Acute Graft versus Host Disease After Liver Transplantation: Patterns of Lymphocyte Chimerism

Domiati‐Saad, Rana; Klintmalm, Göran B.; Netto, George J.; Agura, Edward; Chinnakotla, Srinath; Smith, Douglas M.

doi:10.1111/j.1600-6143.2005.01110.x

Cited by 81 publications

(83 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Similar to other types of organ transplantation, chimerism can develop after LT with the chimeric cells either circulating or integrated into the parenchyma. 2 Several types of reciprocal chimerisms after LT have been reported, including (1) recipient-derived cells in the donor organ 3,4 ; (2) hematopoietic chimerism of donor origin in the recipient blood [5][6][7] ; and (3) donor origin cells in the skin and lymph nodes. 8 Donor lymphocyte chimerism is common after LT, but it usually decreases and often disappears within 3 weeks.…”

Section: Cd45mentioning

confidence: 99%

Hematopoietic chimerism in liver transplantation patients and hematopoietic stem/progenitor cells in adult human liver

Wang

Chen

et al. 2012

Hepatology

View full text Add to dashboard Cite

Liver transplantation (LT) is a cure for many liver diseases. Blood chimerism of donor origin can develop after LT, which raises the possibility of the existence of hematopoietic stem/progenitor cells (HSPCs) in the liver. We characterized the blood chimerism in a large cohort of 249 LT patients and analyzed putative HSPCs in adult human livers. The overall incidence of chimerism was 6.43%, of which 11.11% was among short-term (1 day to 6 months) and 3.77% was among long-term (6 months to 8 years CD451 or CD45 1 liver cells could be engrafted into hematopoietic cells in an immunodeficient mouse model. These results are the first evidence of the presence of putative HSPC populations in the adult human liver, where the liver is a good ectopic niche. The discovery of the existence of HSPCs in the adult liver have implications for the understanding of extramarrow hematopoiesis, liver regeneration, mechanisms of tolerance in organ transplantation, and de novo cancer recurrence in LT patients. Conclusion: The human adult liver contains a small population of HSPCs. In LT patients, there are two types of chimerisms: transient chimerism, resulting from mature leucocytes, and long-term chimerism, derived from putative HSPCs in the liver graft. (HEPATOLOGY 2012;56:1557-1566

show abstract

Section: Cd45mentioning

confidence: 99%

Hematopoietic chimerism in liver transplantation patients and hematopoietic stem/progenitor cells in adult human liver

Wang

Chen

et al. 2012

Hepatology

View full text Add to dashboard Cite

show abstract

“…11 However, patients with GVHD have higher levels of donor T cells. 11 In the current case, donor-specific T lymphocytes were 5% to 10% at 5 months after liver transplant.…”

Section: Discussionmentioning

confidence: 99%

“…4 The mean level of donor T cells after liver transplant is approximately 5% on the second postoperative day and decreases subsequently. 11 At 8 weeks after liver transplant, recipients still may exhibit 3% donor T lymphocytes in peripheral blood. 11 However, patients with GVHD have higher levels of donor T cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of Liver Transplant Graft-Versus-Host Disease With Antibodies Against Tumor Necrosis Factor-α

Blank

Li²,

Kratt³

et al. 2012

Exp Clin Transplant

View full text Add to dashboard Cite

Acute graft-versus-host disease is uncommon after liver transplant. We recently treated a 60-year-old man with liver transplant for hepatocellular carcinoma. After the primary liver transplant graft did not function, revision liver transplant resulted in excellent function. Subsequently, the patient developed watery diarrhea, systemic inflammatory response syndrome, a skin rash on his limbs and trunk, and palmar erythema. Skin biopsy suggested viral exanthems consistent with cytomegalovirus. Despite treatment for cytomegalovirus, intestinal symptoms worsened. Analysis of peripheral blood with fluorescence-activated cell sorting showed a high proportion of T lymphocytes, with 5% to 10% T cells specific to the second donor, suggestive of graft-versus-host disease. Within 48 hours after beginning therapy with antibodies against tumor necrosis factor-α (infliximab), the skin rash disappeared and endoscopy showed slight improvement of the mucosal regeneration. However, despite antifungal prophylaxis with caspofungin, the patient developed angioinvasive pulmonary aspergillosis and multiple organ failure, and he died. In conclusion, typical clinical symptoms of graftversus-host disease after liver transplant may include skin rash and gastrointestinal symptoms, and diagnosis may be confirmed by histologic examination and testing for blood chimerism. A consensus for the treatment of graft-versus-host disease still is lacking, but tumor necrosis factor-α is an encouraging target for therapy to decrease the symptoms of graft-versus-host disease and enable mucosal regeneration.

show abstract

“…This finding was not unexpected. Donor lymphocyte chimerism post organ transplant may change with time elapsed transplant [22]. Chimerism, the coexisting of donor and recipient immune system [23], could have complicated the investigation in post liver transplant recipients.…”

Section: Discussionmentioning

confidence: 99%

Influences of Donor and Recipient Gene Polymorphisms on Tacrolimus Dosing and Pharmacokinetics in Asian Liver Transplant Patients

Yee¹,

Tan²,

Sia³

et al. 2013

OJOTS

View full text Add to dashboard Cite

Background: Tacrolimus pharmacokinetics has large inter-individual variability. Objectives: This study aimed to investigate the impact of donor and recipient gene polymorphisms on tacrolimus dosing and pharmacokinetics in Asian liver transplant patients. Methods: Steady-statetacrolimus concentrations at 0, 1, 2, 4 and 6 h were measured. Pharmacokinetic parameters were estimated with a one-compartment linear model using WinNonlin 6.1 program. DNA from donor liver and recipient blood samples were genotyped for CYP3A and ABCB1 polymorphisms. 3) (64.48 versus 129.21 (mcg/L)/(mg/kg/day), P = 0.040). Hence, the dose required to achieve target concentration in patients with donor genotype CYP3A5 expressors was higher than non-expressors (0.12 versus 0.08 mg/kg, P = 0.045). Recipient with ABCB1-C3435T genotype TT demonstrated higher apparent oral clearance of tacrolimus as compared to genotype CC (17.7 versus 7.9 L/h, P = 0.033). Conclusions: Donor liver CYP3A polymorphism could potentially affect tacrolimus C0/D ratio as early as the first week post liver transplant. Genotyping of liver donors may be useful to achieve the optimal drug concentration during this critical period.

show abstract

Acute Graft versus Host Disease After Liver Transplantation: Patterns of Lymphocyte Chimerism

Cited by 81 publications

References 28 publications

Hematopoietic chimerism in liver transplantation patients and hematopoietic stem/progenitor cells in adult human liver

Hematopoietic chimerism in liver transplantation patients and hematopoietic stem/progenitor cells in adult human liver

Treatment of Liver Transplant Graft-Versus-Host Disease With Antibodies Against Tumor Necrosis Factor-α

Influences of Donor and Recipient Gene Polymorphisms on Tacrolimus Dosing and Pharmacokinetics in Asian Liver Transplant Patients

Contact Info

Product

Resources

About