Perihepatic lymphadenopathy in children with chronic viral hepatitis
Identifieur interne : 004156 ( Pmc/Corpus ); précédent : 004155; suivant : 004157Perihepatic lymphadenopathy in children with chronic viral hepatitis
Auteurs : Dagmar Schreiber-Dietrich ; Margret Pohl ; Xin-Wu Cui ; Barbara Braden ; Christoph F. Dietrich ; Liliana ChioreanSource :
- Journal of Ultrasonography [ 2084-8404 ] ; 2015.
Abstract
To assess whether lymph node enlargement in the hepatoduodenal ligament occurs in children with chronic viral hepatitis B and C in comparison to healthy controls.
In 49 patients with chronic viral hepatitis (38 with chronic hepatitis B, 11 with chronic hepatitis C, 31 male, 18 female; age range 1 to 17 years), and in 51 healthy controls (25 male, 26 female; age range 4 to 16 years), the total perihepatic lymph node volume was assessed using transabdominal ultrasonography as previously described in adult patients.
Adequate visualization of the liver hilum was achieved in 46/49 (94%) pediatric patients with chronic viral hepatitis and in 46/51 (90%) pediatric healthy controls. In patients with adequate liver hilum visualization, enlarged perihepatic lymph nodes (longitudinal diameter >14 mm) were detected in 32/46 (70%) patients with chronic viral hepatitis and in 5/46 (11%) healthy controls. The total perihepatic lymph nodes volume [mean ± SD] was 1.0 ± 1.2 mL (0.1–5.4 mL) in patients with chronic viral hepatitis and 0.1 ± 0.1 mL (0.0–0.4 mL) in healthy controls (
Transabdominal ultrasound can detect lymph nodes within the hepatoduodenal ligament not only in adults but also in children. Paediatric patients with chronic viral hepatitis have significantly enlarged perihepatic lymph nodes compared to controls. Therefore, sonographic assessment of perihepatic lymphadenopathy might be a non-invasive diagnostic tool to screen paediatric patients for chronic viral hepatitis.
Url:
DOI: 10.15557/JoU.2015.0012
PubMed: 26676184
PubMed Central: 4579752
Links to Exploration step
PMC:4579752Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Perihepatic lymphadenopathy in children with chronic viral hepatitis</title><author><name sortKey="Schreiber Dietrich, Dagmar" sort="Schreiber Dietrich, Dagmar" uniqKey="Schreiber Dietrich D" first="Dagmar" last="Schreiber-Dietrich">Dagmar Schreiber-Dietrich</name><affiliation><nlm:aff id="AF0001">Innere Medizin 2, Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany</nlm:aff></affiliation></author><author><name sortKey="Pohl, Margret" sort="Pohl, Margret" uniqKey="Pohl M" first="Margret" last="Pohl">Margret Pohl</name><affiliation><nlm:aff id="AF0003">Zentrum der Kinderheilkunde Abteilung für Kindergastroenterologie und Mukoviszidose, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany</nlm:aff></affiliation></author><author><name sortKey="Cui, Xin Wu" sort="Cui, Xin Wu" uniqKey="Cui X" first="Xin-Wu" last="Cui">Xin-Wu Cui</name><affiliation><nlm:aff id="AF0001">Innere Medizin 2, Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany</nlm:aff></affiliation></author><author><name sortKey="Braden, Barbara" sort="Braden, Barbara" uniqKey="Braden B" first="Barbara" last="Braden">Barbara Braden</name><affiliation><nlm:aff id="AF0004">Translational Gastroenterology Unit, Oxford University Hospitals, Headley Way, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Dietrich, Christoph F" sort="Dietrich, Christoph F" uniqKey="Dietrich C" first="Christoph F." last="Dietrich">Christoph F. Dietrich</name><affiliation><nlm:aff id="AF0001">Innere Medizin 2, Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany</nlm:aff></affiliation></author><author><name sortKey="Chiorean, Liliana" sort="Chiorean, Liliana" uniqKey="Chiorean L" first="Liliana" last="Chiorean">Liliana Chiorean</name><affiliation><nlm:aff id="AF0001">Innere Medizin 2, Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="AF0005">Département d'imagerie médicale, Clinique des Cévennes, Annonay, France</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26676184</idno><idno type="pmc">4579752</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579752</idno><idno type="RBID">PMC:4579752</idno><idno type="doi">10.15557/JoU.2015.0012</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">004156</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004156</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Perihepatic lymphadenopathy in children with chronic viral hepatitis</title><author><name sortKey="Schreiber Dietrich, Dagmar" sort="Schreiber Dietrich, Dagmar" uniqKey="Schreiber Dietrich D" first="Dagmar" last="Schreiber-Dietrich">Dagmar Schreiber-Dietrich</name><affiliation><nlm:aff id="AF0001">Innere Medizin 2, Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany</nlm:aff></affiliation></author><author><name sortKey="Pohl, Margret" sort="Pohl, Margret" uniqKey="Pohl M" first="Margret" last="Pohl">Margret Pohl</name><affiliation><nlm:aff id="AF0003">Zentrum der Kinderheilkunde Abteilung für Kindergastroenterologie und Mukoviszidose, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany</nlm:aff></affiliation></author><author><name sortKey="Cui, Xin Wu" sort="Cui, Xin Wu" uniqKey="Cui X" first="Xin-Wu" last="Cui">Xin-Wu Cui</name><affiliation><nlm:aff id="AF0001">Innere Medizin 2, Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany</nlm:aff></affiliation></author><author><name sortKey="Braden, Barbara" sort="Braden, Barbara" uniqKey="Braden B" first="Barbara" last="Braden">Barbara Braden</name><affiliation><nlm:aff id="AF0004">Translational Gastroenterology Unit, Oxford University Hospitals, Headley Way, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Dietrich, Christoph F" sort="Dietrich, Christoph F" uniqKey="Dietrich C" first="Christoph F." last="Dietrich">Christoph F. Dietrich</name><affiliation><nlm:aff id="AF0001">Innere Medizin 2, Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="AF0002">Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany</nlm:aff></affiliation></author><author><name sortKey="Chiorean, Liliana" sort="Chiorean, Liliana" uniqKey="Chiorean L" first="Liliana" last="Chiorean">Liliana Chiorean</name><affiliation><nlm:aff id="AF0001">Innere Medizin 2, Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="AF0005">Département d'imagerie médicale, Clinique des Cévennes, Annonay, France</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Ultrasonography</title><idno type="ISSN">2084-8404</idno><idno type="eISSN">2451-070X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="st1"><title>Objective</title><p>To assess whether lymph node enlargement in the hepatoduodenal ligament occurs in children with chronic viral hepatitis B and C in comparison to healthy controls.