Development and validation of a nomogram to predict allograft survival after pediatric liver transplantation.

BACKGROUND: Liver transplantation is the main treatment for cholestatic liver disease and some metabolic liver diseases in children. However, no accurate prediction model to determine the survival probability of grafts prior to surgery exists. This study aimed to develop an effective prognostic model for allograft survival after pediatric liver transplantation. METHODS: This retrospective cohort study included 2032 patients who underwent pediatric liver transplantation between January 1, 2006, and January 1, 2020. A nomogram was developed using Cox regression and validated based on bootstrap sampling. Predictive and discriminatory accuracies were determined using the concordance index and visualized using calibration curves; net benefits were calculated for model comparison. An online Shiny application was developed for easy access to the model. RESULTS: Multivariable analysis demonstrated that preoperative diagnosis, recipient age, body weight, graft type, preoperative total bilirubin, interleukin-1ß, portal venous blood flow direction, spleen thickness, and the presence of heart disease and cholangitis were independent factors for survival, all of which were selected in the nomogram. Calibration of the nomogram indicated that the 1-, 3-, and 5-year predicted survival rates agreed with the actual survival rate. The concordance indices for graft survival at 1, 3, and 5 years were 0.776, 0.757, and 0.753, respectively, which were significantly higher than those of the Pediatric End-Stage Liver Disease and Child-Pugh scoring systems. The allograft dysfunction risk of a recipient could be easily predicted using the following URL: https://aspelt.shinyapps.io/ASPELT/ / CONCLUSION: The allograft survival after pediatric liver transplantation (ASPELT) score model can effectively predict the graft survival rate after liver transplantation in children, providing a simple and convenient evaluation method for clinicians and patients.

The utility of two-dimensional shear wave elastography and texture analysis for monitoring liver fibrosis in rat model.

BACKGROUND: Liver fibrosis is a common pathological change caused by a variety of etiologies. Early diagnosis and timely treatment can reverse or delay disease progression and improve the prognosis. This study aimed to assess the potential utility of two-dimensional shear wave elastography and texture analysis in dynamic monitoring of the progression of liver fibrosis in rat model. METHODS: Twenty rats were divided into control group (n = 4) and experimental groups (n = 4 per group) with carbon tetrachloride administration for 2, 3, 4, and 6 weeks. The liver stiffness measurement was performed by two-dimensional shear wave elastography, while the optimal texture analysis subsets to distinguish fibrosis stage were generated by MaZda. The results of elastography and texture analysis were validated through comparing with histopathology. RESULTS: Liver stiffness measurement was 6.09 ± 0.31 kPa in the control group and 7.10 ± 0.41 kPa, 7.80 ± 0.93 kPa, 8.64 ± 0.93 kPa, 9.91 ± 1.13 kPa in the carbon tetrachloride induced groups for 2, 3, 4, 6 weeks, respectively (P < 0.05). By texture analysis, histogram and co-occurrence matrix had the most frequency texture parameters in staging liver fibrosis. Receiver operating characteristic curve of liver elasticity showed that the sensitivity and specificity were 95.0% and 92.5% to discriminate liver fibrosis and non-fibrosis, respectively. In texture analysis, five optimal parameters were selected to classify liver fibrosis and non-fibrosis. CONCLUSIONS: Two-dimensional shear wave elastography showed potential applications for noninvasive monitoring of the progression of hepatic fibrosis, even in mild fibrosis. Texture analysis can further extract and quantify the texture features in ultrasonic image, which was a supplementary to further visual information and acquired high diagnostic accuracy for severe fibrosis.

Shear wave elastography for evaluation of the urgency of liver transplantation in pediatric patients with biliary atresia.

BACKGROUND: To investigate the role of two-dimensional shear wave elastography (2D-SWE) in the preoperative evaluation of pediatric patients with biliary atresia awaiting liver transplantation. METHODS: Among a total of 152 pediatric patients enrolled in this single-institution prospective study between March 2018 and August 2019, 143 patients (age range, 4-97 months; median age, 7 months; 84 males, 59 females) who underwent successful routine ultrasound examination, SWE examination, and blood test before liver transplantation were included in the final analysis. The values of liver stiffness measured by SWE were compared with ultrasound and blood test parameters by Spearman's correlation analysis. RESULTS: The overall median liver stiffness with 2D-SWE was 29.0 ± 10.9 kPa, with a range of 9.0-53.3 kPa. The success rate of 2D-SWE measurements was 98.0% (149/152). Liver stiffness measurement (LSMs) had no significant correlation with gender, age, weight, and height of the pediatric recipients. LSMs were correlated with ultrasound parameters including portal vein (PV) maximum velocity, PV direction, hepatic artery resistance index (HARI), spleen diameter, ascites, and blood test parameters (albumin level, platelet count level, and international normalized ratio). In the pediatric recipients with hepatofugal PV flow, high HARI (HARI â‰§ 0.90), and ascites, or without Kasai operation, LSMs were significantly higher (P < .05). CONCLUSIONS: SWE is feasible and valuable for assessing liver damage in children with biliary atresia awaiting liver transplantation and might be used as selection criteria for children in need of priority access to liver transplantation.

