306 Rifaximin Therapy for Patients With Primary Sclerosing Cholangitis—an Open Label Clinical Trial

Introduction Primary sclerosing cholangitis (PSC) is a chronic liver disease leading to biliary fibrosis and liver cirrhosis, eventually necessitating liver transplantation or resulting in death. In the absence of an effective treatment it is important to reliably predict survival. Previous studies indicated that improvement of alkaline phosphatase (ALP) during the disease course is associated with a better prognosis. Aim of this study was to evaluate if normalization of ALP within one year after diagnosis is associated with better event-free survival. Methods Patient charts from a large population-based PSC cohort were reviewed for laboratory results and the use of ursodeoxycholic acid (UDCA). Patients without documented ALP both at diagnosis, as well as 1 year after diagnosis (+/-3 months) were excluded. Clinical endpoints were development of cholangiocarcinoma, liver transplantation and PSC-related death. Univariable logistic regression analyses were performed to determine laboratory and clinical variables associated with outcome. Kaplan Meier survival curve was used to estimate event free survival between those who attained normalization of ALP within 1 year after diagnosis and those who did not. To correct for possible confounding co-variables on reaching an endpoint, Cox proportional hazard analysis was used. Results We included 247 patients with a median follow up of 95 months (range 12-347). Mean age at diagnosis was 40 years (± 13), 61% was male. In 75 patients (30%) ALP normalized within one year after diagnosis, in 172 patients (70%) ALP did not normalize. In the first group 7 patients (9%) reached an endpoint, compared to 38 (22%) in the second group (p=0.019). Patients in the first group had a significantly longer event-free survival than the second group (p=0.028, fig. 1). Univariable logistic regression showed that UDCA use and normalization of ALP within one year after diagnosis were significantly associated with outcome. In multivariate Cox regression analysis only ALP normalization within one year after diagnosis proved to be a significant predictor of long-term outcome. (Odds Ratio 0.43, 95% CI 0.19 0.97). Conclusion Normalization of ALP within the first year after diagnosis is associated with a better long-term survival in PSC patients. These results corroborate ALP as a candidate surrogate parameter in future PSC intervention studies. Furthermore ALP may serve as an important factor in prognostic modelling in PSC.