Fulminant hepatic failure

Opinion statement The rare but potentially devastating clinical syndrome of fulminant hepatic failure has as its components severe encephalopathy and finally cerebral edema, hemodynamic instability, renal failure, coagulopathy, profound metabolic disturbances and a particular susceptibility to bacterial and fungal infection. Despite advances in medical management, fulminant hepatic failure in its most severe form carries a high mortality rate unless urgent orthotopic liver transplantation is carried out. However, availability of cadaveric donor organs is limited and, due to the rapidly progressive clinical course in many cases, a substantial proportion of patients will die or develop contraindications to transplantation before the procedure can be performed. Consequently, recent interest has centred on living donor transplantation and the possibility of providing temporary liver support, either through auxiliary partial organ transplantation, extracorporeal perfusion or transplantation of hepatocytes, to allow time for either a liver graft to become available or native liver regeneration, on which spontaneous survival ultimately depends, to occur.     

Fulminant hepatic failure

Opinion statement Fulminant hepatic failure is a rapidly progressive and often fatal syndrome, and the only definitive treatment is liver transplantation. However, given the scarcity of available grafts, the mainstay of therapy remains supportive care until there is spontaneous recovery or until a suitable donor liver becomes available. After initial assessment and stabilization, patients should be transferred to the nearest liver transplant center as soon as possible, as they can deteriorate rapidly. All patients with fulminant hepatic failure must be monitored closely and treated for hepatic encephalopathy, coagulopathy, gastrointestinal bleeding, renal failure, cerebral edema, and metabolic derangement.     

Transplantation of the liver in adults and children with fulminant hepatic failure

Fulminant hepatic failure has a high mortality rate despite intensive medical treatment. Urgent hepatic transplantation was considered over a 3 year period in 26 (36%) of 73 patients with the worst prognostic features of fulminant hepatic failure. The criteria for patient selection were based on the duration of advanced hepatic coma and the deterioration of liver function. Sixteen patients were transplanted, and 9 (56%) are currently alive. The median duration of follow-up is 16 months and actuarial 1 year survival 55%. Six patients died because of the absence of offers of organ donation. Twenty-two (85%) of the 26 patients considered were referred with advanced encephalopathy or hepatorenal syndrome. Of the 57 patients not transplanted, 18 (95%) of 19 patients with grade I/II encephalopathy survived compared to 13 (34%) of 38 patients with grade III/IV encephalopathy. Transplantation does improve the chance of survival in selected patients with fulminant hepatic failure, early referral and availability or organ donation being important factors.     

Intensive therapy for fulminant hepatic failure: importance of co-operation between physicians of internal medicine and transplantation surgery]

We followed up the patients with fulminant hepatic failure who admitted in our hospital and investigated clinical problems raised in the patients who underwent living-related liver transplantation (LRLT). Among 15 patients with fulminant hepatic failure 6 were managed without LRLT and 3 patients survived, and the survival rate was 50%. Other 9 patients received LRLT, and 2 of these 9 died with their complications after the transplantation. Thus the survival rate by LRLT in fulminant hepatic failure was 77.8%. Brain CT scan examination showed severe brain edema in a patient and the edema did not improve after LRLT. Another patient suffered from development of fungal infection in her lungs after LRLT. We suspected the presence of subclinical infection in the preoperation period. The recovery from brain edema and the existence of subclinical infection are mostly difficult to evaluate but are very important for obtaining a good output. These results suggest that LRLT is a promising procedure for treatment of fulminant hepatic failure but a close cooperation between physicians of internal medicine and transplantation surgery from preoperative management until postoperative period is necessary.     

