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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C is a common infection with worldwide prevalence. It has a variable course and can lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Until recently alpha-interferon (IFN-alpha) was the only effective treatment available. Combination therapy with IFN-alpha and ribavirin has been found to be more efficacious than IFN-alpha alone. Various side effects have been ascribed to interferon, such as arthralgias, myalgias, fatigue, and gastrointestinal and neuropsychiatric symptoms. Interstitial pneumonitis is a rare but known complication of IFN-alpha when given at a high dosage of 6 to 10 million units per day. Ribavirin is associated with dose-dependent hemolytic anemia, cough, dyspnea, rash, depression, and dyspepsia, although a potential role in interferon-induced interstitial pneumonitis has not been described. We describe a patient with an excellent clinical response of chronic hepatitis C to combination therapy with IFN-alpha at a dosage of 3 million units per day and ribavirin. The patient developed interstitial pneumonitis that resolved after discontinuation of IFN-alpha and ribavirin. Given that interstitial pneumonitis has previously been reported with high-dose IFN-alpha, this case suggests that this complication may occur with lower dosages of IFN-alpha, although a potential role for ribavirin in this disorder at present remains speculative.
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PMID:Interstitial pneumonitis in a patient treated with alpha-interferon and ribavirin for hepatitis C infection. 1167 22

Tolerance of interferon-a therapy for hepatitis C is often poor and medication is expensive. Compliance with diagnostic procedures and, even more important, with medical treatment is obviously critical to minimize the rate of dropouts and to maximize cost efficiency. Moreover, a good concordance with scheduled follow-ups is important for early recognition and treatment of interferon-associated side effects. Therefore, we investigated psychiatric symptoms, interpersonal problems, different modes of acquisition, and sociodemographic factors in HCV-infected patients as possible predictor variables of good versus poor compliance. In a longitudinal study, 74 patients with chronic hepatitis C (CHC) who fulfilled the criteria for treatment with interferon (IFN)-alpha-2b with or without ribavirin were investigated prospectively to identify those at risk for poor compliance during IFN medication. To assess predictive factors, we used both IIP-C (Inventory of Interpersonal Problems) and SCL-90-R (Symptom Check List 90 Items Revised) as psychometric instruments. Sociodemographic and somatic variables as well as compliance during IFN therapy were also evaluated. Poor compliance before or during medication was demonstrated by 23% (N = 17) of HCV patients. Sociodemographic factors and mode of acquisition, particularly former intravenous drug (IVD) abuse were not significantly linked with compliance. Logistic regression analysis demonstrated that the subgroup of patients with compliance problems was best identified by both pretherapeutic psychiatric symptoms and interpersonal problems. Predictive value was best and significant for anger-hostility (P = 0.009), intrusive (P = 0.014), depression (P = 0.015), and phobic anxiety (P = 0.049). Adopting this statistical prediction model, sensitivity was 47.1%, but specificity reached 98.3%. In total, 86.5% of cases were classified correctly. In situations of unclear indication for IFN therapy, psychological variables assessment of before the beginning of treatment may represent an additional decision-making factor.
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PMID:Compliance with therapy in patients with chronic hepatitis C: associations with psychiatric symptoms, interpersonal problems, and mode of acquisition. 1168 May 76

