Severe Cholestasis Predicts Recurrent Primary Sclerosing Cholangitis Following Liver Transplantation.

Abstract

Primary sclerosing cholangitis (PSC) may reoccur following liver transplantation (LT), and the diagnosis established once imaging studies demonstrate the diagnostic cholangiographic appearance. To evaluate whether the development of recurrent PSC (rPSC) is associated with cholestasis soon after LT, we studied whether changes in hepatic biochemistry within the first 12 months were linked with the development of rPSC and graft loss. We conducted a retrospective cohort analysis of 158 transplant recipients with PSC in Canada and 549 PSC transplant recipients from the United Kingdom. We evaluated serum liver tests within 12 months after LT and the subsequent development of a cholangiographic diagnosis of rPSC as a time-dependent covariate using Cox regression. Severe cholestasis was defined as either alkaline phosphatase > 3× upper limit of normal or total bilirubin > 100 μmol/L. Patients who developed rPSC were more likely to have severe cholestasis vs those without at 3 months (20.5% vs 8.2%, P = 0.011), at 6 months (17.9% vs 10.0%, P = 0.026), and 12 months (15.4% vs 7.8%, P = 0.051) in the Canadian cohort and at 12 months in the UK cohort (27.9% vs 12.6%, P < 0.0001). By multivariable analysis, development of severe cholestasis in the Canadian cohort at 3 months (hazard ratio [HR] = 2.41, P = 0.046) and in the UK cohort at 12 months (HR = 3.141, P < 0.0001) was both associated with rPSC. Severe cholestasis at 3 months in the Canadian cohort was predictive of graft loss (HR = 3.88, P = 0.0001). The development of cholestasis within 3-12 months following LT was predictive of rPSC and graft loss.