References

The liver in antiquity and the beginnings of anatomy. College of Physicians Philadelphia 1907 29 117-138. 2. Rothschuh KE. History of physiology. Transl GB Risse Huntington, NY Krieger 1973 155-160. 3. Knell AJ. Liver function and failure The evolution of liver physiology. J Royal Coll Physicians of London 1980 14 205-08. 4. Dobson JF. Herophilus of Alexandria. Proc Roy Soc Med 1925 18 19-32. 5. Dobson JF. Erasistratus. Proc Roy Soc Med 1927 20 825-832. 6. French RK. The thorax in...

Vasogenic and Cytotoxic Mechanisms

There are two principal theories regarding the final common path leading to cerebral edema. The vasogenic theory postulates primary disruption of the blood-brain barrier with subsequent leakage of plasma into the extracellular space the cytotoxic hypothesis postulates that a primary alteration of cellular osmoregulation causes direct intracellular edema.3 In acute hepatic encephalopathy, it seems most likely that a cytotoxic mechanism predominates, although both may have a role during different...

Transplantation of Fetal Rat Hepatocytes

In contrast to adult hepatocytes, fetal hepatocytes (FH) are thought to be less immuno-genic and relatively more resistant to cryopreservation and ischemic injuries. These qualities could enhance transplanted cell engraftment. Nonetheless, only a few attempts have been made to transplant fetal liver tissue cells in rats with liver failure and heritable disorders of liver metabolism.30-32 Although some studies provided evidence of transplanted cell function, several issues regarding...

Virus Harvesting

Producer cell lines containing the virus were grown to confluence on T-75 tissue culture flasks using DMEM and 10 FBS. At cellular confluence, media were changed and the following day (16-24 hours later) were collected, spun at 2000 rpm for 5 minutes and the supernatant was filtered (0.22 m) and stored at -70 C. Supernatant infectivity was tested on control NIH 3T3 cells. Highly infective batches (> 106 virions ml) of supernatant were used and the others were discarded. Virus supernatants...

Transplant Evaluation

Patients with FHF are admitted to a surgical intensive care unit for management, as discussed in a previous section of the monograph. In addition to aggressive ICU care, transplant surgeons and hepatologists have to assess the patient's overall condition, attempt to determine the underlying etiology of the disease, predict the chances of spontaneous recovery and complete an emergency evaluation for liver transplantation. At our center, the King's College criteria are used as a guideline to...

Drug Induced Hepatotoxicity

Many drugs are known to be hepatotoxic.78,79 Drug toxicity accounts for 15 of FHF and SFHF cases and runs a subfulminant course in 70 of patients.4 Toxicity is usually unpredictable. Drug ingestion results in liver injury in less than 1 of patients, with 20 developing FHF or SFHF (Table 2.3).3,80 Risk of either FHF or SFHF increases with an increase in total dose, simultaneous ingestion of other drugs which induce or inhibit hepatic enzymes and continuation of drug administration after the...

Late Onset Hepatic Failure LOHF

The above definitions did not take into account patients with prolonged illness prior to the onset of encephalopathy. Various terms have been used to describe this disease entity, including subacute or subchronic atrophy of the liver, subacute hepatitis, subacute (fatal) hepatitis and subacute hepatic necrosis. More recently, the term LOHF has been introduced by Gimson to describe patients who develop encephalopathy 2-6 months after the onset of liver dysfunction (Table 2.1).7 Generally, in...

Walid S Arnaout David Reybould

Fulminant hepatic failure (FHF) continues to be one of the most devastating conditions affecting thousands of individuals each year. By definition, these are patients who were previously healthy without any known underlying liver disease. Historically, the outcome of these patients in most cases has been poor. With the introduction of orthotopic liver transplantation in the late seventies and following the NIH consensus conference on liver transplantation in 1983, orthotopic liver...

