Accuracy of Transient Elastography Data Combined With APRI in Detection and Staging of Liver Disease in Pediatric Patients With Cystic Fibrosis
Liver disease develops in 15%–72% of patients with cystic fibrosis, and 5%–10% develop cirrhosis or portal hypertension, usually during childhood. Transient elastography (TE) is a noninvasive method to measure liver stiffness. We aimed to validate its accuracy in detection of liver disease and asses...
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| Veröffentlicht in: | Clinical gastroenterology and hepatology 2019-11, Vol.17 (12), p.2561-2569.e5 |
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| creator | Lewindon, Peter J. Puertolas-Lopez, Mora V. Ramm, Louise E. Noble, Charlton Pereira, Tamara N. Wixey, Julie A. Hartel, Gunter F. Calvopina, Diego A. Leung, Daniel H. Ramm, Grant A. |
| description | Liver disease develops in 15%–72% of patients with cystic fibrosis, and 5%–10% develop cirrhosis or portal hypertension, usually during childhood. Transient elastography (TE) is a noninvasive method to measure liver stiffness. We aimed to validate its accuracy in detection of liver disease and assessment of fibrosis in children with cystic fibrosis.
We performed a cross-sectional study to evaluate the accuracy of TE in analysis of liver disease in 160 consecutive children who presented with cystic fibrosis (9.0 ± 0.4 years old, 53% male) at a tertiary referral pediatric center in Australia, from 2011 through 2016. Patients were classified as having cystic fibrosis-associated liver disease (CFLD) or cystic fibrosis without liver disease (CFnoLD) based on clinical, biochemical, and imaging features. Fibrosis severity was determined from histologic analysis of dual-pass liver biopsies from children with CFLD, as the reference standard. Data from healthy children without cystic fibrosis (n = 64, controls) were obtained from a separate study. Liver stiffness measurements (LSMs) were made by Fibroscan analysis, using the inter-quartile range/median ≤30% of 10 valid measurements. Children with macronodularity or portal hypertension with heterogeneous changes on ultrasound without available biopsy were assigned to the category of stage F3–F4 fibrosis.
LSM was made reliably in 86% of children; accuracy increased with age. LSMs were significantly higher in children with CFLD (10.7 ± 2.4 kPa, n = 33) than with CFnoLD (4.6 ± 0.1 kPa, n = 105) (P < .0001) or controls (4.1 ± 0.1kPa) (P < .0001); LSMs were higher in children with CFnoLD than controls (P < .05). At a cut-off value of 5.55kPa, LSM identified children with CFLD with an area under the receiver operating characteristic (AUROC) curve of 0.82, 70% sensitivity, and 82% specificity (P < .0001). Classification and regression tree models that combined LSM and aspartate aminotransferase to platelet ratio index (APRI) identified children with CFLD with an AUROC curve of 0.89, 87% sensitivity, and 74% specificity (odds ratio, 18.6). LSMs correlated with fibrosis stage in patients with CFLD (r = 0.67, P = .0001). A cut-off value of 8.7kPa differentiated patients with stage F3–F4 fibrosis from patients with stage F1–F2 fibrosis (AUROC, 0.87; 75% sensitivity; 100% specificity, P=.0002). The combination of LSMs and APRI improved the differentiation of patients with F3–F4 fibrosis vs F1–F2 fibrosis (AUROC, 0.92; 83% sensit |
| doi_str_mv | 10.1016/j.cgh.2019.03.015 |
| format | Article |
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We performed a cross-sectional study to evaluate the accuracy of TE in analysis of liver disease in 160 consecutive children who presented with cystic fibrosis (9.0 ± 0.4 years old, 53% male) at a tertiary referral pediatric center in Australia, from 2011 through 2016. Patients were classified as having cystic fibrosis-associated liver disease (CFLD) or cystic fibrosis without liver disease (CFnoLD) based on clinical, biochemical, and imaging features. Fibrosis severity was determined from histologic analysis of dual-pass liver biopsies from children with CFLD, as the reference standard. Data from healthy children without cystic fibrosis (n = 64, controls) were obtained from a separate study. Liver stiffness measurements (LSMs) were made by Fibroscan analysis, using the inter-quartile range/median ≤30% of 10 valid measurements. Children with macronodularity or portal hypertension with heterogeneous changes on ultrasound without available biopsy were assigned to the category of stage F3–F4 fibrosis.
