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

Interferon and ribavirin combination therapy for chronic hepatitis C produces a number of well-described side effects that are dominated by fatigue, influenza-like symptoms, hematologic abnormalities, and neuropsychiatric symptoms. Combination therapy with pegylated interferons (peginterferon alfa-2a and alfa-2b) yields an adverse event profile similar to standard interferon, although the frequency of certain adverse events may vary by preparation. Premature withdrawal from therapy due to adverse events was required in 10% to 14% of participants in registration trials of these agents. Most adverse events were safely and effectively managed by dose reduction using predetermined criteria. The most common indications for dose reduction were hematologic abnormalities, such as anemia and neutropenia, with the latter more frequent in peginterferon treatment arms. Recent data suggest that maintaining adherence to a prescribed treatment regimen can enhance antiviral response. Strategies to maximize adherence are being developed and, in the future, may include early identification of and therapy for depression and the selective use of hematopoietic growth factors to ameliorate hematologic abnormalities.
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PMID:Side effects of therapy of hepatitis C and their management. 1240 99

Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureussis. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA-negative strand, which is the viral replicative form, was determined by strand-specific Tth-based reverse-transcriptase polymerase chain reaction. Viral sequences were compared by means of single-strand conformation polymorphism and direct sequencing. HCV RNA-negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA-negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5' untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. The exact lineage of cells permissive for HCV replication and the possible interaction between viral replication and cerebral function that may lead to depression remain to be elucidated.
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PMID:Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation. 1242 14

The aim of this study was to assess the impact of fatigue on the quality of life of patients with chronic hepatitis C (CHC) and to examine its relationship with various parameters of the disease, including viral load. The Fatigue Impact Scale (FIS), a self-report questionnaire, was applied to 92 patients with CHC, and the results were compared to those of an age-matched cohort of 213 healthy blood donors. Fatigue was frequent and disabling, being present in 67% of CHC patients, and the FIS was significantly increased in CHC patients compared to the healthy controls. Fatigue severity was not correlated with the activity of the disease or with the level of viremia. The FIS proved to be a valuable tool to assess this symptom. It should be of help for better evaluation of the clinical spectrum of the disease and should be included in trials assessing the efficacy of therapeutic interventions.
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PMID:Assessment of fatigue in patients with chronic hepatitis C using the Fatigue Impact Scale. 1249 84

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

In a 49-year-old man and a 28-year-old woman, both of whom complained of fatigue, HFE-gen related respectively non-HFE-gen related primary haemochromatosis was diagnosed, based on the elevated serum transferrin saturation, the elevated serum ferritin levels, DNA studies and liver biopsy with qualitative respectively quantitative iron measurements. Their complaints diminished after bloodletting. Three women respectively 64, 61 and 46 years of age, were also suspected of primary haemochromatosis. The latter two presented with complaints of fatigue and malaise and chronic hepatitis C respectively. All three showed an elevated serum transferrin saturation and serum ferritin concentration. Further investigation showed the presence of secundary iron overload. Causes for it being excessive alcohol consumption, overweight and a poorly regulated diabetes mellitus type 2, and chronic hepatitis C respectively. These patients received specific therapy. Primary haemochromatosis is a common disorder of iron metabolism in individuals of Northern European descent. Diagnosis is based on an elevated serum transferrin saturation in combination with both elevated serum ferritin levels and homozygosity for the Cys282Tyr-mutation in the HFE-gen. The presence of an elevated serum transferrin saturation in combination with an elevated serum ferritin level is not always sufficient for the diagnosis, since these may be affected by other disorders. Moreover, iron overload may be caused by a form of haemochromatosis that is not HFE-related. In case of doubt as to the diagnosis, histological examination of the liver with a qualitative or quantitative iron determination is the golden standard.
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PMID:[Diagnosis of 5 patients with possible primary hemochromatosis]. 1271 48

