Graft and systemic disease in long-term survivors of liver transplantation

Slapak, G.; Saxena, Romit; Portmann, B; Gane, Ed; Devlin, John; Calne, Sir Roy; Williams, Roger

doi:10.1016/s0928-4346(97)85788-x

Cited by 40 publications

(73 citation statements)

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“…Histological abnormalities have been reported in 36-90% of patients who nonetheless displayed normal LFTs [5,9,13]. Among our patients with normal LFTs, 27/33 had histological abnormalities and 6/33 had normal histological findings (poor PPV of 18%).…”

Section: Discussionmentioning

confidence: 55%

“…Hepatic structural abnormalities complicated 20% of our patients; the most severe (i.e., NRH) affected 10% of them and 20-30% of the biopsies in other studies [9,[11][12][13]. Many of them caused no obvious clinical manifestations but some patients developed signs of portal hypertension necessitating reLT [9,12]. Two of our patients presented with symptoms (oedema and ascites), while in the Devarbhavi's study [11], patients were all asymptomatic.…”

Section: Discussionmentioning

confidence: 56%

“…At a time when efforts are being made to minimize the long-term adverse effects of immunosuppressive drugs, a cautious approach should nevertheless be adopted because CR may reflect insufficient immunosuppression in some patients. Hepatic structural abnormalities complicated 20% of our patients; the most severe (i.e., NRH) affected 10% of them and 20-30% of the biopsies in other studies [9,[11][12][13]. Many of them caused no obvious clinical manifestations but some patients developed signs of portal hypertension necessitating reLT [9,12].…”

Section: Discussionmentioning

confidence: 74%

“…The second most common abnormality was CR (23%). Rates of 0%, 18%, and 3% were found at follow-up of 20 [7], 7 [8], and 8.4 years [9], respectively. CR is probably more common than has often been appreciated by some teams insofar, as it accounts for ductopenia >50%.…”

Section: Discussionmentioning

confidence: 99%

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Twenty-year protocol liver biopsies: Invasive but useful for the management of liver recipients

Sebagh

Samuel

Antonini

et al. 2012

Journal of Hepatology

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Twenty-year protocol liver biopsies: Invasive but useful for the management of liver recipients

Sebagh

Samuel

Antonini

et al. 2012

Journal of Hepatology

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confidence: 99%

Chronic rejection: The result of uncontrolled remodelling of graft tissue by recipient mesenchymal cells? Data from two rodent models and the effects of immunosupressive therapies

Brazelton

Adams

Shorthouse

et al. 1999

Inflammation Research

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IntroductionChronic rejection lesions develop in both vessels and airways and are an important cause of long-term morbidity and mortality following organ transplantation [1][2][3]. Chronic vascular rejection (CVR) is characterized by smooth muscle cell proliferation and thickening of the intimal layer of vessels within grafted organs leading to luminal narrowing. Chronic airway rejection, termed obliterative bronchiolitis (OB), is a fibroproliferative, inflammatory lung disease which results in obliteration of small airway lumens [1]. Thus, both types of chronic rejection lesions are the result of an uncontrolled migration and proliferation of mesenchymal cells followed by connective tissue deposition.Our laboratory has developed novel models of both OB and CVR using allografted tracheas and femoral artery segments, respectively. We have previously shown that the development of chronic rejection lesions in these animal models can occur in response to a wide variety of tissue insults in addition to direct alloimmune reactivity [4,5] and have argued that consequently, improved immunosuppression alone may not be sufficient to prevent the development of chronic rejection in clinical organ transplantation [6].In this study, we used these rodent models to identify the origin of the proliferating mesenchymal cells in CVR and OB, to characterize the temporal pattern of recipient and donor cell infiltration and proliferation, and to evaluate the effects of immunosuppressive therapies on this process. Materials and methodsBrown Norway (BN) (RT1.A n ) rat tracheas were allografted into the greater omentum of Lewis (LEW) (RT1.A l ) rats for 3, 7, 14, 21, or 28 days. Twenty-eight day tracheal allograft recipients were treated daily with (in mg/kg/day): cyclosporine A (CsA) (5), rapamycin (RPM) (6), deoxyspergualin (DSG) (2.5), leflunomide (LFM) (20), mycophenolic acid (MPA) (40), or no treatment. Femoral artery segments from BN rats were transplanted orthotopically into LEW recipients for 40 days. BN to BN and LEW to LEW isograft controls were performed for both models. Tracheal sections were stained with antibodies (mAB) specific for BN or LEW major histocompatibility complex class I antigens (MHC I). Staining intensity was rated 0-4 (0 = no staining, 4 = intense staining). Luminal obliteration and cellular infiltration were evaluated by computerized image analysis and standard immunohistochemistry. Results and discussionUntreated rat tracheal allografts (but not isografts) heterotopically implanted into the greater omentum of recipients developed obliterative lesions by day 28 (mean luminal obliteration of 100% for allografts and 0% for isografts) that were histologically similar to those seen in clinical OB.Each anti-MHC-I-antibody specifically stained smooth muscle, fibroblast, mononuclear, epithelial and endothelial cells of isografts from the corresponding rat strain only. In allografted BN tracheas, a progressive infiltration of mononuclear LEW cells was observed on days 3 and 7. By day 14, infiltrating LEW mononuclear...

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Graft fibrosis after pediatric liver transplantation

et al. 2009

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Previously we reported the presence of portal fibrosis in 31% (n ‫؍‬ 84) of the grafts in protocol biopsies 1 year after pediatric liver transplantation (LTx). To assess the natural history of graft fibrosis after pediatric liver transplantation, we extended the analysis of graft histology in follow-up protocol biopsy specimens obtained 5 and 10 years after transplantation. We correlated histological results with clinical parameters at the time of LTx and during follow-up, to allow identification of risk factors for the development of fibrosis. From 1 year to 5 years after LTx, the prevalence of fibrosis increased from 31% to 65% (n ‫؍‬ 66) but remained stable thereafter (at 10 years, 69%, n ‫؍‬ 55). At 10 years after LTx, however, the percentage of patients with severe fibrosis had increased from 10% (at 5 years) to 29%. Of the 69% of children without fibrosis at 1 year post-transplantation, 64% (n ‫؍‬ 39) had developed some degree of fibrosis at 10 years. Fibrosis was strongly related to transplant-related factors such as prolonged cold ischemia time, young age at the time of transplantation, high donor/recipient age ratio, and the use of partial grafts (P < 0.05). Fibrosis was not significantly related to rejection, chronic hepatitis, or the nature of the immunosuppressive therapy. Conclusion: Biopsies after pediatric LTx show that most grafts developed fibrosis within 5 years. At 10 years after LTx, the graft fibrosis had progressed to severe fibrosis in at least 25% of the patients. Development of fibrosis, starting either before or after the first year post-LTx, was strongly related to transplantrelated factors, indicating the importance of these factors to long-term graft prognosis.

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Graft and systemic disease in long-term survivors of liver transplantation

Cited by 40 publications

References 0 publications

Twenty-year protocol liver biopsies: Invasive but useful for the management of liver recipients

Twenty-year protocol liver biopsies: Invasive but useful for the management of liver recipients

Chronic rejection: The result of uncontrolled remodelling of graft tissue by recipient mesenchymal cells? Data from two rodent models and the effects of immunosupressive therapies

Graft fibrosis after pediatric liver transplantation

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