Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bile acid levels were measured in the sera, cerebrospinal fluid (CSF), and brain tissue of 10 patients immediately after death from fulminant hepatic (FHF). Serum bile acids in FHF were predominantly conjugated, and total bile acid levels were higher in all 10 patients than in normal controls (85.9 +/- SE 8.4 compared with 5.7 +/- 0.4 nmol/ml, P less than 0.001). Small but significant amounts could be detected in CSF (range 1.2-5.3 nmol total bile acid/ml) and brain biopsies (1.0-18.8 nmol/g wet weight) of FHF patients, whereas none could be detected in CSF and brain biopsies of patients dying without evidence of liver disease. There was no relationship between serum, CSF, or brain levels and duration of coma, or presence of cerebral oedema found in five FHF patients at necropsy. However, serum bile acid levels were similar in FHF to those found in chronic liver disease without encephalopathy and lower than those found to inhibit brain respiration in vitro. A primary role for these compounds in the pathogenesis of coma in FHF therefore seems unlikely.
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PMID:Serum, cerebrospinal fluid, and brain levels of bile acids in patients with fulminant hepatic failure. 60 89

Coated charcoal hemoperfusion started in the earlier grades of coma appears to improve the survival rate of drug-induced FHF. This is based on randomized control animal studies and clinical trials using historical controls. Even if randomized clinical trials in patients should substantiate these findings, it is still a very small step in artificial liver support. Viral-induced FHF and cirrhotic encephalopathy are much more common conditions that still cannot be supported. However, this initial promising step should encourage us to become more optimistic about the possibility of developing artificial livers for the higher levels of support. A multifaceted approach in research should include evaluations of combined approaches. Increased basic knowledge in toxic and essential substances will be another important requirement.
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PMID:Experimental artificial liver support with emphasis on fulminant hepatic failure: concepts and review. 352 8

Fulminant or subfulminant liver failure, complicated by encephalopathy and in many cases by death is seen to be a syndrome that may result from numerous causes. Although viral hepatitis, drug-induced hepatitis, and hepatitis due to various types of poisonings, in decreasing frequency, account for 90% of all cases, a variety of miscellaneous conditions account for the remainder. Consideration of the possibility of these less common etiologies by the clinician is of considerable importance, since some, including massive malignant involvement (such as leukemia) or acute fulminant Wilson's disease, may respond to specific treatment measures. Thus, unless hepatic transplantation proves to be applicable in FHF of many etiologic diagnosis may continue to have important therapeutic indications in at least some cases with this syndrome.
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PMID:Fulminant and subfulminant liver failure: definitions and causes. 352 10

1. Levels of BZ receptor ligands are elevated in the brain of animal models of FHF and humans with FHF. Some of these ligands have agonist properties and some are known 1, 4-BZs which bind to the DS receptor. Much of the BZ receptor ligand activity in HE is unidentified and it is possible that some may bind to receptor subtypes other than the DS receptor. 2. Average levels of BZ receptor ligands in the brain in HE do not appear to be sufficient to augment GABAergic tone to a degree that would result in severe encephalopathy (i.e. coma). However, these ligands have a heterogeneous distribution in the brain and their neuroinhibitory effects may be potentiated by increased availability of GABA at GABAA receptors. Furthermore, that these ligands may contribute to HE is suggested by anecdotal reports of ameliorations of HE being induced in a majority of patients by the BZ receptor antagonist flumazenil. 3. The response of HE to flumazenil in humans is usually incomplete and in animal models may be modest. Potential explanations for these findings include pharmacokinetics, BZ receptor subtype specificity and higher levels of BZ receptor ligands in the brain in humans with HE than in animal models. 4. Certain BZ receptor ligands e.g. Ro 15-3505 and Ro 15-4513, that are structurally related to flumazenil, are more efficacious at ameliorating HE than flumazenil in animal models. These findings may be more dependent on differences in BZ receptor subtype specificity than differences in intrinsic activity. The properties of an ideal BZ receptor ligand for administration to a patient with HE would appear to be: (i) antagonist action at BZ receptors, (ii) no intrinsic activity apparent after a conventional pharmacologic dose, (iii) high specificity and affinity for BZ receptors, (iv) slow metabolism, and (v) absence of toxic effects. Promising ligands, such as Ro 15-3505, with weak partial inverse agonist actions and hence analeptic potential, require careful evaluation of their therapeutic index before clinical application. 5. BZ receptor ligands may be useful in the management of HE. Specifically, they may be given IV: (i) to reverse effects of exogenous BZs; (ii) to aid in the differential diagnosis of encephalopathy; (iii) to provide prognostic information; and (iv) to optimize brain function. They may also be given orally with the objective of reducing dietary protein intolerance in patients with chronic liver disease.
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PMID:Do benzodiazepine ligands contribute to hepatic encephalopathy? 811 87

