Psoas Muscle Density in Combination with Model for End-Stage Liver Disease Score Can Improve Survival Predictability in Transjugular Intrahepatic Portosystemic Shunts.
Shoreibah Mohamed Galal,Mahmoud Khalid,Aboueldahab Noha A,Vande Lune Patrick,Massoud Mustafa,Bae Sejong,El Khudari Husameddin,Gunn Andrew J,Abdel Aal Ahmed Kamel
Journal of vascular and interventional radiology : JVIR
PURPOSE:To examine the role of psoas muscle density (PD) measurement before transjugular intrahepatic portosystemic shunt (TIPS) creation in predicting survival when combined with Model for End-stage Liver Disease (MELD) score. MATERIALS AND METHODS:The medical records of 241 patients with cirrhosis who underwent TIPS creation between June 2005 and June 2015 were retrospectively reviewed. The patients were divided into 2 groups: those with variceal bleeding (VB; n = 113) and those with volume overload (VO; n = 128). The study included 149 men (62%), and mean patient age was 56 years ± 9.6 (range 24-83). Mean MELD score before TIPS creation was 11.8 ± 5.7. A threshold sensitivity of pre-TIPS PD for the assessment of mortality was calculated and then correlated with survival after TIPS creation. Receiver operating characteristic curves comparing 12-month mortality were used to assess the improvement in survival predictability after TIPS creation when the PD threshold was combined with MELD score vs MELD score alone. RESULTS:Mean post-TIPS follow-up was 29.9 month ± 34.1 (range 1-3700 days). There was no significant difference in 3- or 12-month mortality rates between the VB and VO groups (32.7% vs 25.8% [P = .23] and 46% vs 46.1% [P = .99], respectively). The MELD score threshold for prediction of survival was 15 (P < .0001). There was no difference in the mean PD between VB and VO groups (34.2 HU ± 8.8 and 33.1 HU ± 10.3, respectively; P = .359). The increase in MELD score after TIPS creation was significant in both groups (VB, P = .0013; VO, P < .0001). The threshold of pre-TIPS PD for discrimination of survival was 29.4 HU (P < .0001), and PD measurements greater than this threshold were associated with a lower risk of mortality (hazard ratio, 0.27; 95% confidence interval, 0.13-0.57; P = .0006). Compared with the use of MELD score alone, the addition of PD measurement significantly increased the area under the curve from 0.61 to 0.68 (P = .0006). CONCLUSIONS:Measurement of PD improved overall survival predictability in patients with cirrhosis undergoing TIPS creation when used in conjunction with MELD score. The best survival outcome was observed in patients with MELD score < 15 in combination with PD > 29.4 HU.
Prognostic significance of low skeletal muscle mass compared with protein-energy malnutrition in liver cirrhosis.
Nishikawa Hiroki,Enomoto Hirayuki,Ishii Akio,Iwata Yoshinori,Miyamoto Yuho,Ishii Noriko,Yuri Yukihisa,Takata Ryo,Hasegawa Kunihiro,Nakano Chikage,Nishimura Takashi,Yoh Kazunori,Aizawa Nobuhiro,Sakai Yoshiyuki,Ikeda Naoto,Takashima Tomoyuki,Iijima Hiroko,Nishiguchi Shuhei
Hepatology research : the official journal of the Japan Society of Hepatology
AIMS:To investigate the impact of low skeletal muscle mass (LSMM) on survival as compared with protein-energy malnutrition (PEM) in patients with liver cirrhosis (LC). METHODS:A total of 206 individuals with LC were analyzed. We retrospectively examined the impact of LSMM, as defined by psoas muscle mass at the third lumber on computed tomography, on survival as compared with PEM. In terms of comparison of the effects of LSMM and PEM on survival, we used time-dependent receiver operating characteristics (ROC) analysis. RESULTS:Our study cohort included 115 men and 91 women with a median age of 67 years. There were 140 patients with Child-Pugh A, 62 with Child-Pugh B, and 4 with Child-Pugh C. A total of 117 patients (56.8%) had LSMM and 52 patients (25.2%) had PEM. The proportion of PEM in patients with LSMM (31.62%, 37/117) was significantly higher than in patients without LSMM (16.85%, 15/89) (P = 0.0229). In the multivariate analysis for the entire cohort, the presence of hepatocellular carcinoma, lower body mass index, presence of LSMM, lower triglyceride value, poorer renal function, and higher des-γ-carboxy prothrombin value were found to be significant adverse predictors linked to overall survival, while presence of PEM tended to be significant. In the time-dependent ROC analysis, all area under the ROCs for survival in LSMM at each time point were higher than those in PEM except for Child-Pugh B patients. CONCLUSION:In this comparison of LSMM and PEM on clinical outcomes in LC patients, it was shown that LSMM may have stronger prognostic impact than PEM.
Effect of psoas muscle mass after endoscopic therapy for patients with esophageal varices.
