Effects of ursodeoxycholic acid and colestilan versus ursodeoxycholic acid alone on serum bile acids and pruritus: a randomized, open-label study

Abstract

Background: Pruritus associated with primary biliary cirrhosis (PBC) is often difficult to manage and may affect the quality of life of patients. The cause of pruritus in liver disease is unknown but is thought to be related to the deposition of bile salts in the skin. Objective: We studied the effects of ursodeoxycholic acid (UDCA) alone and in combination with colestilan (CLL) on refractory pruritus and bile acid levels in patients with PBC. Methods: Eleven patients with pruritus associated with PBC were entered into this trial. Six patients received UDCA 600 mg/d (200 mg TID after meals) for 8 weeks. The remaining 5 patients received UDCA 600 mg/d (200 mg TID after meals) for 4 weeks and UDCA 600 mg/d (200 mg TID after meals) plus CLL 6.42 g/d (2.14 g TID before meals) for 4 weeks. The intensity of pruritus was graded at baseline and at 2-week intervals using a self-administered questionnaire with a scale of 1 (no itching) to 10 (severe and constant itching). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (γ-GTP), immunoglobulin M (IgM), and total bilirubin levels were determined immediately before administration of the drug and at weeks 4 and/or 8. Serum bile acid levels were analyzed using high-performance liquid chromatography. Results: In the UDCA monotherapy group, AST, ALT, ALP, γ-GTP, and IgM levels were significantly reduced versus baseline ( P < 0.05) after 8 weeks of therapy. In the UDCA-CLL combination therapy group, AST, ALT, ALP, γ-GTP, and IgM levels were significantly reduced versus baseline after the initial 4 weeks of UDCA monotherapy ( P < 0.05) and were further reduced after 4 weeks of UDCA-CLL combination therapy; however, the difference between values at week 4 and week 8 was not statistically significant. In the UDCA monotherapy group, the chenodeoxycholic acid/cholic acid (CDCA/CA) ratio increased and the proportion of UDCA increased to > 50%. The pruritus score did not change significantly versus values at baseline (3.7 ± 0.3 at study entry vs 2.5 ± 0.3 at week 8). In the UDCA-CLL combination therapy group, total bile acid levels decreased markedly, but the CDCA/CA ratio decreased and the UDCA level was maintained at > 50%. A significant improvement ( P < 0.05) in pruritus score was observed after 4 weeks of UDCA-CLL combination therapy (1.2 ± 0.2) compared with baseline scores (4.0 ± 0.3) and scores after 4 weeks of UDCA monotherapy (3.8 ± 0.4). Conclusion: Clinical and biochemical data after 4 weeks' treatment with UDCA-CLL suggest that the combination may be effective in the management of pruritus associated with PBC.