LSM was made reliably in 86% of children; accuracy increased with age. LSMs were significantly higher in children with CFLD (10.7 ± 2.4 kPa, n = 33) than with CFnoLD (4.6 ± 0.1 kPa, n = 105) (P < .0001) or controls (4.1 ± 0.1kPa) (P < .0001); LSMs were higher in children with CFnoLD than controls (P < .05). At a cut-off value of 5.55kPa, LSM identified children with CFLD with an area under the receiver operating characteristic (AUROC) curve of 0.82, 70% sensitivity, and 82% specificity (P < .0001). Classification and regression tree models that combined LSM and aspartate aminotransferase to platelet ratio index (APRI) identified children with CFLD with an AUROC curve of 0.89, 87% sensitivity, and 74% specificity (odds ratio, 18.6). LSMs correlated with fibrosis stage in patients with CFLD (r = 0.67, P = .0001). A cut-off value of 8.7kPa differentiated patients with stage F3–F4 fibrosis from patients with stage F1–F2 fibrosis (AUROC, 0.87; 75% sensitivity; 100% specificity, P=.0002). The combination of LSMs and APRI improved the differentiation of patients with F3–F4 fibrosis vs F1–F2 fibrosis (AUROC, 0.92; 83% sensitivity; and 100% specificity (P < .01).
LSMs made by TE accurately detect liver disease in children with cystic fibrosis; diagnostic accuracy increases when LSMs are combined with APRI. LSMs also differentiate between children with cystic fibrosis with mild-moderate fibrosis vs advanced fibrosis.</description><identifier>ISSN: 1542-3565</identifier><identifier>EISSN: 1542-7714</identifier><identifier>DOI: 10.1016/j.cgh.2019.03.015</identifier><identifier>PMID: 30880274</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Aspartate Aminotransferases - blood ; CART Analysis Decision Tree ; Child ; Cross-Sectional Studies ; Cystic Fibrosis ; Elasticity Imaging Techniques ; Female ; Hepatic Fibrosis ; Humans ; Liver Cirrhosis - diagnosis ; Male ; Pediatric Cholestatic Liver Disease ; Platelet Count ; Sensitivity and Specificity ; Severity of Illness Index ; Ultrasound-based Diagnosis of Liver Disease</subject><ispartof>Clinical gastroenterology and hepatology, 2019-11, Vol.17 (12), p.2561-2569.e5</ispartof><rights>2019 AGA Institute</rights><rights>Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-b81d34500efd1b9f986edf99ebfcc0d911b57d916eb52aa2646cf250d4d1f0e73</citedby><cites>FETCH-LOGICAL-c353t-b81d34500efd1b9f986edf99ebfcc0d911b57d916eb52aa2646cf250d4d1f0e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cgh.2019.03.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30880274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lewindon, Peter J.</creatorcontrib><creatorcontrib>Puertolas-Lopez, Mora V.</creatorcontrib><creatorcontrib>Ramm, Louise E.</creatorcontrib><creatorcontrib>Noble, Charlton</creatorcontrib><creatorcontrib>Pereira, Tamara N.</creatorcontrib><creatorcontrib>Wixey, Julie A.</creatorcontrib><creatorcontrib>Hartel, Gunter F.</creatorcontrib><creatorcontrib>Calvopina, Diego A.</creatorcontrib><creatorcontrib>Leung, Daniel H.</creatorcontrib><creatorcontrib>Ramm, Grant A.</creatorcontrib><title>Accuracy of Transient Elastography Data Combined With APRI in Detection and Staging of Liver Disease in Pediatric Patients With Cystic Fibrosis</title><title>Clinical gastroenterology and hepatology</title><addtitle>Clin Gastroenterol Hepatol</addtitle><description>Liver disease develops in 15%–72% of patients with cystic fibrosis, and 5%–10% develop cirrhosis or portal hypertension, usually during childhood. Transient elastography (TE) is a noninvasive method to measure liver stiffness. We aimed to validate its accuracy in detection of liver disease and assessment of fibrosis in children with cystic fibrosis.
