Antoine Hadengue

Pulmonary Hypertension Complicating Portal Hypertension: Prevalence and Relation to Splanchnic Hemodynamics

The prevalence of pulmonary hypertension in 507 patients hospitalized with portal hypertension but without known pulmonary hypertension who underwent cardiac catheterization was prospectively studied. Ten (2%) of these patients, 6 of whom were clinically asymptomatic, had primary pulmonary hypertension. Second, 26 patients with symptomatic pulmonary hypertension complicating portal hypertension were reviewed. Pulmonary hypertension occurred later after diagnosis of portal hypertension in patients with a surgical shunt (10 patients) than in those without a shunt (147 +/- 49 vs. 44 +/- 27 months; P less than 0.0001). Cardiac index correlated inversely with pulmonary arterial pressure (r = -0.45; P less than 0.01) and was lower in the 5 patients who died of pulmonary hypertension than in the 5 who died of liver failure (1.52 +/- 0.14 vs. 3.69 +/- 1.88 L/min.m2; P less than 0.05). Third, systemic and splanchnic hemodynamics were compared in 285 patients with alcoholic cirrhosis and 29 controls. No significant relation was found between elevated pulmonary vascular resistance and increased portal pressure, zzygos blood flow, or cardiac index. Pulmonary hypertension is considerably more frequent than was previously estimated in patients with portal hypertension. The risk of developing pulmonary hypertension could increase with the duration of portal hypertension without any clear relation to the degree of portal hypertension, hepatic failure, or amount of blood shunted.

Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial

Abstract Background/Aims: Transjugular intrahepatic portosystemic shunts reduce portal pressure and can control ascites in patients with cirrhosis. We carried out a controlled study to evaluate this procedure for the management of refractory ascites in patients with cirrhosis and to clarify its mechanism of action. Methods: Twenty-five patients with refractory ascites were included in the trial; 13 were randomly assigned to shunts and 12 to paracentesis. Four patients in each group were Child-Pugh class C and the others were class B. Follow-up ranged from 9 to 34 months. Hemodynamic values, liver and renal tests and neurohumoral factors were measured before and at 4 months after inclusion. Results: Shunts were successfully placed in 10 out of 13 patients. At 4 months, ascites had improved in all class B patients in the shunt group and in none of the patients in the paracentesis group ( p p Conclusions: In this trial, intrahepatic shunts were effective on refractory ascites in patients with cirrhosis. However, the overall survival rate was lower in shunted patients than in those treated with paracentesis. The efficacy of intrahepatic shunts on ascites was only observed in class B patients. Survival did not improve in class B patients, and decreased in class C patients compared to paracentesis. The efficacy of shunts on ascites might be due to neurohumoral factors which control natriuresis and depend on hepatic sinusoidal pressure.

The changing scene of hepatic vein thrombosis: Recognition of asymptomatic cases

BACKGROUND/AIMS Hepatic vein thrombosis is thought to be manifested by ascites, abdominal pain, and hepatomegaly, with a uniformly poor prognosis. However, new imaging techniques allow for the diagnosis of hepatic vein thrombosis in asymptomatic cases. The aim of our study was to re-evaluate symptoms and prognosis in patients with hepatic vein thrombosis. METHODS Eighty-one patients with hepatic vein thrombosis were analyzed. Forty-seven patients were admitted from 1970 to June 1987 (group I, before Doppler ultrasonography and magnetic resonance imaging were introduced at our hospital) and 34 from July 1987 to June 1991 (group II). RESULTS When comparing the two groups, age, sex ratio, and causes of hepatic vein thrombosis did not differ. Eight group II patients (asymptomatic patients) had no ascites, hepatomegaly, or abdominal pain. One major hepatic vein remained patent in 41% of group II patients, compared with 12% in group I (P < 0.05). Intrahepatic collaterals were seen in 79% of group II patients, compared with 21% of group I patients (P < 0.01). All asymptomatic patients had large intrahepatic and portasystemic collaterals. At 3 years, death occurred in 22% of group II patients and in 45% of group I patients. No asymptomatic patient died. CONCLUSIONS Asymptomatic hepatic vein thrombosis is associated with the spontaneous development of large intrahepatic and portosystemic collaterals. In asymptomatic patients, prognosis at 3 years seems to be good, and surgical therapy may not be required.

