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      Detection of hepatitis C virus in patients with terminal renal disease undergoing dialysis in southern Brazil: prevalence, risk factors, genotypes, and viral load dynamics in hemodialysis patients

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          Abstract

          Hepatitis C (HCV) is a serious public health issue, and it is estimated that 3% of the world’s population is infected. Patients in hemodialysis units have an increased risk for contracting HCV, and high prevalence rates have been found in hemodialysis units around the world. This study is aimed at determining the prevalence of HCV in patients with terminal chronic renal disease (tCRD) who have been submitted to hemodialysis and peritoneal dialysis in southern Brazil to characterize the most prevalent genotypes, the viral load, and possible risk factors and to assess the validity between the ELISA and RT-PCR detection methods. Of 320 patients from three dialysis units, 318 participated in this study. According to the medical records, 55 patients were reactive to HCV, as determined via ELISA. All 318 samples were submitted to RT-PCR and genotyped using an Abbott Realtime® m2000 system. Data obtained through a questionnaire and chemical variables were associated with the HCV. Results: The prevalence of HCV was 18.24% (58), and the concordance between the HCV serology and the RT-PCR was 94%. Three patients were diagnosed to be negative for HCV using the ELISA assay but positive when using RT-PCR. Genotype 1 was the most prevalent (46.7%) genotype, within which subtype 1a was the most frequent (74.1%). One of the risk factors associated with HCV infection was the length of time that the patient had been undergoing hemodialysis treatments (p < 0.001). Additionally, the viral load was found to vary when tested before and after hemodialysis (p < 0.001). Conclusion: The prevalence of HCV in dialysis units continues to remain high, indicating nosocomial contamination. RT-PCR detected the presence of the hepatitis C virus in patients with a non-reactive serology, which highlights the importance of performing molecular tests on dialysis patients. The variation in the viral load in patients submitted to hemodialysis indicates a possible destruction or gripping of viral particles to the dialyzer membrane.

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          The online version of this article (doi:10.1186/s12985-015-0238-z) contains supplementary material, which is available to authorized users.

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          Hepatitis C infection and the patient with end-stage renal disease.

          Hepatitis C virus (HCV) remains common in patients with end-stage renal disease (ESRD) and is an important cause of liver disease in this population. Acquisition of HCV infection continues to occur in dialysis patients because of nosocomial spread. The natural history of HCV in dialysis patients remains controversial because the course of HCV typically extends over decades, whereas dialysis patients have higher morbidity and mortality rates than those of the general population limiting long-term follow-up. However, recent reports suggest that HCV infection affects the survival of chronic dialysis patients as well as renal transplant (RT) recipients. The severity of preexisting liver disease on pretransplantation liver biopsy may provide useful prognostic information about clinical outcome after RT; liver biopsy should be incorporated in the evaluation and management of RT candidates with HCV. Recent surveys with long-term follow-up have documented adverse effects of HCV on patient and graft survival. Use of renal grafts from HCV-infected donors in recipients with HCV does not appear to result in a greater burden of liver disease albeit with short-term follow-up. There is only limited data about interferon (IFN) therapy in chronic dialysis patients, although sustained responses are reported. Preliminary data on IFN plus ribavirin therapy in dialysis patients with hepatitis C have given encouraging results, but randomized trials are needed. Interferon remains contraindicated post-RT because of concern about precipitating graft dysfunction.
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            Geographic distribution of hepatitis C virus genotypes in Brazil

            Brazil is a country of continental dimension with a population of different ethnic backgrounds. Thus, a wide variation in the frequencies of hepatitis C virus (HCV) genotypes is expected to occur. To address this point, 1,688 sequential samples from chronic HCV patients were analyzed. HCV-RNA was amplified by the RT-PCR from blood samples collected from 1995 to 2000 at different laboratories located in different cities from all Brazilian States. Samples were collected in tubes containing a gel separator, centrifuged in the site of collection and sent by express mail in a refrigerated container to Laboratório Bioquímico Jardim Paulista, São Paulo, SP, Brazil. HCV- RNA was extracted from serum and submitted to RT and nested PCR using standard procedures. Nested PCR products were submitted to cycle sequencing reactions without prior purification. Sequences were analyzed for genotype determination and the following frequencies were found: 64.9% (1,095) for genotype 1, 4.6% (78) for genotype 2, 30.2% (510) for genotype 3, 0.2% (3) for genotype 4, and 0.1% (2) for genotype 5. The frequencies of HCV genotypes were statistically different among Brazilian regions (P = 0.00017). In all regions, genotype 1 was the most frequent (51.7 to 74.1%), reaching the highest value in the North; genotype 2 was more prevalent in the Center-West region (11.4%), especially in Mato Grosso State (25.8%), while genotype 3 was more common in the South (43.2%). Genotypes 4 and 5 were rarely found and only in the Southeast, in São Paulo State. The present data indicate the need for careful epidemiological surveys throughout Brazil since knowing the frequency and distribution of the genotypes would provide key information for understanding the spread of HCV.
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              Decreased serum aminotransferase activity in patients with chronic renal failure: impact on the detection of viral hepatitis.

