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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic encephalopathy is a complex neuropsychiatric syndrome, which derives from liver failure associated with severe liver damage such as fulminant hepatitis and liver cirrhosis, and vascular abnormalities associated with liver cirrhosis. Although the cause is explained by a multifactorial theory, the accumulation of ammonia has traditionally been considered to have an important role in the pathogenesis of hepatic encephalopathy. In addition, a number of other possible mechanisms have recently proposed, including production of false neurotransmitter, activation of central gamma-aminobutyric acid-benzodiazepine receptors by ligands of endogenous origin, altered cerebral metabolism. These pathogenetic mechanisms are not necessarily exclusive. The principle of treatment is to remove or correct aggravating factors and inhibit the transfer of toxic substances such as ammonia into the bloodstream by minimizing the interaction of intestinal bacteria and nitrogen substances. Most treatments of proved value are based on the ammonia hypothesis. Ammonia metabolism is regulated by numerous factors, among which zinc has long been indicated to be involved, and its clinical application has drawn attention recently.
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PMID:Ammonia metabolism and hepatic encephalopathy. 1560 43

We report a 3-year-old Italian patient with the hyperornithinaemia, hyperammonaemia, homocitrullinuria (HHH) syndrome who presented with neurological deterioration after an intercurrent infection. Hyperammonaemia, coagulopathy and moderate hypertransaminasaemia were detected on hospital admission. Severe hepatocellular necrosis with hypertransaminasaemia (aspartate aminotransferase 20,000 UI/L, alanine aminotransferase 18,400 UI/L) and coagulopathy (PT < 5%) rapidly developed within few days, prompting evaluation for liver transplantation. A protein-restricted diet and arginine supplementation were immediately started, with a rapid improvement of the patient's neurological conditions and normalization of liver function tests and blood ammonia. The diagnosis of HHH syndrome was based on the presence of the typical metabolic abnormalities. Molecular analysis of the SLC25A15 gene showed that the patient was heterozygous for two novel mutations (G113C and M273K). The diagnosis of HHH syndrome should be considered in patients with fulminant hepatitis-like presentations. Early identification and treatment of these patients can be life-saving and can avoid liver transplantation.
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PMID:HHH syndrome (hyperornithinaemia, hyperammonaemia, homocitrullinuria), with fulminant hepatitis-like presentation. 1660 89

Here we report a familial cluster of 3 cases of coxsackievirus B3 infection: a recent history of illness in a woman's 3-year-old son with a coxsackievirus B3-positive stool culture indicated that he probably infected his mother at home during her last week of pregnancy. Consequently, she delivered an infected neonate who developed severe hepatitis, disseminated intravascular coagulation, and bilateral intracranial hemorrhage. The neonate remained well for the first 2 days of life. On the third day, he developed fever (39 degrees C) and poor peripheral circulation. On the fourth day, he developed petechiae and bruises over his chest wall and extremities, and prolonged bleeding was observed over venipuncture sites. Investigations revealed severe thrombocytopenia (platelets: 41 x 10(9)/L) and a markedly deranged coagulation profile (prothrombin time: 19 seconds [reference: < 10 seconds]; activated partial thromboplastin time: > 120 seconds [reference: 24.2-37.0 seconds], serum D-dimers: 6722 ng/mL [reference: < 500 ng/mL]), suggestive of disseminated intravascular coagulopathy. Clinical examination revealed yellow sclera, hepatomegaly (5 cm), and splenomegaly (2 cm), consistent with hepatitis. Serial chest radiographs showed bilateral pleural effusions, and an ultrasound of the abdomen demonstrated ascites. An echocardiogram showed normal cardiac structure and good contractility of both ventricles. However, a cranial ultrasound revealed bilateral grade 2 intraventricular hemorrhages. Serum C-reactive protein increased to 33.9 mg/L. Liver-function tests were also markedly deranged at this time, with maximum values for serum alanine transferase, bilirubin, alkaline phosphatase, and ammonia concentration of 1354 IU/L, 258 micromol/L, 189 IU/L, and 147 micromol/L, respectively. Serum glucose levels were normal. Over the next 3 days, his fever subsided, and his liver function and clotting profile normalized by day 13 after onset of illness. A stool sample from the older brother, collected 14 days after his onset of illness at home, was positive for coxsackievirus B3 by both virus culture and enterovirus reverse-transcription polymerase chain reaction. He had neutralizing coxsackievirus B3 antibody titers of 1:2560 and 1:1280 on days 14 and 28 after his onset of illness, respectively. No virus was cultured from the mother's stool sample, collected 5 days after her onset of illness, but the enterovirus polymerase chain reaction was positive and maternal sera neutralized the coxsackievirus B3 isolated from the neonate. The maternal sera also showed a more than fourfold rise in antibody titer from 1:80 to 1:640 on days 5 and 16 after her onset of illness, respectively. Neonatal antibody titers also showed a more than fourfold rise from < 1:80 to 1:2560 on days 1 and 21 after his onset of illness, respectively. This demonstrates that both the mother and the neonate had had recent coxsackievirus B3 infections. Serially collected neonatal throat swab and stool samples were culture negative for enterovirus by 4 and 8 days after his onset of illness, respectively. However, enterovirus RNA remained detectable by reverse-transcription polymerase chain reaction in these samples for considerably longer, only becoming undetectable by 16, 23, and 41 days after his onset of illness. We show that even mild household infections may have potentially serious consequences for pregnant women and their infants.
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PMID:Probable intrafamilial transmission of coxsackievirus b3 with vertical transmission, severe early-onset neonatal hepatitis, and prolonged viral RNA shedding. 1690 22

