Clinical Significance of Serum Bilirubin Levels Under Ursodeoxycholic Acid Therapy in Patients With Primary Biliary Cirrhosis

Abstract

We determined whether the normalization of serum bilirubin level (SBL) induced by ursodeoxycholic acid (UDCA) therapy was associated with an improved clinical outcome in patients with primary biliary cirrhosis (PBC). We estimated the prognostic values of SBL measured after 6 months of UDCA treatment for survival free of orthotopic liver transplantation (OLT). We used a database of 548 patients with PBC followed in three trials of UDCA. Among UDCA-treated patients, we compared survival free of OLT in patients with normalized SBL (I17 mol/L) with those who had persistently elevated SBL. Difference in survival was tested between UDCA-treated patients whose SBL normalized with treatment and placebo patients who had normal baseline SBL. We evaluated, in each treatment group, the prognostic value of 6-month SBL. Survival was estimated using the Kaplan-Meier method and compared by the Cox model. Survival free of OLT was significantly longer in patients who had normalized SBL (P F .0001; relative risk [RR]: 3.7, UDCA group). Survival free of OLT was not significantly different between UDCA patients with normalized SBL and placebo patients with a normal baseline SBL (P ‫؍‬ .69). For several cutoffs of 6-month SBL, RRs of OLT or death were similar in UDCA-treated and placebo patients: the RR of OLT or death associated with a 6-month SBL more than 30 mol/L was 6.0 for UDCA and 5.7 for placebo groups. In conclusion, normalization of SBL during therapy is associated with improved clinical outcome. SBL under UDCA therapy is a prognostic factor in PBC. SBL under UDCA therapy should be interpreted as in untreated patients. (HEPATOLOGY 1999;29:39-43.)

American Association for the Study of Liver Diseases Endpoints Conference: Design and Endpoints for Clinical Trials in Primary Biliary Cirrhosis

“…Of all the serum markers studied to date, serum bilirubin is the best independent predictor of survival. [36][37][38] Table 1 lists several of the more compelling features upon which to consider subject stratification. Determining which ones are important enough to use for stratification of subjects in a clinical trial depends on the endpoint being examined.…”

“…Bilirubin has been consistently demonstrated to be the single most important serum marker of survival [36][37][38] and therefore is a desirable endpoint. The limiting factor of using bilirubin as an endpoint is that it only becomes abnormal in late stages of the disease and thus is not a sensitive outcome measure.…”

Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis

“…[10][11][12] However, these prognostic indices have some limitations: (1) hyperbilirubinemia concerns a minority of treated patients; and (2) histological examination of the liver implies an invasive procedure, that is, biopsy, that precludes its repeated use. Biochemical response to UDCA, especially changes in the serum activities of alkaline phosphatase (ALP) and aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase…”

Silymarin in the Treatment of Patients With Primary Biliary Cirrhosis With A Suboptimal Response to Ursodeoxycholic Acid

“…Serum bilirubin levels, a useful prognostic marker in treated 29,30 and untreated [23][24][25][26][27][28]31 patients with PBC, were not affected by the combination of UDCA and silymarin, and none of our patients showed a complete normalization of liver biochemistries during combination therapy. In addition, although the effect of silymarin on survival or development of liver-related complications was not the primary end-point of the current study, the Mayo risk score, a cross-validated index of survival in PBC, 11,23,29,32 was not improved; indeed, it increased at the end of the treatment period, further reflecting the lack of a significant effect of silymarin on clinically relevant outcomes.…”