Severe cholestasis during the first year post-transplant predicts primary sclerosing cholangitis recurrence

• Author / Creator

  Aziz, Bishoi H. G.

• Background Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic disease of unknown etiology, whose only definitive management is liver transplantation. One of the dilemmas that PSC patients face is the recurrence of the disease in the graft, which may shorten the organ’s life expectancy due to failure. To date, there is little consensus on how PSC recurrence (rPSC) affects the graft”? Our research team implicated rPSC as an inducer of early cholestasis during the first three months post-transplant.
  Aim 1) Demonstrate the link between early cholestasis and rPSC and/or graft survival post-transplant; 2) Investigate the effect of rPSC on graft survival.
  Methodology We constructed a retrospective cohort for patients who received liver transplant for PSC in the University of Alberta transplant center between 1985 and 2019. The database included several characteristics of both the recipients and the donors, time to rPSC and graft loss, graft loss reasons and liver enzymes collected pretransplant, at 1, 3, 6, 9, and 12 months following transplantations. We collaborated with a multicenter team in the United Kingdom (UK) to obtain an external validation cohort. Predictors of rPSC were assessed using a Cox regression and the results were validated using the UK cohort. After that, the rPSC effect on graft survival was investigated using a semi-Markov model as a time-dependent covariate. The end point for the latter was graft loss through death or retransplant due to failure.
  III
  Results The recurrence rate from 158 PSC cases in our database was 30.4% over 34 years. In comparison, the recurrence rate in the UK database was 13.8% over 20 years.
  To predict the occurrence of rPSC, we assessed the clinical and lab variables with a Cox regression. An increase in Alkaline Phosphatase (ALP) was significantly associated with an rPSC incidence in both univariate and multivariable analyses. It remained significant at all time points starting from one month post-transplant (HR=1.3, p =0.027). Also, patients with severe cholestasis three months post-transplant were at a higher risk of contracting rPSC (HR=2.41, p =0.046).
  We found that rPSC negatively impacted the graft survival (HR=8.63, p <0.0001). The multivariable semi-Markov analysis showed that severe cholestasis was an independent predictor of graft survival in the models at all time points (HR=4.77, p =0.021).
  Conclusion Early cholestasis within three months following Liver transplant (LT) is predictive of rPSC. Patients who developed rPSC were more likely to have their graft fail than those who did not. Cholestasis is also a predictor of graft loss independent from the rPSC effect. The reason for the early inflammation and disease recurrence is complex; however, early inflammation and disease recurrence is also consistent with the course of the infectious hepatic diseases.

• Subjects / Keywords

  • Medicine
  • Primary Sclerosing Cholangitis
  • Recurrent Primary Sclerosing Cholangitis
  • Liver transplant
  • Semi-Markov
  • Autoimmune liver disease

• Graduation date

  Fall 2021

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-vrjm-2y91

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.