Abstract
Background
Sarcopenia is often ignored in clinical practice despite being an important prognostic marker. SARC-F is a simple bedside score to assess muscle abnormalities in cirrhosis patients. However, there is limited Indian data on the validity of this score. Hence, we aimed to assess the validity of SARC-F score in a tertiary care center.
Methods
A prospective observational study including consecutive 100 cirrhosis patients attending the gastroenterology outpatient department in Osmania Medical College and Hospital, Hyderabad, India, was conducted from Jan 2018 to Dec 2019. The primary aim was to assess the mean muscle volume loss (MVL) by computed tomography and handgrip (HG) strength for muscle strength decline (MSD) and compare the SARC-F score with standard cut-off values.
Results
We included 100 cirrhosis patients (mean age: 45 years; males: 86%; child-pugh class B/C: 42/58). Sixty-nine percent of the patients had a SARC-F score of ≥4, whereas MVL and MSD were noted in 62% and 86% patients, respectively. Mid-arm circumference, skin-fold thickness, mid-arm muscle circumference (MAMC), and HG strength were significantly lower in patients with SARC-F score ≥4 than in those with SARC-F score <4 (P < 0.05). The Pearson correlation plot suggested a significant inverse correlation between the SARC-F score and MSD and SARC-F score and MVL. A SARC-F score of ≥4 had a sensitivity and specificity of 80.7% and 50% for MVL and 75.6% and 71.4% for MSD, respectively, whereas it was 83.3% and 52.5% for MSD and MVL combined, respectively. Area under the receiver operating characteristic curve for SARC-F as a predictor of MVL was 0.75 (95% confidence interval: 0.64–0.82; P=<0.001). On multivariate analysis, a high SARC-F score and low MAMC were predictive of MVL in cirrhosis patients.
Conclusion
SARC-F score has good sensitivity as a bedside screening tool for sarcopenia in patients with cirrhosis. A high SARC-F score and low MAMC indicates the presence of MVL and warrants further evaluation for sarcopenia.
Keywords: cirrhosis, sarcopenia, SARC-F score, chronic liver disease, mid-arm muscle circumference
Graphical abstract
Sarcopenia is a clinical indicator of malnutrition and is widely recognized as an independent predictor of prognosis and mortality risk.1 The prevalence of sarcopenia in cirrhosis is variable, ranging from 40% in early stages to 70% in advanced stages of cirrhosis.2 Patients with low Model for End-stage liver disease (MELD) score and sarcopenia have similar clinical outcome as patients with high MELD score with or without sarcopenia. The lack of inclusion of nutritional status and disabilities of the patients has been found to be the most common and consistently reported limitation of the MELD score. The MELD sarcopenia score, proposed in a recent study, was found superior to the MELD score but is yet to be validated.3
Sarcopenia is a preferred indicator to assess the nutritional status as it can be assessed objectively. Sarcopenia assessment involves measurements of muscle mass, muscle strength, and muscle function. Computed tomography (CT) scan is a precise and gold standard test to evaluate and diagnose skeletal muscle abnormalities objectively. CT-assisted measurement of cross-sectional area of the psoas major muscle at the third lumbar vertebra L3 is a strong indicator of whole-body muscle mass.4
The use of dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and computed tomography (CT) for sarcopenia assessment has been limited due to patient inconvenience, high costs, and/or radiological characteristics. To combat these difficulties and to identify sarcopenia in the early stages, simple, sensitive, and cost-effective screening tools are required. These tools have the potential to assist clinicians in the convenient bedside diagnosis of sarcopenia.
