Sex mismatch as a risk factor for chronic rejection of liver allografts

doi:10.1016/S0140-6736(95)91797-7

The Lancet

Volume 346, Issue 8983, 28 October 1995, Pages 1117-1121

https://doi.org/10.1016/S0140-6736(95)91797-7 Get rights and content

Abstract

Summary

Chronic irreversible rejection is a major cause of graft loss and retransplantation after orthotopic liver allo-transplantation. To identify risk factors we retrospectively analysed 423 adult consecutive primary liver allograft recipients.

The endpoint of the study was graft failure due to chronic rejection leading either to retransplantation or death. Chronic rejection developed in 22 (5·2%) patients. Pretransplant diagnosis of primary biliary cirrhosis or autoimmune hepatitis, recipient age less than 30 years, 1 or more episodes of acute cellular rejection, and transplantation of an organ from cytomegalovirus (CMV). IgG positive donor to an IgG negative recipient were identified as risk factors for chronic rejection. Transplantation of a liver from a male donor into a female recipient was also associated with an increased probability of chronic rejection. By logistic regression analysis, the probability of chronic rejection was predicted by: sex and cytomegalovirus match of donor and recipient, the presence of acute rejection, recipient age, transplantation for autoimmune hepatitis or primary biliary cirrhosis, and recipients receiving no azathioprine during the third month after transplantation. Sensitisation to antigens expressed by bile-duct epithelium as in primary biliary cirrhosis or exposure to donor bile-duct minor histocompatibility antigens, such as the male sex related H-Y antigen, may provide an explanation.

More selective allocation of donor organs may allow a reduction in the incidence of ductopaenic rejection and graft loss.

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Citation Excerpt :
As ACR and CR are immune related, predisposing factors are largely common. These include autoimmune etiology of underlying liver disease before liver transplantation (primary biliary sclerosis, primary sclerosing cholangitis and autoimmune hepatitis), cytomegalovirus infection, low levels or noncompliance to immunosuppression, positive lymphocyte cross-match, higher lower recipient age, donor-recipient ethnic origin, male donor into female recipient, higher donor age, higher cold ischemia time and living versus deceased donor liver translantation.4,14,29,39 A review of 18 studies (1437 transplant recipients) showed that ACR developed in 24–80% (mean 49%) of recipients among various studies.31
While antibody mediated hyper-acute vasculitic rejection is rare in liver transplant recipients, acute and chronic rejection have clinical significance. The liver allograft behaves differently to other solid organ transplants as acute rejection generally does not impair graft survival and chronic rejection (CR) is uncommon. The incidence of acute and chronic rejection has declined in current era due to improved immunosuppressive regimens. Acute rejection generally improves with steroid boluses and steroid resistant rejection is uncommon. CR may improve with escalation of immunosuppression or may result in irreversible loss of graft function leading to retransplantation or death. The current review discusses diagnosis and management of acute and chronic liver allograft rejection.
Prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation
2016, Clinics
Chronic rejection remains a major cause of graft failure with indication for re-transplantation. The incidence of chronic rejection remains high in the pediatric population. Although several risk factors have been implicated in adults, the prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation are not known. Hence, the current study aimed to determine the factors involved in the progression or reversibility of pediatric chronic rejection by evaluating a series of chronic rejection cases following liver transplantation.
Chronic rejection cases were identified by performing liver biopsies on patients based on clinical suspicion. Treatment included maintaining high levels of tacrolimus and the introduction of mofetil mycophenolate. The children were divided into 2 groups: those with favorable outcomes and those with adverse outcomes. Multivariate analysis was performed to identify potential risk factors in these groups.
Among 537 children subjected to liver transplantation, chronic rejection occurred in 29 patients (5.4%). In 10 patients (10/29, 34.5%), remission of chronic rejection was achieved with immunosuppression (favorable outcomes group). In the remaining 19 patients (19/29, 65.5%), rejection could not be controlled (adverse outcomes group) and resulted in re-transplantation (7 patients, 24.1%) or death (12 patients, 41.4%). Statistical analysis showed that the presence of ductopenia was associated with worse outcomes (risk ratio=2.08, p=0.01).
The presence of ductopenia is associated with poor prognosis in pediatric patients with chronic graft rejection.
Long-Term Outcomes of Living-Donor Liver Transplantation for Primary Biliary Cirrhosis: A Japanese Multicenter Study
2016, American Journal of Transplantation
The factors that influence long-term outcomes after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC) are not well known. Compared with deceased-donor transplantation, LDLT has an increased likelihood of a related donor and a decreased number of human leukocyte antigen (HLA) mismatches. To clarify the effects of donor relatedness and HLA mismatch on the outcomes after LDLT, we retrospectively analyzed 444 Japanese patients. Donors were blood relatives for 332 patients, spouses for 105, and “other” for 7. The number of HLA A-B-DR mismatches was none to two in 141, three in 123, and four to six in 106 patients. The 15-year survival rate was 52.6%, and PBC recurred in 65 patients. Recipient aged 61 years or older, HLA mismatches of four or more (maximum of six), graft:recipient weight ratio less than 0.8, and husband donor were adverse indicators of patient survival. IgM 554 mg/dL or greater, donor–recipient sex mismatch, and initial immunosuppression with cyclosporine were significant risks for PBC recurrence, which did not affect patient survival. In subgroup analysis, conversion to cyclosporine from tacrolimus within 1 year diminished recurrence. Prospective studies are needed to determine the influence of pregnancy-associated sensitization and to establish an optimal immunosuppressive regimen in LDLT patients.
Clinical outcomes and genetic expression profile in human liver graft dysfunction during ischemia/reperfusion injury
2015, Transplantation Proceedings
Citation Excerpt :
There are some reports on poor prognosis in female recipients with donor mismatch, which is considered an independent risk factor for primary graft nonfunction [33]. The causes are yet to be clarified, but the role of minor histocompatibility antigens such as H-Y antigen, codified by genes from Y chromosome, has been suggested in literature; further studies are awaited [34]. The main limitation of this study is the small number of patients enrolled.
This study aims to compare the molecular gene expression during ischemia reperfusion injury. Several surgical times were considered: in the beginning of the harvesting (T0), at the end of the cold ischemia period (T1), and after reperfusion (T2) and compared with graft dysfunction after liver transplant (OLT).
We studied 54 patients undergoing OLT. Clinical, laboratory data, and histologic data (Suzuki classification) as well as the Survival Outcomes Following Liver Transplantation (SOFT) score were used and compared with the molecular gene expression of the following genes: Interleukin (IL)-1b, IL-6, tumor necrosis factor-α, perforin, E-selectin (SELE), Fas-ligand, granzyme B, heme oxygenase-1, and nitric oxide synthetase.
Fifteen patients presented with graft dysfunction according to SOFT criteria. No relevant data were obtained by comparing the variables graft dysfunction and histologic variables. We observed a statistically significant relation between SELE at T0 (P = .013) and IL-1β at T0 (P = .028) and early graft dysfunction.
We conclude that several genetically determined proinflammatory expressions may play a critical role in the development of graft dysfunction after OLT.

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ArticlesSex mismatch as a risk factor for chronic rejection of liver allografts

Abstract

Lancet

Rev Fr Transfus Hemobiol

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Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure

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Sex mismatch as a risk factor for chronic rejection of liver allografts