High Diagnostic Value of Transient Elastography for Advanced Fibrosis and Cirrhosis in Patients With Chronic Hepatitis Delta

Liver biopsy remains the gold standard for fibrosis staging in patients with chronic hepatitis delta (CHD). Here, we comparatively evaluated the performance of transient elastography (TE) and biomarkers for the diagnosis of liver fibrosis in patients with CHD. A total of 230 HDV-infected RNA-positiv...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Clinical gastroenterology and hepatology 2024-08
Hauptverfasser: Roulot, Dominique, Brichler, Ségolène, Layese, Richard, D’alteroche, Louis, Ganne-Carrie, Nathalie, Stern, Christiane, Saviano, Antonio, Leroy, Vincent, Roudot-Thoraval, Françoise, De Ledinghen, Victor, Loustaud-Ratti, Véronique, Silvain, Christine, Benali, Souad, Ingiliz, Patrick, Gouton, Martial, Guyader, Dominique, Roche, Bruno, Chazouillères, Olivier, Asselah, Tarik, Ziol, Marianne
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue
container_start_page
container_title Clinical gastroenterology and hepatology
container_volume
creator Roulot, Dominique
Brichler, Ségolène
Layese, Richard
D’alteroche, Louis
Ganne-Carrie, Nathalie
Stern, Christiane
Saviano, Antonio
Leroy, Vincent
Roudot-Thoraval, Françoise
De Ledinghen, Victor
Loustaud-Ratti, Véronique
Silvain, Christine
Benali, Souad
Ingiliz, Patrick
Gouton, Martial
Guyader, Dominique
Roche, Bruno
Chazouillères, Olivier
Asselah, Tarik
Ziol, Marianne
description Liver biopsy remains the gold standard for fibrosis staging in patients with chronic hepatitis delta (CHD). Here, we comparatively evaluated the performance of transient elastography (TE) and biomarkers for the diagnosis of liver fibrosis in patients with CHD. A total of 230 HDV-infected RNA-positive patients from various centers who underwent liver biopsy and liver stiffness measurements (LSMs) using Fibroscan, within a period of 6 months maximum, were investigated retrospectively. Area under the receiver operating characteristic curve and Youden index were used to establish cutoff values of LSM. TE was compared with other noninvasive tests: aspartate aminotransferase to platelet ratio index, Fibrosis-4, and Delta-4 fibrosis scores. Histologic fibrosis stage distribution was: 20.4% for F0-F1; 27.0% for F2; 18.7% for F3; and 33.9% for F4. TE demonstrated good diagnostic performance for detecting cirrhosis and advanced fibrosis with an Area under the receiver operating characteristic curve of 0.88 and 0.86, which were significantly higher than those obtained with the other noninvasive tests (P = .004 and P < .001). With a cutoff value of >12 kPa for cirrhosis, the sensitivity was 70.5%, specificity was 86.2%, positive predictive value was 72.4%, negative predictive value was 85.1%, and accuracy was 80.9%. Using 10.4 kPa as the cutoff value for F3, the sensitivity was 70.2%, specificity was 83.5%, positive predictive value was 82.5%, negative predictive value was 71.7%, and accuracy was 76.5%. In 89% of patients with LSM ≤6.2 kPa, liver biopsy disclosed only absent or minimal fibrosis. TE demonstrated good diagnostic performance for advanced fibrosis and cirrhosis in patients with CHD. Advanced fibrosis is highly probable for LSM values ≥10 kPa. LSM values
doi_str_mv 10.1016/j.cgh.2024.08.008