Evoked responses have not been studied in patients with acute severe hepatitis (ASH) with or without hepatic encephalopathy. This prospective study was undertaken to find out diagnostic as well as prognostic value of visual evoked responses (VER), and brain stem auditory evoked responses (BAER) in patients with ASH with or without encephalopathy. Visual evoked responses and BAER were studied in 20 patients (14 males and six females) with ASH. The patients were diagnosed as having severe hepatitis if acute hepatitis was associated with raised serum bilirubin and serum transaminases, and if they had a prothrombin time index of < 50%. After a detailed neuropsychiatric examination of each patient, the study sample was divided into two groups of 10 patients: ASH without encephalopathy (ASH-WOE), and ASH with encephalopathy (fulminant hepatic failure, FHF). The median P100 latencies of FHF patients were significantly increased compared with controls and patients in the ASH-WOE group. Abnormal P100 latencies, exceeding 95th percentile values of the controls, were present in one patient in the ASH-WOE group and six patients in the FHF group. The median interpeak latencies I-III, III-V and I-V were significantly prolonged in the FHF group. Interpeak latencies III-V were also increased significantly in patients in the ASH-WOE group. While abnormal BAER were seen frequently in both groups, VER abnormalities were largely confined to patients in the FHF group. In the FHF group, six out of 10 patients survived and exhibited clinical improvement in the status of hepatic encephalopathy. Evoked responses were repeated after 2-3 weeks of recovery in these patients and VER abnormalities showed a tendency to normalize, thereby suggesting a prognostic implication. The incidence of abnormal VER in hepatic encephalopathy complicating ASH far exceeded that of abnormal BAER. Markedly prolonged P100 latencies in FHF patients indicate poor prognosis.
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PMID:Visual and auditory evoked responses in acute severe hepatitis. 925 51

Fulminant hepatic failure is a devastating illness that carries considerable mortality and affects patients with previously healthy livers. Although the etiology of FHF remains unclear in a significant number of cases, viral hepatitis and drug-induced liver injury account for the majority of identifiable causes. The clinical presentation varies widely, but is always characterized by the presence of encephalopathy. Markedly elevated transaminases are seen, but do not correlate with extent of liver injury. Prothrombin time, bilirubin, creatinine, and arterial pH are prognostic indicators of survival in FHF. FHF and its consequences must be readily recognized so that appropriate triage and treatment can be administered. All patients should be managed in an intensive care setting pending transfer to a liver transplantation center. Supportive care remains the mainstay of treatment, with liver transplantation reserved for select patients.
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PMID:Fulminant hepatic failure. 956 13

