Evidence map›Paper›PMID 42486812›Full record

ArticleHepatology communications2026

Extended haplotypes at the complement factor H gene locus are associated with liver transplant rejection.

Lianne M Nieuwenhuis, Bao-Li Loza, Stefan P Berger, Bernadien H Jansen, Hans Blokzijl, Mohamed R Daha, Rosa G M Lammerts, Abraham Shaked, Sumeet Asrani, Ton Lisman and 5 more

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Article in Hepatology communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Lianne M NieuwenhuisDepartment of Surgery, Section of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0003-1159-787
Bao-Li LozaDepartment of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0003-3917-6129
Stefan P BergerDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0003-2228-4676
Bernadien H JansenDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Hans BlokzijlDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0003-4240-7506
Mohamed R DahaDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Rosa G M LammertsTransplantation Immunology, Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-9970-9006
Abraham ShakedDepartment of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Sumeet AsraniBaylor University Medical Center, Dallas, Texas, USA.ORCID 0000-0001-9174-5670
Ton LismanDepartment of Surgery, Section of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-3503-7140
Rinse K WeersmaDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0001-7928-7371
Eleonora A M FestenDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-3255-6930
Vincent E de MeijerDepartment of Surgery, Section of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-7900-5917
Felix PoppelaarsDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-5173-8078
TransplantLines Investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAcute T-cell-mediated rejection (ACR) remains an important complication after liver transplantation. Polymorphisms in the factor H gene (CFH) and factor H-related protein genes (CFHRs) affect the risk of multiple complement-related diseases. Given the complement system's key role in alloimmunity, we hypothesized that variants in CFH and CFHRs associate with ACR risk after liver transplantation.

methodsIn 689 donor-recipient pairs, the deletion of CFHR1 and CFHR3 (CFHR3,1Δ), a low-expression variant of CFHR2, and CFH haplotypes were extracted from both donor and recipient genotypes following appropriate imputation and quality control steps.

resultsKaplan-Meier survival curves and multivariable Cox regression analysis showed increased ACR incidence after transplantation of donor livers carrying 2 copies of the CFHR3,1Δ (log-rank p=0.03, HR: 2.76, 95% CI: 1.18-6.45) or the related CFH-H4a haplotype (log-rank p=0.03, HR: 1.65, 95% CI: 1.04-2.63). In contrast, a lower ACR incidence was observed after transplanting donor livers with a low-expressing CFHR2 variant (log-rank p=0.04, HR: 0.66, 95% CI: 0.45-0.96) or the related CFH-H2 haplotype (log-rank p=0.01, HR: 0.58, 95% CI: 0.37-0.92). When analyzing recipient genotypes, only CFHR3,1Δ was associated with ACR (log-rank: p=0.01, HR: 2.55, 95% CI: 1.15-5.65).

conclusionsCommon functional variants in the CFH-CFHR region are associated with rejection risk after liver transplantation, highlighting a previously overlooked relevance of the complement system in liver transplantation.

Indexed as

Complement C3b Inactivator ProteinsComplement Factor HGraft RejectionLiver TransplantationBlood ProteinsFemaleHaplotypesHumansKaplan-Meier EstimateMaleBlood ProteinsCFHR1 protein, humanCFHR3 protein, humanComplement C3b Inactivator ProteinsComplement Factor Hacute cellular rejectiongeneticsimmunologyliver diseaseliver transplantation

Identifiers

PMID42486812
PMCPMC13671603

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