Beneficial effects of the 2-day administration of terlipressin in patients with cirrhosis and hepatorenal syndrome

Background/Aims: A treatment to induce a sustained increase in glomerular filtration rate in patients with hepatorenal syndrome has not yet been identified. Thus, the aim of the present study was to investigate the effects of terlipressin for 2 days on the glomerular filtration rate in patients with cirrhosis and hepatorenal syndrome. Methods: A double-blind, cross-over randomized study was performed in nine patients. Patients received terlipressin (2 mg/day for 2 days) and a placebo for 2 days in a randomized order. Results: Terlipressin administration significantly increased creatinine clearance (from 15 ± 2 ml/min to 27 ± 4 ml/min) and urine output (from 628 ± 67 ml/day to 811 ± 76 ml/day), but did not significantly change urinary sodium concentrations. Urinary sodium excretion was not significantly different after placebo administration (0.6 ± 0.1 mmol/24 h) and terlipressin administration (9.3 ± 7.2 mmol/24 h). Terlipressin administration significantly decreased plasma concentrations of renin and aldosterone but not atrial natriuretic peptide levels. Placebo elicited no significant effects. Conclusions: This study shows that 2-day terlipressin administration increases the glomerular filtration rate in patients with cirrhosis and hepatorenal syndrome.

Peroxisome proliferator-activated receptor-α and -γ mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection

Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis.

Hypoxemia in patients with cirrhosis: relationship with liver failure and hemodynamic alterations

BACKGROUND/AIMS The relationship between hypoxemia, liver failure and the hemodynamic alterations in cirrhosis are unknown. This study examined the relationship between arterial hypoxemia, the severity of liver disease and hyperkinetic circulation in patients with cirrhosis. METHODS Arterial blood gases, the severity of cirrhosis (Child-Pugh score), and splanchnic and systemic hemodynamics were measured in 120 patients with cirrhosis and without cardiopulmonary disease. Hypoxemia was considered to be present when PaO2 was < or = 70 mmHg. RESULTS Seventeen patients had hypoxemia (14%). Hypoxemic patients had significantly lower pulmonary vascular resistance and a significantly higher alveolar-arterial oxygen gradient, Child-Pugh score and hepatic venous pressure gradient than non-hypoxemic patients. Cardiac index and right atrial and pulmonary pressures did not significantly differ between the two groups. CONCLUSIONS Hypoxemia occurs mainly in patients with severe liver disease and is associated with pulmonary vasodilation.

Reduction of Intrahepatic Vascular Space in the Pathogenesis of Portal Hypertension In Vitro and In Vivo Studies in the Rat

To elucidate a possible role for reduction of intrahepatic vascular space in the pathogenesis of portal hypertension, we studied a partially hepatectomized rat model in vitro and in vivo. The in vitro study used livers from normal, 1/3-hepatectomized, and 2/3-hepatectomized rats, and rats with cirrhosis caused by chronic bile duct ligation, for isolated, perfused flow-pressure plotting. Resistance to perfusion increased such that significant differences were found between all groups except the last two, which showed similar resistances. The in vivo study measured splanchnic blood flow by radioactive microspheres and portal pressure in anesthetized sham-operated and 1/3- and 2/3-hepatectomized rats. Although absolute portal tributary blood flows did not change, portal flow per gram of remnant liver showed significant increases: 1.57 +/- 0.32 ml/min X g liver, 2.52 +/- 0.60 ml/min X g liver, p less than 0.01; 3.48 +/- 1.04 ml/min X g liver, p less than 0.01, respectively. Although intrahepatic resistance increased significantly only in the 2/3-hepatectomized group, portal pressures increased significantly in both groups of hepatectomized rats: normal, 7.5 +/- 1.1 mmHg; 1/3-hepatectomized, 9.4 +/- 1.1 mmHg; and 2/3-hepatectomized, 11.1 +/- 1.2 mmHg. Thus, decreased intrahepatic vascular space caused by resection and hepatocellular hypertrophy leads to portal hypertension, thereby suggesting that this reduction in space may be the pathogenic factor common to a number of different theories of portal hypertension.

