Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease
Alcohol is the most common cause of liver-related mortality and morbidity. We therefore aimed to assess and compare the prognostic performance of elastography and blood-based markers to predict time to the first liver-related event, severe infection, and all-cause mortality in patients with a histor...
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| Veröffentlicht in: | Journal of hepatology 2021-11, Vol.75 (5), p.1017-1025 |
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| creator | Rasmussen, Ditlev Nytoft Thiele, Maja Johansen, Stine Kjærgaard, Maria Lindvig, Katrine Prier Israelsen, Mads Antonsen, Steen Detlefsen, Sönke Krag, Aleksander Anastasiadou, Ema Arumugam, Manimozhian Bork, Peer Hansen, Torben Hartoft, Christina Israelsen, Hans Karsdal, Morten Legido-Quigley, Cristina Melberg, Hans Olav Thiele, Maja Trebicka, Jonel Krag, Aleksander Mann, Mathias Matthijnssens, Jelle |
| description | Alcohol is the most common cause of liver-related mortality and morbidity. We therefore aimed to assess and compare the prognostic performance of elastography and blood-based markers to predict time to the first liver-related event, severe infection, and all-cause mortality in patients with a history of excess drinking.
We performed a prospective cohort study in patients with early, compensated alcohol-related liver disease. At baseline, we obtained a liver biopsy, transient elastography (TE), 2-dimensional shear-wave elastography (2D-SWE), enhanced liver fibrosis test (ELF), FibroTest, fibrosis-4 index (FIB-4), non-alcoholic fatty liver fibrosis score (NFS) and Forns index. We compared C-statistics and time-dependent AUC for prognostication. We used validated cut-off points to create 3 risk groups for each test: low, intermediate and high risk.
We followed 462 patients for a median of 49 months (IQR 31–70). Median age was 57 years, 76% were males, 20% had advanced fibrosis. Eighty-four patients (18%) developed a liver-related event after a median of 18 months (7-34). TE had the highest prognostic accuracy, with a C-statistic of 0.876, and time-dependent AUC at 5 years of 0.889, comparable to 2D-SWE and ELF. TE, ELF and 2D-SWE outperformed FibroTest, FIB4, NFS, Forns index and biopsy-verified fibrosis stage. Compared to patients with TE 15 kPa. Periods of excessive drinking during follow-up increased the risk of progressing to liver-related events, except for patients in the low-risk groups.
TE, ELF and 2D-SWE are highly accurate prognostic markers in patients with alcohol-related liver disease. Easy-to-use cut-offs can distinguish between substantially different risk profiles.
Alcohol is the leading cause of death and illness due to liver disease. In this study, we assessed the ability of biomarkers to predict the risk of developing symptomatic liver disease in patients with early stages of alcohol-related liver disease. We found that several tests accurately predicted the risk of liver-related events such as ascites, esophageal varices and hepatic encephalopathy during an average follow-up of 4.1 years. Liver stiffness measurements by ultrasound elastography and the enhanced liver fibrosis test performed best. By using them, we were able to stratify patients into 3 groups with significantly different risks.
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•462 patient |
| doi_str_mv | 10.1016/j.jhep.2021.05.037 |
| format | Article |
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We performed a prospective cohort study in patients with early, compensated alcohol-related liver disease. At baseline, we obtained a liver biopsy, transient elastography (TE), 2-dimensional shear-wave elastography (2D-SWE), enhanced liver fibrosis test (ELF), FibroTest, fibrosis-4 index (FIB-4), non-alcoholic fatty liver fibrosis score (NFS) and Forns index. We compared C-statistics and time-dependent AUC for prognostication. We used validated cut-off points to create 3 risk groups for each test: low, intermediate and high risk.
We followed 462 patients for a median of 49 months (IQR 31–70). Median age was 57 years, 76% were males, 20% had advanced fibrosis. Eighty-four patients (18%) developed a liver-related event after a median of 18 months (7-34). TE had the highest prognostic accuracy, with a C-statistic of 0.876, and time-dependent AUC at 5 years of 0.889, comparable to 2D-SWE and ELF. TE, ELF and 2D-SWE outperformed FibroTest, FIB4, NFS, Forns index and biopsy-verified fibrosis stage. Compared to patients with TE <10 kPa, the hazard ratios for liver-related events for TE 10–15 kPa were 8.1 (3.2–20.4), and 27.9 (13.8–56.8) for TE >15 kPa. Periods of excessive drinking during follow-up increased the risk of progressing to liver-related events, except for patients in the low-risk groups.
