A Case of Acute Liver Failure After Intravenous Administration of Recommended Therapeutic Dose Acetaminophen for Relief of Stage IV Lung Cancer Pain

Introduction: There are many reports about hepatotoxicity associated with acute overdose or long-term use of acetaminophen, but few reports of that associated with therapeutic doses. We present a case of acute liver failure with hepatic coma caused by therapeutic doses of intravenous acetaminophen for cancer pain relief in palliative care setting. Case: The patient was a 56-year-old woman with stage IV lung cancer and normal liver function. She was admitted to the hospital because of anorexia and cancer pain. She received 1g intravenous acetaminophen every six hours for analgesia of pleural and rib metastasis. The patient’s AST/ALT levels were elevated at 3104/1212 IU/L, while she was receiving 11 doses of intravenous acetaminophen. She was treated with oral N-acetylcysteine, hemadsorption and plasma exchange therapy. Liver function returned to normal soon. Discussion: Therapeutic doses of intravenous acetaminophen is generally used in palliative care setting, and hepatic failure may occur due to glutathione depletion in patients with cancer anorexia. The potential hazard of rare but serious complications should always be kept in mind even with therapeutic doses.

​Efficacy Of Early N-Acetylcysteine In Rat Killer Paste Poisoning

Introduction: Rat killer paste (yellow phosphorous) is one of the most common forms of poisoning in South India. It causeshepatotoxicity. No specific antidote has been found. Recently, N-acetylcysteine is used as supportive therapy in many casesof acute liver failure.Aim: This study aims to evaluate the effectiveness of early N-acetylcysteine in preventing the rat killer paste poisoning.Methods: Patients who ingested rat killer paste poison and age >12 years were included in the study. Patients having jaundice,liver disease, and age <12 years were excluded from the study.Results: Among 30 patients studied, five patients died, seven patients developed hepatitis, one patient developed acute kidneyinjury with hepatitis, and one patient developed hyponatremia.Conclusion: Early initiation of N-acetylcysteine had a significant impact in reducing mortality.

Fatal neurological complication after liver transplantation in acute hepatic failure patient with hepatic encephalopathy / 고신대학교의과대학학술지

Liver transplantation is a current definitive treatment for those with end-stage liver disease. Hepatic encephalopathy is a common complication of hepatic failure, which can be improved and aggravated by various causes. It is important to differentiate hepatic encephalopathy from other diseases causing brain dysfunction such as cerebral hemorrhage, which is also related to high mortality after liver transplant surgery. A 37-year-old patient was presented with acute liver failure and high ammonia levels and seizure-like symptoms. Computed tomography (CT) of his brain showed mild brain atrophy, regarded as a symptom of hepatic encephalopathy, and treated to decrease blood ammonia level. Deceased donor liver transplantation was performed and liver function and ammonia level normalized after surgery, but the patient showed symptoms of involuntary muscle contraction and showed loss of pupil reflex and fixation without recovery of consciousness. Brain CT showed brain edema and bilateral cerebral infarction, and the patient died after a few days. The purpose of this case report is to emphasize the importance of preoperative neurological evaluation, careful transplantation decision, and proper perioperative management of liver transplantation in patients with acute hepatic encephalopathy.

Leucemia linfoblástica aguda con grave alteración hepática como manifestación inicial: presentación de dos casos y revisión de la literatura / Acute lymphoblastic leukemia causing hepatic failure: report of two cases

Hematological diseases may cause acute hepatic failure and are seldom sought. We report two cases illustrating this situation. A 16-year-old male presented with an acute liver failure: a bone marrow biopsy showed complete infiltration with lymphoid type blasts. A flow cytometry confirmed the presence of an acute lymphoblastic leukemia. The patient died days later. A 20-year-old female presented with acute liver failure: due to a pancytopenia, a bone marrow biopsy was performed, which confirmed the presence of an acute lymphoblastic leukemia. Chemotherapy was started immediately. The patient had a favorable evolution.