</p></sec><sec id="st2"><title>Subject and methods</title><p>In 49 patients with chronic viral hepatitis (38 with chronic hepatitis B, 11 with chronic hepatitis C, 31 male, 18 female; age range 1 to 17 years), and in 51 healthy controls (25 male, 26 female; age range 4 to 16 years), the total perihepatic lymph node volume was assessed using transabdominal ultrasonography as previously described in adult patients.</p></sec><sec id="st3"><title>Results</title><p>Adequate visualization of the liver hilum was achieved in 46/49 (94%) pediatric patients with chronic viral hepatitis and in 46/51 (90%) pediatric healthy controls. In patients with adequate liver hilum visualization, enlarged perihepatic lymph nodes (longitudinal diameter >14 mm) were detected in 32/46 (70%) patients with chronic viral hepatitis and in 5/46 (11%) healthy controls. The total perihepatic lymph nodes volume [mean ± SD] was 1.0 ± 1.2 mL (0.1–5.4 mL) in patients with chronic viral hepatitis and 0.1 ± 0.1 mL (0.0–0.4 mL) in healthy controls (<italic>p</italic> < 0.05). A maximal lymph node diameter >14 mm identified patients with chronic viral hepatitis with 70% sensitivity and 89% specificity.</p></sec><sec id="st4"><title>Conclusion</title><p>Transabdominal ultrasound can detect lymph nodes within the hepatoduodenal ligament not only in adults but also in children. Paediatric patients with chronic viral hepatitis have significantly enlarged perihepatic lymph nodes compared to controls. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Ultrason</journal-id><journal-id journal-id-type="iso-abbrev">J Ultrason</journal-id><journal-id journal-id-type="publisher-id">JoU</journal-id><journal-title-group><journal-title>Journal of Ultrasonography</journal-title></journal-title-group><issn pub-type="ppub">2084-8404</issn><issn pub-type="epub">2451-070X</issn><publisher><publisher-name>Medical Communications Sp. z o.o.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26676184</article-id><article-id pub-id-type="pmc">4579752</article-id><article-id pub-id-type="publisher-id">0012</article-id><article-id pub-id-type="doi">10.15557/JoU.2015.0012</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Paper</subject></subj-group></article-categories><title-group><article-title>Perihepatic lymphadenopathy in children with chronic viral hepatitis</article-title><trans-title-group xml:lang="pl"><trans-title>Limfadenopatia węzłów chłonnych wątrobowych u dzieci z przewlekłym wirusowym zapaleniem wątroby</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name><surname>Schreiber-Dietrich</surname><given-names>Dagmar</given-names></name><xref ref-type="aff" rid="AF0001">1</xref><xref ref-type="aff" rid="AF0002">2</xref></contrib><contrib contrib-type="author"><name><surname>Pohl</surname><given-names>Margret</given-names></name><xref ref-type="aff" rid="AF0003">3</xref></contrib><contrib contrib-type="author"><name><surname>Cui</surname><given-names>Xin-Wu</given-names></name><xref ref-type="aff" rid="AF0001">1</xref></contrib><contrib contrib-type="author"><name><surname>Braden</surname><given-names>Barbara</given-names></name><xref ref-type="aff" rid="AF0004">4</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Dietrich</surname><given-names>Christoph F.</given-names></name><xref ref-type="aff" rid="AF0001">1</xref><xref ref-type="aff" rid="AF0002">2</xref></contrib><contrib contrib-type="author"><name><surname>Chiorean</surname><given-names>Liliana</given-names></name><xref ref-type="aff" rid="AF0001">1</xref><xref ref-type="aff" rid="AF0005">5</xref></contrib></contrib-group><aff id="AF0001"><label>1</label>Innere Medizin 2, Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany</aff><aff id="AF0002"><label>2</label>Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany</aff><aff id="AF0003"><label>3</label>Zentrum der Kinderheilkunde Abteilung für Kindergastroenterologie und Mukoviszidose, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany</aff><aff id="AF0004"><label>4</label>Translational Gastroenterology Unit, Oxford University Hospitals, Headley Way, Oxford, UK</aff><aff id="AF0005"><label>5</label>Département d'imagerie médicale, Clinique des Cévennes, Annonay, France</aff><author-notes><corresp id="cor1">Correspondence: Prof. Christoph F. Dietrich, MD, PhD, Innere Medizin 2, Caritas Krankenhaus, Uhlandstr. 7, D-97980 Bad Mergentheim, Germany. tel.: 49 7931 58 2201, fax: 49 7931 58 2290. e-mail: <email xlink:href="christoph.dietrich@ckbm.de">christoph.dietrich@ckbm.de</email></corresp></author-notes><pub-date pub-type="epub"><day>30</day><month>6</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>6</month><year>2015</year></pub-date><volume>15</volume><issue>61</issue><fpage>137</fpage><lpage>150</lpage><history><date date-type="received"><day>04</day><month>2</month><year>2015</year></date><date date-type="rev-recd"><day>01</day><month>4</month><year>2015</year></date><date date-type="accepted"><day>21</day><month>4</month><year>2015</year></date></history><permissions><copyright-statement>2015 Polish Ultrasound Society. Published by Medical Communications Sp. z o.o. All rights reserved.