Donor age (≥45 years) and reduced immunosuppression are associated with the recurrent primary sclerosing cholangitis after liver transplantation – a multicenter retrospective study

Abstract

The present study investigated the possible risk factors, including relationship/HLA matching between donor and recipient, and immunosuppressive therapies on the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LT). Subjects were 197 recipients of LT for PSC, among whom 180 surviving more than 1 year after LT were further analyzed for risk factors of recurrence. The 5-and 10-year patient-and graft survival rates were 83% and 68%, and 71% and 62%, respectively. The overall PSC recurrence rate was 25% with a 5-and 10-year graft survival rate of 34% and 18%, which was significantly lower than the survival rate of those without recurrence (P < 0.001). Univariate analysis identified the following as risk factors for recurrence: donor age (P < 0.001), cyclosporine use (P = 0.012), mono or no immunosuppressive agent (P < 0.001), postoperative biliary complication (P < 0.001), and active intestinal bowel disease after LT (P < 0.001). Among these factors, donor age ≥45 years [hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.21-2.69; P = 0.003] and mono or no immunosuppressive agent 1-year after LT (HR, 2.38; 95% CI, 1.23-3.45; P = 0.011) were identified as independent risk factors in the final multivariate Cox regression model. The results were similar in sub-analysis for ABO-identical/compatible adult living donor LT cases.

Longitudinal analysis of transplant candidates with primary sclerosing cholangitis in an Asian liver transplant center

“…Multiple adverse effects of LT include acute rejection, chronic rejection, biliary complications, infection and recurrence of PSC [11,15,17,53,54]. Akamatsu et al [25] analyzed the overall outcome of 197 Japanese patients who had undergone LT for PSC and showed that after the exclusion of 18 patients who died within the first year after LT, the 5-and 10-year patient-and graft survival rates were 83 and 68%, and 71 and 62%, respectively, implying that if patients survived the first post-transplant year, they could probably enjoy a comparable life span as Caucasians. However, the inferior outcome of early post-transplant survival in Japan and Taiwan than that in Western countries suggested that ethnicity may be a crucial contributing factor in modifying transplant outcomes [25,54].…”

“…Akamatsu et al [25] analyzed the overall outcome of 197 Japanese patients who had undergone LT for PSC and showed that after the exclusion of 18 patients who died within the first year after LT, the 5-and 10-year patient-and graft survival rates were 83 and 68%, and 71 and 62%, respectively, implying that if patients survived the first post-transplant year, they could probably enjoy a comparable life span as Caucasians. However, the inferior outcome of early post-transplant survival in Japan and Taiwan than that in Western countries suggested that ethnicity may be a crucial contributing factor in modifying transplant outcomes [25,54]. Kasahara et al [55] analyzed outcomes of pediatric LT in Japan by etiology of liver disease and demonstrated that PSC was associated with significantly worse survival in comparison to other diseases.…”

“…Moreover, these studies have revealed different age distribution at diagnosis and a lower prevalence of inflammatory bowel disease (IBD) as a comorbidity in Japan and Singapore than in Europe and North America [21][22][23][24][25]. Aside from a relatively large retrospective multicenter study performed in Japan [25], overall longitudinal data for the Asian population remain limited [2,[23][24][25][26][27]. The association between ethnicity and the clinical features of PSC remains unclear.…”

“…The available published data suggest that PSC is rarer in Japan and Singapore than in Western countries; however, the number of reported cases has been increasing, with 10 cases of PSC diagnosed over 10 years in Singapore and the numbers nearly doubling in Japan (192 in 1997 and 388 in 2003) [21][22][23][24]. Moreover, these studies have revealed different age distribution at diagnosis and a lower prevalence of inflammatory bowel disease (IBD) as a comorbidity in Japan and Singapore than in Europe and North America [21][22][23][24][25]. Aside from a relatively large retrospective multicenter study performed in Japan [25], overall longitudinal data for the Asian population remain limited [2,[23][24][25][26][27].…”

Liver transplantation for primary sclerosing cholangitis—morbidities including disease recurrence

“…Azathioprine is rarely used in LTx today, however, the protective effect of mycophenolate mofetil seems promising among PSC recipients. A recent Japanese nationwide study ( 13 ) revealed that cyclosporine use as a calcineurin inhibitor and mono or no immunosuppressive regimen during the maintenance phase were risk factors for recurrent PSC, the latter being an independent risk factor. Japanese transplant clinicians have tended to use a triple regimen (tacrolimus, steroid, and mycophenolate mofetil) or to increase the maintenance dose of tacrolimus and steroid among PSC recipients.…”