OBJECTIVE: To see whether intravenous acetylcysteine would improve outcome in patients with fulminant hepatic failure after paracetamol overdose. DESIGN: A prospective randomised controlled study. SETTING: The Institute of Liver Studies, King's College Hospital, London. PATIENTS: 50 consecutive patients (21 male) aged 16-60 with fulminant hepatic failure after paracetamol overdose who had not previously received acetylcysteine. INTERVENTIONS: Conventional intensive liver care plus either acetylcysteine (25 patients) in the same dose regimen as used early after a paracetamol overdose, except that the infusion was continued until recovery from encephalopathy or death, or an equivalent volume of 5% dextrose (25 patients). MAIN OUTCOME MEASURES: Survival; incidence of cerebral oedema, renal failure, and hypotension requiring inotropic support; liver function as assessed by prolongation of the prothrombin time; and degree of encephalopathy. RESULTS: The rate of survival was significantly higher in the acetylcysteine treated group than in the controls (48% (12/25 patients) v 20% (5/25); p = 0.037, 95% confidence interval for difference in proportions surviving 3% to 53%). Acetylcysteine treated patients had a lower incidence of cerebral oedema (40% (10/25) v 68% (17/25); p = 0.047, 95% confidence interval for difference in incidence 2% to 54%), and fewer developed hypotension requiring inotropic support (48% (12/25) v 80% (20/25); p = 0.018, 95% confidence interval 7% to 57%). Rates of deterioration and recovery of liver function, however, were similar in the two groups. No adverse reactions to acetylcysteine were seen. CONCLUSIONS: Acetylcysteine is safe and effective in fulminant hepatic failure after paracetamol overdose.

Acetaminophen↗

PubMed1991

Safety of alcohol after viral hepatitis.

To test the validity of the generally held belief that moderate consumption of alcohol during convalescence from acute viral hepatitis adversely affects outcome, 87 adults recovering from acute viral hepatitis (hepatitis A in 36, hepatitis B in 34, hepatitis non-A, non-B in 17) were studied. Criteria for entry to the study attempted to ensure that no patient was a chronic hepatitis B carrier. Patients were randomised either to a moderate alcohol intake, or to continued complete abstention. Drinkers consumed 26 g alcohol daily (mean) and none remained abstinent. At 3 months all patients were well, with normal liver function tests. There were no significant differences between the two groups at anytime. The findings suggest that moderate alcohol intake during convalescence from acute viral hepatitis does not seem to be harmful.

Acute Disease↗

PubMed1991

Measurement reproducibility of two commercial knee test devices.

Objective evaluation of patients' knee motion using mechanical devices, whether for diagnostic purposes or for assessing rehabilitative procedures, requires that these devices be reproducible, in order to avoid errors independent of the patients' condition. This study prospectively evaluates the reproducibility of two commercial knee test systems, the KT 1000 Knee Ligament Arthrometer and the Genucom Knee Analysis System, by performing repeated measurements on twenty normal men. Average knee motion, between-subject variance, and within-subject variance were determined by performing repeat tests on the same day and one week later. No significant difference was found between measurements taken on the two different test days, but the within-subject variation was high. We found that larger applied forces or moments resulted in a larger variation in mean displacements. However, the percent variation about the mean (coefficient of variation) decreased with increasing applied loads. The coefficient of variation for the KT 1000 varied from 8 to 33% and for the Genucom, from 13 to 87%. On an individual basis, large variations were found in repeated measures for both devices. To minimize errors, we recommend that repeated tests be performed, higher forces and moments utilized, and specific flexion angles be used for each device and test. Even under these conditions, caution must be exercised when evaluating individual subjects.

Adult↗

PubMed1991

Human atrial natriuretic factor and renin-aldosterone in paracetamol induced fulminant hepatic failure.