</copyright-statement><copyright-year>2015</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-nd"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (CC BY-NC-ND). Reproduction is permitted for personal, educational, non-commercial use, provided that the original article is in whole, unmodified, and properly cited.</license-p></license></permissions><abstract><sec id="st1"><title>Objective</title><p>To assess whether lymph node enlargement in the hepatoduodenal ligament occurs in children with chronic viral hepatitis B and C in comparison to healthy controls.</p></sec><sec id="st2"><title>Subject and methods</title><p>In 49 patients with chronic viral hepatitis (38 with chronic hepatitis B, 11 with chronic hepatitis C, 31 male, 18 female; age range 1 to 17 years), and in 51 healthy controls (25 male, 26 female; age range 4 to 16 years), the total perihepatic lymph node volume was assessed using transabdominal ultrasonography as previously described in adult patients.</p></sec><sec id="st3"><title>Results</title><p>Adequate visualization of the liver hilum was achieved in 46/49 (94%) pediatric patients with chronic viral hepatitis and in 46/51 (90%) pediatric healthy controls. In patients with adequate liver hilum visualization, enlarged perihepatic lymph nodes (longitudinal diameter >14 mm) were detected in 32/46 (70%) patients with chronic viral hepatitis and in 5/46 (11%) healthy controls. The total perihepatic lymph nodes volume [mean ± SD] was 1.0 ± 1.2 mL (0.1–5.4 mL) in patients with chronic viral hepatitis and 0.1 ± 0.1 mL (0.0–0.4 mL) in healthy controls (<italic>p</italic> < 0.05). A maximal lymph node diameter >14 mm identified patients with chronic viral hepatitis with 70% sensitivity and 89% specificity.</p></sec><sec id="st4"><title>Conclusion</title><p>Transabdominal ultrasound can detect lymph nodes within the hepatoduodenal ligament not only in adults but also in children. Paediatric patients with chronic viral hepatitis have significantly enlarged perihepatic lymph nodes compared to controls. Therefore, sonographic assessment of perihepatic lymphadenopathy might be a non-invasive diagnostic tool to screen paediatric patients for chronic viral hepatitis.</p></sec></abstract><trans-abstract xml:lang="pl"><sec id="st5"><title>Cel</title><p>Celem pracy była ocena występowania powiększonych węzłów chłonnych więzadła wątrobowo-dwunastniczego u dzieci z przewlekłym wirusowym zapaleniem wątroby typu B i C w porównaniu ze zdrową grupą kontrolną.</p></sec><sec id="st6"><title>Pacjenci i metoda</title><p>Objętość całkowitą węzłów chłonnych wątrobowych zbadano u 49 pacjentów z przewlekłym wirusowym zapaleniem wątroby (38 z przewlekłym wirusowym zapaleniem wątroby typu B, 11 z przewlekłym wirusowym zapaleniem wątroby typu C; 31 chłopców, 18 dziewcząt; wiek pacjentów od 1 do 17 lat) oraz u zdrowych dzieci stanowiących grupę kontrolną (25 chłopców, 26 dziewcząt; wiek od 4 do 16 lat) za pomocą ultrasonografii jamy brzusznej, zgodnie z poprzednim opisem dotyczącym dorosłych pacjentów.</p></sec><sec id="st7"><title>Wyniki</title><p>Poprawną wizualizację wnęki wątroby uzyskano u 46/49 (94%) dzieci z przewlekłym wirusowym zapaleniem wątroby oraz u 46/51 (90%) zdrowych dzieci z grupy kontrolnej. Wśród tych pacjentów powiększone węzły chłonne wątrobowe (o wymiarze podłużnym >14 mm) wykryto u 32/46 (70%) pacjentów z przewlekłym zapaleniem wątroby oraz 5/46 (11%) zdrowych dzieci z grupy kontrolnej. Objętość całkowita węzłów chłonnych wątrobowych (średnia ± SD) u pacjentów z przewlekłym wirusowym zapaleniem wątroby wynosiła 1,0 ± 1,2 ml (0,1–5,4 ml), natomiast w grupie kontrolnej 0,1 ± 0,1 ml (0,0–0,4 ml) (p < 0,05). Na podstawie maksymalnej średnicy węzłów chłonnych wynoszącej >14 mm zidentyfikowano pacjentów z przewlekłym wirusowym zapaleniem wątroby z czułością 70% i swoistością 89%.</p></sec><sec id="st8"><title>Wnioski</title><p>Badanie ultrasonograficzne jamy brzusznej pozwala na wykrycie węzłów chłonnych w obrębie więzadła wątrobowo-dwunastniczego nie tylko u osób dorosłych, ale również u dzieci. U dzieci z przewlekłym wirusowym zapaleniem wątroby występują znacznie powiększone węzły chłonne wątrobowe w porównaniu z grupą kontrolną. W związku z tym ocena ultrasonograficzna powiększenia węzłów chłonnych wątroby może stanowić nieinwazyjne narzędzie diagnostyczne do badań przesiewowych dzieci w kierunku przewlekłego wirusowego zapalenia wątroby.</p></sec></trans-abstract><kwd-group><kwd>ultrasonography</kwd><kwd>lymphadenopathy</kwd><kwd>chronic hepatitis</kwd><kwd>liver hilum</kwd><kwd>pediatric</kwd></kwd-group></article-meta></front><body><sec sec-type="intro" id="S0001"><title>Introduction</title><p>The clinical value of transabdominal ultrasound (TUS) in the detection of perihepatic lymph nodes (LNs) in adult patients is well established<sup>(<xref rid="CIT0001" ref-type="bibr">1</xref>–<xref rid="CIT0006" ref-type="bibr">6</xref>)</sup>. Normal or enlarged LNs in the liver hilum can be identified by TUS between the inferior vena cava and the portal vein, just next to the right renal artery<sup>(<xref rid="CIT0007" ref-type="bibr">7</xref>)</sup>. Since inflammatory processes in organs frequently lead to hyperpla sia of regional LNs<sup>(<xref rid="CIT0008" ref-type="bibr">8</xref>–<xref rid="CIT0011" ref-type="bibr">11</xref>)</sup>, LN enlargement within the hepatoduodenal ligament is present in patients with acute or chronic liver disease. Enlarged perihepatic LNs have been detected in patients with chronic viral hepatitis B (CHB)<sup>(<xref rid="CIT0002" ref-type="bibr">2</xref>, <xref rid="CIT0012" ref-type="bibr">12</xref>)</sup>, chronic viral hepatitis C (CHC)<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>, <xref rid="CIT0013" ref-type="bibr">13</xref>–<xref rid="CIT0016" ref-type="bibr">16</xref>)</sup>, primary biliary cirrhosis<sup>(<xref rid="CIT0006" ref-type="bibr">6</xref>, <xref rid="CIT0017" ref-type="bibr">17</xref>)</sup> and primary slcerosing cholangitis<sup>(<xref rid="CIT0018" ref-type="bibr">18</xref>)</sup>. The total perihepatic LN volume (LNV) is associated with viremia and liver histology in adult patients with CHC<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>, <xref rid="CIT0019" ref-type="bibr">19</xref>)</sup>. It changes with progressive normalization according to the antiviral response and the liver histology improvement<sup>(<xref rid="CIT0016" ref-type="bibr">16</xref>)</sup>. The LNV reflects progression of disease in primary biliary cirrhosis<sup>(<xref rid="CIT0006" ref-type="bibr">6</xref>)</sup>. In patients with perihepatic lymphadenopathy of unknown origin malignant diseases have to be ruled out.