Acute liver failure

Acute liver failure, also called fulminant hepatic failure, is characterized by sudden hepatic synthetic dysfunction associated with coagulopathy and hepatic encephalopathy. Acute liver failure has most recently been defined based on the timing from onset of jaundice to encephalopathy as follows: 1) hyperacute (1-7 days); 2) acute (8-28 days), and 3) subacute (29-60 days). Rapid onset of encephalopathy in hyperacute liver failure is paradoxically associated with highest rate of spontaneous recovery, and subacute liver failure is associated with worst prognosis. The etiology of liver failure is established by history, serologic assays, and exclusion of alternative causes. Acute liver failure is most frequently caused by drug hepatotoxicity, including acetaminophen toxicity and idiosyncratic drug reactions, with viral hepatitis playing a lesser role in recent surveys. A substantial number of cases have an indeterminate etiology. Major complications of acute liver failure that require active intervention include metabolic disorders, coagulopathy, cerebral edema, renal failure, and infection. The focus of management of acute liver failure is comprehensive supportive care in an intensive care unit and assessment of the need for liver transplantation.     

Liver transplantation in mushroom poisoning

Liver transplantation plays an important role in the treatment of patients with fulminant hepatic failure (FHF). Early determination of prognosis in cases of FHF is important to allow prompt decision-making regarding the need for liver transplantation. Mushroom poisoning is a rare cause of FHF, and as a result, prognostic criteria are not well recognized. It appears that the severity of coagulopathy and encephalopathy predicts a poor outcome, whereas the degree of bilirubin elevation may not. We present a case of FHF related to mushroom poisoning that required liver transplantation. The clinical presentation, medical management, and prognostic criteria in mushroom poisoning are discussed.     

Acute liver failure

Acute liver failure (ALF) (sometimes referred to as fulminant hepatic failure) is a clinical syndrome from a variety of causes resulting from rapid loss in hepatocyte function, typically associated with coagulopathy and encephalopathy in a patient without preexisting liver disease or cirrhosis. Cerebral edema is a cardinal feature and may produce uncal herniation, yielding brain stem compression and death. The typical interval from onset of symptoms to onset of encephalopathy is 1 to 2 weeks, but cases evolving more slowly, up to 6 months, may still be included in the definition. ALF is rare, affecting 2000 patients annually in the United States, and comprises ～7% of liver transplants annually. Currently, in the United States, acetaminophen accounts for ～50% of all cases of ALF, but other etiologies include hepatitis, drug-induced liver injury, autoimmune hepatitis. Prior to the availability of liver transplantation (LT), mortality of ALF was extremely high, often exceeding 90%; most common causes of death were multiorgan failure, hemorrhage, infection, and cerebral edema. Fortunately, survival has improved considerably in the last 3 decades (overall survival now exceeds 60%). In large part, this improved survival reflects the option of LT but also reflects the high frequency of acetaminophen toxicity as a cause of ALF. In fact, most patients with ALF are not candidates for LT. Critical care of patients with ALF is key to their survival, and decisions must sometimes be made with inadequate information. We review standard practices (medical, pharmacological, and LT) and new research initiatives and findings for this interesting but vexing orphan disease. Particular attention will be paid to practical matters for clinicians to consider in approaching the ALF patient.     

Efficacy of liver assisting in patients with hepatic encephalopathy with special focus on plasma exchange

Severe liver injury result in development of hepatic encephalopathy (HE) and often also in brain edema that is a potentially fatal complication. HE and brain edema are correlated to the level and persistence of hyperammonemia and the presence of systemic inflammation. Treatment of HE and brain edema is based on restoring and keeping normal physiological variables including tonicity, blood gasses, lactate, temperature and vascular resistance by a wide variety of interventions. In addition liver support devices improve the stage of HE, cerebral metabolic rate for oxygen and glucose, and are used either as a bridge to liver transplantation or liver recovery in patients with fulminant hepatic failure and in patients with acute-on-chronic liver failure. This short review will mainly focus on the management and efficacy of doing plasma exchange on HE in patients with acute HE.     

