Prevalence, Risk Factors, and Impact of Donor‐Specific Alloantibodies After Adult Liver Transplantation
The incidence and impact of anti–human leukocyte antigen donor‐specific alloantibodies (DSAs) developing after liver transplantation (LT) remains controversial and not extensively studied. The aim of the present study was to assess the incidence of DSAs, to identify risk factors for the development...
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| Veröffentlicht in: | Liver transplantation 2018-08, Vol.24 (8), p.1091-1100 |
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| creator | Vandevoorde, Katia Ducreux, Stéphanie Bosch, Alexie Guillaud, Olivier Hervieu, Valérie Chambon‐Augoyard, Christine Poinsot, Domitille André, Patrice Scoazec, Jean‐Yves Robinson, Philip Boillot, Olivier Dubois, Valérie Dumortier, Jérôme |
| description | The incidence and impact of anti–human leukocyte antigen donor‐specific alloantibodies (DSAs) developing after liver transplantation (LT) remains controversial and not extensively studied. The aim of the present study was to assess the incidence of DSAs, to identify risk factors for the development of DSAs, and to understand the impact of DSAs in a large population of adult LT recipients. This single‐center retrospective study included all adult patients who underwent a first LT between 2000 and 2010 in our center. The study population mainly consisted of male patients, the mean age was 52.4 years, and the main indication was alcoholic cirrhosis (54.1%). From the 297 patients included in the cross‐sectional study, 14 (4.7%) had preformed DSAs, and 59 (19.9%) presented de novo DSAs (12.2% at 1 year, 13.4% at 5 years, and 19.5% at 10 years). Multivariate analysis found that female donor sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.12‐2.01; P = 0.01) and delay between LT and DSA screening (HR, 1.10; 95% CI, 1.01‐1.20; P = 0.03) were associated with occurrence of de novo DSAs. From the 190 patients included in the subgroup longitudinal analysis, exposure to tacrolimus (mean trough level during the periods 0‐2 years and 0‐3 years) was significantly lower for patients having DSAs at 5 years. Concerning histology, only acute rejection (P = 0.04) and portal fibrosis ≥2 (P = 0.02) were more frequent at 1 year for patients with DSAs. Patient survival and graft survival were not significantly different according to the presence or not of DSAs at 1 year. Among the 44 patients who had de novo or persistent preformed DSAs, the diagnosis of antibody‐mediated rejection was made in 4 (9.1%) patients after 1, 47, 61, and 74 months following LT. In conclusion, the results of the present study suggest that DSAs are observed in a minority of LT adult patients, with limited overall impact on graft and patient outcome. |
| doi_str_mv | 10.1002/lt.25177 |
| format | Article |
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The aim of the present study was to assess the incidence of DSAs, to identify risk factors for the development of DSAs, and to understand the impact of DSAs in a large population of adult LT recipients. This single‐center retrospective study included all adult patients who underwent a first LT between 2000 and 2010 in our center. The study population mainly consisted of male patients, the mean age was 52.4 years, and the main indication was alcoholic cirrhosis (54.1%). From the 297 patients included in the cross‐sectional study, 14 (4.7%) had preformed DSAs, and 59 (19.9%) presented de novo DSAs (12.2% at 1 year, 13.4% at 5 years, and 19.5% at 10 years). Multivariate analysis found that female donor sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.12‐2.01; P = 0.01) and delay between LT and DSA screening (HR, 1.10; 95% CI, 1.01‐1.20; P = 0.03) were associated with occurrence of de novo DSAs. From the 190 patients included in the subgroup longitudinal analysis, exposure to tacrolimus (mean trough level during the periods 0‐2 years and 0‐3 years) was significantly lower for patients having DSAs at 5 years. Concerning histology, only acute rejection (P = 0.04) and portal fibrosis ≥2 (P = 0.02) were more frequent at 1 year for patients with DSAs. Patient survival and graft survival were not significantly different according to the presence or not of DSAs at 1 year. Among the 44 patients who had de novo or persistent preformed DSAs, the diagnosis of antibody‐mediated rejection was made in 4 (9.1%) patients after 1, 47, 61, and 74 months following LT. In conclusion, the results of the present study suggest that DSAs are observed in a minority of LT adult patients, with limited overall impact on graft and patient outcome.