Complication Of Acute Liver Failure Research Articles

Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure

Increased intracranial pressure as a complication of acute liver failure has a mortality of about 90% in patients who do not respond to treatment with mannitol and ultrafiltration. We investigated the safety and efficacy of moderate hypothermia for uncontrolled increase in intracranial pressure in patients with acute liver failure. We studied seven consecutive patients aged 16-46 years (five women, four candidates for orthotopic liver transplantation [OLT]) with acute liver failure who fulfilled criteria for poor-prognosis liver failure and had increased intracranial pressure that was unresponsive to two treatments with mannitol and ultrafiltration. We used cooling blankets to lower the patients' core temperature to 32-33 degrees C. Patients who were not suitable candidates for OLT (patients 1-3) were cooled for 8 h and then gradually rewarmed over 1 h to a baseline temperature of 37 degrees C. Patients who were suitable candidates for OLT (patients 4-7) were cooled before and during the OLT procedure. We measured cerebral blood flow and metabolic indices before and after cooling. The four patients who were candidates for OLT were successfully maintained until transplantation with 13 (range 10-14) h of hypothermia. The three patients who were unsuitable candidates for OLT died after rewarming. Intracranial pressure before cooling was 45 (25-49) mm Hg and was reduced in all patients to 16 (13-17) mm Hg (p<0.05). Cerebral blood flow decreased from 103 (25-134) mL 100 g(-1) min(-1) before cooling to 44 (24-75) mL 100 g(-1) min(-1) after cooling (p<0.05). The corresponding changes for cerebral perfusion pressure was an increase from 45 (37-56) mm Hg to 70 (60-78) mm Hg (p<0.05) and for cardiac index a decrease from 9.8 (7-13) to 5.1 (4.3-6.1) L per min per m2 of body surface area. During hypothermia there was no significant relapse of increased intracranial pressure. Arterial ammonia and cerebral uptake of ammonia were significantly reduced with cooling. No adverse effects of hypothermia were observed. Moderate hypothermia is useful in the treatment of uncontrolled increase in intracranial pressure in patients with acute liver failure and may serve as a bridge to OLT.

Cerebral oedema in acute liver failure

One of the most hazardous complications of acute liver failure (ALF) is raised intracranial pressure and the development of cerebral oedema. Until very recently it had been cited as the commonest mode of death, with an incidence of between 50 and 80% amongst those patients who progress to the deepest grades of coma, although that situation may now be changing. The purpose of this article is to discuss why failure of the liver leads to cerebral oedema and what treatment options are available.

Decreased glutamate transporter ( GLT-1) expression in frontal cortex of rats with acute liver failure

It has been suggested that reduced astrocytic uptake of neuronally released glutamate contributes to the pathogenesis of hepatic encephalopathy in acute liver failure. In order to further address this issue, the recently cloned and sequenced astrocytic glutamate transporter GLT-1 was studied in brain preparations from rats with ischemic liver failure induced by portacaval anastomosis followed 24 h later by hepatic artery ligation and from appropriate sham-operated controls. GLT-1 expression was studied using reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of GLT-1 transcript was significantly decreased in frontal cortex at coma stages of acute liver failure. Western blotting using a polyclonal antibody to GLT-1 revealed a concomitant decrease in expression of transporter protein in the brains of rats with acute liver failure. Reduced capacity of astrocytes to reuptake neuronally released glutamate, resulting from a GLT-1 transporter deficit and the consequently compromised neuron-astrocytic trafficking of glutamate could contribute to the pathogenesis of hepatic encephalopathy and brain edema, two major complications of acute liver failure.

Taurine in hepatic encephalopathy.

Liver and brain are the major organs responsible for taurine synthesis. In both acute and chronic liver failure, brain taurine concentrations are decreased and, since taurine appears to be implicated in K+ and Ca2+ homeostasis in brain, such losses could contribute to the pathophysiology of hepatic encephalopathy. Furthermore, taurine concentrations in cerebrospinal fluid in experimental acute liver failure are increased early in the progression of encephalopathy and prior to the onset of cerebral edema, a potentially fatal complication of acute liver failure. These findings suggest an osmoregulatory role for taurine in brain in acute liver failure. Monitoring of cerebrospinal fluid taurine may be of prognostic value in this severe, frequently fatal disorder.

Evaluation of extracorporeal bioartificial liver devices.

