Improved liver tests and greater biliary enrichment with high dose ursodeoxycholic acid in early stage primary biliary cirrhosis.

BACKGROUND: Ursodeoxycholic acid is currently used for the treatment of primary biliary cirrhosis at 13-15 mg/kg/day, but liver tests of some patients do not return to normal at this dose. Studies reported here were designed to test whether a higher dose of ursodeoxycholic acid than is currently used would induce still greater biliary enrichment of ursodeoxycholic acid and whether such enrichment would lead to still further improvement in liver tests in patients with early primary biliary cirrhosis. METHODS: A total of 20 patients with histologically proven primary biliary cirrhosis were enrolled. Patients had early stage primary biliary cirrhosis as serum bilirubin levels were normal and the Mayo risk score 4.2 +/- 0.5. Group 1 received 600, 1200 and 1800 mg/day of ursodeoxycholic acid; group 2 received 900, 1500 and 2100 mg/day. The order of periods was randomized. Each treatment period lasted 3 months followed by a further 3 months during which a standard dose of ursodeoxycholic acid was given. At the end of each treatment period, liver tests were evaluated, and biliary bile acid pattern of duodenal bile was determined using high pressure liquid chromatography. RESULTS: Biliary bile acid became enriched in ursodeoxycholic acid in direct relationship to dosage [r = 0.84, p < 0.001). At doses of 1800 mg/day (25-35 mg/kg/day), biliary ursodeoxycholic acid averaged 69 +/- 6.6%. A progressive decrease of alanine aminotransferase [p < 0.0001), aspartate aminotransferase [p < 0.001) and alkaline phosphatase [p < 0.02) was observed with increasing concentrations of ursodeoxycholic acid in bile. Biochemical liver tests showed a stronger correlation with biliary concentrations of ursodeoxycholic acid than with the administered dose. CONCLUSIONS: In early primary biliary cirrhosis, higher dose ursodeoxycholic acid appears to be more effective than doses currently recommended.

Long-term results with interferon therapy in chronic type B hepatitis: a prospective randomized trial.

OBJECTIVES: The aims of this long-term, prospective randomized study were to evaluate the clinical usefulness of alpha-interferon in treating chronic HBV infection and to establish whether clearance of viral replication markers and normalization of liver function tests induced by alpha-interferon were sustained. METHODS: Sixty-four patients with chronic wild type (HBeAg-positive) hepatitis B, enrolled between 1983 and 1987, were randomized into two groups. Thirty-three patients received alpha-interferon (5 MU/m2 three times weekly for 6 months; treated group), and 31 were not treated (controls). Treated and control patients were prospectively followed for a mean of 86.4 +/- 6.96 and 79.7 +/- 6.8 (p = NS) months, respectively. RESULTS: Clearance of the following viral markers was found in treated and control patients as follows: HBV-DNA, 26 (78.9%) and 18 (58.1%) (p = 0.106); HBeAg, 30 (90.9%) and 19 (61.2%) (p < 0.007); and HBsAg, 12 (36.4%) and three (9.8%) (p < 0.017). Persistent abnormal ALT levels were found in 11 (33.3%) treated and in 22 (70.9%) control patients (p < 0.025). Four control and three treated patients developed portal hypertension whereas two control and one treated patient developed hepatocellular carcinoma. Seven patients (five treated and two controls) were retrospectively found to have hepatitis C virus (HCV) coinfection before enrollment. To date, all coinfected patients remain positive for HCV-RNA. Also, all HCV coinfected patients, except one in the treated group, had persistent increased serum ALT levels. One of the coinfected patients developed portal hypertension. CONCLUSIONS: Chronic HBV hepatitis patients responding to interferon treatment had a faster, more complete, and sustained clearance of viral markers than controls; HCV coinfection does not seem to negatively affect the clearance of HBV replicative markers. However when coinfection occurs, hepatic disease persists despite HBV marker clearance.

[Intrahepatic cholestasis in chronic liver disease]. / La colestasi intraepatica nella malattia cronica di fegato.

Cholestasis syndromes are characterized by a reflux of compounds usually excreted with bile. ATP dependent carriers and cytoskeleton proteins guarantee physiological bile flux. There are several clinical conditions in which this system is affected. Intrahepatic cholestasis is characterized by damage to hepatocytes or intrahepatic bile ducts. Primary biliary cirrhosis and primary sclerosing cholangitis represent examples of cholestatic chronic liver disease. The pathogenesis of these two conditions seems to be mediated by immunological reactions. Moreover, hepatitis viruses are able to induce cholestasis.