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)

Wilson's disease and Menkes disease are inherited genetic disorders of copper metabolism. Each disease results from the absence or dysfunction of homologous copper-transporting ATPases present in the trans-Golgi network of cells. The Wilson ATPase transports copper into the hepatocyte secretory pathway for incorporation into ceruloplasmin and excretion into the bile. Thus, patients with Wilson's disease of the autosomal recessive trait present with signs and symptoms arising from impaired biliary copper excretion. The Menkes ATPase transports copper across the placenta, gastrointestinal tract, and blood-brain barrier, and the clinical features of this X-linked disease arise from copper deficiency. Despite striking differences in the clinical presentation of these two diseases, the respective ATPases function in precisely the same fashion within the cell. The different clinical features of each disease are the results of the tissue specific expression of these ATPases. In Wilson's disease, impaired biliary copper excretion leads to accumulation of this metal in the liver. When the capacity for hepatic storage is exceeded, cell death ensues, with copper release into the plasma resulting in hemolysis and deposition of copper in extrahepatic tissues. Affected patients usually present in the first or second decade of life with chronic hepatitis and cirrhosis or acute liver failure. Copper accumulation in the cornea results in Kayser-Fleischer rings. Neuropsychiatric symptoms are more common in adults and include dystonia, tremor, personality changes, and cognitive impairment as a results of copper accumulation in the basal ganglia and other brain regions. The diagnosis of Wilson's disease is confirmed by decreased serum ceruloplasmin, increased urinary copper, and elevated hepatic copper concentration. A large number of different mutations occur in the genes of patients with Wilson disease. Copper chelation drugs and zinc are effective in most cases. New treatment guidelines now advise physicians to start patients on zinc.
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PMID:[Genetic disorders of copper transport--diagnosis and new treatment for the patients of Wilson's disease]. 1577 21

It is well-known that liver cirrhosis is frequently accompanied by a wide range of neuropsychiatric abnormalities, including general and specific cognitive impairment. The aim of this study was to investigate which cognitive functions are selectively compromised in Hepatic Encephalopathy (HE) and to clarify the relationship between clinically overt or nonovert HE and the different forms and degrees of decay in cognitive deficits. Twenty-two patients without overt HE and 12 patients who showed overt HE at the first level of severity, along with matched control subjects, were compared in several cognitive domains. The results showed significant differences in some measures of attention between patients with minimal HE (mHE) and patients with overt HE. There were also notable differences in verbal short-term memory between patients with mHE and healthy subjects. Thus, we can hypothesize that there is a linear diminution in short-term memory and attentional performance starting from healthy patients, moving toward patients with mHE, and finally progressing toward patients with the first grade of overt HE. There are two types of diminution that we noted: between patients with mHE and the overt form, the decline in the attentional domain was more evident, while between healthy subjects and mHE patients, short-term memory showed a more evident decline.
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PMID:Distinguishing between clinical and minimal hepatic encephalopathy on the basis of specific cognitive impairment. 1616 2

Neuroimaging and post-mortem studies indicate that chronic alcohol use induces global changes in brain morphology, such as cortical and subcortical atrophy. Recent studies have shown that frontal lobe structures are specifically susceptible to alcohol-related brain damage and shrinkage in this area is largely due to a loss of white matter. This may explain the high incidence of cognitive dysfunction observed in alcoholics. Using a proteomics-based approach, changes in protein expression in the dorsolateral prefrontal region (BA9) white matter were identified in human alcoholic brains. Protein extracts from the BA9 white matter of 25 human brains (10 controls; eight uncomplicated alcoholics; six alcoholics complicated with hepatic cirrhosis; one reformed alcoholic) were separated using two-dimensional gel electrophoresis. Overall, changes in the relative expression of 60 proteins were identified (P<0.05, ANOVA) in the alcoholic BA9 white matter. In total, 18 protein spots have been identified using MALDI-TOF; including hNP22, alpha-internexin, transketolase, creatine kinase chain B, ubiquitin carboxy-terminal hydrolase L1 and glyceraldehyde-3-phosphate dehydrogenase. Several of these proteins have been previously implicated in alcohol-related disorders and brain damage. By identifying changes in protein expression in this region from alcoholics, hypotheses may draw upon more mechanistic explanations as to how chronic ethanol consumption causes white matter damage.
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PMID:Differential protein expression in the prefrontal white matter of human alcoholics: a proteomics study. 1617 12

