Background: The aim of the study was to determine the influence of fractionated plasma separation and absorption (FPSA) on intracranial pressure (ICP) in acute liver failure (ALF). Methods: A surgical model of ALF in pigs (35–40 kg) was used. We compared laboratory data and haemodynamic parameters from the ALF control group to the ALF group treated by Prometheus using ANOVA with repeated measures and grouping factors, by calculating the area under the curve, and by the Mann-Whitney rank test. Results: Bilirubin levels differed significantly in favour of the FPSA treatment group: after 6 h 12.81 ± 6.54 versus 29.84 ± 9.99, after 9 h 11.94 ± 4.14 versus 29.95 ± 12.36 (p < 0.01) and after 12 h 13.88 ± 6.31 versus 26.10 ± 12.23 mmol/l (p < 0.05). ICP values differed significantly in favour of the FPSA treatment group: after 9 h 19.1 ± 4.09 versus 24.1 ± 2.85 (p < 0.01), after 10 h 21.9 ± 3.63 versus 25.1 ± 2.19, after 11 h 22.5 ± 3.98 versus 26.3 ± 3.50, and after 12 h 24.0 ± 4.66 versus 29.8 ± 5.88 mm Hg (p < 0.05). Conclusion: The authors demonstrated that a significant decrease in ICP was found in pigs with ALF following treatment by FPSA.

Kidney paired donation (KPD) is a valuable tool to overcome immunological barriers in living donor transplantation. While small national registries encounter difficulties in finding compatible matches, multinational KPD may be a useful strategy to facilitate transplantation. The Czech (Prague) and Austrian (Vienna) KPD programs, both initiated in 2011, were merged in 2015. A bi-national algorithm allowed for ABO-and low-level HLA antibody-incompatible exchanges, including the option of altruistic donorinitiated domino chains. Between 2011 and 2019, 222 recipients and their incompatible donors were registered. Of those, 95.7% (Prague) and 67.9% (Vienna) entered into KPD registries, and 81 patients received a transplant (95% 3-year graft survival). Inclusion of ABO-incompatible pairs in the Czech program contributed to higher KPD transplant rates (42.6% vs. 23.6% in Austria). After 2015 (11 bi-national match runs), the median pool size increased to 18 pairs, yielding 33 transplants (8 via cross-border exchanges). While matching rates doubled in Austria (from 9.1% to 18.8%), rates decreased in the Czech program, partly due to implementation of more stringent HLA antibody thresholds. Our results demonstrate the feasibility of merging small national KPD programs to increase pool sizes and may encourage the implementation of multinational registries to expand the full potential of KPD.

The artificial liver support system FPSA reduced ICP values more effectively than the Performer O. Liver RanD BAL system. Compared with this BAL system, the nonbiological elimination method of FPSA is a simpler application with the advantage that it can be applied in a more continuous way.

Aim: The study was designed to develop a readily reproducible model of acute liver failure (ALF) in the minipig, to gain an 8-hour therapeutic window to mimic, as closely as possible, acute liver failure in man. Method: We used reversible devascularization model of ALF in the minipig involving hepatic artery ligation and establish an end-to-side portocaval anastomosis. Standard laboratory monitoring was complemented with intracranial pressure (ICP) measurement. Material: Twenty minipigs (weight 25–30 kg) were used for the experiment. The animals were divided into 3 groups: I: 10 animals in an experimental group with ALF; II: 5 animals in an experimental group with ALF and ICP measurement, and III: 5 animals in a control group without ALF. Results: Laboratory testing has shown the significant changes in levels of AST (33.44 ± 39.96 vs. 1.56 ± 0.50 mmol/l), lactate (2.97 ± 1.16 vs. 1.18 ± 0.61 mmol/l), and ammonia (264.3 ± 93.05 vs. 42.5 ± 12.98 mmol/l) between ALF groups and controls (p < 001) 6 h after the operative procedure, and significant changes in hypoglycemia and intracranial pressure were found 4 h after the operative procedure. The difference in Quick values (67.4 ± 17.03 vs. 75.2 ± 2.68) was not significant. We assume that the therapeutic window starts 4 h after the beginning of the experiment. Conclusion: Our devascularization model of ALF is simple and readily reproducible. The therapeutic window occurring shortly after surgery and persisting for a mean 9 h is suitable to evaluate bioartificial liver devices.

BackgroundCerebral edema is a well-recognized and potentially fatal complication of acute liver failure (ALF). The effectiveness of treatments that address intracranial hypertension is generally assessed by measuring intracranial pressure (ICP). The aim of this study was to determine the role of cerebral microdialysis in monitoring the efficacy of fractionated plasma separation and adsorption (FPSA) treatment for ALF. We hypothesized that in ALF cerebral microdialysis reflects the benefits of FPSA treatment on cerebral edema before ICP.MethodsA surgical resection model of ALF was used in 21 pigs. We measured plasma ammonia concentration, brain concentrations of glucose, lactate, pyruvate, glutamate and glutamine, and ICP. Animals were randomized into three groups: in one group eight animals received 6 hours of FPSA treatment 2 hours after induction of ALF; in another group 10 animals received supportive treatment for ALF only; and in the final group three underwent sham surgery.ResultsThe ICP was significantly higher in the ALF group than in the FPSA group 9 hours after surgery. The lactate/pyruvate (L/P) ratio was significantly lower in the FPSA group than the ALF group 5 hours after surgery, before any significant difference in ICP was detected. Indeed, significant changes in the L/P ratio could be observed within 1 hour of treatment. Glutamine levels were significantly lower in the FPSA group than the ALF group between 6 hours and 10 hours after surgery.ConclusionsBrain lactate/pyruvate ratio and concentration of glutamine measured by cerebral microdialysis reflected the beneficial effects of FPSA treatment on cerebral metabolism more precisely and rapidly than ICP in pigs with fulminant ALF. The role of glutamine as a marker of the efficacy of FPSA treatment for ALF appears promising, but needs further evaluation.