The urgent need for evaluating recurrent primary sclerosing cholangitis in living donor liver transplantation

Abstract

In an earlier issue this year, Alabraba and colleagues1 evaluated the risk factors for recurring primary sclerosing cholangitis (PSC); we read with great interest their article entitled “A Re-Evaluation of the Risk Factors for the Recurrence of Primary Sclerosing Cholangitis in Liver Allografts.” Analyzing prospectively collected data for 230 consecutive deceased donor liver transplantation (DDLT) procedures for PSC over a 20-year period with an 83-month follow-up, the authors reported that 54 (24%) of the DDLT recipients presented with recurrent PSC at a median of 4.6 years after transplantation. An analysis of the risk factors indicated that colectomy offered a protective effect against PSC recurrence, whereas the use of grafts recovered under extended donor criteria (EDC) was associated with a higher rate of recurrence. Indeed, although liver transplantation has become an accepted treatment for PSC with liver failure with excellent overall survival, recurrent disease continues to be a threat with a higher rate of retransplantation.2 Identification of the factors affecting recurrence is therefore important. In this context, we were disappointed that some of the recently reported disturbing aspects of living donor liver transplantation (LDLT) are not discussed in the article.1 In contrast to Western countries, liver transplantation from a living donor remains the most realistic option in the Far East. Following the successful results with DDLT reported from the West, LDLT has been applied for PSC with liver failure in Japan. One concern in applying LDLT for PSC has been the unknown effect of a shared genetic disposition in a blood-related recipient and donor pair, which may affect the recurrence of PSC and hence graft survival over the long term. Until recently, however, only sporadic case reports have been published with short follow-up periods, and little information on this aspect has been available. To fill the void, we conducted a retrospective study on the clinical course of PSC after LDLT at our institution. The results of our analysis indicated that PSC not only recurred as in the DDLT series but also recurred at a much higher rate.3 When the analysis was restricted to cases with biologically related live donors, recurrent PSC occurred in 50% of the recipients with a mean time to diagnosis from LDLT of 3.3 years. An observation supporting this finding was reported by another high-volume center.4 Among the 22 patients who survived for more than a year in the series, 13 (59%) presented with PSC recurrence with a mean follow-up period of 2.6 years, 5 of whom died or required retransplantation for graft failure. These preliminary reports have raised considerable concerns, and currently, a nationwide survey, supported by the Ministry of Health, Labor, and Welfare, is ongoing in Japan. The first study by the authors analyzing the risk factors for recurrent PSC in the allograft was published in 2002,5 and since then, LDLT has evolved and spread worldwide, becoming a realistic option in the West and in the East because of the universal organ shortage. Findings regarding the mid-term to long-term outcomes of LDLT for PSC from European or North American series, however, have not been reported despite the rapid accumulation of adult-to-adult LDLT cases. In their analysis, Alabraba and colleagues1 reported that the use of EDC grafts resulted in a 5-fold increase of recurrent PSC, with a 5-year recurrence-free survival of 71% versus 91% for non-EDC grafts. Preliminary studies in LDLT, however, have suggested a further significant impact when a graft donated by a blood-related living donor is used for PSC. In this era of severe graft shortage, the interpretation of these outcomes requires caution, but the implications are nonetheless alarming. Further validation is urgently needed. Currently, however, PSC accounts for less than 3% of all LDLT procedures performed in Japan because of its rarity in comparison with the higher prevalence in Nordic countries and the United States. Studies focusing on the outcomes of LDLT for PSC in a Western series are greatly anticipated. Sumihito Tamura*, Yasuhiko Sugawara*, Noriyo Yamashiki*, Junichi Kaneko*, Norihiro Kokudo*, * Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo Tokyo, Japan.