It has been postulated that deficiency of a putative natriuretic factor, or resistance to such a factor, may contribute to sodium retention in fulminant hepatic failure. Levels of plasma human atrial natriuretic factor (h-ANF), plasma renin activity, and aldosterone concentration were measured in 33 patients with fulminant hepatic failure due to paracetamol overdose, and 12 healthy control subjects. Levels of h-ANF were raised only in patients with evidence of severe renal impairment (serum creatinine greater than 300 mumol/l and urine output less than 100 ml/24 hours). h-ANF values were median 4.15, range 2-9 pmol/l and 10.1, 1-25 pmol/l for the control and severe renal impairment groups respectively (p less than 0.001). In the latter plasma renin activity was raised compared to that in control subjects (median 19.8, range 1.04-41.7 and 2.86, 1.87-5.9 pmol/l/h respectively, p less than 0.02). Plasma aldosterone concentration was also raised in patients (2176, 199-6894 pmol/l compared to 368, 133-578 pmol/l in control subjects, p less than 0.01). Haemodialysis induced changes in circulating h-ANF which correlated with volume and right atrial pressure changes (p less than 0.001 and p less than 0.05 respectively). In six patients with no or mild renal failure infusion of 900 ml 5% human albumin solution caused a significant increase in plasma h-ANF (p less than 0.05) without natriuresis or diuresis, a finding compatible with the hypothesis that there may be resistance to h-ANF in this group. The present findings indicate that there is no deficiency of h-ANF in fulminant hepatic failure and that known mechanisms of h-ANF release are not impaired.

Acetaminophen↗

PubMed1991

Cystic disease of the liver and biliary tract.

The widespread availability of ultrasound imaging has led to more frequent recognition of cystic disease affecting the liver and biliary tract. There is a wide range of possible causes. Cystic disease of infective origin is usually caused by an Echinococcal species, or as the sequel of a treated amoebic or pyogenic abscess. The clinical and radiological features are often then distinctive and will not be dwelt upon in this review, except in respect of their contribution to the differential diagnosis of non-infective disorders. The principal non-infective cysts can be conveniently divided between the simple cyst, the polycystic syndromes (usually with coexistent renal disease), Caroli's syndrome, and choledochal cysts. The overlap between constituent members of these groups, and the association of cystic disease with hepatic fibrosis (especially with congenital hepatic fibrosis) has attracted considerable attention, and it has been suggested that they may all be considered to belong to a hepatobiliary fibrocystic continuum. In addition there are a variety of cystic neoplasms and a miscellany of unusual forms.

Biliary Tract Diseases↗

PubMed1991

Abdominal pain in HIV infection.

The causes of abdominal pain in patients with AIDS are different from those of the general population, and there are no guidelines as to which investigations are optimal. We reviewed our experience of 63 patients who presented with abdominal pain as the main reason for admission to the AIDS unit at St Stephen's and Westminster Hospital between January 1988 and January 1990. All patients were assessed within the same structured diagnostic programme. Thirty-five had upper abdominal pain, predominantly in the right upper quadrant in 27; seven had lower abdominal pain, which was concentrated in the right iliac fossa in three; 21 had diffuse abdominal pain. The causes of pain were determined satisfactorily in the majority of patients using routine gastroenterological investigations. The predominant site of pain had considerable predictive value in the diagnosis. The commonest cause of right upper quadrant pain was sclerosing cholangitis (17 of 27); endoscopic retrograde cholangio-pancreatography was necessary for a confident diagnosis. Diarrhoea was frequently associated (15 of 21) with diffuse abdominal pain; the commonest cause (six of 21) was cytomegalovirus colitis. Neoplasia was the cause of abdominal pain in eight patients. The other causes of abdominal pain and the utility of various investigations are discussed. An investigatory route which may provide maximum information has been suggested.

Abdomen↗

PubMed1991

Antithrombin III supplementation reduces heparin requirement and platelet loss during hemodialysis of patients with fulminant hepatic failure.

Previous studies have shown that antithrombin III levels are low in fulminant hepatic failure, and heparin kinetics are abnormal, making control of heparinization difficult during hemodialysis of these patients who are at risk of bleeding. In this study, we have performed a controlled, randomized trial of antithrombin III supplementation on heparin activity, occurrence of bleeding and the platelet count and activation during hemodialysis in 24 patients with fulminant hepatic failure. The treated group of 12 patients was given 3,000 units of antithrombin III before hemodialysis. Antithrombin III supplementation was shown to normalize antithrombin III levels during hemodialysis (prelevels: 0.22 +/- 0.03 U/ml S.E.; at 1 hr 0.99 +/- 0.06 U/ml; p less than 0.001; control prelevels: 0.24 +/- 0.03 U/ml; at 1 hr 0.23 +/- 0.04 U/ml). Total heparin usage was significantly decreased by antithrombin III supplementation (median 5,200 U; range = 2,000 to 13,000) as compared with the control group (median 10,200 U; range = 5,000 to 16,500; p less than 0.005). Blood heparin level (antifactor Xa activity) after the initial bolus was significantly greater in the antithrombin III-supplemented subjects (0.40 +/- 0.07 U/ml compared with 0.22 +/- 0.05 U/ml in the control group; p less than 0.05). The significant reduction in platelet count observed in the control patients (18% +/- 6% at 1 hr; p less than 0.05) did not occur in antithrombin III patients (6% +/- 4% at 1 hr), which was reflected by a lower release of the platelet-specific protein beta-thromboglobulin. Two of 12 patients in both groups showed minor bleeding around vascular access sites during the first hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗

PubMed1990

Failure of insulin and glucagon infusion to stimulate liver regeneration in fulminant hepatic failure.

A randomised controlled trial of insulin and glucagon infusion was carried out in 18 patients in grade III or IV coma from fulminant hepatic failure due to viral or drug-induced hepatic necrosis to see whether mortality could be reduced by stimulating hepatic regeneration. Nine patients received a continuous infusion of insulin 3 U/h and glucagon 200 micrograms/h made up in 5% dextrose containing 1% human albumin solution (HAS) while controls received 5% dextrose and HAS alone. Baseline plasma insulin and glucagon levels were comparably raised in both groups and, on infusion, rose significantly higher in the insulin- and glucagon-treated patients compared to controls. Two control and one treated patient recovered. Median survival time from enrolment to death was similar for insulin- and glucagon-treated patients and controls--2 and 3 days, respectively. Insulin and glucagon therapy did not enhance hepatic synthetic function, as measured by a fall in prothrombin time or a rise in alpha-fetoprotein; nor did it stimulate hepatic regeneration, only one patient in each group showed histological evidence of hepatic regeneration at post-mortem.

Adult↗

PubMed1990

Changing epidemiology and clinical aspects of hepatitis A.

The picornavirus responsible for hepatitis A is no longer thought directly cytopathic; it is probable that pathogenesis is dependent on T-cell mediation. Although well known to cause a generally milder illness in young children, it is now clear that the severity of hepatitis A continues to increase steadily with increasing age through adulthood also. Earlier and controversial reports of relapsing hepatitis A are now better supported by investigatory data. Cyclic epidemics are becoming less apparent in the developed world, where particular groups, such as intravenous drug abusers and those in contact with children, account for an increasing proportion of cases. Endemicity is gradually being overcome in developing countries, an effect mainly of improved sanitation, and it has been shown that hepatitis A may disappear entirely from isolated communities.

Age Factors↗

PubMed1990

Diagnosis of eosinophilic fasciitis.

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Arthritis, Juvenile↗

PubMed1990

The value of barium enema and colonoscopy in patients infected with HIV.

Double contrast barium enema (DCBE) and colonoscopy were prospectively compared with rigid sigmoidoscopy, rectal biopsy and microbiological examination in the analysis of stool specimens in 58 HIV-1-infected patients with diarrhoea (more than three liquid motions/day for greater than 1 month). In 26 patients no cause for the diarrhoea was found. In 17 patients the cause of diarrhoea was microbiological, and in 19 rectal histology provided a specific diagnosis. In all these patients sigmoidoscopic appearances were abnormal except in those with Cryptosporidium alone. Colonoscopy provided additional information in only one individual, with cytomegalovirus ulcers of the transverse colon. DCBE was abnormal in only seven cases (cytomegalovirus in three, Kaposi's sarcoma in two, Giardia lamblia in two) and in no case provided additional information. A combination of stool microbiology and rectal histology gave a sensitivity of 97% with a positive predictive value of 100%. The sensitivities of DCBE and colonoscopy with histology were low (16 and 62%, respectively) although the specificity for each test was high, with high positive predictive values. We conclude that neither barium enema nor colonoscopy add usefully to rigid sigmoidoscopic biopsy and stool microscopy in HIV-positive patients with diarrhoea.

Barium Sulfate↗

PubMed1990

Thrombin-antithrombin III complex in fulminant hepatic failure: evidence for disseminated intravascular coagulation and relationship to outcome.

Indirect evidence has suggested that intravascular coagulation may occur in patients with fulminant hepatic failure (FHF), the most severe form of acute liver disease. Thrombin is inhibited in circulation by antithrombin III, and measurement of the thrombin-antithrombin III complex (TAT) is a direct measure of thrombin formation. Using a new rapid enzyme-linked immunosorbent assay we have measured TAT in 54 patients on admission, with fulminant hepatic failure. TAT was significantly increased in patients with FHF compared with control subjects (25.8 +/- 2.7 micrograms l-1) compared with 2.6 +/- 0.2 micrograms l-1; n = 10: P less than 0.001). Patients who survived had significantly lower TAT levels than those who did not (17.2 +/- 2.7 micrograms l-1; n = 27 compared with 34.0 +/- 4.2 micrograms l-1; n = 27: P less than 0.005) and patients with FHF caused by viral hepatitis had significantly lower TAT levels than those with FHF due to paracetamol overdose (14.6 +/- 4.7 micrograms l-1; n = 9 compared with 28.0 +/- 3.1 micrograms l-1; n = 45: P less than 0.05). Levels of TAT correlated significantly with prothrombin time (r = 0.36, P less than 0.01) and inversely with fibrinogen (r = -0.51, P less than 0.001). There was no significant correlation with antithrombin III concentration. Thus, using a simple and rapid technique, we have been able to demonstrate increased levels of TAT complex in patients with FHF. This provides more direct evidence of intravascular coagulation and thrombin generation in these patients. These results confirm that the coagulation system is activated in FHF.

Acetaminophen↗

PubMed1990

Vancomycin in resistant hepatic encephalopathy.

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Hepatic Encephalopathy↗

PubMed1990

Investigation of seemingly pathogen-negative diarrhoea in patients infected with HIV1.

Thirty three consecutive patients infected by human immunodeficiency virus type 1 (HIV1) with persistent diarrhoea which remained undiagnosed after microbiological examination of six stool samples and rectal histology were investigated for malabsorption. All had xylose and Schilling tests, distal duodenal biopsy, comprehensive barium studies, microbiological examination of six further stool samples, and repeat rectal histology. A microbiological or histological diagnosis of infection was made in 12 patients (multiple organisms in three). Cryptosporidia were identified on five occasions, cytomegalovirus on four, Giardia lamblia on two, and herpes simplex, Campylobacter jejuni, Salmonella enteritidis, and Entamoeba histolytica once each. No organism was found when weight loss was less than 5 kg or stool volume less than 400 ml/day (n = 9). Pathogens were identified in nine of 13 patients (69%) with weight loss greater than 10 kg and stool volume more than 800 ml/day. Barium studies were normal except for ileal flocculation in two patients with cryptosporidiosis. Evidence for malabsorption existed in 24 patients--impaired xylose absorption (n = 19) and abnormal Schilling test (n = 21). Of the patients with a severely abnormal Schilling test, a pathogen was identified in 11 (79%) (including all five with cryptosporidia, and two of the patients with only moderate diarrhoea and weight loss). A simple scoring system based on degree of weight loss and Schilling test result may help to identify the HIV positive patient with seemingly pathogen-negative diarrhoea in whom further investigations are likely to show a specific cause.

Acquired Immunodeficiency Syndrome↗