Recombinant human interleukin 12 (IL-12) is an immunomodulatory cytokine that is active against several viruses. Treatment options in patients with chronic hepatitis C with nonresponse to interferon (IFN)-based therapy are limited. Prior dose-ranging studies have indicated drug tolerability and transient suppression of hepatitis C virus (HCV) RNA by IL-12. The aim of this study was to determine the safety and efficacy of prolonged IL-12 therapy in patients who have failed treatment with IFN-alpha +/- ribavirin. A total of 225 patients at 21 U.S. sites who had a history of nonresponse to IFN-alpha or combination IFN-alpha plus ribavirin for treatment of HCV were randomized to 500 ng/kg IL-12 or placebo subcutaneously twice weekly for 12 weeks. The groups were then unblinded; patients receiving IL-12 continued for another 36 weeks, and the placebo group received 48 weeks of treatment with IL-12 in an open-label fashion. HCV RNA, serum alanine aminotransferase (ALT) level, and a repeat liver biopsy were assessed at 24 weeks following therapy. Approximately 1% (2 of 160) of nonresponsive patients enrolled for treatment had a sustained virologic response to IL-12 therapy, but 3% (7 of 225) developed severe adverse events probably related to treatment, resulting in early termination of the trial. Common adverse effects reported by most patients included chills, fever, fatigue, headache, and arthralgia. At termination of the study, 160 patients had received at least 8 weeks of treatment with IL-12. Paired liver biopsy specimens were available for evaluation in 54 patients, but there were no significant changes in Knodell fibrosis or histologic activity index (HAI) scores. In conclusion, IL-12 as monotherapy at the doses used in this trial for chronic hepatitis C has low efficacy, was poorly tolerated, and is unlikely to provide an alternative to conventional IFN-based therapy.
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PMID:A multicenter study of recombinant human interleukin 12 for the treatment of chronic hepatitis C virus infection in patients nonresponsive to previous therapy. 1277 16

The results of lamivudine therapy in 4 patients with chemotherapy-induced hepatitis B virus (HBV) reactivation are reported. Cancer chemotherapy-induced reactivation is a known complication in patients with chronic HBV infection or history of HBV infection with recovery. Reactivation of HBV infection has a broad spectrum of manifestations ranging from mild elevation of aminotransferase levels to fatal fulminant hepatitis. Lamivudine is a nucleoside analogue and a potent inhibitor of HBV reverse transcription. The 4 patients treated with lamivudine included 1 woman with breast cancer and 3 men with non-Hodgkin lymphoma, ranging from 41 to 63 years of age. All 4 patients were undergoing standard, multi-agent chemotherapy when they presented with HBV reactivation manifested by sudden onset of fatigue, jaundice, and HBV serology consistent with active HBV infection (detectable serum HBV DNA) in the absence of other known causes of acute hepatitis. Lamivudine therapy (100 mg/d in 3 patients and 150 mg/d in 1 patient) was initiated from 1 to 18 days following the diagnosis of HBV reactivation. All 4 patients showed rapid decrease in aminotransferase levels within 2 weeks after initiating lamivudine therapy. Unfortunately, hepatic synthetic function failed to improve in 2 patients, who both died. The remaining 2 patients had suppression of HBV DNA to undetectable levels after 1 and 4 months of treatment and had biochemical and clinical improvement. The 2 patients who died received lamivudine therapy for 8 days and for 3 weeks. There have been no randomized clinical trials to study the role of lamivudine for prophylaxis or treatment of HBV reactivation associated with chemotherapy. However, based on our limited experience, lamivudine may be efficacious in suppressing potentially fatal HBV reactivation secondary to chemotherapy in patients with chronic HBV infection or prior infection with recovery. Patients who undergo chemotherapy should be screened for the presence of markers of chronic hepatitis B infection or previous HBV infection. We recommend that patients with chronic HBV infection (positive HBV DNA and/or positive HBsAg) or history of HBV infection with recovery (positive hepatitis B core antibody with or without HBsAb) be considered for prophylactic lamivudine use to prevent chemotherapy-induced HBV reactivation.
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PMID:Prophylaxis against chemotherapy-induced reactivation of hepatitis B virus infection with Lamivudine. 1281 Dec 13