USE OF TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT AS A BRIDGE TO TRANSPLANTATION IN FULMINANT HEPATIC FAILURE DUE TO BUDD CHURI SYNDROME

We report a case of fulminant hepatic failure in a 55-yr-old man due to Budd-Chiari syndrome in the setting of polycythemia rubra vera. The patient presented with acute hepatic failure, which rapidly progressed to grade IV hepatic encephalopathy. Placement of a transjugular intrahepatic portosystemic shunt resulted in marked improvement of the encephalopathy and stabilized the liver failure. Suhsequently, he underwent successful nonemergent orthotopic liver transplantation. Transjugular intrahepatic portosystemic shunt placement is a safe, effective, therapeutic option to bridge patients with fulminant Budd-Chiari to liver transplantation.     

Multimodal brain monitoring in fulminant hepatic failure

Acute liver failure, also known as fulminant hepatic failure(FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting.     

Major complications of acute and chronic liver disease

Many advances have been made in the understanding, diagnosis, and management of severe complications of liver disease. The pathogenesis of hepatic encephalopathy remains a challenge. Several toxins including ammonia, mercaptans, short-chain fatty acids, benzodiazepine-like substances, GABA-like substances, and impaired glutamatergic neurotransmission are at the top of the list of candidates. Use of the benzodiazepine antagonists is an experimental but promising new therapy in patients with hepatic encephalopathy. In patients with cirrhosis, spontaneous bacterial peritonitis (SBP) remains a common and highly lethal complication. The diagnosis of SBP is based on the polymorphonuclear cell count in the ascites and confirmed by culture of ascitic fluid. Early diagnosis and aggressive treatment has reduced mortality of SBP from greater than 90 per cent to 30 to 50 per cent. The appearance of cerebral edema in severe acute hepatocellular failure is associated with high mortality and conventional neurologic signs may be unreliable indicators of brain swelling. Current management of cerebral edema in fulminant hepatocellular failure may include early placement of an extradural sensor for continuous monitoring of intracranial pressure, so that short-term measures can be instituted making later liver transplantation safer. Coagulopathy remains a serious problem in patients with liver disease. Exchange plasmapheresis is a promising short-term adjuvant therapy. However, liver transplantation should be considered the definitive treatment for fulminant hepatocellular failure. The gastroenterologist often encounters multiorgan failure in patients with severe liver disease. Liver transplantation is now an important therapeutic consideration in almost every patient with severe, irreversible liver disease. Efforts should be targeted to early diagnosis of irreversible disease and coordination of patient care with a liver transplant center.     

Liver transplantation in acute liver failure:A challenging scenario

Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, intervalbetween jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation.     

Acute liver failure in Japan: definition, classification, and prediction of the outcome

Acute liver failure is a clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to severe impairment of liver function caused by massive or submassive liver necrosis. Viral hepatitis is the most important and frequent cause of acute liver failure in Japan. The diagnostic criteria for fulminant hepatitis, including that caused by viral infections, autoimmune hepatitis, and drug allergy induced-liver damage, were first established in 1981. Considering the discrepancies between the definition of fulminant hepatitis in Japan and the definitions of acute liver failure in the United States and Europe, the Intractable Hepato-Biliary Disease Study Group established the diagnostic criteria for "acute liver failure" for Japan in 2011, and performed a nationwide survey of patients seen in 2010 to clarify the demographic and clinical features and outcomes of these patients. According to the survey, the survival rates of patients receiving medical treatment alone were low, especially in those with hepatic encephalopathy, despite artificial liver support, consisting of plasma exchange and hemodiafiltration, being provided to almost all patients in Japan. Thus, liver transplantation is inevitable to rescue most patients with hepatic encephalopathy. The indications for liver transplantation had, until recently, been determined according to the guideline published by the Acute Liver Failure Study Group in 1996. Recently, however, the Intractable Hepato-Biliary Disease Study Group established a scoring system to predict the outcomes of acute liver failure patients. Algorithms for outcome prediction have also been developed based on data-mining analyses. These novel guidelines need further evaluation to determine their usefulness.     

Emergency liver transplantation for fulminant liver failure in infants and children.

