The value of different CT-based methods for diagnosing low muscle mass and predicting mortality in patients with cirrhosis.

Low muscle mass impacts on morbidity and mortality in cirrhosis. The skeletal-muscle index (SMI) is a well-validated tool to diagnose muscle wasting, but requires specialized radiologic software and expertise. Thus, we compared different Computed tomography (CT)-based evaluation methods for muscle wasting and their prognostic value in cirrhosis. Consecutive cirrhotic patients included in a prospective registry undergoing abdominal CT scans were analysed. SMI, transversal psoas muscle thickness (TPMT), total psoas volume (TPV) and paraspinal muscle index (PSMI) were measured. Sarcopenia was defined using SMI as a reference method by applying sex-specific cut-offs (males: <52.4 cm2 /m2 ; females: <38.5 cm2 /m2 ). One hundred and nine patients (71.6% male) of age 57 ± 11 years, MELD 16 (8-26) and alcoholic liver disease (63.3%) as the main aetiology were included. According to established SMI cut-offs, low muscle mass was present in 69 patients (63.3%) who also presented with higher MELD (17 vs 14 points; P = .025). The following optimal sex-specific cut-offs (men/women) for diagnosing low muscle mass were determined: TPMT: <10.7/ <7.8 mm/m, TPV: <194.9/ <99.2 cm3 and PSMI <26.3/ <20.8 cm2 /m2 . Thirty (27.5%) patients died during a follow-up of 15 (0.3-45.7) months. Univariate competing risks analyses showed a significant risk for mortality according to SMI (aSHR:2.52, 95% CI: 1.03-6.21, P = .043), TPMT (aSHR: 3.87, 95% CI: 1.4-8.09, P = .007) and PSMI (aSHR: 2.7, 95% CI: 1.17-6.23, P = .02), but not TPV (P = .18) derived low muscle mass cut-offs. In multivariate analysis only TPMT (aSHR: 2.82, 95% CI: 1.20-6.67, P = .018) was associated with mortality, SMI (aSHR: 1.93, 95% CI: 0.72-5.16, P = .19) and PSMI (aSHR: 1.93, 95% CI: 0.79-4.75, P = .15) were not. Low muscle mass was highly prevalent in our cohort of patients with cirrhosis. Gender-specific TPMT, SMI and PSMI cut-offs for low muscle mass can help identify patients with an increased risk for mortality. Importantly, only TPMT emerged as an independent risk factor for mortality in patients with cirrhosis.

Paternostro R ，Lampichler K ，Bardach C ，Asenbaum U ，Landler C ，Bauer D ，Mandorfer M ，Schwarzer R ，Trauner M ，Reiberger T ，Ferlitsch A ... -  《-》

Poor performance of psoas muscle index for identification of patients with higher waitlist mortality risk in cirrhosis.