The clinical presentation of acute liver failure and hepatic encephalopathy (HE) in patients with cirrhosis differs significantly. The most serious neurological complication of acute liver failure is the development of devastating brain oedema. Therefore, intracranial pressure monitoring is urgently needed in these patients. Brain oedema is amplified by hypoglycemia, hypoxia and seizures, which are also frequent complications of acute liver failure. Therefore, these parameters must also be monitored. In contrast to acute liver failure in which cerebral dysfunction progresses rapidly, cognitive decline may be clinically undetectable for a long time in cirrhotic patients, until clinically overt symptoms such as psychomotor slowing, disorientation, confusion, extrapyramidal and cerebellar symptoms or a decrease in consciousness occur. Clinically, overt HE is preceded by minimal alterations of cerebral function that can only be detected by neuropsychological or neurophysiological measures, but which nevertheless interfere with the patient's daily living. Rapidly progressing spastic paraparesis (hepatic myelopathy) is a rare complication of cirrhosis. In contrast to HE, it does not respond to blood ammonia lowering therapies but must be considered as an indication for urgent liver transplantation. Cognitive dysfunction has recently been detected in hepatitis C virus (HCV)-infected patients with normal liver function. The patients presented with severe fatigue, cognitive dysfunction and mood disorders. Alterations in brain metabolites, as detected by magnetic resonance spectroscopy, indicated central nervous system alteration in these patients. In contrast to patients with HE, HCV-infected patients did not show motor symptoms or deficits in visual perception, but considerable deficits in attention and concentration ability.
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PMID:Neurological and neuropsychiatric syndromes associated with liver disease. 1625 35

Minimal hepatic encephalopathy (MHE) is the earliest stage of hepatic encephalopathy and is associated with changes in cognitive functions, in electrophysiological parameters, and in cerebral neurochemical/neurotransmitter homeostasis. MHE can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy (HE). At present, no data are available on a possible olfactory dysfunction in such a syndrome, although the pathophysiology of HE may alter olfactory functions since some of the neurotransmitters impaired in the syndrome are involved in the transmission of olfactory information. In the present paper, we performed a preliminary study aimed at detecting whether identification and recognition odor memory is altered in patients with MHE. Twelve patients diagnosed as MHE on the basis of their scores at the portosystemic encephalopathy (PSE)-syndrome test battery, and 12 age-matched controls were studied. Consistent with the hypothesis, patients performed significantly worse than controls for both odor identification and recognition tasks. In addition, a significant correlation between the two olfactory tests and the PSE-syndrome test score was found. This pattern supports the notion that olfactory alterations related to cognitive dysfunction in patients with MHE may be linked to the pathophysiology of HE.
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PMID:Olfactory deficits in patients affected by minimal hepatic encephalopathy: a pilot study. 1643 87

Patients with chronic hepatitis C virus (HCV) infection frequently describe neuropsychological symptoms. Although hepatic encephalopathy is the best established neurological association of HCV infection, there is a growing body of literature on cerebral dysfunction, occurring at an early stage of chronic HCV infection, well before the development of cirrhosis. In this review we describe recent studies that have documented mild, but significant neurocognitive impairment in HCV infection. These deficits in patients with minimal or absent liver disease do not appear to be attributable to a history of substance abuse, coexistent depression or hepatic encephalopathy. Recent studies employing in-vivo magnetic resonance spectroscopy have suggested that a biological mechanism associated with the virus may be responsible. The hypothesis that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment is supported by molecular virological studies of post-mortem brain tissue.
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PMID:Central nervous system changes in hepatitis C virus infection. 1653 3

It is widely accepted that the chronic use of alcohol induces metabolic abnormalities and neuronal damage in the brain, which can lead to cognitive dysfunction. Neuroimaging studies reveal that alcohol-induced brain damage is region specific and prominent damage has been observed in both gray and white matter of the prefrontal cortex, and a wide range of white matter structures including the corpus callosum. Molecular mechanisms underlying these structural changes are largely unknown. Using proteomics we have analysed the changes in protein expression in the splenium of the corpus callosum in two different alcoholic groups. Protein extracts from splenium of 22 human brains (nine controls, seven uncomplicated alcoholics and six complicated alcoholics with hepatic cirrhosis-designated complicated) were separated using two-dimensional gel electrophorosis. Image analysis revealed that there were significant alterations in protein expression for 25 protein spots in the uncomplicated alcoholic group and 45 in the complicated group compared to control (P<0.05; ANOVA). In a total of 72 spots (identified as 36 proteins), 15 (identified as 14 proteins) spots overlapped between two alcoholic groups. Another 32 protein spots (26 different proteins) were identified only in the complicated alcoholics. It is therefore possible that these 26 proteins in the complicated group are likely to be the results of hepatic compromise. When compared with our previous data of white matter from the prefrontal cortex in alcoholics, large numbers of identified proteins in the splenium are different. This suggests that there may be different mechanisms causing alcohol-induced brain damage in different regions of the white matter. Our data also indicate the importance of other pathways including oxidative stress, lipid peroxidation and apoptosis as potential causes of alcohol-induced brain damage.
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PMID:Differential protein expression in the corpus callosum (splenium) of human alcoholics: a proteomics study. 1714 22

