Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122
Summary As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between...
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| Veröffentlicht in: | Journal of viral hepatitis 2013-03, Vol.20 (3), p.158-166 |
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| creator | van der Meer, A. J. Farid, W. R. R. Sonneveld, M. J. de Ruiter, P. E. Boonstra, A. van Vuuren, A. J. Verheij, J. Hansen, B. E. de Knegt, R. J. van der Laan, L. J. W. Janssen, H. L. A. |
| description | Summary
As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between hepatocyte‐derived microRNAs in serum and liver injury in patients with chronic hepatitis C. The hepatocyte‐derived miR‐122 and miR‐192 were analysed in sera of 102 chronic HCV‐infected patients and 24 healthy controls. Serum levels of miR‐122 and miR‐192 correlated strongly with ALT (R = 0.67 and R = 0.65, respectively, P |
| doi_str_mv | 10.1111/jvh.12001 |
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As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between hepatocyte‐derived microRNAs in serum and liver injury in patients with chronic hepatitis C. The hepatocyte‐derived miR‐122 and miR‐192 were analysed in sera of 102 chronic HCV‐infected patients and 24 healthy controls. Serum levels of miR‐122 and miR‐192 correlated strongly with ALT (R = 0.67 and R = 0.65, respectively, P < 0.001 for both). Median levels of miR‐122 and miR‐192 in HCV‐infected patients were 23 times and 8 times higher as in healthy controls (P < 0.001 for both). Even within the HCV‐infected patients with a normal ALT (n = 38), the levels of miR‐122 and miR‐192 were 12 times and 4 times higher compared with healthy controls (P < 0.001 for both). Multivariate logistic regression analyses showed that only miR‐122 was a significant predictor of the presence of chronic HCV infection (P = 0.026). Importantly, miR‐122 was also superior in discriminating chronic HCV‐infected patients with a normal ALT from healthy controls compared with the ALT level (AUC = 0.97 vs AUC = 0.78, P = 0.007). In conclusion, our study confirmed that liver injury is associated with high levels of hepatocyte‐derived microRNAs in circulation and demonstrated that in particular miR‐122 is a sensitive marker to distinguish chronic hepatitis C patients from healthy controls. More sensitive blood markers would benefit especially those patients with minor levels of hepatocellular injury, who are not identified by current screening with ALT testing.</description><identifier>ISSN: 1352-0504</identifier><identifier>EISSN: 1365-2893</identifier><identifier>DOI: 10.1111/jvh.12001</identifier><identifier>PMID: 23383654</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Alanine Transaminase - blood ; ALT ; Biomarkers - blood ; Blood ; chronic hepatitis C ; Female ; Hepatitis C virus ; Hepatitis C, Chronic - diagnosis ; Hepatitis C, Chronic - pathology ; Humans ; Liver - pathology ; liver injury ; Male ; microRNA ; MicroRNAs - blood ; Middle Aged ; miRNA-122 ; Sensitivity and Specificity</subject><ispartof>Journal of viral hepatitis, 2013-03, Vol.20 (3), p.158-166</ispartof><rights>2012 Blackwell Publishing Ltd</rights><rights>2012 Blackwell Publishing Ltd.</rights><rights>Copyright © 2013 Blackwell Publishing Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjvh.12001$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjvh.12001$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23383654$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van der Meer, A. J.</creatorcontrib><creatorcontrib>Farid, W. R. R.</creatorcontrib><creatorcontrib>Sonneveld, M. J.</creatorcontrib><creatorcontrib>de Ruiter, P. E.</creatorcontrib><creatorcontrib>Boonstra, A.</creatorcontrib><creatorcontrib>van Vuuren, A. J.</creatorcontrib><creatorcontrib>Verheij, J.</creatorcontrib><creatorcontrib>Hansen, B. E.</creatorcontrib><creatorcontrib>de Knegt, R. J.</creatorcontrib><creatorcontrib>van der Laan, L. J. W.</creatorcontrib><creatorcontrib>Janssen, H. L. A.</creatorcontrib><title>Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122</title><title>Journal of viral hepatitis</title><addtitle>J Viral Hepat</addtitle><description>Summary