We report our results with orthotopic liver transplantation in children with fulminant liver failure. Thirty-five children with fulminant liver failure were evaluated for liver transplantation. The main causes of liver failure were viral hepatitis (54.2%), drug-induced liver injury (14.2%) and Wilson's disease (11.4%). Children were considered as candidates for liver transplantation only if hepatic encephalopathy was associated with a decrease in the level of factor V to below 25%. Seven children (20%) did not meet this criterion and recovered spontaneously. Six children (17.1%) had contraindications for liver transplantation and died. In three of these six children, contraindications included irreversible brain damage at the time of admission. Twenty-two children (62.8%) met the criteria for liver transplantation and were placed on the emergency transplant list. Three of them died awaiting grafts. Nineteen children underwent liver transplantation; 13 of them (68.4%) are alive without sequelae, after 6 mo to 4 yr of follow-up, at this writing. Four of the children who died after surgery had severe encephalopathy on admission that did not improve after liver transplantation. In conclusion, emergency liver transplantation appears to be an effective treatment for children with fulminant liver failure. Nevertheless, irreversible brain damage developed in 10 patients, and they died before or after surgery. We postulate that many of these deaths could have been avoided if children had been transferred to a liver transplantation facility and had undergone transplantation earlier. We emphasize that children with acute liver failure should be transferred to a center that performs liver transplantation before the development of hepatic encephalopathy.     

The development of low-grade cerebral edema in cirrhosis is supported by the evolution of (1)H-magnetic resonance abnormalities after liver transplantation.

BACKGROUND/AIMS: Liver failure may cause brain edema through an increase in brain glutamine. However, usually standard neuroimaging techniques do not detect brain edema in cirrhosis. We assessed magnetization transfer ratio and (1)H-magnetic resonance (MR) spectroscopy before and after liver transplantation to investigate changes in brain water content in cirrhosis. METHODS: Non-alcoholic cirrhotics without overt hepatic encephalopathy (n=24) underwent (1)H-MR of the brain and neuropsychological tests. (1)H-MR results were compared with those of healthy controls (n=10). In a subgroup of patients (n=11), the study was repeated after liver transplantation. RESULTS: Cirrhotic patients showed a decrease in magnetization transfer ratio (31.5+/-3.1 vs. 37.1+/-1.1, P<0.01) and an increase in glutamine/glutamate signal (2.22+/-0.47 vs. 1.46+/-0.26, P<0.01). The increase in glutamine/glutamate signal was correlated to the decrease in magnetization transfer ratio and to neuropsychological function. Following liver transplantation, there was a progressive normalization of magnetization transfer ratio, glutamine/glutamate signal and neuropsychological function. Accordingly, correlations between these variables were lost after liver transplantation. CONCLUSIONS: Cirrhotic patients show reversible changes in magnetization transfer ratio that are compatible with the development of low-grade cerebral edema. Minimal hepatic encephalopathy and low-grade cerebral edema appear to be the consequences of the metabolism of ammonia in the brain.     

Prognostic factors for fatal outcomes prior to receiving liver transplantation in patients with non-acetaminophen-related fulminant hepatic failure

BACKGROUND AND AIM: Many patients continue to die due to the rapid development of cerebral edema and/or multiple organ failure prior to receiving a liver transplantation. METHODS: We investigated the prognostic factors associated with 1-week fatal outcomes after the diagnosis of fulminant hepatic failure, which were associated with fatal outcomes prior to receiving liver transplantation, in 104 patients with non-acetaminophen-related fulminant hepatic failure. RESULTS: With a multivariate logistic regression analysis, age (>40 years), systemic inflammatory response syndrome (SIRS) and plasma prothrombin activities (40 years), cause of fulminant hepatic failure (viral hepatitis), plasma prothrombin activity (相似文献   

Fulminant liver failure induced by hepatosplenic alphabeta T-cell lymphoma

Since survival rates of fulminant liver failure are low, early consideration of liver transplantation in patients developing hepatic encephalopathy due to progressive liver failure is mandatory. Rapid diagnostic work-up is necessary to identify the underlying disease and to rule out contraindications to liver transplantation. We report the case of a 35-year-old patient presenting with fulminant hepatitis and a four-week history of biopsy-proven autoimmune hepatitis. Despite high-dose steroid-treatment liver function progressively worsened and hepatic encephalopathy rapidly developed. Histopathologic evaluation of a liver biopsy specimen revealed necrotizing hepatitis and rare atypical lymphocytes. Surgical biopsy specimens confirmed the suspicion of an aggressive hepatosplenic alphabeta T-cell lymphoma which represents a contraindication to liver transplantation.     

