Ian A.D. Bouchier

Exercise-induced left ventricular dysfunction in alcoholic and non-alcoholic cirrhosis

BACKGROUND/AIMS Autonomic and cardiac dysfunction have been reported in patients with cirrhosis. We studied left ventricular and autonomic function in 20 patients with both alcoholic and non-alcoholic cirrhosis. METHODS Autonomic function was assessed by a standard battery of cardiovascular reflex tests. Supine exercise radionuclide ventriculography was used to assess the cardiac response to exercise. RESULTS Exercise capacity was reduced in all patients in association with marked chronotropic incompetence (peak heart rates 120.5 +/- 6 bpm). Unlike normal subjects there was no increase in left ventricular ejection fraction on exercise. Stroke volume increased by 23 +/- 6%, mediated by an increase in end-diastolic.volume of > 20%. Cardiac output was subnormal at maximal exercise, increasing by only 96 +/- 14% and 97 +/- 11% in alcoholic and non-alcoholic groups respectively. The majority (83%) of our patients had autonomic reflex abnormalities. CONCLUSIONS Patients with cirrhosis of alcohol and non-alcohol related aetiologies have significantly impaired cardiovascular responses to exercise, which are similar to those of a denervated heart. This may have important clinical implications for the ability of these patients to withstand cardiovascular stress.

A comparison between gastric and oesophageal variceal haemorrhage treated with transjugular intrahepatic portosystemic stent shunt (TIPSS)

Background: Transjugular intrahepatic portosystemic stent‐shunts (TIPSS) are becoming widely used in the management of oesophageal variceal haemorrhage (OVH). Their place in the treatment of gastric variceal haemorrhage (GVH), a condition with a traditionally poor prognosis, remains unclear. The aims of our study were to compare portal haemodynamics and patient outcome in patients undergoing TIPSS for either GVH or OVH.

Clofibrate therapy and gallstone induction.

Two hundred consecutive patients, referred to a clinic established for the management of serum lipid disorders, were studied to assess the prevalence of gallbladder disease: 163 patients agreed to cholecystography of whom 23 had gallstones; 5 other patients had had cholecystectomy. There was a strong associction between clofibrate therapy and gallstones, which were found in 9 of 18 patients. Fifty-six patients with normal gallbladders had duodenal bile analyzed for lipid composition, and results were compared with those from 15 other patients with gallstones but normal serum lipids. Bile in hyperlipidemia and normolipidemic controls contained less cholesterol (9.21±3.48 mol/100 mol) than in clofibrate-treated patients (13.33±3.48 mol/100 mol, P<0.01), and in gallstone patients with normal serum lipids (11.87±4.52 mol/100 mol). There was no relationship demonstrable between patterns of hyperlipidemia or ischemic heart disease and the presence of gallbladder disease. There was also no association between biliary lipid composition and serum lipids or low-animal-fat diet. It is concluded that clofibrate therapy markedly increases biliary cholesterol content and is a potent lithogenic agent in patients not otherwise especially prone to gallstones. Since its role in prevention of ischemic heart disease is now uncertain, its continued wide use warrants close scrutiny.

Acute haemodynamic changes after oral carvedilol, a vasolidating beta-blocker, in patients with cirrhosis

Abstract Background/Aims: Combinations of beta-blockers and vasodilators have been assessed for their ability to lower portal pressure and so prevent variceal haemorrhage. However, reservations have been raised particularly with respect to renal function and perfusion after the use of these medicines in patients with chronic liver disease. We studied the acute effects of carvedilol, a new vasodilating beta-blocker which combines non-selective beta-blockade with alpha-1 receptor antagonism, upon the haemodynamics of patients with cirrhosis. Methods: Sixteen patients completed the study which measured the changes approximately 1 h after the administration of 25 mg oral carvedilol. Results: The hepatic venous pressure gradient fell from 16.7±0.9 to 13.6±1.0 mmHg ( p p =0.0001), which was particularly apparent in the diastolic blood pressure of those patients with ascites. The heart rate only fell significantly in the ascitic subjects. No significant changes occurred in the cardiac output or systemic vascular resistance. Unilateral renal vein flow as measured by the reverse thermodulution technique remained constant. Conclusions: Carvedilol is therefore a potent acute portal hypotensive agent which does not appear to compromise renal perfusion. However, patients with ascites are a greater risk of its systemic hypotensive action.

Gas-liquid chromatographic assay of serum bile acids.