</p><p>Previous studies reported that adequate sonographic visualization of the liver hilum can be achieved in more than 90% of adult patients and LNs in the hepatoduodenal ligament can noninvasively be assessed<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>, <xref rid="CIT0016" ref-type="bibr">16</xref>)</sup>. The method used has been validated in postmortem examinations, healthy subjects and patients with inflammatory liver disease<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>, <xref rid="CIT0005" ref-type="bibr">5</xref>)</sup>. Furthermore, validation for correct sonographic detection of perihepatic LNs (location and size) was obtained in patients undergoing elective abdominal surgery. The predicted size by TUS revealed a high correlation with the anatomical size which was assessed after excision of the LNs (<italic>r</italic> = 0.94 for examination during autopsy)<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>)</sup>. The reproducibility of the method was also previously investigated by our team by repeated TUS examinations of the LNs in the hepatoduodenal ligament in 10 healthy subjects for 7 consecutive days. The mean coefficient of variation for intraindividual assessment of LNV was 12%<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>)</sup>.</p><p>In healthy children, TUS has been reported to occasionally detect small LNs around the portal vein, with the largest diameter up to 10 mm<sup>(<xref rid="CIT0020" ref-type="bibr">20</xref>)</sup>. Still little is known about TUS findings in children with chronic viral hepatitis (CVH), even if hepatitis B and C viral infections are the most common causes of CVH and liver cirrhosis in older children in Europe<sup>(<xref rid="CIT0021" ref-type="bibr">21</xref>–<xref rid="CIT0028" ref-type="bibr">28</xref>)</sup><bold></bold>. In contrast to adult patients, portal lymphadenopathy has not been systematically examined in children with CVH in comparison to healthy controls (HC).</p><p>In the present, prospective, controlled study, therefore, we investigated detection rate and size of LNs (expressed as LNV) within the hepatoduodenal ligament in children with CHB and CHC, and healthy subjects serving as controls.</p></sec><sec id="S0002"><title>Patients and methods</title><sec id="S20003"><title>Patients and controls</title><p>49 consecutive pediatric patients with CVH attending our gastroenterology outpatient clinic and 51 HC were primarily enrolled into the present study. The epidemiological data are summarized in <xref ref-type="table" rid="T0001">Table 1</xref>.
</p><table-wrap id="T0001" position="float"><label>Tab. 1</label><caption><p>Demographic, Biochemical, and Serological Profile of Patients with Chronic Virus Hepatitis (CVH) and Healthy Controls (HC)</p></caption><table frame="border" rules="all"><thead><tr><th align="left" rowspan="1" colspan="1">Characteristics</th><th align="center" rowspan="1" colspan="1">CVH</th><th align="center" rowspan="1" colspan="1">HC</th></tr></thead><tbody><tr><td align="left" colspan="3" rowspan="1">Demography</td></tr><tr><td align="left" rowspan="1" colspan="1"> No (M/F)</td><td align="center" rowspan="1" colspan="1">49 (31/18)</td><td align="center" rowspan="1" colspan="1">51 (25/26)</td></tr><tr><td align="left" rowspan="1" colspan="1"> Mean age (yr)<xref ref-type="table-fn" rid="TF0001">*</xref></td><td align="center" rowspan="1" colspan="1">12 ± 3.8 (1–17)</td><td align="center" rowspan="1" colspan="1">12 ± 2.8 (4–16)</td></tr><tr><td colspan="3" align="left" rowspan="1">Biochemistry<xref ref-type="table-fn" rid="TF0001">*</xref></td></tr><tr><td align="left" rowspan="1" colspan="1"> Alanine aminotransferase (U/L)</td><td align="center" rowspan="1" colspan="1">30 ± 24.3 (10–152)</td><td align="center" rowspan="1" colspan="1">-</td></tr><tr><td align="left" rowspan="1" colspan="1"> Aspartate aminotransferase (U/L)</td><td align="center" rowspan="1" colspan="1">15.9 ± 8.8 (5–53)</td><td align="center" rowspan="1" colspan="1">-</td></tr><tr><td align="left" rowspan="1" colspan="1"> γ-Glutamyl transpeptidase (U/L)</td><td align="center" rowspan="1" colspan="1">12.7 ± 5.2 (6–30)</td><td align="center" rowspan="1" colspan="1">-</td></tr><tr><td align="left" rowspan="1" colspan="1"> Bilirubin (mg/dL)</td><td align="center" rowspan="1" colspan="1">0.5 ± 0.4 (0.1–2)</td><td align="center" rowspan="1" colspan="1">-</td></tr><tr><td colspan="3" align="left" rowspan="1">Serology</td></tr><tr><td align="left" rowspan="1" colspan="1"> HBV-DNA positive</td><td align="center" rowspan="1" colspan="1">38/49 (77.5%)</td><td align="center" rowspan="1" colspan="1">0/51 (0%)</td></tr><tr><td align="left" rowspan="1" colspan="1"> HCV-RNA positive</td><td align="center" rowspan="1" colspan="1">11/49 (22.5%)</td><td align="center" rowspan="1" colspan="1">0/51 (0%)</td></tr></tbody></table><table-wrap-foot><fn><p>Abbreviations: HBV-DNA, hepatitis B virus DNA; HCV-RNA, hepatitis C virus RNA.</p></fn><fn id="TF0001"><label>*</label><p>Mean ± SD (range).