TE, ELF and 2D-SWE are highly accurate prognostic markers in patients with alcohol-related liver disease. Easy-to-use cut-offs can distinguish between substantially different risk profiles.
Alcohol is the leading cause of death and illness due to liver disease. In this study, we assessed the ability of biomarkers to predict the risk of developing symptomatic liver disease in patients with early stages of alcohol-related liver disease. We found that several tests accurately predicted the risk of liver-related events such as ascites, esophageal varices and hepatic encephalopathy during an average follow-up of 4.1 years. Liver stiffness measurements by ultrasound elastography and the enhanced liver fibrosis test performed best. By using them, we were able to stratify patients into 3 groups with significantly different risks.
[Display omitted]
•462 patients with compensated ALD experienced 84 liver-related events during a median of 4.1 years of follow-up, and 76 patients died.•Elastography and the ELF test are accurate prognostic tests and outperform biopsy-verified fibrosis stage.•3-5% of patients with F0-1, liver stiffness by FibroScan <10 kPa, or ELF test <9.8 experienced liver-related events during follow up.•This increased to 53–64% of patients with F3-4, liver stiffness >15 kPa, or ELF >10.5.•The hazard ratio for liver-related events was 8 for patients with liver stiffness of 10-15 kPa, and 28 for >15 kPa.</description><identifier>ISSN: 0168-8278</identifier><identifier>EISSN: 1600-0641</identifier><identifier>DOI: 10.1016/j.jhep.2021.05.037</identifier><identifier>PMID: 34118335</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Aged ; Alcohol ; Alcohol Drinking - adverse effects ; Alcohol Drinking - epidemiology ; Alcohol Drinking - physiopathology ; Alcoholic liver disease ; Ascites ; Biomarkers ; Biomarkers - analysis ; Biopsy ; Biopsy - methods ; Biopsy - standards ; Biopsy - statistics & numerical data ; Cohort Studies ; Decompensation ; Denmark - epidemiology ; Drinking behavior ; Elasticity Imaging Techniques - methods ; Elasticity Imaging Techniques - statistics & numerical data ; Esophagus ; Fatty liver ; Female ; Fibrosis ; Hepatic encephalopathy ; Humans ; Liver - pathology ; Liver diseases ; Liver Diseases - diagnosis ; Liver Diseases - epidemiology ; Liver stiffness ; Male ; Middle Aged ; Morbidity ; Mortality ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Risk Factors ; Risk groups</subject><ispartof>Journal of hepatology, 2021-11, Vol.75 (5), p.1017-1025</ispartof><rights>2021 The Authors</rights><rights>Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Nov 2021</rights><rights>2021 The Authors 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-a732c78287c4a9e1e2d567b4e232dd2a90767b5b0ecb326c95834923c8fd12733</citedby><cites>FETCH-LOGICAL-c483t-a732c78287c4a9e1e2d567b4e232dd2a90767b5b0ecb326c95834923c8fd12733</cites><orcidid>0000-0002-5031-2294 ; 0000-0002-3414-5369 ; 0000-0002-9598-4932 ; 0000-0001-9443-5846 ; 0000-0003-1854-1924 ; 0000-0001-5670-1840</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168827821004116$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34118335$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rasmussen, Ditlev Nytoft</creatorcontrib><creatorcontrib>Thiele, Maja</creatorcontrib><creatorcontrib>Johansen, Stine</creatorcontrib><creatorcontrib>Kjærgaard, Maria</creatorcontrib><creatorcontrib>Lindvig, Katrine Prier</creatorcontrib><creatorcontrib>Israelsen, Mads</creatorcontrib><creatorcontrib>Antonsen, Steen</creatorcontrib><creatorcontrib>Detlefsen, Sönke</creatorcontrib><creatorcontrib>Krag, Aleksander</creatorcontrib><creatorcontrib>Anastasiadou, Ema</creatorcontrib><creatorcontrib>Arumugam, Manimozhian</creatorcontrib><creatorcontrib>Bork, Peer</creatorcontrib><creatorcontrib>Hansen, Torben</creatorcontrib><creatorcontrib>Hartoft, Christina</creatorcontrib><creatorcontrib>Israelsen, Hans</creatorcontrib><creatorcontrib>Karsdal, Morten</creatorcontrib><creatorcontrib>Legido-Quigley, Cristina</creatorcontrib><creatorcontrib>Melberg, Hans Olav</creatorcontrib><creatorcontrib>Thiele, Maja</creatorcontrib><creatorcontrib>Trebicka, Jonel</creatorcontrib><creatorcontrib>Krag, Aleksander</creatorcontrib><creatorcontrib>Mann, Mathias</creatorcontrib><creatorcontrib>Matthijnssens, Jelle</creatorcontrib><creatorcontrib>on behalf of the GALAXY</creatorcontrib><creatorcontrib>MicrobLiver consortia</creatorcontrib><creatorcontrib>GALAXY</creatorcontrib><title>Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease</title><title>Journal of hepatology</title><addtitle>J Hepatol</addtitle><description>Alcohol is the most common cause of liver-related mortality and morbidity. We therefore aimed to assess and compare the prognostic performance of elastography and blood-based markers to predict time to the first liver-related event, severe infection, and all-cause mortality in patients with a history of excess drinking.