Abstract A sensitive method has been established for the analysis of serum bile acids by gas-liquid chromatography (glc). Bile acids are extracted from 0.5–2 ml of serum and analysed as methyl ester trifluoroacetates following enzymatic hydrolysis of the taurine and glycine conjugates. The method as described has been used to estimate serum bile acid levels in health and disease although bile acid sulphates are not detected. Inclusion of a solvolysis procedure before enzymatic hydrolysis would allow their measurement.

Neutrophil activation in chronic liver disease.

Objective To assess the relationship between neutrophil activation and indices of disease severity in patients with chronic liver disease. Methods: Plasma neutrophil elastase was measured by radioimmunoassay as a marker of neutrophil activation, and disease severity assessed by standard clinical, biochemical, haematological and histological techniques. Patients: Eighty-eight patients with chronic liver disease were studied. Thirty-nine had alcohol-induced liver disease (ALD), 18 autoimmune chronic hepatitis, 13 cryptogenic cirrhosis, seven primary biliary cirrhosis, six primary sclerosing cholangitis, three haemochromatosis and two secondary biliary cirrhosis. Seventy-three patients were cirrhotic and 15 were non-cirrhotic, confirmed by biopsy. Results: Levels of neutrophil elastase were raised in Childs C cirrhotic patients with ALD compared with Childs A or B patients with ALD (P<0.01), Childs A or B patients with non-ALD (P<0.01), and Childs C patients with non-ALD (P=0.02). In patients with ALD, neutrophil elastase correlated with prothrombin time (r = 0.679, P=0.001), bilirubin (r = 0.587, P<0.001), Child-Pugh score (r = 0.546, P< 0.001) and inversely with serum albumin (r = −0.511, P<0.001). In patients with non-ALD, there were no correlations with these measurements or with transaminase levels. Conclusion: Neutrophil activation, as measured by plasma neutrophil elastase, is a marker of disease severity in patients with alcohol-induced chronic liver damage, but not in those with other causes of liver disease.

The correction of autonomic dysfunction in cirrhosis by captopril

BACKGROUND/AIMS Vagal dysfunction is reported in about 70% of patients with cirrhosis, irrespective of aetiology, as detected by cardiovascular reflex tests. We have previously shown that RR-variability on 24-h ECG is a more sensitive marker of vagal dysfunction in cirrhosis. Angiotensin II inhibits vagal function in animals, and it is elevated in cirrhosis and may be the cause of the vagal dysfunction. Our aim was to observe the effect of captopril on vagal dysfunction in cirrhosis. METHODS Eight patients with cirrhosis (biopsy proven, male two, female six, mean age 54.25) had 24-h ECG RR-variability performed. They then received captopril 25 mg t.d.s. for 48 h. The 24-h ECG was repeated on therapy. RESULTS Mean blood pressure remained unchanged: baseline 89.8 +/- 4.8 mmHg (mean +/- sem) versus 91.8 +/- 5.9 mmHg, p = not significant. Median baseline RR-variability was 791 (range 18-5344) counts/24 h and increased in all but one patient, with captopril, to 1548 (56-4824) p = 0.008. Three increased into the normal range. CONCLUSION The vagal dysfunction of cirrhosis is caused by neuromodulation by angiotensin II and is not due to a neuropathy.

The estimation of phospholipids in bile

Total and lipid phosphorus were measured in the duodenal aspirate of 24 fasting subjects following an injection of cholecystokinin. The lipid phosphorus values were lower than the total phosphorus, a difference most pronounced in dilute samples. Storage at -20 degrees C over 4 weeks resulted in a loss of over 50% lipid phosphorus. Such alterations in the lipid phosphorus affected the calculation of biliary phospholipid and hence the saturation index of cholesterol in bile causing it to be erroneously elevated. It is concluded that analysis of bile samples should be undertaken on freshly obtained samples and include a preliminary step for the extraction of lipids.

Effect of propranolol on prevention of first variceal bleed and survival in patients with chronic liver disease

Background: Propranolol has been shown to be effective in both primary and secondary treatment of variceal haemorrhage; most primary prevention trials have only included patients with large oesophageal varices.

Glutathione S-transferase levels in autoimmune chronic active hepatitis: A more sensitive index of hepatocellular damage than aspartate transaminase

Glutathione S-transferase (GST; EC 2.5.1.18), a sensitive marker of hepatocellular damage, was measured in patients on therapy for histologically proven, autoimmune chronic active hepatitis at various stages of the disease. GST levels were elevated in 65% of serum samples despite immuno-suppressive treatment compared with aspartate transaminase (AST) which was increased in only 23% of samples. In 55% of samples with normal AST concentrations, GST was elevated. No samples demonstrated abnormal transaminase with normal GST levels. It is concluded that continuing hepatocellular damage occurs in patients with autoimmune chronic active hepatitis on immuno-suppressive treatment.