After 1 year of UDCA treatment, the serum albumin level was slightly but significantly elevated (P < 0.0001), the serum activities of ALP, GGT, AST, and ALT were decreased by about 50% (P < 0.0001), and the serum concentrations of total bilirubin and IgM were decreased by 30% (P < 0.0001) compared with baseline values. The patients were followed up under UDCA therapy for a mean period of 5.9 RG7204 solubility dmso ± 2.6 years

(median, 5.8 years; range, 1.3-14 years). An adverse outcome was recorded in 37 patients, including eight liver-related deaths, four liver transplantations, and 25 complications of cirrhosis (six ascites, nine variceal bleeding, five with both ascites and variceal bleeding, four with hepatic encephalopathy and ascites, and one hepatocellular carcinoma). The survival rates without

adverse outcome at 5 years and 10 years were 86% and 63%, respectively (Fig. 2). In univariate analysis, the baseline factors associated with an adverse outcome were a serum activity of ALP >3× ULN, GGT >5× ULN, AST >2× ULN, an abnormal serum concentration of total bilirubin, and a decreased serum level of albumin (Table 2). In multivariate analysis, a serum activity of ALP >3× ULN, elevated bilirubin level, and decreased albumin level were independent risk factors significantly associated with an adverse outcome (Supporting Table 1). The Barcelona, Paris, Rotterdam, Toronto, and Ehime definitions of biochemical responses to UDCA were evaluated for their ability to discriminate patients MCE公司 according check details to the long-term outcome (Table 3). For each definition, the rates of biochemical response after 3, 6, or 12 months of UDCA therapy were comparable. The highest rate of biochemical response was observed at the sixth month according to the Paris (71.0%), Barcelona (74.5%), and Toronto (69.0%) definitions, whereas the highest level occurred after 1 year of UDCA therapy according

to the Rotterdam (48.5%) and Ehime (58.0%) definitions. The Paris, Barcelona, Toronto, and Ehime definitions significantly discriminated the patients in terms of long-term outcome, whereas no significant association was found with the Rotterdam definition (Table 3 and Fig. 3). Responders differed significantly from nonresponders and had lower baseline bilirubin, ALT, AST, ALP, and GGT levels and higher albumin levels (Supporting Table 2). The responders were more likely to have early disease (by histological stage, P < 0.05; by the Dutch prognostic class,5 P < 0.001). The biochemical responses evaluated at 3, 6, and 12 months of UDCA treatment were highly comparable. We also examined the influence of the initial severity of disease on the prognostic performance of biochemical response at 3, 6, and 12 months. Both histological and nonhistological (the Dutch prognostic class5) criteria were used to grade the initial severity of the disease.