<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.9068.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Research Article</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                    <subj-group>
                        <subject>Epidemiology</subject>
                    </subj-group>
                    <subj-group>
                        <subject>Global Health</subject>
                    </subj-group>
                    <subj-group>
                        <subject>Methods for Diagnostic &amp; Therapeutic Studies</subject>
                    </subj-group>
                    <subj-group>
                        <subject>Methods of Clinical Decision-Making</subject>
                    </subj-group>
                    <subj-group>
                        <subject>Viral Infections (without HIV)</subject>
                    </subj-group>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Prevalence of hepatitis B and C infections in hemodialysis patients</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 1 approved, 1 approved with reservations, 2 not approved]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Salvatierra</surname>
                        <given-names>Karina</given-names>
                    </name>
                    <uri content-type="orcid">https://orcid.org/0000-0002-6634-4776</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Florez</surname>
                        <given-names>Hector</given-names>
                    </name>
                    <uri content-type="orcid">https://orcid.org/0000-0002-5339-4459</uri>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Faculty of Exact, Chemical and Natural Sciences, Universidad Nacional de Misiones, Posadas, 3300, Argentina</aff>
                <aff id="a2">
                    <label>2</label>Faculty of Technology, Universidad Distrital Francisco Jos&#x00e9; de Caldas, Bogot&#x00e1;, Colombia</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:kariales@gmail.com">kariales@gmail.com</email>
                </corresp>
                <fn fn-type="con">
                    <p>Karina Salvatierra: study design, sample processing, data analysis, discussion of results, and writing the manuscript. Hector Florez: design and analysis of data, drafting the manuscript. Both authors agreed to the final content of the manuscript.</p>
                </fn>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>3</day>
                <month>8</month>
                <year>2016</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2016</year>
            </pub-date>
            <volume>5</volume>
            <elocation-id>1910</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>1</day>
                    <month>8</month>
                    <year>2016</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2016 Salvatierra K and Florez H</copyright-statement>
                <copyright-year>2016</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/5-1910/pdf"/>
            <abstract>
                <p>
					
                    <bold>Introduction</bold>: Infections with hepatitis B and C viruses (HBV and HCV) are a major global health problem. Patients with chronic renal failure (CRF) on hemodialysis constitute a population at risk of HBV and HCV infections.</p>
                <p>
					
                    <bold>Objective</bold>: Determining prevalence of the surface antigen of hepatitis B virus (HBsAg) and antibodies to hepatitis C virus (anti-HCV) in patients who attended dialysis units in the city of Posadas (Argentina).</p>
                <p>
					
                    <bold>Materials and methods</bold>: The studied population comprised 172 patients with CRF in hemodialysis. HBsAg and anti-HCV antibodies were evaluated by enzyme-linked immunosorbent assay (ELISA).</p>
                <p>
					
                    <bold>Results</bold>: On a total of 172 hemodialysis patients included in the study, 98 were males (57%) and 74 were females (43%), aged between 12 and 85 years (mean 53.4). 8.7% (15/172) of the patients were positive for HBsAg and 9.9% (17/172) were positive for anti-HCV reagents. 72.1% of patients had a hemodialysis treatment time of less than 5 years. A history of having received previous transfusions was observed in both HBsAg positive cases (7/15) and the anti-HCV positive cases (5/17). Elevated transaminase levels were observed in patients with positive and negative serology.</p>
                <p>
					
                    <bold>Conclusion</bold>: The results of this study demonstrate a high prevalence of serological markers for HBV and HCV in patients with CRF on hemodialysis in city of Posadas (Argentina), as compared to cities in developed countries.</p>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>hepatitis B</kwd>
                <kwd>hepatitis C</kwd>
                <kwd>chronic kidney failure</kwd>
                <kwd>hemodialysis</kwd>
                <kwd>serological markers</kwd>
            </kwd-group>
            <funding-group>
                <funding-statement>This work has been supported by the Information Technologies Innovation (ITI) Research Group.</funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec sec-type="intro">
            <title>Introduction</title>
            <p>Infections with hepatitis B and C viruses (HBV and HCV, respectively) are a major global health problem affecting 240 million people who suffer from chronic HBV infection and about 150 million who suffer from HCV infection
                <sup>
                    <xref ref-type="bibr" rid="ref-1">1</xref>,
                    <xref ref-type="bibr" rid="ref-2">2</xref>
                </sup>. In most cases, these viruses cause chronic infection whose natural course leads to liver cirrhosis, liver failure and/or hepatocarcinoma in affected patients
