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We tested whether rat liver preservation performed by machine perfusion (MP) at 20°C can enhance the functional integrity of steatotic livers versus simple cold storage. We also compared MP at 20°C with hypothermic MP at 8°C, and 4°C. Obese and lean male Zucker rats were used as liver donors. MP was performed for 6 hours with a glucose and N-acetylcysteine-supplemented Krebs-Henseleit solution. Both MP and cold storage preserved livers were reperfused with Krebs-Henseleit solution (2 hours at 37°C). MP at 4°C and 8°C reduced the fatty liver necrosis compared with cold storage but we further protected the organs using MP at 20°C. Necrosis did not differ in livers from lean animals submitted to the different procedures; the enzymes released in steatotic livers preserved by MP at 20°C were similar to those showed in nonsteatotic organs. The adenosine triphosphate/adenosine diphosphate ratio and bile production were higher and the oxidative stress and biliary enzymes were lower in steatotic livers preserved by MP at 20°C as compared with cold storage. In livers from lean rats, the adenosine triphosphate/adenosine diphosphate ratio appears better conserved by MP at 20°C as compared with cold storage. In steatotic livers preserved by cold storage, a 2-fold increase in tumor necrosis factor-alpha levels and caspase-3 activity was observed as compared with organs preserved by MP at 20°C. These data are substantiated by better morphology, higher glycogen content, and lower reactive oxygen species production by sinusoidal cells in steatotic liver submitted to MP at 20°C versus cold storage. MP at 20°C improves cell survival and leads to a marked improvement in hepatic preservation of steatotic livers as compared with cold storage. Liver Transpl 15:20-29, 2009.

Response to therapy is a potentially effective tool for prioritizing HCC patients for LT.

As zebrafish emerge as a species of choice for the investigation of biological processes, a number of experimental protocols are being developed to study their social behaviour. While live stimuli may elicit varying response in focal subjects owing to idiosyncrasies, tiredness and circadian rhythms, video stimuli suffer from the absence of physical input and rely only on two-dimensional projections. Robotics has been recently proposed as an alternative approach to generate physical, customizable, effective and consistent stimuli for behavioural phenotyping. Here, we contribute to this field of investigation through a novel four-degree-of-freedom robotics-based platform to manoeuvre a biologically inspired three-dimensionally printed replica. The platform enables three-dimensional motions as well as body oscillations to mimic zebrafish locomotion. In a series of experiments, we demonstrate the differential role of the visual stimuli associated with the biologically inspired replica and its three-dimensional motion. Three-dimensional tracking and information-theoretic tools are complemented to quantify the interaction between zebrafish and the robotic stimulus. Live subjects displayed a robust attraction towards the moving replica, and such attraction was lost when controlling for its visual appearance or motion. This effort is expected to aid zebrafish behavioural phenotyping, by offering a novel approach to generate physical stimuli moving in three dimensions.

Whether beta-blockers (BB) or banding is the best therapy for primary prophylaxis of variceal bleeding is subject to debate. A randomized comparison between the 2 treatments was performed in candidates for liver transplantation (LT). A total of 62 patients with Child-Turcotte-Pugh B-C cirrhosis and high risk varices received propranolol (31) or variceal banding (31). The primary endpoint was variceal bleeding. There were 2 variceal hemorrhages (6.5%) in the banding group, related to postbanding ulcers, and 3 (9.7%) in the propranolol group (P ϭ not significant [n.s.]). Deaths and bleeding related deaths were 3 and 1 for banding and 3 and 2 for BB, respectively (P ϭ n.s.). A total of 14 patients underwent LT in the banding group and 10 in the propranolol group (P ϭ n.s.). Adverse events were 2 postbanding ulcer bleedings in ligated patients (1 fatal) and 5 were intolerant to propranolol (P ϭ n.s.). Mean costs per patient were higher with banding than with propranolol treatment (4,289 Ϯ 285 vs. 1,425 Ϯ 460 U.S. dollars, P Ͻ 0.001). In conclusion, propranolol and banding are similarly effective in reducing the incidence of variceal bleeding in candidates for LT, but ligation can be complicated by fatal bleeding and is more expensive. Our results suggest that banding should not be utilized as primary prophylaxis in transplant candidates who can be treated with BB.

Antioxidant agents have the potential to reduce ischemia/reperfusion damage to organs for liver transplantation (LT). In this prospective, randomized study, we tested the impact of an infusion of N-acetylcysteine (NAC) during liver procurement on post-LT outcomes. Between December 2006 and July 2009, 140 grafts were transplanted into adult candidates with chronic liver disease who were listed for first LT, and according to a sequential, closed-envelope, single-blinded procedure, these patients were randomly assigned in a 1/1 ratio to an NAC protocol (69 patients) or to the standard protocol without NAC [71 patients (the control group)]. The NAC protocol included a systemic NAC infusion (30 mg/kg) 1 hour before the beginning of liver procurement and a locoregional NAC infusion (300 mg through the portal vein) just before cross-clamping. The primary endpoint was graft survival. The graft survival rates at 3 and 12 months were 93% and 90%, respectively, in the NAC group and 82% and 70%, respectively, in the control group (P ¼ 0.02). An adjusted Cox analysis showed a significant NAC effect on graft survival at both 3 months [hazard ratio ¼ 1.65, 95% confidence interval (CI) ¼ 1.01-2.93, P ¼ 0.04] and 12 months (hazard ratio ¼ 1.73, 95% CI ¼ 1.14-2.76, P 0.01). The incidence of postoperative complications was lower in the NAC group (23%) versus the control group (51%, P < 0.01). In the subgroup of 61 patients (44%) receiving suboptimal grafts (donor risk index > 1.8), the incidence of primary dysfunction of the liver was lower (P ¼ 0.09) for the NAC group (15%) versus the control group (32%). In conclusion, the NAC harvesting protocol significantly improves graft survival. The effect of NAC on early graft function and survival seems higher when suboptimal grafts are used. Liver Transpl 19:135-144, 2013. V C 2012 AASLD.Received April 3, 2012; accepted July 7, 2012.Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval; DRI, donor risk index; GSH, glutathione; ICU, intensive care unit; INR, international normalized ratio; IRI, ischemia/reperfusion injury; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; NAC, N-acetylcysteine; PDF, primary dysfunction; PNF, primary nonfunction; POD, postoperative day.Francesco D'Amico contributed to the study concept and design, the acquisition and analysis of data, and the supervision of the study and manuscript. Alessandro Vitale contributed to the analysis and interpretation of data, the drafting of the manuscript, and the statistical analysis. Anna Chiara Frigo contributed to the statistical analysis. Umberto Cillo contributed to the analysis and interpretation of data and the supervision of the study. Alessandra Bertacco contributed to the acquisition and analysis of data and the critical revision of the manuscript. Donatella Piovan, Domenico Bassi, Rafael Ramirez Morales, Pasquale Bonsignore, Enrico Gringeri, Michele Valmasoni, Greta Garbo, Enrico Lodo, Francesco Enrico D'Amico, Michele Scopelliti, Amedeo Carraro, ...

The study provides a valid premise for a development of AF-based optical biopsy techniques for a real-time discrimination of liver anatomo-pathological patterns.