Features of Severe Liver Disease With Portal Hypertension in Patients with Cystic Fibrosis
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Auteurs : Jaclyn R. Stonebraker [États-Unis] ; Chee Y. Ooi [Australie] ; Rhonda G. Pace [États-Unis] ; Harriet Corvol [France] ; Michael R. Knowles [États-Unis] ; Peter R. Durie [Canada] ; Simon C. Ling [Canada]Source :
- Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association [ 1542-3565 ] ; 2016.
Abstract
Liver disease is the third leading cause of death in patients with cystic fibrosis (CF), but features of patients with CF, severe liver disease, and portal hypertension have not been fully characterized.
We performed a retrospective analysis of data from 561 patients with CF (63% male, 99% with pancreatic insufficiency), liver disease (hepatic parenchymal abnormalities consistent with cirrhosis, confirmed by imaging), and portal hypertension (esophageal varices, portosystemic collaterals, or splenomegaly), with no alternate causes of liver disease. All patients were enrolled in the Genetic Modifier Study of Severe CF Liver Disease at 76 international centers, from January 1999 through July 2013.
Male patients were diagnosed with liver disease at a younger age than female patients (10 vs 11 years;
In patients with CF, severe liver disease develops early in childhood (around 10 years of age) and is more common in boys than girls. Patients with varices and those who receive liver transplants have more abnormal platelet counts and APRi and FIB-4 scores.
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DOI: 10.1016/j.cgh.2016.03.041
PubMed: 27062904
PubMed Central: 4955685
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Ooi</name><affiliation wicri:level="1"><nlm:aff id="A2"> Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3"> Department of Gastroenterology, Sydney Children's Hospital Randwick, Sydney, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Department of Gastroenterology, Sydney Children's Hospital Randwick, Sydney</wicri:regionArea></affiliation></author><author><name sortKey="Pace, Rhonda G" sort="Pace, Rhonda G" uniqKey="Pace R" first="Rhonda G." last="Pace">Rhonda G. Pace</name><affiliation wicri:level="1"><nlm:aff id="A1"> Marsico Lung Institute / Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Marsico Lung Institute / Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Corvol, Harriet" sort="Corvol, Harriet" uniqKey="Corvol H" first="Harriet" last="Corvol">Harriet Corvol</name><affiliation wicri:level="1"><nlm:aff id="A4"> Assistance Publique-Hôpitaux de Paris (AP-HP), Trousseau Hospital, Pediatric Pulmonology Department; Institut National de la Santé et la Recherche Médicale (INSERM), Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Assistance Publique-Hôpitaux de Paris (AP-HP), Trousseau Hospital, Pediatric Pulmonology Department; Institut National de la Santé et la Recherche Médicale (INSERM), Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A5"> Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris</wicri:regionArea></affiliation></author><author><name sortKey="Knowles, Michael R" sort="Knowles, Michael R" uniqKey="Knowles M" first="Michael R." last="Knowles">Michael R. Knowles</name><affiliation wicri:level="1"><nlm:aff id="A1"> Marsico Lung Institute / Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Marsico Lung Institute / Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Durie, Peter R" sort="Durie, Peter R" uniqKey="Durie P" first="Peter R." last="Durie">Peter R. Durie</name><affiliation wicri:level="1"><nlm:aff id="A6"> Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A7"> Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A8"> Department of Pediatrics, University of Toronto, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Pediatrics, University of Toronto</wicri:regionArea></affiliation></author><author><name sortKey="Ling, Simon C" sort="Ling, Simon C" uniqKey="Ling S" first="Simon C." last="Ling">Simon C. Ling</name><affiliation wicri:level="1"><nlm:aff id="A7"> Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A8"> Department of Pediatrics, University of Toronto, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Pediatrics, University of Toronto</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27062904</idno><idno type="pmc">4955685</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955685</idno><idno type="RBID">PMC:4955685</idno><idno type="doi">10.1016/j.cgh.2016.03.041</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">001E17</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001E17</idno><idno type="wicri:Area/Pmc/Curation">001C73</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001C73</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Features of Severe Liver Disease With Portal Hypertension in Patients with Cystic Fibrosis</title><author><name sortKey="Stonebraker, Jaclyn R" sort="Stonebraker, Jaclyn R" uniqKey="Stonebraker J" first="Jaclyn R." last="Stonebraker">Jaclyn R. Stonebraker</name><affiliation wicri:level="1"><nlm:aff id="A1"> Marsico Lung Institute / Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Marsico Lung Institute / Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Ooi, Chee Y" sort="Ooi, Chee Y" uniqKey="Ooi C" first="Chee Y." last="Ooi">Chee Y. Ooi</name><affiliation wicri:level="1"><nlm:aff id="A2"> Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3"> Department of Gastroenterology, Sydney Children's Hospital