1,721,012 research outputs found
Hepatobiliary manifestations of cystic fibrosis
No full textCystic fibrosis is the most common, potentially lethal genetic defect in the Caucasian population. During recent years it has been increasingly associated with a number of hepatic and biliary abnormalities, of which chronic cholestatic liver disease is by far the most relevant. Plugging of intrahepatic bile ducts with inspissated secretions is thought to play a major role in the pathogenesis. Attempts have been made to provide uniform criteria to identify patients with early, possibly reversible, hepatic lesions, as well as to assess severity of liver disease. It has been estimated that bout 13% of cystic fibrosis patients present serum liver enzyme abnormalities, but prevalence of liver involvement is likely to be higher. Due to decreasing mortality from extrahepatic causes in cystic fibrosis and to the widespread use of laboratory tests and ultrasound examination, patients with minor degree of liver involvement will be increasingly represented in future. Oral bile acid therapy is promising, but its long-term benefits in terms of survival and prevention of major complications of liver cirrhosis remain to be established. Liver transplantation is the only potentially curative treatment for patients with advanced stage liver disease and mild pulmonary involvement
Liver and biliary problems in cystic fibrosis
No full textLiver disease associated with cystic fibrosis has been increasingly diagnosed during recent years probably due to the combined effect of systematic hepatic assessment and reduced death from extra-hepatic causes of CF patients. In a group of 173 CF patients regularly followed at our Center, cumulative incidence of liver disease was 17% over a mean period of 10 years. Although it generally runs a mild course, it is considered a major complication of CF which may limit survival and quality of life of affected patients. CF-associated liver disease should be considered as the first inherited liver disorder in which the primary defect affects cholangiocyte transport systems. Although data assessing the effects of defective CFTR on cholangiocyte pathobiology are not yet available, the impaired secretory function of the biliary epithelium is considered responsible for reduced biliary fluidity and alkalinity and for subsequent bile duct damage by cytotoxic compounds or infectious agents. No clear association with specific CFTR mutations has been observed. Treatment with ursodeoxycholic acid, aimed at improving biliary secretion in terms of bile viscosity and bile acid composition, is currently the most useful therapeutic approach in CF-associated liver disease. Beneficial effects on liver biochemistry, hepatic excretory function, liver histology, and essential fatty acid status have been reported, but no long-term data exist on its effectiveness on clinically relevant outcomes, such as death or need for transplantation. The effectiveness of bile acid therapy may be higher if started in patients with early stage liver disease, before symptoms have become clinically evident. Early diagnosis and identification of CF patients who are more liable to develop liver disease should be actively pursued
Liver disease in cystic fibrosis: A prospective study on incidence, risk factors, and outcome
No full textIncidence of liver disease (LD) associated with cystic fibrosis (CF) and its clinical characterization still is unsettled. We have assessed prospectively the incidence and risk factors of this complication, and its impact on the clinical course of CF. Between 1980 and 1990, we enrolled 177 CF patients without LD in a systematic clinical, laboratory, ultrasonography screening program of at least a 10-year duration. During a 14-year median follow-up (2,432 patient-years), 48 patients developed LD, with cirrhosis already present in 5. Incidence rate (number of cases per 100 patient-years) was 1.8% (95% confidence interval: 1.3-2.4), with sharp decline after the age of 10 years and higher risk in patients with a history of meconium ileus (incidence rate ratio, 5.5; 2.7-11), male sex (2.5; 1.3-4.9), or severe mutations (2.4; 1.2-4.8) at multivariate analysis. Incidence of cirrhosis was 4.5% (2.3-7.8) during a median period of 5 years from diagnosis of liver disease. Among the 17 cirrhotic patients, 13 developed portal hypertension, 4 developed esophageal varices, 1 developed liver decompensation requiring liver transplantation. Development of LD did not condition different mortality (death rate ratio, 0.4; 0.1-1.5) or higher incidence of other clinically relevant outcomes. In conclusion, LD is a relatively frequent and early complication of CF, whose detection should be focused at the first life decade in patients with history of meconium ileus, male sex, or severe genotype. Although LD does not condition a different clinical course of CF, in some patients it may progress rapidly and require liver transplantation