</p></fn></table-wrap-foot></table-wrap><p>Inclusion criteria were the diagnosis of CHC viral infection based on the consistent detection of serum hepatitis C virus RNA by reverse transcription-polymerase chain reaction assay for more than 6 months or the diagnosis of CHB viral infection based on the detection of serum hepatitis B virus DNA by reverse transcription-polymerase chain reaction assay for more than 6 months.</p><p>Other possible causes of perihepatic LN enlargement (e.g. acute hepatitis, autoimmune liver disease, including primary biliary cirrhosis, hereditary liver disease, and malignant diseases) were excluded by appropriate clinical, laboratory, and imaging investigations as recently described<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>)</sup>.</p><p>All HC had no complaints, liver function tests were within the normal range and chronic liver diseases (infectious, metabolic, toxic, autoimmune, and hereditary) were excluded by appropriate biochemical and serological tests.</p><p>Institutional board approval for the study and informed consent from parents/legal tutors were obtained in all patients and HC.</p></sec><sec id="S20004" sec-type="methods"><title>Methods</title><sec><title>Detection of lymph nodes in the hepatoduodenal ligament by transabdominal sonography</title><p>In all patients and HC the number and size [the long (a) and the short (b) diameters] of all detectable perihepatic LNs were determined as previously described for adult patients<sup>(<xref rid="CIT0001" ref-type="bibr">1</xref>)</sup>. The individual LN volume was calculated assuming a (rotating) ellipsoid [volume = (a/2) × (b/2)<xref rid="CIT0002" ref-type="bibr">2</xref> × (4/3) × π]<sup>(<xref rid="CIT0001" ref-type="bibr">1</xref>, <xref rid="CIT0002" ref-type="bibr">2</xref>, <xref rid="CIT0016" ref-type="bibr">16</xref>)</sup>. The volume of all individual LNs within the hepatoduodenal ligament were subsequently summarized and expressed as total perihepatic lymph node volume (LNV).</p><p>Perihepatic LNs of all patients and controls were assessed by the same experienced investigator (CFD), who was blinded to patients’ data at time of examination. All US examinations were performed with a 3.5 MHz probe using high resolution B-mode scanner (Siemens Elegra, Siemens, Erlangen, Germany or Acuson Sequoia, Siemens, Erlangen, Germany).</p><p>A sonographically definite diagnosis of LNs in the hepatoduodenal ligament is possible only if the size is more than 5 mm, as previously reported<sup>(<xref rid="CIT0029" ref-type="bibr">29</xref>)</sup>; therefore we included only LNs of 5 mm or more in size. Lymphadenopathy was defined as a longitudinal LN diameter >14 mm, value found to be the best cut-off by receiver operator curve analysis.</p></sec><sec><title>Serological and molecular laboratory tests</title><p>Testing for anti-hepatitis C virus antibodies (2<sup>nd</sup> generation), hepatitis B surface antigen, hepatitis B core antibodies or anti-human immunodefiency virus antibodies 1 and 2 were performed using commercially available enzyme-linked immunosorbent assays.</p></sec><sec><title>Statistical analysis</title><p>Demographic, clinical and sonographic characteristics of patients were expressed as mean SD. Students <italic>t</italic> test was used to compare the LN volume between CVH/CHB/CHC and HC. The distribution of the variables was checked and the variables were normally distributed. Chi-square test was applied to compare the percentage of visible liver hilum, detectable hilar LNs and perihepatic lymphadenopathy between CVH/CHB/CHC and HC (<italic>p</italic> < 0.05 was judged to be statistically significant). LNs with more than 14 mm in length were considered pathologically enlarged.</p></sec></sec></sec><sec sec-type="results" id="S0008"><title>Results</title><p>In the present study, we investigated 49 consecutive patients with CVH and 51 HC. The clinical, biochemical, and serological characteristics of patients are summarized in <xref ref-type="table" rid="T0001">Table 1</xref>. Even young children <4 years tolerated the ultrasound investigation of the liver hilum well without sedation.</p><p>Adequate visualization of the liver hilum was obtained in 46/49 (94%) CVH patients, and in 46/51 (90%) HC. In subjects with adequate visualization of the liver hilum, LNs within the hepatoduodenal ligament were detectable in all 46/46 (100%) patients with CVH, and in 41/46 (89%) of the HC. Representative examples for sonographic visualization of LNs within the hepatoduodenal ligament are shown in <xref ref-type="fig" rid="F0001">Fig. 1 A, B</xref>. Lymphadenopathy, defined as >14 mm in the longitudinal diameter was detectable in 32/46 patients with CVH, and in 5/46 HC. Values for sensitivity, specificity, positive and negative predictive values, and accuracy for sonographically detection of enlarged LNs within the hepatoduodenal ligament in CVH patients were of 70%, 89%, 86%, 75%, and 79%, respectively.</p><fig id="F0001" position="float"><label>Fig. 1</label><caption><p>Transabdominal image of perihepatic lymph nodes (LN or LK) in a patient with chronic viral hepatitis C [conventional B-mode (<bold>A</bold>) and Colour Doppler imaging (<bold>B</bold>)]. Liver (L), pancreatic head (PH), portal vein (PV), and renal arteries (RA, NA1, NA2) are also indicated. Arrow: hepatic artery</p></caption><graphic xlink:href="JoU-2015-0012-g001"></graphic></fig><p>The total perihepatic LN volume (LNV) was calculated in each subject as sum of each detected LN volume. The mean LNV was 1.0 ± 1.2 mL (0.1–5.4 mL) in patients and 0.1 ± 0.1 mL (0.0–0.4 mL) in controls. In patients with CHB, mean LNV was 0.87 ± 1.19 mL (0.08–5.41 mL), while in patients with CHC it was 1.43 ± 1.19 mL (0.06–3.28 mL). In patients with CVH, the mean total volume values were significantly higher than in healthy subjects (<italic>p</italic> < 0.05). The LNV in CHB and CHC patients did not differ significantly (<italic>p</italic> = 0.23). <xref ref-type="table" rid="T0002">Table 2</xref> presents the sonographic findings in patients with CVH and HC.