Nishikawa Hiroki,Yuri Yukihisa,Enomoto Hirayuki,Ishii Akio,Iwata Yoshinori,Miyamoto Yuho,Ishii Noriko,Hasegawa Kunihiro,Nakano Chikage,Nishimura Takashi,Yoh Kazunori,Aizawa Nobuhiro,Sakai Yoshiyuki,Ikeda Naoto,Takashima Tomoyuki,Takata Ryo,Iijima Hiroko,Nishiguchi Shuhei
We aimed to investigate the impact of decrease of muscle mass on survival after eradication of esophageal varices (EVs) treated by endoscopic therapies as a primary prophylaxis in patients with liver cirrhosis (LC). In all, 177 LC individuals with EVs undergoing endoscopic therapies were analyzed. We retrospectively examined the impact of muscle mass decrease as determined by psoas muscle mass (PMM) at the third lumber on computed tomography (depletion of PMM [DPMM]) on survival as compared with serum sodium combined Model for End-stage Liver Disease (MELD-Na). In comparison of the effects of these parameters, we used time-dependent receiver-operating characteristics (ROC) analysis. We also investigated parameters related to overall survival in the univariate and multivariate analyses. This study included 116 males and 61 females with a median age of 66 years. The median follow-up periods were 2.7 years (range 0.1-9.6 years). In all, 110 patients (62.1%) had DPMM. The median MELD-Na score was 7.200 (range -3.451 to 30.558). The MELD-Na score in patients with DPMM (median 7.685) was significantly higher than that in patients without DPMM (median 6.235) (P = .0212). In the multivariate analysis, presence of hepatocellular carcinoma (P < .0001), presence of DPMM (P < .0001), and MELD-Na ≥7.2 (P = .0438) were revealed to be significant predictors related to overall survival. In time-dependent ROC analyses, all area under the ROCs for DPMM in each time point were higher than those for MELD-Na in the entire cohort and in patients without hepatocellular carcinoma at baseline (n = 133). In conclusion, for LC patients treated by endoscopic therapies for EVs, DPMM had stronger prognostic impact than MELD-Na.
Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score.
Kalafateli Maria,Mantzoukis Konstantinos,Choi Yau Yan,Mohammad Ali O,Arora Simran,Rodrigues Susana,de Vos Marie,Papadimitriou Kassiani,Thorburn Douglas,O'Beirne James,Patch David,Pinzani Massimo,Morgan Marsha Y,Agarwal Banwari,Yu Dominic,Burroughs Andrew K,Tsochatzis Emmanuel A
Journal of cachexia, sarcopenia and muscle
BACKGROUND:Although malnutrition and sarcopenia are prevalent in cirrhosis, their impact on outcomes following liver transplantation is not well documented. METHODS:The associations of nutritional status and sarcopenia with post-transplant infections, requirement for mechanical ventilation, intensive care (ICU) and hospital stay, and 1 year mortality were assessed in 232 consecutive transplant recipients. Nutritional status and sarcopenia were assessed using the Royal Free Hospital-Global Assessment (RFH-GA) tool and the L3-psoas muscle index (L3-PMI) on CT, respectively. RESULTS:A wide range of RFH-SGA and L3-PMI were observed within similar Model for End-stage Liver Disease (MELD) sub-categories. Malnutrition and sarcopenia were independent predictors of all outcomes. Post-transplant infections were associated with MELD (OR = 1.055, 95%CI = 1.002-1.11) and severe malnutrition (OR = 6.55, 95%CI = 1.99-21.5); ventilation > 24 h with MELD (OR = 1.1, 95%CI = 1.036-1.168), severe malnutrition (OR = 8.5, 95%CI = 1.48-48.87) and suboptimal donor liver (OR = 2.326, 95%CI = 1.056-5.12); ICU stay > 5 days, with age (OR = 1.054, 95%CI = 1.004-1.106), MELD (OR = 1.137, 95%CI = 1.057-1.223) and severe malnutrition (OR = 7.46, 95%CI = 1.57-35.43); hospital stay > 20 days with male sex (OR = 2.107, 95%CI = 1.004-4.419) and L3-PMI (OR = 0.996, 95%CI = 0.994-0.999); 1 year mortality with L3-PMI (OR = 0.996, 95%CI = 0.992-0.999). Patients at the lowest L3-PMI receiving suboptimal grafts had longer ICU/hospital stay and higher incidence of infections. CONCLUSIONS:Malnutrition and sarcopenia are associated with early post-liver transplant morbidity/mortality. Allocation indices do not include nutritional status and may jeopardize outcomes in nutritionally compromised individuals.
Muscle fat infiltration assessed by total psoas density on computed tomography predicts mortality in cirrhosis.
Kalafateli Maria,Karatzas Andreas,Tsiaoussis Georgios,Koutroumpakis Efstratios,Tselekouni Paraskevi,Koukias Nikolaos,Konstantakis Christos,Assimakopoulos Stelios,Gogos Charalambos,Thomopoulos Konstantinos,Kalogeropoulou Christina,Triantos Christos
Annals of gastroenterology
Background:Ongoing evidence suggests that sarcopenia adversely affects outcomes in cirrhosis. The aim of this study was to evaluate muscle fat infiltration as a component of sarcopenia and its prognostic value in this setting. Methods:In 98 consecutive patients with cirrhosis, muscle density was measured during a computed tomography scan at the level of the fourth to fifth lumbar (L4) vertebrae. Univariate and multivariate Cox regression analysis was used to determine predictors of survival. Results:Body mass index: median 26 (range 17-45.2); model for end-stage liver disease (MELD) score: median 11 (6-29); Child-Pugh (CP) score: median 7 (5-13), CP class: A=49 (50.5%), B=39 (40%), C=10 (9.5%); hepatocellular carcinoma: 14 (14.3%); follow up: median 45 (1-140) months. Median L4 total psoas area (TPA): 2022 (777-3806) mm; L4 average total psoas density (ATPD): 42.52 (21.26-59.8) HU. ATPD was significantly correlated with age (=-0.222, P=0.034), creatinine (=-0.41, P<0.001), albumin (=0.224, P=0.035), MELD score (=-0.218, P=0.034), and TPA (=0.415, P<0.001). Fifty-four patients (55.1%) died during follow up. In the multivariate analysis, higher CP score (hazard ratio [HR] 1.2, 95% confidence interval [CI] 1.04-1.41), advanced age (HR 1.038, 95%CI 1.006-1.07) and lower ATPD (HR 0.967, 95%CI 0.937-0.997) were predictors of mortality. Conclusion:Muscle fat infiltration, as a result of sarcopenia, is a negative predictive factor of survival in cirrhosis, emphasizing the need for early identification of this subgroup of patients.
Muscle Gain after Transjugular Intrahepatic Portosystemic Shunt Creation: Time Course and Prognostic Implications for Survival in Cirrhosis.