                <sup>
                    <xref ref-type="bibr" rid="ref-3">3</xref>
                </sup>.</p>
            <p>Patients with chronic renal failure (CRF) on hemodialysis are at high risk of contracting viral infections with HBV and HCV, the most common cause of liver disease in these patients
                <sup>
                    <xref ref-type="bibr" rid="ref-4">4</xref>,
                    <xref ref-type="bibr" rid="ref-5">5</xref>
                </sup>. Therefore, strict procedures for the control of hepatitis must be introduced in all dialysis units
                <sup>
                    <xref ref-type="bibr" rid="ref-6">6</xref>
                </sup>.</p>
            <p>The geographical distribution of HBV infection is not uniform throughout the world. Depending on the prevalence, different areas are classified as high, intermediate or low endemicity. HBV infection is highly prevalent (8&#x2013;15%) in Southeast Asia, China, the Philippines, Africa, the Amazon basin and the Middle East. In Eastern Europe, Central Asia, Japan, Israel and Russia the prevalence is intermediate (2.7%), while in North America, Western Europe, Australia and South America the prevalence is low (&lt;2%)
                <sup>
                    <xref ref-type="bibr" rid="ref-7">7</xref>
                </sup>. In Latin America it ranges from 2 to 7%
                <sup>
                    <xref ref-type="bibr" rid="ref-8">8</xref>
                </sup>. In developed countries the prevalence of HBV in patients treated with hemodialysis is 1%
                <sup>
                    <xref ref-type="bibr" rid="ref-9">9</xref>
                </sup>, while in developing countries the prevalence ranges from 2% to 20%
                <sup>
                    <xref ref-type="bibr" rid="ref-4">4</xref>,
                    <xref ref-type="bibr" rid="ref-10">10</xref>,
                    <xref ref-type="bibr" rid="ref-11">11</xref>
                </sup>.</p>
            <p>The prevalence of HCV in hemodialysis patients ranges from 2.6 to 22.9% (mean 13.5%) in developed countries, but can reach up to 70% in developing countries
                <sup>
                    <xref ref-type="bibr" rid="ref-12">12</xref>&#x2013;
                    <xref ref-type="bibr" rid="ref-15">15</xref>
                </sup>. In Latin America, the prevalence of HCV is also highly variable in hemodialysis patients, even within the same country. In Mexico, the prevalence is 6.7%
                <sup>
                    <xref ref-type="bibr" rid="ref-16">16</xref>
                </sup>, in Colombia it ranges from 2.9 to 42.2%
                <sup>
                    <xref ref-type="bibr" rid="ref-17">17</xref>,
                    <xref ref-type="bibr" rid="ref-18">18</xref>
                </sup>, while in Brazil ranges from 6&#x2013;72% (mean 52%)
                <sup>
                    <xref ref-type="bibr" rid="ref-19">19</xref>
                </sup>.</p>
            <p>In recent years there was a significant decrease in the prevalence of both HBV and HCV infections in industrialized countries
                <sup>
                    <xref ref-type="bibr" rid="ref-20">20</xref>
                </sup>. This decline is attributed, among other factors, to the decrease in transfusions, vaccination against HBV and introduction of general biosecurity measures to prevent transmission of infection in hemodialysis units.</p>
            <p>The aim of this study was to evaluate the prevalence of HBV and HCV in hemodialysis population dialysis units of four hemodialysis centers in the city of Posadas (Argentina).</p>
        </sec>
        <sec sec-type="methods">
            <title>Methods</title>
            <p>In this study, a total of 172 patients diagnosed with CRF under hemodialysis attending four hemodialysis centers of the city of Posadas (Argentina) were included. Ethical approval to conduct the study was obtained by the hemodialysis centres involved in Posada, Argentina: Instituto Privado de Nefrologia srl Roque Saenz Pe&#x00f1;a I; Instituto Privado de Nefrologia srl Roque Saenz Pe&#x00f1;a II, Instituto de Nefrologia IOT (Instituto de Ortopedia, Traumatolog&#x00ed;a y Medicina Laboral de alta complejidad); Instituto de Nefrologia Boratti. Institutional Review Board approval from the University of Misiones was not required as the private centers involved are not affiliated with the University and the study was considered a human health research without risks. The protection and control mechanisms for this type of research in Argentina includes inclusion of a written informed consent obtained from each participant".</p>
            <p>: Patients who participated in the study went daily to a hemodialysis center and participation was voluntary. Inclusion criteria encompassed individuals with CRF who were just starting hemodialysis treatment 30 days before obtaining blood samples.</p>
            <p>All patients signed an informed consent statement for joining the study after explaining the scope of the study. A unique and anonymous code was assigned to each patient and patient confidentiality was ensured.</p>
            <p>Blood samples were collected through venipuncture or by finger/heel stick in dry tubes (9.5 ml) with vacuum. After clot retraction, samples were centrifuged at 1,500 rpm for 5 minutes and stored in 5mL aliquots at -20&#x00b0;C (
                <ext-link ext-link-type="uri" xlink:href="http://www.cdc.gov/measles/lab-tools/serology.html">http://www.cdc.gov/measles/lab-tools/serology.html</ext-link>).</p>
            <p>Serological markers: surface antigen of hepatitis B virus (HBsAg) and antibodies to hepatitis C virus (antiHCV) were detected by enzyme-linked immunosorbent assay (ELISA) using commercially available kits (Wiener, Lab. S.A.I.C.).</p>
