Role of serum toll-like receptors 2 and 4 in non-alcoholic steatohepatitis and liver fibrosis

Background and Aim Non‐alcoholic fatty liver disease is a common cause of chronic liver disease, including non‐alcoholic steatohepatitis (NASH). Our aim was to investigate whether serum toll‐like receptors 2 and 4 (TLR2 and TLR4) levels are correlated with NASH and able to predict liver fibrosis, as...

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Published in:Journal of gastroenterology and hepatology 2015-07, Vol.30 (7), p.1190-1196
Main Authors: Cengiz, Mustafa, Ozenirler, Seren, Elbeg, Sehri
Format: Article
Language:English
Subjects:
Adult
Aged
Biomarkers - blood
Dobutamine
Forecasting
Humans
Liver Cirrhosis - blood
Liver Cirrhosis - diagnosis
Middle Aged
Molecular Sequence Data
NASH
Non-alcoholic Fatty Liver Disease - blood
non-invasive marker
Toll-Like Receptor 2 - blood
Toll-Like Receptor 4 - blood
toll-like receptors
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cited_by cdi_FETCH-LOGICAL-c3634-6d939e1c7d01a08f82ab45a4f8fd25fca0c49131a35287714794ae0980a19be73
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container_title Journal of gastroenterology and hepatology
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creator Cengiz, Mustafa
Ozenirler, Seren
Elbeg, Sehri
description Background and Aim Non‐alcoholic fatty liver disease is a common cause of chronic liver disease, including non‐alcoholic steatohepatitis (NASH). Our aim was to investigate whether serum toll‐like receptors 2 and 4 (TLR2 and TLR4) levels are correlated with NASH and able to predict liver fibrosis, as well as to compare these markers with other non‐invasive fibrosis scores (aspartate aminotransferase [AST] to alanine aminotransferase ratio, AST to platelet ratio index, fibrosis index, fibrosis 4, and fibrosis cirrhosis index). Methods Serum samples were obtained from consecutive biopsy proven NASH patients and healthy controls. Serum TLR2 and TLR4 were measured using ELISA. Stage of fibrosis was evaluated using the Brunt Criteria. The different non‐invasive fibrosis scores were compared using areas under the curve. Results Fifty‐seven patients with NASH and 57 healthy individuals were enrolled in the study. Serum TLR2 levels were not significantly different between the healthy controls and NASH patients. The medians were 3.88 ng/mL ± 0.29 versus 3.81 ng/mL ± 0.32, respectively (P = 0.587). In comparing the levels of TLR4 between groups, the medians were 1.05 ng/mL ± 0.13 versus 1.46 ng/mL ± 0.27, respectively (P 
doi_str_mv 10.1111/jgh.12924
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Our aim was to investigate whether serum toll‐like receptors 2 and 4 (TLR2 and TLR4) levels are correlated with NASH and able to predict liver fibrosis, as well as to compare these markers with other non‐invasive fibrosis scores (aspartate aminotransferase [AST] to alanine aminotransferase ratio, AST to platelet ratio index, fibrosis index, fibrosis 4, and fibrosis cirrhosis index). Methods Serum samples were obtained from consecutive biopsy proven NASH patients and healthy controls. Serum TLR2 and TLR4 were measured using ELISA. Stage of fibrosis was evaluated using the Brunt Criteria. The different non‐invasive fibrosis scores were compared using areas under the curve. Results Fifty‐seven patients with NASH and 57 healthy individuals were enrolled in the study. Serum TLR2 levels were not significantly different between the healthy controls and NASH patients. The medians were 3.88 ng/mL ± 0.29 versus 3.81 ng/mL ± 0.32, respectively (P = 0.587). In comparing the levels of TLR4 between groups, the medians were 1.05 ng/mL ± 0.13 versus 1.46 ng/mL ± 0.27, respectively (P &lt; 0.001). In NASH patients, the levels of serum TLR4 increased with the stage of fibrosis: TLR4 medians were F0:1.01, F1:1.46, F2:2.14, F3:3.74, F4:5.83 (P &lt; 0.001). TLR4 produced AUCs for ≥ F1, ≥ F2, and ≥ F3 of 0.862, 0.810, and 0.905, respectively (P &lt; 0.001). TLR4 levels were more predictive than other non‐invasive fibrosis scores in liver fibrosis. Conclusion Serum TLR4 levels but not TLR2 were elevated in NASH patients in comparison with healthy controls. And in NASH patients, serum TLR4 levels both correlated with and were able to predict liver fibrosis.