Jahangiri Younes,Pathak Priya,Tomozawa Yuki,Li Lei,Schlansky Barry L,Farsad Khashayar
Journal of vascular and interventional radiology : JVIR
PURPOSE:To examine the association of transjugular intrahepatic portosystemic shunt (TIPS) creation with muscle gains and patient mortality, and to identify the timeframe of these changes. MATERIALS AND METHODS:Patients with cirrhosis undergoing TIPS creation with available abdominal computed tomography before and after TIPS from 2004-2015 were included (n = 76). The primary indications for TIPS included refractory ascites (52.6%) or variceal bleeding (47.4%). Axial truncal muscle area and attenuation were measured at the L4 level using free-hand region of interest technique, and pre- and post-TIPS values were compared. The association of TIPS-related muscle changes with mortality was evaluated using Cox multiple regression. Logistic regression analysis was performed to evaluate associations of baseline muscle area and clinical variables with post-TIPS changes. RESULTS:TIPS creation was associated with significant increases in psoas, paraspinal, and total muscle areas (P < .001, 0.004, and 0.002), and psoas muscle attenuation (P = .022) at a median of 13.5 months after TIPS. Maximal muscle gains occurred within 6 months after TIPS creation (P < .001). Muscle gain at 1-year after TIPS was independently associated with lower mortality (psoas hazard ratio [HR] 0.14, P = .016; paraspinal HR 0.15, P = .016; abdominal HR 0.05, P = .005; core HR 0.06, P = .001; and total HR 0.05, P = .003). Baseline demographic or clinical variables were not associated with muscle gain after TIPS. CONCLUSIONS:TIPS creation was strongly associated with truncal muscle gains and attenuation in patients with cirrhosis. Maximal muscle gain occurred within 6 months after TIPS creation. TIPS-related increased muscle mass was independently associated with lower patient mortality.
Sarcopenia and failure to rescue following liver transplantation.
Underwood Patrick W,Cron David C,Terjimanian Michael N,Wang Stewart C,Englesbe Michael J,Waits Seth A
INTRODUCTION:Sarcopenic liver transplant recipients have higher rates of mortality, but mechanisms underlying these rates remain unclear. Failure to rescue (FTR) has been shown to be a primary driver of mortality following major general and vascular surgery. We hypothesized that FTR is common in sarcopenic liver transplant recipients. METHODS:We retrospectively reviewed 348 liver transplant recipients with perioperative CT scans. Analytic morphomic techniques were used to assess trunk muscle size via total psoas area (TPA). One-yr major complication and FTR rates were calculated across TPA tertiles. RESULTS:The one-yr complication rate was 77% and the FTR rate was 19%. Multivariate regression showed TPA as a significant predictor of FTR (OR = 0.27 per 1000 mm(2) increase in TPA, p < 0.001). Compared to patients in the largest muscle tertile, patients in the smallest tertile had 1.4-fold higher adjusted complication rates (91% vs. 66%) and 2.8-fold higher adjusted FTR rates (22% vs. 8%). DISCUSSION:These results suggest that mortality in sarcopenic liver transplant recipients may be strongly related to FTR. Efforts aimed at early recognition and management of complications may decrease postoperative mortality. Additionally, this work highlights the need for expanded multicenter collaborations aimed at collection and analysis of postoperative complications in liver transplant recipients.
Association between sarcopenia and the risk of serious infection among adults undergoing liver transplantation.
Krell Robert W,Kaul Daniel R,Martin Andrew R,Englesbe Michael J,Sonnenday Christopher J,Cai Shijie,Malani Preeti N
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
Although sarcopenia (muscle loss) is associated with increased mortality after liver transplantation, its influence on other complications is less well understood. We examined the association between sarcopenia and the risk of severe posttransplant infections among adult liver transplant recipients. By calculating the total psoas area (TPA) on preoperative computed tomography scans, we assessed sarcopenia among 207 liver transplant recipients. The presence or absence of a severe posttransplant infection was determined by a review of the medical chart. The influence of posttransplant infections on overall survival was also assessed. We identified 196 episodes of severe infections among 111 patients. Fifty-six patients had more than 1 infection. The median time to the development of an infection was 27 days (interquartile range = 13-62 days). When the patients were grouped by TPA tertiles, patients in the lowest tertile had a greater than 4-fold higher chance of developing a severe infection in comparison with patients in the highest tertile (odds ratio = 4.6, 95% confidence interval = 2.25-9.53). In a multivariate analysis, recipient age (hazard ratio = 1.04, P = 0.02), pretransplant TPA (hazard ratio = 0.38, P < 0.01), and pretransplant total bilirubin level (hazard ratio = 1.05, P = 0.02) were independently associated with the risk of developing severe infections. Patients with severe posttransplant infections had worse 1-year survival than patients without infections (76% versus 92%, P = 0.003). In conclusion, among patients undergoing liver transplantation, a lower TPA was associated with a heightened risk for posttransplant infectious complications and mortality. Future efforts should focus on approaches for assessing and mitigating vulnerability in patients undergoing transplantation.
Body composition predicts mortality and decompensation in compensated cirrhosis patients: A prospective cohort study.