Patients with liver cirrhosis with normal neurological and mental status examination may present minimal forms of hepatic encephalopathy, showing intellectual function impairment that cannot be detected through general clinical examination but can be unveiled using specific neuropsychological or neurophysiological examination. Evaluation of minimal hepatic encephalopathy (MHE) in cirrhotic patients would have prognostic value. The psychometric hepatic encephalopathy score (PHES) has been recommended as the "gold standard" in the diagnosis of MHE. Altered modulation of cyclic GMP (cGMP) levels in the brain seems to be responsible for the impairment of some types of cognitive function in liver disease. In animal models of liver disease, some of the alterations in modulation of cGMP levels in the brain are reproduced in lymphocytes. The aim of the present work was to assess whether there is a correlation between the alterations in different parameters involved in modulation of cGMP levels and the presence of MHE in patients with liver disease. We studied in 46 patients with liver cirrhosis and 26 controls the performance in the PHES battery of psychometric tests and the critical flicker frequency (CFF), the concentration of cGMP in plasma and lymphocytes, activation of guanylate cyclase by nitric oxide (NO) in lymphocytes, and several parameters likely involved in altered cGMP homeostasis in liver disease such as ammonia, NO metabolites, and atrial natriuretic peptide (ANP). Activation of guanylate cyclase by NO in lymphocytes and cGMP in plasma were higher and CFF lower in patients with MHE than in patients without MHE. Ammonia, ANP, and metabolites of NO were higher in patients than in controls but were no different in patients with or without MHE. Alteration in activation of guanylate cyclase by NO in lymphocytes correlates with PHES performance, CFF, and ammonia levels. This suggests that altered modulation of guanylate cyclase by NO in lymphocytes would reflect a parallel alteration in the brain occurring in patients with MHE that would be involved in their cognitive impairment.
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PMID:Activation of soluble guanylate cyclase by nitric oxide in lymphocytes correlates with minimal hepatic encephalopathy in cirrhotic patients. 1727 19

The hepatitis C virus (HCV) is a common blood-borne illness that affects up to 2% of the world's population and almost 4 million Americans. Cognitive impairment, or difficulty with thinking, has become a well-established symptom in persons with end stage liver disease. It was previously assumed that cognitive impairment was a consequence of cirrhosis-associated hepatic encephalopathy. Recent evidence, however, suggests that approximately one-third of people with chronic HCV experience cognitive impairment even in the absence of cirrhosis and that its occurrence is unrelated to other indices of liver function, such as laboratory values, viral load, and genotype. In the present review, evidence outlining the presence of cognitive deficits associated with HCV, possible etiological factors, effects of antiviral therapy, and co-infection with human immunodeficiency virus (HIV) is presented. Implications of these findings and directions for future work are discussed.
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PMID:Cognitive dysfunction in chronic hepatitis C: a review. 1770 62

Minimal hepatic encephalopathy (MHE), formerly known as subclinical hepatic encephalopathy, is the mild cognitive impairment commonly seen in patients who have cirrhosis. Current understanding suggests that MHE forms part of the spectrum of hepatic encephalopathy, although this remains to be proven. Although traditionally viewed as having negligible clinical significance, MHE has a significant impact on quality of life. MHE often goes undiagnosed because in many patients there is no evidence of clinically overt signs of impaired cognition. In addition, the diagnostic criteria for MHE have not been standardized, which means that the exact characteristics of MHE remain in question. This Review focuses on the pathogenesis and neuropsychological findings (incorporating neuroimaging) of MHE, as well as the effect of MHE on quality of life and survival, and developments in treatment.
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PMID:Minimal hepatic encephalopathy. 1804 77


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