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.

Assessment of hepatic steatosis by transplant surgeon and expert pathologist: a prospective, double-blind evaluation of 201 donor livers.

An accurate clinical assessment of hepatic steatosis before transplantation is critical for successful outcomes after liver transplantation, especially if a pathologist is not available at the time of procurement. This prospective study investigated the surgeon's accuracy in predicting hepatic steatosis and organ quality in 201 adult donor livers. A steatosis assessment by a blinded expert pathologist served as the reference gold standard. The surgeon's steatosis estimate correlated more strongly with large-droplet macrovesicular steatosis [ld-MaS; nonparametric Spearman correlation coefficient (rS ) = 0.504] versus small-droplet macrovesicular steatosis (sd-MaS; rS = 0.398). True microvesicular steatosis was present in only 2 donors (1%). Liver texture criteria (yellowness, absence of scratch marks, and round edges) were mainly associated with ld-MaS (variance = 0.619) and were less associated with sd-MaS (variance = 0.264). The prediction of ≥30% ld-MaS versus <30% ld-MaS was excellent when liver texture criteria were used (accuracy = 86.2%), but it was less accurate when the surgeon's direct estimation of the steatosis percentage was used (accuracy = 75.5%). The surgeon's quality grading correlated with the degree of ld-MaS and the surgeon's steatosis estimate as well as the incidence of poor initial function and primary nonfunction. In conclusion, the precise estimation of steatosis remains challenging even in experienced hands. Liver texture characteristics are more helpful in identifying macrosteatotic organs than the surgeon's actual perception of steatosis. These findings are especially important when histological assessment is not available at the donor's hospital.

Activation of cyclic adenosine monophosphate-dependent protein kinase a signaling prevents liver ischemia/reperfusion injury in mice.

Hepatic ischemia/reperfusion injury (IRI) occurs in multiple clinical settings, including liver transplantation. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway inhibits hepatocellular apoptosis and regulates toll-like receptor 4-triggered inflammation responses in vitro. Here we examined the function and therapeutic potential of cAMP-PKA activation in a murine (C57/BL6) model of liver warm ischemia (90 minutes) followed by reperfusion. Liver IRI triggered cAMP-PKA activation, whereas the administration of its specific inhibitor, H89, exacerbated hepatocellular damage. Conversely, forskolin therapy, which activates PKA by elevating cAMP levels, protected livers from IRI; this was evidenced by diminished serum alanine aminotransferase levels and well-preserved tissue architecture. Liver protection due to cAMP-PKA stimulation was accompanied by diminished neutrophil and macrophage infiltration/activation, reduced hepatocyte necrosis/apoptosis, and increased cAMP response element-binding protein (CREB) expression and augmented interleukin-10 (IL-10) expression. The neutralization of IL-10 restored liver damage in otherwise ischemia/reperfusion-resistant, forskolin-treated mice. In vitro, cAMP-PKA activation diminished macrophage tumor necrosis factor α, IL-6, and IL-12 in an IL-10-dependent manner and prevented necrosis/apoptosis in primary mouse hepatocyte cultures. Our novel findings in a mouse model of liver IRI document the importance of cAMP-PKA signaling in hepatic homeostasis and cytoprotection in vivo. The activation of cAMP-PKA signaling differentially regulates local inflammation and prevents hepatocyte death, and this provides a rationale for novel therapeutic approaches to combating liver IRI in transplant recipients.