</description><identifier>ISSN: 1527-6465</identifier><identifier>EISSN: 1527-6473</identifier><identifier>DOI: 10.1002/lt.25177</identifier><identifier>PMID: 29665189</identifier><language>eng</language><publisher>United States: Wolters Kluwer Health, Inc</publisher><subject>Adult ; Alloantibodies ; Cirrhosis ; Cross-Sectional Studies ; Female ; Fibrosis ; Follow-Up Studies ; Graft rejection ; Graft Rejection - blood ; Graft Rejection - epidemiology ; Graft Rejection - immunology ; Graft Rejection - prevention & control ; Graft Survival ; Histocompatibility antigen HLA ; HLA Antigens - immunology ; Human health and pathology ; Humans ; Immunosuppressive Agents - therapeutic use ; Incidence ; Isoantibodies - blood ; Isoantibodies - immunology ; Isoantibodies - isolation & purification ; Life Sciences ; Liver cirrhosis ; Liver Cirrhosis, Alcoholic - mortality ; Liver Cirrhosis, Alcoholic - surgery ; Liver transplantation ; Liver Transplantation - adverse effects ; Liver transplants ; Male ; Middle Aged ; Multivariate analysis ; Patients ; Population studies ; Postoperative Complications - blood ; Postoperative Complications - epidemiology ; Postoperative Complications - immunology ; Postoperative Complications - prevention & control ; Prevalence ; Retrospective Studies ; Risk Factors ; Sex ratio ; Survival Analysis ; Tacrolimus ; Tacrolimus - therapeutic use ; Transplant Recipients ; Treatment Outcome</subject><ispartof>Liver transplantation, 2018-08, Vol.24 (8), p.1091-1100</ispartof><rights>2018 The Authors. Liver Transplantation published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.</rights><rights>2018 The Authors. Liver Transplantation published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.</rights><rights>2018 by the American Association for the Study of Liver Diseases</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4497-154aa802f50fd70f48578fc2fdd2c0b81b57afd90be4350913d75c7c017010043</citedby><cites>FETCH-LOGICAL-c4497-154aa802f50fd70f48578fc2fdd2c0b81b57afd90be4350913d75c7c017010043</cites><orcidid>0000-0002-7824-5396 ; 0000-0002-5834-7395</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Flt.25177$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Flt.25177$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,778,782,883,1414,27911,27912,45561,45562</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29665189$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04173168$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Vandevoorde, Katia</creatorcontrib><creatorcontrib>Ducreux, Stéphanie</creatorcontrib><creatorcontrib>Bosch, Alexie</creatorcontrib><creatorcontrib>Guillaud, Olivier</creatorcontrib><creatorcontrib>Hervieu, Valérie</creatorcontrib><creatorcontrib>Chambon‐Augoyard, Christine</creatorcontrib><creatorcontrib>Poinsot, Domitille</creatorcontrib><creatorcontrib>André, Patrice</creatorcontrib><creatorcontrib>Scoazec, Jean‐Yves</creatorcontrib><creatorcontrib>Robinson, Philip</creatorcontrib><creatorcontrib>Boillot, Olivier</creatorcontrib><creatorcontrib>Dubois, Valérie</creatorcontrib><creatorcontrib>Dumortier, Jérôme</creatorcontrib><title>Prevalence, Risk Factors, and Impact of Donor‐Specific Alloantibodies After Adult Liver Transplantation</title><title>Liver transplantation</title><addtitle>Liver Transpl</addtitle><description>The incidence and impact of anti–human leukocyte antigen donor‐specific alloantibodies (DSAs) developing after liver transplantation (LT) remains controversial