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Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 degrees C. Clinically cryoglobulinemia is manifested in a variety of symptoms on different organs. The most important clinical symptoms are fatigue, peripheral neuropathy and vasculitis associated skin lesions. Pathophysiologically cryoglobulinemia is based on a disturbed immunocascade with an elevated B-cell-activity. Often a cryoglobulinemia progresses smoothly to a Non-Hodgkin-Lymphoma. The main activator of a cryoglobulinemia is a Hepatitis C virus infection. Other causes for developing a cryoglobulinemia are rheumatological and haematological diseases. In the past cryoglubulinemia has predominantly been treated with plasmapheresis and immunosuppression, nowadays antiviral strategies are becoming more important. Cases of rapid worsening under therapy with interferon alpha have also been reported. A promising new option is the use of rituximab.
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PMID:[Hepatitis associated cryoglobulinemia]. 1832 17

More than 4 million (2%) people in the United States have been infected with the hepatitis C virus, of whom 2.7 million are chronically infected. The current treatment for chronic hepatitis C patients is Interferon and ribavirin combination therapy, which is associated with numerous neuropsychiatric side effects. The most common are fatigue, depression, cognitive dysfunction, and anxiety. Early identification and treatment of these symptoms may not only improve the patient's mental health, but also may increase the patient's functional ability and overall quality of life. Psychiatric nurses can play a pivotal role in the successful management of the neuropsychiatric symptoms.
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PMID:Neuropsychiatric symptoms of hepatitis C. 1834 Jun 9

Interferon (IFN)-alpha has been used to investigate pathways by which innate immune cytokines influence the brain and behavior. Accordingly, the impact of IFN-alpha on diurnal secretion of hypothalamic-pituitary-adrenal (HPA) axis hormones was assessed in 33 patients eligible for treatment with IFN-alpha plus ribavirin for hepatitis C. In addition, the relationship between IFN-alpha-induced HPA axis changes and proinflammatory cytokines and behavior was examined. Plasma ACTH and cortisol as well as tumor necrosis factor (TNF)-alpha, interleukin-6 and their soluble receptors, were measured hourly between 0900 and 2100 hours at baseline and following approximately 12 weeks of either no treatment (n=13) or treatment with IFN-alpha/ribavirin (n=20). Plasma IFN-alpha was also measured at each visit. Depression and fatigue were assessed using the Montgomery-Asberg depression rating scale and the multidimensional fatigue inventory. Compared to no treatment, IFN-alpha/ribavirin administration was associated with significant flattening of the diurnal ACTH and cortisol slope and increased evening plasma ACTH and cortisol concentrations. Flattening of the cortisol slope and increases in evening cortisol were correlated with increases in depression (r=0.38, P<0.05 and r=0.36, P<0.05, respectively) and fatigue (r=0.43, P<0.05 and r=0.49, P<0.01, respectively). No relationship was found between immune and HPA axis measures, although increases in plasma IFN-alpha, TNF-alpha and soluble TNF-alpha receptor2 were independently correlated with behavioral endpoints. These data indicate that chronic exposure to innate immune cytokines may contribute to the altered diurnal HPA axis activity and behavior found in medically ill individuals. However, given the lack of correlation between HPA axis and immune measures, the mechanism by which chronic cytokine exposure influences HPA axis function remains to be determined.
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PMID:Interferon-alpha effects on diurnal hypothalamic-pituitary-adrenal axis activity: relationship with proinflammatory cytokines and behavior. 1852 Oct 89

Ten female and 2 male patients with chronic hepatitis C infection had fibromyalgia as a prominent musculoskeletal problem. In 9 patients, the fibromyalgia developed a mean of 13.4 years after the hepatitis C infection. In 2 patients, the 2 diseases occurred within weeks to a few months of each other, and in 1 patient, preexisting fibromyalgia was apparently aggravated by the hepatitis C infection. All patients had a possible blood or body fluid exposure event or high risk activity: intravenous blood products in 3, occupational needle stick in 1, tattoos in 3, intravenous drug use in 3 and promiscuous sexual practices in 2. Transaminases were moderately elevated in 10 patients, and chronic active hepatitis was found in 4 patients who were biopsied. All patients had prominent fatigue. Additional features not commonly seen in fibromyalgia patients included fluctuating synovitis in 5 patients, biopsy-proven leukocytoclastic vasculitis in 5, sicca symptoms in 3, Raynaud's phenomenon in 3, and cryoglobulinemia in 2. One patient died in multi-organ failure after treatment for systemic vasculitis. Rheumatologists and internists should be aware that patients with hepatitis C infection can have fibromyalgia that occurs concomitantly with other extrahepatic manifestations of hepatitis C.
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PMID:Fibromyalgia: a prominent feature in patients with musculoskeletal problems in chronic hepatitis C: a report of 12 patients. 1907 62

