Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease.

OBJECTIVE: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients. DESIGN: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation. RESULTS: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM. CONCLUSION: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.

Endothelial cells do not express GSTA1: potential relevance to busulfan-mediated endothelial damage during haematopoietic stem cell transplantation.

Busulfan-mediated endothelial damage is believed to be a common mechanism in a variety of vascular disorders that occur during haematopoietic stem cell transplantation. The alkylating capacity of busulfan is compromised in vivo by enzymatic conjugation with glutathione, principally catalysed by glutathione S-transferase alpha (GST alpha). We investigated whether the susceptibility of endothelial cells to busulfan-mediated damage is related to their intrinsic deficiency in GST alpha expression. We tested for the expression of GST alpha mRNA by real-time quantitative PCR and the GST protein by enzyme-linked immunosorbent assay in various independently derived endothelial cell types (human bone marrow-derived endothelial cell line and endothelial cells from human vein umbilical cord ) and in a control hepatic cell line, HepG2. We demonstrate that endothelial cells, contrary to hepatic cells do not express GST alpha either at mRNA or protein levels and hence are potentially susceptible to busulfan-mediated cytotoxic damage.