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Management of hepatitis C virus infection in childhood
Marcela Galoppo
,
Corresponding author
mgaloppo@hotmail.com
crisgaloppo@gmail.com

Correspondence and reprint request:
, Cristina Galoppo*
* Pediatric Hepatologist
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Infection with hepatitis C virus &#40;HCV&#41; is a worldwide health problem with more than 170 million infected individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> There is geographic variation in the incidence and prevalence of this infection&#46;</p><p id="p0010" class="elsevierStylePara elsevierViewall">HCV antibodies in children are between 0&#46;2&#37; and 0&#46;4&#37;&#44; with an age-dependent increase in seropreva-lence &#40;0&#46;2&#37; for children aged 6-11 years and 0&#46;4&#37; for children aged 12-19 years&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Since 1992 almost all infections occurred through vertical transmission from an infected mother to her newborn infant&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">A recent report of Italy showed 40&#37; reduction in the number of infected children seen from 2000 to 2004 by comparison with the previous 5 years&#46; The low prevalence of HCV infection in children can be explained by the disappearance of post transfusion hepatitis in developed countries and the low efficacy of mother-to-child transmission&#44; which has become the principal source of infection in the pediatric set-ting&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">Natural history of HCV infection in children is not yet well defined&#59; most children are asymptomatic and may remain so for decades&#46; Diagnosis is generally made screening risk factor patients&#44; elevated aminotransferases in routine tests and household HCV infected adults&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="p0025" class="elsevierStylePara elsevierViewall">Treatment strategies in adults have had a significant impact on the management of children with HCV chronic infection&#46; All efforts now are towards to early diagnosis&#44; safety and efficacy treatment&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Epidemiology and Risk of Transmission</span><p id="p0030" class="elsevierStylePara elsevierViewall">After blood donor screening began in the 1990&#8217;s&#44; the risk of contracting HCV from blood and derivatives became extremely low in developed countries&#44; in-travenous drug abuse and high-risk sexual behavior are maintaining the reservoir of infection in adults and groups of adolescents&#46; Transmission through in-fected blood products&#44; however&#44; remains a risk in countries where strict recommendations for screening blood products are not reliably adhered to&#46; Horizontal transmission for family members is uncommon&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="p0035" class="elsevierStylePara elsevierViewall">In children vertical transmission is responsible for most &#8220;new infections&#8221;&#44; however&#44; has an efficiency of only about 5&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="p0040" class="elsevierStylePara elsevierViewall">Risk of maternal-infant transmission is increased &#40;up to 22&#37;&#41; by level of maternal HCV viral load such as HIV co infection&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="p0045" class="elsevierStylePara elsevierViewall">Vertical transmission is almost always confined to women who have detectable HCV RNA&#46; There is an extremely low risk of transmission with undetec-table or intermittent viremia&#44; even though the risk of infection in this clinical situation is as low as 0&#46;3&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="p0050" class="elsevierStylePara elsevierViewall">Presumably&#44; both intrauterine and intrapartum infections occur&#46; The mode of delivery does not affect risk of HCV transmission&#46; Membrane ruptures longer than six hours and internal fetal monitoring were associated with an increased risk of transmission&#46; Current recommendations are that women with HCV without HIV co-infection can be advised to breast feed&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="p0055" class="elsevierStylePara elsevierViewall">Recent studies showed that girls were twice as likely to be infected as boys&#46; This finding&#44; may reflects differences between males and females in hormonal or genetic susceptibility or immunological response to infections&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="p0060" class="elsevierStylePara elsevierViewall">Diagnoses of HCV infection in exposed infants is hampered by passive transfer of maternal antibodies during pregnancy persisting up to 13 to 18 months of life&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> HCVRNA polymerase chain reaction &#40;PCR&#41; testing is highly specific&#44; but its sensitivity is low at birth and in the first days of life &#40;22&#37;&#41; while it increases at one month of age and thereafter &#40;&#62; 75&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="p0065" class="elsevierStylePara elsevierViewall">A child born to a seropositive mother is conside-rer to be infected if serum HCVRNA is detectable in at least two separate determinations between 2-6 months and whit persistence of anti-HCV antibodies after the first year of life&#46; Chronic infection is defined as the persistence of HCV RNA for at least six months and resolution is determined by the persistent disappearance of HCVRNA&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Natural History and