Effect of donor HSD17B13 genotype on patient survival after liver transplant: a retrospective cohort study.
Effect of donor HSD17B13 genotype on patient survival after liver transplant: a retrospective cohort study.
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DOI：
10.1016/j.eclinm.2023.102350
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发表时间：
2024-01
影响因子：
15.1
通讯作者：
MacConmara, Malcolm P.
中科院分区：
文献类型：
--
作者：
Kozlitina, Julia;Cohen, Naomi M.;Sturtevant, Drew;Cohen, Jonathan C.;Murphey-Half, Cathi;Saltarrelli, Jerome G.;Jindra, Peter;Askar, Medhat;Hwang, Christine S.;Vagefi, Parsia A.;Lacelle, Chantale;Hobbs, Helen H.;MacConmara, Malcolm P.
几种遗传变异与慢性肝病有关。这些变异在肝移植（LT）后预后中的作用尚不确定。本研究的目的是确定供体基因型在PNPLA3 （rs738409 C>G, p.I148M）和HSD17B13 （rs72613567 T>TA; rs80182459, p.A192Lfs * 8）的风险相关变异中是否影响lt后的生存。在这项回顾性队列研究中，从器官共享联合网络（UNOS）获得了1999年1月1日至2020年6月30日期间首次接受肝移植的2346名成年人的数据，这些成年人在美国德克萨斯州的五个大型移植免疫学实验室有供体DNA样本。排除重复、供体DNA基因分型不足的患者、移植时年龄<18岁、既往移植或缺失基因型数据的患者。主要结局是移植后患者和移植物的生存。使用Kaplan-Meier方法和多变量校正Cox比例风险模型检查供体基因型与移植后生存之间的关系。肝移植受者的中位年龄为57岁[四分位间距（IQR）， 50-62岁]；女性837例（35.7%）；白人1362人（58.1%），西班牙裔713人（30.4%），黑人/非裔182人（7.8%）。中位随访时间为3.95年。移植后的生存率不受供体PNPLA3基因型的影响，但与接受无HSD17B13 LoF等位基因肝脏的患者相比，移植两种HSD17B13 LoF变异肝脏的患者生存率显著降低（未经调整的一年生存率：82.6% vs 93.9%, P < 0.0001；五年生存率：73.1% vs 82.9%, P = 0.0017；调整后的风险比[HR]为2.25；调整受体年龄、性别和自我报告的种族后，95% CI为1.61-3.15）。过高的死亡率局限于接受类固醇诱导免疫抑制的患者（肝移植后90天的粗死亡率，有两个HSD17B13 LoF等位基因的肝脏移植者为9.3% [95% CI, 1.9% - 16.1%]，而没有HSD17B13 LoF等位基因的肝脏移植者为1.9% [95% CI, 0.9%-2.9%], P = 0.0012；年龄、性别和种族调整后的HR， 2.85; 95% CI, 1.72-4.71, P < 0.0001）。未接受类固醇诱导的患者死亡率未见降低（90天死亡率3.1% [95% CI, 0%-7.3%] vs 2% [95% CI, 0.9%-3.1%], P = 0.65；调整后危险比1.17;95% CI, 0.66-2.08, P = 0.60）。供体HSD17B13基因型对接受类固醇诱导的患者肝移植后生存有不利影响。需要更多的研究来证实这种关联。和合作科学家补助金
Several genetic variants are associated with chronic liver disease. The role of these variants in outcomes after liver transplantation (LT) is uncertain. The aim of this study was to determine if donor genotype at risk-associated variants in PNPLA3 (rs738409 C>G, p.I148M) and HSD17B13 (rs72613567 T>TA; rs80182459, p.A192Lfs∗8) influences post-LT survival. In this retrospective cohort study, data on 2346 adults who underwent first-time LT between January 1, 1999 and June 30, 2020 and who had donor DNA samples available at five large Transplant Immunology Laboratories in Texas, USA, were obtained from the United Network for Organ Sharing (UNOS). Duplicates, patients with insufficient donor DNA for genotyping, those who were <18 years of age at the time of transplant, had had a previous transplant or had missing genotype data were excluded. The primary outcomes were patient and graft survival after LT. The association between donor genotype and post-LT survival was examined using Kaplan–Meier method and multivariable-adjusted Cox proportional hazards models. Median age of LT recipients was 57 [interquartile range (IQR), 50–62] years; 837 (35.7%) were women; 1362 (58.1%) White, 713 (30.4%) Hispanic, 182 (7.8%) Black/African-American. Median follow-up time was 3.95 years. Post-LT survival was not affected by donor PNPLA3 genotype but was significantly reduced among recipients of livers with two HSD17B13 loss-of-function (LoF) variants compared to those receiving livers with no HSD17B13 LoF alleles (unadjusted one-year survival: 82.6% vs 93.9%, P < 0.0001; five-year survival: 73.1% vs 82.9%, P = 0.0017; adjusted hazard ratio [HR], 2.25; 95% CI, 1.61–3.15 after adjustment for recipient age, sex, and self-reported ethnicity). Excess mortality was restricted to those receiving steroid induction immunosuppression (crude 90-day post-LT mortality, 9.3% [95% CI, 1.9%–16.1%] vs 1.9% [95% CI, 0.9%–2.9%] in recipients of livers with two vs no HSD17B13 LoF alleles, P = 0.0012; age, sex, and ethnicity-adjusted HR, 2.85; 95% CI, 1.72–4.71, P < 0.0001). No reduction was seen among patients who did not receive steroid induction (90-day mortality 3.1% [95% CI, 0%–7.3%] vs 2% [95% CI, 0.9%–3.1%], P = 0.65; adjusted HR, 1.17; 95% CI, 0.66–2.08, P = 0.60). Donor HSD17B13 genotype adversely affects post-LT survival in patients receiving steroid induction. Additional studies are required to confirm this association. and Collaborative Scientist Grant
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DOI：
10.1002/hep.30350
发表时间：
2019-04
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Ma Y;Belyaeva OV;Brown PM;Fujita K;Valles K;Karki S;de Boer YS;Koh C;Chen Y;Du X;Handelman SK;Chen V;Speliotes EK;Nestlerode C;Thomas E;Kleiner DE;Zmuda JM;Sanyal AJ;(for the Nonalcoholic Steatohepatitis Clinical Research Network);Kedishvili NY;Liang TJ;Rotman Y
通讯作者：
Rotman Y
影响因子：
3.7
作者：
Valenti L;Motta BM;Soardo G;Iavarone M;Donati B;Sangiovanni A;Carnelutti A;Dongiovanni P;Rametta R;Bertelli C;Facchetti F;Colombo M;Fargion S;Fracanzani AL
通讯作者：
Fracanzani AL
影响因子：
39
作者：
Lee, Brian P.;Vittinghoff, Eric;Terrault, Norah A.
通讯作者：
Terrault, Norah A.
DOI：
10.1111/liv.12310
发表时间：
2014-04
期刊：
Liver international : official journal of the International Association for the Study of the Liver
影响因子：
--
作者：
Burza MA;Molinaro A;Attilia ML;Rotondo C;Attilia F;Ceccanti M;Ferri F;Maldarelli F;Maffongelli A;De Santis A;Attili AF;Romeo S;Ginanni Corradini S
通讯作者：
Ginanni Corradini S
影响因子：
4.1
作者：
Friedrich, Kilian;Wannhoff, Andreas;Gotthardt, Daniel Nils
通讯作者：
Gotthardt, Daniel Nils