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We aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. In liver biopsies obtained at liver transplantation, we measured the magnesium content in liver tissue in 27 cirrhotic patients (CIRs) and 16 deceased donors with healthy liver (CTRLs) by atomic absorption spectrometry and within hepatocytes of 15 CIRs using synchrotron-based X-ray fluorescence microscopy. In 31 CIRs and 10 CTRLs, we evaluated the immunohistochemical expression in hepatocytes of the transient receptor potential melastatin 7 (TRPM7), a magnesium influx chanzyme also involved in inflammation. CIRs showed a lower hepatic magnesium content (117.2 (IQR 110.5–132.9) vs. 162.8 (IQR 155.9–169.8) μg/g; p < 0.001) and a higher percentage of TRPM7 positive hepatocytes (53.0 (IQR 36.8–62.0) vs. 20.7 (10.7–32.8)%; p < 0.001) than CTRLs. In CIRs, MELDNa and serum AST at transplant correlated: (a) inversely with the magnesium content both in liver tissue and hepatocytes; and (b) directly with the percentage of hepatocytes stained intensely for TRPM7. The latter also directly correlated with the worsening of MELDNa at transplant compared to waitlisting. Magnesium depletion and overexpression of its influx chanzyme TRPM7 in hepatocytes are associated with severity of hepatocyte injury and prognosis in cirrhosis. These data represent the pathophysiological basis for a possible beneficial effect of magnesium supplementation in cirrhotic patients. [ABSTRACT FROM AUTHOR]

Background & Aims: Sarcopenia in liver transplantation (LT) cirrhotic candidates has been connected with higher dropouts and graft losses after transplant. The study aims to create an 'urgency' model combining sarcopenia and Model for End‐stage Liver Disease Sodium (MELDNa) to predict the risk of dropout and identify an appropriate threshold of post‐LT futility. Methods: A total of 1087 adult cirrhotic patients were listed for a first LT during January 2012 to December 2018. The study population was split into a training (n = 855) and a validation set (n = 232). Results: Using a competing‐risk analysis of cause‐specific hazards, we created the Sarco‐Model2. According to the model, one extra point of MELDNa was added for each 0.5 cm2/m2 reduction of total psoas area (TPA) < 6.0 cm2/m2. At external validation, the Sarco‐Model2 showed the best diagnostic ability for predicting the risk of 3‐month dropout in patients with MELDNa < 20 (area under the curve [AUC] = 0.93; P =.003). Using the net reclassification improvement, 14.3% of dropped‐out patients were correctly reclassified using the Sarco‐Model2. As for the futility threshold, transplanted patients with TPA < 6.0 cm2/m2 and MELDNa 35‐40 (n = 16/833, 1.9%) had the worse results (6‐month graft loss = 25.5%). Conclusions: In sarcopenic patients with MELDNa < 20, the 'urgency' Sarco‐Model2 should be used to prioritize the list, while MELDNa value should be preferred in patients with MELDNa ≥ 20. The Sarco‐Model2 played a role in more than 30% of the cases in the investigated allocation scenario. In sarcopenic patients with a MELDNa value of 35‐40, 'futile' transplantation should be considered. [ABSTRACT FROM AUTHOR]

Psychopathological symptoms and reduced health related quality of life (HRQoL) are frequent in cirrhotics, but no data on their association with cirrhosis prognosis assessed by the MELDNa score are available. Prospective data on the long-term effect of deceased donor liver transplantation (LT) on psychopathological symptoms are needed. Before entering the LT waiting list, 44 consecutive LT cirrhotic candidates without a major psychiatric disorder underwent a psychopathological assessment, including Symptom Checklist-90-revised (SCL-90-R) and Defense Style Questionnaire (DSQ). HRQoL was measured by Short Form 36 Health Survey (SF-36). Abnormal performance at each questionnaire was defined by using 44 age, gender, BMI and education-matched healthy subjects. Separate binary logistic regression models were used to test the association of the Child-Pugh, MELD and MELDNa scores with abnormal performance at each questionnaire. Fourteen patients repeated the battery tests 3 years after LT. Before LT, increasing MELDNa was the only prognostic score independently associated with an abnormal SCL-90-R global psychopathological score index (OR: 1.207; 95% CI: 1.026-1.420; P = 0.02) and the best independent predictor of reduced HRQoL. After LT, compared to status prior to LT, performance at SF-36 general health perception scale ameliorated ( P = 0.02), performance at SCL-90-R somatization scale ( P = 0.001) and global psychopathological score index ( P < 0.001) worsened and the negative correlation between the psychopathological global score index and HRQoL disappeared. The severity of cirrhosis in LT candidates should be monitored by the MELDNa score to better establish the right psychological counselling. Psychopathology, and in particular somatization, worsens after LT and should be carefully investigated. [ABSTRACT FROM AUTHOR]

