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Inclusion of Sarcopenia Within MELD (MELD-Sarcopenia) and the Prediction of Mortality in Patients With Cirrhosis.

Montano-Loza AJ, Duarte-Rojo A, Meza-Junco J, Baracos VE, Sawyer MB, Pang JX, Beaumont C, Esfandiari N, Myers RP - Clin Transl Gastroenterol (2015)

Bottom Line: By Cox regression analysis adjusted for age, gender, and hepatocellular carcinoma, both MELD (hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.06-1.10, P<0.001), and the L3 SMI (HR 0.97, 95% CI 0.96-0.99, P<0.001) were associated with mortality.The c-statistics for 3-month mortality in patients with MELD<15 (0.85 vs. 0.69, P=0.02) and refractory ascites (0.74 vs. 0.71, P=0.01) were significantly higher for MELD-sarcopenia compared with MELD.External validation of this prognostic index in larger cohorts of cirrhotic patients is warranted.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton, Alberta, Canada.

ABSTRACT

Objectives: Limitations of the Model for End-Stage Liver Disease (MELD) score include its failure to assess the nutritional and functional status of cirrhotic patients. Our objectives were to evaluate the impact of sarcopenia in cirrhosis and whether the inclusion of muscularity assessment within MELD could improve the prediction of mortality in patients with cirrhosis.

Methods: We included 669 cirrhotic patients who were consecutively evaluated for liver transplantation. Skeletal muscle index at the third lumbar vertebra (L3 SMI) was measured by computed tomography, and sarcopenia was defined using previously published gender and body mass index-specific cutoffs. Using Cox proportional hazards regression, a novel MELD-sarcopenia score was derived.

Results: Sarcopenia was present in 298 patients (45%); sarcopenic patients had shorter median survival than non-sarcopenic patients (20±3 vs. 95±24 months, P<0.001). By Cox regression analysis adjusted for age, gender, and hepatocellular carcinoma, both MELD (hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.06-1.10, P<0.001), and the L3 SMI (HR 0.97, 95% CI 0.96-0.99, P<0.001) were associated with mortality. Overall, the c-statistics for 3-month mortality were 0.82 (95% CI 0.78-0.87) for MELD and 0.85 (95% CI 0.81-0.88) for MELD-sarcopenia (P=0.1). Corresponding figures for 1-year mortality were 0.73 (95% CI 0.69-0.77) and 0.77 (95% CI 0.73-0.80), respectively (P=0.03). The c-statistics for 3-month mortality in patients with MELD<15 (0.85 vs. 0.69, P=0.02) and refractory ascites (0.74 vs. 0.71, P=0.01) were significantly higher for MELD-sarcopenia compared with MELD.

Conclusions: Modification of MELD to include sarcopenia is associated with improved prediction of mortality in patients with cirrhosis, primarily in patients with low MELD scores. External validation of this prognostic index in larger cohorts of cirrhotic patients is warranted.

No MeSH data available.


Related in: MedlinePlus

Comparison of two female patients with cirrhosis. Abdominal computed tomography images taken at third lumbar vertebra. Red color indicates skeletal muscle, green color indicates intermuscular adipose tissue, yellow color indicates visceral adipose tissue, and teal indicates subcutaneous adipose tissue. The patient at the left has severe sarcopenia (lumbar skeletal index, 35 cm2/m2) and the patient at the right is not sarcopenic (lumbar skeletal index, 54 cm2/m2).
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fig2: Comparison of two female patients with cirrhosis. Abdominal computed tomography images taken at third lumbar vertebra. Red color indicates skeletal muscle, green color indicates intermuscular adipose tissue, yellow color indicates visceral adipose tissue, and teal indicates subcutaneous adipose tissue. The patient at the left has severe sarcopenia (lumbar skeletal index, 35 cm2/m2) and the patient at the right is not sarcopenic (lumbar skeletal index, 54 cm2/m2).

Mentions: CT scans used for muscularity analysis were performed as part of the routine liver transplantation assessment. A transverse CT image from L3 was assessed from each scan. Images were analyzed with the SliceOmatic V4.3 software (Tomovision, Montreal, QC Canada), which enables specific tissue demarcation using previously reported Hounsfield unit (HU) thresholds.15 Skeletal muscle was identified and quantified using HU thresholds of −29 to +150. Muscles in the L3 region encompass psoas, erector spinae, quadratus lumborum, transversus abdominus, external and internal obliques, and rectus abdominus. The following HU thresholds were used for adipose tissues: −190 to −30 for subcutaneous and intermuscular adipose tissue,16 and −150 to −50 for visceral adipose tissue.17 Using these specific HU thresholds, measurements of the skeletal muscle index are not influenced by the presence of ascites, overweight, or obesity in patients with cirrhosis. Cross-sectional areas (cm2) were automatically computed by summing tissue pixels and multiplying by pixel surface area. All CT images were analyzed by two trained observers (C.B., N.E.) who demonstrated an intraobserver coefficient of variation of approximately 1%, and the sarcopenia assessment was blinded to MELD score. Cross-sectional area of muscle and adipose tissue was normalized for stature (cm2/m2) as reported elsewhere18 and this value is referred to as the L3 skeletal muscle index (L3 SMI). Sarcopenia was defined according to a CT-based study in patients with solid tumors using optimal stratification, a statistical method similar to receiver operating characteristic curve analysis that links specific threshold values for L3 SMI to an outcome (i.e., death) (L3 SMI: ≤41 cm2/m2 for women and ≤53 cm2/m2 for men with body mass index (BMI) ≥25 kg/m2 and ≤43 cm2/m2 in all patients with BMI<25 kg/m2.19 Representative images of two female cirrhotic patients with and without sarcopenia are illustrated in Figure 2.