and not extensively studied. The aim of the present study was to assess the incidence of DSAs, to identify risk factors for the development of DSAs, and to understand the impact of DSAs in a large population of adult LT recipients. This single‐center retrospective study included all adult patients who underwent a first LT between 2000 and 2010 in our center. The study population mainly consisted of male patients, the mean age was 52.4 years, and the main indication was alcoholic cirrhosis (54.1%). From the 297 patients included in the cross‐sectional study, 14 (4.7%) had preformed DSAs, and 59 (19.9%) presented de novo DSAs (12.2% at 1 year, 13.4% at 5 years, and 19.5% at 10 years). Multivariate analysis found that female donor sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.12‐2.01; P = 0.01) and delay between LT and DSA screening (HR, 1.10; 95% CI, 1.01‐1.20; P = 0.03) were associated with occurrence of de novo DSAs. From the 190 patients included in the subgroup longitudinal analysis, exposure to tacrolimus (mean trough level during the periods 0‐2 years and 0‐3 years) was significantly lower for patients having DSAs at 5 years. Concerning histology, only acute rejection (P = 0.04) and portal fibrosis ≥2 (P = 0.02) were more frequent at 1 year for patients with DSAs. Patient survival and graft survival were not significantly different according to the presence or not of DSAs at 1 year. Among the 44 patients who had de novo or persistent preformed DSAs, the diagnosis of antibody‐mediated rejection was made in 4 (9.1%) patients after 1, 47, 61, and 74 months following LT. In conclusion, the results of the present study suggest that DSAs are observed in a minority of LT adult patients, with limited overall impact on graft and patient outcome.</description><subject>Adult</subject><subject>Alloantibodies</subject><subject>Cirrhosis</subject><subject>Cross-Sectional Studies</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Follow-Up Studies</subject><subject>Graft rejection</subject><subject>Graft Rejection - blood</subject><subject>Graft Rejection - epidemiology</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - prevention & control</subject><subject>Graft Survival</subject><subject>Histocompatibility antigen HLA</subject><subject>HLA Antigens - immunology</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Incidence</subject><subject>Isoantibodies - blood</subject><subject>Isoantibodies - immunology</subject><subject>Isoantibodies - isolation & purification</subject><subject>Life Sciences</subject><subject>Liver cirrhosis</subject><subject>Liver Cirrhosis, Alcoholic - mortality</subject><subject>Liver Cirrhosis, Alcoholic - surgery</subject><subject>Liver transplantation</subject><subject>Liver Transplantation - adverse effects</subject><subject>Liver transplants</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Patients</subject><subject>Population studies</subject><subject>Postoperative Complications - blood</subject><subject>Postoperative Complications - epidemiology</subject><subject>Postoperative Complications - immunology</subject><subject>Postoperative Complications - prevention & control</subject><subject>Prevalence</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>Sex ratio</subject><subject>Survival Analysis</subject><subject>Tacrolimus</subject><subject>Tacrolimus - therapeutic use</subject><subject>Transplant Recipients</subject><subject>Treatment Outcome</subject><issn>1527-6465</issn><issn>1527-6473</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kdFqFTEQhoMotlbBJ5CANwrdOskmm83lUq0tLCh6vA7ZbIKpOZs12T3SOx_BZ_RJTD31CIJXmQwfHzPzI_SUwBkBoK_CckY5EeIeOiaciqphor5_qBt-hB7lfA1ACJfwEB1R2TSctPIY-ffJ7nSwk7Gn-IPPX_CFNktM-RTracRX27l8cXT4dZxi-vn9x8fZGu-8wV0IUU-LH-LobcadW2zC3biGBfd-V-pN0lOeQ2H04uP0GD1wOmT75O49QZ8u3mzOL6v-3dur866vDGNSVIQzrVugjoMbBTjWctE6Q904UgNDSwYutBslDJbVHCSpR8GNMEAElFuw-gS93Hs_66Dm5Lc63aiovbrsenXbA0ZETZp2Rwr7Ys_OKX5dbV7U1mdjQxnaxjUrClRA04KUBX3-D3od1zSVTQolaVM3TPK_QpNizsm6wwQE1G1UKizqd1QFfXYnXIetHQ_gn2wKUO2Bbz7Ym_-KVL_ZC38B0vObJQ</recordid><startdate>201808</startdate><enddate>201808</enddate><creator>Vandevoorde, Katia</creator><creator>Ducreux, Stéphanie</creator><creator>Bosch, Alexie</creator><creator>Guillaud, Olivier</creator><creator>Hervieu, Valérie</creator><creator>Chambon‐Augoyard, Christine</creator><creator>Poinsot, Domitille</creator><creator>André, Patrice</creator><creator>Scoazec, Jean‐Yves</creator><creator>Robinson, Philip</creator><creator>Boillot, Olivier</creator><creator>Dubois, Valérie</creator><creator>Dumortier, Jérôme</creator><general>Wolters