Pierre Reding

ORAL ZINC SUPPLEMENTATION IMPROVES HEPATIC ENCEPHALOPATHY: Results of a Randomised Controlled Trial

22 cirrhotic patients with chronic encephalopathy were given oral zinc supplementation or placebo in a double-blind randomised trial. In the group which received zinc acetate 600 mg a day for 7 days, serum zinc had been restored to normal by day 8. On day 8 hepatic encephalopathy, as assessed by a trailmaking test, was improved in the supplemented group but not in the placebo group. There was also a significant increase in blood urea nitrogen in the supplemented group. Short-term oral zinc supplementation probably improved hepatic encephalopathy by correcting the zinc deficiency that compromises conversion of ammonia to urea. The duration of this improvement requires further investigation.

Insulin-like growth factor I : a good indicator of functional hepatocellular capacity in alcoholic liver cirrhosis

To assess the value of serum insulinlike growth factor I (IGF-I) determination in liver disease, 21 patients hospitalized for active alcoholic cirrhosis (19 males, 2 females), 56 ± 2 y (mean ± SE) were studied at admission. Individual scores of hepatic alterations (Child score) ranged from 6 to 12 (mean: 9 ± 1). Basal IGF-I levels were dramatically decreased, averaging 0.11 ± 0.02 U/ml vs 0.70 ± 0.08 U/ml in 15 control subjects. In cirrhotic patients, IGF-I values were inversely correlated with the modified Child index (r= −0.57, p < 0.01). A highly significant positive correlation (r = 0.68, p < 0.001) was evidenced between IGF-I levels and aminopyrine breath test values (which provide quantitative estimates of the hepatic functional capacity). In contrast, no significant relationship was found between IGF-I levels and various nutritional parameters (albumin, prealbumin, retinol binding protein) after partial correlation analysis. The present data suggest that, in alcoholic cirrhosis, the decrease of circulating IGF-I values is mainly related to alterations of liver function, and that IGF-I can be used as a good indicator of functional hepatocellular capacity.

Treatment of portal hypertension with isosorbide dinitrate alone and in combination with vasopressin

Experimental animal studies have suggested that certain vasodilators could minimize the adverse cardiovascular effects of vasopressin. We investigated the hemo-dynamic effects of isosorbide dinitrate, alone and in combination with vasopressin, in patients with liver cirrhosis. In 10 patients, isosorbide dinitrate, 5 mg sublingually, reduced portal pressure by 21% as assessed by the gradient between wedged and free hepatic venous pressure, but also decreased mean arterial pressure (MAP) by 20%, pulmonary artery wedge pressure (WP) by 50%, and oxygen delivery (&U1E0A;O2) by 13%. In 6 other patients, isosorbide dinitrate, 5 mg sublingually, combined with vasopressin, 0.4 U/min iv, reduced portal pressure by 37%, increased MAP by 13%, and mean pulmonary artery pressure (MPAP) by 70%, and decreased &U1E0A;O2 by 32%. Thus, isosorbide dinitrate reduces effectively portal hypertension in patients with liver cirrhosis, but also decreases &U1E0A;O2 to the tissues as a consequence of a fall in cardiac output due to decreased preload. At the dosage used in this study, isosorbide dinitrate does not prevent the adverse hemodynamic effects of vasopressin.

Effect of vasopressin and somatostatin on hemodynamics and blood gases in patients with liver cirrhosis.

The effects of somatostatin and vasopressin on blood gases, pulmonary and systemic hemodynamics, and portal pressure assessed by the gradient between occluded and free hepatic vein pressures, were investigated in 18 patients with liver cirrhosis. In the first 10 patients, an iv bolus of 250 microgram somatostatin, followed by an infusion of 125 microgram somatostatin over 30 min, caused a sudden rise in pulmonary and systemic vascular pressures lasting 2 to 5 min and accompanied by bradycardia. There was a slight and transient increase in venous admixture (Qsp/Qt) and alveolar-arterial oxygen tension gradients (P(A-a)O2), and a transient reduction in O2 delivery (O2 del) (-11% of the baseline values) and portal pressures (-14%). In the next 8 patients, vasopressin, 0.4 U/min infused over 30 min, caused a more persistent pulmonary and systemic hypertension and bradycardia, a slight increase in P(A.a)O2 and Qsp/Qt, a reduction in O2 del (-27%) and a decrease in portal pressures (-32%). These effects were marked during the entire vasopressin infusion period. Both somatostatin and vasopressin had vasoconstrictive properties and exerted negative effects on hemodynamics and blood gases. Vasopressin appeared to be a more potent drug than somatostatin.