            <p>The following information from medical records were obtained: age, gender, time on hemodialysis, alanine aminotransferase (ALT) index, history of transfusions and history of drug abuse. An online information system was developed to analyze the information (available at 
                <ext-link ext-link-type="uri" xlink:href="http://bioinf.itiud.org/hemodialysis.php">http://bioinf.itiud.org/hemodialysis.php</ext-link>). The system allows computational analysis and deployment of information through generation of reports and statistics charts, designed to provide a simple reading of the results of the study. A descriptive analysis was performed by calculating means, medians and frequencies. Chi-square test was used to analyze the significant relationships between categorical data and Mann&#x2013;Whitney U test was used for the comparison of continuous data (p&lt;0.005). Data were managed and analyzed using 
                <italic toggle="yes">InfoStat</italic> software.</p>
        </sec>
        <sec sec-type="results">
            <title>Results</title>
            <p>Our final sample consisted of 172 patients: 98 males (57%) and 74 females (43%). Their ages ranged from 12 to 85 years with a mean age of 53.4 years (
                <xref ref-type="other" rid="DS0">Dataset 1</xref>).</p>
            <p>All patients had not history of tattooing, piercing, or use illegal drugs, and no human immunodeficiency virus (HIV) coinfection was found in any of the cases.</p>
            <p>The cause of CRF in  patients on hemodialysis was unknown in 31.4% of the cases, followed by diabetic nephropathy (22.1%). The etiology of CRF for these patients is detailed in 
                <xref ref-type="fig" rid="f1">Figure 1</xref>.</p>
            <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                <label>Figure 1. </label>
                <caption>
                    <title>Etiology of chronic renal failure (CRF) for the studied population.</title>
                </caption>
                <graphic orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/9759/5333ca5d-d7bb-49ea-9e51-bb1e1c4afab0_figure1.gif"/>
            </fig>
            <p>Serum samples from hemodialysis patients were tested for presence of HBsAg and antiHCV by ELISA. Fifteen (15/172) cases were positives for HBsAg, whereas 17 (17/172) cases were positives for antiHCV. 
                <xref ref-type="fig" rid="f2">Figure 2</xref> shows the distribution of HBsAg and antiHCV cases by age group.</p>
            <fig fig-type="figure" id="f2" orientation="portrait" position="float">
                <label>Figure 2. </label>
                <caption>
                    <title>Cases of HBsAg and antiHCV by age group.</title>
                </caption>
                <graphic orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/9759/5333ca5d-d7bb-49ea-9e51-bb1e1c4afab0_figure2.gif"/>
            </fig>
            <p>The majority of HBsAg positive cases were females (9/15), but this was not statistically significant (p = 0.16), while of the majority of cases positive for HCV markers were males (14/17); this result was statistically significant (p = 0.02). 
                <xref ref-type="fig" rid="f3">Figure 3</xref> presents the distribution of HBsAg and antiHCV markers of by gender.</p>
            <fig fig-type="figure" id="f3" orientation="portrait" position="float">
                <label>Figure 3. </label>
                <caption>
                    <title>Cases of HBsAg and antiHCV by gender.</title>
                    <p>Chi-square Pearson test. HBsAg: p = 0.16;  antiHCV: p = 0.02.</p>
                </caption>
                <graphic orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/9759/5333ca5d-d7bb-49ea-9e51-bb1e1c4afab0_figure3.gif"/>
            </fig>
            <p>All patients participating in this study had 4-hour hemodialysis sessions three times a week and 72.1% of patients showed a mean time of hemodialysis less than 5 years (
                <xref ref-type="fig" rid="f4">Figure 4</xref>). The duration of hemodialysis was not a significant risk factor for HBsAg (p = 0.9) and antiHCV (p = 0.2) presence.</p>
            <fig fig-type="figure" id="f4" orientation="portrait" position="float">
                <label>Figure 4. </label>
                <caption>
                    <title>Cases of HBsAg and antiHCV by time of hemodialysis sessions.</title>
                    <p>Chi-square Pearson test. HBsAg: p = 0.9;  antiHCV: p = 0.2.</p>
                </caption>
                <graphic orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/9759/5333ca5d-d7bb-49ea-9e51-bb1e1c4afab0_figure4.gif"/>
            </fig>
            <p>Transfusion history was observed in 47% (7/15) of cases positives for HBsAg. Positivity for HBsAg significantly correlated with transfusion (p = 0.003), while 29.4% (5/17) of cases positives for antiHCV did not show correlation with transfusion (p = 0.23) (
                <xref ref-type="fig" rid="f5">Figure 5</xref>).</p>
            <fig fig-type="figure" id="f5" orientation="portrait" position="float">
                <label>Figure 5. </label>
                <caption>
                    <title>Distribution of cases of HBsAg and  antiHCV by blood transfusion.</title>
                    <p>Chi-square Pearson test. HBsAg: p = 0.003;  antiHCV: p = 0.23.</p>
                </caption>
                <graphic orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/9759/5333ca5d-d7bb-49ea-9e51-bb1e1c4afab0_figure5.gif"/>
            </fig>
            <p>In our patient population, 154 (89,5%) cases showed normal concentration of serum ALT level (&lt; 40 U/L), and 18 (10,5%) showed elevation in serum ALT level (&gt;40 IU/L) (
