The primary objective of drug therapy in portal hypertension is the prevention of variceal bleeding. The use of nonselective ␤-blockers that reduce portal pressure by lowering splanchnic blood inflow 1 has proved effective in this indication. Treatment with propranolol or nadolol reduces the risk of first hemorrhage 2 as well as that of further bleeding episodes in patients with a history of variceal bleeding. 3 However, the average reduction in portal pressure by 15% achieved with ␤-blockers is moderate, 4 and no relevant decrease is observed in more than 30% of patients despite adequate dosage. 5 To enhance the pressure-lowering effect on portal hypertension, ␤-blockers are combined with isosorbide-5 mononitrate, 6 an agent that reduces portal pressure in cirrhosis because of its vasodilator properties. 7 One study demonstrated a mean reduction in portal pressure of 19% during therapy with the combination of propranolol and isosorbide-5 mononitrate. 6 In patients with sodium retention and ascites, however, serious deterioration of renal function was observed with the combination of ␤-blockers and nitrates. 8 The limited effect on portal pressure, the incidence of adverse effects-15% for nonselective ␤-blockers alone, 9 16% for nadolol plus isosorbide-5 mononitrate 10 -and the timeconsuming dose-finding are a stimulant for the search for new antihypertensive substances.Angiotensin II is considered a potential mediator of intrahepatic portal hypertension, because its plasma level is elevated in cirrhosis 11 and its administration induces a rise in portal pressure. 12 Enhancement of the adrenergic vasoconstrictor influence on the portal systems, 13 direct contractile influence on stellate cells, 14 which serve as regulators of the sinusoidal blood flow, 15,16 and sodium and fluid retention induced by the stimulation of aldosterone secretion 17 may be mechanisms that contribute to the portal hypertensive effect of angiotensin II. Losartan is an angiotensin II receptor antagonist with dilatory effects on arteries and veins. 18 The substance has recently been approved for the treatment of arterial hypertension. As yet, its influence on portal hypertension has not been investigated. The aim of this study was to determine the antihypertensive effects of losartan on portal pressure with particular attention paid to potential side effects. PATIENTS AND METHODSPatients. In patients with cirrhosis and esophageal varices, portal hypertension was evaluated by the determination of hepatic venous pressure gradient (HVPG). Thirty consecutive patients with HVPG Ն 20 mm Hg (severe portal hypertension) were assigned to losartan treatment according to the below-mentioned protocol. In accordance with Armonis et al., 19 our preliminary investigations had shown a variability of Ϯ 1 mm Hg in the measurement of HVPG independent from the height of the values. Therefore, this initial selection of patients with high HVPG values was performed to reduce the influence of variability on the percentage change in HVPG caused by losartan. Later,...

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From 1 January 1983 to 1 January 1989 123 cirrhotic patients with hepatocellular cancer (n = 122) or cholangiocarcinoma (n = 1) were screened using liver function tests, alpha-fetoprotein determination, ultrasonography with biopsy (and in selected cases computed tomography or nuclear magnetic resonance), laparoscopy and angiography, Child-Pugh classification and urea-nitrogen synthesis rate. Twenty-three patients were selected for surgical resection because the tumour was smaller than 5 cm, not centrally located and at least 1 cm away from main structures; there was no evidence of multicentricity or metastatic disease; and the Child-Pugh classification was A or B and the urea-nitrogen synthesis rate at least 6 g/day. Upper gastrointestinal endoscopy was used routinely to identify oesophageal varices which were present in 17 cases; ten patients with a history of variceal haemorrhage (43 per cent) had preoperative endoscopic sclerotherapy. In cases with recurrent haemorrhage, surgery was used to prevent intraoperative and postoperative bleeding. Tumour resection was carried out using controlled hypotension and hepatoduodenal ligament clamping. Twelve bisegmentectomies, ten segmentectomies and one atypical resection were performed. The operative mortality rate was 13 per cent with liver failure and sepsis as the causes of death. The 'recurrence rate' was 26 per cent and the late mortality rate for the whole group up to 1 January 1990 was 30 per cent; 13 patients were still alive. The 12-month survival rate was 77 per cent and after 5 years it was 49 per cent. Thus, surgical resection of small liver tumours is the treatment of choice in this selected group of patients.

Controlled trials of sclerotherapy for the prevention of the first variceal hemorrhage in cirrhotics have given conflicting results, in spite of an initial positive controlled trial. We designed therefore a new study in which only 89 of 396 investigated patients were randomized to sclerotherapy (44 patients) or a control group (45 patients). The admission criteria were: no history of variceal bleeding, the presence of high risk varies, i.e., varices of degrees III and IV with minivarices on the surface of them, and portal pressure over 16 mmHg. Sclerotherapy sessions were performed at 0, 7, 14, 21, and 28 days, until the varices were reduced in size and completely covered by fibrous tissue. Follow-up endoscopy was performed at four-month and thereafter at six-month intervals. The control patients underwent repeated clinical investigation and endoscopy at six-month intervals. Bleeding episodes were treated by emergency endoscopic sclerotherapy in both groups, whenever possible. The mean follow-up was 33 months. The results were analyzed using Student's t-test and the log-rank test. Variceal bleeding occured in 11 sclerotherapy patients (25%) and 34 controls (75.6%) (p < 0.05). The overall mortality was 25% (11 patients) among the sclerotherapy patients and 69% (31 patients) in the controls (p < 0.01). Prophylactic endoscopic sclerotherapy was able to prolong survival in Child-Pugh classes A and B, but not in C. It is concluded that prophylactic endoscopic sclerotherapy does reduce the incidence of first variceal bleeding in cirrhotic patients, and is able to prolong survival if only high-risk patients are selected and the treatment is performed by endoscopic experts.

Fifty-seven patients with failed sclerotherapy received a mesocaval interposition shunt with an externally supported, ringed polytetrafluoroethylene prosthesis of either 10 or 12 mm diameter. Thirty-one patients had Child-Pugh grade A disease and 26 grade B; all had a liver volume of 1000-2500 ml. Follow-up ranged from 16 months to 6 years 3 months. Three patients (5 per cent) died in the postoperative period. There were two postoperative recurrences of variceal haemorrhage and one recurrent bleed in the second year after surgery. The cumulative shunt patency rate was 95 per cent and the incidence of encephalopathy 9 per cent; the latter was successfully managed by protein restriction and/or lactulose therapy. The actuarial survival rate for the whole group at 6 years was 78 per cent, for those with Child-Pugh grade A 88 per cent and for grade B 67 per cent. Small-lumen mesocaval interposition shunting achieves portal decompression, preserves hepatopetal flow, has a low incidence of shunt thrombosis, prevents recurrent variceal bleeding and is not associated with significant postoperative encephalopathy.