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      Is Open Access

      Spontaneous clearance of chronic hepatitis C is rare in HIV-infected patients after effective use of combination antiretroviral therapy

      1 , 1 , 2 , 2 , 1 , 1 , 2 , 1 , 1 , * , for the Grupo de Estudio de Hepatitis Virales (HEPAVIR) of the Sociedad Andaluza de Enfermedades Infecciosas (SAEI)

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          Abstract

          Objective

          To evaluate the rate of spontaneous resolution of chronic hepatitis C (CHC) infection in a cohort of HIV-infected patients.

          Methods

          A retrospective analysis of 509 HIV-infected patients with chronic HCV infection was performed at two reference hospitals in Andalusia. The main variable of the study was spontaneous clearance of CHC, defined as a negative HCV RNA result after at least two previous quantitative measurements of HCV RNA separated by a minimum of 12 months.

          Results

          Of 509 patients, 3 (0.59%; 95% CI: 0.15%-1.6%) experienced spontaneous clearance of CHC. After combination antiretroviral therapy (cART) initiation, two of three cases experienced an increased CD4 + count, coinciding with HCV viral clearance. All patients were IL28B CC carriers, 2 were co-infected with HCV genotype 3 (the HCV genotype of the remaining patient was not available).

          Conclusions

          Spontaneous clearance of CHC is a rare event in the context of HIV/HCV co-infected patients and may be associated with the effective use of cART and thus HIV suppression.

          Related collections

          Most cited references 15

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          Coinfection with HIV-1 and HCV--a one-two punch.

           Raymond Chung,  H. Kim (2009)
          Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, cirrhosis, and death; it is estimated that 180 million persons are infected with HCV worldwide. The consequences of HCV are worse in those who are coinfected with human immunodeficiency virus 1 (HIV-1), which is unfortunately a common scenario because of shared risk factors of the viruses. More studies into effects of HCV/HIV-1 coinfection are needed, but efforts have been hampered by limitations in our understanding of the combined pathogenesis of the 2 viruses. Gaining insight into the mechanisms that underlie the immunopathogenesis of these persistent viral infections could lead to new therapeutic strategies for patients with HCV/HIV-1 coinfection.
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            Activation of natural killer cells during acute infection with hepatitis C virus.

            Natural killer (NK) cells are essential early after infection, not only for viral containment but also for timely and efficient induction of adaptive responses. An inhibitory effect of hepatitis C virus (HCV)-E2 proteins on NK cells has been reported, but the features of NK cell responses in the acute phase of hepatitis C are still largely undefined. Therefore, the aim of this study was to characterize the function and phenotype of NK cells in the acute phase of infection and compare individuals with chronic and self-limited outcomes. Twenty-two individuals with acute HCV infection, 14 with chronic evolution, and 8 with self-limited infection, were studied using NK phenotypic and functional assays. An increased expression of NKG2D on both CD56(bright) and CD56(dim) NK cells was detected in patients with acute HCV, irrespective of the outcome, as compared with healthy controls. Also, interferon gamma production and cytotoxicity by NK cells were higher in individuals with acute HCV infection than in healthy controls. Subset analysis showed increased interferon gamma production in both NK cell subsets carrying group 1 and group 2 HLA-C-specific killer cell immunoglobulin-like receptors. However, increased CD107a was noted only on NK cells expressing the group 1 HLA-C-specific killer cell immunoglobulin-like receptor and was maximal in self-limited infection. Our data show that in the acute phase of HCV infection, NK cells are activated regardless of outcome, with no evidence of a suppressive effect of HCV on NK cell function. 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              The use of transient elastometry for assessing liver fibrosis in patients with HIV and hepatitis C virus coinfection.

              Transient elastometry (TE) is accurate for detecting significant liver fibrosis and cirrhosis in hepatitis C virus (HCV)-monoinfected patients. However, this procedure has been insufficiently validated in patients with human immunodeficiency virus (HIV) and HCV coinfection. The purpose of this study was to validate reported cutoff values of TE that discriminate significant liver fibrosis and cirrhosis in HIV-HCV-coinfected subjects. Liver stiffness measurements were obtained for 169 HIV-HCV-coinfected adult patients who had undergone a liver biopsy or who had received a nonhistologic diagnosis of cirrhosis within 12 months before or after a liver stiffness measurement. Patients had received no prior therapy for HCV infection. TE measurements ranged from 3.6 kPa to 75 kPa. The area under the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.84-0.93) for significant liver fibrosis and 0.95 (95% confidence interval, 0.92-0.99) for cirrhosis. To diagnose significant liver fibrosis, a cutoff value of 7.2 kPa was associated with a positive predictive value of 88% and a negative predictive value of 75%. Thirty-four patients (20%) were misclassified when this cutoff value was used. Thirteen (24%) of 54 patients with liver stiffness values <7.2 kPa had significant liver fibrosis detected by liver biopsy. To diagnose cirrhosis, a cutoff value of 14.6 kPa was associated with a positive predictive value of 86% and a negative predictive value of 94%. Thus, 13 patients (10%) had disease that was misclassified using this cutoff value. We found that the diagnostic accuracy of TE was high for detecting cirrhosis and good for diagnosis of significant liver fibrosis. However, the performance of TE was low for discriminating mild fibrosis from significant liver fibrosis, which might limit the applicability of this technique in clinical practice.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 May 2017
                2017
                : 12
                : 5
                Affiliations
                [1 ]Infectious Diseases Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía de Córdoba, Córdoba, Spain
                [2 ]Infectious Diseases and Microbiology Unit, Hospital La Línea, AGS Campo de Gibraltar, Cádiz, Spain
                Harvard Medical School, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: ARJ FT AR.

                • Data curation: MF MPP AC IM SLM PLL AR.

                • Formal analysis: MF ARJ FT MPP IM SLM PLL AR.

                • Funding acquisition: AC AR.

                • Investigation: MF ARJ FT MPP AC SLM AR.

                • Methodology: MF ARJ FT AC IM AR.

                • Project administration: ARJ AR.

                • Software: MF ARJ.

                • Supervision: ARJ FT AR.

                • Validation: ARJ FT AR.

                • Writing – original draft: MF ARJ AR.

                • Writing – review & editing: MF ARJ AR FT MPP AC IM SLM PLL AR.

                ¶ Membership of the Grupo de Estudio de Hepatitis Virales (HEPAVIR) of the Sociedad Andaluza de Enfermedades Infecciosas (SAEI) is provided in the Acknowledgments.

                Article
                PONE-D-17-06896
                10.1371/journal.pone.0177141
                5417670
                28472191
                © 2017 Frias et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 1, Tables: 1, Pages: 8
                Product
                Funding
                Funded by: Spanish AIDS Research Network (RIS)
                Award ID: RD16/0025/0034
                Award Recipient :
                Funded by: Fundación Progreso y Salud de la Junta de Andalucía
                Award ID: PI0187/2013
                Award Recipient :
                Funded by: Fundación para la Investigación en Salud del Instituto de Salud Carlos III
                Award ID: PI15/01017
                Award Recipient :
                Funded by: Consejería de Salud de la Junta de Andalucía
                Award ID: A-0025-2016
                Award Recipient :
                This work was supported by the SPANISH AIDS Research Network (RIS) RD16/0025/0034-ISCIII-FEDER, Fundación Progreso y Salud de la Junta de Andalucía (0187/2013), and Fundación para la Investigación en Salud del Instituto de Salud Carlos III (PI15/01017). A.R is the recipient of a Research Support grant from the Consejería de Salud de la Junta de Andalucía (A-0025-2016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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