Although mild thrombocytopenia is a common adverse effect of interferon therapy, severe life-threatening thrombocytopenia is extremely rare. Here, we report a case of chronic hepatitis C patient that developed severe thrombocytopenia during alpha-interferon therapy, possibly due to an autoimmune mechanism. A 24-year-old female presented chronic hepatitis C in May, 1998. Based on the clinicopathological findings including a liver biopsy, administration of alpha-interferon was begun. In the fourth week of therapy, she experienced mild dyspnea and general fatigue. Complete blood count demonstrated thrombocytopenia (48,000/microL). Despite the immediate withdrawal of interferon, her platelet count further decreased to 1,100/microL. Bone marrow aspirate and elevated platelet-associated IgG antibodies were suggestive of immune thrombocytopenia. She was treated with intravenous and oral administration of steroids. Her platelet count returned to normal level 5 days later. Response to steroid treatment was consistent with the diagnosis of alpha-interferon-induced immune thrombocytopenia in this patient.
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PMID:Life-threatening severe immune thrombocytopenia during alpha-interferon therapy for chronic hepatitis C. 1282

Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculoskeletal pain and fatigue. There is a growing body of evidence supporting a link between cytokines and somatic complaints. This review discusses alterations of cytokines in fibromyalgia, including increased serum levels of interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist; increased IL-1 and IL-6 produced by stimulated peripheral blood mononuclear cell in patients with FM for longer than 2 years; increased gp130, which is a neutrophil cytokine transducing protein; increased soluble IL-6 receptor and soluble IL-1 receptor antagonist only in patients with fibromyalgia who are depressed; and IL-1 beta, IL-6, and TNF-a by reverse transcriptase-polymerase chain reaction in skin biopsies of some patients with fibromyalgia. In addition, this review describes the mechanism by which alterations in cytokines in fibromyalgia and chronic hepatitis C infection can produce hyperalgesia and other neurally mediated symptoms through the presence of cytokine receptors on glial cells and opiate receptors on lymphocytes and the influence of cytokines on the hypothalamus-pituitary-adrenal axis such as IL-1, IL-6, and TNF-a activating and IL-2 and IFN-a down-regulating the HPA axis, respectively. The association between chronic hepatitis C infection and fibromyalgia is discussed, including a description of key cytokine changes in chronic hepatitis C infection. Future studies are encouraged to further characterize these immunologic alterations with potential pathophysiologic and therapeutic implications.
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PMID:Fibromyalgia, hepatitis C infection, and the cytokine connection. 1294 86

Chronic hepatitis has many causes. Symptoms include upper abdominal pain. To allow for a better understanding of this pain we compare HCV patients with other liver diseases and normal controls on their reporting of pain over one month and describe associations. A cross-sectional, case control study was performed. Three groups are studied: (1) normal individuals (NC) (N = 64), (2) patients with chronic liver diseases other than HCV (LD) (N = 53), and (3) HCV infection (N = 64). A dyspepsia questionnaire was utilized, which inquired about a one-month symptom presence of upper abdominal pain and associated symptoms. There was a one-month period prevalence of upper abdominal pain of 45.3% in the HCV group vs 32% in the LD and 20.3% in the NC groups (P = 0.01). The LD (22.6%) and HCV (26.6%) groups had markedly more pain that was worsened by eating compared with NC (1.6%) (P = .003). On univariate analysis, when comparing those with upper abdominal pain to those without, there was a lower age (41.3 vs 44.5), a higher BMI (30.3 vs 26), and more symptoms of fatigue, bloating, and pain worsened by eating and early satiety. On multivariate analysis, age < 50 (OR 5.1; CI 1.5-17), BMI > 30 (OR 4.1; CI 1.5-10.9), nausea (OR 4.1; CI 1.6-10.4), and pain with eating (OR 30: CI 6.7-133) predicted upper abdominal pain. In conclusion, upper abdominal pain is more commonly reported over one month in those with chronic liver diseases. That the abdominal pain worsened after meals in liver patients but not in the normal subjects was a surprise. Possible explanations for this finding are offered.
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PMID:Characteristics of upper abdominal pain in those with chronic liver disease. 1462 32


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