</p><table-wrap id="T0002" position="float"><label>Tab. 2</label><caption><p>Sonographic findings in children with chronic hepatitis B and C and in healthy controls</p></caption><table frame="border" rules="all"><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="center" rowspan="1" colspan="1">Liver Hilum Visible</th><th align="center" rowspan="1" colspan="1">Hilar LNs Detectable</th><th align="center" rowspan="1" colspan="1">No. of Hilar LNs Detected<xref ref-type="table-fn" rid="TF0002">*</xref></th><th align="center" rowspan="1" colspan="1">Perihepatic Lymphadenopathy</th><th align="center" rowspan="1" colspan="1">Total LNs Volume (mL)<xref ref-type="table-fn" rid="TF0002">*</xref></th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Healthy controls</td><td align="center" rowspan="1" colspan="1">46/51 (90%)</td><td align="center" rowspan="1" colspan="1">41/46 (89%)</td><td align="center" rowspan="1" colspan="1">1.3 ± 0.9 [0–4]</td><td align="center" rowspan="1" colspan="1">5/46 (11%)</td><td align="center" rowspan="1" colspan="1">0.1 ± 0.1 mL (0.0–0.4 mL)</td></tr><tr><td align="left" rowspan="1" colspan="1">Chronic virus hepatitis</td><td align="center" rowspan="1" colspan="1">46/49 (94%)</td><td align="center" rowspan="1" colspan="1">46/46 (100%)</td><td align="center" rowspan="1" colspan="1">3.1 ± 1.8 [1–7]</td><td align="center" rowspan="1" colspan="1">32/46 (70%)<xref ref-type="table-fn" rid="TF0003">¤</xref></td><td align="center" rowspan="1" colspan="1">1.0 ± 1.2 mL (0.1–5.4 mL)<xref ref-type="table-fn" rid="TF0003">¤</xref></td></tr><tr><td align="left" rowspan="1" colspan="1">Cronic virus hepatitis B</td><td align="center" rowspan="1" colspan="1">36/38 (95%)</td><td align="center" rowspan="1" colspan="1">36/36 (100%)</td><td align="center" rowspan="1" colspan="1">2.9 ± 1.7 [1–7]</td><td align="center" rowspan="1" colspan="1">25/36 (69%)<xref ref-type="table-fn" rid="TF0003">¤</xref></td><td align="center" rowspan="1" colspan="1">0.87 ± 1.19 mL (0.08–5.41 mL)<xref ref-type="table-fn" rid="TF0003">¤</xref></td></tr><tr><td align="left" rowspan="1" colspan="1">Cronic virus hepatitis C</td><td align="center" rowspan="1" colspan="1">10/11 (91%)</td><td align="center" rowspan="1" colspan="1">10/10 (100%)</td><td align="center" rowspan="1" colspan="1">3.7 ± 2.2 [1–7]</td><td align="center" rowspan="1" colspan="1">7/10 (70%)<xref ref-type="table-fn" rid="TF0003">¤</xref></td><td align="center" rowspan="1" colspan="1">1.43 ± 1.19 mL (0.06–3.28 mL)<xref ref-type="table-fn" rid="TF0003">¤</xref></td></tr></tbody></table><table-wrap-foot><fn id="TF0002"><label>*</label><p>Mean ± SD (range)</p></fn><fn id="TF0003"><label>¤</label><p>statistically different from healthy control.</p></fn></table-wrap-foot></table-wrap><sec id="S20009"><title>Perihepatic lymph node analysis in healthy subjects</title><p>An adequate visualization of the liver hilum and adequate sonographic visualization of the hepatoduodenal ligament was achieved in 46/51 healthy subjects. In 41 healthy subjects, LNs were depictable. Mean (±SD) number of detected LNs was 1.43 ± 0.80 (0–4). The largest size of detected LNs was 17 × 5 mm (0.2 mL). No healthy person has had more than two detectable LNs in the ventral and dorsal hepatoduodenal ligament, respectively.</p></sec><sec id="S20010"><title>Lymph node analysis in patients with chronic virus hepatitis B</title><p>Of the 49 patients with CVH, 38 patients had CHB. In 36/38 (95%) of the CHB patients, adequate visualization of the liver hilum and adequate sonographic visualization of the hepatoduodenal ligament was achieved. In 36/36 (100%) of patients with CHB and adequate visualization of the liver hilum, perihepatic LNs were detectable. The largest size of the detected LNs was 35 × 14 mm (3.6 mL). The largest number of detected LNs in the ventral and dorsal hepatoduodenal ligament was <italic>n</italic> = 7 in one patient. Perihepatic lymphadenopathy was found in 25/36 (69%) CHB patients. The total perihepatic LN volume was 0.87 ± 1.19 mL (0.08–5.41 mL). Values for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for sonographically detection of enlarged LNs within the hepatoduodenal ligament in CHB patients were of 69%, 89%, 83%, 79%, and 80%, respectively.</p></sec><sec id="S20011"><title>Lymph node analysis in patients with chronic virus hepatitis C</title><p>Of the 49 patients with CVH, 11 patients had CHC. In 10/11 (91%) of the CHC patients, adequate visualization of the liver hilum and adequate sonographic visualization of the hepatoduodenal ligament was achieved. In 10/10 (100%) of patients with CHC and adequate visualization of the liver hilum, perihepatic LNs were detectable. The largest size of the detected LN was 32 × 10 mm (1.7 mL). The largest number of detected LNs at the level of the hepatoduodenal ligament was 7 in one patient. Perihepatic lymphadenopathy was found in 7/10 CHC patients (70%). The total perihepatic LN volume was 1.43 ± 1.19 mL (0.06–3.28 mL). Values for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for sonographically detection of enlarged LNs within the hepatoduodenal ligament in CHC patients were of 70%, 89%, 58%, 93%, and 86%, respectively.</p></sec><sec id="S20012"><title>Lymph node analysis in patients with chronic virus hepatitis B and C</title><p>An adequate visualization of the liver hilum and adequate sonographic visualization of the hepatoduodenal ligament was achieved in 46/49 (94%) patients with CVH (CHB and CHC). In all patients with adequate liver hilum visualization, perihepatic LNs were detectable. The largest size of the detected LNs was 35 × 14 mm (3.6 mL) seen in a patient with CHB. The largest number of detected LNs at the level of the hepatoduodenal ligament was <italic>n</italic> = 7 (one patient with CHB, and one patient with CHC). In 32/46 (70%) patients with CVH and adequate visualization of the liver hilum perihepatic lymphadenopathy was found, whereas only 5/46 (11%) of the HC with adequate liver hilum visualization revealed lymphadenopathy. Total lymph node volume in CVH patients was 1.0 ± 1.2 mL (0.1–5.4 mL). Values for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for sonographically detection of enlarged LNs within the hepatoduodenal ligament in CVH patients were of 70%, 89%, 86%, 75%, and 79%, respectively.</p></sec></sec><sec sec-type="discussion" id="S0013"><title>Discussion</title><p>Studies in adults have proved that TUS technology enables accurate visualization, not only of enlarged, but also of normally sized perihepatic LNs within the hepatoduodenal ligament in healthy subjects as well as in patients with infectious, autoimmune, or neoplastic liver disease. The sonographic method in assessing the total perihepatic LN volume has been validated by TUS studies in patients undergoing elective surgery, and by postmortem examinations<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>)</sup>. However, the diagnostic importance of sonographically detectable perihepatic lymphadenopathy in pediatric patients with CVH has never been systematically evaluated. Even more, sonographically detection of perihepatic LNs in healthy children has previously been evaluated only by Toppet <italic>et al</italic>. The results of their study showed that in healthy children, TUS can occasionally detect small LNs around the portal vein, with the largest diameter of 7 to 10 mm<sup>(<xref rid="CIT0020" ref-type="bibr">20</xref>)</sup>. The data of the present study confirm that LNs within the hepatoduodenal ligament can readily be detected by TUS in healthy children and in children suffering from CVH.