</description><identifier>ISSN: 0815-9319</identifier><identifier>EISSN: 1440-1746</identifier><identifier>DOI: 10.1111/jgh.12924</identifier><identifier>PMID: 25684563</identifier><language>eng</language><publisher>Australia: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Biomarkers - blood ; Dobutamine ; Forecasting ; Humans ; Liver Cirrhosis - blood ; Liver Cirrhosis - diagnosis ; Middle Aged ; Molecular Sequence Data ; NASH ; Non-alcoholic Fatty Liver Disease - blood ; non-invasive marker ; Toll-Like Receptor 2 - blood ; Toll-Like Receptor 4 - blood ; toll-like receptors</subject><ispartof>Journal of gastroenterology and hepatology, 2015-07, Vol.30 (7), p.1190-1196</ispartof><rights>2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd</rights><rights>2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3634-6d939e1c7d01a08f82ab45a4f8fd25fca0c49131a35287714794ae0980a19be73</citedby><cites>FETCH-LOGICAL-c3634-6d939e1c7d01a08f82ab45a4f8fd25fca0c49131a35287714794ae0980a19be73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25684563$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cengiz, Mustafa</creatorcontrib><creatorcontrib>Ozenirler, Seren</creatorcontrib><creatorcontrib>Elbeg, Sehri</creatorcontrib><title>Role of serum toll-like receptors 2 and 4 in non-alcoholic steatohepatitis and liver fibrosis</title><title>Journal of gastroenterology and hepatology</title><addtitle>J Gastroenterol Hepatol</addtitle><description>Background and Aim Non‐alcoholic fatty liver disease is a common cause of chronic liver disease, including non‐alcoholic steatohepatitis (NASH). Our aim was to investigate whether serum toll‐like receptors 2 and 4 (TLR2 and TLR4) levels are correlated with NASH and able to predict liver fibrosis, as well as to compare these markers with other non‐invasive fibrosis scores (aspartate aminotransferase [AST] to alanine aminotransferase ratio, AST to platelet ratio index, fibrosis index, fibrosis 4, and fibrosis cirrhosis index). Methods Serum samples were obtained from consecutive biopsy proven NASH patients and healthy controls. Serum TLR2 and TLR4 were measured using ELISA. Stage of fibrosis was evaluated using the Brunt Criteria. The different non‐invasive fibrosis scores were compared using areas under the curve. Results Fifty‐seven patients with NASH and 57 healthy individuals were enrolled in the study. Serum TLR2 levels were not significantly different between the healthy controls and NASH patients. The medians were 3.88 ng/mL ± 0.29 versus 3.81 ng/mL ± 0.32, respectively (P = 0.587). In comparing the levels of TLR4 between groups, the medians were 1.05 ng/mL ± 0.13 versus 1.46 ng/mL ± 0.27, respectively (P &lt; 0.001). In NASH patients, the levels of serum TLR4 increased with the stage of fibrosis: TLR4 medians were F0:1.01, F1:1.46, F2:2.14, F3:3.74, F4:5.83 (P &lt; 0.001). TLR4 produced AUCs for ≥ F1, ≥ F2, and ≥ F3 of 0.862, 0.810, and 0.905, respectively (P &lt; 0.001). TLR4 levels were more predictive than other non‐invasive fibrosis scores in liver fibrosis. Conclusion Serum TLR4 levels but not TLR2 were elevated in NASH patients in comparison with healthy controls. And in NASH patients, serum TLR4 levels both correlated with and were able to predict liver fibrosis.</description><subject>Adult</subject><subject>Aged</subject><subject>Biomarkers - blood</subject><subject>Dobutamine</subject><subject>Forecasting</subject><subject>Humans</subject><subject>Liver Cirrhosis - blood</subject><subject>Liver Cirrhosis - diagnosis</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>NASH</subject><subject>Non-alcoholic Fatty Liver Disease - blood</subject><subject>non-invasive marker</subject><subject>Toll-Like Receptor 2 - blood</subject><subject>Toll-Like Receptor 4 - blood</subject><subject>toll-like receptors</subject><issn>0815-9319</issn><issn>1440-1746</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp1kMlOwzAQQC0EgrIc-AHkIxwCduzY8ZG1ZUcIhISELNeZUIMbFztl-XsCBW7MZS5vnkYPoXVKtmk3O0-Po22aq5zPoR7lnGRUcjGPeqSkRaYYVUtoOaUnQggnslhES3khSl4I1kMP18EDDjVOEKdj3AbvM--eAUewMGlDTDjHpqkwx67BTWgy420YBe8sTi2YNoxgYlrXuvSNefcKEdduGENyaRUt1MYnWPvZK-j26PBmf5CdXfaP93fPMssE45moFFNArawINaSsy9wMeWF4XdZVXtTWEMsVZdSwIi-lpFwqboCokhiqhiDZCtqceScxvEwhtXrskgXvTQNhmjQVigiuRJl36NYMtd2HKUKtJ9GNTfzQlOivmrqrqb9rduzGj3Y6HEP1R_7m64CdGfDmPHz8b9In_cGvMptduK7e-9-Fic9aSCYLfXfR14O9q9OD8_sLzdgn0ZSM-A</recordid><startdate>201507</startdate><enddate>201507</enddate><creator>Cengiz, Mustafa</creator><creator>Ozenirler, Seren</creator><creator>Elbeg, Sehri</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>201507</creationdate><title>Role