Diagnosis</span><p id="p0070" class="elsevierStylePara elsevierViewall">Most infected individuals &#40;60-80&#37;&#41;&#44; regardless of their age at infection&#44; become chronically infected with HCV&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="p0075" class="elsevierStylePara elsevierViewall">Spontaneous resolution in children appears to be infrequent&#58; in three large series&#44; including vertical and horizontal acquisition&#44; HCV clearance occurred in 5&#46;6-10&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> children infected with genotype 3 &#40;81&#37; of whom were vertically infected&#41; had the highest rate of viral clearance &#40;22&#37;&#41; compared to other genotypes&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="p0080" class="elsevierStylePara elsevierViewall">In 266 vertically HCV infected children&#44; 17&#37; showed viral clearance by 2&#44; 24&#37; by 3&#44; and 25&#37; by 5 years of age &#40;median age 14&#46; 9 m&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="p0085" class="elsevierStylePara elsevierViewall">Transfusion acquired infection have a higher chance of spontaneous clearance than vertical acquisition&#46; HCV genotype&#44; viral load and immunoto-lerance in young infants&#44; were proposed to influence viral resolution&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="p0090" class="elsevierStylePara elsevierViewall">Once chronicity is established&#44; such as in older children&#44; serological and histological features seem to be independent of the source and time of infec-tion&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Illness is generally asymptomatic and characterized by a bening course during the first two decades of life&#46; Advanced liver disease is rare during childhood and there are no reports of acute liver failure in HCV pediatric infected patient&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Clinical symptoms are mild and nonspecific in only 20&#37; of cases during early childhood&#46; Hepatomegaly is present in 10&#37; of infected children&#46;</p><p id="p0095" class="elsevierStylePara elsevierViewall">HCV-associated cryoglobulinemia&#44; vasculitis and porphyria cutanea tarda are not reported in chil-dren&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="p0100" class="elsevierStylePara elsevierViewall">Aminotransferases remains usually normal or mildly abnormal levels but it is not a reliable indicator of abscense of hepatic injury&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="p0105" class="elsevierStylePara elsevierViewall">Positive HCV antibody implicate that patient has been exposed to the virus &#40;EIA test&#41;&#46; Anti-HCV antibodies may be undetectable during first few weeks after HCV exposure or in immunocompromised pa-tients&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="p0110" class="elsevierStylePara elsevierViewall">To discriminate between active or resolved HCV viral infection it is necessary to perform HCV RNA &#40;PCR&#41;&#46; HCV RNA PCR may be intermittently negative&#46;</p><p id="p0115" class="elsevierStylePara elsevierViewall">HCV genotype and HCV-RNA viral load provide useful information for predicting response to therapy&#46; HCV genotype is also used to determine the length of therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="p0120" class="elsevierStylePara elsevierViewall">Liver biopsy assess degree of liver injury and exclude concurrent diseases specially in children with normal transaminases who are being considered for treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Histological picture is similar to those of adults&#46; Necrotic inflammation and fibrosis are usually milder&#44; though liver damage is greater in older patients and progression to cirrhosis has been noted&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Treatment</span><p id="p0125" class="elsevierStylePara elsevierViewall">HCV chronic infection is slow progressive in childhood therefore&#8217; there is no uniform consensus about timing for treatment&#46; Progression of fibrosis seems to be a function of infection duration&#8217; when no other risk factors for liver damage are present&#46; HCV cirrhosis and its complications in adulthood and universal recurrence in post transplant recipients justify medical decision in favor of treatment&#46; Therefore&#44; children are ideal candidates for treatment&#46; The shorter the duration of infection with mild histological disease&#44; the better the response to treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="p0130" class="elsevierStylePara elsevierViewall">A review of published trials with Interferon &#40;IFN&#41; monotherapy in 105 children showed average an end-of-treatment response &#40;ETR&#41; of 54&#37; and sustained virological response &#40;SVR&#41; of 36&#37;&#46; The SVR in genotype 1 was 27&#37; versus 70&#37; for non genotype 1 &#40;p&#58; 0&#46;001&#41;&#46; The SVR rates were higher than those reported in adults&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="p0135" class="elsevierStylePara elsevierViewall">Different trials with combination therapy were done and others are in progress <a class="elsevierStyleCrossRef" href="#t0005">&#40;Table 1&#41;</a>&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Primary Goal of Treatment</span><p id="p0140" class="elsevierStylePara elsevierViewall">Clearance viral infection &#40;HCV RNA non detectable in serum&#41;&#44; regression or delay in liver fibrosis&#44; prevention of chronic liver disease and development of HCC and improve quality of life&#46;</p><p id="p0145" class="elsevierStylePara