Sarcopenia, characterized by low muscle mass, associates with mortality in patients with cirrhosis. Skeletal muscle area in a single computed tomography image at the level of the third lumbar vertebrate (L3) is a valid representative of whole body muscle mass. Controversy remains regarding applicability of psoas muscle to identify patients at greater risk of mortality. We aimed to determine psoas muscle index (PMI) association with skeletal muscle index (SMI) and to evaluate the capacity of PMI to predict liver transplant waitlist mortality. We evaluated listed adult patients with cirrhosis from 2012 to 2013 at four North American liver transplant centres. From L3 computed tomography images within 3 months of listing, we determined SMI and PMI expressed by cm2 /m2 . Low SMI was defined as SMI <39 cm2 /m2 in women and <50 cm2 /m2 in men as published by us earlier. Cut-offs for PMI to predict mortality were established using a receiver-operating characteristic analysis. Mortality predictors were determined using competing-risk analysis with reported results as subdistribution hazard ratios (sHRs). Of 353 waitlist candidates, 68% were men, mean age 56 ± 9 years, and Model for End-stage Liver Disease of 16 ± 8 points. Low SMI was present more frequently in men than women (51 vs. 36%, P = 0.02). Moderately strong correlation between SMI and PMI was observed (r > 0.7, P < 0.001). Low PMI (males < 5.1 cm2 /m2 ; females < 4.3 cm2 /m2 ) yielded poor and moderate concordance with low SMI in men and women, respectively (Kappa coefficient 0.31 and 0.63). SMI (39 ± 9 vs. 43 ± 7 cm2 /m2 ; P = 0.009) and PMI (4.4 ± 1.3 vs. 5.2 ± 1.1 cm2 /m2 ; P = 0.001) were lower in women who died and/or were delisted (compared with non-deceased patients) whereas men who died and/or were delisted had only lower SMI (47 ± 7 vs. 51 ± 9 cm2 /m2 ; P = 0.003), but not PMI compared with non-deceased patients. In women, both SMI (sHR 0.94, P = 0.048) and PMI (sHR 0.58, P = 0.002) were predictors of mortality, while in men, SMI was significant (sHR 0.95, P = 0.001) and PMI showed a trend to be (sHR 0.85, P = 0.09) associated with mortality. Overall, 104 patients (29%) were misclassified between SMI and PMI categories. Using PMI cut-offs, 66% and 28% of low SMI men and women, who have a higher risk of mortality, were incorrectly classified as low risk. Skeletal muscle index is a more complete and robust measurement than PMI, especially in men with cirrhosis. Low PMI identifies an incomplete subset of patients at increased risk of mortality indicated by low SMI. Given the poor performance of PMI, SMI should not be substituted by PMI.

Ebadi M ，Wang CW ，Lai JC ，Dasarathy S ，Kappus MR ，Dunn MA ，Carey EJ ，Montano-Loza AJ ，From the Fitness, Life Enhancement, and Exercise in Liver Transplantation (FLEXIT) Consortium ... -  《-》

Prognostic value of muscle atrophy in cirrhosis using psoas muscle thickness on computed tomography.

Waiting-list mortality in patients with cirrhosis and a relatively low MELD score is a matter of concern. The aim of this study was to determine whether a marker of muscle waste could improve prognostication. A pre-MELD cohort (waiting time-based allocation; n=186) and a MELD-era cohort (n=376) were examined. At evaluation, transversal psoas muscle thickness (TPMT) was measured on a computed tomography (CT) image at the level of the umbilicus. In the pre-MELD cohort, TPMT/height (mm/m) and the MELD score were entered in univariate and multivariate models to predict mortality after registration. Applicability of pre-MELD findings was tested in the MELD-era. In the pre-MELD cohort, the MELD score and TPMT/height were significantly associated with mortality. The discrimination of a score combining MELD and TPMT/height (MELD-psoas) was 0.84 (95% CI, 0.62-0.95). In the MELD-era, TPTM/height was significantly associated with mortality, independent of the MELD and MELD-Na scores. There was a 15% increase in mortality risk per unit decrease in TPMT/height. The discrimination of MELD-psoas score (0.82; 95% CI, 0.64-0.93) was superior to that of the MELD score and similar to that of the MELD-Na score. In patients with refractory ascites, mortality was significantly higher when TPMT/height was <16.8 mm/m (42% vs. 9%, p=0.02). TPMP/height on CT at the level of the umbilicus, an objective marker of muscle waste, may be predictive of mortality in cirrhotic patients, independent of the MELD and MELD-Na scores. It may help to better assess the prognosis of patients with refractory ascites.

Durand F ，Buyse S ，Francoz C ，Laouénan C ，Bruno O ，Belghiti J ，Moreau R ，Vilgrain V ，Valla D ... -  《-》

Loss of paraspinal muscle mass is a gender-specific consequence of cirrhosis that predicts complications and death.