As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between hepatocyte‐derived microRNAs in serum and liver injury in patients with chronic hepatitis C. The hepatocyte‐derived miR‐122 and miR‐192 were analysed in sera of 102 chronic HCV‐infected patients and 24 healthy controls. Serum levels of miR‐122 and miR‐192 correlated strongly with ALT (R = 0.67 and R = 0.65, respectively, P < 0.001 for both). Median levels of miR‐122 and miR‐192 in HCV‐infected patients were 23 times and 8 times higher as in healthy controls (P < 0.001 for both). Even within the HCV‐infected patients with a normal ALT (n = 38), the levels of miR‐122 and miR‐192 were 12 times and 4 times higher compared with healthy controls (P < 0.001 for both). Multivariate logistic regression analyses showed that only miR‐122 was a significant predictor of the presence of chronic HCV infection (P = 0.026). Importantly, miR‐122 was also superior in discriminating chronic HCV‐infected patients with a normal ALT from healthy controls compared with the ALT level (AUC = 0.97 vs AUC = 0.78, P = 0.007). In conclusion, our study confirmed that liver injury is associated with high levels of hepatocyte‐derived microRNAs in circulation and demonstrated that in particular miR‐122 is a sensitive marker to distinguish chronic hepatitis C patients from healthy controls. More sensitive blood markers would benefit especially those patients with minor levels of hepatocellular injury, who are not identified by current screening with ALT testing.</description><subject>Adult</subject><subject>Aged</subject><subject>Alanine Transaminase - blood</subject><subject>ALT</subject><subject>Biomarkers - blood</subject><subject>Blood</subject><subject>chronic hepatitis C</subject><subject>Female</subject><subject>Hepatitis C virus</subject><subject>Hepatitis C, Chronic - diagnosis</subject><subject>Hepatitis C, Chronic - pathology</subject><subject>Humans</subject><subject>Liver - pathology</subject><subject>liver injury</subject><subject>Male</subject><subject>microRNA</subject><subject>MicroRNAs - blood</subject><subject>Middle Aged</subject><subject>miRNA-122</subject><subject>Sensitivity and Specificity</subject><issn>1352-0504</issn><issn>1365-2893</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtP4zAUhS0EAgZY8AeQJTazCfgRJ84SVbRl1GGk4bW0HOeWuqRJsZ1CF_Pfx6HAgg3e3CP5O_fq6CB0TMkZje98vpqdUUYI3UL7lGciYbLg270WLCGCpHvoh_fzCHAm6C7aY5zLyKX76N8NNN4GuwJcQQATbNvgdopnsNShNVDXXa0dts28c-s4sJm5trFmA0SjxwPcK2iCxy82zLCxzkRTsM3jx5p1gKQCF69UeGGNa_9eXySUsUO0M9W1h6P3eYDuhpe3g3Ey-TO6GlxMEssFoYkutTAgdClNykxWUlblRZGmUnAzzacpL3heahlTF4xoTmOyXGZcQJXrDCrDD9DPzd6la5878EEtrO_D6QbazivKqcgoyVj-PcqkIJIIJiJ6-gWdt51rYpCeSjlJKZGROnmnunIBlVo6u9BurT46iMD5BnixNaw__ylRfbkqlqveylW_7sdvIjqSjcP6AK-fDu2eVJbzXKiH65HKxsPfxXA0VBP-H77HpXQ</recordid><startdate>201303</startdate><enddate>201303</enddate><creator>van der Meer, A. J.</creator><creator>Farid, W. R. R.</creator><creator>Sonneveld, M. J.</creator><creator>de Ruiter, P. E.</creator><creator>Boonstra, A.</creator><creator>van Vuuren, A. J.</creator><creator>Verheij, J.</creator><creator>Hansen, B. E.</creator><creator>de Knegt, R. J.</creator><creator>van der Laan, L. J. W.</creator><creator>Janssen, H. L. A.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201303</creationdate><title>Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122</title><author>van der Meer, A. J. ; Farid, W. R. R. ; Sonneveld, M. J. ; de Ruiter, P. E. ; Boonstra, A. ; van Vuuren, A. J. ; Verheij, J. ; Hansen, B. E. ; de Knegt, R. J. ; van der Laan, L. J. W. ; Janssen, H. L. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i3501-aba5ce5ab8c42c6b12d79944853cf7f43937ba8289920a3165478635ed7a6edc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Alanine Transaminase - blood</topic><topic>ALT</topic><topic>Biomarkers - blood</topic><topic>Blood</topic><topic>chronic hepatitis C</topic><topic>Female</topic><topic>Hepatitis C virus</topic><topic>Hepatitis C, Chronic - diagnosis</topic><topic>Hepatitis C, Chronic - pathology</topic><topic>Humans</topic><topic>Liver - pathology</topic><topic>liver injury</topic><topic>Male</topic><topic>microRNA</topic><topic>MicroRNAs - blood</topic><topic>Middle Aged</topic><topic>miRNA-122</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van der Meer, A. J.</creatorcontrib><creatorcontrib>Farid, W. R. R.</creatorcontrib><creatorcontrib>Sonneveld, M. J.</creatorcontrib><creatorcontrib>de Ruiter, P. E.</creatorcontrib><creatorcontrib>Boonstra, A.</creatorcontrib><creatorcontrib>van Vuuren, A. J.</creatorcontrib><creatorcontrib>Verheij, J.</creatorcontrib><creatorcontrib>Hansen, B. E.</creatorcontrib><creatorcontrib>de Knegt, R. J.</creatorcontrib><creatorcontrib>van der Laan, L. J. W.</creatorcontrib><creatorcontrib>Janssen, H. L. A.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of viral hepatitis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van der Meer, A. J.</au><au>Farid, W. R. R.</au><au>Sonneveld, M. J.</au><au>de Ruiter, P. E.</au><au>Boonstra, A.</au><au>van Vuuren, A. J.</au><au>Verheij, J.</au><au>Hansen, B. E.</au><au>de Knegt, R. J.</au><au>van der Laan, L. J. W.</au><au>Janssen, H. L. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122</atitle><jtitle>Journal of viral hepatitis</jtitle><addtitle>J Viral Hepat</addtitle><date>2013-03</date><risdate>2013</risdate><volume>20</volume><issue>3</issue><spage>158</spage><epage>166</epage><pages>158-166</pages><issn>1352-0504</issn><eissn>1365-2893</eissn><abstract>Summary
As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between hepatocyte‐derived microRNAs in serum and liver injury in patients with chronic hepatitis C. The hepatocyte‐derived miR‐122 and miR‐192 were analysed in sera of 102 chronic HCV‐infected patients and 24 healthy controls. Serum levels of miR‐122 and miR‐192 correlated strongly with ALT (R = 0.67 and R = 0.65, respectively, P < 0.001 for both). Median levels of miR‐122 and miR‐192 in HCV‐infected patients were 23 times and 8 times higher as in healthy controls (P < 0.001 for both). Even within the HCV‐infected patients with a normal ALT (n = 38), the levels of miR‐122 and miR‐192 were 12 times and 4 times higher compared with healthy controls (P < 0.001 for both). Multivariate logistic regression analyses showed that only miR‐122 was a significant predictor of the presence of chronic HCV infection (P = 0.026). Importantly, miR‐122 was also superior in discriminating chronic HCV‐infected patients with a normal ALT from healthy controls compared with the ALT level (AUC = 0.97 vs AUC = 0.78, P = 0.007). In conclusion, our study confirmed that liver injury is associated with high levels of hepatocyte‐derived microRNAs in circulation and demonstrated that in particular miR‐122 is a sensitive marker to distinguish chronic hepatitis C patients from healthy controls. More sensitive blood markers would benefit especially those patients with minor levels of hepatocellular injury, who are not identified by current screening with ALT testing.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23383654</pmid><doi>10.1111/jvh.12001</doi><tpages>9</tpages></addata></record> |
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| subjects | Adult Aged Alanine Transaminase - blood ALT Biomarkers - blood Blood chronic hepatitis C Female Hepatitis C virus Hepatitis C, Chronic - diagnosis Hepatitis C, Chronic - pathology Humans Liver - pathology liver injury Male microRNA MicroRNAs - blood Middle Aged miRNA-122 Sensitivity and Specificity |
| title | Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122 |
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