Role of hyperbilirubinemia in the impairment of osteoblast proliferation associated with cholestatic jaundice.

Because the osteoporosis occurring in chronic cholestatic liver disease (CCLD) is associated with decreased bone formation and is reversible by liver transplantation, substances retained in plasma during cholestasis may impair osteoblast function. This hypothesis was tested using a new bioassay that measures plasma mitogenic activity (PMA) for normal human osteoblast-like (hOB) cells. In 29 jaundiced patients, mean PMA was 56.4% (P < 0.001) of that in 29 age- and sex-matched normal subjects, and the decrease in PMA was similar in the 14 with CCLD and the 15 with other causes of jaundice. Bile acids and bilirubin are the two major groups of products retained during cholestasis. The common conjugated bile acids and bilirubin were added to normal human plasma in concentrations simulating those found in patients with CCLD. Various bile salts had no effect on PMA whereas unconjugated bilirubin decreased PMA in a dose-dependent fashion (r = -0.98, P < 0.0001) without affecting cell viability. Relatively selective removal of bilirubin from the plasma by photobleaching normalized the decreased PMA in five jaundiced patients but produced no apparent change in five normal subjects. These data support the hypothesis that hyperbilirubinemia or possibly other photolabile substances impair osteoblast proliferative capacity and thus may play a major role in the pathogenesis of the osteoporosis associated with CCLD.

Bone disease in primary biliary cirrhosis: does ursodeoxycholic acid make a difference?

Ursodeoxycholic acid (UDCA) has been proposed as beneficial therapy for patients with primary biliary cirrhosis (PBC). The effects of UDCA on metabolic bone disease, a major source of morbidity in patients with PBC, are essentially unknown. Preliminary information suggests that UDCA may improve biochemical indices of bone disease, although information about the effects of UDCA on bone density is lacking. In this study, we describe the effects of UDCA on lumbar spine bone mineral densities over a 3-year period during which patients were enrolled in a randomized, double-blind, therapeutic trial of UDCA for the treatment of PBC. Lumbar spine dual-photon densitometry was measured at entry and annually. Eighty-eight patients, 50 in the UDCA group and 38 in the placebo group, had serial measurements available for up to 3 years. There was no statistical difference between the two treatment groups at entry with respect to histological stage, total bilirubin, age, use of calcium supplement, vitamin D levels, or estrogen. After 3 years of treatment, there was no significant difference in the lumbar spine bone densitometry measurements between the UDCA-treated and placebo groups. We conclude that, after 3 years of treatment, UDCA is not associated with statistically significant differences in the rate of bone loss from the lumbar spine in patients when compared with placebo despite beneficial effects of treatment on the underlying liver disease. Further efforts to define effective treatments for the bone disease need to be pursued.

Short-term effects of recombinant human insulin-like growth factor I on bone turnover in normal women.

Because insulin-like growth factor I (IGF-I) is a potent stimulator of osteoblast proliferation, it has potential in the treatment of osteoporosis. However, IGF-I affects multiple organ systems, and it is unclear whether treatment can stimulate bone formation without producing unacceptable side effects. Therefore, we evaluated the effects of treatment with recombinant human IGF-I in 18 postmenopausal women who received various dosages (30, 60, 120, or 180 micrograms/kg.day) by sc injections for 6 days. Serum IGF-I concentrations increased by 2- to 4-fold during treatment. There were dose-dependent increases in serum type I procollagen carboxyl-terminal propeptide concentration (r = 0.85, P < 0.001), an index of collagen synthesis, and of urinary excretion of deoxypyridinoline (r = 0.75, P = 0.001), an index of bone collagen breakdown. At the two higher dosages, recombinant human IGF-I caused orthostatic hypotension, sinus tachycardia, bilateral parotid discomfort, weight gain, and edema in some women. Hypoglycemia did not occur. However, treatment at the 2 lower dosages increased serum type I procollagen carboxyl-terminal propeptide significantly and produced minimal or no side effects. Long-term studies on the effects and the safety of low dosage recombinant human IGF-I on bone mass should now be undertaken in osteoporotic women.

Liver cell adenoma at the age of 3 years and transplantation 19 years later after development of carcinoma: a case report.

A 3-yr-old child underwent biopsy of a nonresectable liver cell adenoma. She was well thereafter, but at the age of 22 yr, she underwent orthotopic liver transplantation because the lesion had grown. The alpha-fetoprotein level was 4,300. The specimen showed poorly differentiated hepatocellular carcinoma in a noncirrhotic liver. At this writing, the patient is well 32 mo after transplantation.

Outcome of patients hospitalized for complications after outpatient liver biopsy.

OBJECTIVE: To determine the safety of outpatient liver biopsies by analyzing the outcome of patients hospitalized for complications. DESIGN: Retrospective review. SETTING: Large clinic referral center. PATIENTS: All patients admitted after outpatient liver biopsy at the Mayo Clinic from 1 April 1989 to 1 April 1991. RESULTS: During this period, 405 outpatients underwent biopsy. Of the 405 patients, 13 (3.2%) were admitted with complications after biopsy. Five patients (38%) were admitted with persistent localized pain, five (38%) with orthostatic hypotension, one (8%) with both pain and hypotension, one (8%) with peritoneal signs, and one (8%) with lightheadedness but no orthostatic changes. All complications were noted within 3 hours after the biopsy. Bleeding, potentially the most serious complication, was radiographically defined in 5 of the 13 patients (38%) admitted. Only two patients, however, required blood transfusions. No patient required invasive management such as surgery or chest tube placement. The average length of the hospital stay was 1.5 days. CONCLUSION: Complications after outpatient liver biopsy occur early and rarely require invasive management. Outpatient liver biopsy is safe when done on carefully selected patients in a setting that provides close observation for at least 3 hours after liver biopsy.