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 ( C hronic hepatitis C (HCV) infection is estimated to affect 170 million people worldwide 1 and constitutes a major public health problem. It causes a fluctuating chronic hepatitis that may progress to cirrhosis and hepatocellular carcinoma. Attempts to understand the natural history of this infection have largely focused on the viral and host factors that predict progression of liver pathology from necroinflammation and fibrosis to cirrhosis and hepatocellular carcinoma. Consequently, the decision to treat patients is normally based on an assessment of these factors, including staging of disease with a liver biopsy, 2 rather than on particular symptoms. There is, however, emerging literature suggesting that, even in the absence of clinically significant liver disease, chronic HCV infection causes a substantial reduction in quality of life 3 that improves following successful antiviral treatment. 4 These findings are in agreement with the clinical observation that patients with chronic HCV infection frequently report fatigue, lassitude, depression, and a perceived inability to function effectively. 5,6 The etiology of these symptoms is unknown. The symptoms do not appear to be associated with the degree of hepatitis, the presence of autoimmune disorders 5 or cirrhosis, 3 a history of intravenous drug usage (IVDU), 3 or the level of circulating cytokines. 7 We have previously reported cerebral metabolite abnormalities in patients with histologically proven mild HCV infection using proton magnetic resonance spectroscopy ( 1 H MRS). 8 These abnormalities are similar to the 1 H MRS changes reported in cerebral human immunodeficiency virus (HIV) infection in both cognitively impaired 9,10 and asymptomatic individuals. 11 In this study, we address the hypothesis that HCV infection can result in cerebral dysfunction, which may underlie both the neuropsychological symptoms and the 1 H MRS abnormalities described. We used a cognitive assessment battery to determine whether cognitive impairment exists in patients with histologically defined mild chronic HCV infection and 1 H MRS to determine whether cerebral metabolite abnormalities are associated with impaired cognitive function.
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Delayed seroconversion in HIV-positive individuals with acute HCV may result in delayed diagnosis and treatment. Where there is a clinical suspicion of recent HCV infection, for example, elevated alanine transaminase levels, HIV-infected patients should be screened for HCV RNA by RT-PCR.
Oral fluid testing is an effective alternative to serum antibody testing for surveillance of human immunodeficiency virus (HIV) and hepatitis B infections, and is being extended to hepatitis C infections. The objective of this study was to determine and compare the sensitivity and specificity of a modified commercial assay for the detection of antibody to hepatitis C virus (anti-HCV) in oral fluids collected by two different oral fluid collection devices (the Epitope OraSure trade mark and Sarstedt Salivette ) and in dried fingerprick blood spots. In this study, 253 anti-HCV seropositive patients and 394 blood donors (all anti-HCV negative) were recruited between August 2000 and January 2001. Each participant provided oral fluid specimens by OraSure and Salivette, and at least one dried blood spot. Serum specimens were collected from the patients whenever possible. For those injecting drug users who did not provide a serum specimen, HCV status was established on the basis of previous testing. All the nonserum samples were tested for the presence of anti-HCV, using a modified Ortho HCV 3.0 SAVe enzyme-linked immunosorbent assay (ELISA) protocol. The recommended preliminary cutoffs for the modified ELISA were suboptimal. Further, the sensitivity, specificity, and positive and negative predictive values could be improved by varying the cutoff and taking into account the likely prevalence of HCV in the population under investigation. For instance, given a population with a 50% prevalence of anti-HCV, the optimal sensitivities of the modified assay on OraSure, Salivette, and dried blood spots were 92%, 83%, and virtually 100%, respectively, in contrast to 83%, 59%, and 99% using the preliminary cutoffs. The respective optimal specificities were 99%, 93%, and 100%. In conclusion, oral fluids collected by the OraSure device provide an extremely useful method to conduct public health surveillance of not only HIV, but also hepatitis C, among injecting drug users. In addition, dried blood spot specimens may be useful for surveillance and could be employed as a first line diagnostic specimen.
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