Serum autoantibodies in patients with primary sclerosing cholangitis.

BACKGROUND/AIM: Primary sclerosing cholangitis is a chronic cholestatic syndrome with a presumed autoimmune basis frequently associated with inflammatory bowel disease. The aim of this study was to determine the profile and significance of serum autoantibodies in patients with primary sclerosing cholangitis. METHODS: Serum samples taken from 73 untreated patients (32 female and 41 male, median age 45 years) with well-defined primary sclerosing cholangitis, and from 75 healthy age- and sex-matched controls were assayed for 20 different autoantibodies. RESULTS: Of 73 patients, 71 (97%) were positive for at least 1 autoantibody; whereas 59/73 patients (81%) were positive for > or =3 antibodies. Patients with primary sclerosing cholangitis had a significantly greater rate of positivity than controls for antinuclear, anticardiolipin, antineutrophil cytoplasmic, and antithyroperoxidase antibodies as well as rheumatoid factor. The rate of positivity and serum levels of any of these 20 autoantibodies were not significantly different between patients with primary sclerosing cholangitis and inflammatory bowel disease and those without inflammatory bowel disease. Anticardiolipins were the single group of antibodies that had a significant correlation with the Mayo risk score (r=0.49, p<0.001) and histologic stage of disease (r=0.30, p<0.01). CONCLUSIONS: Primary sclerosing cholangitis is associated with a high proportion of non-organ specific autoantibodies. Anticardiolipin antibodies appear to be related to the severity of primary sclerosing cholangitis and may be a useful prognostic marker.

Comparison of three doses of ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a randomized trial.

BACKGROUND/AIM: Ursodeoxycholic acid in doses of 13-15 mg x kg(-1) x day(-1), is a safe and cost-effective treatment for patients with primary biliary cirrhosis. However, very limited information exists regarding the most appropriate dose of ursodeoxycholic acid. The aim of the study was to compare three dosages of ursodeoxycholic acid with respect to changes in liver biochemistries, Mayo risk score, biliary enrichment with ursodeoxycholic acid and side effects over at least a 1-year period. METHODS: A total of 155 patients were randomized to receive low- (5-7 mg x kg(-1) x day(-1)), standard-(13-15 mg x kg(-1) x day(-1)), and high- (23-25 mg x kg(-1) x day(-1)) doses of ursodeoxycholic acid. RESULTS: The improvements in alkaline phosphatase (p = 0.0001), aspartate aminotransferase (p = 0.0001), Mayo risk score (p = 0.002), and ursodeoxycholic acid enrichment (p = 0.0001) were significantly greater in the standard- and high-dose groups compared to the low-dose group, but not between the standard- and high-dose groups. Changes in serum bilirubin were similar between the three groups (p = 0.07). No significant effects on symptoms were noted with any dose. No patients discontinued ursodeoxycholic acid because of side effects or toxicity. CONCLUSIONS: Ursodeoxycholic acid in doses of 5-25 mg x kg(-1) x day(-1) is safe and well tolerated. The dose of 13-15 mg x kg(-1) x day(-1) appears to be the preferred dose for patients with primary biliary cirrhosis.

Oral nicotine in treatment of primary sclerosing cholangitis: a pilot study.

Currently, no accepted medical therapy for patients with primary sclerosing cholangitis (PSC) is available. Case-control studies have shown an inverse association between PSC and smoking behavior, suggesting that nicotine might have a beneficial effect in PSC. The aim of this study was to evaluate the safety and estimate the efficacy of oral nicotine in the treatment of PSC. Eight PSC patients who had never smoked received oral nicotine at a maximum dose of 6 mg four times a day for up to one year. Liver biochemistries and plasma cotinine levels were determined at entry and at three-month intervals during the study duration. Five patients completed one year of treatment, but three of them had to temporarily reduce the dose due to side effects. One patient completed only four months of treatment due to dizziness and heart palpitations. Two patients completed only one month of treatment due to reactivation of colitis requiring corticosteroid therapy. No significant changes in liver biochemistries were noted during the treatment period despite a significant increase in plasma cotinine levels. In conclusion, oral nicotine seems to have no beneficial effects in the treatment of PSC, and it is frequently associated with side effects necessitating permanent drug cessation.

Bone disease in patients with primary sclerosing cholangitis: prevalence, severity and prediction of progression.