Inclusion of Sarcopenia Within MELD (MELD-Sarcopenia) and the Prediction of Mortality in Patients With Cirrhosis.

Montano-Loza AJ, Duarte-Rojo A, Meza-Junco J, Baracos VE, Sawyer MB, Pang JX, Beaumont C, Esfandiari N, Myers RP - Clin Transl Gastroenterol (2015)

Comparison of two female patients with cirrhosis. Abdominal computed tomography images taken at third lumbar vertebra. Red color indicates skeletal muscle, green color indicates intermuscular adipose tissue, yellow color indicates visceral adipose tissue, and teal indicates subcutaneous adipose tissue. The patient at the left has severe sarcopenia (lumbar skeletal index, 35 cm2/m2) and the patient at the right is not sarcopenic (lumbar skeletal index, 54 cm2/m2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4816259&req=5

fig2: Comparison of two female patients with cirrhosis. Abdominal computed tomography images taken at third lumbar vertebra. Red color indicates skeletal muscle, green color indicates intermuscular adipose tissue, yellow color indicates visceral adipose tissue, and teal indicates subcutaneous adipose tissue. The patient at the left has severe sarcopenia (lumbar skeletal index, 35 cm2/m2) and the patient at the right is not sarcopenic (lumbar skeletal index, 54 cm2/m2).
Mentions: CT scans used for muscularity analysis were performed as part of the routine liver transplantation assessment. A transverse CT image from L3 was assessed from each scan. Images were analyzed with the SliceOmatic V4.3 software (Tomovision, Montreal, QC Canada), which enables specific tissue demarcation using previously reported Hounsfield unit (HU) thresholds.15 Skeletal muscle was identified and quantified using HU thresholds of −29 to +150. Muscles in the L3 region encompass psoas, erector spinae, quadratus lumborum, transversus abdominus, external and internal obliques, and rectus abdominus. The following HU thresholds were used for adipose tissues: −190 to −30 for subcutaneous and intermuscular adipose tissue,16 and −150 to −50 for visceral adipose tissue.17 Using these specific HU thresholds, measurements of the skeletal muscle index are not influenced by the presence of ascites, overweight, or obesity in patients with cirrhosis. Cross-sectional areas (cm2) were automatically computed by summing tissue pixels and multiplying by pixel surface area. All CT images were analyzed by two trained observers (C.B., N.E.) who demonstrated an intraobserver coefficient of variation of approximately 1%, and the sarcopenia assessment was blinded to MELD score. Cross-sectional area of muscle and adipose tissue was normalized for stature (cm2/m2) as reported elsewhere18 and this value is referred to as the L3 skeletal muscle index (L3 SMI). Sarcopenia was defined according to a CT-based study in patients with solid tumors using optimal stratification, a statistical method similar to receiver operating characteristic curve analysis that links specific threshold values for L3 SMI to an outcome (i.e., death) (L3 SMI: ≤41 cm2/m2 for women and ≤53 cm2/m2 for men with body mass index (BMI) ≥25 kg/m2 and ≤43 cm2/m2 in all patients with BMI<25 kg/m2.19 Representative images of two female cirrhotic patients with and without sarcopenia are illustrated in Figure 2.

Bottom Line: By Cox regression analysis adjusted for age, gender, and hepatocellular carcinoma, both MELD (hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.06-1.10, P<0.001), and the L3 SMI (HR 0.97, 95% CI 0.96-0.99, P<0.001) were associated with mortality.The c-statistics for 3-month mortality in patients with MELD<15 (0.85 vs. 0.69, P=0.02) and refractory ascites (0.74 vs. 0.71, P=0.01) were significantly higher for MELD-sarcopenia compared with MELD.External validation of this prognostic index in larger cohorts of cirrhotic patients is warranted.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton, Alberta, Canada.

ABSTRACT

Objectives: Limitations of the Model for End-Stage Liver Disease (MELD) score include its failure to assess the nutritional and functional status of cirrhotic patients. Our objectives were to evaluate the impact of sarcopenia in cirrhosis and whether the inclusion of muscularity assessment within MELD could improve the prediction of mortality in patients with cirrhosis.

Methods: We included 669 cirrhotic patients who were consecutively evaluated for liver transplantation. Skeletal muscle index at the third lumbar vertebra (L3 SMI) was measured by computed tomography, and sarcopenia was defined using previously published gender and body mass index-specific cutoffs. Using Cox proportional hazards regression, a novel MELD-sarcopenia score was derived.

Results: Sarcopenia was present in 298 patients (45%); sarcopenic patients had shorter median survival than non-sarcopenic patients (20±3 vs. 95±24 months, P<0.001). By Cox regression analysis adjusted for age, gender, and hepatocellular carcinoma, both MELD (hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.06-1.10, P<0.001), and the L3 SMI (HR 0.97, 95% CI 0.96-0.99, P<0.001) were associated with mortality. Overall, the c-statistics for 3-month mortality were 0.82 (95% CI 0.78-0.87) for MELD and 0.85 (95% CI 0.81-0.88) for MELD-sarcopenia (P=0.1). Corresponding figures for 1-year mortality were 0.73 (95% CI 0.69-0.77) and 0.77 (95% CI 0.73-0.80), respectively (P=0.03). The c-statistics for 3-month mortality in patients with MELD<15 (0.85 vs. 0.69, P=0.02) and refractory ascites (0.74 vs. 0.71, P=0.01) were significantly higher for MELD-sarcopenia compared with MELD.

Conclusions: Modification of MELD to include sarcopenia is associated with improved prediction of mortality in patients with cirrhosis, primarily in patients with low MELD scores. External validation of this prognostic index in larger cohorts of cirrhotic patients is warranted.

No MeSH data available.


Related in: MedlinePlus