There is growing evidence that hepatitis C virus (HCV)-infection may affect the brain. About half of the HCV-infected patients complain of chronic fatigue irrespective of their stage of liver disease or virus replication rate. Even after successful antiviral therapy fatigue persists in about one third of the patients. Many patients, in addition, report of deficits in attention, concentration and memory, some also of depression. Psychometric testing revealed deficits in attention and verbal learning ability as characteristic for HCV-afflicted patients with normal liver function. Magnetic resonance spectroscopic studies showed alterations of the cerebral choline, N-acetyl-aspartate, and creatine content in the basal ganglia, white matter and frontal cortex, respectively. Recently, pathologic cerebral serotonin and dopamine transporter binding and regional alterations of the cerebral glucose utilisation compatible with alterations of the dopaminergic attentional system were observed. Several studies detected HCV in brain samples or cerebro-spinal fluid. Interestingly, viral sequences in the brain often differed from those in the liver, but were closely related to those found in lymphoid tissue. Therefore, the Trojan horse hypothesis emerged: HCV-infected mononuclear blood cells enter the brain, enabling the virus to reside within the brain (probably in microglia) and to infect brain cells, especially astrocytes.
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PMID:Hepatitis C virus infection and the brain. 1913 Jan 96

The revised Dutch College of General Practitioners' practice guideline 'Viral hepatitis and other liver diseases' offers advice in the diagnosis and management of viral hepatitis A, B and C and other liver diseases. The guideline is important for general practitioners as well as specialists in internal medicine and gastroenterology. The emphasis is on the management of chronic hepatitis B en C, because the prevalence of these diseases has increased in the Netherlands and, in addition, the treatment options for chronic hepatitis have improved. Consequently, timely recognition and adequate referral of patients with chronic hepatitis B or hepatitis C have become more important. However, many patients with a chronic liver disease have no symptoms. Therefore, the general practitioner should be aware that a patient visiting the practice with fatigue and malaise could have a liver disease if he or she belongs to a high-risk group or has had high-risk contacts. If the general practitioner repeatedly finds increased liver transaminase values during routine examination of asymptomatic patients, additional diagnostic tests should be performed. Further tests should focus on viral hepatitis as well as on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis or, depending on the history-taking, liver damage due to excessive alcohol, medication or drug use.
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PMID:[Summary of the practice guideline 'Viral hepatitis and other liver diseases' (second revision) from the Dutch College of General Practitioners]. 1913 64

Hepatitis C is caused by the hepatitis C virus (HCV) infection. According to World Health Organization data, 3% of the world population (approximately 170 million people) is infected with HCV; in Poland there are over 700,000. Over 70% of those infected manifest no symptoms in the acute phase of the disease, and in about 70-80% the acute phase progresses into a chronic form. Patients with symptoms in the acute phase of HCV infection most commonly present with unspecific signs and symptoms that may develop in other viral liver infections, e.g. malaise, fatigue, abdominal pain, mild hepato- and splenomegaly and arthralgia. These symptoms usually persist for 2 to 12 weeks. In the chronic phase a subset of patients complain of malaise, nausea, abdominal pain and itching. With time, chronic hepatitis C may develop into liver cirrhosis. The basic diagnostic methods in HCV infection involve determination of anti-HCV antibodies using the ELISA immunoassay and examination of HCV-RNA with the RT-PCR method. The current treatment of HCV infection involves administration of pegylated interferon a and ribavirin over a period of 48 weeks in HCV-1 genotype infection, and 24 weeks for HCV-2 and 3 genotypes. Effectiveness of therapy depends on the HCV genotype. HCV elimination can be achieved in 78% of patients with HCV-2 and 3 genotypes, and in 55% of patients with HCV-1 genotype.
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PMID:Viral hepatitis C. 1920 52

