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Background & Aims: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model., Methods: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses., Results: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD., Conclusions: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed., Lay Summary: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Sorafenib has become the standard first-line treatment for patients with advanced HCC and acts by inducing alterations in tumor vascularity. We wanted to evaluate the feasibility of dynamic CEUS (D-CEUS) as a predictor of early tumor response to sorafenib and to correlate functional parameters with clinical efficacy end points., Methods: Twenty-eight HCC patients treated with sorafenib 400mg bid were prospectively enrolled. CEUS was performed at baseline (T0) and after 15 (T1) and 30 (T2) days of treatment. Tumor vasculature was assessed in a specific harmonic mode associated with a perfusion and quantification software (Q-Lab, Philips). Variations between T1/T2 and T0 were calculated for five D-CEUS functional parameters (peak intensity, PI; time to PI, TP; area under the curve, AUC; slope of wash in, Pw; mean transit time, MTT) and were compared for responders and non-responders. The correlation between D-CEUS parameters, overall survival (OS), and progression-free survival (PFS) was also assessed. A p value <0.05 was considered statistically significant., Results: The percentage variation at T1 significantly correlated with response in three D-CEUS parameters (AUC, PI and Pw; p=0.002, <0.001, and 0.003, respectively). A decrease of AUC (p=0.045) and an increased/unchanged value of TP (p=0.029) and MTT (p=0.010) were associated with longer survival. Three D-CEUS parameters (AUC, TP, Pw) were significantly associated with PFS., Conclusions: D-CEUS provides a reliable and early measure of efficacy for anti-angiogenic therapies and could be an excellent tool for selecting patients who will benefit from treatment., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Adrenal insufficiency (AI) is reported in critically ill patients with cirrhosis and is associated with increased mortality. It is unclear if AI is an underlying condition or triggered by critical events (e.g. sepsis). We investigated AI in cirrhosis without infection or hemodynamic instability., Methods: A total of 101 consecutive patients with cirrhosis were studied. AI was defined by a total serum cortisol (TC) <18 μg/dl at 20 or 30 min after injection of 1 μg of tetracosactrin. Transcortin, calculated free cortisol (cFC), and free cortisol index (FCI) were assessed in a subgroup of 41 patients, with FCI>12 representing normal adrenal function., Results: AI was present in 38 patients (38%). Child score (median, 10 vs 7, p<0.0001), MELD score (median, 17 vs 12, p<0.0001), ascites (68% vs 37%, p<0.01), basal TC (median,7.6 vs 14.9 μg/dl, p<0.001), albumin (28 ± 0.8 vs 33 ± 0.7 g/L, p<0.0001), INR (median, 1.6 vs 1.2, p<0.0001), total bilirubin (median, 51 vs 31 μmol/L, p<0.05), total cholesterol (median, 120 vs 142, p<0.05), and LDL (median, 76 vs 81, p<0.05) were significantly different between those with and without AI. ROC curves showed a basal TC ≤ 12.8 μg/dl to be a cut-off value closely associated with AI. The cFC was significantly related to TC for baseline values (R=0.94, p<0.0001), peak values (R=0.90, p<0.0001), and delta values (R=0.95, p<0.0001), in patients with and without AI. However, no patient had a FCI<12., Conclusions: AI defined by an abnormal response to 1 μg tetracosactrin is frequent in stable patients with cirrhosis, in the absence of infections or hemodynamic instability and is related to the severity of liver disease. However, evaluation of the true incidence of AI should comprise direct assays of free cortisol. Clinical consequences of AI need to be explored., (Copyright © 2010 European Association for the Study of the Liver. All rights reserved.)