Randwick, Sydney, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Department of Gastroenterology, Sydney Children's Hospital Randwick, Sydney</wicri:regionArea></affiliation></author><author><name sortKey="Pace, Rhonda G" sort="Pace, Rhonda G" uniqKey="Pace R" first="Rhonda G." last="Pace">Rhonda G. Pace</name><affiliation wicri:level="1"><nlm:aff id="A1"> Marsico Lung Institute / Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Marsico Lung Institute / Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Corvol, Harriet" sort="Corvol, Harriet" uniqKey="Corvol H" first="Harriet" last="Corvol">Harriet Corvol</name><affiliation wicri:level="1"><nlm:aff id="A4"> Assistance Publique-Hôpitaux de Paris (AP-HP), Trousseau Hospital, Pediatric Pulmonology Department; Institut National de la Santé et la Recherche Médicale (INSERM), Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Assistance Publique-Hôpitaux de Paris (AP-HP), Trousseau Hospital, Pediatric Pulmonology Department; Institut National de la Santé et la Recherche Médicale (INSERM), Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A5"> Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris</wicri:regionArea></affiliation></author><author><name sortKey="Knowles, Michael R" sort="Knowles, Michael R" uniqKey="Knowles M" first="Michael R." last="Knowles">Michael R. Knowles</name><affiliation wicri:level="1"><nlm:aff id="A1"> Marsico Lung Institute / Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Marsico Lung Institute / Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Durie, Peter R" sort="Durie, Peter R" uniqKey="Durie P" first="Peter R." last="Durie">Peter R. Durie</name><affiliation wicri:level="1"><nlm:aff id="A6"> Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A7"> Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A8"> Department of Pediatrics, University of Toronto, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Pediatrics, University of Toronto</wicri:regionArea></affiliation></author><author><name sortKey="Ling, Simon C" sort="Ling, Simon C" uniqKey="Ling S" first="Simon C." last="Ling">Simon C. Ling</name><affiliation wicri:level="1"><nlm:aff id="A7"> Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A8"> Department of Pediatrics, University of Toronto, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Pediatrics, University of Toronto</wicri:regionArea></affiliation></author></analytic><series><title level="j">Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association</title><idno type="ISSN">1542-3565</idno><idno type="eISSN">1542-7714</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background & Aims</title><p id="P2">Liver disease is the third leading cause of death in patients with cystic fibrosis (CF), but features of patients with CF, severe liver disease, and portal hypertension have not been fully characterized.</p></sec><sec id="S2"><title>Methods</title><p id="P3">We performed a retrospective analysis of data from 561 patients with CF (63% male, 99% with pancreatic insufficiency), liver disease (hepatic parenchymal abnormalities consistent with cirrhosis, confirmed by imaging), and portal hypertension (esophageal varices, portosystemic collaterals, or splenomegaly), with no alternate causes of liver disease. All patients were enrolled in the Genetic Modifier Study of Severe CF Liver Disease at 76 international centers, from January 1999 through July 2013.</p></sec><sec id="S3"><title>Results</title><p id="P4">Male patients were diagnosed with liver disease at a younger age than female patients (10 vs 11 years; <italic>P</italic>=.01). Splenomegaly was observed in 99% of patients and varices in 71%. Levels of liver enzymes were near normal in most patients. Thrombocytopenia affected 70% of patients and was more severe in patients with varices (88×10<sup>9</sup>/L vs 145×10<sup>9</sup>/L; <italic>P</italic><.0001). Ninety-one patients received liver transplants (16%), at a median age of 13.9 years. Compared to patients who did not receive liver transplants, patients who received liver transplants had lower platelet counts (78×10<sup>9</sup>/L vs 113×10<sup>0</sup>/L; <italic>P</italic><.0001), higher international normalized ratios (<italic>P</italic><.0001), and lower levels of albumin (<italic>P</italic>=.0002). The aminotransferase to platelet ratio index (APRi) and fibrosis index based on 4 factor (FIB-4) values were above diagnostic thresholds for CF liver disease in 96% and 90% of patients, respectively. Patients who received liver transplants or who had varices had higher APRi and FIB-4 values than patients who did not.</p></sec><sec id="S4"><title>Conclusions</title><p id="P5">In patients with CF, severe liver disease develops early in childhood (around 10 years of age) and is more common in boys than girls. Patients with varices and those who receive liver transplants have more abnormal platelet counts and APRi and FIB-4 scores.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101160775</journal-id><journal-id journal-id-type="pubmed-jr-id">31839</journal-id><journal-id journal-id-type="nlm-ta">Clin Gastroenterol Hepatol</journal-id><journal-id journal-id-type="iso-abbrev">Clin. Gastroenterol. Hepatol.