                <xref ref-type="fig" rid="f6">Figure 6</xref>).</p>
            <fig fig-type="figure" id="f6" orientation="portrait" position="float">
                <label>Figure 6. </label>
                <caption>
                    <title>Distribution of cases based on information of alanine aminotransferase (ALT) (U/L) levels.</title>
                    <p>Mann-Whitney 
                        <italic toggle="yes">U</italic> test. HBsAg: p = 0.001;  antiHCV: p = 0.002.</p>
                </caption>
                <graphic orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/9759/5333ca5d-d7bb-49ea-9e51-bb1e1c4afab0_figure6.gif"/>
            </fig>
            <p>A total of six HBsAg positive cases out of 15 (33.3%) showed elevation in serum ALT level, whereas one (5.5%) of the cases positive for HCV out of 17 showed increased serum ALT level. This correlation was statistically significant (p = 0.001 and p = 0.002 respectively).</p>
            <supplementary-material id="DS0" orientation="portrait" position="float" xlink:href="https://f1000researchdata.s3.amazonaws.com/datasets/9068/935d3762-6287-4ace-87db-842b3a3b7f07_Raw_data.zip">
                <label>Information from hemodialysis patients</label>
                <caption>
                    <p>The raw analysis data for each patient are shown. A description of the data is provided in the text file.</p>
                </caption>
            </supplementary-material>
        </sec>
        <sec sec-type="discussion">
            <title>Discussion</title>
            <p>Patients with CRF on hemodialysis are a group at high risk for HBV and HCV infections.</p>
            <p>In Argentina the prevalence of HBsAg varies between the provinces, from 0.17% to 1.79%, and prevalence of antiHCV varies between 1.70% and 21%
                <sup>
                    <xref ref-type="bibr" rid="ref-21">21</xref>
                </sup>. In our study we found a relatively high prevalence of serological markers for HBV and HCV in hemodialysis patients in Posadas (Argentina). The HBsAg antibody (indicator of active HBV infection) was found in 8.7% of the studied cases and antiHCV in 9.9%.</p>
            <p>These values are comparable to values reported in several studies on hemodialysis patients. In Peru, HBsAg prevalence ranges from 0.2% to 4.8%
                <sup>
                    <xref ref-type="bibr" rid="ref-22">22</xref>
                </sup>, in Brazil varies between 4% and 28%
                <sup>
                    <xref ref-type="bibr" rid="ref-23">23</xref>,
                    <xref ref-type="bibr" rid="ref-24">24</xref>
                </sup>, in Cuba is 4%
                <sup>
                    <xref ref-type="bibr" rid="ref-25">25</xref>
                </sup>, and in Colombia HBsAg is 22%
                <sup>
                    <xref ref-type="bibr" rid="ref-26">26</xref>
                </sup>.</p>
            <p>Various studies in hemodialysis units show different prevalence rates for HCV: in Peru between 90% and 4.65%
                <sup>
                    <xref ref-type="bibr" rid="ref-22">22</xref>
                </sup>, in Uruguay from 16% to 3%
                <sup>
                    <xref ref-type="bibr" rid="ref-27">27</xref>
                </sup>, in Brazil 33.4% to 16%
                <sup>
                    <xref ref-type="bibr" rid="ref-23">23</xref>,
                    <xref ref-type="bibr" rid="ref-28">28</xref>
                </sup>, in Mexico 6.7%
                <sup>
                    <xref ref-type="bibr" rid="ref-16">16</xref>
                </sup>, and in Cuba 90%
                <sup>
                    <xref ref-type="bibr" rid="ref-25">25</xref>
                </sup>. The antiHCV prevalence in dialysis units in Cali (2.9%) and Bogot&#x00e1; (2.7%) is very low
                <sup>
                    <xref ref-type="bibr" rid="ref-17">17</xref>,
                    <xref ref-type="bibr" rid="ref-29">29</xref>
                </sup>, while in Medellin is high (42,2%)
                <sup>
                    <xref ref-type="bibr" rid="ref-18">18</xref>
                </sup>.</p>
            <p>By exploring the correlation between risk factors and seropositivity for HBV and HCV in hemodialysis patients, it seemed that timing of hemodialysis was not a risk factor. History of transfusion correlated with the risk of HBV infection, but not with risk of HCV infection. The elevation of ALT enzyme activity was not a good index for HBV and HCV infection in these patients, since normal values were observed in a high percentage of patients positive for HBsAg and antiHCV.</p>
        </sec>
        <sec sec-type="conclusions">
            <title>Conclusion</title>
            <p>The results of this study demonstrate a high prevalence of serological markers for HBV and HCV infections in CRF patients on hemodialysis in Argentina, compared with results obtained from patients in developed countries.</p>
            <p>Therefore, an effective strategy to prevent nosocomial transmission of HBV and HCV in hemodialysis units and reduce the prevalence of infection should be implemented in strict compliance with biosafety standards, measures of education, hygiene and HBV vaccination plans to prevent the infection.</p>
        </sec>
        <sec>
            <title>Consent</title>
            <p>Written informed consent to participate in the study and publish clinical data was obtained by the patients.</p>
        </sec>
        <sec>
            <title>Data availability</title>
            <p>The data referenced by this article are under copyright with the following copyright statement: Copyright: &#x00ef;&#x00bf;&#x00bd; 2016 Salvatierra K and Florez H</p>
            <p>Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).