Decreased white matter lesion volume and improved cognitive function after liver transplantation

Focal T2-weighted white matter lesions (WML) on brain magnetic resonance imaging (MRI), mimicking those seen in cerebrovascular small-vessel disease described in patients with persistent hepatic encephalopathy, decreased in volume with the improvement of hepatic encephalopathy. This outcome has been interpreted as a decrease in the edema that it is proposed to be involved in the pathogenesis of hepatic encephalopathy. We designed a study to further investigate potential changes in focal WML in the brains of patients with cirrhosis following liver transplantation and to study the relationship between these changes and overall cognitive function. We used MRI to measure the volume of supratentorial focal WML and a neuropsychological examination to assess cognitive function before and after liver transplantation in 27 patients with cirrhosis without signs of overt hepatic encephalopathy. Baseline MRI identified focal T2-weighted lesions in 19 patients (70.3%). The presence of WML was associated with older age but not with vascular risk factors, severity of liver function, or psychometric tests. A significant reduction in lesion volume was observed after liver transplantation (from a median of 1.306 cm(3) to 0.671 cm(3), P = 0.001). This decrease correlated with an improvement in an index of global cognitive function (r = -0.663; P < 0.001). This evolution indicates that lesion volume is partially related to a reversible type of tissue damage, which is compatible with brain edema. CONCLUSION: Focal WML probably induced by age-related microvascular injury can decrease their volume with liver transplantation. The associated improvement of cognitive function supports a relationship between brain edema and minimal hepatic encephalopathy.     

Complete recovery from fulminant hepatic failure with severe coma by living donor liver transplantation

In Japan, living donor liver transplantation has been established as a therapeutic strategy for the rescue of terminal liver disease, including fulminant hepatic failure that shows no signs of recovery. We performed living donor liver transplantation for a subacute type fulminant hepatic failure patient, who had developed a hepatic coma of grade V (no right reflex, no response to pain stimuli). The electroencephalogram indicated almost flat waves. However, cranial computed tomography revealed that brain edema was not severe in this case. The recipient did not have hepatitis virus and had not taken medication that had been determined to cause hepatitis. The recipient was a 12-year-old boy, 165.5 cm in height and 45.5 kg in weight. The donor was his mother, who was 42 years old; her blood type, type B, was identical to that of the boy. The mother's right hepatic lobe was transplanted to her son (the recipient). The post-transplantation condition of recipient was quite excellent. He recovered consciousness 3 days after liver transplantation, and rapidly attained normal hepatic function. The donor was discharged on the 20th postoperative day without any problems. The recipient was discharged on the 79th postoperative day without any neurological deficits. This case suggests that deep coma without electroencephalogram waves may not be a contraindication for living donor liver transplantation in fulminant hepatic failure patients, if the brain edema is not severe.     

Fulminant hepatic failure

The term "fulminant hepatic failure" (FHF) encompasses a pattern of clinical symptoms and pathophysiological responses associated with rapid arrest of normal hepatic function. The syndrome is defined by the presence of hepatic encephalopathy in association with coagulopathy and jaundice. In many cases, the clinical picture is complicated by cerebral edema, renal impairment, sepsis, and multiorgan failure. In this review, we examine the specific causes of FHF, including acetaminophen-related hepatotoxicity, drug- and viral-related FHF, and other less common causes of FHF such as pregnancy and vascular related disease. The approach to FHF should be multidisciplinary and requires a thorough understanding of the biochemical, metabolic, and physiological changes associated with hepatic necrosis. Also examined are management issues pertinent to these complex situations and the role of liver transplantation and liver assist devices are considered.