We performed a prospective cohort study in patients with early, compensated alcohol-related liver disease. At baseline, we obtained a liver biopsy, transient elastography (TE), 2-dimensional shear-wave elastography (2D-SWE), enhanced liver fibrosis test (ELF), FibroTest, fibrosis-4 index (FIB-4), non-alcoholic fatty liver fibrosis score (NFS) and Forns index. We compared C-statistics and time-dependent AUC for prognostication. We used validated cut-off points to create 3 risk groups for each test: low, intermediate and high risk.
We followed 462 patients for a median of 49 months (IQR 31–70). Median age was 57 years, 76% were males, 20% had advanced fibrosis. Eighty-four patients (18%) developed a liver-related event after a median of 18 months (7-34). TE had the highest prognostic accuracy, with a C-statistic of 0.876, and time-dependent AUC at 5 years of 0.889, comparable to 2D-SWE and ELF. TE, ELF and 2D-SWE outperformed FibroTest, FIB4, NFS, Forns index and biopsy-verified fibrosis stage. Compared to patients with TE <10 kPa, the hazard ratios for liver-related events for TE 10–15 kPa were 8.1 (3.2–20.4), and 27.9 (13.8–56.8) for TE >15 kPa. Periods of excessive drinking during follow-up increased the risk of progressing to liver-related events, except for patients in the low-risk groups.
TE, ELF and 2D-SWE are highly accurate prognostic markers in patients with alcohol-related liver disease. Easy-to-use cut-offs can distinguish between substantially different risk profiles.
Alcohol is the leading cause of death and illness due to liver disease. In this study, we assessed the ability of biomarkers to predict the risk of developing symptomatic liver disease in patients with early stages of alcohol-related liver disease. We found that several tests accurately predicted the risk of liver-related events such as ascites, esophageal varices and hepatic encephalopathy during an average follow-up of 4.1 years. Liver stiffness measurements by ultrasound elastography and the enhanced liver fibrosis test performed best. By using them, we were able to stratify patients into 3 groups with significantly different risks.
[Display omitted]
•462 patients with compensated ALD experienced 84 liver-related events during a median of 4.1 years of follow-up, and 76 patients died.•Elastography and the ELF test are accurate prognostic tests and outperform biopsy-verified fibrosis stage.•3-5% of patients with F0-1, liver stiffness by FibroScan <10 kPa, or ELF test <9.8 experienced liver-related events during follow up.•This increased to 53–64% of patients with F3-4, liver stiffness >15 kPa, or ELF >10.5.•The hazard ratio for liver-related events was 8 for patients with liver stiffness of 10-15 kPa, and 28 for >15 kPa.</description><subject>Aged</subject><subject>Alcohol</subject><subject>Alcohol Drinking - adverse effects</subject><subject>Alcohol Drinking - epidemiology</subject><subject>Alcohol Drinking - physiopathology</subject><subject>Alcoholic liver disease</subject><subject>Ascites</subject><subject>Biomarkers</subject><subject>Biomarkers - analysis</subject><subject>Biopsy</subject><subject>Biopsy - methods</subject><subject>Biopsy - standards</subject><subject>Biopsy - statistics & numerical data</subject><subject>Cohort Studies</subject><subject>Decompensation</subject><subject>Denmark - epidemiology</subject><subject>Drinking behavior</subject><subject>Elasticity Imaging Techniques - methods</subject><subject>Elasticity Imaging Techniques - statistics & numerical data</subject><subject>Esophagus</subject><subject>Fatty liver</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Hepatic encephalopathy</subject><subject>Humans</subject><subject>Liver - pathology</subject><subject>Liver diseases</subject><subject>Liver Diseases - diagnosis</subject><subject>Liver Diseases - epidemiology</subject><subject>Liver stiffness</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Risk Factors</subject><subject>Risk groups</subject><issn>0168-8278</issn><issn>1600-0641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGK1TAUhoMozp3RF3AhATduWk-SpklBBBl0FAZ0oeuQpqdzU9umJr0X7tubcsdBXbgK4XznJ38-Ql4wKBmw-s1QDntcSg6clSBLEOoR2bEaoIC6Yo_JLkO60FzpC3KZ0gAAAprqKbkQFWNaCLkj_dcY7uaQVu_ogrEPcbKzQxp6qmjrw2TjD4yJujAtNmJH10BHf8S4DZd0on6maON4onZ0YR_GIuJo1wyeqc4ntAmfkSe9HRM-vz-vyPePH75dfypuv9x8vn5_W7hKi7WwSnCnNNfKVbZBhryTtWor5IJ3HbcNqHyVLaBrBa9dI7WoGi6c7jvGlRBX5N05dzm0E3YO5zXa0SzR5yInE6w3f09mvzd34Wi05FxDlQNe3wfE8POAaTWTTw7H0c4YDslwWYFkUoPO6Kt_0CEc4pzrGV6DrGsm5RbIz5SLIaWI_cNjGJhNoxnMptFsGg1IkzXmpZd_1nhY-e0tA2_PAObPPHqMJjmPWVznI7rVdMH_L_8XBSKvgA</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Rasmussen, Ditlev Nytoft</creator><creator>Thiele, Maja</creator><creator>Johansen, Stine</creator><creator>Kjærgaard, Maria</creator><creator>Lindvig, Katrine Prier</creator><creator>Israelsen, Mads</creator><creator>Antonsen, Steen</creator><creator>Detlefsen, Sönke</creator><creator>Krag, Aleksander</creator><creator>Anastasiadou, Ema</creator><creator>Arumugam, Manimozhian</creator><creator>Bork, Peer</creator><creator>Hansen, Torben</creator><creator>Hartoft, Christina</creator><creator>Israelsen, Hans</creator><creator>Karsdal, Morten</creator><creator>Legido-Quigley, Cristina</creator><creator>Melberg, Hans Olav</creator><creator>Thiele, Maja</creator><creator>Trebicka, Jonel</creator><creator>Krag, Aleksander</creator><creator>Mann, Mathias</creator><creator>Matthijnssens, Jelle</creator><general>Elsevier B.V</general><general>Elsevier Science Ltd</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><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>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5031-2294</orcidid><orcidid>https://orcid.org/0000-0002-3414-5369</orcidid><orcidid>https://orcid.org/0000-0002-9598-4932</orcidid><orcidid>https://orcid.org/0000-0001-9443-5846</orcidid><orcidid>https://orcid.org/0000-0003-1854-1924</orcidid><orcidid>https://orcid.org/0000-0001-5670-1840</orcidid></search><sort><creationdate>202111</creationdate><title>Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease</title><author>Rasmussen, Ditlev Nytoft ; Thiele, Maja ; Johansen, Stine ; Kjærgaard, Maria ; Lindvig, Katrine Prier ; Israelsen, Mads ; Antonsen, Steen ; Detlefsen, Sönke ; Krag, Aleksander ; Anastasiadou, Ema ; Arumugam, Manimozhian ; Bork, Peer ; Hansen, Torben ; Hartoft, Christina ; Israelsen, Hans ; Karsdal, Morten ; Legido-Quigley, Cristina ; Melberg, Hans Olav ; Thiele, Maja ; Trebicka, Jonel ; Krag, Aleksander ; Mann, Mathias ; Matthijnssens, Jelle</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-a732c78287c4a9e1e2d567b4e232dd2a90767b5b0ecb326c95834923c8fd12733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Alcohol</topic><topic>Alcohol Drinking - adverse effects</topic><topic>Alcohol Drinking - epidemiology</topic><topic>Alcohol Drinking - physiopathology</topic><topic>Alcoholic liver disease</topic><topic>Ascites</topic><topic>Biomarkers</topic><topic>Biomarkers - analysis</topic><topic>Biopsy</topic><topic>Biopsy - methods</topic><topic>Biopsy - standards</topic><topic>Biopsy - statistics & numerical data</topic><topic>Cohort Studies</topic><topic>Decompensation</topic><topic>Denmark - epidemiology</topic><topic>Drinking behavior</topic><topic>Elasticity Imaging Techniques - methods</topic><topic>Elasticity Imaging Techniques - statistics & numerical data</topic><topic>Esophagus</topic><topic>Fatty liver</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Hepatic encephalopathy</topic><topic>Humans</topic><topic>Liver - pathology</topic><topic>Liver diseases</topic><topic>Liver Diseases - diagnosis</topic><topic>Liver Diseases - epidemiology</topic><topic>Liver stiffness</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Risk Factors</topic><topic>Risk groups</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rasmussen, Ditlev Nytoft</creatorcontrib><creatorcontrib>Thiele, Maja</creatorcontrib><creatorcontrib>Johansen, Stine</creatorcontrib><creatorcontrib>Kjærgaard, Maria</creatorcontrib><creatorcontrib>Lindvig, Katrine Prier</creatorcontrib><creatorcontrib>Israelsen, Mads</creatorcontrib><creatorcontrib>Antonsen, Steen</creatorcontrib><creatorcontrib>Detlefsen, Sönke</creatorcontrib><creatorcontrib>Krag, Aleksander</creatorcontrib><creatorcontrib>Anastasiadou, Ema</creatorcontrib><creatorcontrib>Arumugam, Manimozhian</creatorcontrib><creatorcontrib>Bork, Peer</creatorcontrib><creatorcontrib>Hansen, Torben</creatorcontrib><creatorcontrib>Hartoft, Christina</creatorcontrib><creatorcontrib>Israelsen, Hans</creatorcontrib><creatorcontrib>Karsdal, Morten</creatorcontrib><creatorcontrib>Legido-Quigley, Cristina</creatorcontrib><creatorcontrib>Melberg, Hans Olav</creatorcontrib><creatorcontrib>Thiele, Maja</creatorcontrib><creatorcontrib>Trebicka, Jonel</creatorcontrib><creatorcontrib>Krag, Aleksander</creatorcontrib><creatorcontrib>Mann, Mathias</creatorcontrib><creatorcontrib>Matthijnssens, Jelle</creatorcontrib><creatorcontrib>on behalf of the GALAXY</creatorcontrib><creatorcontrib>MicrobLiver consortia</creatorcontrib><creatorcontrib>GALAXY</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rasmussen, Ditlev Nytoft</au><au>Thiele, Maja</au><au>Johansen, Stine</au><au>Kjærgaard, Maria</au><au>Lindvig, Katrine Prier</au><au>Israelsen, Mads</au><au>Antonsen, Steen</au><au>Detlefsen, Sönke</au><au>Krag, Aleksander</au><au>Anastasiadou, Ema</au><au>Arumugam, Manimozhian</au><au>Bork, Peer</au><au>Hansen, Torben</au><au>Hartoft, Christina</au><au>Israelsen, Hans</au><au>Karsdal, Morten</au><au>Legido-Quigley, Cristina</au><au>Melberg, Hans Olav</au><au>Thiele, Maja</au><au>Trebicka, Jonel</au><au>Krag, Aleksander</au><au>Mann, Mathias</au><au>Matthijnssens, Jelle</au><aucorp>on behalf of the GALAXY</aucorp><aucorp>MicrobLiver consortia</aucorp><aucorp>GALAXY</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease</atitle><jtitle>Journal of hepatology</jtitle><addtitle>J Hepatol</addtitle><date>2021-11</date><risdate>2021</risdate><volume>75</volume><issue>5</issue><spage>1017</spage><epage>1025</epage><pages>1017-1025</pages><issn>0168-8278</issn><eissn>1600-0641</eissn><abstract>Alcohol is the most common cause of liver-related mortality and morbidity. We therefore aimed to assess and compare the prognostic performance of elastography and blood-based markers to predict time to the first liver-related event, severe infection, and all-cause mortality in patients with a history of excess drinking.
We performed a prospective cohort study in patients with early, compensated alcohol-related liver disease. At baseline, we obtained a liver biopsy, transient elastography (TE), 2-dimensional shear-wave elastography (2D-SWE), enhanced liver fibrosis test (ELF), FibroTest, fibrosis-4 index (FIB-4), non-alcoholic fatty liver fibrosis score (NFS) and Forns index. We compared C-statistics and time-dependent AUC for prognostication. We used validated cut-off points to create 3 risk groups for each test: low, intermediate and high risk.
