Role of Innate Immunity in Pediatric Post-transplant Idiopathic Liver Fibrosis

Wu, Yue; Huang, Min; Sun, Haojie; Zhou, Xiying; Zhou, Ruoqiao; Gu, Guangxiang; Xia, Qiang

doi:10.3389/fimmu.2020.02111

Cited by 5 publications

(3 citation statements)

References 68 publications

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“…TLR9 also activate Kupffer cells, the hepatic macrophages that promote fibrosis by aggregating pro-inflammatory cytokines and chemokines in early stages and secreting matrix metalloproteinases (MMPs) in late stages. Kupffer cells produce CXCL16, attracting NKT cells promoting progression of liver fibrosis [ 26 ]. There is a complex crosstalk between innate immunity and adaptive immunity in the process of fibrosis after liver transplantation.…”

Section: Resultsmentioning

confidence: 99%

The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection

Uebayashi

Okajima

Yamamoto

et al. 2022

JCM

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Antibody-mediated rejection (AMR) of liver allograft transplantation was considered as anecdotal for many decades. However recently, AMR has gained clinical awareness as a potential cause of chronic liver injury, leading to liver allograft fibrosis and eventual graft failure. (1) Methods: Literature on chronic AMR (cAMR) in pediatric post-liver transplant patients was reviewed for epidemiologic data, physiopathology, diagnosis, and treatment approaches. (2) Results: Accurate incidence of cAMR in pediatric liver transplantation remains unknown. Diagnostic criteria of cAMR were suggested by the Banff Working Group in 2016 and are based on standardized histopathological findings, C4d staining pattern, associated with the presence of donor-specific antibodies (DSA). Physio-pathological mechanisms are not clear for the technically difficult-to-obtain animal models reproducing cAMR. Treatment protocols are not established, being limited to case reports and case series, based on experience in ABO incompatible transplantation and kidney transplantation. Immunosuppression compliance with adequate dose adjustment may prevent cAMR. Conversion of Cyclosporine to Tacrolimus may improve pathological findings if treated in early phase. The association of steroids, Mycophenolate Mofetil (MMF) and mTOR inhibitors have shown some synergistic effects. Second-line treatments such as intravenous immunoglobulin (IVIG) and plasma exchange may decrease antibody titers based on ABO incompatible transplant protocols. The use of anti-CD20 (Rituximab) and proteasome inhibitors (Bortezomib) is controversial due to the lack of qualified studies. Therefore, multicenter randomized trials are needed to establish the best therapeutic strategy. In refractory cases, re-transplantation is the only treatment for allograft failure. (3) Conclusions: This literature review collects recent clinical, histopathological, and therapeutical advances of cAMR in liver allograft transplantation of pediatric patients. There are many physio-pathological aspects of cAMR to be clarified. Further efforts with multicenter prospective protocols to manage patients with cAMR are needed to improve its outcome.

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Section: Resultsmentioning

confidence: 99%

The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection

Uebayashi

Okajima

Yamamoto

et al. 2022

JCM

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“…As is known, the innate immune cells of the liver are crucial to the influence of liver fibrosis; the stability of liver immune function is an important factor to maintain normal liver function ( Wu et al, 2020 ; Sepulveda-Crespo et al, 2021 ). Autophagy balances inflammation in innate immunity, and when liver injury occurs, the autophagy function of liver innate immune cells will also change.…”

Section: The Role Of Autophagy In the Livermentioning

confidence: 99%

Crosstalk Between Autophagy and Innate Immunity: A Pivotal Role in Hepatic Fibrosis

et al. 2022

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Liver fibrosis is a repair process of chronic liver injuries induced by toxic substances, pathogens, and inflammation, which exhibits a feature such as deposition of the extracellular matrix. The initiation and progression of liver fibrosis heavily relies on excessive activation of hepatic stellate cells (HSCs). The activated HSCs express different kinds of chemokine receptors to further promote matrix remodulation. The long-term progression of liver fibrosis will contribute to dysfunction of the liver and ultimately cause hepatocellular carcinoma. The liver also has abundant innate immune cells, including DCs, NK cells, NKT cells, neutrophils, and Kupffer cells, which conduct complicated functions to activation and expansion of HSCs and liver fibrosis. Autophagy is one specific type of cell death, by which the aberrantly expressed protein and damaged organelles are transferred to lysosomes for further degradation, playing a crucial role in cellular homeostasis. Autophagy is also important to innate immune cells in various aspects. The previous studies have shown that dysfunction of autophagy in hepatic immune cells can result in the initiation and progression of inflammation in the liver, directly or indirectly causing activation of HSCs, which ultimately accelerate liver fibrosis. Given the crosstalk between innate immune cells, autophagy, and fibrosis progression is complicated, and the therapeutic options for liver fibrosis are quite limited, the exploration is essential. Herein, we review the previous studies about the influence of autophagy and innate immunity on liver fibrosis and the molecular mechanism to provide novel insight into the prevention and treatment of liver fibrosis.

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“…It is noteworthy to consider that the paediatric immune system is quite distinctive from that of the adult population[ 20 , 21 ]. Depending upon the age at LT, their immune system is in various stages of development and maturation.…”

Section: Mechanisms Of Long-term Liver Allograft Fibrosismentioning

confidence: 99%

Long-term liver allograft fibrosis: A review with emphasis on idiopathic post-transplant hepatitis and chronic antibody mediated rejection

Vij¹,

Rammohan²,

Rela³

2022

WJH

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Liver transplantation (LT) is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease. With improvements in organ preservation techniques, perioperative care, and immunosuppression, there is better patient and graft survival following LT, and assessment of the liver allograft in long-term survivors is becoming increasingly important. Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults. However, no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients, as they have been transplanted for non-recurrent liver diseases. Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes. Pathological findings are frequently present in liver biopsies obtained after a year post LT. The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters. This narrative review summaries the factors predisposing to long-term liver allograft fibrosis, highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.

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Role of Innate Immunity in Pediatric Post-transplant Idiopathic Liver Fibrosis

Cited by 5 publications

References 68 publications

The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection

The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection

Crosstalk Between Autophagy and Innate Immunity: A Pivotal Role in Hepatic Fibrosis

Long-term liver allograft fibrosis: A review with emphasis on idiopathic post-transplant hepatitis and chronic antibody mediated rejection

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