L. Todros

Effects of long-term Irbesartan in reducing portal pressure in cirrhotic patients: comparison with propranolol in a randomised controlled study

BACKGROUND/AIMS The role of angiotensin II (AT-II) type I receptor antagonists in the treatment of portal hypertension remains controversial. We tested the efficacy of Irbesartan (Irb) vs. Propranolol (Pro) in reducing portal pressure and evaluated its systemic haemodynamic effects. METHODS Thirty-four patients were randomly assigned to receive either Irb 300 mg/day (19 patients) or Pro 40-120 mg/day (15 patients) for 2 months. RESULTS Irb was discontinued in five patients (26%). No major side effect occurred in the Pro group. On an average, the portal pressure gradient decreased significantly more in the Pro than in the Irb group (median -19.5%, range -11/-31% vs. -4.8%, +2.5/-10%, P<0.001). A clinically significant decrease was seen in one (7%) of the patients given Irb vs. five (33%) given Pro (P<0.02). The fall in mean arterial pressure was significantly higher with Irb than with Pro (median -29%, range -15/-45% vs. -4.9%, +8/-19%, P<0.02). Irb significantly modified the blood creatinine clearance (median -29 ml/m, range +9/-61 ml/m, -30, -24/-35% P<0.0001 vs. basal). CONCLUSIONS Irb offers no advantage over Pro in the control of portal hypertension. Moreover, its therapeutic profile is limited by important side effects.

EFFICACY OF IRBESARTAN, A RECEPTOR SELECTIVE ANTAGONIST OF ANGIOTENSIN II, IN REDUCING PORTAL HYPERTENSION

The use of angiotensin II antagonists in the treatment of portal hypertension remains controversial. Our aims were to assess the effect of Irbesartan on portal pressure and to evaluate its safety in cirrhotic patients with portal hypertension. Twenty-five cirrhotic patients were treated in a pilot study with Irbesartan 300 mg orally once daily for 60 days. Hemodynamic evaluations and biochemical tests were performed before therapy and after two months of treatment. Three patients (12%) discontinued treatment for symptomatic arterial hypotension (mean arterial pressure −26.% ± 3.1 versus basal). In the 18 responders, the hepatic venous pressure gradient diminished by a mean of 18.1% ± 10.5 from baseline (p = 0.02); the gradient decreased by 20% or more in only 5 patients (23%). The mean arterial pressure decreased significantly during therapy (92 ± 7 vs 109 ± 25 mm Hg, P < 0.001). In conclusions, Irbesartan induced a marginal reduction in portal pressure and its safety was limited by the pronounced effects on arterial pressure.

Lymphocytic gastritis and protein-losing gastropathy

Lymphocytic gastritis is a histopathological entity of unknown aetiology which is characterized by dense surface and foveolar epithelial T-cell infiltration. We report here an uncommon clinical presentation in a young female presenting with unexplained recurrent weight loss and peripheral oedema. Endoscopic and histological features before and after successful therapy with omeprazole are described.

Systemic nitric oxide production and renal function in nonazotemic human cirrhosis: A reappraisal

OBJECTIVES: Several studies in human cirrhosis have demonstrated increased nitric oxide (NO) production. In experimental animals, intracerebroventricular administration of NO donors causes a marked depression of the endogenous dopaminergic activity, a function known to be physiologically recruited and exerting a natriuretic function in patients with compensated cirrhosis. The aim of this study is to evaluate the interaction between the systemic plasma levels of NO, the endogenous dopaminergic activity and the main parameters of renal function in patients with liver cirrhosis of differing degrees of severity. METHODS: A total of 21 patients (11 with preascitic and 10 with nonazotemic diuretic-free ascitic cirrhosis) and 10 healthy control subjects underwent the following tests: a) basal plasma renin activity (PRA) and aldosterone levels; b) renal clearances of sodium, potassium, inulin, para-minohippurate and lithium (the latter being a measure of the fluid delivery to the distal nephron); c) NO systemic plasma levels measured through paramagnetic resonance spectroscopy as nitrosylhemoglobin complexes; d) endogenous dopaminergic activity, evaluated by means of the incremental prolactin and aldosterone plasma levels after dopaminergic blockade with i.v. metoclopramide. RESULTS: NO plasma values and endogenous dopaminergic activity, although significantly increased with respect to healthy controls, were not different in the two groups of patients. The plasma NO/PRA ratio was significantly higher in the group of compensated patients with respect to ascitic cirrhotics (respectively, 18.3 ± 11.8 vs 3.5 ± 2.6 A.U./ng/ml/h, p < 0.001). Compared with compensated cirrhotics, patients with ascites showed significantly lower values of glomerular filtration rate (GFR) and renal plasma flow (RPF). Interestingly, GFR values were substantially the same in the ascitic patients and the control subjects. Compensated patients displayed a significant positive correlation between metoclopramide-induced incremental aldosterone plasma levels (i.e., endogenous dopaminergic tone) and fractional excretion of sodium (r = 0.58; p < 0.05). In the group of compensated patients, NO levels correlated inversely with creatinine plasma concentrations (r = −0.85; p < 0.001) and directly with inulin clearance (r = 0.65; p < 0.05). CONCLUSIONS: These data show that, at least in compensated cirrhotic patients, the stimulation of systemic NO production and the increased dopaminergic function may be mechanisms preventing renal perfusion, GFR, and fractional excretion of sodium from precocious reductions.