We performed a cross-sectional study to evaluate the accuracy of TE in analysis of liver disease in 160 consecutive children who presented with cystic fibrosis (9.0 ± 0.4 years old, 53% male) at a tertiary referral pediatric center in Australia, from 2011 through 2016. Patients were classified as having cystic fibrosis-associated liver disease (CFLD) or cystic fibrosis without liver disease (CFnoLD) based on clinical, biochemical, and imaging features. Fibrosis severity was determined from histologic analysis of dual-pass liver biopsies from children with CFLD, as the reference standard. Data from healthy children without cystic fibrosis (n = 64, controls) were obtained from a separate study. Liver stiffness measurements (LSMs) were made by Fibroscan analysis, using the inter-quartile range/median ≤30% of 10 valid measurements. Children with macronodularity or portal hypertension with heterogeneous changes on ultrasound without available biopsy were assigned to the category of stage F3–F4 fibrosis.
LSM was made reliably in 86% of children; accuracy increased with age. LSMs were significantly higher in children with CFLD (10.7 ± 2.4 kPa, n = 33) than with CFnoLD (4.6 ± 0.1 kPa, n = 105) (P < .0001) or controls (4.1 ± 0.1kPa) (P < .0001); LSMs were higher in children with CFnoLD than controls (P < .05). At a cut-off value of 5.55kPa, LSM identified children with CFLD with an area under the receiver operating characteristic (AUROC) curve of 0.82, 70% sensitivity, and 82% specificity (P < .0001). Classification and regression tree models that combined LSM and aspartate aminotransferase to platelet ratio index (APRI) identified children with CFLD with an AUROC curve of 0.89, 87% sensitivity, and 74% specificity (odds ratio, 18.6). LSMs correlated with fibrosis stage in patients with CFLD (r = 0.67, P = .0001). A cut-off value of 8.7kPa differentiated patients with stage F3–F4 fibrosis from patients with stage F1–F2 fibrosis (AUROC, 0.87; 75% sensitivity; 100% specificity, P=.0002). The combination of LSMs and APRI improved the differentiation of patients with F3–F4 fibrosis vs F1–F2 fibrosis (AUROC, 0.92; 83% sensitivity; and 100% specificity (P < .01).
LSMs made by TE accurately detect liver disease in children with cystic fibrosis; diagnostic accuracy increases when LSMs are combined with APRI. LSMs also differentiate between children with cystic fibrosis with mild-moderate fibrosis vs advanced fibrosis.</description><subject>Adolescent</subject><subject>Aspartate Aminotransferases - blood</subject><subject>CART Analysis Decision Tree</subject><subject>Child</subject><subject>Cross-Sectional Studies</subject><subject>Cystic Fibrosis</subject><subject>Elasticity Imaging Techniques</subject><subject>Female</subject><subject>Hepatic Fibrosis</subject><subject>Humans</subject><subject>Liver Cirrhosis - diagnosis</subject><subject>Male</subject><subject>Pediatric Cholestatic Liver Disease</subject><subject>Platelet Count</subject><subject>Sensitivity and Specificity</subject><subject>Severity of Illness Index</subject><subject>Ultrasound-based Diagnosis of Liver Disease</subject><issn>1542-3565</issn><issn>1542-7714</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1qGzEUhUVoSVKnD5BN0LIbT_UzmrHoythOGjDUtAldCo10ZcuMZ1xJNvgp8srRYLfLro4Q5366Ogehe0oKSmj1dVuY9aZghMqC8IJQcYVuqSjZuK5p-eFy5qISN-hTjFtCmCxlfY1uOJlMCKvLW_Q2NeYQtDnh3uGXoLvooUt40eqY-nXQ-80Jz3XSeNbvGt-Bxb992uDp6ucz9h2eQwKTfN9h3Vn8K-m179YDaumPEPDcR9ARBucKrNcpeINXOg1vxDNpdoopXz76JvTRxzv00ek2wueLjtDr4-Jl9n28_PH0PJsux4YLnsbNhFpeCkLAWdpIJycVWCclNM4YYiWljaizVNAIpjWryso4JogtLXUEaj5CX87cfej_HCAmtfPRQNvqDvpDVIxKXjFeZxkheraavGEM4NQ--J0OJ0WJGnpQW5V7UEMPinCVe8gzDxf8odmB_TfxN_hs-HY2QP7k0UNQ0eRUTE4p5ESV7f1_8O_VoZnw</recordid><startdate>201911</startdate><enddate>201911</enddate><creator>Lewindon, Peter J.