Acute fulminant hepatic failure

Fulminant hepatic failure is the rapid onset of life-threatening hepatic decompensation in patients who have no previous history of liver disease. This condition has a multifactorial etiology, including viral hepatitis and drug toxicity. At this time there is no specific therapy for FHF. However, early diagnosis and treatment of the complications--in particular, cerebral edema--may prolong survival and prevent irreversible neurologic complications. Once the diagnosis has been made, patients with FHF should promptly be transferred to a specialized liver care unit where liver transplantation is available. Liver transplantation is now the treatment of choice for patients with clinical characteristics suggesting a poor chance of survival.     

Management options in fulminant hepatic failure

The diagnosis of FHF carries with it a high mortality rate. Though the early results of OLT for FHF are encouraging, some have called for caution as these results are in a select population and may be similar to the optimistic early reports of now-discredited therapies. However, OLT differs fundamentally from all other interventions and, as such, it is ethically unjustified to withhold potentially life-saving therapy from patients with a predicted mortality in excess of 60%. Therefore, patients with FHF should be transferred at an early stage to an experienced liver unit where the option of liver transplantation can be considered.     

Halothane induced fulminant hepatic failure

A rare case of halothane-induced fulminant hepatic failure is reported in a 22 years old male, who developed fever, jaundice, coma and deranged coagulation profile, 2 days after undergoing laparotomy under halothane anaesthesia. Despite all supportive care, he died of fulminant hepatic failure, 6 days after surgery. Postmortem liver biopsy revealed massive predominantly centrilobular hepatic necrosis.     

Structural alterations to the pulmonary circulation in fulminant hepatic failure.

Like patients with chronic liver disease, those with coma due to fulminant hepatic failure may show arterial hypoxaemia even in the absence of pulmonary complications, and in both it is attributed to increased intrapulmonary arteriovenous admixture. This study is concerned with the structural alterations in the pulmonary circulation of patients who have died from fulminant hepatic failure. Precise quantitative morphometric techniques applied to the injected and inflated lung have shown the major abnormality to be a diffuse dilatation of the pulmonary vascular bed affecting arteries and veins of all structural types. At an intra-acinar level the diameter of arteries accompanying respiratory bronchioles was 232.97 micron (+/-SD 46.35) compared with 177.76 micron (+/-SD 30.43) in controls (P less than 0.01). In two-thirds of the patients pleural spider naevi were seen and, throughout the lung, similar significant dilatation of precapillary vessels; but in only one patient were precapillary anastomoses shown. While intrapulmonary venous admixture undoubtedly contributes to hypoxia in fulminant hepatic failure, its exact relation to the structural changes is not yet determined.     

Transcranial Doppler sonography in fulminant hepatic failure

The clinical course of patients with fulminant hepatic failure (FHF) is often worsened by the presence of cerebral edema and endocranial hypertension. In spite of the multiple studies using Transcranial Doppler Sonography (TCDS), few have shown the cerebral blood flow (CBF) pattern among patients with encephalopathy resulting from FHF. OBJECTIVE: Our objective was to characterize the CBF pattern in these patients through the use of TCDS to provide therapeutic strategies. METHOD: The TCDS pattern was assessed in five patients diagnosed with FHF and compared with a control group who displayed critical neurologic conditions not associated with FHF. Pulsatile index, systolic, diastolic, and mean velocity of the middle cerebral artery were measured. RESULTS: The mean age of patients with FHF was 45.4 years. One hundred percent were women, with viral hepatitis as the predominant etiology. A cerebral hypoperfusion pattern was found in 80% of the FHF group and 40% of the control group. In the former group there was no evidence of hyperemia, as there was among 20% of the control group. The mean values of velocity and pulsatile index were 36.6 cm/sec and 2.4, respectively, in the FHF group and 47.8 cm/s and 1.8 in the control group (P=0.268, P=0.402). CONCLUSIONS: FHF patients show a predominance of cerebral hypoperfusion pattern with mean velocities lower than normal values and an increased pulsatile index. We recommend that clinicians take appropriate measures to improve cerebral perfusion and avoid hypoxia. Hyperventilation as a first level measure is contraindicated.     