FHF is a devastating illness of varied causes, carrying considerable mortality and affecting patients with previously healthy livers. The clinical presentation varies widely but encephalopathy is the defining criterion. Management requires a multidisciplinary approach, including rapid triage, monitoring, and referral to a transplantation center for further evaluation. Early prognostication and timely availability of donor livers are essential for a successful outcome. A donor shortage, however, continues to pose problems for both hepatologists and surgeons. Effective liver support devices may greatly prolong the window of opportunity to provide a donor liver, or alternatively to allow the native liver to regenerate. Despite decades of great progress in the field of liver support systems, the ideal system is still a long-cherished goal in hepatology. Hybrid systems have garnered most of the recent attention, but the quest for improved synthetic function has not yet been realized. It is hoped that rapid conceptual and technologic developments with respect to hybrid systems, hepatocyte transplantation, and xenografting will yield a safe and accessible tool for managing these critically ill patients. Controlled, multicenter trials in well-defined patient groups and with standard outcome measures are essential to evaluate the clinical value of these devices. A better understanding of mechanisms responsible for liver cell death and multiorgan failure, and the development of strategies to enhance liver regeneration, may allow a more targeted approach to therapy.
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PMID:Fulminant hepatic failure. 1469 3

FHF is characterized by a high percentage of unknown causes leading to acute liver failure and furthermore by an increased morbidity and mortality prior to and post-Ltx. In different transplant centers, the reasons leading to FHF differ significantly as well as outcome. We report our single center experience with 30 pediatric patients receiving a liver transplant for FHF, out of a total of 83 children presenting with FHF. The time to transfer patients to the transplant center after the diagnosis of FHF was long, with a median of 14 days (Ltx group) and 12 days (controls), respectively. In nearly half of the patients (n = 14) in the Ltx group, we were not able to establish an exact diagnosis prior to Ltx: 50% suffered from encephalopathy, and 13 patients were treated in the intensive care unit prior to transplant. Because of the availability of different surgical techniques, all children received a timely transplant [split (n = 18), living donor (n = 9), whole organ (n = 2), and reduced liver (n = 1)]. Patient survival was 93.4%, and graft survival was 83.4% for at least one yr follow-up. Severe complications following Ltx included three cases with aplastic anemia and one child suffering from systemic mitochondrial depletion syndrome. The survival of patients treated medically was 83%. We conclude that a strong focus should be made on early referral to a specialized center and on improvement of diagnostic tools to timely detect the underlying reason for FHF. Results following Ltx for FHF are good.
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PMID:Liver transplantation for fulminant hepatic failure in infancy: a single center experience. 1906 12

Brain edema is a leading cause of death in fulminant hepatic failure (FHP). Animal studies are needed to gain further insight into its pathogenesis. The authors describe and analyze the results of brain studies in two animal models of FHF, the rabbit with galactosamine induced hepatitis and the anhepatic model of liver desvascularization. A gravimetric technique is used to determine water content in brain samples as small as 10 mg in weight. Results showed that water content is increased and correlates with the severity of encephalopathy in both experimental models of encephalopathy. The possible pathogenic role of ammonia and octanoic acid are discussed.
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PMID:Brain edema in acute liver failure. Insight from experimental studies. 1925 51

Hepatitis A virus can cause liver damage ranging from mild illness to fulminant hepatic failure, constituting 0.35% of all cases of fulminant liver failure. While rates of spontaneous remission are higher for hepatitis A, recent outbreaks attributable to vaccine shortages in highly populated urban cities plagued by insufficient affordable housing and inaccessible sanitation, and changes in the epidemiology of viral strains have resulted in increased hospitalizations and deaths. While the prognosis for patients with FHF has improved since the introduction of transplantation, the decision to transplant is often difficult to reach. We present five patients with HAV and subsequent FHF, one of whom successfully received a liver transplant. We have reviewed all published cases of HAV FHF in the literature and report ten patients, seven of whom received liver transplantation. There are few predictive models that attempt to distinguish between fulminant hepatitis A and spontaneous recovery. Patients found to have positive hepatitis A IgM, encephalopathy, worsening LFT's and coagulation should be monitored closely and referred to transplant centers urgently for management.
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PMID:Liver transplant evaluation for fulminant liver failure due to acute hepatitis A infection: Case series and literature review. 3298 49


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