of serum toll-like receptors 2 and 4 in non-alcoholic steatohepatitis and liver fibrosis</title><author>Cengiz, Mustafa ; Ozenirler, Seren ; Elbeg, Sehri</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3634-6d939e1c7d01a08f82ab45a4f8fd25fca0c49131a35287714794ae0980a19be73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biomarkers - blood</topic><topic>Dobutamine</topic><topic>Forecasting</topic><topic>Humans</topic><topic>Liver Cirrhosis - blood</topic><topic>Liver Cirrhosis - diagnosis</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>NASH</topic><topic>Non-alcoholic Fatty Liver Disease - blood</topic><topic>non-invasive marker</topic><topic>Toll-Like Receptor 2 - blood</topic><topic>Toll-Like Receptor 4 - blood</topic><topic>toll-like receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cengiz, Mustafa</creatorcontrib><creatorcontrib>Ozenirler, Seren</creatorcontrib><creatorcontrib>Elbeg, Sehri</creatorcontrib><collection>Istex</collection><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>Journal of gastroenterology and hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cengiz, Mustafa</au><au>Ozenirler, Seren</au><au>Elbeg, Sehri</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of serum toll-like receptors 2 and 4 in non-alcoholic steatohepatitis and liver fibrosis</atitle><jtitle>Journal of gastroenterology and hepatology</jtitle><addtitle>J Gastroenterol Hepatol</addtitle><date>2015-07</date><risdate>2015</risdate><volume>30</volume><issue>7</issue><spage>1190</spage><epage>1196</epage><pages>1190-1196</pages><issn>0815-9319</issn><eissn>1440-1746</eissn><abstract>Background and Aim Non‐alcoholic fatty liver disease is a common cause of chronic liver disease, including non‐alcoholic steatohepatitis (NASH). Our aim was to investigate whether serum toll‐like receptors 2 and 4 (TLR2 and TLR4) levels are correlated with NASH and able to predict liver fibrosis, as well as to compare these markers with other non‐invasive fibrosis scores (aspartate aminotransferase [AST] to alanine aminotransferase ratio, AST to platelet ratio index, fibrosis index, fibrosis 4, and fibrosis cirrhosis index). Methods Serum samples were obtained from consecutive biopsy proven NASH patients and healthy controls. Serum TLR2 and TLR4 were measured using ELISA. Stage of fibrosis was evaluated using the Brunt Criteria. The different non‐invasive fibrosis scores were compared using areas under the curve. Results Fifty‐seven patients with NASH and 57 healthy individuals were enrolled in the study. Serum TLR2 levels were not significantly different between the healthy controls and NASH patients. The medians were 3.88 ng/mL ± 0.29 versus 3.81 ng/mL ± 0.32, respectively (P = 0.587). In comparing the levels of TLR4 between groups, the medians were 1.05 ng/mL ± 0.13 versus 1.46 ng/mL ± 0.27, respectively (P &lt; 0.001). In NASH patients, the levels of serum TLR4 increased with the stage of fibrosis: TLR4 medians were F0:1.01, F1:1.46, F2:2.14, F3:3.74, F4:5.83 (P &lt; 0.001). TLR4 produced AUCs for ≥ F1, ≥ F2, and ≥ F3 of 0.862, 0.810, and 0.905, respectively (P &lt; 0.001). TLR4 levels were more predictive than other non‐invasive fibrosis scores in liver fibrosis. Conclusion Serum TLR4 levels but not TLR2 were elevated in NASH patients in comparison with healthy controls. And in NASH patients, serum TLR4 levels both correlated with and were able to predict liver fibrosis.</abstract><cop>Australia</cop><pub>Blackwell Publishing Ltd</pub><pmid>25684563</pmid><doi>10.1111/jgh.12924</doi><tpages>7</tpages></addata></record>
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subjects Adult
Aged
Biomarkers - blood
Dobutamine
Forecasting
Humans
Liver Cirrhosis - blood
Liver Cirrhosis - diagnosis
Middle Aged
Molecular Sequence Data
NASH
Non-alcoholic Fatty Liver Disease - blood
non-invasive marker
Toll-Like Receptor 2 - blood
Toll-Like Receptor 4 - blood
toll-like receptors
title Role of serum toll-like receptors 2 and 4 in non-alcoholic steatohepatitis and liver fibrosis
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