Cerebrospinal fluid drainage and cranial decompression prolong survival in rats with fulminant hepatic failure

Fulminant hepatic failure (FHF) is a devastating disease. Liver transplantation is the definitive treatment. However, a third of these patients die due to brain edema before a donor becomes available. Cerebrospinal fluid (CSF) drainage and decompressive craniectomy have been used to treat brain edema in brain trauma and hemispheric stroke. However, their role in brain edema associated with FHF has not been examined. In this study we evaluated the potential effects of CSF drainage and decompressive craniectomy on survival in FHF using an experimental model in rats. In CSF drainage experiments all animals had ventriculostomy placed. Five days later FHF was induced with d-galactosamine. Those FHF rats that progressed into comatose stages either received CSF aspiration or did not. In separate experiments the study rats had either a decompressive craniectomy or a sham procedure. FHF was induced 5 days later. We found that both CSF drainage and decompressive craniectomy significantly increased survival of FHF rats compared with the controls: 53.2 +/- 1.1 vs. 48.7 +/- 1.5 h (P = 0.031), and 69.4 +/- 3.9 vs. 53.7 +/- 3.2 h (P = 0.009), respectively. In conclusion, these findings suggest that CSF drainage and decompressive craniectomy may increase the window of opportunity for liver transplantation.     

Liver transplant for fulminant hepatic failure

Fulminant hepatic failure is a challenging indication for liver transplantation because of associated multiple organ failure, profound neurologic abnormalities and coagulopathy. Sixteen patients have undergone emergent orthotopic liver transplantation for this indication at the University of Michigan, Ann Arbor, Michigan. Despite the associated problems, patient survival (68.2% at 2 years), intra-operative blood product utilization and duration of surgery were comparable to patients receiving liver transplants for other indications. All patients experienced complete recovery from preoperative neurologic abnormalities. Recurrent viral hepatitis did occur but did not result in allograft loss. For selected patients, orthotopic liver transplantation is excellent therapy for patients presenting with fulminant hepatic failure.     

Liver transplantation for fulminant hepatic failure: Importance of renal failure

One hundred eighty-one consecutive patients with fulminant hepatic failure (FHF) presenting in a 2-year period were reviewed. In this cohort we examined the impact of pretransplant renal failure on mortality and morbidity following orthotopic liver transplantation (OLTx). Twenty-seven patients (18 female, 9 male) with a median age of 43.5 years (range 19–65 years) underwent OLTx. FHF was due to idiosyncratic drug reaction (n = 4), paracetamol overdose (n = 3), seronegative hepatitis (n = 17), hepatitis B (n = 1), veno-occlusive disease (n = 1), and Wilson's disease (n = 1). Renal failure was present in 14 patients, 7 of whom died (whereas there was 100% survival in patients without renal failure). Pretransplant renal failure was associated with prolonged mechanical ventilation (13 days vs 6 days,P = 0.05), prolonged intensive care stay (17 days vs 8 days,P = 0.01) and prolonged hospital stay (27 vs 21 days,P = NS). Pretransplant renal failure did not predict renal dysfunction at 1 year after OLTx. We conclude that the survival of patients transplanted for FHF is inferior to that of patients transplanted for chronic liver disease (67% vs 88% 1-year survival in Birmingham). For patients with FHF undergoing transplantation, pretransplant renal failure strongly predicts poor outcome with significantly greater consumption of resources.     

Liver transplantation for fulminant hepatic failure: importance of renal failure

Abstract One hundred eighty-one consecutive patients with fulminant hepatic failure (FHF) presenting in a 2-year period were reviewed. In this cohort we examined the impact of pretransplant renal failure on mortality and morbidity following orthotopic liver transplantation (OLTx). Twenty-seven patients (18 female, 9 male) with a median age of 43.5 years (range 19–65 years) underwent OLTx. FHF was due to idiosyncratic drug reaction ( n = 4), paracetamol overdose ( n = 3), seronegative hepatitis ( n = 17), hepatitis B ( n = 1), veno-occlusive disease ( n = 1), and Wilson's disease ( n = 1). Renal failure was present in 14 patients, 7 of whom died (whereas there was 100 % survival in patients without renal failure). Pretransplant renal failure was associated with prolonged mechanical ventilation (13 days vs 6 days, P = 0.05), prolonged intensive care stay (17 days vs 8 days, P - 0.01) and prolonged hospital stay (27 vs 21 days, P = NS). Pretransplant renal failure did not predict renal dysfunction at 1 year after OLTx. We conclude that the survival of patients transplanted for FHF is inferior to that of patients transplanted for chronic liver disease (67 % vs 88 % 1-year survival in Birmingham). For patients with FHF undergoing transplantation, pretransplant renal failure strongly predicts poor outcome with significantly greater consumption of resources.     

