A rapid, reproducible, noninvasive predictor of liver graft survival

Background Clinical and laboratory criteria are not reliable predictors of deceased donor liver graft quality. Intraoperative assessment of experienced surgeons is the gold standard. Standardizing and quantifying this assessment is especially needed now that regional sharing is the rule. We prospectively evaluated a novel, simple, rapid, noninvasive, quantitative measure of liver function performed before graft procurement. Materials and methods Using a portable, finger-probe-based device, indocyanine green plasma disappearance rates (ICG-PDR) were measured in adult brain-dead donors in the local donor service area before organ procurement. Results were compared with graft function and outcomes. Both donor and recipient teams were blinded to ICG-PDR measurements. Results Measurements were performed on 53 consecutive donors. Eleven liver grafts were declined by all centers because of quality; the other 42 grafts were transplanted. Logistic regression analysis showed ICG-PDR to be the only donor variable to be significantly associated with 7-d graft survival. Donor risk index, donor age, and transaminase levels at peak or procurement were not significantly associated with 7-d graft survival. Conclusions We report the successful use of a portable quantitative means of measuring liver function and its association with graft survival. These data warrant further exploration in a variety of settings to evaluate acceptable values for donated liver grafts

Liver transplantation in recipients receiving renal replacement therapy: outcomes analysis and the role of intraoperative hemodialysis.

The Model for End-Stage Liver Disease (MELD) system has dramatically increased the number of recipients requiring pretransplant renal replacement therapy (RRT) prior to liver transplantation (LT). Factors affecting post-LT outcomes and the need for intraoperative RRT (IORRT) were analyzed in 500 consecutive recipients receiving pretransplant RRT, including comparisons among recipients not receiving IORRT (No-IORRT, n = 401), receiving planned IORRT (Pl-IORRT, n = 70), and receiving emergent, unplanned RRT after LT initiation (Em-IORRT, n = 29). Despite a median MELD of 39, overall 30-day, 1-, 3- and 5-year survivals were 93%, 75%, 68% and 65%, respectively. Em-IORRT recipients had significantly more intraoperative complications (arrhythmias, postreperfusion syndrome, coagulopathy) compared with both No-IORRT and Pl-IORRT and greater 30-day graft loss (28% vs. 10%, p = 0.004) and need for retransplantation (24% vs. 10%, p = 0.099) compared with No-IORRT. A risk score based on multivariate predictors of IORRT accurately identified recipients with chronic (sensitivity 84%, specificity 72%, concordance-statistic [c-statistic] 0.829) and acute (sensitivity 93%, specificity 61%, c-statistic 0.776) liver failure requiring IORRT. In this largest experience of LT in recipients receiving RRT, we report excellent survival and propose a practical model that accurately identifies recipients who may benefit from IORRT. For this select group, timely initiation of IORRT reduces intraoperative complications and improves posttransplant outcomes

Liver transplantation in recipients receiving renal replacement therapy: outcomes analysis and the role of intraoperative hemodialysis.

The Model for End-Stage Liver Disease (MELD) system has dramatically increased the number of recipients requiring pretransplant renal replacement therapy (RRT) prior to liver transplantation (LT). Factors affecting post-LT outcomes and the need for intraoperative RRT (IORRT) were analyzed in 500 consecutive recipients receiving pretransplant RRT, including comparisons among recipients not receiving IORRT (No-IORRT, n = 401), receiving planned IORRT (Pl-IORRT, n = 70), and receiving emergent, unplanned RRT after LT initiation (Em-IORRT, n = 29). Despite a median MELD of 39, overall 30-day, 1-, 3- and 5-year survivals were 93%, 75%, 68% and 65%, respectively. Em-IORRT recipients had significantly more intraoperative complications (arrhythmias, postreperfusion syndrome, coagulopathy) compared with both No-IORRT and Pl-IORRT and greater 30-day graft loss (28% vs. 10%, p = 0.004) and need for retransplantation (24% vs. 10%, p = 0.099) compared with No-IORRT. A risk score based on multivariate predictors of IORRT accurately identified recipients with chronic (sensitivity 84%, specificity 72%, concordance-statistic [c-statistic] 0.829) and acute (sensitivity 93%, specificity 61%, c-statistic 0.776) liver failure requiring IORRT. In this largest experience of LT in recipients receiving RRT, we report excellent survival and propose a practical model that accurately identifies recipients who may benefit from IORRT. For this select group, timely initiation of IORRT reduces intraoperative complications and improves posttransplant outcomes

Digital quantitation of HCC-associated stem cell markers and protein quality control factors using tissue arrays of human liver sections.

The most common type of liver cancer, hepatocellular carcinoma (HCC), affects over 500,000 people in the world. In the present study, liver tumor resections were used to prepare tissue arrays to examine the intensity of fluorescence of IHC stained stem cell markers in liver tissue from malignant HCC tumors and accompanying surrounding non-tumor liver. We hypothesized that a correlation exists between the fluorescence intensity of IHC stained HCC and surrounding non-tumor liver compared to liver tissue from a completely normal liver. 120 liver resection specimens (including four normal controls) were placed on a single slide to make a tissue array. They were examined by digitally quantifying the intensity of fluorescence using immuno-histochemically stained stem cell markers and protein quality control proteins. The stem cell markers were OCT3/4, Nanog, CD133, pEZH2, CD49F and SOX2. The protein quality control proteins were FAT10, UBA-6 and ubiquitin. The data collected was used to compare normal liver tissue with HCCs and parent liver tissue resected surgically using antibodies to stem cell markers and quality control protein markers. The measurements of the stem cell marker CD133 indicated an increase of fluorescence intensity for both the parent liver tissue and the HCC liver tissues. The other stem cell markers changed as follows: Nanog and OCT3/4 were decreased in both the HCCs and the parent livers; PEZH2 was reduced in the HCCs; SOX2 was increased in the parent livers compared to the controls; and CD49f was decreased in HCCs only. Protein quality control markers FAT10 and ubiquitin were downregulated in both the HCCs and the adjacent non-tumor tissue compared to the controls. UBA6 was increased in both the HCCs and the parent livers, and the levels were higher in the HCCs compared to the parent livers

Intestinal crypt organoids as experimental models

When it comes to studying the effect of food bioactives on gut health, one of the essential steps that needs to be assessed is characterizing specific effects of the bioactives on the physical barrier of the lumen, the gastrointestinal tissue. In addition to studying the effects on transport function (e.g. by using Ussing chambers or cell culture systems), it is of great interest to evaluate the effects on morphology, cell biology, gene expression, and relevant functions of different cell types that are resident in the gastrointestinal (GI) tract. An ideal near-physiological model should contain a mixture of different GI epithelial cells (e.g. Paneth cells, goblet cells, absorptive and hormone secretive epithelial cells), which can be cultured indefinitely. Recently, the culture and applications of long-term primary multi-cellular cluster structures gastrointestinal organoids (or enteroids) have been demonstrated, and within the last 5 years the number of researchers that commonly use this tissue culture model has increased rapidly. This multi-cellular system may be a promising addition for existing ex vivo and alternative for animal models for testing effects of food bioactives on the intestinal tissue, and could provide a model for pre-screening of compounds prior to moving to the large scale testing systems. Moreover, intestinal organoids can be cultured from different species (e.g. human, pig and mouse). In this chapter we will focus on organoids cultured from mouse and pig crypt cells. We will give a short overview on how to isolate, culture, incubate, and apply them in different research fields

Immunosuppressive Drug Resistant Armored TCR T cells for immune-therapy of HCC in liver transplant patients

10.1002/hep.31662Hepatolog