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3099801720</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1542356524007766</els_id><sourcerecordid>3099801720</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1506-2d8e43d9b339b79e378100f08828a2c2698d27c063fd8353b3b975a22bebf4d33</originalsourceid><addsrcrecordid>eNp9kE1vEzEQhi1ERUvhB3BBPnLJMrb3wxanKm0JUiV6KHC0vPZs1tFmHWynUqX-eBwSeuQ0Hut5X2keQj4wqBiw9vOmsuux4sDrCmQFIF-RC9bUfNF1rH59eoumbc7J25Q2AFzVqntDzoXioJhqL8jzyq9Heu3Neg4pe0t_mmmPNAz0IZo5eZwzvZlMymEdzW58okOI9Mo9mtmio7e-jyH5RM3s6NLHOP7d_EzvTT5kE_3l80iXYwxzKV_hrvznglzjlM07cjaYKeH707wkP25vHparxd33r9-WV3cLyxpoF9xJrIVTvRCq7xSKTjKAAaTk0nDLWyUd7yy0YnBSNKIXveoaw3mP_VA7IS7Jp2PvLobfe0xZb32yOE1mxrBPWoBSEljHoaDsiNpyWIo46F30WxOfNAN9kK43ukjXB-kapC7SS-bjqX7fb9G9JP5ZLsCXI4DlyEePUSdb7BSDPqLN2gX_n_o_C4GSbA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3099801720</pqid></control><display><type>article</type><title>High Diagnostic Value of Transient Elastography for Advanced Fibrosis and Cirrhosis in Patients With Chronic Hepatitis Delta</title><source>Elsevier ScienceDirect Journals Complete</source><creator>Roulot, Dominique ; Brichler, Ségolène ; Layese, Richard ; D’alteroche, Louis ; Ganne-Carrie, Nathalie ; Stern, Christiane ; Saviano, Antonio ; Leroy, Vincent ; Roudot-Thoraval, Françoise ; De Ledinghen, Victor ; Loustaud-Ratti, Véronique ; Silvain, Christine ; Benali, Souad ; Ingiliz, Patrick ; Gouton, Martial ; Guyader, Dominique ; Roche, Bruno ; Chazouillères, Olivier ; Asselah, Tarik ; Ziol, Marianne</creator><creatorcontrib>Roulot, Dominique ; Brichler, Ségolène ; Layese, Richard ; D’alteroche, Louis ; Ganne-Carrie, Nathalie ; Stern, Christiane ; Saviano, Antonio ; Leroy, Vincent ; Roudot-Thoraval, Françoise ; De Ledinghen, Victor ; Loustaud-Ratti, Véronique ; Silvain, Christine ; Benali, Souad ; Ingiliz, Patrick ; Gouton, Martial ; Guyader, Dominique ; Roche, Bruno ; Chazouillères, Olivier ; Asselah, Tarik ; Ziol, Marianne ; DELTAVIR study group</creatorcontrib><description>Liver biopsy remains the gold standard for fibrosis staging in patients with chronic hepatitis delta (CHD). Here, we comparatively evaluated the performance of transient elastography (TE) and biomarkers for the diagnosis of liver fibrosis in patients with CHD. A total of 230 HDV-infected RNA-positive patients from various centers who underwent liver biopsy and liver stiffness measurements (LSMs) using Fibroscan, within a period of 6 months maximum, were investigated retrospectively. Area under the receiver operating characteristic curve and Youden index were used to establish cutoff values of LSM. TE was compared with other noninvasive tests: aspartate aminotransferase to platelet ratio index, Fibrosis-4, and Delta-4 fibrosis scores. Histologic fibrosis stage distribution was: 20.4% for F0-F1; 27.0% for F2; 18.7% for F3; and 33.9% for F4. TE demonstrated good diagnostic performance for detecting cirrhosis and advanced fibrosis with an Area under the receiver operating characteristic curve of 0.88 and 0.86, which were significantly higher than those obtained with the other noninvasive tests (P = .004 and P &lt; .001). With a cutoff value of &gt;12 kPa for cirrhosis, the sensitivity was 70.5%, specificity was 86.2%, positive predictive value was 72.4%, negative predictive value was 85.1%, and accuracy was 80.9%. Using 10.4 kPa as the cutoff value for F3, the sensitivity was 70.2%, specificity was 83.5%, positive predictive value was 82.5%, negative predictive value was 71.7%, and accuracy was 76.5%. In 89% of patients with LSM ≤6.2 kPa, liver biopsy disclosed only absent or minimal fibrosis. TE demonstrated good diagnostic performance for advanced fibrosis and cirrhosis in patients with CHD. Advanced fibrosis is highly probable for LSM values ≥10 kPa. LSM values &lt;6 kPa almost totally exclude significant fibrosis. Between 6 and 10 kPa, liver biopsy should be discussed.