Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing cholangitis

Abstract

Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range: 10-15 mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography/tandem mass spectrometry was used for quantification of 29 plasma bile acid metabolites. Pruritus and health-related quality of life (HRQoL) were assessed with a 10-point numeric rating scale, the Medical Outcomes Study Short Form-36 (SF-36), and PBC-40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of alkaline phosphatase of 75.6%; P < 0.0001; gamma-glutamyl transpeptidase of 117.9%, P < 0.0001; bilirubin of 50.0%, P < 0.001; alanine aminotransferase of 63.9%, P < 0.005; and aspartate aminotransferase of 45.0%, P < 0.005) and increase of Mayo Risk Score for PSC (change from baseline of 10.5 point; P < 0.003). Bile acid analysis revealed a significant decrease in lithocholic acid and its derivatives after UDCA withdrawal, but no effect on concentrations of primary bile acids aside from an increased accumulation of their taurine conjugates. After UDCA removal cholestatic parameters, taurine species of cholic acid and chenodeoxycholic acid correlated with serum FGF19 levels. No significant effect on HRQoL after UDCA withdrawal was observed; however, 42% of patients reported a deterioration in their pruritus. Conclusion: At 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites. A proportion of patients report increased pruritus, but other short-term markers of quality of life are unaffected. (HEPATOLOGY 2014;60:931-940)

Primary sclerosing cholangitis: A review and update

“…162 Though some studies have found beneficial effects with UDCA in PSC, societal guidelines recommend against it or offer no specific recommendation regarding its use in PSC. 6,163 However, given the limitations of the existing trials and the suggestion of clinical benefits in some patients, 164 a therapeutic trial of intermediate-dose UDCA in select patients has been proposed as new therapies are awaited. 44 Other pharmacotherapies currently under investigation for PSC, including but not limited to obeticholic acid, have been recently reviewed elsewhere.…”

Long-Term Ursodeoxycholic Acid Therapy Does Not Alter Lithocholic Acid Levels in Patients with Cystic Fibrosis with Associated Liver Disease

“…39 They reported a highly significant deterioration of liver biochemistries, an increase in Mayo Risk Score, and with respect to serum bile acid composition, a significant decrease in LCA levels and its derivatives with accumulation of taurine conjugated primary bile acids. These patients also reported impairment in disease-related symptoms, with 42% complaining of increased pruritus severity.…”

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

“…Although these criteria need prospective validation, they may be useful for prognostic purposes. However, it is important to emphasize that late responses can occur (even after two years of therapy) and that the suspension of UDCA may lead to significant clinical and laboratory worsening (79,87) . Thus there is no evidence that UDCA should be stopped in the absence of significant biochemical response, except in cases of suspected UDCA-related disease progression.…”