Ursodeoxycholic acid, a dihydroxyl bile acid normally present in human beings in minimal amounts, becomes incorporated into the bile salt pool when taken orally. In cholestasis, bile acids are retained in the liver and are hepatotoxic. Ursodeoxycholic acid is the least-known hepatotoxic bile acid, has choleretic properties and is reported to benefit patients with chronic cholestasis. In a nationwide Canadian controlled trial, 222 patients with primary biliary cirrhosis were treated with ursodeoxycholic acid (14 mg/kg/body wt/day) or placebo for 24 mo. Only patients with a diagnosis confirmed by liver biopsy and serum positive for antimitochondrial antibodies were enrolled; 88% were symptomatic on entry. The primary outcome measure was percent change in total serum bilirubin from baseline to final follow-up. Treated patients (111) and controls (111) were comparable with regard to age, gender, biochemical parameters and liver histological condition. Although treatment was not associated with any improvement in symptoms, ursodeoxycholic acid therapy caused the bilirubin to fall significantly within the first 3 mo of therapy (p < 0.001). Significant falls in serum alkaline phosphatase, aminotransferases, cholesterol and IgM levels were also noted in the treated group. Improvement in some histological features was observed but there was no difference between the groups in the number of patients who reached the endpoints of death or liver transplantation. Ursodeoxycholic acid, given to patients with primary biliary cirrhosis, leads to an improvement in serum markers of cholestasis. A larger sample size is needed to determine whether ursodeoxycholic acid therapy has a beneficial effect on the survival of patients with primary biliary cirrhosis.

Treatment of patients with primary biliary cirrhosis eral prognostic indicators have been proposed and (PBC) using ursodeoxycholic acid (UDCA) leads to a re-prognostic indexes developed to predict survival. duction in serum bilirubin. The first objective of this Shapiro et al. 1 showed that serum bilirubin is a good study was to assess the performance of certain prognos-predictor of survival in PBC, and elevated serum bilirutic indicators for PBC after the introduction of treat-bin levels have been used to decide when to refer pament with UDCA. Serum bilirubin is an important prog-tients for transplantation.2 Other groups have develnostic indicator for PBC and an important component oped prognostic indexes that combine bilirubin with of the Mayo model for grading patients into risk categoseveral other variables to arrive at a predictive score. ries. In an analysis of patients enrolled in the CanadianThe European model 3 uses serum bilirubin, serum almulticenter trial, the Mayo score was calculated before bumin, age, the presence of cirrhosis and cholestasis and after treatment with UDCA. After treatment, the Mayo score continued to divide patients with PBC into on liver biopsy, and azathioprine use. The Yale model groups with varying risk. In addition, the serum biliru-combines age, serum bilirubin, hepatomegaly, and the bin alone was shown to do the same even after the intro-presence of portal fibrosis or cirrhosis. 4 A third model duction of treatment with UDCA. A second objective was developed for nonalcoholic cirrhosis and PBC uses seto establish whether UDCA had an effect on long-term rum bilirubin, serum albumin, age, hepatitis B surface The Mayo group 6 devised a further model which emPrimary biliary cirrhosis (PBC) is a chronic progres-ploys serum bilirubin, serum albumin, age, prothromsive cholestatic liver disease for which the only defini-bin time, and the presence of edema. The Mayo model tive treatment is orthotopic liver transplantation. One was based on data from a group of 312 patients inof the most difficult questions in the management of volved in a trial of D-penicillamine and has been exterpatients with PBC is when to intervene with trans-nally cross-validated. 7 plantation to optimize quality and length of life. SevAll of the models mentioned above use the patient's data collected at the time of referral to predict the remaining life span. Both the European and Mayo models Abbreviations: PBC, primary biliary cirrhosis; UDCA, ursodeoxycholic acid.

In Canada, budesonide has been successfully used in seven of nine patients with autoimmune hepatitis who were either intolerant to prednisone and azathioprine or prednisone-dependent. No adverse effects were reported with budesonide. Budesonide is potentially a valuable treatment option for AIH patients refractory or intolerant to standard therapy, and is deserving of further study.

No abstract

No abstract