</description><identifier>ISSN: 1542-3565</identifier><identifier>ISSN: 1542-7714</identifier><identifier>EISSN: 1542-7714</identifier><identifier>DOI: 10.1016/j.cgh.2024.08.008</identifier><identifier>PMID: 39209196</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Chronic Hepatitis D ; Cirrhosis ; Hepatitis Delta Virus ; Noninvasive Tests ; Transient Elastography</subject><ispartof>Clinical gastroenterology and hepatology, 2024-08</ispartof><rights>2024 AGA Institute</rights><rights>Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1506-2d8e43d9b339b79e378100f08828a2c2698d27c063fd8353b3b975a22bebf4d33</cites><orcidid>0000-0003-0926-3563</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1542356524007766$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39209196$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Roulot, Dominique</creatorcontrib><creatorcontrib>Brichler, Ségolène</creatorcontrib><creatorcontrib>Layese, Richard</creatorcontrib><creatorcontrib>D’alteroche, Louis</creatorcontrib><creatorcontrib>Ganne-Carrie, Nathalie</creatorcontrib><creatorcontrib>Stern, Christiane</creatorcontrib><creatorcontrib>Saviano, Antonio</creatorcontrib><creatorcontrib>Leroy, Vincent</creatorcontrib><creatorcontrib>Roudot-Thoraval, Françoise</creatorcontrib><creatorcontrib>De Ledinghen, Victor</creatorcontrib><creatorcontrib>Loustaud-Ratti, Véronique</creatorcontrib><creatorcontrib>Silvain, Christine</creatorcontrib><creatorcontrib>Benali, Souad</creatorcontrib><creatorcontrib>Ingiliz, Patrick</creatorcontrib><creatorcontrib>Gouton, Martial</creatorcontrib><creatorcontrib>Guyader, Dominique</creatorcontrib><creatorcontrib>Roche, Bruno</creatorcontrib><creatorcontrib>Chazouillères, Olivier</creatorcontrib><creatorcontrib>Asselah, Tarik</creatorcontrib><creatorcontrib>Ziol, Marianne</creatorcontrib><creatorcontrib>DELTAVIR study group</creatorcontrib><title>High Diagnostic Value of Transient Elastography for Advanced Fibrosis and Cirrhosis in Patients With Chronic Hepatitis Delta</title><title>Clinical gastroenterology and hepatology</title><addtitle>Clin Gastroenterol Hepatol</addtitle><description>Liver biopsy remains the gold standard for fibrosis staging in patients with chronic hepatitis delta (CHD). Here, we comparatively evaluated the performance of transient elastography (TE) and biomarkers for the diagnosis of liver fibrosis in patients with CHD. A total of 230 HDV-infected RNA-positive patients from various centers who underwent liver biopsy and liver stiffness measurements (LSMs) using Fibroscan, within a period of 6 months maximum, were investigated retrospectively. Area under the receiver operating characteristic curve and Youden index were used to establish cutoff values of LSM. TE was compared with other noninvasive tests: aspartate aminotransferase to platelet ratio index, Fibrosis-4, and Delta-4 fibrosis scores. Histologic fibrosis stage distribution was: 20.4% for F0-F1; 27.0% for F2; 18.7% for F3; and 33.9% for F4. TE demonstrated good diagnostic performance for detecting cirrhosis and advanced fibrosis with an Area under the receiver operating characteristic curve of 0.88 and 0.86, which were significantly higher than those obtained with the other noninvasive tests (P = .004 and P &lt; .001). With a cutoff value of &gt;12 kPa for cirrhosis, the sensitivity was 70.5%, specificity was 86.2%, positive predictive value was 72.4%, negative predictive value was 85.1%, and accuracy was 80.9%. Using 10.4 kPa as the cutoff value for F3, the sensitivity was 70.2%, specificity was 83.5%, positive predictive value was 82.5%, negative predictive value was 71.7%, and accuracy was 76.5%. In 89% of patients with LSM ≤6.2 kPa, liver biopsy disclosed only absent or minimal fibrosis. TE demonstrated good diagnostic performance for advanced fibrosis and cirrhosis in patients with CHD. Advanced fibrosis is highly probable for LSM values ≥10 kPa. LSM values &lt;6 kPa almost totally exclude significant fibrosis. Between 6 and 10 kPa, liver biopsy should be discussed.