Primary Sclerosing Cholangitis: Clinical Outcomes

Digestive Disease Week (DDW) 2017

William F. Balistreri, MD


July 27, 2017

Significant advances in the clinical practice of hepatology were addressed during this year's Digestive Disease Week. This review focuses on data regarding the clinical outcomes of patients with primary sclerosing cholangitis (PSC).

Posttransplantation Patient and Graft Survival

Mousa and colleagues[1] assessed predictors of patient and graft survival in those undergoing deceased donor liver transplantation for PSC.

They examined the liver transplant database at Mayo Clinic Jacksonville and identified adult patients with PSC who underwent liver transplantation over a 3-year period. After excluding split organ, multiorgan, and prior liver transplant recipients, 131 out of 2208 patients were eligible. The mean recipient age was 49 years; 65% were male, 74% were white, 11% had cholangiocarcinoma, and 2% had hepatocellular carcinoma. The mean biologic Model for End-Stage Liver Disease (MELD) score at transplant was 19 (range, 6-40).

The estimated patient survival probabilities at 5, 10, and 15 years were 83%, 70%, and 62%, respectively, and were comparable to graft survival rates. Compared with those without cholangiocarcinoma, Kaplan-Meier patient survival distributions were statistically different among those with cholangiocarcinoma at 5 years (50% vs 88%; log-rank P = .01) and 10 years (42% vs 73%; log-rank P = .01). Longer waiting time and having cholangiocarcinoma before or at the time of transplantation were significant predictors of lower survival rates on univariate analysis. On multivariate Cox-regression hazard model, the presence of cholangiocarcinoma and waiting time were important factors for prediction of survival.

The impact of the longer waiting time in these patients raises questions regarding their prioritization for transplant under the current guidelines.

Characteristics and Long-term Outcomes of PSC in Children

Ricciuto and coworkers[2] aimed to evaluate disease characteristics and long-term outcomes of PSC in children with and without inflammatory bowel disease (IBD).

Using data from the Pediatric PSC Consortium, a large international collaboration of 36 centers, they performed a survival analysis from the time of diagnosis of PSC to any of the following: a portal hypertensive complication (ascites, encephalopathy, or esophageal varices); a dominant biliary stricture requiring stent, dilation, or drainage; liver transplantation; cholangiocarcinoma; and/or liver-related death.

Overall, 76% of patients with PSC had concomitant IBD (83% ulcerative colitis and 17% Crohn disease).

PSC without IBD was more common in females and more likely to be associated with PSC/autoimmune hepatitis overlap (51% vs 28%) and higher baseline MELD (4 vs 0), AST-to-Platelet Ratio Index (APRI; 1.57 vs 0.68), and ALT values (286 vs 176; all P < .001).

The probability of portal hypertensive and biliary complications within 5 years of diagnosis in the isolated PSC vs PSC-IBD groups was 31% vs 21% and 24% vs 12%, respectively (P < .01).

Event-free survival at 5 years was worse in patients with isolated PSC versus those with PSC-IBD (58% vs 73%; P < .001). In univariate analysis, concomitant IBD, a small duct phenotype, and a lower baseline MELD score were independently associated with a higher probability of event-free survival.

The investigators concluded that patients with PSC-IBD experienced fewer adverse liver outcomes during follow-up compared with those with PSC but without IBD. It is unclear whether the difference in baseline disease characteristics reflects the routine practice of liver enzyme monitoring in patients with IBD and thus an earlier diagnosis of PSC or a more aggressive cholangiopathy in patients with isolated PSC.

Bazerbachi and colleagues[3] quantified the occurrence of recurrent PSC after liver transplantation and characterized risk factors for recurrence using the large, multicenter cohort of pediatric patients with PSC discussed above (the Pediatric PSC Consortium). Risk factors previously implicated in recurrent PSC have included younger age at time of the diagnosis of PSC, gender, concomitant IBD, episodes of rejection, prolonged steroid use, and lymphocyte-depleting therapy.

They assessed patients with PSC diagnosed prior to the age of 18 years who required liver transplantation (mean age at initial diagnosis, 10.5 years). Recurrent PSC was defined as the occurrence of a cholestatic biochemical profile, with cholangiographic and/or histologic features of PSC not caused by chronic rejection, cytomegalovirus infection, or hepatic artery thrombosis. Of 781 pediatric patients with PSC, 113 received a liver transplant. The mean age at transplant was 14.8 years, and 85 of the liver transplant patients had IBD (83% ulcerative colitis and 17% Crohn disease), while 30% of the patients had autoimmune hepatitis and 27% had small duct phenotype. Follow-up (median, 3 years) beyond the immediate posttransplant hospitalization was available in 92 patients.

Recurrent PSC was identified in 16 patients, with a median time for recurrence after transplant of 2.2 years. The 5-year probability of recurrent PSC after transplant was 23%. Patients with recurrent PSC were younger at the time of transplant (12 vs 15 years), with a larger prevalence of overlap with autoimmune hepatitis (63% vs 26%). There were no differences in sex, IBD prevalence, or small vs large duct phenotype between groups. In a multivariate regression, the hazard ratio for recurrent PSC in patients with PSC and autoimmune hepatitis overlap was 4.1 compared with patients with PSC alone.

Further insight into donor graft characteristics and posttransplant immunosuppression regimens in this large cohort is awaited.

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