Dual Effect of Hepatic Macrophages on Liver Ischemia and Reperfusion Injury during Liver Transplantation.

Ischemia-reperfusion injury (IRI) is a major complication in liver transplantation (LT) and it is closely related to the recovery of grafts' function. Researches has verified that both innate and adaptive immune system are involved in the development of IRI and Kupffer cell (KC), the resident macrophages in the liver, play a pivotal role both in triggering and sustaining the sterile inflammation. Damage-associated molecular patterns (DAMPs), released by the initial dead cell because of the ischemia insult, firstly activate the KC through pattern recognition receptors (PRRs) such as toll-like receptors. Activated KCs is the dominant players in the IRI as it can secret various pro-inflammatory cytokines to exacerbate the injury and recruit other types of immune cells from the circulation. On the other hand, KCs can also serve in a contrary way to ameliorate IRI by upregulating the anti-inflammatory factors. Moreover, new standpoint has been put forward that KCs and macrophages from the circulation may function in different way to influence the inflammation. Managements towards KCs are expected to be the effective way to improve the IRI.

Effects of xenogeneic adipose-derived stem cell transplantation on acute-on-chronic liver failure.

BACKGROUND: Adipose-derived stem cells (ADSCs) are particularly attractive in future clinical applications of stem cell-based therapy for acute-on-chronic liver failure (ACLF). This study was undertaken to evaluate the therapeutic potential of ADSCs on ACLF. METHODS: ADSCs isolated from porcine fat tissue were expanded and labeled with BrdU. Rabbit models of ACLF were created by administration of D-Gal following CCl4-induced cirrhosis. One day after administration of D-Gal, rabbits of the ACLF/ADSCs group (n=15) were received ADSCs transplantation, while those in the ACLF/saline group (n=15) were treated with the same volume of saline. Biochemical parameters and histomorphological scoring were evaluated; the distribution and characteristics of transplanted ADSCs as well as the pathology of the liver were examined. RESULTS: ADSCs transplantation improved the survival rate and the liver function of rabbits with ACLF. Biochemical parameters of the ACLF/ADSCs group were improved compared with those of the ACLF/saline group, and histomorphological scoring of the ACLF/ADSCs group was significantly lower than that of the ACLF/saline group. ADSCs were identified in the periportal region of the liver after cell transplantation. CONCLUSION: Xenogenic ADSCs have therapeutic efficacy in the ACLF rabbit model.

In vitro analysis of cryopreserved alginate-poly-L-lysine-alginate-microencapsulated human hepatocytes.

BACKGROUND: The availability of well-characterized human hepatocytes that can be frozen and thawed will be critical for cell therapy. We addressed whether human hepatocytes can recover after microencapsulated cryopreservation and investigated whether these cryopreserved microencapsulated hepatocytes can be used for clinical applications. METHODS: Adult hepatocytes of 18 separate donors were isolated with a two-step extracorporeal collagenase perfusion technique. After pre-incubation at 4 degrees C for 12-24 h in HepatoZYME-SFM, hepatocytes were microencapsulated using alginate-poly-L-lysine-alginate microcapsules. The microencapsulated hepatocytes were transferred to a complete medium containing 10% dimethyl sulphoxide. They were immediately placed into an isopropanol progressive freezing container at -80 degrees C overnight and immersed in liquid nitrogen the next day. During the post-thawing culture period, albumin secretion, urea synthesis, cell cycle, mRNA and protein levels, as well as the morphology and pathology structure of pre-incubation before microencapsulated cryopreservation (PMC) groups were analysed. RESULTS: Compared with the immediate cryopreservation (IC) groups, we found significant improvement in the mRNA and protein levels in the attached cells, and higher secretion of albumin and urea levels after thawing. In the attached cultured human cryopreserved/thawed hepatocytes from the PMC group, albumin production was not significantly different from those of the direct culture groups on days 2, 3 and 4. The preserved morphology in the PMC group compared with the IC group was obvious. CONCLUSIONS: The results of the present study suggested recovery of the functional and morphological integrity of human hepatocytes after pre-incubation at 4 degrees C for 12-24 h before microencapsulated cryopreservation. These studies offer the possibility for clinical applications in pharmacotoxicology, bioartificial liver and cell therapy in humans.