3 patients with liver failure developed hepatic encephalopathy. 2 patients, men aged 60 and 72 years, had chronic liver disease and presented with episodes of confusion. They recovered after being treated with lactulose. The third patient, a 37-year-old woman, became comatose shortly after the onset of acute liver failure due to acute autoimmune hepatitis. She died before a suitable donor liver became available. Hepatic encephalopathy is a syndrome of potential reversible neurological symptoms. Especially in the early stages of the condition, hepatic encephalopathy can be difficult to diagnose. Patients may present with mild cognitive impairment or episodes characterized by neurological symptoms. Hepatic encephalopathy is a clinical diagnosis. The pathophysiologic mechanism is only partly understood but toxicity of ammonia on the central nervous system seems to be of major importance. Raised ammonia concentrations or EEG findings consistent with metabolic encephalopathy may support but are not essential to the diagnosis. Episodes of hepatic encephalopathy are often elicited by an underlying disease such as infection or gastro-intestinal bleeding. It is important to recognize hepatic encephalopathy in its early stages because adequate treatment of the condition and any underlying disease reduces morbidity and mortality.
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PMID:[Confusion and abnormal liver enzyme levels: problems with diagnosing hepatic encephalopathy]. 1836 Nov 99

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

Cytosolic enzymes AMP deaminase and adenosine deaminase (ADA) catalyze AMP and adenosine deamination, constitute rate-limiting steps of adenine nucleotide catabolism and play important roles in cellular energy metabolism. In this study, AMP deaminase and ADA activities of rat liver, neocortex, cerebellum, striatum and hippocampus were investigated in acute ammonia intoxication and subacute CCl(4)-induced hepatitis. Activities of both AMP deaminase and ADA in the liver were elevated by 2.4-4.2-fold (p<0.0001) in both models of hepatotoxic injury as compared with controls. In acute hyperammonemia activities of AMP, deaminase and ADA increased by 46-59% (p<0.02) in the neocortex and did not change in the striatum. In the hippocampus of hyperammonemic rats, only AMP deaminase activity was increased by 48% (p=0.0004), and in the cerebellum only ADA activity was increased significantly (by 26%, p<0.05). The adenylate pool size and energy charge were greatly reduced in the neocortex of hyperammonemic rats. Results suggested that two parallel pathways of AMP breakdown, including AMP deaminase and ADA, respectively, are up-regulated under pathological conditions, probably in order to overcome compensatory synthesis of adenylates, to ensure prompt adenylate pool depletion and reduce the adenylate energy charge in liver and selected brain regions.
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PMID:AMP deaminase and adenosine deaminase activities in liver and brain regions in acute ammonia intoxication and subacute toxic hepatitis. 1990 Apr 20

Application of hyperbaric oxygenation (HBO, 3 ata, 1 session for 50 min per day) during the first three days after liver resection (LR, 15-20% from the organ mass) in animals with chronic toxic hepatitis (CCl4, 50%, 0,1 ml/per 100 g of body mass, subcutaneously, once in 2 days, 65 days) eliminates a deficit of glutamine and glutamate in an operated liver and prevents accumulation of the endogenic toxin, ammonia, caused by combined effects of CCl4 and LR. Thus hyperbaric oxygen modulates the effect of the LR on the activity of key enzymes of the glutamine metabolism in liver: glutamine synthetases (GS) and phosphate-dependent glutaminases (PDG). HBO enhanced and prolonged the LR effect of the GS activity and restricted analogous changes in PDG during an early (3 day) postoperative period and promoted a delayed transient stimulation in the late (7 day) postoperative period. In contrast to non-oxygenated animals with LR this was not accompanied by accumulation of ammonia and the decrease in glutamine concentration in the liver.
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PMID:[Correction of glutamine metabolism impairments in the operated liver with chronic hepatitis by hyperbaric oxygen]. 2000 Jan 27

A 42-year-old Indian man received 450 mg rifampicin (RIF) and 150 mg isoniazid (INH) daily after being diagnosed of a latent tuberculosis infection. Baseline serum aminotransferase and total bilirubin levels were within normal limits. On day 31 of treatment, the patient experienced epigastric discomfort and general malaise and one week later he developed nausea and episodic vomiting. The patient missed his first scheduled clinic appointment and he continued taking RIF-INH despite his symptoms. He visited the tuberculosis clinic on day 47 of treatment where he was found to be jaundiced and his liver enzymes were elevated. RIF-INH was stopped and the patient was admitted to our hospital as a case of RIF-INH induced hepatitis. On the 7th day of hospitalization, the patient developed consciousness disturbance with flapping tremor and high ammonia level. The patient was diagnosed with fulminant hepatic failure and transferred immediately to the medical intensive care unit, where he died 4 days later.
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PMID:Rifampicin-isoniazid induced fatal fulminant hepatitis during treatment of latent tuberculosis: A case report and literature review. 2085 96

We studied the effect of acute ammonia poisoning and CCl4-induced subacute hepatitis on activities of AMP deaminase and adenosine deaminase in rat liver. Both models of liver failure were accompanied by an increase in activities of AMP deaminase and adenosine deaminase in the cytoplasmic fraction of the liver (by 2.4-4.2 times compared to the control). A direct correlation was found between activities of AMP deaminase and adenosine deaminase. We believe that two parallel pathways of AMP degradation are activated simultaneously, which leads to rapid depletion of adenylate reserves under pathological conditions.
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PMID:Activation of AMP deaminase and adenosine deaminase in the liver during ammonia poisoning and hepatitis. 2116 Oct 45

The developmental potential of human embryonic stem cells (hESCs) holds great promise to provide a source of human hepatocytes for use in drug discovery, toxicology, hepatitis research, and extracorporeal bioartificial liver support. There are, however, limitations to induce fully functional hepatocytes on conventional two-dimensional (2D) static culture. It had been shown that dynamic three-dimensional (3D) perfusion culture is superior to induce maturation in fetal hepatocytes and prolong hepatic functions of primary adult hepatocytes. We investigated the potential of using a four-compartment 3D perfusion culture to induce hepatic differentiation in hESC. Undifferentiated hESC were inoculated into hollow fiber-based 3D perfusion bioreactors with integral oxygenation. Hepatic differentiation was induced with a multistep growth factor cocktail protocol. Parallel controls were operated under equal perfusion conditions without the growth factor supplementations to allow for spontaneous differentiation, as well as in conventional 2D static conditions using growth factors. Metabolism, hepatocyte-specific gene expression, protein expression, and hepatic function were evaluated after 20 days. Significantly upregulated hepatic gene expression was observed in the hepatic differentiation 3D culture group. Ammonia metabolism activity and albumin production was observed in the 3D directed differentiation culture. Drug-induced cytochrome P450 gene expression was increased with rifampicin induction. Using flow cytometry analysis the mature hepatocyte marker asialoglycoprotein receptor was found on up to 30% of the cells in the 3D system with directed hepatic differentiation. Histological and immunohistochemical analysis revealed structural formation of hepatic and biliary marker-positive cells. In contrast to 2D culture, the 3D perfusion culture induced more functional maturation in hESC-derived hepatic cells. 3D perfusion bioreactor technologies may be useful for further studies on generating hESC-derived hepatic cells.
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PMID:Hepatic differentiation of human embryonic stem cells is promoted by three-dimensional dynamic perfusion culture conditions. 2121 Jul 20


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