Experimental study on acute hepatotoxicity in beagles induced by Amanita exitialis / 中华急诊医学杂志

Objective To establish acute hepatotoxic model induced by Amanita exitialis and to study the characteristics of acute toxic liver failure induced by mushrooms containing peptide toxins,in hope for providing some help to experimental research on poisoning induced by mushrooms containing peptide toxins.Methods UPLC-MS/MS (Ultra performance liquid chromatography-tandem mass spectrometry) method was used to detect peptide toxins in Amanita exitialis.To establish acute toxic liver hepatic failure model,the beagles were fed with 60 mg/kg of lyophilized powder of Amanita exitialis fungus which encapsulated in starch capsules.Toxic sighs were observed,coagulation function,hepatic and renal function,liver histopathological morphology,peptide toxin concentration in plasma and urine were detected during the experiment.Results Total peptide toxins in Amanita exitialis was (3 482.6 ± 124.94) mg/ kg.All the beagles had toxic signs including vomiting and diarrhea in 12-48 h after ingestion.On 24 h after ingestion,the beagles' ALT,AST,TBIL,ALP,PT and APTT levels increased obviously.On 36 h after ingestion,the beagles' ALT,AST,PT and APTT values reached their peaks (ALT:283.2 ± 112.9 Kallmann unit;AST:223.9 ±93.8 Kallmann units;PT:132.9 ± 152.6 s;APTT:131.4 ± 153.9 s).On 48 h after ingestion,the beagles' TBIL and ALP levels reached their peaks (TBIL:23.3 ± 14.6 mol/L;ALP:274.5 ± 115.5 U/L).The beagles' TBIL,TP and APTT returned to normal 1 week after ingestion,their ALT,AST and ALP levels returned to normal 3 weeks after ingestion.Three dogs died during 24-72 h after ingestion.Liver histopathological morphology study showed hemorrhagic necrosis of hepatocytes.Peptide toxins can be detected in plasma within 24 h after ingestion.Peptide toxins can be detected in urine within 96 h after ingestion.Conclusion Amanita peptide toxins can cause hemorrhagic necrosis of liver cells and lead to acute liver failure.This model is consistent with clinical pathophysiological process of acute toxic liver failure induced by mushrooms containing peptide toxins,and it can be applied to the study of diagnosis and treatment of poisoning induced by mushrooms containing peptide toxins.

Recent advances in research on animal models of acute hepatic failure / 中国比较医学杂志

Acute hepatic failure (AHF) is a severe liver disease associated with a variety of clinical symptoms . AHF is difficult to treat and with a high mortality rate.Therefore, it is necessary to establish animal models of AHF for the investigation of therapy.In this article, the preparation methods of AHF animal models are reviewed which are applicable to different types of animals.

Definition and common etiology of acute liver failure in children / 中国小儿急救医学

Acute liver failure (ALF)in children is life-threatening clinical syndrome.There is an obvious difference between children and adults in the definition of ALF.The etiologies of ALF in children are related to virus infection,inherited metabolic diseases and drug intoxication.But in the infants,the etiological factors are significantly different to the elder children in ALF.The definition and etiology of ALF in children are reviewed in the paper.

A Case of Exertional Heat Stroke with Acute Hepatic Failure Treated with Plasma Exchange: A Case Report / 대한구급학회지

Heat stroke is a hyperthermia-induced systemic inflammatory response which may cause multiorgan dysfunction syndrome. We report a case of exertional heat stroke with acute hepatic failure in an 11-year-old boy. He initially presented hyperthermia and unconsciousness, which occurred after heavy exercise. His neurological state improved after terminating the hyperthermia by intensive cooling therapy. However, 24 hours after the initial recovery, his neurological state deteriorated again as acute hepatic injury progressed rapidly. We applied 4 times of total plasma exchange as an immunotherapy for systemic inflammatory response syndrome and acute hepatic failure expecting it to remove endogenous inflammatory factors and hepatotoxic cytokines. Following the plasma exchange, his mental state became normal and serial laboratory findings indicated improvement. He made a complete recovery without sequelae. We experienced successful treatment regarding exertional heat stroke with acute hepatic failure using plasma exchange.

