Histopathology of 460 liver allografts removed at retransplantation: A shift in disease patterns over 27 years

Souza, Lara Neves; Martino, Rodrigo; Sánchez‐Fueyo, Alberto; Rela, Mohamed; Dhawan, Anil; O’Grady, John; Heaton, Nigel; Quaglia, Alberto

doi:10.1111/ctr.13227

Cited by 21 publications

(21 citation statements)

References 45 publications

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“…Oh et al noted that chronic rejection appeared to be significantly decreasing over time in their series due to improvements in immunosuppression. Neves Souza et al also echoed these findings in their single‐center report of liver retransplants between 1987 and 2014, where they observed that chronic rejection was the primary histologic cause for liver retransplantation between 1987 and 1994; the second indication for re‐LT (after hepatic artery thrombosis) between 1995 and 2001; and the fourth indication for re‐LT (after hepatic artery thrombosis, biliary complications, chronic fibrosing hepatitis) between 2002 and 2014. The decline of chronic rejection noted by these authors may be reflective of several factors: improvements in immunosuppression over the years; tacrolimus became the main calcineurin inhibitor used in the last two eras; and an increase in the elective use of induction therapy.…”

Section: Discussionmentioning

confidence: 84%

“…What is striking however is that even in the modern era, despite the introduction of new immunosuppressive agents and strategies, chronic rejection continues to be reported as a cause of graft loss . Neves Souza observed the presence of an unspecified chronic hepatitis associated with bridging fibrosis in children, which progressed to graft failure. It is possible that histologic features like this will need to be evaluated as possibly a new form of “chronic rejection.”…”

Section: Discussionmentioning

confidence: 99%

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20‐ to 25‐year patient and graft survival following a single pediatric liver transplant—Analysis of the United Network of Organ Sharing database: Where to go from here

Ekong

Gupta

Urban³

et al. 2019

Pediatric Transplantation

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To understand factors contributing to liver graft loss and patient death, we queried a national database designed to follow pediatric patients transplanted between 1987 and 1995 till adulthood. A comparison was made to a cohort transplanted between 2000 and 2014. The 5‐, 10‐, 15‐, 20‐, and 25‐year patient survival and graft survival were 95.5%, 93.7%, 89.1%, 80.8%, and 73.1%, and 92.5%, 86.7%, 77.6%, 68.7%, and 62.2%, respectively. The twenty‐year patient/graft survival was significantly worse in those transplanted between 5 and 17 years of age compared to those transplanted at <5 years of age (P < 0.001). For the modern era cohort, the 3‐year patient survival was significantly lower in children transplanted at 16‐17 years of age compared to those transplanted at <5 and 11‐15 years of age (P ≤ 0.02). The 3‐year graft survival was similarly lower in children transplanted at 16‐17 years of age compared to those transplanted at <5, 5‐10, and 11‐15 years of age (P ≤ 0.001). Infection as a cause of death occurred either early or >15 years post‐transplant. Chronic rejection remained the leading cause of graft loss in both cohorts and the commonest indication for retransplantation 20‐25 years following primary transplant. Further research is required to identify modifiable factors contributing to development of chronic rejection.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

20‐ to 25‐year patient and graft survival following a single pediatric liver transplant—Analysis of the United Network of Organ Sharing database: Where to go from here

Ekong

Gupta

Urban³

et al. 2019

Pediatric Transplantation

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“…In addition to regarding these histopathological outcomes, comorbidities and adverse effects of immunosuppressive drugs are taken into account (Figure 1). mTOR inhibitors, which are started no earlier than 1 month after OLT, are preferred, for example, in patients with significant graft fibrosis, hepatocellular carcinoma before OLT, patients with moderate‐to‐severe kidney insufficiency or after CMV reactivation 7,21–24 …”