⁎4532 Clinical application of endoscopic ultrasound in portal hypertension: eus can predict variceal recurrence in endoscopically treated patients.

BACKGROUND AND AIM: 210 After endoscopic eradication of oesophageal varices by means of sclerotherapy or rubber-band ligation, varices recurrence remains a maior problem. Some studies suggested that in patients with endoscopic signs of varices obliteration, EUS may demostrate still patent residual lumina in the esophageal wall. The aim of our study was to assess if EUS can supply usefull information in the evaluation of endoscopic varices eradication in order to predict variceal recurrence and rebleeding.MATERIAL AND METHODS: 107 patients (74 men, mean age 56±11 years) bleeding from gastroesophageal varices underwent endoscopic treatment by means of sclerotherapy or rubber-band ligation until obtaining endoscopic eradication of oesophageal varices in 104 of them. Then they underwent EUS with a rotating sector scanner (Olympus GF-UM3/UMQ130) within 1 month from the treatment. Eighty-six of the 104 eradicated patients had an endoscopic follow-up (8.8 ± 7.1 months) to evaluate the recurrence of oesophageal varices. RESULTS: 56 of the endoscopically eradicated patients (65%) were not judged completely eradicated by EUS, because it made possible to identify still patent variceal lumina or just partially thrombosed vessels or some small residual anechoic structures in the oesophageal wall. Forty-one of them (73%) developed recurrence of oesophageal varices, while just 8 out of the remaining 30 patients (27%), judged eradicated by both endoscopy and EUS, showed oesophageal varices in the follow-up (Chi-square P=0.02). CONCLUSIONS: EUS detects more patent residual vessels in the esophageal wall than endoscopy after endoscopic variceal eradication by means of sclerotherapy or rubber-band ligation. These EUS findings may have a precise clinical impact: predicting variceal recurrence they can indicate the need of further endoscopic therapy.

4756 Eus can supply information of clinical usefulness and prognostic value in evaluating patients with portal hypertension (ph).

Purpose: EUS can be of value in evaluating gastroesophageal signs of PH. The aim of our study was to show that EUS may add usefull information to the endoscopic diagnosis of gastroesophageal complications of PH and it can be more sensitive than endoscopy at gastric level. Methods: 149 patients (pts) (105 men, mean age 55±12 years) with endoscopic signs of PH underwent EUS with a rotating sector scanner (Olympus GFUM3/UMQ130). 107 pts were endoscopically treated after bleeding until obtaining oesophageal eradication in 104. Afterward they underwent EUS within 1 month. 109 pts were followed up by endoscopy. Results: gastric varices were diagnosed in 14 of the 109 followed up pts (13%) by endoscopy and in 32 (29%) by EUS. Of the 95 pts without gastric varices at endoscopy 21 (22%) were positive at EUS and 2/21 (9%) developed them during the follow-up. Conversely 3/74 pts without gastric varices at endoscopy and EUS developed them successively (4%). About junctional varices 18/109 (16%) pts were positive at endoscopy, 54/109 (50%) at EUS. Of the 91 pts without junctional varices at endoscopy 43 resulted positive at EUS (47%) and 11/43 (26%) developed them during the follow-up versus 2/48 pts (4%) without junctional varices at EUS (Fisher exact test P=0.026). 111/148 showed EUS features described as typical for congestive gastropathy (CG), while only 61/148 were positive at endoscopy (Chi-square P=0.023). Conversely 37/148 pts did not show any typical signs of CG at EUS versus 87/148 at endoscopy (Chi-square P=0.001). Conclusion: according to the literature in our study EUS detected more gastric and junctional varices than endoscopy. EUS supplied usefull information to predict the development of new junctional varices during the follow-up of pts previously endoscopically negative. Unluckily the number of pts is still too small for any statistically significant meaning of EUS in predicting the development of new gastric varices. Furthermore EUS seems to have a very high positive and an even higher negative predictive value in detecting CG compared to endoscopy.