Inadequate dietary intake but not renal tubular acidosis is associated with bone demineralization in primary biliary cirrhosis.

BACKGROUND: Metabolic bone disease associated with primary biliary cirrhosis (PBC) is inadequately characterized. Renal tubular acidosis (RTA) may lead to bone loss through chronic mobilization of skeletal calcium salts to buffer increased acid load. AIM: To evaluate the prevalence of RTA in PBC and establish the relationships among bone mineral density (BMD), renal function and nutritional status. METHODS: We enrolled 69 female patients with compensated PBC and 35 control patients with chronic hepatitis C. RTA was searched in all patients, and 24-h dietary recalls were collected at enrolment. BMD was measured by dual-energy X-ray absorptiometry at the femur neck, lumbar spine and radius ultradistalis sites. RESULTS: No patients received a diagnosis of RTA. BMD values (Z-scores) showed only little deviation from normal population with no difference between PBC and controls. Osteopoenic PBC patients (T-score < 1) showed significantly lower daily phosphorus intake [median: 672 (288-1374) vs. 921 (253-1923) mg/day; P = 0.037], with a trend towards lower caloric intake than their nonosteopoenic counterparts. CONCLUSIONS: Renal tubular acidosis is uncommon in compensated PBC. Cholestasis is not associated with an increased risk of bone demineralization. Inadequate dietary intake may be a preventable factor contributing to bone loss in PBC.

Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis.

Liver disease is increasingly recognized as a major cause of morbidity in cystic fibrosis (CF). Preliminary data suggest that ursodeoxycholic acid (UDCA) may be beneficial for treatment of this manifestation. We performed a double-blind, multicenter trial in these patients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides standard liver function tests. We also intended to establish whether taurine supplementation has a beneficial effect in patients receiving UDCA. From June to December 1990, we enrolled in 12 centers 55 CF patients with liver disease (39 male subjects; median age, 13.8 years). They were randomly assigned to receive for 1 year one of the following treatments: UDCA (15 mg/kg body weight daily) plus taurine (30 mg/kg body weight daily), UDCA plus placebo, placebo plus taurine, or double placebo. Clinical and laboratory evaluations were performed every 3 months. After 1 year, deterioration of overall clinical conditions, as indicated by the Shwachman-Kulczycki score (SKS), occurred in patients who received placebo but not in those who received UDCA (P = .025). Patients treated with UDCA also showed an improvement in gamma-glutamyl transpeptidase (GGT) (P = .004) and 5'-nucleotidase (P = .006) levels. Treatment with taurine was followed by a significant increase in serum prealbumin levels (P = .053), a trend toward a reduction in fat malabsorption, and no effect on the biochemical profile. No severe side effects occurred with any treatment. Thus, we concluded that UDCA administration improves clinical and biochemical parameters in CF patients with liver disease. Taurine supplementation may be indicated in patients with severe pancreatic insufficiency and poor nutritional status.

Parenteral calcitonin for metabolic bone disease associated with primary biliary cirrhosis.

No satisfactory treatment is available for metabolic bone disease associated with primary biliary cirrhosis. On the basis of the similarities to postmenopausal osteoporosis, the rationale exists for calcitonin to be tested in clinical studies in patients with primary biliary cirrhosis-associated osteoporosis. We evaluated the effect of calcitonin on bone metabolism and mineral density in 25 women with primary biliary cirrhosis and severe osteopenia. After 6 mo of observation, patients received a synthetic calcitonin or a control treatment consisting of less than one hundredth of the recommended dose of porcine calcitonin. The two treatments were administered in sequence to each patient for two 6-mo periods, with a 3-mo washout between them, according to a crossover design. After the observation period, oral calcium supplementation was started. Bone mineral density was measured by dual-photon absorptiometry of the lumbar spine at study entry and at the beginning and the end of each treatment period. During the observation period bone mineral density fell by 3.5% whereas during the following 6 mo it increased in both the patients who received calcitonin (4.3%) and those who received the control treatment (4.9%). Conversely, after the crossover, bone mineral density decreased during both calcitonin (-2.7%) and control treatment (-2.9%). A significant difference was observed between the two periods but not between the two treatments or between the two sequences of treatment administration. In conclusion, our findings indicate that parenterally administered calcitonin for 6 mo is ineffective in halting bone loss in patients with primary biliary cirrhosis-associated metabolic bone disease, whereas calcium supplementation may have a transient beneficial effect.

Efficacy and safety of a combination of chenodeoxycholic acid and ursodeoxycholic acid for gallstone dissolution: a comparison with ursodeoxycholic acid alone.

Chenodeoxycholic acid (CDC) and ursodeoxycholic acid (UDC) have distinct physicochemical and metabolic properties which, being complementary, should favor more rapid removal of cholesterol from gallstones when both bile acids are administered together. To see if the combination is more effective and well tolerated, we have compared 5 mg/kg of CDC plus 5 mg/kg of UDC with a 10-mg/kg dose of UDC alone in 120 patients with radiolucent, sonographically confirmed gallstones and characteristics favoring complete dissolution. Ursodeoxycholic acid was chosen as the reference because it dissolves stones faster and is better tolerated than CDC. To minimize the influence of stone size, the major determinant of dissolution, patients were divided, on admission, into two groups according to the maximum stone diameter: 50 had stones less than or equal to 5 mm, 70 had stones greater than 5 mm but less than 15 mm. The effects of treatment on stone dissolution evaluated by cholecystography and ultrasonography at 6, 12, and 24 mo, were analyzed by the actuarial life-table method. In the group with smaller stones, significantly more patients had obtained complete dissolution after treatment with the combination (52%) than after treatment with UDC alone (24%) at 6 mo. After longer periods, results were still better with the combination, although the differences from UDC alone became smaller. In the patients with larger stones, rates of complete and partial dissolutions were higher after treatment with the combination (51% vs. 24% with UDC) at 6 mo and again the differences had become smaller after longer treatment. Although not statistically significant, stone calcification occurred more often with UDC (7 cases) than with the combination (1 case). We conclude that CDC plus UDC is preferable to UDC alone because it dissolves stones more quickly, with a lower incidence of stone calcification, and may result in reduced cost of treatment.

Effects of a preparation containing a standardized ginseng extract combined with trace elements and multivitamins against hepatotoxin-induced chronic liver disease in the elderly.

A preparation containing a standardized ginseng extract which has been shown to exert anti-hepatotoxic activity in vitro, combined with trace elements and multi-vitamins was compared to placebo in 24 elderly out-patients with toxin-induced (alcohol and drugs) chronic liver disease in order to evaluate its effect on liver function. Each patient was blindly treated either with the preparation containing ginseng extract or placebo for 12 weeks. The preparation containing ginseng extract significantly modified bromsulphthalein retention and blood zinc levels when compared to pre-treatment levels and to placebo. Serum bile acids, and gamma-glutamyl transpeptidase before and after a fatty meal were significantly reduced after treatment with the test preparation and not with placebo. When the two treatment groups were compared, however, no significant difference in these parameters was observed. These results suggest that treatment with the preparation containing ginseng extract could improve the detoxifying activity of the liver in elderly patients with toxin-induced chronic liver disease.