Kluwer Health, Inc</general><general>Wiley</general><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>K9.</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-7824-5396</orcidid><orcidid>https://orcid.org/0000-0002-5834-7395</orcidid></search><sort><creationdate>201808</creationdate><title>Prevalence, Risk Factors, and Impact of Donor‐Specific Alloantibodies After Adult Liver Transplantation</title><author>Vandevoorde, Katia ; Ducreux, Stéphanie ; Bosch, Alexie ; Guillaud, Olivier ; Hervieu, Valérie ; Chambon‐Augoyard, Christine ; Poinsot, Domitille ; André, Patrice ; Scoazec, Jean‐Yves ; Robinson, Philip ; Boillot, Olivier ; Dubois, Valérie ; Dumortier, Jérôme</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4497-154aa802f50fd70f48578fc2fdd2c0b81b57afd90be4350913d75c7c017010043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Alloantibodies</topic><topic>Cirrhosis</topic><topic>Cross-Sectional Studies</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Follow-Up Studies</topic><topic>Graft rejection</topic><topic>Graft Rejection - blood</topic><topic>Graft Rejection - epidemiology</topic><topic>Graft Rejection - immunology</topic><topic>Graft Rejection - prevention & control</topic><topic>Graft Survival</topic><topic>Histocompatibility antigen HLA</topic><topic>HLA Antigens - immunology</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Incidence</topic><topic>Isoantibodies - blood</topic><topic>Isoantibodies - immunology</topic><topic>Isoantibodies - isolation & purification</topic><topic>Life Sciences</topic><topic>Liver cirrhosis</topic><topic>Liver Cirrhosis, Alcoholic - mortality</topic><topic>Liver Cirrhosis, Alcoholic - surgery</topic><topic>Liver transplantation</topic><topic>Liver Transplantation - adverse effects</topic><topic>Liver transplants</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multivariate analysis</topic><topic>Patients</topic><topic>Population studies</topic><topic>Postoperative Complications - blood</topic><topic>Postoperative Complications - epidemiology</topic><topic>Postoperative Complications - immunology</topic><topic>Postoperative Complications - prevention & control</topic><topic>Prevalence</topic><topic>Retrospective Studies</topic><topic>Risk Factors</topic><topic>Sex ratio</topic><topic>Survival Analysis</topic><topic>Tacrolimus</topic><topic>Tacrolimus - therapeutic use</topic><topic>Transplant Recipients</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vandevoorde, Katia</creatorcontrib><creatorcontrib>Ducreux, Stéphanie</creatorcontrib><creatorcontrib>Bosch, Alexie</creatorcontrib><creatorcontrib>Guillaud, Olivier</creatorcontrib><creatorcontrib>Hervieu, Valérie</creatorcontrib><creatorcontrib>Chambon‐Augoyard, Christine</creatorcontrib><creatorcontrib>Poinsot, Domitille</creatorcontrib><creatorcontrib>André, Patrice</creatorcontrib><creatorcontrib>Scoazec, Jean‐Yves</creatorcontrib><creatorcontrib>Robinson, Philip</creatorcontrib><creatorcontrib>Boillot, Olivier</creatorcontrib><creatorcontrib>Dubois, Valérie</creatorcontrib><creatorcontrib>Dumortier, Jérôme</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Liver transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vandevoorde, Katia</au><au>Ducreux, Stéphanie</au><au>Bosch, Alexie</au><au>Guillaud, Olivier</au><au>Hervieu, Valérie</au><au>Chambon‐Augoyard, Christine</au><au>Poinsot, Domitille</au><au>André, Patrice</au><au>Scoazec, Jean‐Yves</au><au>Robinson, Philip</au><au>Boillot, Olivier</au><au>Dubois, Valérie</au><au>Dumortier, Jérôme</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prevalence, Risk