The initial clinical studies on artificial liver support were performed at King's College Hospital, London during the late 1970s. Initially using charcoal haemoperfusion, and subsequently resin haemoperfusion, and these studies culminated in a controlled clinical trial of charcoal haemoperfusion in which overall survival was high, but no statistically significant benefit was found. From this study, much information was also obtained about the clinical importance of the various complications of acute liver failure, and the experience of King's over the last 2 decades exceeds 1,000 patients. The aim of this article is to review the potential of the exciting new developments in this field of bioartificial liver support incorporating hepatocytes. It focuses on the published findings of early clinical use of these systems and attempts to identify what is needed in further studies. It is of paramount importance that future trials are designed to give the greatest information on the effects of bioartificial liver support. For these, the biocompatibility of the systems should to be confirmed with detailed assessment and sensitive tests need to be developed to determine the metabolic functional efficacy of these devices. The possible relationship of treatment to liver regeneration has been considered, because without this these systems will in many cases be limited to use as a bridge to liver transplantation. Finally, some of the possible future modifications of the cell-based liver support systems are discussed.

Alcoholic liver damage–toxicity, autoimmunity and allergy

Alcoholic liver damage–toxicity, autoimmunity and allergy

Reticuloendothelial System Function Following Acute Liver Failure Induced by 90% Hepatectomy in the Rat

Sepsis and bacterial infections are frequent complications of acute liver failure and following major liver resection. The mechanisms underlying this phenomenon are unclear. In this study, RES function and blood clearance of radiolabelled E. coli was immediately impaired following 90% hepatectomy, although the reduction in liver volume resulted in an increase in splenic (temporary) and pulmonary (persisting) uptake. A significant correlation between liver function and host RES function was observed. The uptake capacity of the RES in the liver remnant and spleen did not correlate with subserosal blood flow. The uptake in the brain gradually increased with time, paralleling an increased leakage across the blood-brain barrier. Thus, a significantly impaired RES function resulted from experimental 90% hepatectomy-induced acute liver failure, which might explain the high incidence of septic events in the clinical situation.

Fungal infection: a common, unrecognised complication of acute liver failure

The true incidence and clinical relevance of fungal infection was ascertained in a prospective study of 50 consecutive patients with acute liver failure. Fungal infection was present in 16 (32%) patients (15 Candida, one aspergillus) and in seven was considered the major cause of death. All six untreated died, while five of ten patients treated with anti-fungal therapy survived. The diagrusis was made on positive cultures from at least one significant site or on histological evidence of tissue invasion. All 16 hed concomitant bacterial infection and shared features suggestive of a clinical syndrome: deterioration in coma grade after initial improvement; pyrexia unresponsive to antibiotics; established renal failure; and a markedly elevated white cell count. Fungal infection is a common, serious complication of acute liver failure and therapy is indicated for those with positive cultures. A prophylactic trial would be justified in those surviving 5 days, especially, with established renal failure.

Does hypophosphatemia play a role in acute liver failure?

This is the first record of hypophosphataemia in acute liver failure induced by paracetamol; it occurred in most of the patients and was severe (&lt;0.3 mmol/l) in more than one third. At this level hypophosphataemia produces impaired oxygen transport and tissue hypoxia, abnormal leucocyte function, depressed platelet numbers and function, generalised muscle weakness, and disorder of the central nervous system; these are frequent complications of acute liver failure. The similarity of the effects of liver failure and hypophosphataemia on the central nervous system (irritability, muscle weakness, dysarthria, confusion, and coma) suggests that phosphate depletion may be important in hepatic encephalopathy, and a progressive defect of phosphate metabolism in brain tissue of patients with chronic liver disease was shown recently by nuclear magnetic resonance spectroscopy. The cause of hypophosphataemia in acute liver failure remains unclear. None of the recognised causes of moderate (0.3-0.7 mmol/l) hypophosphataemia correlated with the phosphate concentrations in our patients. The reduced maximum tubular reabsorption of phosphate in two patients suggests an increased loss of renal phosphate, perhaps due to a direct effect of paracetamol, although the correlation between plasma phosphate and creatinine concentrations suggests that renal failure may protect against hypophosphataemia. Because of the serious clinical implications of phosphate imbalance in acute liver failure the homoeostatic mechanisms of bone and renal phosphate reabsorption in this condition need to be studied urgently. Plasma phosphate concentrations should be monitored carefully during infusion of glucose in patients with liver failure.