                <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/"/>
            </p>
            <p>F1000Research: Dataset 1. Patient characteristics, 
                <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.5256/f1000research.9068.d131385">10.5256/f1000research.9068.d131385</ext-link>
                <sup>
                    <xref ref-type="bibr" rid="ref-30">30</xref>
                </sup>
            </p>
        </sec>
    </body>
    <back>
        <ack>
            <title>Acknowledgments</title>
            <p>The authors would like to thank the hemodialysis patients, authorities, and the staff of the four dialysis centers that collaborated in the study, making this research possible. Both authors agreed to the final content of the article.</p>
        </ack>
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    <sub-article article-type="reviewer-report" id="report15836">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.9759.r15836</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Ferrari</surname>
                        <given-names>Rafaela</given-names>
                    </name>
                    <xref ref-type="aff" rid="r15836a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <aff id="r15836a1">
                    <label>1</label>Cavanilles Institute of Biodiversity and Evolutionary Biology (ICBiBE), University of Valencia, Valencia, Spain</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>21</day>
                <month>3</month>
                <year>2017</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2017 Ferrari R</copyright-statement>
                <copyright-year>2017</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport15836" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.9068.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>Even though it is a descriptive research, I think it's important for local researchers. However, I suggest some changes: 
                <list list-type="bullet">
                    <list-item>
                        <p>the title &#x201c;Prevalence of hepatitis B and C infections in hemodialysis patients&#x201d; should be completed to include the geographical region</p>
                    </list-item>
                    <list-item>
                        <p>P-values &lt;0.05 were considered significant, not &lt;0.005, is possible there were a typing error</p>
                    </list-item>
                    <list-item>
                        <p>How many of the patients presented the symptomatology of hepatitis?</p>
                    </list-item>
                    <list-item>
                        <p>How many of the patients included in the study were being vaccinated against hepatitis B virus?</p>
                    </list-item>
                </list>
            </p>
            <p>Reviewer Expertise:</p>
            <p>NA</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment3073-15836">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>salvatierra</surname>
                            <given-names>karina</given-names>
                        </name>
                        <aff>Universidad Nacional de Misiones, Argentina</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>30</day>
                    <month>9</month>
                    <year>2017</year>
                </pub-date>
            </front-stub>
            <body>
                <p>Dear Reviewer&#x00a0; Rafaela Ferrari.&#x00a0;</p>
                <p> Thank you so much for your feedback.&#x00a0; We want to inform you:</p>
                <p> 1. In the abstract and in the text we describe the geographic location.</p>
                <p> 2.&#x00a0; We have changed the P-values as you suggested. Mann&#x2013;Whitney U test was used for the comparison of continuous non-normal data. P-values &lt;0.05 were considered significant.</p>
                <p> 3. Hepatitis C is usually asymptomatic it rarely causes symptoms. Hepatitis C &#x00a0;may&#x00a0;not&#x00a0;produce&#x00a0;symptoms. The spectrum of the symptomatology of hepatitis B disease varies from subclinical hepatitis to icteric hepatitis to fulminant, acute, and subacute hepatitis during the acute phase, and from an asymptomatic chronic infection state to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) during the chronic phase.</p>
                <p> In this case, patients was not presented symptomatology of hepatitis.</p>
                <p> 4. In respect of hepatitis B vaccination, 125/172 (73%) of the patients completed the vaccination scheme, while none of the HBsAg (+) cases have had HBV vaccination.</p>
                <p> 
                    <bold>Thank you so much</bold>
                </p>
                <p> 
                    <bold>Best Regards</bold>
                </p>
                <p> </p>
                <p> </p>
            </body>
        </sub-article>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report15421">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.9759.r15421</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Hassan</surname>
                        <given-names>Rocio</given-names>
                    </name>
                    <xref ref-type="aff" rid="r15421a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <aff id="r15421a1">
                    <label>1</label>Center for Bone Marrow Transplantation (CEMO), Instituto Nacional de C&#x00e2;ncer (INCA), Rio de Janerio, Brazil</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>21</day>
                <month>12</month>
                <year>2016</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2016 Hassan R</copyright-statement>
                <copyright-year>2016</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport15421" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.9068.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This is a descriptive work that has as primary aim to evaluate the prevalence of HBV and HCV in a hemodialysis population of the city of Posadas (Argentina).</p>
            <p> </p>
