Long-term prospective study of the effect of ursodeoxycholic acid on cystic fibrosis-related liver disease.

GOALS: To evaluate the efficacy of UDCA in arresting the progression of the early multifocal hepatic lesion to overt CF-related NBC. BACKGROUND: Focal biliary cirrhosis is an early hepatic pathologic change related to the ion transport defect in cystic fibrosis. The factors involved in the progression of focal to nodular biliary cirrhosis are not clear. Ursodeoxycholic--a hydrophilic, nontoxic, choleretic, and hepatoprotective exogenous bile acid--has been reported to be effective in the management of cholestatic liver disease. STUDY: For 10 years at 6-month intervals, 70 individuals with cystic fibrosis (38 men and 32 women; age range, 2--29 years) were examined using hepatosplenomegaly, liver function tests, and ultrasound liver scan. Patients demonstrating evidence of liver involvement at the onset or during the study received ursodeoxycholic acid 20 mg/kg body weight. RESULTS: After the administration of ursodeoxycholic acid, the progression of nodular biliary cirrhosis ultrasound changes was arrested, hepatic function was preserved, and no variceal bleeding was observed. No case of focal biliary cirrhosis progressed to nodular biliary cirrhosis. Furthermore, the multifocal, multilobular changes suggestive of focal biliary cirrhosis on ultrasound scan were reversed to normal. CONCLUSION: Ursodeoxycholic acid is effective in improving cholestasis and hepatic dysfunction in nodular biliary cirrhosis and, also, in reversing the early sonography findings suggestive of focal biliary cirrhosis. It is speculated that ursodeoxycholic acid may prove to affect the natural history of cystic fibrosis-related liver disease.

Role of electroretinography in the assessment of retinal function as an indicator of vitamin A status.

Hypovitaminosis A is associated with exocrine pancreatic insufficiency in cystic fibrosis. Peripheral retinal dysfunction is an early finding of vitamin A deficiency. We evaluated serum retinol and zinc as well as visual adaptation in 41 patients with cystic fibrosis, receiving generous pancreatic enzyme and micronutrient supplementation. Forty-one normal individuals matched for age and sex served as controls. Peripheral retinal function was measured by clinical electroretinography using an Electrophysiologic Personal Interfaced Computer and applying a standard protocol. Serum retinol in cystic fibrosis was significantly lower than that of the control group (0.30+/-0.01 versus 0.39+/-0.02 mg/l, p<0.001). Serum zinc concentrations were normal in the cystic fibrosis group (1.21+/-0.03 mg/l) and significantly higher than that of the control group (1.02+/-0.01 mg/l, p<0.001). The overall visual adaptation, however, was found to be normal and comparable in the two groups. It is concluded that, in cystic fibrosis, despite appropriate vitamin A supplementation, retinol serum concentration may be low. As serum retinol does not reflect vitamin A status, evaluation of visual adaptation may be a more appropriate way to monitor for vitamin A deficiency in cystic fibrosis.

Influence of jejunal morphology changes on exocrine pancreatic function in celiac disease.

BACKGROUND: Concurrent exocrine pancreatic dysfunction may be one of the factors implicated in malabsorption in untreated celiac disease, as shown by studies on bicarbonate and pancreatic enzyme secretion. The purpose of this study was to evaluate exocrine pancreatic function in relation to jejunal morphology in celiac disease. METHODS: Thirty-six patients fulfilling the ESPGHAN criteria for celiac disease, aged 3 to 18 years and 36 control subjects matched for age and sex were investigated. The design of the study included measurement of serum pancreatic isoamylase by a chromogenic method after selective inhibition of sialic isoamylase in the untreated phase in patients consuming a gluten-containing diet and after gluten elimination for a period of 1 year; fecal human elastase activity determined by enzyme-linked immunosorbent assay in patients consuming a gluten-free diet and again after gluten challenge for 6 months; correlation of serum pancreatic isoamylase and fecal elastase to the jejunal morphology, classified by criteria described by Marsch; the enzymes in the control group; and ultrasonography of the pancreas in both groups. RESULTS: Enzyme values obtained from celiac disease patients with normal mucosa were significantly higher than those obtained from patients with villous atrophy (p < 0.001) and comparable to those obtained from the control group. Serum pancreatic isoamylase activity increased to normal after gluten elimination, and human elastase activity decreased to values below 200 microg/g of stool after gluten challenge. Enzyme activity was related inversely to the degree of intestinal damage. The echogenicity of the pancreas was normal, regardless of enzyme activity or gut morphology. CONCLUSIONS: Exocrine pancreatic function is abnormal in celiac disease when mucosal atrophy is present. Exocrine pancreatic function parameters are associated with the changes of intestinal mucosal morphology in three consecutive phases of the disease.

Autoantibodies predicting diabetes mellitus type I in celiac disease.

UNLABELLED: Celiac disease (CD) and diabetes mellitus type I (DM-I) are both autoimmune diseases. Abnormal first-phase insulin response (FPIR) is associated with the prediabetic phase. Glutamic acid decarboxylase (GAD) and islet cell antibodies (ICAs) - especially the tyrosine phosphatase-like protein IA-2 antibodies - are considered to be serological markers of DM-I future development. The aim of this study is to investigate the presence of autoantibodies (GAD, IA-2) in individuals with CD, on a gluten-free diet, who have normal intestinal morphology. Thirty patients with CD (4-22, mean 15 years), 30 newly diagnosed diabetic children (2.5-16, mean 10 years) and 30 healthy subjects (7-35, mean 18 years) were investigated. Serum GAD and IA-2 autoantibodies were assessed by a quantitative enzyme-linked immunosorbent assay (ELISA) method in all patients and controls. Seven CD patients (23%), 28 diabetic children (93%) and none in the control group had positive GAD and IA-2 antibodies. The FPIR was normal in CD patients (>/=46 mU/l). CONCLUSIONS: GAD and IA-2 antibodies are detected in 23% of patients with CD. These patients may be at risk to develop DM-I. Regular follow-up and determination of FPIR for the early diagnosis of the prediabetic phase in patients with CD having circulating autoantibodies is recommended.