Extrahepatic organs in the development of non-alcoholic fatty liver disease in liver transplant patients

Abstract

Importance: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients who undergo liver transplantation (LT). Whereas there is huge data on NAFLD, little is known about NAFLD in LT.Objective: In this review, we aim to explore extrahepatic organs and their potential mechanisms in the development of NAFLD in LT patients and discuss current limitations in preclinical and clinical scenarios with suggestions for future study.Evidence Review: The following keywords, such as NAFLD, NASH, liver transplant, therapy, pathogenesis and biomarkers, were set for literature retrieval. The articles which were published articles in English till 25th June 2020 were included, and there is no limit for the study design type.Findings: Following LT, there are significant shifts in the microbiota and farnesoid X receptor may be a potential therapeutic target for NAFLD in LT settings. The roles of probiotics and diet on NALFD remain inconclusive in LT background. Nevertheless, the adipokines and cytokines disorder and local insulin resistance of adipose tissue may contribute to NAFLD process. Bariatric surgeries are promising in controlling de novo and recurrent NAFLD with significant reduction in abdominal adipose tissue, despite the optimal timing is inconclusive in LT cases. Furthermore, circumstantial evidence indicates that miRNA-33a may function as a mediator bridging sarcopenia and NAFLD of post-LT. β-Hydroxy-β-Methyl-Butyrate treatment could improve muscle status in graft recipients and shows protective potential for NAFLD in LT settings.Conclusions and Relevance: Gut, adipose tissue and muscle are intricately intertwined in promoting NAFLD in LT cases. Further animal studies are needed to deepen our understanding of mechanisms in multi-organ crosstalk. High quality clinical trials are warrant for making guidelines and developing management strategies on NAFLD after LT.

Omics reveal the difference between PTDM and T2D among the liver, pancreas and adipose tissue

“…Furthermore, our ceRNA network analysis uncovered signi cant changes in long intergenic non-coding RNA (lincRNA) and circular RNA (circRNA) networks in the liver and pancreas of PTDM mice. These noncoding RNAs have been increasingly recognized as important regulators of gene expression and could potentially play a role in the development of PTDM or other complications (23). Future studies should explore the functional signi cance of these RNA networks in PTDM pathogenesis.…”