            <p> The research have been conducted with ethical and methodological correctness and results, although of limited reach, contribute with useful information on HBV and HCV prevalence in an at-risk group (hemodialysis patients) from a geographical region with paucity of such studies. Moreover, sero-prevalence of HBV in Misiones Province appear to be high, which may indicate a distinct epidemiological situation closer to that reported for neighbor Brazil than that described for Central and Southern Argentina.</p>
            <p> </p>
            <p> Therefore, I consider that the manuscript is suitable for indexing, provided some restructuring is done in the text.&#x00a0; Moreover, the article has, at present, 147 views and 50 download. This means it has raised interest in the scientific community and for that, I think it deserves to be corrected to include the suggestions of the reviewers.</p>
            <p> </p>
            <p> I would like, then, to make some suggestions that I think may help improving the text. 
                <list list-type="order">
                    <list-item>
                        <p>In first place, and if it is possible, the present title &#x201c;Prevalence of hepatitis B and C infections in hemodialysis patients&#x201d; may be completed to include a characterization of the geographical region from where the results come from. The reader would then have an insight of the specific geographic and epidemiological context from the beginning.</p>
                    </list-item>
                    <list-item>
                        <p>In the introduction, it will be very important to geographically and epidemiologically situate Misiones Province, and specifically Posadas City, describing available results on HBV/HCV prevalence in this specific population.</p>
                    </list-item>
                    <list-item>
                        <p>Methods: It is desirable to check the English syntax and grammar of the first to third paragraphs. The phrase &#x201c;The protection and control mechanisms for this type of research in Argentina includes inclusion of a written informed consent obtained from each participant" is unnecessary, since in the third paragraph it is stated that &#x201c;All patients signed an informed consent statement&#x201d;.</p>
                    </list-item>
                    <list-item>
                        <p>Please, explain better the inclusion criteria. The statement &#x201c;individuals with CRF who were just starting hemodialysis treatment 30 days before obtaining blood samples&#x201d; is misleading, since it gives the impression that all individuals started hemodialysis 30 days before obtaining blood samples for the present study.</p>
                    </list-item>
                    <list-item>
                        <p>In the statistics description, replace &#x201c;Mann&#x2013;Whitney U test was used for the comparison of continuous data (p&lt;0.005)&#x201d; by Mann&#x2013;Whitney U test was used for the comparison of continuous non-normal data. P-values &lt;0.05 were considered significant.</p>
                    </list-item>
                    <list-item>
                        <p>Results: Please clarify the issue of HIV infection (vs. co-infection). Have all patients been tested for HIV infection, or only the HCV/HBV positive ones? If it is the first case, please correct the statement &#x201c;human immunodeficiency virus (HIV) coinfection was found in any of the cases.&#x201d; by &#x201c;human immunodeficiency virus (HIV) infection was not found in any of the cases.&#x201d;</p>
                    </list-item>
                    <list-item>
                        <p>Figure 1, please express decimal notation with periods instead of commas.</p>
                    </list-item>
                    <list-item>
                        <p>&#x00a0;&#x00a0;Gender association in HCV+ and HBV+ patients would be better presented as a stacked column graphic with percentage of male or female individuals for each category. Wouldn&#x2019;t &#x00a0;Fisher&#x2019;s exact test be a better statistical to apply here?. The authors should provide in the Discussion a possible explanation for the gender association found in the study.</p>
                    </list-item>
                    <list-item>
                        <p>What was the specific statistical approach used for testing association between time of dialysis and HCV/HBV serostatus? Was it, as described in Fig. 4, a 2x6 Pearson Chsq test or, alternatively time was categorized in &gt;5 vs 
                            <underline>&lt;</underline> 5 years? Risk is not well modelled by Chsq tests, and so, with the present statistical approach it only can be described as association. To model the risk, a logistic regression with HCV/HBV serostatus as dependent variable may be used instead. Again, the bar graphic with number of pts as scale is not very informative. &#x00a0;&#x00a0;</p>
                    </list-item>
                    <list-item>
                        <p>&#x00a0;Respect of data on serum ALT levels,&#x00a0; in figure 6, results of a Mann-Whitney test are provided, but the representation of data is as categories (till 40U/L - &gt;40 U/L). The authors should either present categorical test results (i.e. Chisq or Fisher&#x2019;s) or a Box-and-whisker plot with data around the median value. This last would be a better graphical depiction for the data.</p>
                    </list-item>
                    <list-item>
                        <p>Discussion needs to be rewritten to&#x00a0;put the results in a stronger theoretical context. The authors should focus at least part of the discussion on the comparison of Misiones data with Brazilian available data and data from the rest of Argentina. In fact, most of the significant references from Brazil are listed in the article reference list, but they have not been used to highlight the similarity of Misiones&#x2019; data. Important references from Misiones (and the rest of Argentina) are lacking, as it was pointed out in a previous review. &#x00a0;</p>
                    </list-item>
                </list> &#x00a0;Additionaly, I would like to ask the authors to include in the revised version of the ms some points addressed by a previous reviewer, which in my opinion are minor revisions. 