elsevierViewall">Benefits of treatment are not restricted to biochemical&#44; histologic or virologic response&#58; quality of life&#44; risk of hepatocellular carcinoma&#44; and mortality risk may be favorably affected by treatment&#44; even in the absence of sustained viral response&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Considering Treatment</span><p id="p0150" class="elsevierStylePara elsevierViewall">IFN alfa is recognized as the drug approved for hepatitis C treatment in pediatric population&#46; As in adults&#44; combination therapy with IFN&#945; or pegylated IFN&#945; and ribavirin in children under clinical trials&#44; support its efficacy in sustained virological response &#40;SVR&#41; compared with IFN&#945; alone&#46; Recently&#44; the US FDA and EMEA have approved combined pegylated-IFN&#945;2b plus ribavirin treatment for children&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Principal advantage of PEG-IFN&#945; is the extended serum half-life conferred by pegylation of the IFN molecule&#44; which confers a once-weekly administration and improved efficacy and a safety profile similar to that of IFN&#945;&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="p0155" class="elsevierStylePara elsevierViewall">Treatment should be considered in children between 3 to 18 years old&#44; anti HCV &#40;&#43;&#41;&#44; HCVRNA &#40;&#43;&#41; for at least 6 months and normal or abnormal ALT&#46;</p><p id="p0160" class="elsevierStylePara elsevierViewall">Patients are excluded if they have comorbid medical conditions that could compromise the safety&#44; efficacy and tolerability of drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="p0165" class="elsevierStylePara elsevierViewall">Liver biopsy remains the gold standard for assessing the severity of inflammation and fibrosis&#44; and rule out concurrent diseases particularly in children whit normal liver tests&#46; Inflammation and fibrosis are less common than in adults but significant fibro-sis and cirrhosis may develop during childhood&#46; In a series of 112 pediatric patients with chronic hepatitis C the degree of fibrosis correlated with age and duration of infection&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="p0170" class="elsevierStylePara elsevierViewall">There are different opinions about performing liver biopsy in genotypes 2 and 3 whose sustained vi-rological response rates exceed 80&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="p0175" class="elsevierStylePara elsevierViewall">HCV genotype should be identify to establish treatment duration and probability of response&#46; For genotypes 1 and 4&#44; therapy is recommended for at least 48 weeks&#44; overall SVR is 50&#37;&#46; Genotypes 2 and 3 should be treated only for 24 weeks&#59; overall SVR is 83-100&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="p0180" class="elsevierStylePara elsevierViewall">Viral load is necessary to evaluate virological response during treatment&#46;</p><p id="p0185" class="elsevierStylePara elsevierViewall">Treatment objective is clearance of HCVRNA below the detection limit of PCR technique employed &#40;30-50IU&#47;mL&#41;&#46; Then&#44; therapy should continue in order to eradicate infection in the liver&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Treatment Schedule and Monitoring</span><p id="p0190" class="elsevierStylePara elsevierViewall">The dose of IFN&#945; monotherapy is 3 MIU&#47;m<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> sub-cutaneously 3 times a week&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="p0195" class="elsevierStylePara elsevierViewall">PEG-IFN&#945;-2b &#40;60 <span class="elsevierStyleItalic">&#956;</span>g&#47;m<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#47;week or 1-1&#46;5 <span class="elsevierStyleItalic">&#956;</span>g&#47;kg&#47;wk&#41; or &#945;2a &#40;100 <span class="elsevierStyleItalic">&#956;</span>g&#47;m<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#47;week&#41; subcutaneously plus Riba-virina &#40;15 mg&#47;kg&#47;day&#41; twice orally is used in combination therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="p0200" class="elsevierStylePara elsevierViewall">Adverse events are common during treatment&#44; particularly transient &#8220;flu-like syndrome&#8221;&#44; leukope-nia and neutropenia related to IFN&#46; Although rare&#44; depression and suicidal ideation attempt occurs in treated children&#46; Antithyroid antibodies are common and clinical thyroid disease occurs but rarely becomes permanent&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="p0205" class="elsevierStylePara elsevierViewall">The most common adverse effect of ribavirin is a reversible hemolytic anemia&#46; Ribavirin is also known to be teratogenic&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="p0210" class="elsevierStylePara elsevierViewall">Liver&#44; hematology&#44; thyroid and other routine tests should be periodically done in order to detect adverse events for evaluate eventually reduction or interruption medication&#46; HCV RNA titers are measured at 4&#44; 12&#44; 24&#44; 36 and 48 weeks&#44; and every 12 weeks for another 6 months after the end of treatment&#46;</p><p id="p0215" class="elsevierStylePara elsevierViewall">Diagnosis and treatment strategies in children should be prescribe and supervise by pediatric hepa-tologist&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span></span>"
    "textoCompletoSecciones" => array:1 [
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          "identificador" => "xres1210341"
          "titulo" => "Abstract"