Tapper Elliot B,Zhang Peng,Garg Rohan,Nault Tori,Leary Kate,Krishnamurthy Venkat,Su Grace L
JHEP reports : innovation in hepatology
Background & Aims:Body composition, particularly sarcopenia, is associated with mortality in patients with decompensated cirrhosis undergoing transplant evaluation. Similar data are limited for non-transplant eligible or compensated patients. Methods:A total of 274 patients with cirrhosis were followed prospectively for ≤5 years after a CT scan. We utilized Analytic Morphomics® to measure body composition (fat, muscle, and bone) which was rendered into relative values (percentiles) in relation to a reference population. The model for end-stage liver disease (MELD) score was used as a reference model for survival prediction. We validated our models in a separate cohort. Results:Our cohort had a mean Child-Pugh score of 7.0 and a mean MELD of 11.3. The median follow-up time was 5.05 years. The proportion of patients alive at 1, 3 and 5 years was 86.5%, 68.0%, and 54.3%; 13 (4.6%) underwent liver transplantation. Child-Pugh B/C ( A) cirrhosis was associated with decreased muscle, subcutaneous, and visceral fat area but increased subcutaneous/visceral fat density. Decreased normal density muscle mass was associated with mortality (hazard ratio [HR] 0.984, <0.001) as well as visceral and subcutaneous fat density (HR 1.013 and 1.014, respectively, <0.001). Models utilizing these features outperformed MELD alone for mortality discrimination in both the derivation and validation cohort, particularly for those with compensated cirrhosis (C-statistics of 0.74 0.58). Using competing risk analysis, we found that subcutaneous fat density was most predictive of decompensation (subdistribution HR 1.018, = 0.0001). Conclusion:The addition of body composition features to predictive models improves the prospective determination of prognosis in patients with cirrhosis, particularly those with compensated disease. Fat density, a novel feature, is associated with the risk of decompensation. Lay summary:Am I at high risk of getting sicker and dying? This is the key question on the mind of patients with cirrhosis. The problem is that we have very few tools to help guide our patients, particularly if they have early cirrhosis (without symptoms like confusion or fluid in the belly). We found that how much muscle and fat the patient has and what that muscle or fat looks like on a CT scan provide helpful information. This is important because many patients have CT scans and this information is hiding in plain sight.
A multicenter study to define sarcopenia in patients with end-stage liver disease.
Carey Elizabeth J,Lai Jennifer C,Wang Connie W,Dasarathy Srinivasan,Lobach Iryna,Montano-Loza Aldo J,Dunn Michael A,
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
Sarcopenia is associated with increased wait-list mortality, but a standard definition is lacking. In this retrospective study, we sought to determine the optimal definition of sarcopenia in end-stage liver disease (ESLD) patients awaiting liver transplantation (LT). Included were 396 patients newly listed for LT in 2012 at 5 North American transplant centers. All computed tomography scans were read by 2 individuals with interobserver correlation of 98%. Using image analysis software, the total cross-sectional area (cm ) of abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI), which normalizes muscle area to patient height, was then calculated. The primary outcome was wait-list mortality, defined as death on the waiting list or removal from the waiting list for reasons of clinical deterioration. Sex-specific potential cutoff values to define sarcopenia were determined with a grid search guided by log-rank test statistics. Optimal search methods identified potential cutoffs to detect survival differences between groups. The overall median SMI was 47.6 cm /m : 50.0 in men and 42.0 in women. At a median of 8.8 months follow-up, mortality was 25% in men and 36% in women. Patients who died had lower SMI than those who survived (45.6 versus 48.5 cm /m ; P < 0.001), and SMI was associated with wait-list mortality (hazard ratio, 0.95; P < 0.001). Optimal search method yielded SMI cutoffs of 50 cm /m for men and 39 cm /m for women; these cutoff values best combined statistical significance with a sufficient number of events to detect survival differences between groups. In conclusion, we recommend that an SMI < 50 cm /m for men and < 39 cm /m for women be used to define sarcopenia in patients with ESLD awaiting LT. Liver Transplantation 23 625-633 2017 AASLD.
Preoperative Assessment of Muscle Mass Using Computerized Tomography Scans to Predict Outcomes Following Orthotopic Liver Transplantation.
Esser Hannah,Resch Thomas,Pamminger Mathias,Mutschlechner Beatrix,Troppmair Jakob,Riedmann Marina,Gassner Eva,Maglione Manuel,Margreiter Christian,Boesmueller Claudia,Oberhuber Rupert,Weissenbacher Annemarie,Cardini Benno,Finkenstedt Armin,Zoller Heinz,Tilg Herbert,Öfner Dietmar,Schneeberger Stefan
BACKGROUND:Sarcopenia is an established risk factor predicting survival in chronically ill and trauma patients. We herein examine the assessment and clinical implication of sarcopenia in liver transplantation (LT). METHODS:Computerized tomography scans from 172 patients waitlisted for LT were analyzed by applying 6 morphometric muscle scores, including 2 density indices (psoas density [PD] and skeletal muscle density [SMD]) and 4 scores based on muscle area (total psoas area, psoas muscle index, skeletal muscle area, and skeletal muscle index). RESULTS:The prevalence of sarcopenia in our cohort ranged from 7.0% to 37.8%, depending on the score applied. Only sarcopenia as defined by the density indices PD and SMD (but not total psoas area, psoas muscle index, skeletal muscle area, or skeletal muscle index) revealed clinical relevance since it correlates significantly with postoperative complications (≥Grade III, Clavien-Dindo classification) and sepsis. Furthermore, sarcopenia predicted inferior patient and graft survival, with low muscle density (PD: <38.5 HU or SMD: <30 HU) representing an independent risk factor in a multivariate regression model (P < 0.05). Importantly, the widely used Eurotransplant donor risk index had a predictive value in nonsarcopenic patients but failed to predict graft survival in patients with sarcopenia. CONCLUSIONS:Sarcopenia revealed by low muscle density correlates with major complications following LT and acts as an independent predictor for patient and graft survival. Therefore, the application of a simple computerized tomography-morphologic index can refine an individual recipient's risk estimate in a personalized approach to transplantation.
Automated Measurements of Muscle Mass Using Deep Learning Can Predict Clinical Outcomes in Patients With Liver Disease.
