The Kupffer Cell Number Affects the Outcome of Living Donor Liver Transplantation from Elderly Donors

Hidaka, Masaaki; Eguchi, Susumu; Takatsuki, Mitsuhisa; Soyama, Akihiko; Ono, Satoshi; Adachi, Tomohiko; Natsuda, Koji; Kugiyama, Tota; Hara, Takanobu; Okada, Satoru; Imamura, Hajime; Miuma, Satoshi; Miyaaki, Hisamitsu

doi:10.1097/txd.0000000000000608

Cited by 20 publications

(23 citation statements)

References 36 publications

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“…The poor outcome with the older donor age group in our study may be attributed to the effect of aging on the liver’s capacity for regeneration . Hidaka et al have attributed that to the significantly fewer Kupffer cells in liver grafts donated from elderly donors than those procured from young donors . They reported that the low Kupffer cell number in elderly liver grafts (>50 years) was a prognostic factor for graft failure after LDLT .…”

Section: Discussionmentioning

confidence: 56%

“…(31) They reported that the low Kupffer cell number in elderly liver grafts (>50 years) was a prognostic factor for graft failure after LDLT. (31) Regarding gene senescence and liver regeneration, Eguchi et al reported that there was no graft rejuvenation in pediatric recipients when grafts from old donors had been used in LDLT. (32) They assessed the transplanted grafts for the expression of the senescence marker protein-30 (SMP-30), which is correlated to hepatocyte proliferation, a decrease of reactive oxygen species, and exertion of a cytoprotective function.…”

Section: Discussionmentioning

confidence: 99%

“…Hidaka et al have attributed that to the significantly fewer Kupffer cells in liver grafts donated from elderly donors than those procured from young donors . They reported that the low Kupffer cell number in elderly liver grafts (>50 years) was a prognostic factor for graft failure after LDLT . Regarding gene senescence and liver regeneration, Eguchi et al reported that there was no graft rejuvenation in pediatric recipients when grafts from old donors had been used in LDLT .…”

Section: Discussionmentioning

confidence: 99%

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Older Donor Age Is a Risk Factor for Negative Outcomes After Adult Living Donor Liver Transplantation Using Small‐for‐Size Grafts

et al. 2019

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Adult‐to‐adult living donor liver transplantation (ALDLT) using small‐for‐size grafts (SFSGs), ie, a graft with a graft‐to‐recipient weight ratio (GRWR) <0.8%, has been a challenge that should be carefully dealt with, and risk factors in this category are unclear. Therefore, we aimed to examine the risk factors and outcomes of ALDLT using SFSGs over a 13‐year period in 121 patients who had undergone their first ALDLT using SFSGs. Small‐for‐size syndrome (SFSS), early graft loss, and 1‐year mortality were encountered in 21.6%, 14.9%, and 18.4% of patients, respectively. By multivariate analysis, older donor age (≥45 years) was an independent risk factor for SFSS (odds ratio [OR], 4.46; P = 0.004), early graft loss (OR, 4.11; P = 0.02), and 1‐year mortality (OR, 3.76; P = 0.02). Child‐Pugh C class recipients were associated with a higher risk of SFSS development (P = 0.013; OR, 7.44). Despite no significant difference between GRWR categories in the multivariate outcome analysis of the whole population, in the survival analysis of the 2 donor age groups, GRWR <0.6% was associated with significantly lower 1‐year survival than the other GRWR categories in the younger donor group. Moreover, in the high final portal venous pressure (PVP) group (>15 mm Hg), younger ABO‐compatible donors showed 100% 1‐year survival with a significant difference from the group of other donors. Older donor age was an independent risk factor for SFSS, early graft loss, and 1‐year mortality after ALDLT using SFSGs. GRWR should not be <0.6%, and PVP modulation is indicated when grafts from older or ABO‐incompatible donors are used.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Older Donor Age Is a Risk Factor for Negative Outcomes After Adult Living Donor Liver Transplantation Using Small‐for‐Size Grafts

et al. 2019

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“…KC treated with gadolinium chloride prevented the induction of portal venous tolerance by inhibiting Ag presentation to lymphocytes, supporting the notion that both Ag presentation to and stimulation of lymphocyte proliferation are necessary for tolerance induction (17). In human studies, a greater number of KC typically found in younger living donors predicts better hepatic allograft survival compared to elderly living donors, suggesting that KC in the donor liver are a relevant prognostic factor influencing post-transplant outcomes (18). Graft-infiltrating DC and KC were also shown to be increased during and after rat liver transplant tolerance induction, again suggesting a possible important role for these cells in shaping the host immune response toward tolerance (19).…”

Section: Intrahepatic Immune Cells Interact With Liver Parenchymal Cementioning

confidence: 62%

Transplant Tolerance Induction: Insights From the Liver

2020

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A comparison of pre-clinical transplant models and of solid organs transplanted in routine clinical practice demonstrates that the liver is most amenable to the development of immunological tolerance. This phenomenon arises in the absence of stringent conditioning regimens that accompany published tolerizing protocols for other organs, particularly the kidney. The unique immunologic properties of the liver have assisted our understanding of the alloimmune response and how it can be manipulated to improve graft function and survival. This review will address important findings following liver transplantation in both animals and humans, and how these have driven the understanding and development of therapeutic immunosuppressive options. We will discuss the liver's unique system of immune and non-immune cells that regulate immunity, yet maintain effective responses to pathogens, as well as mechanisms of liver transplant tolerance in pre-clinical models and humans, including current immunosuppressive drug withdrawal trials and biomarkers of tolerance. In addition, we will address innovative therapeutic strategies, including mesenchymal stem cell, regulatory T cell, and regulatory dendritic cell therapy to promote liver allograft tolerance or minimization of immunosuppression in the clinic.

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“…Kupffer cell number is restored to its initial level after Kupffer cell depletion [ 29 , 30 ]. Also, a high Kupffer cell number increases patient survival rates following liver transplantation [ 31 ], and alterations in Kupffer cell number are associated with specific liver pathologies [ 32 ], although distinguishing bona fide Kupffer cells from infiltrating monocytes and monocyte-derived macrophages is challenging. Akin to other macrophage populations, Kupffer cells were long believed to lack the ability to proliferate [ 33 ], and monocytes were thought to be their sole source for replenishment [ 34 ].…”

Section: Self-renewal Ability Of Kupffer Cellsmentioning

confidence: 99%

Understanding the Biology of Self-Renewing Macrophages

Röszer

2018

Cells

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Macrophages reside in specific territories in organs, where they contribute to the development, homeostasis, and repair of tissues. Recent work has shown that the size of tissue macrophage populations has an impact on tissue functions and is determined by the balance between replenishment and elimination. Macrophage replenishment is mainly due to self-renewal of macrophages, with a secondary contribution from blood monocytes. Self-renewal is a recently discovered trait of macrophages, which can have a major impact on their physiological functions and hence on the wellbeing of the organism. In this review, I discuss our current understanding of the developmental origin of self-renewing macrophages and the mechanisms used to maintain a physiologically stable macrophage pool.

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The Kupffer Cell Number Affects the Outcome of Living Donor Liver Transplantation from Elderly Donors

Cited by 20 publications

References 36 publications

Older Donor Age Is a Risk Factor for Negative Outcomes After Adult Living Donor Liver Transplantation Using Small‐for‐Size Grafts

Older Donor Age Is a Risk Factor for Negative Outcomes After Adult Living Donor Liver Transplantation Using Small‐for‐Size Grafts

Transplant Tolerance Induction: Insights From the Liver

Understanding the Biology of Self-Renewing Macrophages

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