Hepatocyte proliferative activity in human liver cirrhosis
Background/Aims: The objective of this study was to validate, with an independent prospective cohort of patients, our previous data indicating that the proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human cirrhosis and might have prognostic signi...
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| Veröffentlicht in: | Journal of hepatology 1999-03, Vol.30 (3), p.461-471 |
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| container_title | Journal of hepatology |
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| creator | Delhaye, Myriam Louis, Hubert Degraef, Chantal Moine, Olivier Le Devière, Jacques Peny, Marie-Odile Adler, Michael Galand, Paul |
| description | Background/Aims: The objective of this study was to validate, with an independent prospective cohort of patients, our previous data indicating that the proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human cirrhosis and might have prognostic significance for patient survival. We also examined how this proliferative index is related to the expression of transforming growth factor β1 (TGFβ1) as a possible correlate of hepatocyte proliferative activity.
Methods: The present group (
n=70 patients) was similar in composition to our previous group regarding age, sex and severity of liver cirrhosis. PCNA and TGFβ1 immunostaining were analyzed on methanolfixed, paraffin-embedded liver biopsies.
Results: Our data show that PCNA-LI declined significantly with worsening Child class and was negatively correlated with the Pugh score. Twenty-five patients died and 10 underwent liver transplantation during the observation period. Liver function, hepatic venous pressure gradient and hepatocyte PCNA-LI were significantly different in survivors and non-survivors. At a mean follow-up of 356 days, the patients with a PCNA-LI higher than 4.4% (the previously determined best cut-off value) had a significantly higher probability of survival than those with a PCNA-LI≤4.4% (0.87 vs 0.48,
p=0.0009). TGFβ1 expression in liver parenchyma correlated negatively with PCNA-LI, suggesting that this cytokine could be involved in the impaired regeneration observed in worsened liver cirrhosis.
Conclusions: This prospective study strengthens our previous observation that, in cirrhosis, hepatocyte proliferative activity, as evaluated by the PCNA-LI, provides information on liver functional reserve as well as on the patient's prognosis. |
| doi_str_mv | 10.1016/S0168-8278(99)80106-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69668803</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0168827899801068</els_id><sourcerecordid>69668803</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-9307b548a8a7a43204435f1a1611f6d80cd97099f61f505e1fcbdb58b478e4dc3</originalsourceid><addsrcrecordid>eNqFkE1LxDAQhoMouq7-BKUHET1UJ9s0TbyILOoKCx7Uc0jTCRvptmvSLuy_N_uBevMyA8MzMy8PIWcUbihQfvsWi0jFqBBXUl4LoMBTsUcGlAOkwBndJ4Mf5Igch_AJABlIdkiO4gUJRQYDcjfBhe5as-owWfi2dha97twSE21ic90qcU0y6-e6Seo49olx3s_a4MIJObC6Dni660Py8fT4Pp6k09fnl_HDNDWMjbpUZlCUORNa6EKzbASMZbmlmnJKLa8EmEoWIKXl1OaQI7WmrMpclKwQyCqTDcnl9m7M99Vj6NTcBYN1rRts-6C45FwIyCKYb0Hj2xA8WrXwbq79SlFQa2lqI02tjSgp1UaaEnHvfPegL-dY_dnaWorAxQ7Qwejaet0YF345LkGKNXa_xTDaWDr0KhiHjcHKeTSdqlr3T5JvIbCITg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>69668803</pqid></control><display><type>article</type><title>Hepatocyte proliferative activity in human liver cirrhosis</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Delhaye, Myriam ; Louis, Hubert ; Degraef, Chantal ; Moine, Olivier Le ; Devière, Jacques ; Peny, Marie-Odile ; Adler, Michael ; Galand, Paul</creator><creatorcontrib>Delhaye, Myriam ; Louis, Hubert ; Degraef, Chantal ; Moine, Olivier Le ; Devière, Jacques ; Peny, Marie-Odile ; Adler, Michael ; Galand, Paul</creatorcontrib><description>Background/Aims: The objective of this study was to validate, with an independent prospective cohort of patients, our previous data indicating that the proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human cirrhosis and might have prognostic significance for patient survival. We also examined how this proliferative index is related to the expression of transforming growth factor β1 (TGFβ1) as a possible correlate of hepatocyte proliferative activity.
Methods: The present group (
n=70 patients) was similar in composition to our previous group regarding age, sex and severity of liver cirrhosis. PCNA and TGFβ1 immunostaining were analyzed on methanolfixed, paraffin-embedded liver biopsies.
Results: Our data show that PCNA-LI declined significantly with worsening Child class and was negatively correlated with the Pugh score. Twenty-five patients died and 10 underwent liver transplantation during the observation period. Liver function, hepatic venous pressure gradient and hepatocyte PCNA-LI were significantly different in survivors and non-survivors. At a mean follow-up of 356 days, the patients with a PCNA-LI higher than 4.4% (the previously determined best cut-off value) had a significantly higher probability of survival than those with a PCNA-LI≤4.4% (0.87 vs 0.48,
p=0.0009). TGFβ1 expression in liver parenchyma correlated negatively with PCNA-LI, suggesting that this cytokine could be involved in the impaired regeneration observed in worsened liver cirrhosis.