Effect of total nutrient admixture on lipid metabolism in acute hepatic failure rats / 中华临床营养杂志

Objective To study the effect of total nutrient admixture (TNA) on lipid metabolism in rats with acute hepatic failure (AHF). Methods Fifty-six male Wistar rats were randomly divided into four groups: normal diet group, nitrogen-free diet group, fat-free nutrient admixture group, and TNA group. All rats were injected with D-galac- tosamine to induce AHF model Meanwhile, 6 healthy Wistar rats were used as control group. TNA provided energy 221.75 kJ (1 kcal=4.184 kJ), nitrogen 0.365 g, nitrogen to energy ratio 1:145, amino acids 2.28 g (including branched-chain amino acid 0.70 g), glucose 7.85 g, and fat 1.25 g on a daily basis. After 10 days of the operation of Jugular vein puncture tube, blood glucose, blood lipid, liver and renal function were determined. Results The blood glucose level was significantly higher in TNA group than that in fat-free nutrient admixture group (P < 0.05). The levels of serum triglyceride and cholesterol were highest in fat-free nutrition admixture group, and triglyceride level was signif- icantly higher than that in normal diet group and nitrogen-free diet group (P <0.05). The levels of serum triglyceride and cholesterol were significantly higher in TNA group than those in normal diet group (P <0.05). The levels of ala- nine aminotransferase, alkaline phosphatase, total bilirubin and blood urea nitrogen were lower in TNA group than those in fat-free nutrient admixture group (P < 0.05). Conclusion The nutritional proportion of TNA is suitable for the metabolism disorder of hepatic failure, and therefore TNA can reasonably promote the anabolism and reverse the deteri- oration of hepatic failure in rats.

Intoxicación por fósforo blanco en pediatría / White phosphorus poisoning in pediatrics

La intoxicación por fósforo blanco es una patología que es frecuente en festividades navideñas y de fin de año debido al uso de la pólvora recreativa como las martinicas, elementos de fácil acceso para los niños, principalmente lactantes y preescolares, los cuales sin medir consecuencias se convierten en víctimas de intoxicaciones al llevarse estos elementos a la boca y en ocasiones ingerirlos. En esta revisión se describe el caso de una menor intoxicada al ingerir fósforo blanco, con el objetivo de dar a conocer los efectos de este tóxico y advertir a los adultos a cargo acerca de la letalidad de esta patología, con el propósito de derivar a partir de esta revisión políticas encaminadas principalmente hacia prevención del evento. Se describe el caso de una niña de 2 años de edad que ingiere cuatro martinicas, presentando todos los efectos nocivos que ocasiona este tóxico a nivel hepático; la paciente recibió medidas iniciales las cuales fueron insuficientes por lo que tuvo que ser llevada a la unidad de cuidados intensivos con evolución favorable que hasta el momento no ha requerido transplante.

White phosphorus’ poisoning is a frequent pathology during holydays and New Year’s Eve. Fire works such as “martinicas”, are accessible for children – especially toddlers and preschoolers – who can have poisoning when they bring these elements to their mouths and ingest them, by accident. This work describes the case of a minor who was poisoned when she ingested white phosphorus. Our purpose is to show white phosphorus’ toxic effects and warn adults about this lethal pathology, in order to create policies directed towards its prevention. A two years old girl ingested four “martinicas”, presenting with hepatotoxicity. The patient needed an ntensive care unit admission with a favorable outcome and without requiring liver transplant.

Differential Gene Expression Profiles in Acute Hepatic Failure Model in Mice Infected with MHV-3 Virus Intervened by Anti-hepatic Failure Compound / 华中科技大学学报（医学）（英德文版）