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
No full textLiver 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
Failure of ursodeoxycholic acid to prevent a cholestatic episode in a patient with benign recurrent intrahepatic cholestasis: a study of bile acid metabolism
No full textUrsodeoxycholic acid was administered to a patient with benign recurrent intrahepatic cholestasis to prevent cholestatic episodes. A detailed study of bile acid metabolism in this patient was carried out in the anicteric and icteric phases before and after ursodeoxycholic acid (750 mg/day) administration. Urinary, biliary and serum bile acids were measured by gas chromatography-mass spectrometry and by high-performance liquid chromatography techniques. During the anicteric phase the daily urinary excretion and serum concentrations of bile acids were within normal ranges, indicating normal hepatic uptake and secretion of bile acids during the cholestasis-free period. Only slight qualitative differences from normal individuals were observed; the relative proportions of deoxycholic acid in the bile and serum were higher, and 12-oxo-lithocholic acid was the predominant urinary bile acid. During the icteric phase a marked increase in the urinary excretion of primary bile acids and C-1, C-2, C-4 and C-6 hydroxylated metabolites was found. Serum bile acid concentrations increased before the rise in bilirubin, suggesting an acute disturbance in bile acid transport at the onset of the cholestatic attack. After ursodeoxycholic acid administration in the anicteric phase, bile became enriched with the exogenous bile acid, but little qualitative change was found in the other metabolites present in the urine, serum or bile during the anicteric or icteric phases. Prolonged administration of ursodeoxycholic acid failed to prevent recurrence of a cholestatic episode, suggesting that in benign recurrent intrahepatic cholestasis, oral ursodeoxycholic acid may be of little benefit in the treatment or prevention of cholestasis despite marked enrichment of the bile acid pool with this hydrophilic bile acid
Clinical features and management of primary biliary cirrhosis
No full textPrimary biliary cirrhosis (PBQ, which is characterised by progressive destruction of intrahepatic bile ducts, is not a rare disease since both prevalence and incidence are increasing during the last years mainly due to the improvement of case finding strategies. The prognosis of the disease has improved due to both the recognition of earlier and indolent cases, and to the wide use of ursodeoxycholic acid (UDCA). New indicators of prognosis are available that will be useful especially for the growing number of patients with less severe disease. Most patients are asymptomatic at presentation. Pruritus may represent the most distressing symptom and, when UDCA is ineffective, cholestyramine represents the mainstay of treatment. Complications of long-standing cholestasis may be clinically relevant only in very advanced stages. Available data on the effects of UDCA on clinically relevant end points clearly indicate that the drug is able to slow but not to halt the progression of the disease while, in advanced stages, the only therapeutic option remains liver transplantation
Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis. A dose-response study
No full textTauroursodeoxycholic acid, a highly hydrophilic bile acid, may be of therapeutic value for chronic cholestatic liver diseases. We performed a dose-response study on 24 patients with primary biliary cirrhosis who were randomly assigned to receive 500, 1000, or 1500 mg daily of tauroursodeoxycholic acid for six months. Biliary enrichment with ursodeoxycholic acid ranged from 15% to 48% and was not related with the dose. Serum liver enzyme levels decreased significantly after the first month of treatment with all the three doses. No significant difference among the three doses was found, although further reduction over time occurred with 1000 and 1500 mg daily. Plasma total and HDL cholesterol significantly decreased in patients administered the two higher doses. Diarrhea was the only side effect. In conclusion, a dose of about 10 mg/kg body wt/day of tauroursodeoxycholic acid should be used for long-term studies in patients with primary biliary cirrhosis
Effects of a preparation containing a standardized ginseng extract combined with trace elements and multivitamins against hepatotoxin-induced chronic liver disease in the elderly
No full textA 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
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