Conclusions: This prospective study strengthens our previous observation that, in cirrhosis, hepatocyte proliferative activity, as evaluated by the PCNA-LI, provides information on liver functional reserve as well as on the patient's prognosis.</description><identifier>ISSN: 0168-8278</identifier><identifier>EISSN: 1600-0641</identifier><identifier>DOI: 10.1016/S0168-8278(99)80106-8</identifier><identifier>PMID: 10190730</identifier><identifier>CODEN: JOHEEC</identifier><language>eng</language><publisher>Oxford: Elsevier B.V</publisher><subject>Biological and medical sciences ; Biopsy ; Cell Division ; Cirrhosis ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Hepatocyte proliferation ; Humans ; Immunohistochemistry ; Liver - metabolism ; Liver - pathology ; Liver Cirrhosis - metabolism ; Liver Cirrhosis - pathology ; Liver function ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Middle Aged ; Other diseases. Semiology ; Proliferating cell nuclear antigen (PCNA) ; Proliferating Cell Nuclear Antigen - analysis ; Transforming Growth Factor beta - metabolism ; Transforming growth factor β1 (TGFβ1)</subject><ispartof>Journal of hepatology, 1999-03, Vol.30 (3), p.461-471</ispartof><rights>1999</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-9307b548a8a7a43204435f1a1611f6d80cd97099f61f505e1fcbdb58b478e4dc3</citedby><cites>FETCH-LOGICAL-c442t-9307b548a8a7a43204435f1a1611f6d80cd97099f61f505e1fcbdb58b478e4dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168827899801068$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1690980$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10190730$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Delhaye, Myriam</creatorcontrib><creatorcontrib>Louis, Hubert</creatorcontrib><creatorcontrib>Degraef, Chantal</creatorcontrib><creatorcontrib>Moine, Olivier Le</creatorcontrib><creatorcontrib>Devière, Jacques</creatorcontrib><creatorcontrib>Peny, Marie-Odile</creatorcontrib><creatorcontrib>Adler, Michael</creatorcontrib><creatorcontrib>Galand, Paul</creatorcontrib><title>Hepatocyte proliferative activity in human liver cirrhosis</title><title>Journal of hepatology</title><addtitle>J Hepatol</addtitle><description>Background/Aims: The objective of this study was to validate, with an independent prospective cohort of patients, our previous data indicating that the proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human cirrhosis and might have prognostic significance for patient survival. We also examined how this proliferative index is related to the expression of transforming growth factor β1 (TGFβ1) as a possible correlate of hepatocyte proliferative activity.
Methods: The present group (
n=70 patients) was similar in composition to our previous group regarding age, sex and severity of liver cirrhosis. PCNA and TGFβ1 immunostaining were analyzed on methanolfixed, paraffin-embedded liver biopsies.
Results: Our data show that PCNA-LI declined significantly with worsening Child class and was negatively correlated with the Pugh score. Twenty-five patients died and 10 underwent liver transplantation during the observation period. Liver function, hepatic venous pressure gradient and hepatocyte PCNA-LI were significantly different in survivors and non-survivors. At a mean follow-up of 356 days, the patients with a PCNA-LI higher than 4.4% (the previously determined best cut-off value) had a significantly higher probability of survival than those with a PCNA-LI≤4.4% (0.87 vs 0.48,
p=0.0009). TGFβ1 expression in liver parenchyma correlated negatively with PCNA-LI, suggesting that this cytokine could be involved in the impaired regeneration observed in worsened liver cirrhosis.
