BACKGROUND:In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) significant therapeutic effects of glucocorticoids have not been documented. The most important clinical problem in patients with these diseases is fatigue, which is occasionally invalidating. Abnormalities in the hypothalamo-pituitary-adrenal axis have been suggested as a cause of fatigue. Most effects of glucocorticoids are mediated by the glucocorticoid receptor (hGR alpha). Recently a causative role for a splicing variant of the glucocorticoid receptor (hGR beta) has been proposed in glucocorticoid resistance in asthma and ulcerative colitis, whereas another splicing variant (hGR P) might be associated with glucocorticoid-resistant haematological malignancies. The aims of the present pilot study were to assess abnormalities in glucocorticoid receptor expression and to relate these abnormalities to the development of fatigue and to disease activity and severity in autoimmune cholestatic liver disease.METHODS:Five fatigued and five nonfatigued patients with PBC or PSC were included, and the results were compared with healthy controls.RESULTS:The expression of hGR P was not different from controls, but hGR beta mRNA was significantly increased (p=0.02) and hGR alpha mRNA decreased (p=0.015). There were no significant differences between fatigued and nonfatigued patients. A significant negative correlation between the serum activity of alkaline phosphatase and hGR alpha and hGR P mRNA was found.CONCLUSION:Although there was no relation with fatigue, abnormalities in hGR expression appear to occur in patients with these diseases, and may play a role in its pathophysiology and the poor response to glucocorticoid treatment.

PURPOSE:To retrospectively assess the outcome of transjugular intrahepatic portosystemic shunt (TIPS) placement in a nonselected group of consecutive patients.MATERIALS AND METHODS:TIPS placement was attempted in 82 patients. Patients were followed up for at least 3 years according to a standard protocol that included repeated shunt evaluations. Fifty-four patients underwent TIPS placement for variceal bleeding, 24 for refractory ascites, and four for other indications. Recurrent bleeding, effect on ascites, long-term patency, development of encephalopathy, and survival and complication rates were evaluated with Kaplan-Meier survival analysis and Cox multivariate analysis.RESULTS:TIPS placement was successful in 75 patients (91%). Mean follow-up lasted 29.4 months. Primary patency was 22% and 12%, primary-assisted patency was 67% and 46%, and secondary patency was 91% and 91% at 1- and 5-year follow-up, respectively. Nonalcoholic liver disease (P =.007) and increasing platelet counts (P =.006) independently predicted development of shunt insufficiency. The 1- and 5-year rates of recurrent variceal bleeding were 21% and 27%, respectively. In the majority of patients with refractory ascites, a beneficial effect of TIPS placement was observed. The risk for encephalopathy was 25% at 1-month follow-up and 52% at 3-year follow-up. The risk for chronic or severe intermittent encephalopathy was 15% at 1-year follow-up and 20% at 3-year follow-up. Serum creatinine levels (P =.001) and age (P =.02) were independent risk factors. Overall survival rate was 61%, 49%, and 42% at 1-, 3-, and 5-year follow-up, respectively. Age (P =.03), serum albumin level (P =.02), and serum creatinine level (P <.001) were independently related to mortality.CONCLUSION:The risk for definitive loss of shunt function was 17% at 5-year follow-up, indicating that surveillance with shunt revision-when indicated-results in excellent long-term TIPS patency. TIPS placement effectively protects against recurrent bleeding.

Background: Since the introduction of TIPS (the transjugular intrahepatic portosystemic shunt) into clinical practice in 1989, substantial knowledge, partially derived from controlled trials, has become available regarding technical and clinical aspects of the procedure. A number of prospective studies have assessed the long-term patency of radiological shunts, the recognized main technical weakness of the procedure. Methods: Review of published data regarding the optimal indications and long-term patency of TIPS. Results: Information on the long-term patency of TIPS is surprisingly scarce. Within 2 years of TIPS creation, re-interventions to re-establish or maintain the patency of the shunt are required in 70%-90% of patients, and in 20%-40% total occlusion develops. Limited available data suggest, however, that in about 80% of patients the shunt is patent after 3-5 years. There is consensus that TIPS is a main, second-line treatment option for variceal haemorrhage not responding to other therapies. Although widely used for treating refractory ascites, gastric variceal bleeding and Budd-Chiari syndrome, these indications require more study. A number of other potential indications remain poorly defined. Conclusion: TIPS is a major treatment modality to manage the complications of portal hypertension and Budd-Chiari syndrome. The available data indicate that TIPS is not only a short-term treatment option but may provide long-term portosystemic decompression. Technical improvements, e.g. the use of covered or drug-eluting stents, are essential to reduce the high rate of shunt dysfunction.

The review editor sent me a book to review for Gut with holidays looming. He left a week before me and is currently observing whales off the east cost of the USA where I hope he will encounter the albino whale. I, on the other hand, am in a more peaceful location surrounded by the truly magnificent lochs, standing stones, stone circles, chambered cains, duns, and crannogs on the Outer Hebridean island of North Uist. The book Therapeutic Roles of Selective COX-2 Inhibitors is the latest in a series of similar books edited by Vane and Bolting, and I have found it in many ways as interesting and extraordinary as my surroundings. It exceeded all expectations, bringing …

ter Bora, P. C.J.; van Donselaar, M.; Laméris, J. S.; Vleggaar, F. P.; Groeneweg, M.; Hop, W. C.J.; van Buuren, H. R. Author Information