Section: Methodsmentioning

confidence: 99%

“…Renal dysfunction in liver transplant recipients is considered to be mainly due to calcineurin inhibitor (CNI) induced toxicity and leads to higher costs and shorter long‐term survival 2,5,6 . In addition, significant graft fibrosis is one of the main reasons for retransplantation in long‐term follow‐up 7 . Protocol biopsy programs have shown graft fibrosis (Ishak F ≥ 2) in 54% of non‐HCV patients after 5 years, which were largely not detected by routine clinical follow‐up 8 .…”

Section: Introductionmentioning

confidence: 99%

Outcome and safety of a surveillance biopsy guided personalized immunosuppression program after liver transplantation

Saunders

Engel

Höfer

et al. 2022

American Journal of Transplantation

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Graft survival beyond year 1 has not changed after orthotopic liver transplantation (OLT) over the last decades. Likewise, OLT causes comorbidities such as infection, renal impairment and cancer. We evaluated our single‐center real‐world individualized immunosuppression program after OLT, based on 211 baseline surveillance biopsies (svLbx) without any procedural complications. Patients were classified as low, intermediate and high rejection risk based on graft injury in svLbx and anti‐HLA donor‐specific antibodies. While 32% of patients had minimal histological inflammation, 57% showed histological inflammation and 23% advanced fibrosis (>F2), which was not predicted by lab parameters. IS was modified in 79% of patients after svLbx. After immunosuppression reduction in 69 patients, only 5 patients showed ALT elevations and three of these patients had a biopsy‐proven acute rejection, two of them related to lethal comorbidities. The rate of liver enzyme elevation including rejection was not significantly increased compared to a svLbx control cohort prior to the initiation of our structured program. Immunosuppression reduction led to significantly better kidney function compared to this control cohort. In conclusion, a biopsy guided personalized immunosuppression protocol after OLT can identify patients requiring lower immunosuppression or patients with graft injury in which IS should not be further reduced.

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“…Thus, performance of TE could be considered in patients undergoing active immunosuppression withdrawal with the detection of appreciable fibrosis triggering the need for liver biopsy or precluding immunosuppression withdrawal. Late graft hepatitis and fibrosis is increasingly being found in pediatric liver allograft recipients and adult survivors of pediatric transplantation . TE may become important in identifying such patients earlier without the performance of protocol liver biopsy.…”

Section: Methodsmentioning

confidence: 99%

A review of the use of transient elastography in the assessment of fibrosis and steatosis in the post–liver transplant patient

Winters

Mittal

Schiano

2019

Clinical Transplantation

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Liver biopsy is considered the gold standard method for diagnosing and staging liver disease, particularly in the post-liver transplant setting. Given the invasive nature of biopsy, alternate means for accurately assessing liver fibrosis and steatosis are preferred especially as the number of patients with fatty liver disease is increasing.Transient elastography has been validated as a useful tool for evaluation of liver fibrosis, as has controlled attenuation parameter index as a tool for assessing steatosis. It is a non-invasive, rapid, and highly reproducible approach to demonstrate the presence of fibrosis among non-transplant patients with chronic liver disease of various etiologies. However, it has not yet found wide acceptance in liver transplant recipients. There are few published studies evaluating the merits and applicability of transient elastography to assess allografts after liver transplantation. We review the published data on the use of transient elastography with concurrent controlled attenuation parameter in liver transplant recipients and recommend its greater use to follow allograft function over time.

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Histopathology of 460 liver allografts removed at retransplantation: A shift in disease patterns over 27 years

Abstract: We observed a shift in histopathology of failed liver grafts, with increasing relevance of chronic idiopathic hepatitis associated with progressive fibrosis and graft failure.

Cited by 21 publications

References 45 publications

20‐ to 25‐year patient and graft survival following a single pediatric liver transplant—Analysis of the United Network of Organ Sharing database: Where to go from here

20‐ to 25‐year patient and graft survival following a single pediatric liver transplant—Analysis of the United Network of Organ Sharing database: Where to go from here

Outcome and safety of a surveillance biopsy guided personalized immunosuppression program after liver transplantation

A review of the use of transient elastography in the assessment of fibrosis and steatosis in the post–liver transplant patient

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