                <list list-type="bullet">
                    <list-item>
                        <p>Add information on demographics and the prevalence of HCV and HBV separately for each of the four participating hemodialysis centers in the city of Posadas. The data can be included as a supplementary table, if so allowed by the Journal. &#x00a0;</p>
                    </list-item>
                    <list-item>
                        <p>Please, describe the HBV vaccine history of patients.</p>
                    </list-item>
                    <list-item>
                        <p>If possible, include the information of HBV and HCV serological status of CRF patients prior to hemodialysis.</p>
                    </list-item>
                    <list-item>
                        <p>In the Methods section, please state the period of time of sample collection.</p>
                    </list-item>
                    <list-item>
                        <p>In respect to the association between transfusion history and HBsAg, it would be important to indicate the period of transfusion, in order to rule out (if it was a recent event) or strongly suggest (if it occurred before the 1960s) that transfusion was the source of HBV infection.</p>
                    </list-item>
                    <list-item>
                        <p>There is potential for more in-depth analysis and comparison. The authors should include more discussion and compare with their findings. For example, it is known that Misiones is a high HBV prevalence area in Argentina (please read the papers by Delfino
                            <italic>&#x00a0;et al.,</italic>&#x00a0;J ClinVirol 2012 and Arch Virol 2014).</p>
                    </list-item>
                </list>
            </p>
            <p>Reviewer Expertise:</p>
            <p>NA</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.</p>
        </body>
        <back>
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    </sub-article>
    <sub-article article-type="reviewer-report" id="report17997">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.9759.r17997</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Esposito</surname>
                        <given-names>Isabella</given-names>
                    </name>
                    <xref ref-type="aff" rid="r17997a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <contrib contrib-type="author">
                    <name>
                        <surname>Trinks</surname>
                        <given-names>Julieta</given-names>
                    </name>
                    <xref ref-type="aff" rid="r17997a1">1</xref>
                    <role>Co-referee</role>
                </contrib>
                <aff id="r17997a1">
                    <label>1</label>Instituto de Ciencias B&#x00e1;sicas y Medicina Experimental (ICBME), Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>5</day>
                <month>12</month>
                <year>2016</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2016 Esposito I and Trinks J</copyright-statement>
                <copyright-year>2016</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport17997" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.9068.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>reject</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>Patients with chronic renal failure (CRF)&#x00a0;receiving hemodialysis are at higher risk for acquiring Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infections than the general population. The susceptibility to acquire viral hepatitis during hemodialysis has several potential underlying reasons related to both the patient and the hemodialysis procedure. Strict infection control measures are essential to prevent nosocomial transmission.</p>
            <p> </p>
            <p> So the aim of this article was to investigate the prevalence of HBV and HCV infection in the hemodialysis population of a region of Argentina as well as risk factors for infection.</p>
            <p> </p>
            <p> Serum testing for the presence of hepatitis B surface antigen (HBsAg) and anti-HCV antibodies (antiHCV) by ELISA and subsequent correlation of sero-positivity to HBV and HCV with timing of hemodialysis, history of transfusion, alanine aminotransferase (ALT) index, allowed the authors the opportunity to describe HBV and HCV prevalence in the present cohort of hemodialysis patients.</p>
            <p> </p>
            <p> The study is adequately described; however, it could have been more detailed. Some suggestions are as follow: 
                <list list-type="bullet">
                    <list-item>
                        <p>Please compare the difference in sero-positivity results between the four hemodialysis centers in the city of Posadas, which can eventually reflect difference in the biosecurity procedures of each center.</p>
                    </list-item>
                    <list-item>
                        <p>Describe whether&#x00a0;the patients included in the study were being vaccinated against hepatitis B virus.</p>
                    </list-item>
                    <list-item>
                        <p>It would be necessary to clarify the HBV and HCV serological status of patients with CRF before starting hemodialysis treatment.</p>
                    </list-item>
                    <list-item>
                        <p>In the Methods section, please state the period of time of sample collection.</p>
                    </list-item>
                    <list-item>
                        <p>The authors correlated transfusion history with HBsAg or anti-HCV serological status and reported a significant association with positivity for HBsAg. It would be important to indicate the year of transfusion, in order to rule out (if it was a recent event) or strongly suggest (if it occurred before the 1960s) that transfusion was the source of HBV infection.</p>