</journal-id><journal-title-group><journal-title>Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association</journal-title></journal-title-group><issn pub-type="ppub">1542-3565</issn><issn pub-type="epub">1542-7714</issn></journal-meta><article-meta><article-id pub-id-type="pmid">27062904</article-id><article-id pub-id-type="pmc">4955685</article-id><article-id pub-id-type="doi">10.1016/j.cgh.2016.03.041</article-id><article-id pub-id-type="manuscript">NIHMS776329</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Features of Severe Liver Disease With Portal Hypertension in Patients with Cystic Fibrosis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Stonebraker</surname><given-names>Jaclyn R.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ooi</surname><given-names>Chee Y.</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Pace</surname><given-names>Rhonda G.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Corvol</surname><given-names>Harriet</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Knowles</surname><given-names>Michael R.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Durie</surname><given-names>Peter R.</given-names></name><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="author-notes" rid="FN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Ling</surname><given-names>Simon C.</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="author-notes" rid="FN1">*</xref></contrib></contrib-group><aff id="A1"><label>1</label> Marsico Lung Institute / Cystic Fibrosis Research Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States</aff><aff id="A2"><label>2</label> Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia</aff><aff id="A3"><label>3</label> Department of Gastroenterology, Sydney Children's Hospital Randwick, Sydney, Australia</aff><aff id="A4"><label>4</label> Assistance Publique-Hôpitaux de Paris (AP-HP), Trousseau Hospital, Pediatric Pulmonology Department; Institut National de la Santé et la Recherche Médicale (INSERM), Paris, France</aff><aff id="A5"><label>5</label> Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris, France</aff><aff id="A6"><label>6</label> Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada</aff><aff id="A7"><label>7</label> Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada</aff><aff id="A8"><label>8</label> Department of Pediatrics, University of Toronto, Canada</aff><author-notes><fn id="FN1"><label>*</label><p id="P1">Co-senior authors</p></fn><corresp id="CR1"><bold>Corresponding author:</bold> Jaclyn R. Stonebraker, Ph.D., Marsico Lung Institute / Cystic Fibrosis Research Center, The University of North Carolina at Chapel Hill, CB# 7248, 7219B Marsico Hall, Chapel Hill, NC 27599, USA, Voice: (919) 966-0270, Fax: (919) 966-7524, <email>Jaclyn_Stonebraker@med.unc.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>11</day><month>5</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>05</day><month>4</month><year>2016</year></pub-date><pub-date pub-type="ppub"><month>8</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>8</month><year>2017</year></pub-date><volume>14</volume><issue>8</issue><fpage>1207</fpage><lpage>1215.e3</lpage><pmc-comment>elocation-id from pubmed: 10.1016/j.cgh.2016.03.041</pmc-comment>
<abstract><sec id="S1"><title>Background & Aims</title><p id="P2">Liver disease is the third leading cause of death in patients with cystic fibrosis (CF), but features of patients with CF, severe liver disease, and portal hypertension have not been fully characterized.</p></sec><sec id="S2"><title>Methods</title><p id="P3">We performed a retrospective analysis of data from 561 patients with CF (63% male, 99% with pancreatic insufficiency), liver disease (hepatic parenchymal abnormalities consistent with cirrhosis, confirmed by imaging), and portal hypertension (esophageal varices, portosystemic collaterals, or splenomegaly), with no alternate causes of liver disease. All patients were enrolled in the Genetic Modifier Study of Severe CF Liver Disease at 76 international centers, from January 1999 through July 2013.</p></sec><sec id="S3"><title>Results</title><p id="P4">Male patients were diagnosed with liver disease at a younger age than female patients (10 vs 11 years; <italic>P</italic>=.01). Splenomegaly was observed in 99% of patients and varices in 71%. Levels of liver enzymes were near normal in most patients. Thrombocytopenia affected 70% of patients and was more severe in patients with varices (88×10<sup>9</sup>/L vs 145×10<sup>9</sup>/L; <italic>P</italic><.0001). Ninety-one patients received liver transplants (16%), at a median age of 13.9 years. Compared to patients who did not receive liver transplants, patients who received liver transplants had lower platelet counts (78×10<sup>9</sup>/L vs 113×10<sup>0</sup>/L; <italic>P</italic><.0001), higher international normalized ratios (<italic>P</italic><.0001), and lower levels of albumin (<italic>P</italic>=.0002). The aminotransferase to platelet ratio index (APRi) and fibrosis index based on 4 factor (FIB-4) values were above diagnostic thresholds for CF liver disease in 96% and 90% of patients, respectively. Patients who received liver transplants or who had varices had higher APRi and FIB-4 values than patients who did not.</p></sec><sec id="S4"><title>Conclusions</title><p id="P5">In patients with CF, severe liver disease develops early in childhood (around 10 years of age) and is more common in boys than girls. Patients with varices and those who receive liver transplants have more abnormal platelet counts and APRi and FIB-4 scores.</p></sec></abstract><kwd-group><kwd>CFLD</kwd><kwd>ALT</kwd><kwd>phenotype</kwd><kwd>portal pressure</kwd><kwd>INR</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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