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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon therapy may exacerbate health-related quality of life (HRQL) deficits associated with hepatitis C virus (HCV) early in the course of therapy. Treatment with polyethylene glycol-modified interferon (peginterferon) alfa-2a (40 kd) provides improved sustained response over interferon alfa-2a, but its effect on HRQL is unknown. The objective of this study was to (1) evaluate the effect of sustained virologic response on HRQL in patients with HCV and (2) determine whether impairment of HRQL during treatment contributes to early treatment discontinuation. Data consisted of a pooled secondary analysis of patients (n = 1,441) across 3 international, multicenter, open-label, randomized studies that compared peginterferon alfa-2a (40 kd) with interferon alfa-2a. ANCOVA was used to examine the effect of sustained virologic response on HRQL. Repeated-measures mixed-models ANCOVA was used to compare Fatigue Severity Scale (FSS) and SF-36 scores during treatment by treatment group. Logistic regression analysis was used to examine the association between changes at baseline in on-treatment HRQL and early treatment discontinuation. Sustained virologic response was associated with marked improvements from baseline to end of follow-up in all subjects, including patients with cirrhosis. During treatment, patients receiving peginterferon alfa-2a (40 kd) had statistically significantly better scores on both the SF-36 and FSS. Baseline to 24-week changes in fatigue and SF-36 mental and physical summary scores significantly predicted treatment discontinuation. In conclusion, sustained virologic response is associated with improvements in quality of life in patients with or without advanced liver disease. This parameter may be an important consideration in maximizing treatment adherence.
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PMID:Relationship of health-related quality of life to treatment adherence and sustained response in chronic hepatitis C patients. 1219 77

Fatigue is an important symptom and a quality of life determinant in patients with cholestatic liver disease. The pathogenesis of fatigue is obscure, although alterations in central neurotransmission and peripheral muscle dysfunction have been incriminated. No effective treatment is available at present. The available literature on fatigue in cholestatic liver disease is reviewed.
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PMID:Fatigue in cholestatic liver disease--a perplexing symptom. 1215 55

Pruritus, fatigue and metabolic bone disease represent three major extrahepatic manifestations of chronic cholestatic liver disease that considerably affect the patient's quality of life. The present article reviews pathogenetic aspects of and current therapeutic approaches to extrahepatic manifestations of cholestatic liver disease. Pathogenesis of pruritus of cholestasis remains poorly understood. The involvement of putative peripherally acting pruritogens, such as bile acids or endogenous opioids, is being discussed. More recently, central mechanisms, including an increased central opioidergic tone and pertubations in the serotonergic system have been proposed. Treatment of the underlying disease is beneficial also for the control of cholestasis-associated pruritus. Current therapeutic recommendations include ursodeoxycholic acid, cholestyramine, rifampicin and opioid antagonists. Liver transplantation may be indicated when severe pruritus is refractory to medical treatment. Fatigue is being recognized as the most frequent and one of the most disabling complaints in chronic cholestasis. Fatigue is presumably of central origin and its association with other neuropsychiatric disorders (e.g. depression, obsessive-compulsive disorders) is consistent with defective central neurotransmission. No specific therapies are currently available and a healthy lifestyle, regular sleep and avoidance of unnecessary stress and other precipiting factors are recommended. Antidepressant therapy may be warranted in selected patients. Osteopenia and osteoporosis are common in chronic cholestatic liver disease, whereas osteomalacia is rare. The pathophysiology of cholestasis-associated metabolic bone disease is regarded as multifactorial. Therapeutic recommendations include regular exercise, calcium and vitamin D supplementation in late stage disease, hormone replacement therapy in postmenopausal women and bisphosphonates.
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PMID:Extrahepatic manifestations of cholestasis. 1216 13

A number of studies have reported an association between chronic hepatitis C (HCV) infection and significant impairments in health-related quality of life (QOL), which are independent of the severity of liver disease. There are numerous reports documenting the prevalence of symptoms such as fatigue and depression in chronic HCV infection, which may in part account for the reductions in quality of life. Although there are a large number of potential explanations for these symptoms, including depression and anxiety associated with the diagnosis of HCV infection or substance abuse, 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 attributed to substance abuse, coexistent depression or hepatic encephalopathy. In vivo magnetic resonance spectroscopy and neurophysiological studies have suggested that a biological mechanism may underlie these 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.
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PMID:Cerebral dysfunction in chronic hepatitis C infection. 1261 63

Liver disease affects the lungs. The majority of patients exhibit mild to moderate arterial hypoxaemia essentially attributable to an alteration in ventilation/perfusion matching and limited by an increase in ventilation. A minority (some 10%) of patients exhibit a "hepatopulmonary syndrome" defined by severe hypoxaemia with arterial PO2 below 60 mm Hg, dyspnoea, cyanosis, digital clubbing, orthodeoxia, platypnoea and demonstrable pulmonary vascular dilatations causing a true pulmonary shunt and a diffusion/perfusion imbalance. The hepatopulmonary syndrome is incurable but resolves over time after liver transplantation. An even lower proportion of patients, approximately 1%, develop pulmonary hypertension. Clinically this "portopulmonary hypertension" resembles primary pulmonary hypertension, with dyspnoea and fatigue as the main symptoms, histopathology and response to prostacyclin therapy. Portopulmonary hypertension is irreversible. Liver transplantation mortality in patients with portopulmonary hypertension ranges from 50 to 100%. The common cause of the hepatopulmonary syndrome and portopulmonary hypertension is portal hypertension and portosystemic shunting, indicating that vasoactive and angiogenetic factors originating from the liver normally control the pulmonary circulation.
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PMID:Hepatopulmonary syndrome and portopulmonary hypertension. 1271 85

