Noninvasive graft monitoring using donor-derived cell-free DNA in Japanese liver transplantation

被引：5

作者：

Kanamori, Hiroki ^{[1
]}

Yamada, Yohei ^{[1
]}

Ito, Yoko ^{[1
]}

Shirosaki, Koji ^{[1
]}

Yamagishi, Satoko ^{[1
]}

Maeda, Yutaro ^{[1
]}

Kudo, Yumi ^{[1
]}

Umeyama, Tomoshige ^{[2
]}

Takahashi, Nobuhiro ^{[1
]}

Kato, Mototoshi ^{[1
]}

Hasegawa, Yasushi ^{[3
]}

Matsubara, Kentaro ^{[3
]}

Shinoda, Masahiro ^{[4
]}

Obara, Hideaki

Irie, Rie ^{[5
]}

Tsujikawa, Hanako ^{[6
]}

Okita, Hajime ^{[3
,6
]}

Nguyen, Phuong Thanh ^{[7
]}

Saigo, Kenichi ^{[8
]}

Mitsunaga, Shigeki ^{[7
]}

Inoue, Ituro ^{[7
]}

Kitagawa, Yuko ^{[3
]}

Kuroda, Tatsuo ^{[1
,9
]}

机构：

[1] Keio Univ, Sch Med, Dept Pediat Surg, 35 Shinanomachi,Shinjuku Ku, Tokyo 1608582, Japan

[2] St Lukes Int Hosp, Dept Pediat Surg, Tokyo, Japan

[3] Keio Univ, Sch Med, Dept Surg, Tokyo, Japan

[4] Int Univ Hlth & Welf, Mita Hosp, Sch Med, Digest Dis Ctr, Tokyo, Japan

[5] Nippon Koukan Hosp, Dept Diagnost Pathol, Kawasaki, Japan

[6] Keio Univ, Sch Med, Div Diagnost Pathol, Tokyo, Japan

[7] Natl Inst Genet, Human Genet Lab, Mishima, Japan

[8] Japan Community Hlth Care Org, Chiba Hosp, Dept Transplantat Surg, Chiba, Japan

[9] Kanagawa Childrens Med Ctr, Yokohama, Kanagawa, Japan

来源：

HEPATOLOGY RESEARCH | 2024年 / 54卷 / 03期

基金：

日本学术振兴会;

关键词：

biomarker; clinical research; donor-derived cell-free DNA; graft injury; liver transplantation; next generation sequencer; ANTIBODY-MEDIATED REJECTION; FIBROSIS; DISEASE; QUANTIFICATION; RECIPIENTS; BIOMARKER;

D O I：

10.1111/hepr.13978

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Aim: To evaluate the use of donor-derived cell-free DNA (dd-cfDNA) in diagnosing graft injuries in Japanese liver transplantation (LTx), including family-related living donors.Methods: A total of 321 samples from 10 newly operated LTx recipients were collected to monitor the early dynamics of dd-cfDNA levels after LTx. Fifty-five samples from 55 recipients were collected during protocol biopsies (PB), whereas 36 samples from 27 recipients were collected during event biopsies, consisting of 11 biopsy-proven acute rejection (AR), 20 acute dysfunctions without rejection (ADWR), and 5 chronic rejections. The levels of dd-cfDNA were quantified using a next-generation sequencer based on single nucleotide polymorphisms.Results: The dd-cfDNA levels were elevated significantly after LTx, followed by a rapid decline to the baseline in patients without graft injury within 30 days post-LTx. The dd-cfDNA levels were significantly higher in the 11 samples obtained during AR than those obtained during PB (p < 0.0001), which decreased promptly after treatment. The receiver operator characteristic curve analysis of diagnostic ability yielded areas under the curve of 0.975 and 0.897 for AR (rejection activity index [RAI] >= 3) versus PB and versus non-AR (ADWR + PB). The dd-cfDNA levels during AR were elevated earlier and correlated more strongly with the RAI (r = 0.740) than aspartate aminotransferase/alanine aminotransferase. The dd-cfDNA levels were neither associated with graft fibrosis based on histology nor the status of donor-specific antibodies in PB samples.Conclusions: Donor-derived cell-free DNA serves as a sensitive biomarker for detecting graft injuries in LTx. Further large-scale cohort studies are warranted to optimize its use in differentiating various post-LTx etiologies. [GRAPHICS]

引用

页码：300 / 314

页数：15

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