Liver transplantation in fulminant hepatic failure: experience with 40 adult patients over a 17-year period

INTRODUCTION: To evaluate the influence of pretransplantation recipient and donor prognostic factors on graft-patient survival. MATERIALS AND METHODS: Between April 1986 and June 2003, 40 liver transplantation (LT) procedures to treat fulminant hepatic failure were performed (5.7%). Twenty-one pre-LT recipient and donor variables were retrospectively considered for analysis. RESULTS: The indications for LT were hyperacute (62.5%), acute (35%), and subacute hepatic failure (2.5%). Glasgow Coma Scale scores ranged from <5 in 22 patients to > or =5 in 18 patients. The causes were hepatitis B (n = 21), unknown (n = 10), Amanita phalloides (n = 5), and other (n = 4). The 1-year graft and patient survival rates were 48.3% and 61.3%, respectively. Perioperative and late mortality was 27.5% and 22.5%. The only variable statistically significant for graft survival was waiting list time for LT <48 hours (P = .05). DISCUSSION: Liver transplantation is the best treatment for fulminant hepatic failure, with a 1-year patient survival rate of 61.3%. The short waiting list time has an important role in outcome.     

Bioartificial liver treatment prolongs survival and lowers intracranial pressure in pigs with fulminant hepatic failure

Intracranial hypertension leading to brainstem coning is a major cause of death in fulminant hepatic failure (FHF). We have developed a bioartificial liver (BAL) utilizing plasma perfusion through a bioreactor loaded with porcine hepatocytes and a column with activated charcoal. In a Phase I clinical trial, we observed a decrease in intracranial pressure (ICP) in FHF patients. However, these patients received BAL therapy together with other measures. We therefore examined whether BAL therapy alone could prevent development of intracranial hypertension in pigs with surgically induced FHF. Pigs (40-60 kg) underwent end-to-side portacaval shunt, transection of all hepatic ligaments, and placement of slings around the hepatic artery and bile duct. After 3 days, the slings were tightened to induce liver necrosis. After 4 h, Group 1 pigs (n = 6) underwent a 6 h treatment with the BAL utilizing 10 billion cryopreserved pig hepatocytes and a charcoal column, Group 2 pigs (n = 6) with the BAL containing charcoal but no cells, and Group 3 pigs (n = 6) with the BAL containing neither cells nor charcoal. Group 1 pigs maintained a normal ICP during BAL treatment and for 14 h afterward and because of this effect they survived longer than Groups 2 and 3 animals. In contrast, Groups 2 and 3 pigs showed an early (6-8 h) rise in ICP.     

Acute lung injury in fulminant hepatic failure following paracetamol poisoning.

BACKGROUND--There is little information on the incidence of acute lung injury or changes in the pulmonary circulation in acute liver failure. The aim of this study was to record the incidence of acute lung injury in fulminant hepatic failure caused by paracetamol poisoning, to document the associated pulmonary circulatory changes, and to assess the impact of lung injury on patient outcome. METHODS--The degree of lung injury was retrospectively assessed by a standard scoring system (modified from Murray) in all patients with fulminant hepatic failure caused by paracetamol poisoning, admitted to the intensive care unit over a one year period. The severity of liver failure and illness, other organ system failure, and patient outcome were also analysed. RESULTS--Twenty four patients with paracetamol-induced liver failure were admitted and nine developed lung injury of whom eight (33%) had severe injury (Murray score > 2.5). In two patients hypoxaemia contributed to death. Patients with lung injury had higher median encephalopathy grades (4 v 2 in the non-injured group) and APACHE II scores (29 v 16). Circulatory failure, requiring vasoconstrictor support, occurred in all patients with lung injury but in only 40% of those without. Cerebral oedema, as detected by abnormal rises in intracranial pressure, also occurred in all patients with lung injury but in only 27% of the non-injured patients. The incidence of renal failure requiring renal replacement therapy was similar in both groups (67% and 47%). Pulmonary artery occlusion pressures were normal in the lung injury group. Cardiac output was high (median 11.2 1/min), systemic vascular resistance low (median 503 dynes/s/cm-5), and pulmonary vascular resistance low (median 70 dynes/s/cm-5), but not significantly different from the group without lung injury. Mortality was much higher in the lung injury group than in the non-injured group (89% v 13%). CONCLUSIONS--Acute lung injury was common in patients with paracetamol-induced fulminant hepatic failure and was associated with systemic circulatory failure and cerebral oedema. The development of acute lung injury was associated with high mortality.