For the purpose of the present study, all five definitions were applied at 3, 6, and 12 months after UDCA therapy and evaluated using the same endpoint, which was the occurrence of adverse outcome as defined by at least one of the following events: liver-related death, liver transplantation, or complications of cirrhosis (ascites, variceal bleeding, hepatic encephalopathy, or hepatocellular carcinoma). Data were censored at the time of death or liver transplantation for the patient who died or underwent transplantation, and at the time of presenting with a cirrhosis-related

complication Cilomilast concentration or of last follow-up for the living nontransplanted patients. If a living nontransplanted patient developed more than one cirrhosis-related complication during follow-up, data were censored at the time of the first presentation of cirrhosis-related complications. Comparisons between biochemical variables before and after

3, 6, or 12 months of UDCA treatment were performed using the Wilcoxon signed-rank test for paired data. Survival rates without adverse outcome were estimated using the Kaplan-Meier method. The selleck inhibitor effects of baseline factors and of biochemical responses to UDCA on survival rate were estimated using the Cox proportional hazards regression model. The average hazard ratio and 95% confidence interval were used to quantify the strength of the statistical links between the tested variables and survival. The sensitivity (Se), specificity MCE (Sp), positive (PPV) and negative (NPV) predictive values, and positive and negative (NLR) likelihood ratios were calculated

for all definitions to assess their performance for prediction of long-term outcome. Quantitative data are expressed as the mean ± SD and qualitative data as a percentage. All analyses were two-sided, and P < 0.05 was considered statistically significant. The statistical package SPSS 16.0 (SPSS Inc, Chicago, IL) was used to perform the analysis. A total of 187 patients (94% females; age, 51 ± 9 years) met the inclusion criteria. Biochemical data were available in 128 patients for the third month after UDCA treatment, 145 patients for the sixth month, and 157 patients for 1 year. To take full advantage of the available data, we used all of them for analyses. Table 1 shows the characteristics of the patients at baseline and after 1 year of UDCA therapy. Figure 1 shows the evolution of ALT, AST, ALP, GGT, serum bilirubin, albumin, and immunoglobulin M (IgM) levels within the first year of UDCA treatment. A prominent decline in the serum activities of ALP, GGT, AST, and ALT was noted in the first three months (P < 0.0001), which was accompanied by a significant decrease of bilirubin (P < 0.0001) and IgM (P < 0.0001) and elevation of albumin (P < 0.0001).