</description><subject>Chronic Hepatitis D</subject><subject>Cirrhosis</subject><subject>Hepatitis Delta Virus</subject><subject>Noninvasive Tests</subject><subject>Transient Elastography</subject><issn>1542-3565</issn><issn>1542-7714</issn><issn>1542-7714</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kE1vEzEQhi1ERUvhB3BBPnLJMrb3wxanKm0JUiV6KHC0vPZs1tFmHWynUqX-eBwSeuQ0Hut5X2keQj4wqBiw9vOmsuux4sDrCmQFIF-RC9bUfNF1rH59eoumbc7J25Q2AFzVqntDzoXioJhqL8jzyq9Heu3Neg4pe0t_mmmPNAz0IZo5eZwzvZlMymEdzW58okOI9Mo9mtmio7e-jyH5RM3s6NLHOP7d_EzvTT5kE_3l80iXYwxzKV_hrvznglzjlM07cjaYKeH707wkP25vHparxd33r9-WV3cLyxpoF9xJrIVTvRCq7xSKTjKAAaTk0nDLWyUd7yy0YnBSNKIXveoaw3mP_VA7IS7Jp2PvLobfe0xZb32yOE1mxrBPWoBSEljHoaDsiNpyWIo46F30WxOfNAN9kK43ukjXB-kapC7SS-bjqX7fb9G9JP5ZLsCXI4DlyEePUSdb7BSDPqLN2gX_n_o_C4GSbA</recordid><startdate>20240830</startdate><enddate>20240830</enddate><creator>Roulot, Dominique</creator><creator>Brichler, Ségolène</creator><creator>Layese, Richard</creator><creator>D’alteroche, Louis</creator><creator>Ganne-Carrie, Nathalie</creator><creator>Stern, Christiane</creator><creator>Saviano, Antonio</creator><creator>Leroy, Vincent</creator><creator>Roudot-Thoraval, Françoise</creator><creator>De Ledinghen, Victor</creator><creator>Loustaud-Ratti, Véronique</creator><creator>Silvain, Christine</creator><creator>Benali, Souad</creator><creator>Ingiliz, Patrick</creator><creator>Gouton, Martial</creator><creator>Guyader, Dominique</creator><creator>Roche, Bruno</creator><creator>Chazouillères, Olivier</creator><creator>Asselah, Tarik</creator><creator>Ziol, Marianne</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0926-3563</orcidid></search><sort><creationdate>20240830</creationdate><title>High Diagnostic Value of Transient Elastography for Advanced Fibrosis and Cirrhosis in Patients With Chronic Hepatitis Delta</title><author>Roulot, Dominique ; Brichler, Ségolène ; Layese, Richard ; D’alteroche, Louis ; Ganne-Carrie, Nathalie ; Stern, Christiane ; Saviano, Antonio ; Leroy, Vincent ; Roudot-Thoraval, Françoise ; De Ledinghen, Victor ; Loustaud-Ratti, Véronique ; Silvain, Christine ; Benali, Souad ; Ingiliz, Patrick ; Gouton, Martial ; Guyader, Dominique ; Roche, Bruno ; Chazouillères, Olivier ; Asselah, Tarik ; Ziol, Marianne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1506-2d8e43d9b339b79e378100f08828a2c2698d27c063fd8353b3b975a22bebf4d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Chronic Hepatitis D</topic><topic>Cirrhosis</topic><topic>Hepatitis Delta Virus</topic><topic>Noninvasive Tests</topic><topic>Transient Elastography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Roulot, Dominique</creatorcontrib><creatorcontrib>Brichler, Ségolène</creatorcontrib><creatorcontrib>Layese, Richard</creatorcontrib><creatorcontrib>D’alteroche, Louis</creatorcontrib><creatorcontrib>Ganne-Carrie, Nathalie</creatorcontrib><creatorcontrib>Stern, Christiane</creatorcontrib><creatorcontrib>Saviano, Antonio</creatorcontrib><creatorcontrib>Leroy, Vincent</creatorcontrib><creatorcontrib>Roudot-Thoraval, Françoise</creatorcontrib><creatorcontrib>De Ledinghen, Victor</creatorcontrib><creatorcontrib>Loustaud-Ratti, Véronique</creatorcontrib><creatorcontrib>Silvain, Christine</creatorcontrib><creatorcontrib>Benali, Souad</creatorcontrib><creatorcontrib>Ingiliz, Patrick</creatorcontrib><creatorcontrib>Gouton, Martial</creatorcontrib><creatorcontrib>Guyader, Dominique</creatorcontrib><creatorcontrib>Roche, Bruno</creatorcontrib><creatorcontrib>Chazouillères, Olivier</creatorcontrib><creatorcontrib>Asselah, Tarik</creatorcontrib><creatorcontrib>Ziol, Marianne</creatorcontrib><creatorcontrib>DELTAVIR study group</creatorcontrib><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>Roulot, Dominique</au><au>Brichler, Ségolène</au><au>Layese, Richard</au><au>D’alteroche, Louis</au><au>Ganne-Carrie, Nathalie</au><au>Stern, Christiane</au><au>Saviano, Antonio</au><au>Leroy, Vincent</au><au>Roudot-Thoraval, Françoise</au><au>De