Recurrence of Primary Sclerosing Cholangitis After Living Donor Liver Transplantation

Sumihito Tamura; Yasuhiko Sugawara; Junichi Kaneko; Yuichi Matsui; Junichi Togashi; Masatoshi Makuuchi


Liver International. 2007;27(1):86-94. 

In This Article


A case suspected of recurrent PSC following LDLT was first reported by Kita et al..[25] To date, few other studies[26,27,28,29,30,31,32,33,34] have reported the outcome of LDLT for PSC from biologically related donors ( Table 5 ). Among the nine reports in the table, only one case, a case reported by Jabbour et al.,[33] presented with a longer follow-up period than the median follow-up period in our series. The other case reports presented with follow-up periods ranging from 6 to 18 months. Reports on the long-term outcome of LDLT for PSC, especially regarding that of possible recurrence are, therefore, lacking. This might be partially due to the rare incidence of PSC in the far-Eastern regions where LDLT is more common than DDLT. Unlike in the Nordic countries or in the United States, where PSC is one of the most important indications for liver transplantation,[35] the indication accounts for <3% of the total liver transplantations performed in Japan.[36]

LDLT for PSC has been reported in moderate to large LDLT registries worldwide.[37,38,39,40,41] Moon and Lee[37] reported two cases of LDLT for PSC among their large series of 580 LDLT. Soejima et al.[38] reported two cases of LDLT for PSC in their series of 52 cases. These reports, however, lacked specific description of the long-term outcome. Solano et al.[39] summarized the outcome of liver transplantation for PSC in a Canadian series. The report included 111 PSC patients who underwent 132 liver transplantations. Two cases were described as LDLT, but the report lacks further specific details and outcome of these patients. In their report describing the discrepancy between MELD score and outcome of LDLT with 62 patients, Hayashi et al.[40] included 13 patients with PSC. In the study, only 1-year outcomes were evaluated and no further details are available. Finally, a registry analysis by Maheshwari et al.[41] reported the outcome of 3309 PSC patients who underwent liver transplantation, the largest study to date, among whom 69 had undergone LDLT. Only 10 among the 69 have had, however, a follow-up period longer than a year, and no further details regarding the outcome are described.

This report presents the summary of our cumulative experience of LDLT for PSC. The series is small with a rather short median follow-up period. Nonetheless, the series presents with the longest follow-up period after LDLT for PSC described in the literature to date. The recurrence of PSC seems to be a more frequent event than initially considered. When restricted to cases with biologically related live donors (Cases 1-7 and 9), recurrent PSC occurred in 50%. The incidence of PSC recurrence in DDLT is approximately 20% (6-37%), with the diagnosis established approximately 4 years after transplantation.[7,8,14,15,16,42,43,44,45,46,47] The difference suggests that in LDLT, especially in cases with grafts obtained from biologically related donors, the recurrence of PSC might occur earlier and at a higher ratio. The results obtained from our current small series have, however, a large confidence interval and are prone to type 2 error, and require confirmation by a larger series.

Identification of PSC recurrence in the allograft can be problematic, because the distinction between true recurrence and secondary sclerosing cholangitis caused by surgery-related complications can be challenging.[42] Review of nonPSC cases with biliary complications at our institution revealed the development of nonanastomotic biliary strictures of the intrahepatic tree, with typical beading and irregularity occurring 90 days posttransplantation, to be an extremely rare event. In this study, we followed the diagnostic criteria.[15] All patients had a confirmed diagnosis of PSC before LDLT. There were no ABO-incompatible LDLT cases and none of the patients presented with hepatic artery complications, except one, who presented with a late-onset event (Case 6). The patient died without signs of recurrent PSC. The four patients diagnosed with recurrent PSC cases presented with typical radiologic images of nonanastomotic biliary strictures of the intrahepatic biliary tree with beading and irregularity (Fig. 2), which occurred after 90 days postLDLT. For more accurate evaluation of the timing of recurrence, however, periodic protocol cholangiogram using a less-invasive method compared with percutaneous procedures such as magnetic resonance cholangiopancreatography, as described by Brandsaeter et al.,[48] might be helpful.

The precise etiology and pathogenesis of PSC are unknown, but the involvement of both immunologic as well as genetic factors has been suggested.[11] Recently, an association between susceptibility to develop PSC and genes in the HLA complex was investigated. To date, the frequencies of genes encoding HLA-B8 in the class I region and the DR3 (DRB1*03, DQA1*05, DQB1*02), DR2 (DRB1*15, DQA1*0102, DQB1*0602), and DR6 (DRB1*13, DQA1*0103, DQB1*0603) haplotypes of the class II region have been reported to be increased in PSC patients.[49,50,51,52,53,54,55] This aspect has not been examined further in DDLT because HLA matching is not routinely performed and cumulative data are lacking. Brandsaeter et al.[48] reported that the HLA-B8DR3 haplotype was more common among PSC patients than among control patients, but this difference was not statistically significant with regard to recurrent PSC. Further, in their series, the presence of HLA-B8DR3 in the donor was studied based on the hypothesis that liver grafts without the HLA-B8DR3 haplotype would be less prone to develop recurrent disease. In their series of nine cases of recurrent PSC among 49 PSC patients after DDLT, HLA-B8DR3 disparity did not seem to affect the outcome. Although it has not yet been established whether it is the associated HLA genes per se or the closely linked genes that are responsible for the recurrence, LDLT for PSC might offer a unique opportunity to examine the genetic aspects involved.

The frequency distribution of HLA alleles is different among races and ethnicities. In our series, due to the nature of LDLT, high HLA haplotype compatibility was observed both in HLA class I and class II. None, however, presented with an HLA-B8DR3 haplotype, a finding consistent with previous reports suggesting that HLA-B8 is not detected among Japanese.[56,57,58,59] Thus, the influence of the HLA-B8DR3 haplotype on recurrent PSC after liver transplantation remains an open question. HLA-DRB1*0803, -DRB1*0901, -DRB1*1302, -DRB1*1501, and -DRB1*1502 found in recipients with recurrent PSC in our series, are relatively common among the Japanese population with the reported frequencies in the range of 7.6-9.4%, 12.4-15.0%, 5.3-7.7%, 6.1 -8.5%, and 8.7-12.2%, respectively.[56,57,58,59] Owing to the limited size of our series, the magnitude of the findings is inconclusive.

In conclusion, PSC might recur at a higher ratio after LDLT, especially with biologically related donors. Risk factors and susceptible genetic characteristics in LDLT remain unclear. Further prospective study with protocol cholangiogram and genetic considerations with high-resolution HLA haplotype analysis is necessary. Also, a review of a large liver transplant registry or a series for PSC including both DDLT and LDLT may provide important information.

CLICK HERE for subscription information about this journal.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.