Wang Nicholas C,Zhang Peng,Tapper Elliot B,Saini Sameer,Wang Stewart C,Su Grace L
The American journal of gastroenterology
INTRODUCTION:There is increasing recognition of the central role of muscle mass in predicting clinical outcomes in patients with liver disease. Muscle size can be extracted from computed tomography (CT) scans, but clinical implementation will require increased automation. We hypothesize that we can achieve this by using artificial intelligence. METHODS:Using deep convolutional neural networks, we trained an algorithm on the Reference Analytic Morphomics Population (n = 5,268) and validated the automated methodology in an external cohort of adult kidney donors with a noncontrast CT scan (n = 1,655). To test the clinical usefulness, we examined its ability to predict clinical outcomes in a prospectively followed cohort of patients with clinically diagnosed cirrhosis (n = 254). RESULTS:Between the manual and automated methodologies, we found excellent inter-rater agreement with an intraclass correlation coefficient of 0.957 (confidence interval 0.953-0.961, P < 0.0001) in the adult kidney donor cohort. The calculated dice similarity coefficient was 0.932 ± 0.042, suggesting excellent spatial overlap between manual and automated methodologies. To assess the clinical usefulness, we examined its ability to predict clinical outcomes in a cirrhosis cohort and found that automated psoas muscle index was independently associated with mortality after adjusting for age, gender, and child's classification (P < 0.001). DISCUSSION:We demonstrated that deep learning techniques can allow for automation of muscle measurements on clinical CT scans in a diseased cohort. These automated psoas size measurements were predictive of mortality in patients with cirrhosis showing proof of principal that this methodology may allow for wider implementation in the clinical arena.
Low subcutaneous adiposity associates with higher mortality in female patients with cirrhosis.
Ebadi Maryam,Tandon Puneeta,Moctezuma-Velazquez Carlos,Ghosh Sunita,Baracos Vickie E,Mazurak Vera C,Montano-Loza Aldo J
Journal of hepatology
BACKGROUND & AIMS:Two major body compartments, skeletal muscle and adipose tissue, exhibit independent functions. We aimed to explore the prognostic significance of skeletal muscle, visceral and subcutaneous adipose tissue, according to sex, in patients with cirrhosis assessed for liver transplantation (LT). METHODS:CT images taken at the 3rd lumbar vertebra from 677 patients were quantified for three body composition indexes (cm/m), visceral adipose tissue index, subcutaneous adipose tissue index (SATI), and skeletal muscle index (SMI). Cox proportional and competing-risk analysis hazard models were conducted to assess associations between mortality and body composition. RESULTS:The majority of patients were male (67%) with a mean age of 57 ± 7 years, model for end-stage liver disease (MELD) score of 14 ± 8 and mean body mass index of 27 ± 6 kg/m. Despite similar body mass index between the sexes, male patients had greater SMI (53 ± 12 vs. 45 ± 9 cm/m), whereas SATI (67 ± 52 vs. 48 ± 37 cm/m) was higher in females (p <0.001 for each). In sex stratified multivariate analyses after adjustment for MELD score and other confounding variables, SATI in females (hazard ratio [HR] 0.99; 95% CI 0.98-1.00; p = 0.01) and SMI in males (HR 0.98; 95% CI 0.96-1.00; p = 0.02) were significant predictors of mortality. Female patients with low SATI (<60 cm/m) had a higher risk of mortality (HR 2.06; 95% CI 1.08-3.91; p = 0.03). Using competitive risk analysis in female patients listed for LT, low SATI was also an independent predictor of mortality (subdistribution HR 2.80; 95% CI 1.28-6.12; p = 0.01) after adjusting for MELD, and other confounding factors. CONCLUSIONS:A lower SATI is associated with higher mortality in female patients with cirrhosis. Subcutaneous adipose tissue has a favorable metabolic profile - low SATI may reflect depletion of this major energy reservoir, leading to poor clinical outcomes. LAY SUMMARY:We looked at the importance of two of the main body compartments, skeletal muscle and adipose tissue (fat) on the prognosis of males and females with end-stage liver disease. Lower amounts of subcutaneous fat but not visceral fat (around internal organs), are associated with higher mortality in female patients with end-stage liver disease. However, low skeletal muscle predicts mortality in male patients with end-stage liver disease.
Impact of sarcopenia on prognostic value of cirrhosis: going beyond the hepatic venous pressure gradient and MELD score.
Kang Seong Hee,Jeong Woo Kyoung,Baik Soon Koo,Cha Seung Hwan,Kim Moon Young
Journal of cachexia, sarcopenia and muscle
BACKGROUND:Sarcopenia has been reported as a prognostic factor. We evaluated the impact of sarcopenia to the conventional prognostic factors [Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, hepatic venous pressure gradient (HVPG)] in cirrhosis. METHODS:Overall, 452 patients with cirrhosis were stratified by MELD score (low < 15, high ≥ 15), CTP class, and HVPG [non-clinically significant portal hypertension (CSPH), 6-9 mmHg; CSPH, 10-19 mmHg; extremely severe PH, ≥20 mmHg]. L3 skeletal muscle index as marker of sarcopenia was subdivided into quartiles (47.01-52.25-58.22 cm /m ). RESULTS:Among the patients, 42% (190/452) presented with sarcopenia. During a median follow-up period of 21.2 months, sarcopenia was associated with mortality (adjusted hazard ratio = 2.253, P < 0.001) and specifically with compensated and early decompensated stages of cirrhosis, but not with advanced decompensated stages; low (P < 0.001) and high (P = 0.095) MELD scores; CTP classes A (P = 0.034), B (P < 0.001), and C (P = 0.205); and non-CSPH (P = 0.018), CSPH (P < 0.001), and extremely severe PH (P = 0.846). In quartiles of sarcopenia, MELD score, CTP class, and HVPG were independent predictors of mortality in non-sarcopenia, but not in severe sarcopenia (MELD, P = 0.182; CTP, P = 0.187; HVPG, P = 0.077). CONCLUSIONS:Sarcopenia is associated with mortality in compensated and early decompensated cirrhosis, and existing conventional prognostic factors had limited value in severe sarcopenia. Therefore, incorporating sarcopenia in the conventional prognostic factors had added value, particularly in compensated and early decompensated cirrhosis. Subclassification of prognostic factors according to sarcopenia may help to better assess the prognosis of cirrhosis.