              Hepatitis C virus (HCV) infection is common in the dialysis population and patients with chronic renal failure (CRF) not requiring dialysis. HCV is the most important cause of chronic liver disease in dialysis patients; however, its role has been underestimated by the lower aminotransferase activity in the dialysis population. Aminotransferase activity in patients with CRF not requiring dialysis has not been adequately addressed to date. The aim of this study is to investigate whether serum aminotransferase levels in predialysis patients with CRF are less than those obtained in healthy individuals and dialysis patients. We also analyzed the potential association between serum aminotransferase activity and demographic, clinical, and biochemical parameters. Aspartate (AST) and alanine aminotransferase (ALT) activity was greater in antibody to hepatitis C (anti-HCV)-positive than anti-HCV-negative patients with CRF not requiring dialysis (AST, 32.3 +/- 19 versus 18.1 +/- 8 IU/L [P = 0.0001]; ALT, 32.9 +/- 28 versus 17.7 +/- 11 IU/L [P = 0.00001], respectively). Predialysis patients with CRF had lower AST and ALT activity in comparison to healthy individuals (AST, 19.7 +/- 11.2 versus 20.4 +/- 6.8 IU/L [P = 0.00001]; ALT, 19.5 +/- 15.1 versus 21.7 +/- 11.3 IU/L [P = 0.00001], respectively). The difference was much greater after correction for viral markers: AST and ALT levels in hepatitis B surface antigen (HBsAg)-negative anti-HCV-negative predialysis patients with CRF were less than those in the healthy population (AST, 17.9 +/- 8 versus 20.4 +/- 6.8 IU/L [P = 0.00001]; ALT, 17.5 +/- 10 versus 21.7 +/- 11.3 IU/L [P = 0.00001], respectively). Comparison of AST and ALT activity between age-matched healthy and predialysis seronegative CRF groups showed lower AST and ALT values in the study population. HBsAg-negative anti-HCV-negative dialysis patients had lower AST and ALT activity than seronegative predialysis patients with CRF (AST, 16.6 +/- 11.6 versus 17.9 +/- 8 IU/L [P = 0.01]; ALT, 16.3 +/- 9.4 versus 17.5 +/- 10 [P = 0.041], respectively). Multivariate analysis in the predialysis CRF population showed an independent association between AST (P = 0.00001) and ALT (P = 0.00001) activity and anti-HCV positivity, and age was negatively linked to AST (P = 0.011) and ALT levels (P = 0.001). AST level was negatively related to serum creatinine level (P = 0.0001). In conclusion, HCV infection causes significant liver injury in predialysis patients with CRF. These patients have decreased aminotransferase activity compared with the general population. Dialysis patients show lower aminotransferase activity than predialysis patients with CRF. Because serum aminotransferase levels are commonly used to screen for liver disease in the dialysis and predialysis CRF population, recognition of liver damage may be hampered by the reduction in aminotransferase values in these patients. Studies aimed to clarify the pathogenesis of this phenomenon are in progress.
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                Author and article information

                Contributors
                bea-dy@hotmail.com
                nayleoliveira@gmail.com
                rubenslobatobio@gmail.com
                bio.fngermano@gmail.com
                Luisadias_sixcp@hotmail.com
                elvino.barros@gmail.com
                nani60@gmail.com
                Journal
                Virol J
                Virol. J
                Virology Journal
                BioMed Central (London )
                1743-422X
                3 February 2015
                3 February 2015
                2015
                : 12
                : 8
                Affiliations
                [ ]Federal University of Rio Grande (FURG), Rio Grande, Brazil
                [ ]Fluminense Federal University (UFF), Rio de Janeiro, Brazil
                [ ]Federal University of Rio Grande do Sul (UFRGS), Porto alegre, Brazil
                Article
                238
                10.1186/s12985-015-0238-z
                4329191
                25644891
                00aedbc8-287a-46cd-9097-530c48149c0f
                © Vidales-Braz et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 September 2014
                : 2 January 2015
                Categories
                Research
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                © The Author(s) 2015

                Microbiology & Virology
                Microbiology & Virology

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