alanine aminotransferase and or alkaline phosphatase particularly in the early time points posttransplant in living donor patients either due to regeneration or to unrecognized biliary tract disease. However, some caution is required in interpreting the data. First, as with all single-center studies, the sample size is relatively small, with 23 living donor recipients versus 53 deceased donor recipients. Thus, especially at the later time points, the number of patients who were available for biopsy is small this therefore limits statistical significance, and raises the question of the possibility of a Type II error. A second concern is the differences in the baseline characteristics of the population 2 cohorts and whether these differences could confound the results. Among deceased donor transplant recipients there were more males, Abbreviations: LDLT, living donor liver transplantation; MELD, model for end-stage liver disease; DDLT, deceased donor liver transplantation; HCV, hepatitis C virus. From the Center for Liver Disease and Transplantation, Columbia University College of Physicians and Surgeons, New York, NY. Address reprint requests to Robert S. Brown, Jr., MD,MPH, Center for Liver Disease and Transplantation, Columbia University College of Physicians and Surgeons, 622West 168th St., New York, NY 10032. Telephone: 212-305-0662; FAX: 212-305-9139; E-mail: rb464@columbia.edu Copyright © 2004 by the American Association for the Study of Liver Diseases Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/lt.20284