Prognostic value of muscle atrophy in cirrhosis using psoas muscle thickness on computed tomography.
Durand François,Buyse Sophie,Francoz Claire,Laouénan Cédric,Bruno Onorina,Belghiti Jacques,Moreau Richard,Vilgrain Valérie,Valla Dominique
Journal of hepatology
BACKGROUND & AIMS: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. METHODS: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. RESULTS: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). CONCLUSIONS: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.
Relationship Between Relative Skeletal Muscle Mass and Nonalcoholic Fatty Liver Disease: A 7-Year Longitudinal Study.
Kim Gyuri,Lee Seung-Eun,Lee You-Bin,Jun Ji Eun,Ahn Jiyeon,Bae Ji Cheol,Jin Sang-Man,Hur Kyu Yeon,Jee Jae Hwan,Lee Moon-Kyu,Kim Jae Hyeon
Hepatology (Baltimore, Md.)
Nonalcoholic fatty liver disease (NAFLD) has been associated with relative skeletal muscle mass in several cross-sectional studies. We explored the effects of relative skeletal muscle mass and changes in relative muscle mass over time on the development of incident NAFLD or the resolution of baseline NAFLD in a large, longitudinal, population-based 7-year cohort study. We included 12,624 subjects without baseline NAFLD and 2943 subjects with baseline NAFLD who underwent health check-up examinations. A total of 10,534 subjects without baseline NAFLD and 2631 subjects with baseline NAFLD were included in analysis of changes in relative skeletal muscle mass over a year. Subjects were defined as having NAFLD by the hepatic steatosis index, a previously validated NAFLD prediction model. Relative skeletal muscle mass was presented using the skeletal muscle mass index (SMI), a measure of body weight-adjusted appendicular skeletal muscle mass, which was estimated by bioelectrical impedance analysis. Of the 12,624 subjects without baseline NAFLD, 1864 (14.8%) developed NAFLD during the 7-year follow-up period. Using Cox proportional hazard analysis, compared with the lowest sex-specific SMI tertile at baseline, the highest tertile was inversely associated with incident NAFLD (adjusted hazard ratio [AHR] = 0.44, 95% confidence interval [CI] = 0.38-0.51) and positively associated with the resolution of baseline NAFLD (AHR = 2.09, 95% CI = 1.02-4.28). Furthermore, compared with the lowest tertile of change in SMI over a year, the highest tertile exhibited a significant beneficial association with incident NAFLD (AHR = 0.69, 95% CI = 0.59-0.82) and resolution of baseline NAFLD (AHR = 4.17, 95% CI = 1.90-6.17) even after adjustment for baseline SMI. Conclusion: Increases in relative skeletal muscle mass over time may lead to benefits either in the development of NAFLD or the resolution of existing NAFLD.
Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis.
Praktiknjo Michael,Book Marius,Luetkens Julian,Pohlmann Alessandra,Meyer Carsten,Thomas Daniel,Jansen Christian,Feist Andreas,Chang Johannes,Grimm Jochen,Lehmann Jennifer,Strassburg Christian P,Abraldes Juan Gonzalez,Kukuk Guido,Trebicka Jonel
Hepatology (Baltimore, Md.)
Muscle mass seems to be a prognostic marker in patients with liver cirrhosis. However, reported methods to quantify muscle mass are heterogeneous, consented cutoff values are missing, and most studies have used computed tomography. This study evaluated fat-free muscle area (FFMA) as a marker of sarcopenia using magnetic resonance imaging (MRI) in patients with decompensated cirrhosis with transjugular intrahepatic portosystemic shunt (TIPS). The total erector spinae muscle area and the intramuscular fat tissue area were measured and subtracted to calculate the FFMA in 116 patients with cirrhosis by TIPS and MRI. The training cohort of 71 patients compared computed tomography-measured transversal psoas muscle thickness with FFMA. In 15 patients MRI was performed before and after TIPS, and in 12 patients follistatin serum measurements were carried out. The results on FFMA were confirmed in a validation cohort of 45 patients. FFMA correlated with follistatin and transversal psoas muscle thickness and showed slightly better association with survival than transversal psoas muscle thickness. Gender-specific cutoff values for FFMA were determined for sarcopenia. Decompensation (ascites, overt hepatic encephalopathy) persisted after TIPS in the sarcopenia group but resolved in the nonsarcopenia group. Sarcopenic patients showed no clinical improvement after TIPS as well as higher mortality, mainly due to development of acute-on-chronic liver failure. FFMA was an independent predictor of survival in these patients. CONCLUSION:This study offers an easy-to-apply MRI-based measurement of fat-free muscle mass as a marker of sarcopenia in decompensated patients; while TIPS might improve sarcopenia and thereby survival, persistence of sarcopenia after TIPS is associated with a reduced response to TIPS and a higher risk of acute-on-chronic liver failure development and mortality. (Hepatology 2018;67:1014-1026).
Muscle Alterations Are Associated With Minimal and Overt Hepatic Encephalopathy in Patients With Liver Cirrhosis.
Nardelli Silvia,Lattanzi Barbara,Merli Manuela,Farcomeni Alessio,Gioia Stefania,Ridola Lorenzo,Riggio Oliviero
Hepatology (Baltimore, Md.)