Differential gene expression profiles in Balb/cJ mouse model of acute hepatic failure in- fected with MHV-3 virus intervened by anti-hepatic failure compound (AHFC) and the changes of cytokines regulated by genes were investigated. The Balb/cj mice were divided into AHFC-intervened group and control group randomly. Acute hepatic failure model of Balb/cJ mice infected with MHV-3 virus was established. The survival rate in the two groups was observed. It was found that the survival rate in the AHFC-intervened group and control group was 90% and 50% re- spectively 48 h after intrapefitoneal injection of MHV-3 (P<0.05). Before and after the experiment, the cytokines in peripheral blood of the survival mice were determined, and RNA was extracted from survival mouse liver tissue for the analysis of the differential gene expression by a 36 kb mouse oli- gonuleotide DNA array. In all the genes of microarray there were 332 genes expressed differently in the two groups, in which 234 genes were up-regulated and 78 genes down-regulated. Through clustering analysis, the differential expression of immune related genes, including TNF receptor superfamily, Kctd9, Bcl-2, Fg12, IL-8, IL-6, IFN-γ, TNF-α etc. might be related with the curative effectiveness of AHFC. It was suggested that AHFC can balance the immune state of mouse model of acute hepatic failure infected with MHV-3 virus mainly through regulating the expression of immune related genes, decrease the immune damage and inhibit liver cell apoptosis of mouse acute hepatic failure model obviously so as to increase the survival rate of mouse models of acute hepatic failure.

Effect of the Jiedu Huayu Ⅱ Decoction on Mitochondrial Bcl-2 and Cytochrome C Expression in Liver in Rats with Acute Hepatic Failure / 中国康复理论与实践

@#Objective To explore the mechanism of the Jiedu Huayu Ⅱ Decoction in actue hepatic failure.MethodsThe acute hepatic failure rat models were induced with thioacetamide (TAA).84 SPF Wistar rats were divided into 7 groups randomly:blank group,model group,low dose group,middle dose group,high dose group,lactulose group,and the Angong Niuhuang Pill group.The drugs were administrated by gavage 3 d before model-making,5.5 d in total.The expression of Bcl-2,cytochrome C in mitochondrial and cytoplasm were measured with Western Blot.ResultsThe expression of Bcl-2 reduced in mitochondrial,the expression of cytochrome C increased in cytoplasm and reduce in mitochondrial in model group compare with that of blank group.Jiedu Huayu Ⅱ Decoction was able to enhance the expression of Bcl-2 and restrain cytochrome C release from mitochondrial to cytoplasm.Moreover,it shows dose-effect relation.ConclusionThe protection of Jiedu Huayu Ⅱ Decoction for hepatocyte in acute hepatic failure rats maybe relate to the increase of Bcl-2 in mitochondrial,blocking the mitochondrial permeability transition pore to arrest cytochrome C releasing.

A Case of Aplastic Anemia following Hepatic Failure by Acute Hepatitis / 소아과

Aplastic anemia following acute hepatitis or acute hepatic failure is an uncommon disease and has a poor prognosis. We experienced a case of aplastic anemia following acute hepatic failure in a 10- year-old girl. She was admitted because of jaundice and lethargy for 8 days. Laboratory findings revealed marked elevated serum transaminases and bilirubin levels, prolonged prothrombin time and partial thromboplastin time, and massive hepatic necrosis on the pathological study. There was no evidence of metabolic, toxic or autoimmune hepatitis. During the treatment of acute hepatic failure, pancytopenia developed and marked hypocellularity of all hematopoietic elements in bone marrow was revealed. She recovered partially from aplastic anemia after treatment with anti-thymocyte globulin, corticosteroid and cyclosporine.

Effect of Intrasplenic Transplantation of Cryopreserved Hepatocytes into Partially Hepatectomized Rats / 대한간학회지

BACKGROUND/AIMS: Various techniques of hepatocyte transplantation were actively studied as an alternative to liver transplantation, because of the difficulty of obtaining donor organ, technical difficulties, and high cost. Isolated hepatocytes could be appropriately banked and distributed on demand. We tried to investigate the effect of intrasplenic transplantation of allogenic cryopreserved hepatocytes, into spleen prior to 90% partial hepatectomy in rats, on the survival rate. METHODS: Cryopreserved hepatocytes, isolated by collagenase perfusion of the liver via the portal vein, were thawed and transplanted into the spleen of rats prior to induction of acute hepatic failure by resection of all lobes except caudate lobe (2.0x107 hepatocytes/rat). RESULTS: 1. The viability of freshly isolated hepatocyte was 70-5%, but cell viability after cryopreservation 30-0%. 2. Difference of survival in control and transplant group is not statistically significant. but the survival rate, 48 hours after 90% partial hepatectomy, for control (7) and transplanted group (11) were 0% and 18%, respectively. 3. Although the glucose reduction gradient was not significantly different between two groups, it was more prominent in the control group than in the transplanted group. 4. Engraftment and survival of transplanted hepatocytes were noted in the spleen 2 days after transplantation. CONCLUSIONS: We could not observe statistically significant improvement of survival with intrasplenic transplantation of cryopreserved hepatocytes in rats with 90% partial hepatectomy-nduced acute liver failure. However, 18% survival after 90% partial hepatectomy was noted in the transplanted group, compared to no survival in the control group. This suggests that intrasplenic transplantation of cryopreserved hepatocytes might be effective in the treatment of acute liver failure.