</p><sec id="S20014"><title>Lymph node analysis in healthy subjects</title><p>The range of normal sized LNs in the liver hilum is often defined for adults as longitudinal LN diameter up to 19 mm<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>, <xref rid="CIT0006" ref-type="bibr">6</xref>, <xref rid="CIT0016" ref-type="bibr">16</xref>, <xref rid="CIT0030" ref-type="bibr">30</xref>, <xref rid="CIT0031" ref-type="bibr">31</xref>)</sup>. In this study, we calculated the sensitivity and specificity of cut-off 10–17 mm, and found by receiver operator curve analysis that 14 mm is the best cut-off. Therefore, we have considered pathologically enlarged only LNs with a longitudinal diameter of more than 14 mm. In this report, normal sized LNs could be visualized in the liver hilum of healthy children in 89% of the cases.</p></sec><sec id="S20015"><title>Lymph node analysis in patients with chronic virus hepatitis B and C in comparison</title><p>As shown for adults we found a significant difference in lymph node volume between affected children compared to HC, with no significant difference between children suffering chronic viral hepatitis B and C. These data are in accordance with the literature<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>, <xref rid="CIT0006" ref-type="bibr">6</xref>)</sup>. Enlargement of these perihepatic LNs could be predictive for the presence of severe inflammatory activity, with and without cirrhosis, as for adults already published<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>)</sup>. Also, studies in adults with CHC have shown that the total perihepatic LN volume, sonographically determined, is related to liver histology and viral load<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>, <xref rid="CIT0016" ref-type="bibr">16</xref>, <xref rid="CIT0019" ref-type="bibr">19</xref>, <xref rid="CIT0032" ref-type="bibr">32</xref>)</sup>. Further studies should investigate whether successful antiviral therapy may result in a decline of perihepatic LN size together with histological improvement.</p></sec><sec id="S20016"><title>Mechanism</title><p>The mechanism of portal lymphadenopathy with CHC is unknown, but appears to be related to viral replication and the immune-mediated inflammatory response of the host. Recruitment of HCV-infected lymphocytes and/or macrophages into the draining LNs may be another contributing mechanism<sup>(<xref rid="CIT0032" ref-type="bibr">32</xref>)</sup>. Zheng <italic>et al</italic>. demonstrated in a recent experimental study that portal and celiac LNs are draining the mouse liver. Also, their study brought evidence that the liver-draining LNs induce an anti-HBV-specific immune response responsible for HBV clearance<sup>(<xref rid="CIT0033" ref-type="bibr">33</xref>)</sup>.</p><p>Because in the present study, no patients with severe portal hypertension were enrolled, impaired venous drainage of the perihepatic LNs appears unlikely as a relevant component of the LN enlargement. Lymphedema as a possible cause of perihepatic lymphadenopathy can be excluded, since lymphatic drainage of the liver is hepatofugal and most likely not influenced by architectural changes of the liver parenchyma<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>)</sup>.</p></sec><sec id="S20017"><title>The advantages of ultrasound (in general)</title><p>TUS is an important tool in the diagnosis and follow-up of large populations of patients, due to its favourable cost, availability, flexibility, real-time examination, and user friendliness<sup>(<xref rid="CIT0034" ref-type="bibr">34</xref>)</sup>. It stands out as the imaging method with highest temporal and spatial resolution, reasons why it is regarded as the first method of choice to evaluate LNs<sup>(<xref rid="CIT0029" ref-type="bibr">29</xref>, <xref rid="CIT0034" ref-type="bibr">34</xref>)</sup>. Ultrasound evaluation of LNs is an important method to detect pathological changes in nearly all body areas including the abdomen<sup>(<xref rid="CIT0035" ref-type="bibr">35</xref>, <xref rid="CIT0036" ref-type="bibr">36</xref>)</sup>. The currently possible LN detection rate by ultrasound is limited by a minimal required LN size which is between 5–10 mm<sup>(<xref rid="CIT0029" ref-type="bibr">29</xref>)</sup>. Ultrasound equipment may detect LNs in the hepatoduodenal ligament in healthy subjects<sup>(<xref rid="CIT0031" ref-type="bibr">31</xref>)</sup>. LNs are detectable within the hepatoduodenal ligament in almost all patients with CHB<sup>(<xref rid="CIT0012" ref-type="bibr">12</xref>, <xref rid="CIT0013" ref-type="bibr">13</xref>, <xref rid="CIT0032" ref-type="bibr">32</xref>)</sup> and CHC<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>, <xref rid="CIT0016" ref-type="bibr">16</xref>, <xref rid="CIT0032" ref-type="bibr">32</xref>, <xref rid="CIT0037" ref-type="bibr">37</xref>–<xref rid="CIT0039" ref-type="bibr">39</xref>)</sup> as shown by adult studies. In our study, LNs within the hepatoduodenal ligament have been detected in all paediatric patients with CVH and adequate liver hilum visualization. Also, in adults, LNs volume is related to liver histology and viremia, and may be predictive for the presence of severe inflammatory activity<sup>(<xref rid="CIT0004" ref-type="bibr">4</xref>, <xref rid="CIT0039" ref-type="bibr">39</xref>)</sup>. TUS, being a non-invasive technique, may be freely used for repeated follow-up examinations in children with CVH<sup>(<xref rid="CIT0001" ref-type="bibr">1</xref>)</sup>. Since European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPHAGAN) guidelines for management of children with CHB<sup>(<xref rid="CIT0022" ref-type="bibr">22</xref>)</sup> recommend hepatocellular carcinoma surveillance with liver ultrasound every 6–12 months (depending on the stage of fibrosis)<sup>(<xref rid="CIT0040" ref-type="bibr">40</xref>, <xref rid="CIT0041" ref-type="bibr">41</xref>)</sup>, sonographically assessment of perihepatic LNs would be of even more great value if data would report correlations with disease progression.