Antony J. Ellis

TEMPORARY EXTRACORPOREAL LIVER SUPPORT FOR SEVERE ACUTE ALCOHOLIC HEPATITIS USING THE BIOLOGIC-DT

Patients with severe acute alcoholic hepatitis develop multiple organ failure which is associated with production of inflammatory cytokines and a poor prognosis. The aim of the present pilot study was to evaluate the effects of the BioLogic-DT sorption-suspension dialyser in patients with severe acute alcoholic hepatitis. Ten patients with encephalopathy (grade II-IV) were entered into the study, 5 received treatment with the BioLogic-DT for 6 hours daily for 3 days and 5 received conventional treatment as controls. The system was biocompatible with no adverse effects on blood pressure or platelet counts, factor V, fibrinogen or antithrombin III. No bleeding episodes were observed even with the use of small doses of heparin. After 3 days, blood ammonia was lower in the BioLogic-DT treated patients than in the controls, although blood lactate was higher. There were slight increases in plasma TNF and IL-8 during treatment over and above the higher levels present initially, possibly as a result of activation of white cells in the extracorporeal circuit. The further development of the BioLogic-DT dialyser with the addition of a plasma treatment module capable of removing cytokines would be worth evaluating in acute alcoholic hepatitis.

Deaths from low dose paracetamol poisoning.

Patients with serum paracetamol concentrations below the standard treatment line may develop acute liver failure Paracetamol is the most commonly used substance in self poisoning (about 70 000 cases annually in Britain1) and is the most frequent subject of inquiries to the National Poisons Information Services.2 Paracetamol overdose is the commonest cause of acute liver failure in the United Kingdom,3 accounting for at least half of all cases sent to tertiary referral units. To decrease the chance of liver damage in cases of paracetamol overdose, protocols and guidelines for treating patients with an antidote before referral to specialist care have been drawn up. The antidote acetylcysteine should be given to all patients with a serum paracetamol concentration >200 mg/l four hours after ingestion of the drug. A nomogram in which this value is joined to an end point of 25 mg/l at 16 hours allows identification over this period of the patients who should receive the antidote.4 If the antidote is not given, over 60% of patients with serum paracetamol concentrations above the treatment line may develop serious liver damage, and of these about 5% will die.5 Recent studies also suggest that acetylcysteine given after 16 hours, even at the stage of encephalopathy, can reduce the frequency of multiorgan failure and improve survival. 6 7 Factors that have been reported to enhance hepatotoxicity include chronic alcohol misuse,8 eating disorders,9 and enzyme inducing drugs,10 and in each of these contexts treatment is advisable below the treatment line. No deaths have been reported in any of the major treatment trials of paracetamol overdose,11 12 13 14 however high the initial serum paracetamol concentration, provided acetylcysteine was given within 10 hours of the drugs ingestion. Furthermore, there was only a 2% incidence of serious …

Late-onset hepatic failure: clinical features, serology and outcome following transplantation

A further series of 41 adult patients with late-onset hepatic failure was investigates with respect to aetiological factors, particularly hepatitis C and E, which have been identified since our earlier report of this condition. The increased use of transplantation and its impact on survival overall is assessed. Comparison is made with 64 patients admitted over the same period with fulminant hepatic failure of non-A, non-B aetiology. Screening for the hepatitis viruses revealed three cases of hepatitis A and one case of Epstein Barr virus hepatitis. There were no cases of hepatitis C or hepatitis E virus detected by enzyme immunoassay and reverse transcriptase/polymerase chain reaction techniques, although three patients had positivity for IgG anti-hepatitis E virus, demonstrating previous exposure. Serum autoantibodies in a titre greater than or equal to 1:40 were present in 29% of samples tested and in three cases, titres of SMA or ANF were greater than 1:320. In a further five cases, a potentially hepatotoxic agent had been given within 3 months of the onset of symptoms, leaving the majority of patients (29) with no identifiable cause for their disease. The frequency of symptoms, however, including nausea, abdominal discomfort with the subsequent development of ascites, encephalopathy and renal impairment suggest a similar disease process in these patients. Analysis of liver biopsy material showed similar patterns on all cases of map-like necrosis with nodular regeneration and without other additional features of aetiological significance. Differences in clinical and histological changes for the non-A, non-B fulminant hepatic failure comparison group reflect the tempo of disease process rather than the nature and cause of the liver damage. The introduction of transplantation has led to a marked improvement in survival (39% overall in the earlier series). In the 21 patients in whom transplantation was carried out, the 1-year actuarial survival is currently 55%. Treatment of late-onset hepatic failure with corticosteroids and the use of Prostaglandin E1 and interferon in individual cases has been disappointing, and the emphasis in management should be placed on teh early referral of such patients to a centre offering transplantation.

EFFECT OF ELAD LIVER SUPPORT ON PLASMA HGF AND TGF-BETA 1 IN ACUTE LIVER FAILURE

The aim of this study was to investigate the effects of treatment with the extracorporeal liver assist device (ELAD) in patients with acute liver failure (ALF) on plasma hepatocyte growth factor (HGF), the most potent growth factor, and transforming growth factor-β1 (TGF-β1), an inhibitory factor for liver regeneration. Initial plasma HGF, measured by ELISA, was significantly increased in the ALF patients (7.86 ± SEM 1.76 ng/ml) compared with normal subjects (0.10 ± 0.02 ng/ml, p<0.001). After 6 hours of ELAD haemoperfusion, plasma HGF increased further (30.5 ± 6.19 ng/ml, p<0.001), with a subsequent decrease towards the initial value by 48 hours. Initial plasma levels of TGF-β1 determined by ELISA were significantly increased in the ALF patients (43.4 ± 5.9 ng/ml) compared with normal subjects (25.1 ± 2.3 ng/ml, p<0.01), but there was no change in plasma TGF-β1 during the study period in either the ELAD or control ALF group. As HGF is a heparin-binding growth factor and similar changes in HGF were observed during CVVHD, one possible explanation is that heparin administered as anticoagulant for extracorporeal circulation is involved in the effects observed on HGF.

Use of extracorporeal liver assist device and auxiliary liver transplantation in fulminant hepatic failure

The case history of a 14-year-old boy with fulminant hepatic failure secondary to non-A, non-B hepatitis who fulfilled selection criteria for orthotopic liver transplantation is described. Two forms of liver support were used (extracorporeal liver assist device and an auxiliary partial orthotopic liver transplantation) to provide additional time to allow spontaneous recovery to occur. During the 66 h of extracorporeal haemoperfusion through the device, haemodynamic stability was maintained along with improvements in serum bilirubin (555 to 381 mumol/l), and international normalized ratio (INR) (3.7 to 2.9). Deterioration in these parameters was observed following cessation of treatment and 10 h later, after a donor liver had become available, an auxiliary transplant was performed. Clinical recovery, though initially slow, was eventually complete, with histopathological and scintigraphic evidence of full liver regeneration at 3 months. Withdrawal of his immunosuppressive drugs began at 6 months and was complete by 14 months after auxiliary transplantation. He has since remained well with normal liver function tests. Temporary liver support may provide additional time for spontaneous recovery of the native liver to occur in selected cases of fulminant hepatic failure, even when criteria are fulfilled for orthotopic liver grafting.