03; Table 3). Disease severity at entry, as assessed by the total bilirubin level, Mayo risk score, and histological stage, did not seem to considerably affect the baseline bile acid composition, although patients with a baseline total bilirubin level ≥ 0.9

mg/dL had higher values of CA (P = 0.05). In a multivariate analysis model, the only significant relationship that was revealed was between colectomy (P = 0.001), a baseline alkaline phosphatase level ≥ 4 × ULN (P = 0.05), and low levels of DCA. Figure 1 shows the posttreatment percentage of each bile acid per treatment group. No significant changes between selleck compound treatment groups were detected for CA, DCA, or CDCA. UDCA was significantly increased (16.86 versus 0.05 μmol/L, P < 0.0001), and the total bile acid pool was significantly expanded (17.21 versus −0.55 μmol/L, P < 0.0001) in the UDCA group versus the placebo group. LCA was also markedly increased in the UDCA group versus the placebo group (0.22 versus 0.01 μmol/L, P = 0.001). The change in LCA levels after UDCA treatment seemed to positively correlate with the change in UDCA levels (P = 0.19). The UDCA and LCA enrichment did not show any significant relationship with the find more changes in the values of liver tests

(levels of alkaline phosphatase, aspartate aminotransferase, and bilirubin and Mayo risk scores; data not shown). However, female and older patients were more likely to have a greater increase in their LCA value after UDCA treatment (Table 4). Patients who had undergone colectomy (n = 7) tended to have less LCA increase after treatment than those who had not undergone colectomy (Fig. 2). However, patients who had undergone colectomy did not have worse outcomes, regardless of the treatment group. Patients in the UDCA group who reached clinical endpoints during therapy (n = 9) tended to have higher increases in their LCA and total bile acid levels in comparison with those who did not (Fig. 3). The increase in total bile acids was almost entirely

due to enrichment with UDCA. Table 5 summarizes the range of bile acid changes in these patients. The changes were similar dipyridamole in all patients except for one patient (patient 5), and this possibly indicated noncompliance. UDCA has shown some beneficial effects in patients with PSC.2 The inability to demonstrate slowing of disease progression has resulted over the last decade in several studies designed to explore the effectiveness of different UDCA doses.3-6 In the most recent study, high-dose (28-30 mg/kg/day) UDCA treatment was associated with increased rates of serious adverse events without any obvious explanation.7 Modification of the bile acid composition has been speculated to potentially underlie the effects of the drug. In our present study, we investigated the serum bile acid composition in PSC patients under high-dose UDCA treatment. At the baseline, the primary bile acids CA and CDCA predominated.