Loss of skeletal muscle mass is a recognised complication with a prognostic impact in patients with cirrhosis. To explore in a retrospective analysis which muscle compartment most reliably predicts the occurrence of cirrhosis-associated complications and if there are gender-related differences. 795 patients with cirrhosis listed for liver transplantation between 2001 and 2014 met the inclusion and exclusion criteria including an abdominal CT scan (±200). Controls were 109 patients who underwent a CT scan after polytrauma. The paraspinal muscles index (PSMI), the abdominal wall muscles index (AWMI) and its combination skeletal muscle index (SMI) were assessed at L3/L4, normalised to the height (cm2 /m2 ). 62.0% of patients with cirrhosis had alcoholic liver disease, and 70.6% were male. As compared to controls, a reduction in PSMI and SMI but not AWMI was associated with high model of end-stage liver disease (MELD) score, high Child-Pugh class, and the presence or history of cirrhosis-associated complications in males but not females. PSMI independently predicted the occurrence of bacterial infections (HR 0.932), spontaneous bacterial peritonitis (HR 0.901), hepatic encephalopathy (HR 0.961), and hepatorenal syndrome (HR 0.946) by multivariate Cox regression analysis in a gender-independent manner. Post-transplant survival was not associated with the PSMI; neither AWMI nor SMI predicted any clinical endpoints. This study links muscle wasting in patients with cirrhosis predominantly to males. However, the presence of a low PSMI mass is a gender-independent predictor of developing cirrhosis-associated complications and death. Scores combining the MELD with muscle parameters should be re-validated by utilizing the PSMI.

Engelmann C ，Schob S ，Nonnenmacher I ，Werlich L ，Aehling N ，Ullrich S ，Kaiser T ，Krohn S ，Herber A ，Sucher R ，Bartels M ，Surov A ，Hasenclever D ，Kahn T ，Seehofer D ，Moche M ，Berg T ... -  《-》

Cut-off values of skeletal muscle index and psoas muscle index at L3 vertebra level by computerized tomography to assess low muscle mass.

Computerized tomography (CT) is considered the gold standard for the evaluation of total skeletal muscle quantity. Skeletal muscle assessments at the L3 vertebra level revealed significantly correlated with total body muscle measurements. Clinicians need cut-offs to evaluate low muscle mass in various patients who already had CT imaging without any additional cost. This assessment is important to help the physicians to stratify the patients for mortality and other complications. It may also enable the diagnosis of malnutrition by the GLIM criteria. Few studies reported cut-offs in different populations. We aimed to provide cut-off values for total skeletal muscle index (SMI) and psoas muscle mass index (PMI) at the L3 vertebra level in the Turkish population. We assessed the preoperative plain CT images of living adult liver donors who were admitted to a single transplantation center between June 2010 and April 2018. We derived cut-off values with two alternative methods, the 5th percentile value or mean minus two standard deviations and from two groups of study participants, i.e. the total study population and the younger subgroup aged between 18 and 40. The study population involved 601 subjects with a mean age of 32.5 ± 9 (range: 18-59 years) and 326 (54.2%) was male. The younger subgroup was composed of 482 individuals with a mean age of 28.8 ± 5.9 and 55.6% male. In patients aged between 18 and 40, PMI and SMI cut-offs by using the 5th percentile were 5.40 cm2/m2, 41.42 cm2/m2 for males; and 3.56 cm2/m2, 30.70 cm2/m2 for females; respectively. The cut-offs of PMI and SMI by using mean minus two standard deviations were 4.62 cm2/m2, 38.67 cm2/m2 for males; and 2.66 cm2/m2, 27.8 cm2/m2 for females; respectively. These cut-offs were comparable to the other populations. Our study provided cut-offs to be used in CT images for PMI and SMI. There is a need for further longitudinal studies to verify whether these cut-offs are successful in predicting mortality or other adverse outcomes associated with low muscle mass.

Bahat G ，Turkmen BO ，Aliyev S ，Catikkas NM ，Bakir B ，Karan MA ... -  《-》