Advances in immunosuppressive therapy, operative techniques, and perioperative management have resulted in long-term patient survival rates approaching 90% following liver transplantation for chronic viral hepatitis. The increasing number of referrals for liver transplantation reflects the impact of chronic HCV infection as a cause of end-stage liver disease. Unlike hepatitis B, there is still no effective treatment in preventing recurrent hepatitis C after liver transplantation. The spectrum of allograft injury related to universal HCV infection recurrence ranges from no evidence of histologic injury to mild inflammation to severe disease with allograft failure in small proportion of patients. Various factors may explain these differing outcomes, including degree of pretransplantation viremia, HLA compatibility, presence of more pathogenic HCV genotypes, integrity of cellular immune response, and type of immunosuppression. Fortunately, patient survival does not seem to be affected short-term; the long-term outcome of liver transplantation for chronic hepatitis C is unclear but is likely to be decreased. Combination therapy with interferon plus ribavirin seems to be a promising treatment strategy for posttransplantation recurrent hepatitis C, and the use of pegylated interferon plus ribavirin may improve these results. Patients with moderate to severe allograft hepatitis are appropriate candidates for combination antiviral therapy. Histopathologically documented recurrent hepatitis C in liver transplant recipients is associated with impaired quality of life, inferior physical condition, and a higher incidence of depression compared with patients who did not have HCV and in those without HCV recurrence. In conclusion, it is possible that the continued improvements in antiviral therapy against HCV infection may ultimately decrease the number of patients needing liver transplantation. Suitable candidates with chronic HCV infection thus warrant treatment with pegylated interferon plus ribavirin combination therapy in the hope of decreasing disease progression. Recent studies, which require confirmation, suggest that nonresponders to standard antiviral therapy may benefit from maintenance therapy. The donor pool for patients with chronic hepatitis C and decompensated cirrhosis can be improved by using HCV-positive donors and by increasing utilization of newer surgical techniques, including adult-to-adult living-donor liver transplantation and split-liver transplantation.
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PMID:Hepatitis C virus and liver transplantation. 1168 96

Patients with chronic hepatitis C virus (HCV) infection frequently report fatigue, lassitude, depression, and a perceived inability to function effectively. Several studies have shown that patients exhibit low quality-of-life scores that are independent of disease severity. We therefore considered whether HCV infection has a direct effect on the central nervous system, resulting in cognitive and cerebral metabolite abnormalities. Twenty-seven viremic patients with biopsy-proven mild hepatitis due to HCV and 16 patients with cleared HCV were tested with a computer-based cognitive assessment battery and also completed depression, fatigue, and quality-of-life questionnaires. The HCV-infected patients were impaired on more cognitive tasks than the HCV-cleared group (mean [SD]: HCV-infected, 2.15 [1.56]; HCV-cleared, 1.06 [1.24]; P =.02). A factor analysis showed impairments in power of concentration and speed of working memory, independent of a history of intravenous drug usage (IVDU), depression, fatigue, or symptom severity. A subgroup of 17 HCV-infected patients also underwent cerebral proton magnetic resonance spectroscopy (1H MRS). The choline/creatine ratio was elevated in the basal ganglia and white matter in this group. Patients who were impaired on 2 or more tasks in the battery had a higher mean choline/creatine ratio compared with the unimpaired patients. In conclusion, these preliminary results demonstrate cognitive impairment that is unaccounted for by depression, fatigue, or a history of IVDU in patients with histologically mild HCV infection. The findings on MRS suggest that a biological cause underlies this abnormality.
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PMID:Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease. 1182 20

In numerous studies of symptoms in patients with chronic hepatitis C there has been no systematic assessment of both fatigue and extrahepatic manifestations. Our objective was to assess the prevalence of fatigue in patients with hepatitis C virus (HCV) infection, and to identify associations between fatigue and clinical and biological hepatic and extrahepatic manifestations. We studied 1614 patients. Data were prospectively recorded during the first visit of patients infected with HCV and the prevalence of fatigue and its association with dermatological, rheumatological, neurological and nephrological manifestations; diabetes; arterial hypertension; auto-antibodies, and cryoglobulinaemia were assessed. Then, using multivariate analysis, we identified demographic, biochemical, immunological, virological, and histological factors associated with the presence of fatigue. Fatigue was present in 53% of patients (95% confidence interval 51-56). In 17% of patients (95% confidence interval 15-19) fatigue was severe, impairing activity. Five other extrahepatic manifestations had a prevalence above 10% including, in decreasing order: arthralgia, paresthesia, myalgia, pruritus, and sicca syndrome. In univariate and multivariate analyses, fatigue, in comparison with the absence of fatigue, was associated with female gender, age over 50 years, cirrhosis, depression and purpura. Independent of these associations, fatigue was associated with arthralgia, myalgia, paresthesia, sicca syndrome and pruritus. The prevalence of fibromyalgia (as defined by the association of fatigue with arthralgia or myalgia) was 19% (95% confidence interval 17-21). There was no significant association between fatigue and the following characteristics: viral load or genotype, alcohol consumption, abnormal thyroid function, and type and level of cryoglobulinaemia. Hence, fatigue is the most frequent extrahepatic manifestation in patients infected with HCV. Fatigue is independently associated with female gender, age over 50 years, cirrhosis, depression and purpura.
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PMID:Fatigue in patients with chronic hepatitis C. 1208 7

