Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatigue is a symptom of liver disease. Indirect evidence suggests that this type of fatigue is centrally mediated. Non-alcoholic steatohepatitis (NASH), which may lead to cirrhosis, is associated with insulin resistance. An activated hypothalamic pituitary adrenal axis results in increased secretion of cortisol releasing hormone, cortisol and catecholamines. Prolonged exposure to high levels of cortisol is associated with insulin resistance, as exemplified by the metabolic syndrome. Accumulation in visceral fat is an independent factor associated with insulin resistance. Central (visceral) fat is less sensitive to insulin than the rest of body fat and the central nervous system and not peripheral insulin, appears to regulate lipolysis in visceral fat by, at least in part, adrenergic mechanisms. Aerobic training has documented beneficial effects on mental health and fatigue secondary to chronic illness. In addition, aerobic training increases insulin sensitivity. Thus, aerobic training may decrease fatigue in liver disease and improve NASH.
 ...
PMID:Aerobic exercise: a potential therapeutic intervention for patients with liver disease. 1514 52

NAFLD/NASH is now recognised as an increasing clinical problem in children and adolescents. Risk factors include obesity, insulin resistance, and hypertriglyceridaemia. Drug hepatoxicity and genetic or metabolic diseases that can cause hepatic steatosis must be excluded. Affected children are usually asymptomatic although a few may complain of malaise, fatigue, or vague recurrent abdominal pain. Liver biopsy is the gold standard for diagnosis, and is important in determining disease severity and prognosis. The natural history of childhood NASH may be progressive liver disease for a significant minority. Long term follow up studies in this population are still lacking. The mainstay of treatment is weight reduction. The use of pharmacological therapy, though promising, ideally needs further evaluation in well designed randomised controlled studies in children.
 ...
PMID:Fatty liver disease in children. 1521 Apr 98

"Overlap syndromes" have been reported among various autoimmune liver diseases, particularly between primary biliary cirrhosis and autoimmune hepatitis (AIH) in adults and between AIH and autoimmune cholangitis in children. The overlap syndrome of AIH and primary sclerosing cholangitis (PSC), however, has been scarcely reported. Furthermore, in most of the reported cases of AIH/PSC overlap syndrome, PSC and AIH were believed to occur simultaneously. We report a case of a 34-year-old woman who has ulcerative colitis and PSC (diagnosed by colonoscopy, histology, and cholangiogram) and 7 years later develops rapidly progressive liver failure and hemolytic anemia from AIH. Liver biopsy showed dense portal lymphoplasmacytic infiltrate with interface hepatitis and acidophil bodies confirming AIH. She responded well to immunosuppressive therapy with steroids, both with respect to her liver disease and her autoimmune hemolytic anemia. Additionally, her clinical symptoms of fatigue, jaundice, and pruritus improved markedly and quickly. Overlap or "crossover" syndrome should be considered in all patients with PSC when they present with sudden deterioration of the liver function and changes in liver enzymes. By making the diagnosis of AIH in a patient with well-established PSC, appropriate treatment can be initiated, resulting in the patient's prompt recovery.
 ...
PMID:Rapid progression of autoimmune hepatitis in the background of primary sclerosing cholangitis. 1549 11

The available liver disease-specific questionnaires do address severity of symptoms but hardly evaluate how patients experience these specific symptoms during daily activities. The Liver Disease Symptom Index 2.0 (LDSI) includes 18 items that measure symptom severity and symptom hindrance in the past week. In a large survey (n = 1175) conducted in collaboration with the Dutch liver patient association, convergent and divergent construct validity and the surplus value of including symptom severity and symptom hindrance items in the LDSI were examined. The LDSI items showed expected convergent and divergent correlations with Short Form-36 (SF-36) and Multidimensional Fatigue Index-20 (MFI-20) scales. Correlations revealed only a slight to moderate overlap between LDSI items and SF-36 and MFI-20 scales. The impact of symptom severity and symptom hindrance on generic health related quality of life (HRQoL) varied in a different way across liver patients, which indicated that symptom severity items and the symptom hindrance items measure different aspects of HRQoL. We conclude that the LDSI provides information complementary to the information given by the SF-36 and the MFI-20 and that it is psychometrically sound to include both symptom severity items and symptom hindrance items in the LDSI.
 ...
PMID:The Liver Disease Symptom Index 2.0; validation of a disease-specific questionnaire. 1550 42