Factors, and Impact of Donor‐Specific Alloantibodies After Adult Liver Transplantation</atitle><jtitle>Liver transplantation</jtitle><addtitle>Liver Transpl</addtitle><date>2018-08</date><risdate>2018</risdate><volume>24</volume><issue>8</issue><spage>1091</spage><epage>1100</epage><pages>1091-1100</pages><issn>1527-6465</issn><eissn>1527-6473</eissn><abstract>The incidence and impact of anti–human leukocyte antigen donor‐specific alloantibodies (DSAs) developing after liver transplantation (LT) remains controversial and not extensively studied. The aim of the present study was to assess the incidence of DSAs, to identify risk factors for the development of DSAs, and to understand the impact of DSAs in a large population of adult LT recipients. This single‐center retrospective study included all adult patients who underwent a first LT between 2000 and 2010 in our center. The study population mainly consisted of male patients, the mean age was 52.4 years, and the main indication was alcoholic cirrhosis (54.1%). From the 297 patients included in the cross‐sectional study, 14 (4.7%) had preformed DSAs, and 59 (19.9%) presented de novo DSAs (12.2% at 1 year, 13.4% at 5 years, and 19.5% at 10 years). Multivariate analysis found that female donor sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.12‐2.01; P = 0.01) and delay between LT and DSA screening (HR, 1.10; 95% CI, 1.01‐1.20; P = 0.03) were associated with occurrence of de novo DSAs. From the 190 patients included in the subgroup longitudinal analysis, exposure to tacrolimus (mean trough level during the periods 0‐2 years and 0‐3 years) was significantly lower for patients having DSAs at 5 years. Concerning histology, only acute rejection (P = 0.04) and portal fibrosis ≥2 (P = 0.02) were more frequent at 1 year for patients with DSAs. Patient survival and graft survival were not significantly different according to the presence or not of DSAs at 1 year. Among the 44 patients who had de novo or persistent preformed DSAs, the diagnosis of antibody‐mediated rejection was made in 4 (9.1%) patients after 1, 47, 61, and 74 months following LT. In conclusion, the results of the present study suggest that DSAs are observed in a minority of LT adult patients, with limited overall impact on graft and patient outcome.</abstract><cop>United States</cop><pub>Wolters Kluwer Health, Inc</pub><pmid>29665189</pmid><doi>10.1002/lt.25177</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-7824-5396</orcidid><orcidid>https://orcid.org/0000-0002-5834-7395</orcidid></addata></record> |
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| ispartof | Liver transplantation, 2018-08, Vol.24 (8), p.1091-1100 |
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| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | Adult Alloantibodies Cirrhosis Cross-Sectional Studies Female Fibrosis Follow-Up Studies Graft rejection Graft Rejection - blood Graft Rejection - epidemiology Graft Rejection - immunology Graft Rejection - prevention & control Graft Survival Histocompatibility antigen HLA HLA Antigens - immunology Human health and pathology Humans Immunosuppressive Agents - therapeutic use Incidence Isoantibodies - blood Isoantibodies - immunology Isoantibodies - isolation & purification Life Sciences Liver cirrhosis Liver Cirrhosis, Alcoholic - mortality Liver Cirrhosis, Alcoholic - surgery Liver transplantation Liver Transplantation - adverse effects Liver transplants Male Middle Aged Multivariate analysis Patients Population studies Postoperative Complications - blood Postoperative Complications - epidemiology Postoperative Complications - immunology Postoperative Complications - prevention & control Prevalence Retrospective Studies Risk Factors Sex ratio Survival Analysis Tacrolimus Tacrolimus - therapeutic use Transplant Recipients Treatment Outcome |
| title | Prevalence, Risk Factors, and Impact of Donor‐Specific Alloantibodies After Adult Liver Transplantation |
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