Fluvoxamine for fatigue in primary biliary cirrhosis and primary sclerosing cholangitis: a randomised controlled trial [ISRCTN88246634]

BACKGROUND: Fatigue is a major clinical problem in many patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). An effective treatment has not been defined. Recently, a large proportion of patients with these diseases was found to have symptoms of depression. Because fatigue is a frequent symptom of depression and there is some evidence that treatment with an antidepressant improves fatigue in patients with fibromyalgia, we hypothesised that the antidepressant fluvoxamine might improve fatigue related to PBC and PSC. METHODS: Fatigued patients were randomised to receive fluvoxamine (75 mg BID) or placebo for a six-week period. Fatigue and quality of life were quantified using a visual analogue scale, the Fisk Fatigue Severity Scale, the Multidimensional Fatigue Inventory and the SF-36. RESULTS: Seventeen and 16 patients were allocated to fluvoxamine and placebo, respectively. There was no statistically significant beneficial effect of fluvoxamine on fatigue or quality of life. The median VAS scores in the fluvoxamine and placebo groups were 7.40 and 7.45 at day 0, 6.9 and 7.15 at day 14, 7.45 and 7.65 at day 42 and 7.8 and 8.0 four weeks after treatment discontinuation. CONCLUSION: We found no evidence for a beneficial effect of fluvoxamine on fatigue in these patients with cholestatic liver disease and severe chronic fatigue

Prognostic factors and long-term effects of ursodeoxycholic acid on liver biochemical parameters in patients with primary biliary cirrhosis

Serum bilirubin is a prognostic factor in untreated primary biliary cirrhosis (PBC), but this has been less extensively documented for patients treated with UDCA. The aims of this study were to define the effects of UDCA on serum liver tests and to assess prognostic factors in patients on prolonged UDCA treatment. Analysis of laboratory parameters obtained before and during treatment with UDCA of 203 PBC patients who were followed for a mean of 48 months. Univariate and multivariate analyses were performed to assess the prognostic value of pre-entry and follow-up variables with respect to treatment failure and survival. Actuarial 5-year incidences of treatment failure and transplantion-free survival were 27 and 79%, respectively. According to the univariate analysis the following variables were significantly associated with prognosis: pre-entry presence of cirrhosis and pre-treatment levels of serum bilirubin and albumin, bilirubin levels during follow-up, the occurrence of biochemical remission and normalisation of serum bilirubin. Multivariate analysis revealed that bilirubin during follow-up was the best predictor. Alkaline phosphatase, aspartate aminotransferase and IgM decreased significantly during the first 6 months of treatment and subsequently remained at this lower level. Serum bilirubin showed the same initial pattern, but a significant increase was observed after 4 years of treatment. Serum bilirubin in both UDCA-treated and untreated patients is the most powerful predictor of prognosis for PBC. The partial therapeutic efficacy of UDCA is illustrated by the finding that serum bilirubin, in contrast to alkaline phosphatase and the transaminases, appears to increase after 4 years of treatmen

Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: a 1-year randomized, placebo-controlled study

Treatment with ursodeoxycholic acid has been shown to decrease the rate of disease progression in patients with primary biliary cirrhosis, although the effect is modest. Since primary biliary cirrhosis has many features of an autoimmune disorder, immunosuppressives added to ursodeoxycholic acid may be of value in the treatment of primary biliary cirrhosis. A 1-year randomized, double-blind, placebo-controlled trial was carried out in 50 patients with primary biliary cirrhosis, who had already been treated with ursodeoxycholic acid for at least 1 year, but had not achieved complete disease remission. Patients were randomized to additional prednisone (30 mg per day initially, tapered to 10 mg daily after 8 weeks) and azathioprine (50 mg daily) or placebo. A subgroup of patients received cyclical etidronate and calcium. The principal aim of the study was to assess the short-term benefits and risks of the combined bile acid and low-dose immunosuppressive regimen. Primary endpoints were effects on symptoms, liver biochemistry, liver histology, bone mass and the occurrence of adverse events. Pruritus (p=0.02), alkaline phosphatase, aspartate aminotransferase, IgM and procollagen-III-propeptide improved significantly (all p <0.002) in the combined treatment group as compared to the placebo group. Histological scores for disease activity and disease stage decreased significantly within the combination treatment group (p <0.001). In patients with primary biliary cirrhosis receiving ursodeoxycholic acid, there is an additional beneficial effect of 1-year treatment with prednisone and azathioprine on symptoms and biochemical, fibrogenetic and histological parameters. These results strongly encourage the evaluation of this triple treatment regimen in long-term controlled trials of adequate size to document its effect on clinical event