The hepatitis C virus (HCV) infection is a worldwide disease that is characterized by a preferential chronic evolution with mild to severe liver disease, including cirrhosis and, in lesser proportion, hepatocarcinoma. Out of these complications, HCV is frequently reported to complicate extrahepatic manifestations. Among those associated to HCV infection with a high degree of certainty, mixed cryoglobulinemia and its complications (skin, neurological, renal, rheumatological involvement) are the most prevalent (50%) in HCV-infected patients. The other diseases include noncryoglobulinemic systemic vasculitis, splenic lymphoma with villous lymphocytes, fatigue, porphyria cutanea tarda, sicca syndrome, and autoantibodies production. The extrahepatic manifestations that share mild-degree certainty of association with HCV infection include B-cell non-Hodgkin lymphoma, autoimmune thrombocytopenia, pruritus, and type II diabetes mellitus. The other diseases such as autoimmune thyroiditis, lichen planus are more questionable for their eventual association with HCV and others (pulmonary fibrosis with or without polymyositis, progressive encephalomyelitis, Mooren's corneal ulcers, erythema nodosum, chronic polyradiculonevritis) are mostly case reports. Howerver, even in cases of tight association, the mechanisms through which HCV may promote or induce extrahepatic manifestations remain unclear and merit further investigations.
 ...
PMID:Hepatitis C virus-associated extrahepatic manifestations: a review. 1555 28

Neurocognitive morbidity has been reported in individuals with chronic hepatitis C virus (HCV) infection, but the magnitude of such dysfunction in the absence of disease-correlated factors known to affect the central nervous system (e.g., substance abuse, cirrhosis, depression, interferon treatment) and the impact of any such change on functioning is unclear. We investigated a cohort of individuals with HCV, all of whom were carefully screened to exclude relevant comorbidities, to elucidate virus-related changes in the brain using neuropsychological tests and magnetic resonance spectroscopy (MRS). A cohort of 37 patients with chronic HCV infection was culled from 300 consecutive patients presenting to a tertiary care liver clinic. A comparison group of healthy controls (n = 46) was also assessed. Of 10 neurocognitive measures evaluated, the HCV group showed marginally poorer learning efficiency compared with controls; only 13% of patients demonstrated a clinical level of impairment on this test (defined as 1.5 SD below the normative standard). Although patients reported greater levels of fatigue and symptoms of depression, these factors did not correlate with the degree of learning inefficiency. With respect to MRS, the HCV group demonstrated increased choline and reduced N-acetyl aspartate relative to controls in the central white matter. Indicators of liver disease severity did not correlate with either memory or MRS abnormalities. In conclusion, while our findings support an association between hepatitis C and indicators of central nervous system involvement in a cohort of patients carefully screened to eliminate other factors influencing neurocognitive integrity, the clinical significance of these effects is limited.
 ...
PMID:Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. 1579 53

It has been reported that hepatitis C virus (HCV) infection is associated with cognitive dysfunction, fatigue and depression, which do not correlate with the severity of liver disease and cannot be accounted for by hepatic encephalopathy or drug abuse. There is also emerging evidence that HCV infection can have negative neurocognitive effects in HIV-infected cohorts. Magnetic resonance spectroscopy has suggested the likely existence of a biological basis for these effects. HCV replicative forms have recently been detected in autopsy brain tissue and the infected cells have been identified as CD68-positive (macrophages/microglia). These findings raise the possibility that HCV infection of the brain could be directly related to the reported neuropsychological and cognitive changes. HCV is not strictly hepatotropic, as it can also replicate in leukocytes, including monocytes/macrophages. The latter cells could provide access of HCV into the central nervous system ('Trojan horse' mechanism) in a process similar to that postulated for HIV-1. In support of this hypothetical mechanism come reports showing a close relationship between HCV sequences present in the brain and cerebrospinal fluid and sequences found in lymph nodes and peripheral blood mononuclear cells. However, despite some similarities there is a fundamental difference between HIV-1 and HCV infection as the latter does not progress into AIDS-type dementia.
 ...
PMID:Emerging evidence of hepatitis C virus neuroinvasion. 1625 11