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              "identificador" => "abs0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1126758"
          "titulo" => "Key words"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        3 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Epidemiology and Risk of Transmission"
        ]
        4 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Natural History and Diagnosis"
        ]
        5 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Treatment"
        ]
        6 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Primary Goal of Treatment"
        ]
        7 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Considering Treatment"
        ]
        8 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Treatment Schedule and Monitoring"
        ]
        9 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2010-03-20"
    "fechaAceptado" => "2010-04-20"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Key words"
          "identificador" => "xpalclavsec1126758"
          "palabras" => array:6 [
            0 => "Children"
            1 => "Chronic hepatitis C"
            2 => "Hepatitis C virus"
            3 => "IFN"
            4 => "Pegylated IFN"
            5 => "Ribavirin"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abs0005" class="elsevierStyleSection elsevierViewall"><p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Infection with hepatitis C virus &#40;HCV&#41; is a worldwide health problem with more than 170 million infected individuals&#46; In children&#44; since 1992 almost all infections occurred through vertical transmission from an infected mother to her newborn infant&#46; Natural history of HCV infection in children is not yet well defined&#44; most children are asymptomatic and may remain so for decades&#46; Most infected individuals &#40;60-80&#37;&#41;&#44; regardless of their age at infection&#44; become chronically infected with HCV&#46; Spontaneous resolution in children appears to be infrequent&#46; Positive HCV antibody implicate that patient has been exposed to the virus &#40;EIA test&#41;&#46; To discriminate between active or resolved HCV viral infection it is necessary to perform HCV RNA &#40;PCR&#41;&#46; Liver biopsy assess degree of liver injury and exclude concurrent diseases&#46; HCV chronic infection is slow progressive in childhood&#46; Progression of fibrosis seems to be a function of infection duration&#46; Treatment objective is clearance of HCVRNA&#46; IFN&#945; is recognized as the drug approved for hepatitis C treatment in pediatric population&#46; Combination therapy with IFN&#945; or pegylated IFN&#945; plus ribavirin is recently approved by US FDA and EMEA and clinical trials are in progress&#46;</p></span>"
      ]
    ]
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        "identificador" => "t0005"
        "etiqueta" => "<span class="elsevierStyleBold">Table 1&#46;</span>"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:3 [
          "leyenda" => "<p id="np0005" class="elsevierStyleSimplePara elsevierViewall">HCV &#61; hepatitis C virus&#59; IFN &#61; interferon&#59; PEGIFN &#61; pegylated interferon&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="middle" scope="col">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="middle" scope="col">Sustained response<a class="elsevierStyleCrossRef" href="#t1fn2">&#42;&#42;</a> &#40;&#37;&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">N&#176; Studied<a class="elsevierStyleCrossRef" href="#t1fn1">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">Treatment regimen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">All Types&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">HCV type 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">HCV type 2&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Gonz&#225;lez-Peralta&#44; <span class="elsevierStyleBold"><span class="elsevierStyleItalic">et al&#46;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">IFN-ribavirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Strickland&#44; <span class="elsevierStyleBold"><span class="elsevierStyleItalic">et al&#46;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">IFN-ribavirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">N&#47;A <a class="elsevierStyleCrossRef" href="#t1fn3">&#42;&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Bruix and Sherman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">IFN-ribavirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Peters and Terrault&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">118&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">IFN-ribavirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Sasaki&#44; <span class="elsevierStyleBold"><span class="elsevierStyleItalic">et al&#46;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PEGIFN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">Ni&#44; <span class="elsevierStyleBold"><span class="elsevierStyleItalic">et al&#46;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">PEGIFN-ribavirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="middle">lorio&#44; <span class="elsevierStyleBold"><span class="elsevierStyleItalic">et al&#46;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="middle">PEGIFN-ribavirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="middle">50&nbsp;\t\t\t\t\t\t\n
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Article information
ISSN: 16652681
Original language: English
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos