Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of the pathogenesis of hepatic encephalopathy are hampered by the lack of a satisfactory animal model. We examined the neurological features of rats after bile duct ligation fed a hyperammonemic diet (BDL+HD). Six groups were studied: sham, sham pair-fed, hyperammonemic, bile duct ligation (BDL), BDL pair fed, and BDL+HD. The BDL+HD rats were made hyperammonemic via an ammonia-containing diet that began 2 weeks after operation. One week later, the animals were sacrificed. BDL+HD rats displayed an increased level of cerebral ammonia and neuroanatomical characteristics of hepatic encephalopathy (HE), including the presence of type II Alzheimer astrocytes. Both BDL and BDL+HD rats showed activation of the inflammatory system. BDL+HD rats showed an increased amount of brain glutamine, a decreased amount of brain myo-inositol, and a significant increase in the level of brain water. In coordination tests, BDL+HD rats showed severe impairment of motor activity and performance as opposed to BDL rats, whose results seemed only mildly affected. In conclusion, the BDL+HD rats displayed similar neuroanatomical and neurochemical characteristics to human HE in liver cirrhosis. Brain edema and inflammatory activation can be detected under these circumstances.
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PMID:Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis. 1672 29

The paper describes one case of the mixed form of mucoviscidosis, with involvement of the lung (chronic obstructive bronchitis, bronchiectasis, emphysema, pneumosclerosis), liver (cirrhosis), pancreas (lipomatosis with islet atrophy), ileum (enteritis). There were the following complications: cor pulmonale, esophageal varicose veins, ascitis, splenomegaly, secondary diffuse renal amyloidosis of the kidney, adrenals, and spleen, and brain edema. Due to modern therapy the patient reached the age of 25 years, which is a rarity.
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PMID:[Pathomorphology of the mixed form of mycoviscidosis in an adult patient]. 1683 Jun 24

Adult-onset citrullinemia (CTLN2) is a rare hereditary metabolic disorder characterized by highly increased concentration of citrulline and ammonia in the plasma, which is ascribed to a deficiency of argininosuccinate synthetase (ASS), one of the urea cycle enzymes mainly located in the liver. Neurological manifestation in CTLN2 patients closely resemble those of hepatic encephalopathy and in the past, most patients usually followed rapidly deteriorating clinical courses and died of severe brain edema within a few years after onset. However, in 1995 the first CTLN2 patient who was successfully treated by living-related liver transplantation was reported and since then more than 30 patients had underwent this operation in our country, showing good outcomes. No primary defect had not been found within ASS gene locus, but the causative gene of this disorder is now identified as the "citrin gene", which might act as a aspartate/glutamate transporter in mitochondria. Different phenotypes are seen in the individuals with a citrin deficiency: neonatal intrahepatic cholestasis, juvenile-onset chronic pancreatitis and hepatocellular carcinoma without cirrhosis can precede the appearance of CTLN2. The precise pathogenesis of this disease that includes the relationship between the mutations of citrin gene and a deficiency of hepatic ASS activity remains unclear.
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PMID:[Adult-onset citrullinemia]. 1722 80

Adult-onset citrullinemia (CTLN2) is a rare hereditary metabolic disorder characterized by highly increased concentration of citrulline and ammonia in the plasma, which is ascribed to a deficiency of argininosuccinate synthetase (ASS), one of the urea cycle enzymes mainly located in the liver. Neurological manifestation in CTLN2 patients closely resemble those of hepatic encephalopathy and in the past, most patients usually followed rapidly deteriorating clinical courses and died of severe brain edema within a few years after onset. However, in 1995 the first CTLN2 patient who was successfully treated by living-related liver transplantation was reported and since then more than 30 patients had underwent this operation in our country, showing good outcomes. No primary defect had not been found within ASS gene locus, but the causative gene of this disorder is now identified as the "citrin gene", which might act as a aspartate/glutamate transporter in mitochondria. Different phenotypes are seen in the individuals with a citrin deficiency: neonatal intrahepatic cholestasis, juvenile-onset chronic pancreatitis and hepatocellular carcinoma without cirrhosis can precede the appearance of CTLN2. The precise pathogenesis of this disease that includes the relationship between the mutations of citrin gene and a deficiency of hepatic ASS activity remains unclear.
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PMID:[Adult-onset citrullinemia]. 1735 80

Liver failure is associated with hepatic encephalopathy (HE). An imbalance in plasma levels of aromatic amino acids (AAA) phenylalanine, tyrosine, and tryptophan and branched chain amino acids (BCAA) and their BCAA/AAA ratio has been suggested to play a causal role in HE by enhanced brain AAA uptake and subsequently disturbed neurotransmission. Until recently, data on this subject and the role of the liver and splanchnic bed were scarce, particularly in humans, due to inaccessibility of portal and hepatic veins. Here, we discuss, against a background of relevant literature, data obtained in patients undergoing liver resection or with a transjugular intrahepatic portasystemic stent shunt (TIPSS), where these veins are accessible. The BCAA/AAA ratio remained unchanged after major liver resection, but plasma AAA levels were inversely correlated (P < 0.001) with residual liver volume, in keeping with the observed hepatic AAA uptake. In patients with stable cirrhosis and a TIPSS, the plasma BCAA/AAA ratio was lower than in controls (1.19 +/- 0.09 vs. controls: 3.63 +/- 0.34). Gastrointestinal bleeding in cirrhotics with a TIPSS induced disturbances in BCAA levels and the BCAA/AAA ratio and induced catabolism, which could partly be corrected by isoleucine administration. AAA may be important in the pathogenesis of HE, but it is unlikely that they are the sole factors. HE most likely is a syndrome with multifactorial pathogenesis, where hyperammonemia, AAA/BCAA imbalances, inflammation, brain edema, and neurotransmitter changes interact. Novel therapies to normalize AAA levels in patients with liver failure (such as the molecular adsorbent recirculating system dialysis device) should probably be combined with supplementation of e.g. isoleucine and enhancing ammonia excretion by the kidneys.
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PMID:Aromatic amino acid metabolism during liver failure. 1751 30

MR imaging has found abnormalities compatible with low-grade edema in the brain of patients with cirrhosis that have been related to hepatic encephalopathy. We present 3 patients with hepatic encephalopathy who exhibit supratentorial focal or diffuse white matter lesions compatible with small-vessel brain disease. The volume and number of white matter lesions reduced with the improvement of hepatic encephalopathy, suggesting the participation of the blood-brain barrier in the pathogenesis of brain edema in hepatic encephalopathy.
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PMID:Decrease in the volume of white matter lesions with improvement of hepatic encephalopathy. 1784 99

Hepatic encephalopathy is a severe complication of cirrhosis that is related to the effects of ammonia. Analysis of interorgan ammonia trafficking has identified an important role of skeletal muscle in ammonia removal and has highlighted the importance of the nutritional status. Ammonia causes neurotransmitter abnormalities and induces injury to astrocytes that is partially mediated by oxidative stress. These disturbances lead to astrocyte swelling and brain edema, which appear to be involved in the pathogenesis of neurological manifestations. Inflammatory mediators worsen brain disturbances. New methods for assessing hepatic encephalopathy include clinical scales, neuropsychological tests, imaging of portal-systemic circulation, and magnetic resonance of the brain. Reappraisal of current therapy indicates the need for performing placebo-controlled trials and the lack of evidence for administering diets with restricted protein content. Liver transplant should be considered in selected patients with hepatic encephalopathy. Future prospects include new drugs that decrease plasma ammonia, measures to reduce brain edema, and liver-support devices.
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PMID:Hepatic encephalopathy. 1829 78

The term hepatic encephalopathy (HE) includes a spectrum of neuropsychiatric abnormalities occurring in patients with liver dysfunction. Most cases are associated with cirrhosis and portal hypertension or portal-systemic shunts, but the condition can also be seen in patients with acute liver failure and, rarely, with portal-systemic bypass and no associated intrinsic hepatocellular disease. Although HE is a clinical condition, several neuroimaging techniques, particularly MR imaging, may eventually be useful for the diagnosis because they can identify and measure the consequences of central nervous system (CNS) increase in substances that under normal circumstances, are efficiently metabolized by the liver. Classic MR imaging abnormalities include high signal intensity in the globus pallidum on T1-weighted images, likely a reflection of increased tissue concentrations of manganese, and an elevated glutamine/glutamate peak coupled with decreased myo-inositol and choline signals on proton MR spectroscopy, representing disturbances in cell-volume homeostasis secondary to brain hyperammonemia. Recent data have shown that white matter abnormalities, also related to increased CNS ammonia concentration, can also be detected with several MR imaging techniques such as magnetization transfer ratio measurements, fast fluid-attenuated inversion recovery sequences, and diffusion-weighted images. All these MR imaging abnormalities, which return to normal with restoration of liver function, probably reflect the presence of mild diffuse brain edema, which seems to play an essential role in the pathogenesis of HE. It is likely that MR imaging will be increasingly used to evaluate the mechanisms involved in the pathogenesis of HE and to assess the effects of therapeutic measures focused on correcting brain edema in these patients.
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PMID:MR imaging findings in hepatic encephalopathy. 1858 13

Hepatic encephalopathy is a neuropsychiatric manifestation of acute and chronic liver failure. Ammonia plays a key role in the pathogenesis of hepatic encephalopathy by inducing astrocyte swelling and/or sensitizing astrocytes to swelling by a heterogeneous panel of precipitating factors and conditions. Whereas astrocyte swelling in acute liver failure contributes to a clinically overt brain edema, a low grade glial edema without clinically overt brain edema is observed in hepatic encephalopathy in liver cirrhosis. Astrocyte swelling produces reactive oxygen and nitrogen oxide species (ROS/RNOS), which again increase astrocyte swelling, thereby creating a self-amplifying signaling loop. Astroglial swelling and ROS/RNOS increase protein tyrosine nitration and may account for neurotoxic effects of ammonia and other precipitants of hepatic encephalopathy. Recently, RNA oxidation and an increase of free intracellular zinc ([Zn(2+)](i)) were identified as further consequences of astrocyte swelling and ROS/RNOS production. An elevation of [Zn(2+)](i) mediates mRNA expression of metallothionein and the peripheral benzodiazepine receptor (PBR) induced by hypoosmotic astrocyte swelling. Further, Zn(2+) mediates RNA oxidation in ammonia-treated astrocytes. In the brain of hyperammonemic rats oxidized RNA localizes in part to perivascular astrocyte processes and to postsynaptic dendritic spines. RNA oxidation may impair postsynaptic protein synthesis, which is critically involved in learning and memory consolidation. RNA oxidation offers a novel explanation for multiple disturbances of neurotransmitter systems and gene expression and the cognitive deficits observed in hepatic encephalopathy.
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PMID:RNA oxidation and zinc in hepatic encephalopathy and hyperammonemia. 1914 13

Hyponatremic and hepatic encephalopathy are common causes of metabolic encephalopathy that may coexist in patients with cirrhosis. The clinical picture is common to any metabolic encephalopathy and is characterized by a confusional syndrome that may evolve into coma. Chronic mild or minimal manifestations can be seen in both, but motor symptoms are more common in hepatic encephalopathy. Recent advances show that in addition to clinical manifestations both encephalopathies share some pathogenetic mechanisms. Dysfunction of astrocytes, osmotic changes in the brain and brain edema are present in both situations. Recognition of these abnormalities is important to plan therapy. New drugs that affect brain hydration may be useful for both encephalopathies.
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PMID:Hyponatremic and hepatic encephalopathies: similarities, differences and coexistence. 2021 2


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