Background Modifications to the Model for End-Stage Liver Disease ( MELD) have been proposed to improve prioritization of liver transplant ( LT) candidates. Using a U.S. database, we derived a revised MELD including sodium and albumin [5-variable MELD (5v MELD)] that improved prediction of waiting list mortality. Our objectives were to confirm the association between hypoalbuminaemia and mortality and to externally validate 5v MELD in Canadian LT candidates. Methods Among adults registered on the LT waiting list at the University of Alberta (01/2000-10/2009), Cox regression determined the association between albumin and 1-year waiting list mortality. The discrimination of MELD, MELDNa and 5v MELD for predicting 1-year mortality were compared using c-statistics. Results Among 677 patients, 17% died and 51% underwent LT within 1 year of listing. Median serum albumin was 3.1 g/dl (IQR 2.6-3.6) and 70% of patients were hypoalbuminaemic (albumin <3.5 g/dl). One-year mortality in patients with normal serum albumin and hypoalbuminaemia were 14% and 29% respectively ( P = 0.004). For patients with serum albumin between 2.0 and 4.0 g/dl, an approximately linear, inverse relationship was observed between albumin and 1-year mortality [adjusted hazard ratio (HR) 1.45; 95% CI 1.03-2.03; P = 0.03]. For this outcome, the c-statistic of 5vMELD (0.778) was superior to those of MELD (0.754) and MELDNa (0.765) (both P ≤ 0.05). Conclusions Hypoalbuminaemia is an independent predictor of mortality on the LT waiting list. Compared with MELD and MELDNa, 5v MELD improves prediction of mortality suggesting that modification of these scores to include serum albumin should be considered as a means of prioritizing LT candidates. [ABSTRACT FROM AUTHOR]

Abstract: Background: The model for end-stage liver disease (MELD) and serum sodium (Na) are important markers for liver functional reserve in patients with hepatocellular carcinoma. We aimed to determine the best model to define the severity of liver dysfunction in terms of outcome prediction among the 4 currently used systems (MELD, MELDNa, MELD-Na and ReFit MELDNa). Methods: A total of 2308 prospectively enrolled patients with hepatocellular carcinoma were analysed. The prognostic ability was compared by the Akaike information criterion. Results: MELDNa had the best prognostic accuracy overall, and for patients receiving curative and non-curative treatments, followed by MELD-Na, MELD and ReFit MELDNa. When patients were categorized into <8, 8–12, 12–16, 16–20 and >20, the adjusted risk ratios for MELDNa were 1.065 (p =0.46), 0.996 (p =0.973), 1.38 (p =0.048) and 1.563 (p =0.003) for the scores of 8–12, 12–16, 16–20 and >20, respectively, compared to the group with scores <8. The adjusted risk ratio for MELDNa was 1.014 (95% confidence interval, 1.001–1.027; p =0.034) per unit score increment in the Cox model. Conclusions: The MELDNa is the best marker to define the severity of liver dysfunction in hepatocellular carcinoma patients independent of treatment strategy. The ReFit MELDNa does not enhance the predictive accuracy of the MELD. [Copyright &y& Elsevier]

Abstract: Background and aim: The model for end-stage liver disease (MELD) is used to predict the outcome of patients with cirrhosis. Incorporation of serum sodium (Na) into MELD may further increase its prognostic ability. Two Na-containing MELD models, MELD-Na and MELDNa, were proposed to enhance the prognostic ability. This study compared the predictive accuracy of these models for acute decompensated hepatitis. Methods: We investigated the outcome of 182 patients with acute decompensated hepatitis. Results: Twenty (11%) patients died at 3 months. The MELD-Na and MELDNa both had significantly higher area under the receiver operating characteristic curve (AUC) in comparison to MELD (MELD-Na: 0.908, MELDNa: 0.895, MELD: 0.823, p =0.004 and 0.001, respectively). Among 96 patients without specific antiviral treatment, the MELD-Na and MELDNa consistently had significantly higher AUC than the MELD (MELD-Na: 0.901, MELDNa: 0.882, MELD: 0.810, p =0.008 and 0.004, respectively). Three independent indicators, pre-existing cirrhosis (odds ratio [OR]: 5.67, 95% confidence interval [CI]: 1.72–18.7), serum albumin <3.7g/dL (OR: 5.68, 95% CI: 1.18–27.03) and serum sodium (Na)<138mequiv./L (OR: 10.0, 95% CI: 2.08–47.62), were associated with 3-month mortality. Conclusion: MELD-Na and MELDNa provide better prognostic accuracy than the MELD for patients with acute decompensated hepatitis. The adequacy of liver reserve determines the outcome of these patients. [Copyright &y& Elsevier]