Patients with renal disease are at increased risk of acquiring hepatitis C virus (HCV) infection because of their frequent exposure to blood from transfusions or exposure to HCV-contaminated medical equipment during hemodialysis. The prevalence of anti-HCV antibodies among hemodialysis patients varies between 5-10% in the developed world, and 10-70% in developing countries. Acute hepatitis C is often mild and associated with few, if any symptoms. The major complication of acute HCV infection is chronic hepatitis, which occurs in up to 80% of the cases, the long-term outcome being cirrhosis, portal hypertension, hepatic failure, and hepatocellular carcinoma. Interferon alpha (IFN-alpha) has shown activity against HCV. Twenty four to 48 week course of therapy with interferon could lead to a sustained loss of HCV RNA, normalization of alanine aminotrasferase (ALT) levels, and resolution of the liver disease. Sustained viral response was achieved in approximately half of the treated patients. Therapy with interferon was associated with a number of adverse events such as: "flu-like" symptoms, neurological, gastrointestinal symptoms, anemia, fatigue, thrombocytopenia, leucopenia. A major advance in therapy came with the addition of ribavirin to interferon therapy. Peginterferon-alpha-2a (40KD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a, that was developed to improve the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. In our study, fourteen hemodialysis patients with chronic hepatitis C received 135 microg PEG-IFN alpha-2a subcutaneously, once a week, after dialysis session for a period of 48 weeks. In the intention-to-treat analysis, sustained viral response was present in 36% of the patients (five out of fourteen patients) at the end of the follow up period. The biochemical response with normalization of serum ALT levels during the treatment was observed in all treated patients (83 +/- 20.1 U/L at base line vs. 23.4 +/- 4.6 U/L after the 48 weeks; p < 0.01). At present, therapy for hepatitis C should be considered in hemodialysis patients with significant liver disease, minimal other co morbidities, and a reasonable likelihood of prolonged survival or if renal transplantation is planned.
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PMID:New approaches in the therapy of hepatitis C in dialysis patients. 1925 44

Interferon alfa2 (IFN-alpha2) is a parenterally administered cytokine used to treat patients with Hepatitis C and B, and malignancy. Interferon (INF) has a relatively high rate of central nervous system (CNS) adverse effects, including agitation, depression, fatigue, cognitive dysfunction, suicidal thought and drug craving. Using functional magnetic resonance imaging (fMRI) we studied patients with Hepatitis C virus (HCV) infection who were not more than mildly clinically depressed at baseline for their CNS reaction to IFN-alpha2. During fMRI, patients underwent visual stimulation with pictures designed to induce feelings of depression. In the two patients who became clinically depressed or markedly anxious while on treatment with interferon, but not in patients who did not experience these effects, there was a significant activation in specific areas of the brain known to be involved with depression, along with an increase above baseline in the Beck Depression Scale for the patient who developed INF-induced depression. The activation pattern differed from that previously observed for endogenous depression, indicating that INF-induced depression may differ in its underlying neuropathology. Functional magnetic resonance imaging can be an important tool in understanding and monitoring for (INF and other) medication-induced CNS effects, and response to treatment.
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PMID:Use of fMRI to predict psychiatric adverse effects of interferon treatment for Hepatitis C - preliminary report. 1930 May 95

Fatigue is a common and often debilitating symptom for people living with chronic hepatitis C viral infection. Numerous published reports in the past decade have attempted to address the nature and aetiology of fatigue in chronic hepatitis C; however, this field is plagued with lack of clarity about how hepatitis C virus (HCV)-related fatigue occurs and when it is experienced by the infected person. Consequently, both patients and clinicians alike are unclear about how to mediate or prevent the negative consequences of HCV-related fatigue. In the following article, the authors identify areas of ambiguity and incongruity that have evolved primarily from the underlying assumptions and methodological decisions of researchers in the field of HCV-related fatigue. Research related to fatigue in chronic illness is drawn upon to suggest future directions for investigations and interventions in the field of HCV-related fatigue. Future research needs to move beyond the subjective symptomatology of HCV-related fatigue and begin to account for the multidimensional and contextualised nature of the fatigue experience.
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PMID:Future directions for investigation of fatigue in chronic hepatitis C viral infection. 1947 34


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