Characterisation of patients with primary biliary cirrhosis responding to long term ursodeoxycholic acid treatment

Abstract

Background-In some patients with primary biliary cirrhosis, ursodeoxycholic acid causes full biochemical normalisation of laboratory data; in others, indexes improve but do not become normal. Aims-To characterise complete and incomplete responders. Methods-Seventy patients with primary biliary cirrhosis were treated with ursodeoxycholic acid 10-15 mg/kg/day and followed up for 6-13 years. Results-In 23 patients (33%) with mainly stage I or II disease, cholestasis indexes and aminotransferases normalised within 1-5 years, except for antimitochondrial antibodies. Histological findings improved. Indexes were not normalised in 47 patients (67%) although the improvement of their biochemical functions parallelled the trend in the first group. In these incomplete responders histological findings improved to a lesser extent. The only diVerence between the two groups before treatment was higher levels of alkaline phosphatase and glutamyl transpeptidase in the incomplete responders. At onset of treatment the discriminant value separating responders from incomplete responders was 660 U/l for alkaline phosphatase and 131 U/l for glutamyl transpeptidase. One year later it was 239 and 27 U/l (overall predictive value for responders 92%, for incomplete responders 81%). There were no diVerences between the two groups concerning immune status, antimitochondrial antibody subtypes, liver histology, or any other data. HLA-B39, DRB1*08, DQB1*04 dominated in both groups. Conclusions-In patients with mainly early stages of primary biliary cirrhosis, higher values of alkaline phosphatase and glutamyl transpeptidase are the only biochemical indexes which allow discrimination between patients who will completely or incompletely respond to ursodeoxycholic acid treatment. (Gut 2000;46:121-126)

Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid

“…6 Based on experimental findings in cholestatic animals, we hypothesized that activation of nuclear receptors by atorvastatin may improve cholestasis via modulation of bile formation and induction of hepatic bile acid/ bilirubin metabolizing and detoxifying enzymes. 31,32 Statins have previously been shown to act, at least in part, as agonists for the nuclear pregnane X receptor.…”

“…The study was approved by the local ethics committee, and written informed consent was obtained from all participants before enrollment. Inclusion criteria were early-stage PBC (stage I-II on liver biopsy and/or positive antimitochondrial antibodies), an incomplete biochemical response to standard UDCA therapy 6 (defined as an alkaline phosphatase (AP) level of at least 1.5-fold above the upper limit of normal (ULN) after 1 year of UDCA treatment; average dose 11.3 mg/ kg/day) and optionally elevated total cholesterol (200-500 mg/dl). On average, liver biopsy was performed 9 years before study enrollment.…”

“…3,4 However, 39% to 67% of patients may show an incomplete biochemical response to UDCA. 5,6 Whereas patients with a complete biochemical response have a normal survival compared with the general population, 5 patients with an incomplete biochemical response to UDCA remain at increased risk for progression to cirrhosis. 6 Therefore, additional therapeutic options for the treatment of PBC may be necessary.…”

Interleukin-33 Promotes Disease Progression in Patients with Primary Biliary Cirrhosis

“…Currently, ursodeoxycholic acid is the only drug that has been specifically approved for the treatment of PBC. However, 40% of patients have incomplete responsiveness to ursodeoxycholic acid therapy (Leuschner et al 2000), and this fact emphasizes the need to identify immunopathogenesis of PBC and to develop new therapeutic strategies.…”

Cholestatic liver diseases: primary biliary cirrhosis

“…Bei ca. 30% der Patienten kommt es zu einer kompletten Normalisierung der Leberwerte, 70% der Patienten zeigen zwar eine deutliche Besserung, aber keine komplette Normalisierung (19). Bei einigen Patienten bessert sich unter der Therapie auch die Leberhistologie, obwohl dies nicht in allen Studien nachgewiesen werden konnte (15).…”