The Effects of Acute Hepatic Failure by Galactosamine on Mivacurium-induced Neuromuscular Blockade in the Cats / 대한마취과학회지

BACKGROUND: Though the mivacurium is the short acting nondepolarizing neuromuscular blocking agent, the action duration of it is not prospected in condition of hepatic failure owing to its being metabolized by serum cholinesterase and other esterase produced in liver. The purpose of this study is to evaluate neuromuscular effect of the mivacurium in cats with acute hepatic failure. METHODS: Six cats administrated only mivacurium are the control group, and six cats with acute hepatic failure by galactosamine hydrochloride are the experimental group. The force of the anterior tibialis muscle in response to supramaximal common peroneal nerve stimulations were recorded, the time intervals from mivacurium administration to attain 100% twitch depression (onset time), from mivacurium administration to recovery of 25% twitch tension (duration) and from 25% to 75% of twitch recovery (recovery index) were compared between the control group and the experimental group. RESULTS: In experimental group, SGOT and SGPT prior to administration of galatosamine were 28.8+/-5.6 (IU/L) and 43.0+/-7.9 (IU/L), respectively, SGOT and SGPT in acute hepatic failure were 5004.0+/-8113.2 (IU/L) and 3763.0+/-5416.4 (IU/L), respectively, and there were significant differences between the control group and the experimental group. The action duration{47.6+/-18.0 (min)} and the recovery time{7.7+/-3.7 (min)} of mivacurium in the experimental group were more prolonged than the action duration{21.9+/-5.0 (min)} and the recovery time{4.4+/-0.7 (min)} of mivacurium in the control group. CONCLUSIONS: These results indicate that the hepatic failure can prolong the action duration and the recovery index of mivacurium, but the other factors affecting the action of mivacurium must be studied.

The Effects of Amino Acid Electuary (Ganan Elemental Granules) on Experimental Acute Hepatic Failure / 第二军医大学学报

The effects of amino acid electuary (Ganan Elemental Granules) on experimental acute hepatic failure induced by D-galactosamine in rats were studied. The results showed that the electuary could significantly prevent the decrease in body weight and food intake, the prolongation in time of blood coagulation time and increase in the levels of serum glutamic-pyruvic transaminase activity, elevate contents of total serum protein and serum albumin, normalize the serum ratio of BCAA to AAA and disordered amino acid pattern, increase survival of animals and improve encephalopathy in rats with acute hepatic failure. These results suggest that the amino acid electuary has a better protective effects on acute hepatic failure.

AMINO ACID METABOLISM IN EXPERIMENTAL ACTE HEPATIC FAILURE / 营养学报

Acute hepatic failure was induced in rats with intraperitoneal administration of D-galactosamine.Serum and tissue amino acid profiles of the animals were studied. Except for arginine, serum levels of all amino acids were elevated. This is in variance with the findings of Fischer and other investigators. In their studies, the decreased levels of BCAA could be related to the administration of dextrose. In our study, the serum BCAA/AAA ratio was decreased and it was correlated negatively with the dosage of D-galactosamine (r =-0.789). Amino acid profiles in the liver,kidney and muscles were significantly altered. The chracteristics of the changes indicated that enhanced proteolysis of tissue proteins was the major factor accounting for the elevation of serum amino acid levels. Hepatic coma might be related to the increase of aromatic amino acids in the brain. It is usually difficult for glycine, cystine, asparagine and threonine to penetrate the blood-brain-barrier. Elevation of their levels in the brain might be a consequence of increased permeability of the blood-brain-barrier. Further studies are needed to clarify the role of GABA in hepatic coma.