Differences in Phenotypes and Liver Transplantation Outcomes by Age Group in Patients with Primary Sclerosing Cholangitis

Abstract

Background There is increasing evidence for a heterogeneity of phenotypes in primary sclerosing cholangitis (PSC), but differences across the age spectrum in adults with PSC have not been well characterized. Aims To characterize phenotypic variations and liver transplantation outcomes by age group in adults with PSC. Methods The United Network for Organ Sharing database was used to identify waitlist registrations for primary liver transplantation in adults with PSC. Patients were split into three age groups: 18–39 (young), 40–59 (middle-aged), and ≥60 (older). Their clinical characteristics and outcomes on the waitlist and post-transplant were compared. Results Overall, 8272 adults with PSC were listed for liver transplantation during the study period, of which 28.9% were young, 52.0% were middle-aged, and 19.1% were older. The young age group had the greatest male predominance (70.0 vs. 66.2 vs. 65.1%, p = 0.001), the highest proportion of black individuals (20.0 vs. 11.0 vs. 5.5%, p <0.001), and the most patients listed with concomitant autoimmune hepatitis (2.2 vs. 1.0 vs. 0.8%, p <0.001). Older patients experienced the greatest waitlist and post-transplant mortality. Graft survival was greatest in the middle-aged group. Young patients were most likely to experience acute rejection (31 vs. 22.8 vs. 18.0%, p <0.001) and have graft failure due to chronic rejection or PSC recurrence (47.8 vs. 42.3 vs. 17.9%, p < 0.001). Conclusions Age-related differences exist among adults with PSC and are associated with outcomes pre- and post-transplant. Young patients may have a more robust immune-related phenotype that is associated with poorer graft survival. Future studies are needed to further investigate these findings.

Racial differences in primary sclerosing cholangitis mortality is associated with community socioeconomic status

“…Black patients in our cohort were younger at diagnosis than their White counterparts. Our finding is supported by the limited literature published in this arena which also demonstrates that Black patients present earlier than White patients 10,11,27,28 . In our cohort, there was also a trend towards female predominance among Black patients with PSC.…”

“…Our finding is supported by the limited literature published in this arena which also demonstrates that Black patients present earlier than White patients. 10,11,27,28 In our cohort, there was also a trend towards female predominance among Black patients with PSC. This observation is consistent with earlier reports which showed a higher female prevalence in Black patients with PSC compared to published data in White patients.…”

Ethnicity-Specific Differences in Liver Transplant Outcomes Among Adults With Primary Sclerosing Cholangitis: 2005–2017 United Network for Organ Sharing/Organ Procurement and Transplantation Network

“…13,14 Prior studies demonstrated that African Americans with PSC were younger at the time of listing and presented with more severe disease as manifested by phenotypic characteristics and biological MELD score; all factors have been associated with worse outcomes among patients with PSC. 12,15 In addition to ethnicity-specific differences in disease presentation, response to post-LT immunosuppressive therapies has also been hypothesized to partly contribute to the lower survival seen in African Americans after LT. In a single-center study by Nagashima et al 16 , among recipients undergoing transplantation on tacrolimus-based regimens, a reduced immunosuppressive effect was observed in African Americans compared with non-Hispanic whites, which may contribute to higher rates of acute and chronic rejection in African American recipients.…”

“…Most patients had private/commercial insurance. The median MELD score at the time of LT listing was 15 (Interquartile range (IQR) [11][12][13][14][15][16][17][18][19][20]. At the time of LT waitlist registration, half of patients did not have any evidence of ascites and 66% did not have any evidence of hepatic encephalopathy (Table 1).…”

Heterogeneity of Outcomes Following Liver Transplantation for Primary Sclerosing Cholangitis: Age Matters

“…Furthermore, in at least some PSC patients, even with a complicating cholangiocarcinoma, LT may be feasible [2]. In the accompanying article [3], the authors identified 8272 adults with PSC without a diagnosis of cholangiocarcinoma listed for LT using the United Network for Organ Sharing (UNOS) database over the period [2004][2005][2006][2007][2008][2009][2010][2011][2012][2013][2014][2015]. Dividing the patients into three age groups, 18-39, 40-59, and [60 years, they explored age-related differences in presentation, waiting list status, and post-LT outcomes.…”