Muscle alterations (myosteatosis and sarcopenia) are frequent in cirrhosis and related to some complications including overt hepatic encephalopathy (HE). The aim of our study was to investigate the relationship between muscle alterations and minimal HE (MHE) and their role in the risk of overt HE. Sixty-four patients with cirrhosis were administered the Psychometric Hepatic Encephalopathy Score and animal naming test to detect MHE. Computed tomography was used to analyze the skeletal muscle index and attenuation. The incidence of the first episode of HE, taking into account the competing risk nature of the data, was estimated. Myosteatosis was observed in 24 patients (37.5%), sarcopenia in 37 (58%), and MHE in 32 (50%). Both myosteatosis (62.5% versus 12.5%, P < 0.001) and sarcopenia (84% versus 31%, P < 0.001) were more frequent in patients with MHE. The variables independently associated with the presence of MHE were sarcopenia, previous overt HE, and myosteatosis. Thirty-one (48%) patients developed overt HE over 16.1 ± 13 months; myosteatosis was detected in 68% and sarcopenia in 84% of them. Sarcopenia and myosteatosis were also independently associated with the development of overt HE. Venous ammonia was significantly higher in patients with sarcopenia (62.6 ± 17.7 versus 41.4 ± 16.1 μg/dL, P < 0.001) and in patients with myosteatosis (65.2 ± 19.2 versus 46.7 ± 17.1 μg/dL, P < 0.001) and inversely correlated to both parameters. Survival was significantly lower in malnourished patients compared to patients without myosteatosis or sarcopenia (P < 0.001). Conclusion: Myosteatosis and sarcopenia, probably by reducing the handling of ammonia in the muscle, are independently associated with MHE and the risk of overt HE in patients with cirrhosis; in malnourished patients, the amelioration of nutritional status may be a goal to decrease both the prevalence of MHE and the incidence of overt HE.
Relationship between sarcopenia and nonalcoholic fatty liver disease: the Korean Sarcopenic Obesity Study.
Hong Ho Cheol,Hwang Soon Young,Choi Hae Yoon,Yoo Hye Jin,Seo Ji A,Kim Sin Gon,Kim Nan Hee,Baik Sei Hyun,Choi Dong Seop,Choi Kyung Mook
Hepatology (Baltimore, Md.)
UNLABELLED:Previous studies have shown that nonalcoholic fatty liver disease (NAFLD) and sarcopenia may share pathophysiological mechanisms, such as insulin resistance, inflammation, vitamin D deficiency, and decreased physical activity. However, their direct relationship has not been investigated. The association between NAFLD and sarcopenia was examined in 452 apparently healthy adults enrolled in the Korean Sarcopenic Obesity Study (KSOS), an ongoing prospective observational cohort study. The liver attenuation index (LAI), which was measured using abdominal computed tomography (CT), was used as a parameter for the diagnosis of NAFLD. Sarcopenia was defined using a skeletal muscle mass index (SMI) [SMI (%) = total skeletal muscle mass (kg) / weight (kg) × 100] that was measured by dual energy X-ray absorptiometry (DXA). After adjusting for age and sex, both SMI and LAI were negatively correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) (P < 0.001) and high sensitivity C-reactive protein (hsCRP) (P < 0.001) as well as brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness. Furthermore, SMI and LAI had positive relationships with high-density lipoprotein (HDL)-cholesterol, but both had a negative relationship with triglyceride, alanine aminotransferase (ALT), and total body fat. In a multiple logistic regression analysis, the odds ratio for NAFLD risk was 5.16 (95% confidence interval [CI] = 1.63-16.33) in the lowest quartile of SMI compared to the highest after adjusting for potential confounding factors. CONCLUSION:Individuals with lower muscle mass exhibited increased risk of NAFLD. This result may provide a novel insight into the mechanism linking between sarcopenia and NAFLD. (Clinical trial no. NCT01594710.)
Sarcopenia is associated with significant liver fibrosis independently of obesity and insulin resistance in nonalcoholic fatty liver disease: Nationwide surveys (KNHANES 2008-2011).
Lee Yong-ho,Kim Seung Up,Song Kijun,Park Jun Yong,Kim Do Young,Ahn Sang Hoon,Lee Byung-Wan,Kang Eun Seok,Cha Bong-Soo,Han Kwang-Hyub
Hepatology (Baltimore, Md.)
UNLABELLED:Sarcopenia is associated with nonalcoholic fatty liver disease (NAFLD). This study investigated whether sarcopenia is associated with significant liver fibrosis in subjects with NAFLD. Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 database were analyzed. NALFD was defined by NAFLD liver fat score, comprehensive NAFLD score, or hepatic steatosis index. Degree of liver fibrosis was assessed by NAFLD fibrosis score (NFS), FIB-4, and Forns index. Significant liver fibrosis was defined as FIB-4 ≥2.67 and the highest quartile values of NFS and Forns index. Sarcopenia index (= total appendicular skeletal muscle mass [kg]/body mass index (kg/m(2) ]) was calculated using dual-energy X-ray absorptiometry. Using the NAFLD liver fat score, NAFLD was identified in 2761 (28.5%) of 9676 subjects. Of subjects with NAFLD, sarcopenia was identified in 337 (12.2%). Sarcopenia was significantly associated with significant liver fibrosis assessed in fibrosis prediction models (all P < 0.05). In subgroups stratified according to body mass index and homeostasis model assessment of insulin resistance, a significant association between sarcopenia and significant liver fibrosis by NFS was consistently present (odds ratio = 1.76-2.68 depending on the subgroup, all P < 0.05). Multivariate logistic regression analysis demonstrated an independent association between SI and significant liver fibrosis by NFS after adjusting for other confounders (odds ratio = 0.52-0.67, all P < 0.01). Other NAFLD (comprehensive NAFLD score, hepatic steatosis index) and fibrosis prediction models (FIB-4 and Forns index) produced similar results. CONCLUSION:Sarcopenia is associated with significant liver fibrosis in subjects with NAFLD, and the association is independent of obesity and insulin resistance.
Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis.