Summary

Intracranial hypertension has become a major concern in FHF management. Most of the deaths occurring in FHF patients are related to a rise in ICP. The etiology of brain edema is still unknown. An osmotic effect of glutamine accumulation in astrocytes has been proposed several experimental animal models support this hypothesis. Toxic products from the necrotic liver also have been implicated in the genesis of brain edema in FHF patients. Determining the mechanisms of brain edema in FHF should...

Other Viral Causes of Liver Failure

The herpes virus family rarely causes FHF or SFHF. There have been several reports of Herpes simplex virus types 1 and 2 producing massive hepatic necrosis, usually in patients who are pregnant or immunocompromised.68-71 Reports of FHF with cytomegalovirus and Epstein-Barr virus infections have been controversial due to lack of availability of serological confirmation and or exclusion of other etiologies.72,73 Disseminated adenovirus can occur in immunosuppressed patients and presents with...

Critical Clinical Care Issues

The LSU represents a tertiary referral site for patients with severe forms of liver failure. Compulsive attention to detail is the hallmark of care in this setting it has to start before a patient arrives at the Unit. Most patients are transferred to the LSU from other facilities. It is important to establish whether patients require airway protection, sedation and treatment of cerebral edema during transport. A line of communication needs to be established with referring physicians to ensure...

Viral Causes of Liver Failure

The incidence of fulminant and subfulminant HAV is very low and occurs in less than 0.01 of all HAV infections.3 Younger patients rarely develop hepatic failure. HAV accounted for less than 6 of FHF and SFHF cases due to viral hepatitis in the United States and France but 31 of the cases in Britain.14-16 HAV infection results in FHF more frequently than SFHF.17 Survival with medical therapy is relatively high, ranging between 40 and 60 .16,18 Relapse of HAV occurs in 10 of patients, usually...

Hepatic Vein Obstruction

Obstruction of the hepatic veins results in sinusoidal dilatation of the centrilobular region with ischemic necrosis of the surrounding parenchyma. If severe, this will progress to FHF.123 Thrombosis of the large hepatic veins results in Budd-Chiari syndrome and is associated with myeloproliferative disorders, coagulation abnormalities and ingestion of oral contraceptives.124 FHF due to Budd-Chiari syndrome is universally fatal and is often diagnosed at autopsy.125 Liver transplantation or...

Neurologic Examination

The earliest changes of hepatic encephalopathy include only minor variations in mental status. Increased irritability, alterations in sleep wake cycle and subtle personality changes and agitation may occur. The stages of hepatic coma are listed in Table 3.2. Neurologically, early clinical features include a generalized increase in muscle tone which may later progress to decerebrate posturing. A brisk deep tendon reflex may also be an early sign, with sustained clonus manifested at later stages....

Brief Historical Perspective

The United Nations has recommended standardized datingusingBCE, for 'before the common era, instead of BC and CE, for 'common era, instead of AD. Throughout history, man has striven to understand the liver's function and disorders. Early representations of the liver were seen in the form of clay models of sheep livers from the Assyro-Babylonian era (3000-2000 BCE).1 Ancient cultures believed that the liver was responsible for generating heat and blood, qualities essential for life and soul. But...

Fluids Electrolytes and Nutrition

Fluid management in FHF patients requires maintenance of a balance to avoid fluid overload as well as dehydration, as multiorgan failure develops. Central pressure monitoring, cardiac performance and peripheral resistance are determined using a pulmonary artery catheter. Renal failure can occur in the face of pulmonary edema and peripheral vascular collapse strict monitoring of fluid balance is therefore required. Furthermore, cerebral edema and intracranial hypertension require careful fluid...

Toxins

Toxins account for less than 2 of FHF or SFHF.3 Amanita mushroom poisoning and industrial hydrocarbons are involved in the majority of cases. Mushroom toxicity, caused by Amanita phalloides verna and virosa, has been reported in Europe and the United States. The active agents, phallotoxins and amanatoxins, have an enterohepatic circulation and are not destroyed by cooking.100 As in acetaminophen-induced FHF, liver damage from mushroom toxicity is delayed and is usually proceeded by an 1-4 day...