Circulatory effects of somatostatin analogue in two conscious rat models of portal hypertension.

A somatostatin analogue, a long-acting octapeptide (SMS 201-995), has been reported to decrease portal pressure, but the mechanism is unclear. To elucidate the effects of this drug on both systemic and splanchnic hemodynamics, it was administered in two conscious rat models of portal hypertension. The dose-response curves showed that the somatostatin analogue significantly decreased portal pressure at a lower dose in rats with cirrhosis than in portal vein-stenosed rats. Calculated ED50 values were significantly different among all groups. Intravenous infusion of 8 micrograms/kg body wt.h of somatostatin analogue significantly decreased cardiac output by approximately 20% in both groups of portal hypertensive rats and increased mean arterial pressure by 7%. Accordingly, systemic vascular resistance markedly increased, indicating vasoconstrictor effects of this drug. The somatostatin analogue also significantly decreased portal tributary blood flow by 18% in portal vein-stenosed rats and 27% in cirrhotic rats. In sham-operated rats, somatostatin analogue had no effect on the systemic or splanchnic circulation. This study shows that somatostatin analogue decreases portal pressure principally by reducing portal tributary blood flow. This reduction may be due to either a direct vasoconstrictive effect or diminution in vasoactive hormone release.

Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome : corticoresistance and effective treatment by cyclosporine A

SummaryWe report a case of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome treated with cyclosporine A. Features of primary biliary cirrhosis were pruritus, high titer of antimitochondrial antibodies, inflammatory infiltrates surrounding interlobular bile ducts, and periportal granuloma. Features suggestive of autoimmune hepatitis were high titer of antinuclear antibodies, very high total immunoglobulins, and piecemeal necrosis. Because corticosteroids and ursodeoxycholic acid were inefficient, cyclosporine A was started at a dose of 3 mg/kg/day. A dramatic improvement in clinical condition, liver tests, and histology was noted. Discontinuation of cyclosporine A was followed by a clinical and histological relapse. Cyclosporine A reintroduction was again associated with a significant improvement. This case report suggests that in corticoresistant cases cyclosporine A could be an effective therapy for primary biliary cirrhosis-autoimmune hepatitis overlap syndrome.

Long-term sympathetic and hemodynamic responses to clonidine in patients with cirrhosis and ascites

The aim of the present study was to examine the short- and long-term effects of the alpha 2-agonist clonidine on sympathetic overactivity, systemic, splanchnic, and renal circulation changes, and abnormal renal sodium excretion in cirrhotic patients with ascites. Of 17 patients, 8 received clonidine and 9 a placebo. Measurements were taken before and after either a single dose of clonidine (150 micrograms) and placebo or a 1-week treatment with clonidine (150 micrograms/day) and placebo. Clonidine but not placebo induced significant short- and long-term decreases in plasma norepinephrine concentrations in the pulmonary artery and the right renal vein. Acute clonidine administration induced a significant reduction in cardiac output, heart rate, arterial pressure, and hepatic venous pressure gradient but had no effect on renal hemodynamics. Long-term clonidine administration induced a significant decrease in the hepatic venous pressure gradient from 20.1 +/- 1.9 to 17.6 +/- 2.0 mm Hg (mean +/- SEM) but had no significant effects on systemic or renal hemodynamics or renal excretion of sodium. It is concluded that long-term clonidine administration in cirrhotic patients induced a sustained decrease in sympathetic nervous activity and portal pressure. In contrast, clonidine had no prolonged effect on systemic hemodynamics. In addition, short- and long-term clonidine administration did not modify renal hemodynamics or induce a natriuretic response in patients with ascites.