Gerhard Kleber

Prediction of variceal hemorrhage in cirrhosis: A prospective follow-up study

Endoscopic, clinical, and laboratory parameters including presence of varices in the gastric fundus, red color sign, diameter and number of variceal columns, platelet count, and the Child status were assessed in 109 patients with cirrhosis and esophageal varices without previous variceal bleeding. During a mean follow-up period of 21 months, the predictive values of these parameters with regard to first bleeding incidence and mortality rate were studied. The incidence of bleeding was 29%, and the mortality rate 46%. Endoscopic criteria (presence of varices in the gastric fundus, presence of the red color sign, and size of the largest varix) as well as alcoholic etiology of cirrhosis showed a significant positive correlation with the bleeding incidence but not with mortality. Contrary to this, two factors of the Child classification (encephalopathy and ascites) and age positively correlated with mortality but not with the bleeding incidence.

Hepatic arterial flow volume and reserve in patients with cirrhosis: use of intra-arterial Doppler and adenosine infusion.

BACKGROUND & AIMS In cirrhosis, liver blood flow becomes increasingly dependent on the hepatic artery. The aim of this study was to investigate hepatic arterial blood flow volume and resistance and hepatic arterial flow reserve in relation to liver function and systemic hemodynamic alterations in patients with cirrhosis. METHODS In 38 patients with cirrhosis, liver function, cardiac output, and systemic vascular resistance were studied, and hepatic arterial blood flow velocity, flow volume, and pulsatility index at baseline and during intra-arterial administration of adenosine (2-40 microg. min-1. kg body wt-1) were assessed by angiography combined with intravascular Doppler flowmetry. RESULTS Hepatic arterial flow velocity was 21 +/- 11, 31 +/- 17, and 41 +/- 27 cm/s; flow volume was 266 +/- 246, 342 +/- 289, and 417 +/- 220 mL/min; and pulsatility index was 2.2 +/- 0.7, 1.7 +/- 0.6, and 1.5 +/- 0.5 in Child-Pugh classes A, B, and C, respectively (differences not statistically significant). Adenosine-induced changes in these parameters were more marked in Child-Pugh class A (68 +/- 15 cm/s, 1246 +/- 486 mL/min, and -1.14 +/- 0.5) than in class C (45 +/- 23, P < 0.05; 704 +/- 492, P = 0.02; and -0.58 +/- 0.38, P < 0.05). Using analysis of variance, cardiac index, systemic vascular resistance, and ascites, but not Child-Pugh class, were related to baseline values and adenosine-induced changes. CONCLUSIONS Adenosine is a potent dilator of the hepatic artery in humans. The data suggest that hepatic arterial blood flow and adenosine-dependent flow reserve in patients with cirrhosis are under systemic hemodynamic or neurohormonal control.

Manometry of esophageal varices: Comparison of an endoscopic balloon technique with needle puncture

BACKGROUND A noninvasive technique of pressure measurement in esophageal varices using an endoscopic balloon has been shown to be reliable in vitro. In the present study, this method was tested in vivo. METHODS Thirty-seven pressure measurements in esophageal varices were performed in 34 patients by two independent operators (A and B) using an endoscopic balloon and compared with measurements performed by needle puncture by a third operator (C). RESULTS Three measurements performed with the endoscopic balloon were rejected because they were noninterpretable. Measurements performed by A and B correlated well (correlation coefficient, 0.90); interobserver variability (r) was 0.88. Of 37 punctures performed for pressure measurements, 4 resulted in bleeding and 8 measurements were rejected as uninterpretable. Regression analysis showed a good correlation between the needle puncture and balloon techniques for pressure measurements performed by both operators (y = 5.3 + 1.0x, r = 0.8; y = 6.2 + 0.9x, r = 0.8), and analysis of variability showed a measurement bias of -5.3 +/- 4.1 and -4.1 +/- 3.5 cm H2O. No significant difference in variceal size measured with the endoscopic balloon or endoscopic forceps was found. CONCLUSIONS The endoscopic balloon allows measurement of pressure in esophageal varices without hazard to the patient; in addition, it may be used to assess the varix size.

Caffeine elimination: a test of liver function.