Methods

All procedures were conducted in full compliance with the standards of the Institutional Committee for the Protection of Human Subjects, in accordance with the Helsinki Declaration of 1975. Eight patients with acetaminophen-induced FHF who fulfilled the KCH criteria were treated in our Liver Support Unit (Table 9.1). All patients were admitted to a dedicated surgical intensive care unit and were evaluated for urgent OLT. All patients were endotracheally intubated for airway protection and were...

Selection with Hygromycin B

Cells were plated on 35 mm collagen-coated plates (1 x 105 cells plate). During the attachment period, Dulbecco's modified Eagle's medium without glutamine but with 10 fetal bovine serum was used. After three hours, the medium was changed to hormonally-defined serum-free RPMI 1640, which was then replaced every 24 hours. Cultures were maintained at 37 C in a humidified atmosphere (5 CO2 and 95 air). After three days in culture, cells were selected with HB (LD99 500 mg ml) and their viability...

OGrady Classification

The above definitions have attempted to clarify the relationship between prognosis and time of onset of encephalopathy. However, after a detailed review of their FHF patients, O'Grady et al proposed a new terminology (Table 2.1).8 Hyperacute liver failure was defined as the development of encephalopathy within 7 days of the appearance of jaundice. These patients had a fair prognosis with a survival rate of 36 , despite a 69 incidence of cerebral edema. Etiology in this group included all cases...

Hepatic Encephalopathy and Cerebral Edema

The presence of hepatic encephalopathy and cerebral edema significantly influences the management and outcome of FHF. Neurologic deterioration with irreversible brain damage is a contraindication for liver transplantation in up to 30 of patients.1 Neurologic complications represent a major cause (30 ) of posttransplantation mortality.1 Autopsy studies demonstrate cerebral edema in 80 of patients who die from FHF.11,12 The pathogenesis of encephalopathy and increased intracranial hypertension...

Steven D Colquhoun Caroline A Connelly

Hepatic encephalopathy is a neuropsychiatric syndrome that refers to potentially reversible derangement of thought and behavior which accompany liver disease.1 Although there may be significant overlap in symptoms and etiology, both liver disease and hepatic encephalopathy can exist in either acute or chronic forms. Although chronic hepatic encephalopathy is more prevalent, the neurologic changes accompanying acute liver failure are more dramatic and may develop rapidly. Clinically, the...

Support of the Acutely Failing Liver

Frederick D. Watanabe, M.D. Cedars-Sinai Medical Center Los Angeles, California, U.S.A. Landes Bioscience Georgetown, Texas U.S.A. Support of the Acutely Failing Liver Second Edition Tissue Engineering Intelligence Unit Eurekah.com Landes Bioscience Designed by Judith Kemper Copyright 2000 Eurekah.com All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording,...

Frederick D Watanabe Elaine Kahaku Theodore Khalili Paul Ting Anthony Navarro Achilles A Demetriou

In spite of substantial advances in general supportive therapy and critical care, mortality in fulminant hepatic failure (FHF) remains unacceptably high, due primarily to incomplete understanding of the pathophysiology of the disease.1 Despite this, clinicians have attempted to develop rational novel therapeutic modalities focusing mostly on plasma detoxification.2-7 Whole liver perfusion using either human or xenogeneic organs has been used successfully to treat patients with FHF, but is...

Surgical Technique

Veno Venous Bypass Liver Transplant

There are currently several techniques available for liver transplantation, some of which apply only to patients with FHF. Generally, liver transplantation in this group of patients can be done with an orthotopic or a heterotopic approach. Orthotopic liver transplantation involves a total hepatectomy followed by placement of an allograft in the anatomic position. In heterotopic liver transplantation HLT , the native liver is left intact and the liver allograft is placed in a nonanatomic...