                    </list-item>
                    <list-item>
                        <p>It would have been interesting to determine anti-HBc total antibodies as well.</p>
                    </list-item>
                    <list-item>
                        <p>There is potential for more in-depth analysis and comparison. The authors should include more discussion and compare with their findings. For example, it is known that Misiones is a high HBV prevalence area in Argentina (please read the papers by Delfino
                            <italic> et al.,</italic> J ClinVirol 2012 and Arch Virol 2014).</p>
                    </list-item>
                </list> This is a well written but very simple study describing prevalence of HBV and HCV seromarkers in a particular region of Argentina. It could be updated with more detailed information and we do not consider it to be of an acceptable scientific standard. Therefore, this article is not suitable unless the content is extensively edited.</p>
            <p>Reviewer Expertise:</p>
            <p>NA</p>
            <p>We confirm that we have read this submission and believe that we have an appropriate level of expertise to state that we do not consider it to be of an acceptable scientific standard, for reasons outlined above.</p>
        </body>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report15420">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.9759.r15420</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Berenguer</surname>
                        <given-names>Marina C</given-names>
                    </name>
                    <xref ref-type="aff" rid="r15420a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <aff id="r15420a1">
                    <label>1</label>Faculty of Medicine, University of Valencia, Valencia, Spain</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>22</day>
                <month>8</month>
                <year>2016</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2016 Berenguer MC</copyright-statement>
                <copyright-year>2016</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport15420" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.9068.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>reject</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>The aim of this study was to evaluate the prevalence of HBV and HCV in hemodialysis population dialysis units of four hemodialysis centers in the city of Posadas (Argentina).</p>
            <p> Serum samples from hemodialysis patients were tested for presence of HBsAg and antiHCV by ELISA. Fifteen (15/172) cases were positives for HBsAg, whereas 17 (17/172) cases were positives for antiHCV.</p>
            <p> This is a descriptive study on local seroprevalence of HBV and HCV infection in a region of Argentina. The title is appropriate. The abstract provides adequate summary of the content. The methods are adequately described. The conclusions are adequate.</p>
            <p> </p>
            <p> There is though missing information which is relevant: no information on viremia, underlying disease severity, sequential data overtime.</p>
            <p> </p>
            <p> The following questions should be asked to the authors: 
                <list list-type="bullet">
                    <list-item>
                        <p>How many of the patients were viremic?</p>
                    </list-item>
                    <list-item>
                        <p>Was there any information on underlying disease severity</p>
                    </list-item>
                    <list-item>
                        <p>How many were HBV and HCV coinfected?</p>
                    </list-item>
                    <list-item>
                        <p>Do the authors have sequential data to try to clarify whether there is an increase, stability or decrease of positive cases?</p>
                    </list-item>
                    <list-item>
                        <p>Were there HBV patients coinfected with HDV?</p>
                    </list-item>
                    <list-item>
                        <p>Were there differences in positivity results by center?</p>
                    </list-item>
                </list> In essence, this is a simple study describing prevalence of HBV and HCV seromarkers in a particular region of Argentina. There have been many studies published to date on seroprevalence of these viruses around the world.</p>
            <p>Reviewer Expertise:</p>
            <p>NA</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment2166-15420">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>salvatierra</surname>
                            <given-names>karina</given-names>
                        </name>
                        <aff>Universidad Nacional de Misiones, Argentina</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>29</day>
                    <month>8</month>
                    <year>2016</year>
                </pub-date>
            </front-stub>
            <body>
                <p>Dear Reviewer&#x00a0; Marina C Berenguer</p>
                <p> </p>
                <p> Thank you so much for your feedback.&#x00a0; We want to inform you:</p>
                <p> </p>
                <p> - Unfortunately, we do not have information regarding viremic, disease severity, and sequential data.</p>
                <p> - There were not patients coinfected with with HBV and HCV.</p>
                <p> - This is a simple study describing prevalence of HBV and HCV seromarkers in a particular region of Argentina. So far, there is no studies regarding this topic in this region</p>
                <p> Given the limitations on what is counted in the region to do research, this is the first step to go ahead and propose further research.</p>
                <p> </p>
                <p> Thank you so much</p>
                <p> Best Regards</p>
            </body>
        </sub-article>
    </sub-article>
</article>