Conclusions: This prospective study strengthens our previous observation that, in cirrhosis, hepatocyte proliferative activity, as evaluated by the PCNA-LI, provides information on liver functional reserve as well as on the patient's prognosis.</description><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Cell Division</subject><subject>Cirrhosis</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hepatocyte proliferation</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver Cirrhosis - metabolism</subject><subject>Liver Cirrhosis - pathology</subject><subject>Liver function</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Other diseases. Semiology</subject><subject>Proliferating cell nuclear antigen (PCNA)</subject><subject>Proliferating Cell Nuclear Antigen - analysis</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Transforming growth factor β1 (TGFβ1)</subject><issn>0168-8278</issn><issn>1600-0641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LxDAQhoMouq7-BKUHET1UJ9s0TbyILOoKCx7Uc0jTCRvptmvSLuy_N_uBevMyA8MzMy8PIWcUbihQfvsWi0jFqBBXUl4LoMBTsUcGlAOkwBndJ4Mf5Igch_AJABlIdkiO4gUJRQYDcjfBhe5as-owWfi2dha97twSE21ic90qcU0y6-e6Seo49olx3s_a4MIJObC6Dni660Py8fT4Pp6k09fnl_HDNDWMjbpUZlCUORNa6EKzbASMZbmlmnJKLa8EmEoWIKXl1OaQI7WmrMpclKwQyCqTDcnl9m7M99Vj6NTcBYN1rRts-6C45FwIyCKYb0Hj2xA8WrXwbq79SlFQa2lqI02tjSgp1UaaEnHvfPegL-dY_dnaWorAxQ7Qwejaet0YF345LkGKNXa_xTDaWDr0KhiHjcHKeTSdqlr3T5JvIbCITg</recordid><startdate>19990301</startdate><enddate>19990301</enddate><creator>Delhaye, Myriam</creator><creator>Louis, Hubert</creator><creator>Degraef, Chantal</creator><creator>Moine, Olivier Le</creator><creator>Devière, Jacques</creator><creator>Peny, Marie-Odile</creator><creator>Adler, Michael</creator><creator>Galand, Paul</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</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>19990301</creationdate><title>Hepatocyte proliferative activity in human liver cirrhosis</title><author>Delhaye, Myriam ; Louis, Hubert ; Degraef, Chantal ; Moine, Olivier Le ; Devière, Jacques ; Peny, Marie-Odile ; Adler, Michael ; Galand, Paul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-9307b548a8a7a43204435f1a1611f6d80cd97099f61f505e1fcbdb58b478e4dc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Cell Division</topic><topic>Cirrhosis</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hepatocyte proliferation</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver Cirrhosis - metabolism</topic><topic>Liver Cirrhosis - pathology</topic><topic>Liver function</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Other diseases. Semiology</topic><topic>Proliferating cell nuclear antigen (PCNA)</topic><topic>Proliferating Cell Nuclear Antigen - analysis</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Transforming growth factor β1 (TGFβ1)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Delhaye, Myriam</creatorcontrib><creatorcontrib>Louis, Hubert</creatorcontrib><creatorcontrib>Degraef, Chantal</creatorcontrib><creatorcontrib>Moine, Olivier Le</creatorcontrib><creatorcontrib>Devière, Jacques</creatorcontrib><creatorcontrib>Peny, Marie-Odile</creatorcontrib><creatorcontrib>Adler, Michael</creatorcontrib><creatorcontrib>Galand, Paul</creatorcontrib><collection>Pascal-Francis</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 hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Delhaye, Myriam</au><au>Louis, Hubert</au><au>Degraef, Chantal</au><au>Moine, Olivier Le</au><au>Devière, Jacques</au><au>Peny, Marie-Odile</au><au>Adler, Michael</au><au>Galand, Paul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatocyte proliferative activity in human liver cirrhosis</atitle><jtitle>Journal of hepatology</jtitle><addtitle>J Hepatol</addtitle><date>1999-03-01</date><risdate>1999</risdate><volume>30</volume><issue>3</issue><spage>461</spage><epage>471</epage><pages>461-471</pages><issn>0168-8278</issn><eissn>1600-0641</eissn><coden>JOHEEC</coden><abstract>Background/Aims: The objective of this study was to validate, with an independent prospective cohort of patients, our previous data indicating that the proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human cirrhosis and might have prognostic significance for patient survival. We also examined how this proliferative index is related to the expression of transforming growth factor β1 (TGFβ1) as a possible correlate of hepatocyte proliferative activity.
Methods: The present group (
n=70 patients) was similar in composition to our previous group regarding age, sex and severity of liver cirrhosis. PCNA and TGFβ1 immunostaining were analyzed on methanolfixed, paraffin-embedded liver biopsies.
Results: Our data show that PCNA-LI declined significantly with worsening Child class and was negatively correlated with the Pugh score. Twenty-five patients died and 10 underwent liver transplantation during the observation period. Liver function, hepatic venous pressure gradient and hepatocyte PCNA-LI were significantly different in survivors and non-survivors. At a mean follow-up of 356 days, the patients with a PCNA-LI higher than 4.4% (the previously determined best cut-off value) had a significantly higher probability of survival than those with a PCNA-LI≤4.4% (0.87 vs 0.48,
p=0.0009). TGFβ1 expression in liver parenchyma correlated negatively with PCNA-LI, suggesting that this cytokine could be involved in the impaired regeneration observed in worsened liver cirrhosis.
Conclusions: This prospective study strengthens our previous observation that, in cirrhosis, hepatocyte proliferative activity, as evaluated by the PCNA-LI, provides information on liver functional reserve as well as on the patient's prognosis.</abstract><cop>Oxford</cop><pub>Elsevier B.V</pub><pmid>10190730</pmid><doi>10.1016/S0168-8278(99)80106-8</doi><tpages>11</tpages></addata></record> |
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| ispartof | Journal of hepatology, 1999-03, Vol.30 (3), p.461-471 |
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| subjects | Biological and medical sciences Biopsy Cell Division Cirrhosis Female Gastroenterology. Liver. Pancreas. Abdomen Hepatocyte proliferation Humans Immunohistochemistry Liver - metabolism Liver - pathology Liver Cirrhosis - metabolism Liver Cirrhosis - pathology Liver function Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Middle Aged Other diseases. Semiology Proliferating cell nuclear antigen (PCNA) Proliferating Cell Nuclear Antigen - analysis Transforming Growth Factor beta - metabolism Transforming growth factor β1 (TGFβ1) |
| title | Hepatocyte proliferative activity in human liver cirrhosis |
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