BACKGROUND/AIMS: Osteopenia is a common complication in some chronic cholestatic liver diseases. Our aims were to determine the prevalence and severity of bone disease in patients with primary sclerosing cholangitis; and identify risk factors to predict the presence and progression of osteopenia. METHODS: Eighty-one patients involved in a randomized trial of ursodeoxycholic acid were analyzed. Bone mineral density of the lumbar spine was determined at entry and at annual intervals. RESULTS: Bone mineral density of the lumber spine in primary sclerosing cholangitis patients was significantly lower than expected when compared to normal values adjusted for age, sex and ethnic group at entry (p<0.005), and after 1 year (p<0.05), 2 years (p<0.05), 4 years (p<0.005) and 5 years of follow-up (p<0.005). Seven patients (8.6%) had bone mineral density of the lumber spine below the fracture threshold at entry. These patients were significantly older, had a longer duration of inflammatory bowel disease and more advanced primary sclerosing cholangitis. The rate of bone loss in primary sclerosing cholangitis patients and expected in normal controls was 0.01+/-0.02 g x cm(-2) x year(-1) and 0.003+/-0.003 g x cm(-2) x year(-1), respectively (p = NS), and was similar in patients receiving placebo and ursodeoxycholic acid. Age was the only variable inversely related with baseline bone mineral density of the lumber spine (p<0.0001). None of the variables predicted progression of the bone disease. CONCLUSIONS: Severe osteoporosis occurs in few patients with primary sclerosing cholangitis, but it should be suspected in patients with longer duration of inflammatory bowel disease and more advanced liver disease. Its presence, severity and progression cannot be accurately evaluated by routine clinical, biochemical, or histological variables. Ursodeoxycholic acid does not affect the rate of bone loss in primary sclerosing cholangitis.

Relationship between biliary and serum bile acids and response to ursodeoxycholic acid in patients with primary biliary cirrhosis.

OBJECTIVE: Ursodeoxycholic acid (UDCA) improves liver biochemistries and enriches the bile with UDCA in patients with primary biliary cirrhosis. The aim of this study was to determine whether the degree of enrichment of bile correlated with that of serum and whether either of these measures correlated with improvement in measures of liver disease. METHODS: In a randomized study, biliary and serum bile acid analyses were performed at entry and after 2 yr of UDCA or placebo. RESULTS: The percentage of ursodeoxycholic acid in bile increased by 42% in the UDCA group (n = 61) compared with 8% in the placebo group (n = 57) (p < 0.0001). Measurement of serum bile acids in 32 patients (18 ursodeoxycholic acid, 14 placebo) indicated that at 2 yr, ursodeoxycholic acid comprised 65% of serum bile acids in the treated group and 7% in the placebo group. Agreement between bile and serum was fair (r = 0.75, p < or = 0.00002) because in some patients, plasma but not biliary bile acids were enriched with UDCA. Changes in biliary ursodeoxycholic acid correlated significantly but weakly with the changes in serum alkaline phosphatase, AST, bilirubin, and in Mayo risk score. Correlations between changes in serum bile acid composition and biochemical measures of disease activity were even weaker. CONCLUSION: The measurement of biliary bile acids is superior to that of serum bile acids for assessing the compliance and changes in the circulating bile acids in patients receiving ursodeoxycholic acid for the treatment of primary biliary cirrhosis. Furthermore, measures to further increase the proportion of ursodeoxycholic acid in circulating bile acids should be explored.

The natural history of abdominal pain associated with primary biliary cirrhosis.

OBJECTIVES: The aim of the present study was to determine the prevalence and natural history of abdominal pain in patients with primary biliary cirrhosis. METHODS: We studied 178 patients with well-defined primary biliary cirrhosis enrolled in a prospective randomized trial of ursodeoxycholic acid. These patients underwent upper endoscopy and upper abdominal ultrasound prior to entry, at 2 yr, and as indicated. Fourteen patients had additional evaluations including abdominal CT (four), colon x-ray (five), colonoscopy (three), endoscopic retrograde cholangiopancreatography (two), and upper gastrointestinal x-ray (two). RESULTS: Patients with abdominal pain generally presented with right upper quadrant discomfort. Thirty-one patients (17%) had pain at study entry: 33% of these had pain persisting at 1 yr, and 20% of these had pain persisting at 2 yr. The resolution of pain was not clearly affected by ursodeoxycholic acid. Evaluation with ultrasound and upper endoscopy found four patients with asymptomatic cholelithiasis, one with esophageal erosions, four with gastric erosions, one with a gastric ulcer, and two with duodenal erosions. Additional tests were unrevealing in 14 patients. Patients with pain were similar to patients without pain with regard to age, histological stage, gender, and liver biochemistries. CONCLUSIONS: We conclude that chronic right upper quadrant pain is not uncommon in patients with primary biliary cirrhosis, that it usually resolves spontaneously, and that upper endoscopy is the most important diagnostic test to use to exclude treatable causes of pain.