Numerous studies have reported associations between chronic hepatitis C virus (HCV) infection and fatigue, depression and impairments in health-related quality of life, which are independent of the severity of liver disease. Although there are a large number of potential explanations for these symptoms, including a history of substance abuse and associated personality types, or the effect of the diagnosis of HCV infection itself, there has been recent interest in the possibility of a biological effect of HCV infection on cerebral function. There is emerging evidence of mild, but significant neurocognitive impairment in HCV infection, which cannot be wholly attributed to substance abuse, co-existent depression or hepatic encephalopathy. Impairments are predominantly in the domains of attention, concentration and information processing speed. Furthermore, in-vivo cerebral magnetic resonance spectroscopy studies in patients with hepatitis C and normal liver function have reported elevations in cerebral choline-containing compounds and reductions in N-acetyl aspartate, suggesting that a biological mechanism may underlie the cognitive findings. The recent detection of HCV genetic sequences in post-mortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment.
 ...
PMID:A review of cognitive impairment and cerebral metabolite abnormalities in patients with hepatitis C infection. 1625 29

A 70-year-old woman presented with impaired memory and depressive symptoms and two women aged 53 and 30 years, respectively, presented with general malaise and fatigue. All were diagnosed with and treated for autoimmune hepatitis (AIH). The first patient developed a relapse during treatment withdrawal; she recovered and maintained remission after the initial dose of medication had been restarted and the medication was tapered more gradually. The second patient had an incomplete remission and later developed liver failure; she was eligible for a liver transplant. The third woman became pregnant during treatment and developed a relapse after delivery; remission was induced and maintained after the immunosuppression was temporally increased. AIH is a chronic progressive liver disease characterised by abnormal serum levels of liver enzymes, hypergammaglobulinaemia, auto-antibodies against cell nuclei (ANA), smooth muscle (SMA), or liver and kidney microsomes (LKM), interface hepatitis and the absence of other chronic liver disease. Early diagnosis is essential because therapy can markedly improve prognosis. However, there is no specific diagnostic test for AIH. It is important to induce and maintain remission with immunosuppressive therapy.
 ...
PMID:[Three patients with autoimmune hepatitis: the importance of early diagnosis and remission]. 1646 22

Signaling occurs between the liver and brain in cholestatic liver disease, giving rise to sickness behaviors such as fatigue. However, the signaling pathways involved are poorly defined. Circulating inflammatory mediator levels are increased in cholestasis, leading to speculation that they may be capable of activating circulating immune cells that subsequently could gain access to the brain. Indeed, we have identified that at day 10 after bile duct resection-induced cholestasis, there is activation of circulating monocytes that express tumor necrosis factor alpha (TNF-alpha) in conjunction with increased expression of adhesion molecules by cerebral endothelium. Moreover, using intravital microscopy, we have identified markedly enhanced leukocytes rolling along cerebral endothelial cells, mediated by P-selectin, in bile duct-resected (BDR) but not control mice. In addition, we have identified increased infiltration of monocytes (but not lymphocytes) into the brains of BDR mice and found that these infiltrating monocytes produce TNF-alpha. Furthermore, infiltration of TNF-alpha-secreting monocytes into the brains of cholestatic mice is associated with a broad activation of resident brain macrophages to produce TNF-alpha. In conclusion, cholestasis is associated with an activation of cerebral endothelium that recruits TNF-alpha-producing monocytes into the brain. We hypothesize that enhanced TNF-alpha release within the brain may contribute to the development of cholestasis-associated sickness behaviors, including fatigue.
 ...
PMID:TNF-alpha-secreting monocytes are recruited into the brain of cholestatic mice. 1672 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>