Liver transplantation is a well-established treatment for liver failure. Prolongation in survival is accepted, but long-term effects of liver transplantation on cognitive and psychological outcome are unclear. In the present study, psychological data were prospectively collected for 164 patients who were assessed for liver transplantation. Memory impairment, psychomotor slowing, anxiety, and depression were commonly observed. Severity of liver disease at assessment was significantly associated with slowing of reaction time. Memory impairment distinguished those who were not listed for transplantation because of illness severity. One year posttransplantation, follow-up data from transplant recipients showed significant improvement in most psychological domains relative to both healthy comparison participants and patients with chronic liver disease who did not undergo transplantation. Immunosuppression (cyclosporine versus tacrolimus) did not have differential effects on quality of life, fatigue, or affective status, although those administered cyclosporine showed greater improvements at 1-year follow-up on simple and choice reaction times. Elevated levels of anxiety and neuroticism at pretransplantation assessment were associated with worse psychosocial outcome at 1 year posttransplantation. Severity of liver disease was not related to psychological outcome at 1 year. Good psychological outcome at 1 year was maintained at the 3-year follow-up.
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PMID:Psychological outcome and quality of life following liver transplantation: a prospective, national, single-center study. 1282 58

Primary biliary cirrhosis is a chronic cholestatic liver disease of adults. This disorder is characterised histologically by chronic non-suppurative destruction of interlobular bile ducts leading to advanced fibrosis, cirrhosis, and liver failure. The precise aetiopathogenesis of primary biliary cirrhosis remains unknown, although dysregulation of the immune system and genetic susceptibility both seem to be important. Affected patients are typically middle-aged women with abnormal serum concentrations of alkaline phosphatase. Presence of antimitochondrial antibody in serum is almost diagnostic of the disorder. Identification of primary biliary cirrhosis is important, because effective treatment with ursodeoxycholic acid has been shown to halt disease progression and improve survival without need for liver transplantation. However, therapeutic options for disease-related complications-including fatigue and metabolic bone disease-remain unavailable. Mathematical models have been developed that accurately predict the natural history of primary biliary cirrhosis in individuals. Despite advances in understanding of the disease, it remains one of the major indications for liver transplantation worldwide.
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PMID:Primary biliary cirrhosis. 1285 1

Nonalcoholic fatty liver disease is a condition gaining increasing recognition as a cause of cirrhosis and end-stage liver disease. The condition appears identical to alcoholic liver disease histologically, yet occurs in patients with negligible alcohol intake. Nonalcoholic fatty liver disease covers a spectrum of diseases ranging from simple fatty deposition in the liver to fat and inflammation and finally to fibrosis and cirrhosis. Conditions most frequently found in association with nonalcoholic fatty liver disease include obesity, Type 2 diabetes, and hyperlipidemia. Although the exact etiology of nonalcoholic fatty liver disease is not clear, insulin resistance is thought to play an important factor. Patients typically present with asymptomatic serum aminotransferase elevations of 2-3 times normal. Symptoms may include fatigue and abdominal pain. The clinical course is difficult to predict due to a lack of research in the natural history of the disease. It is known a percentage of patients progress to end-stage liver disease and may require liver transplantation. No medical treatment has been found to be totally effective. Patients who are overweight or obese should be encouraged in gradual weight reduction that has been associated with improvement in liver test abnormalities.
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PMID:Nonalcoholic Fatty liver disease. 1292 Apr 29

Thomas Addison described three of the classical autoimmune diseases, so can justifiably be regarded as one of the fathers of the study of autoimmunity. The least well recognised of these conditions, the autoimmune liver disease primary biliary cirrhosis (PBC), is in some ways the most interesting. As a result of the relatively advanced state of knowledge of its immunopathogenesis, it represents a good model for the study of autoimmune disease. The classical pathological lesion of PBC is apoptotic damage to the biliary epithelial cells lining the small intrahepatic bile ducts. The disease is typified by two symptom sets: fatigue and pruritus, which can occur at any stage of the disease process, and the features of advanced liver disease, which occur when secondary liver damage results from bile retention. Although autoantibodies directed at, in particular, pyruvate dehydrogenase complex (PDC) are almost universally present in PBC (and represent an important diagnostic tool), it appears likely that CD8+ cytotoxic T cells reactive with self-PDC derived epitopes are directly responsible for target cell damage. Recent studies in humans and a novel murine disease model have shed light on the mechanism of breakdown of immune tolerance to self-PDC; they provide important insights into the pathogenesis of PBC in particular and of autoimmunity in general.
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PMID:Addison's other disease: primary biliary cirrhosis as a model autoimmune disease. 1293 51

Availability of a drug regimen that eradicates the hepatitis C virus (HCV) in more than half of treated patients provides the medical community with a powerful new weapon to diminish the anticipated future wave of HCV-related liver disease and cancer. Clinicians must understand the benefits, risks, and costs associated with the combination of peginterferon alfa and ribavirin. Major clinical trials with this new standard of HCV therapy have demonstrated sustained virologic responses of 54% and 56% with 48 weeks of combination therapy. Response is highest in those with genotype 2/3, with early virologic response by week 12, in patients with high adherence, and in patients receiving weight-appropriate ribavirin dosages. The most common side effects are manageable and include fatigue, headache, myalgia, rigors, fever, nausea, insomnia, and depression. Neutropenia associated with interferon and anemia associated with ribavirin are more serious side effects that can cause discontinuation or dose reduction. Clinicians can maximize results and reduce costs with a regimen of peginterferon alfa plus ribavirin by choosing patients carefully, educating patients thoroughly, stopping therapy early in those patients who do not respond by week 12 of therapy, and enhancing adherence by managing side effects with appropriate dose reductions and/or selective use of antidepressants or hematopoietic colony stimulators.
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PMID:Managing hepatitis C. 1508 65


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