Graft‐Versus‐Host Disease After Liver Transplantation

Wood, Ashley; Eghtesad, Bijan; Lindenmeyer, Christina C.

doi:10.1002/cld.884

Cited by 12 publications

(25 citation statements)

References 25 publications

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“…Other potential therapies include IL-2 and TNF- α blockers, such as daclizumab, infliximab, and etanercept which have been utilized in conjunction with steroids as well as used as monotherapy, but overall outcomes remain poor [ 8 , 9 ]. Alefacept, which prevents the activation of CD4 and CD8 T-lymphocytes and antithymocyte globulin, eliminates the activated effector T-cells, when used in combination with high dose steroids in patients who develop pancytopenia that have been shown to result in immediate rebound of bone marrow function, but with increased risk of infection [ 10 , 11 ]. Other options include extracorporeal photopheresis, which modulates the immune system and was found in one report to decrease peripheral blood chimerism but had no effect on mortality [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Treatment of Acute Graft-versus-Host Disease in Liver Transplant Recipients

Kim

Adeel

Bozorgzadeh

et al. 2021

Case Reports in Transplantation

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Acute graft-versus-host disease (aGvHD) is a rare complication of liver transplantation associated with high morbidity and mortality. Death typically occurs due to complications related to severe infection, shock, and multiorgan failure. The clinical presentation involves dysfunction of multiple organ systems with overlapping symptoms that often results in a diagnostic delay. As there are a limited number of cases reported in the literature, there are no clear guidelines for treatment. Many different therapeutic measures have been utilized that target various immune system pathways, but steroids remain the first line of therapy. We report on two patients who developed aGvHD after liver transplantation who were treated with ruxolitinib, a novel Janus kinase 1/2 (JAK) inhibitor that has been shown to improve outcomes in steroid refractory cases of aGvHD after allogenic hematopoietic stem cell transplantation. We reviewed the literature to discuss various therapeutic options currently available for aGvHD after liver transplantation.

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Section: Discussionmentioning

confidence: 99%

Treatment of Acute Graft-versus-Host Disease in Liver Transplant Recipients

Kim

Adeel

Bozorgzadeh

et al. 2021

Case Reports in Transplantation

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“…Humoral-type GVHD occurs in ABO blood group patients with incompatible or nonidentical liver grafts and is mediated by antibody production by donor T lymphocytes against the red cell antigen of the recipient. It is characterized by fever and hemolysis; the symptoms are mild with hemolytic anemia[ 1 , 9 ]. On the other hand, cellular-type GVHD is a rare complication with high mortality.…”

Section: Discussionmentioning

confidence: 99%

“…GVHD is a rare but frequently lethal complication after solid organ transplantation (SOT). Acute GVHD (aGVHD) is rare after liver transplantation (LT) than hematopoietic stem cell transplantation (HSCT) with an estimated incidence rate of 0.5%–2%; the high mortality associated with this complication (up to 85%) poses a critical challenge[ 1 - 3 ]. aGVHD after LT could present between 1 and 8 weeks post-transplantation.…”

Section: Introductionmentioning

confidence: 99%

“…Hence, the frequently encountered clinical signs and symptoms including fever, rash, and diarrhea. On the other hand, pancytopenia is observed in advanced stages of the disease[ 1 ]. Pancytopenia, diarrhea, the age difference between donor and recipient, and time from the occurrence of the first symptom to diagnosis and treatment are known as the risk factors that affecting GVHD-related mortality[ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Diagnosis and treatment of acute graft-versus-host disease after liver transplantation: Report of six cases

Tian¹,

Lyu²,

Wang³

et al. 2021

WJCC

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BACKGROUND Graft-versus-host disease (GVHD) following liver transplantation (LT) is an unpredictable complication with poor outcome. However, consensus regarding the diagnosis and therapeutic regimen for the disease is yet lacking. The present study summarized the clinical experience on the diagnosis and treatment of acute GVHD (aGVHD) following LT and reviewed the pertinent literature. CASE SUMMARY Between January 1 st , 2000 and December 31 st , 2020, a total of 1053 LT were performed in the First Affiliated Hospital of Xi’an Jiaotong University. Six recipients developed aGVHD with clinical symptoms of fever, rash, diarrhea, and pancytopenia. The incidence of aGVHD was 0.57%. The median time from LT to the clinical presentation of aGVHD was 22.17 d. The median time from the beginning of the clinical symptom to histopathological diagnosis was 7.5 d. All six cases underwent treatment of immunosuppressant adjustment, corticosteroids, human normal immunoglobulin, and antithymocyte globulin/IL-2 antagonists. Despite intensive treatment strategies, 4 patients were deceased due to sepsis, multiple organ failure, and cerebral hemorrhage. The remaining two cases were discharged as treatment successfully. However, one died because of tuberculosis infection on the 6th month of follow-up, the other one was alive healthy during 30 mo of follow-up. CONCLUSION The rapid diagnosis of aGVHD is mainly based on the time from the first symptom, histopathological features, and the donor T-lymphocyte chimerism. Our cases report highlights massive corticosteroid therapy and age difference between donors and recipients could accelerate to aGVHD. Moreover, gut microbial interventions and donor-targeted serotherapy may provide novel therapeutics.

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“…14 In LT, a susceptible host (i.e., immunocompromised, or in a pro-inflammatory state) may be unable to reject passenger hematopoietic cells resulting in donor T cell interactions with host APC. 16,17 Acute GVHD occurring within the first 100 days after HCT classically involves the skin, liver, and/or gastrointestinal (GI) tract. In LT, the donor liver graft is unaffected by GVHD 18 ; however, there is a risk of pancytopenia and irreversible bone marrow failure (BMF), presumably mediated by donor T lymphocytes targeting recipient HSC akin to an acquired aplastic anemia.…”

Section: Introductionmentioning

confidence: 99%

Graft-versus-host disease after liver transplantation is associated with bone marrow failure, hemophagocytosis, and DNMT3A mutations

Newell

Dunlap

Gatter

et al. 2021

American Journal of Transplantation

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Graft‐versus‐host disease after liver transplantation (LT‐GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT‐GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next‐generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT‐GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT‐GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT‐GVHD had DNMT3A mutations; only 1 of 6 in the non‐GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT‐GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over‐represented, in LT‐GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.

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Graft‐Versus‐Host Disease After Liver Transplantation

Cited by 12 publications

References 25 publications

Treatment of Acute Graft-versus-Host Disease in Liver Transplant Recipients

Treatment of Acute Graft-versus-Host Disease in Liver Transplant Recipients

Diagnosis and treatment of acute graft-versus-host disease after liver transplantation: Report of six cases

Graft-versus-host disease after liver transplantation is associated with bone marrow failure, hemophagocytosis, and DNMT3A mutations

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