We followed 462 patients for a median of 49 months (IQR 31–70). Median age was 57 years, 76% were males, 20% had advanced fibrosis. Eighty-four patients (18%) developed a liver-related event after a median of 18 months (7-34). TE had the highest prognostic accuracy, with a C-statistic of 0.876, and time-dependent AUC at 5 years of 0.889, comparable to 2D-SWE and ELF. TE, ELF and 2D-SWE outperformed FibroTest, FIB4, NFS, Forns index and biopsy-verified fibrosis stage. Compared to patients with TE <10 kPa, the hazard ratios for liver-related events for TE 10–15 kPa were 8.1 (3.2–20.4), and 27.9 (13.8–56.8) for TE >15 kPa. Periods of excessive drinking during follow-up increased the risk of progressing to liver-related events, except for patients in the low-risk groups.
TE, ELF and 2D-SWE are highly accurate prognostic markers in patients with alcohol-related liver disease. Easy-to-use cut-offs can distinguish between substantially different risk profiles.
Alcohol is the leading cause of death and illness due to liver disease. In this study, we assessed the ability of biomarkers to predict the risk of developing symptomatic liver disease in patients with early stages of alcohol-related liver disease. We found that several tests accurately predicted the risk of liver-related events such as ascites, esophageal varices and hepatic encephalopathy during an average follow-up of 4.1 years. Liver stiffness measurements by ultrasound elastography and the enhanced liver fibrosis test performed best. By using them, we were able to stratify patients into 3 groups with significantly different risks.
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•462 patients with compensated ALD experienced 84 liver-related events during a median of 4.1 years of follow-up, and 76 patients died.•Elastography and the ELF test are accurate prognostic tests and outperform biopsy-verified fibrosis stage.•3-5% of patients with F0-1, liver stiffness by FibroScan <10 kPa, or ELF test <9.8 experienced liver-related events during follow up.•This increased to 53–64% of patients with F3-4, liver stiffness >15 kPa, or ELF >10.5.•The hazard ratio for liver-related events was 8 for patients with liver stiffness of 10-15 kPa, and 28 for >15 kPa.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>34118335</pmid><doi>10.1016/j.jhep.2021.05.037</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-5031-2294</orcidid><orcidid>https://orcid.org/0000-0002-3414-5369</orcidid><orcidid>https://orcid.org/0000-0002-9598-4932</orcidid><orcidid>https://orcid.org/0000-0001-9443-5846</orcidid><orcidid>https://orcid.org/0000-0003-1854-1924</orcidid><orcidid>https://orcid.org/0000-0001-5670-1840</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0168-8278 |
| ispartof | Journal of hepatology, 2021-11, Vol.75 (5), p.1017-1025 |
| issn | 0168-8278 1600-0641 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8522804 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Aged Alcohol Alcohol Drinking - adverse effects Alcohol Drinking - epidemiology Alcohol Drinking - physiopathology Alcoholic liver disease Ascites Biomarkers Biomarkers - analysis Biopsy Biopsy - methods Biopsy - standards Biopsy - statistics & numerical data Cohort Studies Decompensation Denmark - epidemiology Drinking behavior Elasticity Imaging Techniques - methods Elasticity Imaging Techniques - statistics & numerical data Esophagus Fatty liver Female Fibrosis Hepatic encephalopathy Humans Liver - pathology Liver diseases Liver Diseases - diagnosis Liver Diseases - epidemiology Liver stiffness Male Middle Aged Morbidity Mortality Predictive Value of Tests Prognosis Prospective Studies Risk Factors Risk groups |
| title | Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T16%3A01%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Prognostic%20performance%20of%207%20biomarkers%20compared%20to%20liver%20biopsy%20in%20early%20alcohol-related%20liver%20disease&rft.jtitle=Journal%20of%20hepatology&rft.au=Rasmussen,%20Ditlev%20Nytoft&rft.aucorp=on%20behalf%20of%20the%20GALAXY&rft.date=2021-11&rft.volume=75&rft.issue=5&rft.spage=1017&rft.epage=1025&rft.pages=1017-1025&rft.issn=0168-8278&rft.eissn=1600-0641&rft_id=info:doi/10.1016/j.jhep.2021.05.037&rft_dat=%3Cproquest_pubme%3E2540515808%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2605661554&rft_id=info:pmid/34118335&rft_els_id=S0168827821004116&rfr_iscdi=true |