Hypouricemia in cirrhosis reflects hemodynamic alterations

In a population of 27 consecutive patients with liver cirrhosis, systemic hemodynamics were investigated and correlated to uric acid concentrations, fractional uric acid excretion, and creatinine clearances. Mean serum uric acid concentration was lower than in normal controls, and this was related to abnormally high uric acid clearances. Uric acid concentrations correlated positively to total peripheral resistances and negatively to cardiac output. Fractional uric acid excretions correlated negatively to total peripheral resistances and positively to cardiac output. There was no correlation between creatinine clearances and any variable of systemic hemodynamics. Serum uric acid concentration and fractional uric acid excretion are dependent of the hemodynamic state in cirrhosis.

The clinical value of 201Tl per rectum scintigraphy in the work-up of patients with alcoholic liver disease

The clinical value of thallium 201 per rectum scintigraphy in the work-up of patients with alcoholic liver disease was evaluated using data obtained in 104 patients. The 25th min ratio of heart to liver activities was used as an index of portal systemic shunting. This ratio was found to be normal in alcoholic patients with normal liver biopsy and also in those presenting only steatosis. It was slightly higher in patients with liver fibrosis and significantly higher values were observed in patients with liver cirrhosis. High values of the ratio were associated with a higher risk of portal systemic encephalopathy and/or gastrointestinal bleeding. The prognostic value of the test was supported by the fact that good correlations were observed between the ratio and widely accepted prognostic scores such as the Child score or the Orrego index. Moreover, high ratios were associated with an increased mortality risk at one year. We conclude that this simple test is interesting in the screening of cirrhotics at risk of encephalopathy, gastrointestinal hemorrhage, or early death.

The Role Of Excess Iron In The Pathogenesis Of Disturbed Neutrophil Functions In Cirrhotic Patients (Neutrophil Functions In Cirrhotic Patients)

SummaryIn the purpose to specify polymorphonuclear neutrophils (PMN) abnormalities and increased susceptibility to infections in cirrhosis, PMN ‘unctions-NBT reduction, phagocytosis, killing rate. myeloperoxydase activity—and incidence of infections were investigated in 25 cirrhotic patients. The patients were classified in a group of decompensated cirrhosis (D.C.) and a group of non evolutive cirrhosis (N.E.C.) according to their plasma bilirubin level.Patients with D.C. had a ccllular phagocytosis defect for both yeast and E. coli in comparison with N.E.C.; a seric abnormality was also observed in the yeast phagocytosis test. Other PMN functions were normal.Iron overload (higher transferrin saturation and ferritin levels) was found in D.C. in comparison with N.E.C. Moreover. Perls’s staining of PMN revealed the presence of iron in PMN of D.C. and its absence in N.E.C.In vitro incubation of normal PMN with high iron concentrations altered their phagocytic functions while the Perls’s staining revealed the...

Thallium scintigraphy in the evaluation of portal systemic shunting. The problem of rectal absorption

Thallium-201 scintigraphy is an attractive method for studying the portal systemic shunting. However, the technique is sometimes hampered by a low rectal absorption. The present work shows that cirrhotic patients present a significantly lower activity in the regions of interest in relation to the low absorption of the tracer as compared with non-cirrhotic subjects (p < 0.01). This study also demonstrates that the dilution of the tracer in a larger volume cannot be envisaged in order to increase the surface contact and secondarily the absorption, because part of the tracer can reach the inferior vena cava via portal systemic communications in the lower part of the rectum. Oral administration of the thallium was also attempted but this route cannot be used in relation to its poor absorption and due to the difficulty in separating liver from intestinal activity. The study also shows that even in the case of low activity in the regions of interest, the interpretation of the test in cirrhotic patients is usually possible on the condition that the curves of radioactivity in the liver and cardiac areas are ascending. Using these criteria, only 6.7% of the tests were in fact not interpretable in this study.

VASCULITE CUTANEE REVELATRICE D'UNE HEPATITE CHRONIQUE: A PROPOS DE 2 CAS

2 cases of cutaneous vasculitis associated with chronic hepatitis and mixed cryoglobulinaemia are reported. Further studies revealed in the first case hypocomplementaemia and glomerulonephritis. The cutaneous lesions of this patient responded dramatically to plasma exchange whereas prednisolone 20 mg/day and azathioprine 50 mg/day for 10 months showed no effect. The second case (chronic active hepatitis with acute colitis) responded well to prednisolone and azathioprine. The cutaneous lesions (vascularitis) may be the only clinical symptom of a chronic hepatitis and the study of those cases sometimes allows an early diagnosis of renal failure to be made.