A longitudinal, cohort study was performed to characterize the clinical features of patients with small-duct primary sclerosing cholangitis (PSC) occurring with and without inflammatory bowel disease (IBD) and to determine the influence of IBD and the effect of ursodeoxycholic acid (UDCA) therapy on the course of the liver disease. Forty-two patients with small-duct PSC (14 women and 28 men; mean age, 36.7 ุ 13.3 years) were followed for up to 24.9 years. At presentation, prevalence of signs of liver disease (none versus 35%, P โซุโฌ 0.002), gastroesophageal varices (5% versus 30%, P โซุโฌ 0.03), and stage III/IV disease (9% versus 45%, P โซุโฌ 0.008) were lower in those with IBD versus those without IBD. During follow-up, 6 patients underwent liver transplantation, and another died of cirrhosis. Using the Cox proportional hazard analysis, concomitant IBD was not associated with liver death or transplant, whereas the revised Mayo risk score for PSC was the only prognostic factor associated with liver-related outcomes (relative risk, 6.47; 95% confidence interval, 1.75-137.5). UDCA (13-15 mg/kg/day) therapy for an average of 40 months showed biochemical improvement (P < 0.001) in UDCA-treated patients, while no significant change occurred in untreated patients. UDCA therapy had no effect on delaying progression of disease (relative risk, 0.95; 95% confidence interval, 0.38-2.36). Conclusion: Small-duct PSC often is recognized at an early stage in patients with IBD; however, IBD has no impact on long-term prognosis. Although UDCA therapy improves liver biochemistries, it may not delay disease progression during the short period of treatment. (HEPATOLOGY 2008;47: 133-142.) S mall-duct primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology characterized by fibrosing inflammation and destruction of interlobular and septal bile ducts in the absence of cholangiographic evidence of sclerosing cholangitis. 1,2 Small-duct PSC represents approximately 6% to 11% of patients with sclerosing cholangitis and commonly coexists with inflammatory bowel disease (IBD). 3,4 Three groups have reported follow-up information from patients with small-duct PSC, which showed that the clinical course of small-duct PSC was more benign than large-duct PSC. [3][4][5] Unfortunately, some patients with small-duct PSC follow a progressive course over time, develop the typical cholangiographic features of large-duct PSC, and advance to biliary cirrhosis and its complications with the consequent necessity of liver transplantation. [3][4][5] However, given that the definition of small-duct PSC varied from study to study in terms of evidence of IBD, the influence of concomitant IBD on the long-term prognosis of patients with small-duct PSC remains largely unstudied.
Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid that is widely used in the treatment of cholestatic liver disease of all causes. UDCA appears to exert a number of effects, all of which may be beneficial in chronic cholestasis: a choleretic effect by an increase in bile flow, a direct cytoprotective effect, an indirect cytoprotective effect by displacement of the more hepatotoxic endogenous hydro-