Ten year incidence of HCV infection in northern Italy and frequency of spontaneous viral clearance.

BACKGROUND: Little is known of the incidence of hepatitis C virus (HCV) infection, and the frequency of spontaneous viral clearance in the general population is unknown. We conducted an epidemiological study in two Apennine towns in northern Italy. METHODS: Anti-HCV (ELISA and RIBA third generation) and HCV-RNA by polymerase chain reaction were tested in thawed sera from an adult general population of Loiano-Monghidoro in 1986 and 1996, obtained in the context of the MICOL (Multicenter Italian Study on Cholelithiasis). In 1999, anti-HCV positive subjects and sex and age matched controls were recalled in order to identify risk factors for acquiring HCV infection and to assess the family composition of anti-HCV+ subjects. RESULTS: For 1646 subjects, sera were available from both 1986 and 1996 (mean age in 1986 43 (0.39) years). In 1986, 57 (3.46%) subjects were HCV antibody positive (HCV-Ab+). Eight new cases were recorded in 1996: adult incidence was 50.3 cases/100 000 inhabitants/year. Fifty three of 63 (84.1%) HCV-Ab+ sera were also HCV-RNA+. Genotype 2a/2c accounted for 44% and 1b for 47.0% of cases. HCV-Ab+ subjects had higher serum levels of alanine aminotransferase with respect to controls (p<0.005), as did subjects infected with genotype 1 with respect to those with genotype 2 (p<0.05). Eleven of 65 (16.9%) HCV-Ab+ subjects spontaneously cleared HCV-Ab; 7/11 also lost HCV-RNA- in both serum and leucocytes. Sixteen anti-HCV+ subjects belonged to families containing more than one infected member. Married couples accounted for 10 of these 16 subjects. In four of these five married couples, HCV genotype was identical in the two spouses. CONCLUSIONS: In rural northern Italy, the adult incidence of HCV is approximately 50 cases/100 000 inhabitants/year. Our findings suggest that as many as 17% of infected subjects may spontaneously clear HCV-Ab. Interfamilial transmission seems to have a role in the spread of infection.

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.

Ursodeoxycholic acid administration in patients with cholestasis of pregnancy: effects on primary bile acids in babies and mothers.

Little is known about the effects on the fetus of ursodeoxycholic acid (UDCA) treatment for intrahepatic cholestasis of pregnancy (ICP). Twenty ICP patients were given UDCA at 1.5 to 2 g/d, to our knowledge the highest dosage yet reported. Effects were evaluated on conjugated bile acids (BA) in amniotic fluid (15 of 20 patients) and umbilical cord serum obtained at delivery (20 of 22 newborns), as compared with 10 untreated patients (amniotic fluid, 9 of 10 patients; cord serum, 9 of 10 newborns). Liver function tests, serum BA and UDCA were evaluated on enrollment and then weekly until 1 week after delivery. Maternal serum conjugated cholic (CCA) and chenodeoxycholic (CCDCA) acids levels fell (18.5 +/- 1.9 to 10.5 +/- 1.9 micromol/L, and 5.8 +/- 0.8 to 2.97 +/- 0.7 micromol/L, respectively [P <.01]) in treated patients, and remained unaffected (20.0 +/- 3.1 vs. 20.3 +/- 2.3, and 5.6 +/- 0.6 vs. 5.4 +/- 0.5, respectively [P = not significant]) in untreated ones. Serum conjugated UDCA levels rose to 16.5 +/- 1.8 micromol/L (P<.001). Median values of CCA and CCDCA in amniotic fluid around delivery were 4.9 +/- 12.4 and 4.8 +/- 7.7 micromol/L, respectively, in treated patients, as against 17.9 +/- 27.5 and 18.5 +/- 20.9 micromol/L in untreated ones. In treated mothers, CCA and CCDCA concentrations in cord blood were 6.0 +/- 0.9 and 5.2 +/- 0.95 micromol/L, respectively, as against 21.9 +/- 5.6 and 18.9 +/- 2.1 micromol/L in untreated ones. In treated patients, median UDCA values in amniotic fluid and cord blood were 0.8 +/- 2.4 and 0.9 +/- 0.14 micromol/L, respectively. We conclude that increasing the dose of UDCA more effectively controls ICP and improves maternal clinical outcome after delivery.