SummaryFasting plasma caffeine concentration and various parameters of caffeine elimination from plasma obtained after a standardized oral dose of 140 mg caffeine have been compared in nine patients with liver cirrhosis, eight patients with non-cirrhotic liver disease and ten healthy volunteers with regard to their ability to discriminate between the different groups. Fasting plasma caffeine concentrations were significantly higher in cirrhotics (11.1±10.5 μmol/l) than in healthy volunteers (1.5±0.8 μmol/l). The respective values measured in patients with non-cirrhotic liver disease (3.1±3.1 μmol/l) did not differ significantly from the controls. Plasma disappearance rate and clearance of caffeine were significantly decreased in cirrhotics (0.11±0.02 h−1; 1.0±0.3 ml/min per kg) and in patients with non-cirrhotic liver disease (0.18±0.04 h−1; 2.2±0.7 ml/min per kg) as compared to healthy volunteers (0.23±0.04 h−1; 3.1±0.9 ml/min per kg). Plasma caffeine concentration determined 12 h after administration of the test dosage discriminated best between patients with cirrhosis (5.4±1.6 μmol/l), patients with noncirrhotic liver disease (2.0±1.4 μmol/l) and healthy volunteers (0.8±0.2 μmol/l). These results, the safety of the test compound and the simplicity of a single caffeine determination in plasma 12 h after a standardized dose of caffeine make this test attractive for evaluation of liver function.

Reduction of transmural oesophageal variceal pressure by metoclopramide

In nineteen patients with portal hypertension and oesophageal varices, transmural variceal blood pressure was determined endoscopically by direct puncture of the varices before and after intravenous administration of 20 mg metoclopramide or placebo. No change in pressure was observed after placebo (mean difference -1.3 +/- 24.5%, N.S.), however, metoclopramide reduced the pressure by 17.6 +/- 18.6% (p = 0.02). Our results suggest that metoclopramide may be beneficial for the prevention or treatment of variceal haemorrhage.

Prophylaxis of first variceal bleeding

Surgical, endoscopic and pharmacological treatment options are available for prophylaxis of first upper intestinal haemorrhage in cirrhotic patients. Randomized controlled trials have revealed that a prophylactic portocaval shunt operation should not be performed because its beneficial effect on the bleeding rate is outweighed by a slightly increased mortality. Prophylactic portal non-decompressive surgery (mainly gastro-oesophageal vascular disconnection) has been shown to reduce the bleeding rate and mortality in Japanese cirrhotic patients. However, further trials in different populations must confirm this positive effect. beta-blockers have fewer side-effects and are probably more effective for prophylaxis of the first bleed than sclerotherapy, but survival is only marginally influenced. Nadolol is preferable to propranolol. The effect of sclerotherapy is in part related to the technical experience of the physician. Although sclerotherapy has only minor effects on the bleeding rate, it is associated with a trend towards a prolonged survival. This may be caused by non-specific effects. On the basis of the published trials, only preliminary recommendations can be given. Prophylactic treatment may be useful in cirrhotic patients who are at high risk of bleeding. Life quality may be improved with continuous beta-blocker treatment. Some studies suggest that alcoholics with large varices may also profit from regular prophylactic sclerotherapy performed by experienced physicians.

Reversible hyperkinesia in a patient with autoimmune polyglandular syndrome type I

SummaryAutoimmune polyglandular syndrome is characterized by a failure of multiple endocrine organs and the presence of circulating organ-specific autoantibodies targeted against the failing organs. Here we describe a patient with autoimmune polyglandular syndrome type I with the endocrine manifestations of hypoparathyroidism, adrenocortical insufficiency, and insulin-dependent diabetes mellitus. Long-standing hypoparathyroidism led to extensive calcification of the basal ganglia which resulted in the clinical presentation of an extrapyramidal movement disorder (choreoathetotic and hemiballistic hyperkinesia of the left extremities). Interestingly, parallel to rehydration and the initiation of cortisol replacement therapy a complete reversion of the hyperkinetic signs was achieved. This case shows a rare multiendocrine organ failure with complex metabolic interactions resulting in marked neurological signs. Furthermore, this case demonstrates for the first time that a hyperkinetic syndrome - most likely due to hypoparathyroidism-induced basal ganglia calcification - can be reversed solely by adequate treatment of the concomitant endocrine failures.

Prophylaxis of first variceal hemorrhage in patients with liver cirrhosis

SummaryProphylaxis of bleeding from esophageal varices is a very tempting concept at first glance, especially under the assumption of a high mortality associated with first variceal hemorrhage. Up to now four different measures have been tried for prophylaxis: portacaval shunt operation, devascularization procedures, sclerotherapy, and drugs. With the exception of portacaval shunts, ongoing controlled trials show a weak trend toward reduction of variceal bleeding and prolongation of survival in selected patients with compensated cirrhosis and large varices. However, prophylaxis of first variceal bleeding must still be regarded as experimental and should be restricted to controlled clinical studies.