Petru Bucur

Although sarcopenia is a common complication of cirrhosis, its diagnosis remains nonconsensual: computed tomography (CT) scan determinations vary and no cutoff values have been established in cirrhotic populations undergoing liver transplantation (LT). Our aim was to compare the accuracy of the most widely used measurement techniques and to establish useful cutoffs in the setting of LT. From the 440 patients transplanted between January 2008 and May 2011 in our tertiary center, we selected 256 patients with cirrhosis for whom a recent CT scan was available during the 4 months prior to LT. We measured different muscle indexes: psoas muscle area (PMA), PMA normalized by height or body surface area (BSA), and the third lumbar vertebra skeletal muscle index (L3SMI). Receiver operating characteristic curves were evaluated and prognostic factors for post‐LT 1‐year survival were then analyzed. PMA offered better accuracy (area under the curve [AUC] = 0.753) than L3SMI (AUC = 0.707) and PMA/BSA (AUC = 0.732), and the same accuracy as PMA/squared height. So, for its accuracy and simplicity of use, the PMA index was used for the remainder of the analysis and to define sarcopenia. In men, the better cutoff value for PMA was 1561 mm 2 (Se = 94%, Sp = 57%), whereas in women, it was 1464 mm 2 (Se = 52%, Sp = 91%). A PMA lower than these values defined sarcopenia in patients with cirrhosis awaiting LT. One‐ and 5‐year overall survival rates were significantly poorer in the sarcopenic group (n = 57) than in the nonsarcopenic group (n = 199), at 59% versus 94% and 54% versus 80%, respectively ( P < 0.001). In conclusion, pre‐LT PMA is a simple tool to assess sarcopenia. We established sex‐specific cutoff values (1561 mm 2 in men, 1464 mm 2 in women) in a cirrhotic population and showed that 1‐year survival was significantly poorer in sarcopenic patients. Liver Transplantation 23 143–154 2017 AASLD

Histological alterations often constitute a fingerprint of toxicity and diseases. The extent to which these alterations are cause or consequence of compromised organ function, and the underlying mechanisms involved is a matter of intensive research. In particular, liver disease is often associated with altered tissue microarchitecture, which in turn may compromise perfusion and functionality. Research in this field requires the development and orchestration of new techniques into standardized processing pipelines that can be used to reproducibly quantify tissue architecture. Major bottlenecks include the lack of robust staining, and adequate reconstruction and quantification techniques. To bridge this gap, we established protocols employing specific antibody combinations for immunostaining, confocal imaging, three-dimensional reconstruction of approximately 100-μm-thick tissue blocks and quantification of key architectural features. We describe a standard procedure termed 'liver architectural staining' for the simultaneous visualization of bile canaliculi, sinusoidal endothelial cells, glutamine synthetase (GS) for the identification of central veins, and DAPI as a nuclear marker. Additionally, we present a second standard procedure entitled 'S-phase staining', where S-phase-positive and S-phase-negative nuclei (stained with BrdU and DAPI, respectively), sinusoidal endothelial cells and GS are stained. The techniques include three-dimensional reconstruction of the sinusoidal and bile canalicular networks from the same tissue block, and robust capture of position, size and shape of individual hepatocytes, as well as entire lobules from the same tissue specimen. In addition to the protocols, we have also established image analysis software that allows relational and hierarchical quantifications of different liver substructures (e.g. cells and vascular branches) and events (e.g. cell proliferation and death). Typical results acquired for routinely quantified parameters in adult mice (C57Bl6/N) include the hepatocyte volume (5,128.3 ± 837.8 μm(3)) and the fraction of the hepatocyte surface in contact with the neighbouring hepatocytes (67.4 ± 6.7 %), sinusoids (22.1 ± 4.8 %) and bile canaliculi (9.9 ± 3.8 %). Parameters of the sinusoidal network that we also routinely quantify include the radius of the sinusoids (4.8 ± 2.25 μm), the branching angle (32.5 ± 11.2°), the length of intersection branches (23.93 ± 5.9 μm), the number of intersection nodes per mm(3) (120.3 × 103 ± 42.1 × 10(3)), the average length of sinusoidal vessel per mm(3) (5.4 × 10(3) ± 1.4 × 10(3)mm) and the percentage of vessel volume in relation to the whole liver volume (15.3 ± 3.9) (mean ± standard deviation). Moreover, the provided parameters of the bile canalicular network are: length of the first-order branches (7.5 ± 0.6 μm), length of the second-order branches (10.9 ± 1.8 μm), length of the dead-end branches (5.9 ± 0.7 μm), the number of intersection nodes per mm(3) (819.1 × 10(3) ± 180.7 × 10(3)), the number of dead-end branches per mm(3) (409.9 × 10(3) ± 95.6 × 10(3)), the length of the bile canalicular network per mm(3) (9.4 × 10(3) ± 0.7 × 10(3) mm) and the percentage of the bile canalicular volume with respect to the total liver volume (3.4 ± 0.005). A particular strength of our technique is that quantitative parameters of hepatocytes and bile canalicular as well as sinusoidal networks can be extracted from the same tissue block. Reconstructions and quantifications performed as described in the current protocols can be used for quantitative mathematical modelling of the underlying mechanisms. Furthermore, protocols are presented for both human and pig livers. The technique is also applicable for both vibratome blocks and conventional paraffin slices.

BACKGROUND: Liver transplantation (LT) from controlled donation after circulatory death (cDCD) was initiated in France in 2015 under a protocol based on the use of normothermic regional perfusion (NRP) before organ procurement. The aim was to compare outcomes following cDCD LT with NRP and donation after brain death (DBD) LT. METHODS: This is a multicenter retrospective study comparing cDCD LT with NRP and DBD LT. A case-matched study (1:2) was performed using the variables such as recipient and donor age, indication of LT. RESULTS: A total of 50 patients from the cDCD group were matched to 100 patients from the DBD group. From postoperative days 1-4, serum transaminase release was significantly lower in the cDCD group compared to the DBD group (P < 0.05). Early allograft dysfunction (cDCD: 18% versus DBD: 32%; P = 0.11), acute kidney injury (26% versus 33%; P = 0.49), 90-d graft loss (2% versus 5%; P = 0.66), and arterial (4% versus 12%; P = 0.19) and biliary (16% versus 17%; P = 0.94) complications were similar between the 2 groups. The 2-y graft survival was 88% for cDCD group and 85% for DBD group (P = 0.91). The 2-y patient survival was 90% for cDCD group and 88% for DBD group (P = 0.68). CONCLUSIONS: This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.