We have recently observed a diffuse slowing of brain waves using serial quantitative electroencephalographic (qEEG) examinations in interferon (IFN)-alpha-treated chronic hepatitis C patients. However, it remains unclear how this alteration could be assessed. We evaluated the correlation between the qEEG changes and three tests of mental status, including the Mini-Mental State Examination (MMSE), in such patients. This is the first study to undertake a clinical evaluation of the adverse effects on brain function due to IFN. We undertook blind, prospective and serial qEEG examinations on 56 chronic hepatitis C patients at three independent hospitals. IFN-alpha was administered intramuscularly at a dose of 9 x 10(6) IU daily for the first 4 weeks and then 3 times/week for the next 20 weeks. Serial EEGs were obtained before, at 2 and 4 weeks of treatment, and after the IFN-alpha treatment. The absolute power values of each frequency band in each patient at different stages of treatment were recorded by qEEG. Each patient was assessed by the MMSE, Hamilton Rating Scale for Depression (HSD), and Hamilton Rating Scale for Anxiety (HSA). We statistically evaluated the correlations between the changes in power values and alterations of scores on the mental status tests during IFN-alpha treatment. The decreased scores observed on the MMSE ranged from 2 to 5 points at both 2 and 4 weeks of IFN-alpha treatment. There were no significant differences in age distribution for each decreased score on the MMSE. As the alteration in MMSE score during IFN treatment increased, the alteration in absolute power values for the slow waves during IFN treatment increased significantly, while that for the alpha 2 and fast waves during treatment decreased significantly. However, the changes in the HDS and HSA revealed no significant correlations. The alteration of the qEEG was reversible after the treatment. MMSE scores represent one screening method for the clinical assessment of IFN-alpha-induced alterations of brain function.
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PMID:Alterations of quantitative EEG and mini-mental state examination in interferon-alpha-treated hepatitis C. 1218

Interferon alpha (IFNalpha) is used for the treatment of several disorders, such as chronic hepatitis or malignant melanoma. During the therapy, IFNalpha may cause severe neuropsychiatric syndromes including depression with suicidal ideation, paranoid psychoses, or confusional states. The reasons and management of these side effects are widely unknown. Our aim is to review research evidence for the contribution of IFNalpha for the etiopathology of psychiatric syndromes. Therefore, research findings of neuropsychiatric syndromes induced by IFNalpha treatment, the putative mechanisms underlying those syndromes, and their treatment are-reviewed. Furthermore, neuropsychiatric syndromes in diseases with high IFNalpha levels such as systemic lupus erythematosus (SLE) are discussed. Finally, the question is addressed whether IFNalpha may contribute to the etiopathology of endogenous psychiatric disorders. IFNalpha may cause psychiatric syndromes in a subset of treated patients. The underlying pathogenetic mechanisms include various effects on neuroendocrine, cytokine, and neurotransmitter systems. Research data on the role of IFNalpha in the pathogenesis of endogenous psychiatric disorders are conflicting. Future research should improve our understanding of the role of IFNalpha for the etiopathology of psychiatric syndromes and has an impact on treatment of IFNalpha-induced psychiatric syndromes.
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PMID:Interferon alpha (IFNalpha) and psychiatric syndromes: a review. 1218 6

The aim of the study was to describe the use of the Brief Symptom Inventory in characterizing the type and severity of emotional distress in 26 patients with chronic hepatitis C who were receiving interferon-alpha-2B and ribavirin. The 6-month actuarial incidence of neuropsychiatric toxicity, determined by physician interview, was 58%. Significant differences in mean depression, anxiety, and somatization Brief Symptom Inventory T scores were noted in the 15 patients with clinically apparent neuropsychiatric toxicity compared to the 11 patients without neuropsychiatric toxicity. Because of its brevity and simplicity, the Brief Symptom Inventory may prove to be a useful adjunct to clinician assessment in detecting and monitoring emotional distress during interferon-alpha treatment of chronic hepatitis C.
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PMID:Emotional distress during interferon-alpha-2B and ribavirin treatment of chronic hepatitis C. 1229 6

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


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