Koo Bo Kyung,Kim Donghee,Joo Sae Kyung,Kim Jung Ho,Chang Mee Soo,Kim Byeong Gwan,Lee Kook Lae,Kim Won
Journal of hepatology
BACKGROUND & AIMS:We explored whether sarcopenia is associated with the histological severity of non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) and significant fibrosis. METHODS:In a biopsy-proven NAFLD cohort, the appendicular skeletal muscle mass (ASM) was measured. Sarcopenia was defined as a ASM/body weight (ASM%) value beyond two standard deviations below the mean for healthy young adults. RESULTS:Among the entire set of 309 subjects, the prevalence of sarcopenia in subjects without NAFLD, with non-alcoholic fatty liver (NAFL), and with NASH were 8.7%, 17.9%, and 35.0%, respectively (p<0.001). ASM% was inversely correlated with the severity of fibrosis (p<0.001), and the prevalence of significant fibrosis (⩾F2) was higher in subjects with sarcopenia than in those without (45.7% vs. 24.7%; p<0.001). A crude analysis revealed that sarcopenia was associated with NAFLD (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.58-9.25), which became insignificant after adjustment for body mass index (BMI), diabetes, and hypertension. Among NAFLD subjects, subjects with sarcopenia were more likely to have NASH than those without sarcopenia through a multivariate analysis adjusted for age, gender, BMI, hypertension, diabetes, and smoking status (OR, 2.28; 95% CI, 1.21-4.30), and this finding was obtained even after adjustment for insulin resistance (OR, 2.30; 95% CI, 1.08-4.93). Sarcopenia was also associated with significant fibrosis independent of BMI and insulin resistance (OR, 2.05; 95% CI, 1.01-4.16). CONCLUSIONS:In this large biopsy-proven NAFLD cohort, sarcopenia was significantly associated with NASH and significant fibrosis. LAY SUMMARY:Low muscle mass was found to be associated with histological severity in non-alcoholic fatty liver disease, and sarcopenia was significantly associated with non-alcoholic steatohepatitis and significant fibrosis, independent of obesity, inflammation, and insulin resistance. Clinical trial number: NCT 02206841.
Sarcopenia in hiding: The risk and consequence of underestimating muscle dysfunction in nonalcoholic steatohepatitis.
Bhanji Rahima A,Narayanan Praveena,Allen Alina M,Malhi Harmeet,Watt Kymberly D
Hepatology (Baltimore, Md.)
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Up to one third of individuals with NAFLD will develop nonalcoholic steatohepatitis (NASH), which is associated with progression to cirrhosis and is rapidly becoming the leading indication for liver transplantation. Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass, strength, and function. It is observed in up to 60% of patients with end-stage liver disease and portends a poor prognosis. Recent studies have shown that sarcopenia is a novel risk factor for developing NAFLD. Pathophysiological mechanisms relating sarcopenia and NASH may include insulin resistance (IR) and increased inflammation. IR leads to accumulation of triglycerides in both muscle tissue and the liver. It also exacerbates proteolysis and leads to muscle depletion. Chronic inflammation leads to liver injury and progression of fibrosis. The inflammatory milieu also stimulates protein catabolism. Viewing skeletal muscle as an endocrine organ that secretes various salutary myokines may help us understand its role in the development of steatosis. A better understanding of the pathophysiology will aid in developing physical and pharmacological therapeutic interventions. In this review, we will explore the complex inter-relationships between sarcopenia and NASH. We will discuss the impact of sarcopenia in patients with NASH and therapeutic options for the management of sarcopenia. (Hepatology 2017;66:2055-2065).
Sarcopenia in Cirrhosis: Looking Beyond the Skeletal Muscle Loss to See the Systemic Disease.
Bhanji Rahima A,Montano-Loza Aldo J,Watt Kymberly D
Hepatology (Baltimore, Md.)
Sarcopenia is a common complication of cirrhosis and is defined as a progressive and generalized loss of skeletal muscle mass, strength, and function. Sarcopenia is associated with poor prognosis and increased mortality. How sarcopenia and muscle wasting relate to such poor outcomes requires looking beyond the overt muscle loss and at this entity as a systemic disease that affects muscles of vital organs including cardiac and respiratory muscles. This review explores the pathophysiological pathways and mechanisms that culminate in poor outcomes associated with sarcopenia. This provides a launching pad to identify potential targets for therapeutic intervention and optimization to improve patient outcomes.
A North American Expert Opinion Statement on Sarcopenia in Liver Transplantation.
Carey Elizabeth J,Lai Jennifer C,Sonnenday Christopher,Tapper Elliot B,Tandon Puneeta,Duarte-Rojo Andres,Dunn Michael A,Tsien Cynthia,Kallwitz Eric R,Ng Vicky,Dasarathy Srinivasan,Kappus Matthew,Bashir Mustafa R,Montano-Loza Aldo J
Hepatology (Baltimore, Md.)
Loss of muscle mass and function, or sarcopenia, is a common feature of cirrhosis and contributes significantly to morbidity and mortality in this population. Sarcopenia is a main indicator of adverse outcomes in this population, including poor quality of life, hepatic decompensation, mortality in patients with cirrhosis evaluated for liver transplantation (LT), longer hospital and intensive care unit stay, higher incidence of infection following LT, and higher overall health care cost. Although it is clear that muscle mass is an important predictor of LT outcomes, many questions remain, including the best modality for assessing muscle mass, the optimal cut-off values for sarcopenia, the ideal timing and frequency of muscle mass assessment, and how to best incorporate the concept of sarcopenia into clinical decision making. For these reasons, we assembled a group of experts to form the North American Working Group on Sarcopenia in Liver Transplantation to use evidence from the medical literature to address these outstanding questions regarding sarcopenia in LT. We believe sarcopenia assessment should be considered in all patients with cirrhosis evaluated for liver transplantation. Skeletal muscle index (SMI) assessed by computed tomography constitutes the best-studied technique for assessing sarcopenia in patients with cirrhosis. Cut-off values for sarcopenia, defined as SMI < 50 cm /m in male and < 39 cm /m in female patients, constitute the validated definition for sarcopenia in patients with cirrhosis. Conclusion: The management of sarcopenia requires a multipronged approach including nutrition, exercise, and additional pharmacological therapy as deemed necessary. Future studies should evaluate whether recovery of sarcopenia with nutritional management in combination with an exercise program is sustainable as well as how improvement in muscle mass might be associated with improvement in clinical outcomes.