Ledinghen, Victor</au><au>Loustaud-Ratti, Véronique</au><au>Silvain, Christine</au><au>Benali, Souad</au><au>Ingiliz, Patrick</au><au>Gouton, Martial</au><au>Guyader, Dominique</au><au>Roche, Bruno</au><au>Chazouillères, Olivier</au><au>Asselah, Tarik</au><au>Ziol, Marianne</au><aucorp>DELTAVIR study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High Diagnostic Value of Transient Elastography for Advanced Fibrosis and Cirrhosis in Patients With Chronic Hepatitis Delta</atitle><jtitle>Clinical gastroenterology and hepatology</jtitle><addtitle>Clin Gastroenterol Hepatol</addtitle><date>2024-08-30</date><risdate>2024</risdate><issn>1542-3565</issn><issn>1542-7714</issn><eissn>1542-7714</eissn><abstract>Liver biopsy remains the gold standard for fibrosis staging in patients with chronic hepatitis delta (CHD). Here, we comparatively evaluated the performance of transient elastography (TE) and biomarkers for the diagnosis of liver fibrosis in patients with CHD. A total of 230 HDV-infected RNA-positive patients from various centers who underwent liver biopsy and liver stiffness measurements (LSMs) using Fibroscan, within a period of 6 months maximum, were investigated retrospectively. Area under the receiver operating characteristic curve and Youden index were used to establish cutoff values of LSM. TE was compared with other noninvasive tests: aspartate aminotransferase to platelet ratio index, Fibrosis-4, and Delta-4 fibrosis scores. Histologic fibrosis stage distribution was: 20.4% for F0-F1; 27.0% for F2; 18.7% for F3; and 33.9% for F4. TE demonstrated good diagnostic performance for detecting cirrhosis and advanced fibrosis with an Area under the receiver operating characteristic curve of 0.88 and 0.86, which were significantly higher than those obtained with the other noninvasive tests (P = .004 and P &lt; .001). With a cutoff value of &gt;12 kPa for cirrhosis, the sensitivity was 70.5%, specificity was 86.2%, positive predictive value was 72.4%, negative predictive value was 85.1%, and accuracy was 80.9%. Using 10.4 kPa as the cutoff value for F3, the sensitivity was 70.2%, specificity was 83.5%, positive predictive value was 82.5%, negative predictive value was 71.7%, and accuracy was 76.5%. In 89% of patients with LSM ≤6.2 kPa, liver biopsy disclosed only absent or minimal fibrosis. TE demonstrated good diagnostic performance for advanced fibrosis and cirrhosis in patients with CHD. Advanced fibrosis is highly probable for LSM values ≥10 kPa. LSM values &lt;6 kPa almost totally exclude significant fibrosis. Between 6 and 10 kPa, liver biopsy should be discussed.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39209196</pmid><doi>10.1016/j.cgh.2024.08.008</doi><orcidid>https://orcid.org/0000-0003-0926-3563</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 1542-3565
ispartof Clinical gastroenterology and hepatology, 2024-08
issn 1542-3565
1542-7714
1542-7714
language eng
recordid cdi_proquest_miscellaneous_3099801720
source Elsevier ScienceDirect Journals Complete
subjects Chronic Hepatitis D
Cirrhosis
Hepatitis Delta Virus
Noninvasive Tests
Transient Elastography
title High Diagnostic Value of Transient Elastography for Advanced Fibrosis and Cirrhosis in Patients With Chronic Hepatitis Delta
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T18%3A09%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20Diagnostic%20Value%20of%20Transient%20Elastography%20for%20Advanced%20Fibrosis%20and%20Cirrhosis%20in%20Patients%20With%20Chronic%20Hepatitis%20Delta&rft.jtitle=Clinical%20gastroenterology%20and%20hepatology&rft.au=Roulot,%20Dominique&rft.aucorp=DELTAVIR%20study%20group&rft.date=2024-08-30&rft.issn=1542-3565&rft.eissn=1542-7714&rft_id=info:doi/10.1016/j.cgh.2024.08.008&rft_dat=%3Cproquest_cross%3E3099801720%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3099801720&rft_id=info:pmid/39209196&rft_els_id=S1542356524007766&rfr_iscdi=true