</p><p>Perihepatic LNs can also be observed on computed tomography (CT) scans, which offer an excellent spatial resolution for measuring LNs<sup>(<xref rid="CIT0042" ref-type="bibr">42</xref>, <xref rid="CIT0043" ref-type="bibr">43</xref>)</sup>. Still, there are limitations. To be considered pathologically enlarged and measurable, a LN must be at least 15 mm in short axis when assessed by CT scan. LNs that are at least 10 mm but less than 15 mm in short axis may be pathologic but are considered non-measurable<sup>(<xref rid="CIT0044" ref-type="bibr">44</xref>–<xref rid="CIT0046" ref-type="bibr">46</xref>)</sup>. Also, on cross-sectional imaging, measurements of long-axis and short-axis LNs diameters are distorted because of variable nodal orientation<sup>(<xref rid="CIT0047" ref-type="bibr">47</xref>)</sup>. There is also the amount of radiation exposure, which should be avoided as much as possible in children.</p></sec><sec id="S20018"><title>The advantages of ultrasound compared to MRI</title><p>Magnetic resonance imaging (MRI) can depict the locations of enlarged LNs relative to adjacent bile ducts or vascular structures, providing better contrast between LNs and the adjacent tissues than does sonography or CT<sup>(<xref rid="CIT0048" ref-type="bibr">48</xref>–<xref rid="CIT0051" ref-type="bibr">51</xref>)</sup>. MRI depicts perihepatic LNs in most patients with CHC. LN number, size, and hyperintensity have been demonstrated to be related to the activity of CHC, but not to the results of liver function tests<sup>(<xref rid="CIT0049" ref-type="bibr">49</xref>)</sup>. Still, MRI is not widely available and it is expensive. In addition, it needs more time for the examination reason why most of the examinations require patient sedation. This can be an impediment in pediatric age group.</p></sec><sec id="S20019"><title>Review of the literature (ultrasound)</title><p>Publications on sonographic evaluation of perihepatic lymph nodes in the paediatric population are limited. Toppet <italic>et al</italic>., sonographically assessed perihepatic LNs in 58 pediatric patients with acute hepatitis A and in 68 controls. Small LNs were occasionally seen in normal subjects, located around the portal vein and their largest diameter was 7 to 10 mm<sup>(<xref rid="CIT0020" ref-type="bibr">20</xref>)</sup>.</p><p>Other studies investigating perihepatic lymphadenopathy were conducted in adults: Ierna <italic>et al</italic>. examined 1222 subjects by TUS and perihepatic lymphadenopathy at the hepatoduodenal ligament was found in 184 subjects (15.1%). Of these 184 subjects, 142 were positive for anti-HCV (77.1%), while only six of 1038 subjects (0.005%) in whom perihepatic lymphadenopathy was not detected were anti-HCV-positive<sup>(<xref rid="CIT0052" ref-type="bibr">52</xref>)</sup>.</p><p>Braden <italic>et al</italic>. assessed the total perihepatic LN volume in 40 consecutive patients with transaminases >500 U/L without known liver disease and compared the results with the US findings in 263 patients with known liver disease and also 49 healthy patients. Perihepatic lymphadenopathy was found in none of the HC, in 94% of patients with acute viral hepatitis, in 86% of patients with chronic viral hepatitis, in 90% of autoimmune disease but in none of the patients with toxic liver damage<sup>(<xref rid="CIT0001" ref-type="bibr">1</xref>)</sup>.</p><p>Dietrich <italic>et al</italic>. examined 59 patients with chronic viral hepatitis C, and the total perihepatic LN volume (LNV) was assessed using TUS before the initiation of antiviral treatment, at the end of treatment, and at the end of a 6-month follow-up period. At the end of follow-up, they found a significantly smaller LNV in patients with a sustained virologic response than in patients who failed to respond to treatment (0.5 ± 0.3 mL versus 2.0 ± 1.2 mL; <italic>p</italic> < 0.0001). In the group of sustained virologic responders, the decline of LNs was associated with an improvement in liver histology<sup>(<xref rid="CIT0016" ref-type="bibr">16</xref>)</sup>.</p><p>Nakanishi <italic>et al</italic>. investigated the relationship between the pathology of chronic liver diseases and the common hepatic arterial LNs using an ultrasonographic diagnostic system. They designated a LN index by multiplying the long and short LN diameters. The results of their study showed that LN appearance rate and LN index were significantly higher in the patients with hepatitis C, primary biliary cirrhosis and autoimmune hepatitis than in the healthy subjects. Also, LN index was significantly correlated with values for alanine aminotransferase and aspartate aminotransferase, with increase of the portal pressure, and with response to interferon therapy in patients with chronic viral hepatitis C<sup>(<xref rid="CIT0053" ref-type="bibr">53</xref>)</sup>.</p><p>Kuo <italic>et al</italic>. evaluated the clinical significance of sonographically enlarged LNs in the hepatoduodenal ligament in 600 outpatients categorized in 4 groups using viral markers (nonviral, CHB, CHC, and CHB and CHC). The incidence of detectable LNs in both the CHB group and the CHC group was significantly increased (56.9% and 69.4%, respectively; both <italic>p</italic> < 0.001) compared with the nonviral group, and this rate was independent of aminotransferase levels. Nodal width was the only significant parameter when viral and nonviral groups were compared (<italic>p</italic> < 0.05). If a width of more than 5 mm was used to predict HBV or HCV infection, the positive predictive rate was 88% and the specificity was 89%<sup>(<xref rid="CIT0054" ref-type="bibr">54</xref>)</sup>.</p><p>Hikita <italic>et al</italic>. evaluated by TUS 846 CHC patients during a six months period regarding presence of perihepatic LNs enlargement (defined as LN with the long axis diameter of more than 10 mm) as well as development of hepatic carcinoma. They concluded that patients with perihepatic LN enlargement had a lower risk of development of hepatocarcinoma than those without perihepatic LN enlargement. Their results may provide new insights regarding hepatocarcinogenesis. In this regard further studies are needed<sup>(<xref rid="CIT0055" ref-type="bibr">55</xref>)</sup>.</p></sec></sec><sec id="S0020"><title>Summary</title><p>In conclusion, TUS can detect LNs within the hepatoduodenal ligament not only in adults but also in children. Patients with CVH have significantly enlarged perihepatic LNs compared to controls. Therefore, sonographic assessment of perihepatic lymphadenopathy might be a non-invasive diagnostic tool to screen paediatric patients for CVH.</p></sec></body><back><ack><title>Acknowledgement</title><p>The authors are grateful to Bad Mergentheimer Leberzentrum e.V. supporting Dr. Xin-Wu Cui.</p></ack><sec id="S0021"><title>Conflict of interest</title><p>The authors do not report any financial or personal connections with other persons or organizations, which might negatively affect the contents of this publication and/or claim authorship rights to this publication.</p></sec><ref-list><title>References</title><ref id="CIT0001"><label>1</label><element-citation publication-type="journal"><person-group 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