</creator><creator>Puertolas-Lopez, Mora V.</creator><creator>Ramm, Louise E.</creator><creator>Noble, Charlton</creator><creator>Pereira, Tamara N.</creator><creator>Wixey, Julie A.</creator><creator>Hartel, Gunter F.</creator><creator>Calvopina, Diego A.</creator><creator>Leung, Daniel H.</creator><creator>Ramm, Grant A.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201911</creationdate><title>Accuracy of Transient Elastography Data Combined With APRI in Detection and Staging of Liver Disease in Pediatric Patients With Cystic Fibrosis</title><author>Lewindon, Peter J. ; Puertolas-Lopez, Mora V. ; Ramm, Louise E. ; Noble, Charlton ; Pereira, Tamara N. ; Wixey, Julie A. ; Hartel, Gunter F. ; Calvopina, Diego A. ; Leung, Daniel H. ; Ramm, Grant A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-b81d34500efd1b9f986edf99ebfcc0d911b57d916eb52aa2646cf250d4d1f0e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adolescent</topic><topic>Aspartate Aminotransferases - blood</topic><topic>CART Analysis Decision Tree</topic><topic>Child</topic><topic>Cross-Sectional Studies</topic><topic>Cystic Fibrosis</topic><topic>Elasticity Imaging Techniques</topic><topic>Female</topic><topic>Hepatic Fibrosis</topic><topic>Humans</topic><topic>Liver Cirrhosis - diagnosis</topic><topic>Male</topic><topic>Pediatric Cholestatic Liver Disease</topic><topic>Platelet Count</topic><topic>Sensitivity and Specificity</topic><topic>Severity of Illness Index</topic><topic>Ultrasound-based Diagnosis of Liver Disease</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lewindon, Peter J.</creatorcontrib><creatorcontrib>Puertolas-Lopez, Mora V.</creatorcontrib><creatorcontrib>Ramm, Louise E.</creatorcontrib><creatorcontrib>Noble, Charlton</creatorcontrib><creatorcontrib>Pereira, Tamara N.</creatorcontrib><creatorcontrib>Wixey, Julie A.</creatorcontrib><creatorcontrib>Hartel, Gunter F.</creatorcontrib><creatorcontrib>Calvopina, Diego A.</creatorcontrib><creatorcontrib>Leung, Daniel H.</creatorcontrib><creatorcontrib>Ramm, Grant A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical gastroenterology and hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lewindon, Peter J.</au><au>Puertolas-Lopez, Mora V.</au><au>Ramm, Louise E.</au><au>Noble, Charlton</au><au>Pereira, Tamara N.</au><au>Wixey, Julie A.</au><au>Hartel, Gunter F.</au><au>Calvopina, Diego A.</au><au>Leung, Daniel H.</au><au>Ramm, Grant A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Accuracy of Transient Elastography Data Combined With APRI in Detection and Staging of Liver Disease in Pediatric Patients With Cystic Fibrosis</atitle><jtitle>Clinical gastroenterology and hepatology</jtitle><addtitle>Clin Gastroenterol Hepatol</addtitle><date>2019-11</date><risdate>2019</risdate><volume>17</volume><issue>12</issue><spage>2561</spage><epage>2569.e5</epage><pages>2561-2569.e5</pages><issn>1542-3565</issn><eissn>1542-7714</eissn><abstract>Liver disease develops in 15%–72% of patients with cystic fibrosis, and 5%–10% develop cirrhosis or portal hypertension, usually during childhood. Transient elastography (TE) is a noninvasive method to measure liver stiffness. We aimed to validate its accuracy in detection of liver disease and assessment of fibrosis in children with cystic fibrosis.
