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Background: The global incidence of liver diseases is rising, yet there remains a dearth of precise research models to mimic these diseases. The use of normothermic machine perfusion (NMP) to study diseased livers recovered from liver transplantation (LT) recipients presents a promising avenue. Accordingly, we have developed a machine perfusion system tailored specifically for the human whole diseased livers and present our experience from the NMP of diseased livers. Methods: Six diseased livers recovered from LT recipients with different diagnoses were collected. The diseased livers were connected to the machine perfusion system that circulated tailored perfusate, providing oxygen and nutrients. The pressure and flow of the system were recorded, and blood gas analysis and laboratory tests of perfusate and bile were examined to analyze the function of the diseased livers. Liver tissues before and after NMP were collected for histological analysis. Results: Experiments showed that the system maintained the diseased livers in a physiological state, ensuring stable hemodynamics and a suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory tests demonstrated a restoration and sustenance of metabolism with minimal damage. Notably, a majority of the diseased livers exhibited bile production continuously, signifying their vivid functional integrity. The pathological characteristics remained stable before and after NMP. Conclusion: We successfully established the machine perfusion system tailored specifically for diseased human whole livers. Through the application of this system, we have developed a novel in vitro model that faithfully recapitulates the main features of human liver disease. This model holds immense promise as an advanced disease modeling platform, offering profound insights into liver diseases and potential implications for research and therapeutic development. [ABSTRACT FROM AUTHOR]

Viral infection seriously affects the survival and life quality of transplanted patients without an accurate diagnosis during the early stage. Herein, we aimed to develop a novel diagnostic method based on non-coding RNAs expression in peripheral blood. An immunosuppressive mouse model of viral infection after transplantation was established. Differentially expressed non-coding RNAs were distinguished by microarray analyses in the virus-infected group. After homology analysis, 46 miRNAs and 24 lncRNAs were further verified by qRT-PCR in the peripheral blood samples of transplanted patients. Compared with normal transplanted patients, miR-29b, miR-185, and NR_073415.2 were significantly downregulated in the PBMC of post-transplant patients with viral infection. Based on the expression of the above three RNAs, principal component analysis (PCA) identified a slight overlap between the two groups. A 3-non-coding-RNA detection panel was constructed by the support vector machine analysis (SVM), whose loss rate was 14.71%. The area under the curve of it was 0.909. With the optimal cut-off value (Y = 0.328), the sensitivity was 0.929 and the specificity was 0.781. Therefore, based on non-coding RNAs expressions, a detection panel for viral infection after organ transplantation was formed with high diagnostic specificity and sensitivity. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) caused by hepatitis B virus (HBV) is common type of liver failure in the world, with high morbidity and mortality rates. However, the prevalence, genetic background and factors determining the development of HBV‐related ALF are rarely studied. In this study, we examined three Gene Expression Omnibus (GEO) data sets by bioinformatics analysis to identify differentially expressed genes (DEGs), key biological processes and pathways. Immune infiltration analysis showed high immune cells infiltration in HBV‐related ALF tissue. We then confirmed natural killer cells and macrophages infiltration in clinical samples by immunohistochemistry assay, implying these cells play a significant role in HBV‐ALF. We found 1277 genes were co‐up‐regulated and that 1082 genes were co‐down‐regulated in the 3 data sets. Inflammation‐related pathways were enriched in the co‐up‐regulated genes and synthetic metabolic pathways were enriched in the co‐down‐regulated genes. WGCNA also revealed a key module enriching in immune inflammation response and identified 10 hub genes, differentially expressed in an independent data set. In conclusion, we identified fierce immune inflammatory response to elucidate the immune‐driven mechanism of HBV‐ALF and 10 hub genes based on gene expression profiles. [ABSTRACT FROM AUTHOR]