We performed a cross-sectional study to evaluate the accuracy of TE in analysis of liver disease in 160 consecutive children who presented with cystic fibrosis (9.0 ± 0.4 years old, 53% male) at a tertiary referral pediatric center in Australia, from 2011 through 2016. Patients were classified as having cystic fibrosis-associated liver disease (CFLD) or cystic fibrosis without liver disease (CFnoLD) based on clinical, biochemical, and imaging features. Fibrosis severity was determined from histologic analysis of dual-pass liver biopsies from children with CFLD, as the reference standard. Data from healthy children without cystic fibrosis (n = 64, controls) were obtained from a separate study. Liver stiffness measurements (LSMs) were made by Fibroscan analysis, using the inter-quartile range/median ≤30% of 10 valid measurements. Children with macronodularity or portal hypertension with heterogeneous changes on ultrasound without available biopsy were assigned to the category of stage F3–F4 fibrosis.
LSM was made reliably in 86% of children; accuracy increased with age. LSMs were significantly higher in children with CFLD (10.7 ± 2.4 kPa, n = 33) than with CFnoLD (4.6 ± 0.1 kPa, n = 105) (P < .0001) or controls (4.1 ± 0.1kPa) (P < .0001); LSMs were higher in children with CFnoLD than controls (P < .05). At a cut-off value of 5.55kPa, LSM identified children with CFLD with an area under the receiver operating characteristic (AUROC) curve of 0.82, 70% sensitivity, and 82% specificity (P < .0001). Classification and regression tree models that combined LSM and aspartate aminotransferase to platelet ratio index (APRI) identified children with CFLD with an AUROC curve of 0.89, 87% sensitivity, and 74% specificity (odds ratio, 18.6). LSMs correlated with fibrosis stage in patients with CFLD (r = 0.67, P = .0001). A cut-off value of 8.7kPa differentiated patients with stage F3–F4 fibrosis from patients with stage F1–F2 fibrosis (AUROC, 0.87; 75% sensitivity; 100% specificity, P=.0002). The combination of LSMs and APRI improved the differentiation of patients with F3–F4 fibrosis vs F1–F2 fibrosis (AUROC, 0.92; 83% sensitivity; and 100% specificity (P < .01).
LSMs made by TE accurately detect liver disease in children with cystic fibrosis; diagnostic accuracy increases when LSMs are combined with APRI. LSMs also differentiate between children with cystic fibrosis with mild-moderate fibrosis vs advanced fibrosis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30880274</pmid><doi>10.1016/j.cgh.2019.03.015</doi></addata></record> |
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| subjects | Adolescent Aspartate Aminotransferases - blood CART Analysis Decision Tree Child Cross-Sectional Studies Cystic Fibrosis Elasticity Imaging Techniques Female Hepatic Fibrosis Humans Liver Cirrhosis - diagnosis Male Pediatric Cholestatic Liver Disease Platelet Count Sensitivity and Specificity Severity of Illness Index Ultrasound-based Diagnosis of Liver Disease |
| title | Accuracy of Transient Elastography Data Combined With APRI in Detection and Staging of Liver Disease in Pediatric Patients With Cystic Fibrosis |
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