Muscle mass loss with a clear symptom as weakness can be assessed clinically, unlike bone loss, which cannot be assessed clinically. “SARC-F is one such score with a five-component questionnaire: (S) strength, (A) assistance while walking, (R) rise from a chair, (C) climb stairs, and (F) falls”. Various components of the SARC-F questionnaire assess muscular function and strength by using self-reported information regarding disabilities in day-to-day activities due to sarcopenia. The SARC-F score ranges from 0 to 10 (i.e., each component is graded from 0 to 2; the total score ranges from 0 = best to 10 = worst) and was dichotomized to represent symptomatic (≥4) vs healthy (0–3) status.1 The score was validated initially in the ≥60-year age group, who have age-related sarcopenia, but has not been widely used in cirrhosis patients. The aim of the present study was to evaluate the role of SARC-F score in screening of cirrhosis patients for muscle abnormalities.
METHODOLOGY
Ethical approval
The study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Osmania Medical College and Hospital, Hyderabad on 02-04-2018 (Registration number ECR/300/Inst/AP/2013/RR-16)
Patient consent
Informed consent was taken from all patients enrolled in the study.
A prospective observational study including consecutive 100 cirrhosis patients was conducted in the outpatient Department of Gastroenterology, Osmania Medical College and Hospital, Hyderabad, from Jan 2018 to Dec 2019, with prior approval from the Institute Human Ethics Committee. In the present study, no formal sample size calculation was done as it was a pilot study.
Inclusion Criteria
-
a)
Age: 18–60 years.
-
b)
Patients with cirrhosis due to any etiology (hepatitis B virus (HBV) infection/hepatitis C virus (HCV) infection/alcohol/nonalcoholic steatohepatitis (NASH)/autoimmune/primary sclerosing cholangitis/primary biliary cholangitis/alpha-1 anti-trypsin deficiency/Wilson disease/cryptogenic) were enrolled in the study.
Exclusion Criteria
-
a)
Acute on chronic liver failure.
-
b)
Acute liver failure.
-
c)
Active malignant disease.
-
d)
Hepatocellular carcinoma.
-
e)
Renal failure.
-
f)
Congestive heart failure.
-
g)
End-stage chronic obstructive lung disease.
-
h)
Neuromuscular disorder.
Evaluation of Liver Disease
Diagnosis of cirrhosis was based on standard clinical, biochemical parameters, imaging examination, or endoscopic evidence of varices. Each patient underwent investigations including complete blood count, liver function tests, renal function, electrolytes, international normalized ratio (INR), viral screening, and noncontrast CT abdomen. Height, weight, and body mass index (BMI) were also recorded for each patient. The liver disease severity was evaluated according to the Child–Turcotte–Pugh classification (CTP score)5 and MELD score.6
Evaluation of Muscle Strength
The measurement for mid-arm circumference (MAC) was done at the midpoint between the tip of the acromion and the olecranon process on the nondominant side of the body using a flexible tape measure. The measurement of triceps skinfold thickness (TSF) was conducted on the nondominant side of the participants. This was done in a comfortable standing position, utilizing the Harpenden skinfold caliper (British Indicators Ltd., West Sussex, UK). A standard equation was used to measure mid-arm muscle circumference (MAMC) (MAMC = MAC - [3.1415 × TSF]). Handgrip (HG) strength is a simple and inexpensive tool to assess sarcopenia in patients with cirrhosis.7,8,9 The measurement of HG strength was done using a standard digital dynamometer in the nondominant hand (Takei Scientific Instruments Co., LTD, Japan). The maximum grip strength was determined by selecting the best of three consistent readings, with approximately 1 min of rest time between each reading. The cut-off levels for muscle strength decline (MSD) were defined as <26 kilograms for men and <18 kilograms for women.7,10
Evaluation of Muscle Mass
The measurement of skeletal muscle index (SMI) requires dedicated software, whereas psoas muscle area can be calculated manually. The available literature suggests that psoas muscle area or psoas muscle index (psoas muscle area divided by height squared) correlates well with SMI.11,12 A research on Indian patients with alcoholic cirrhosis determined the cut-offs for SMI to be 36.5 cm2/m2 and 30.2 cm2/m2 in males and females, respectively.13 Muscle mass measurement can be done by CT scan or by bioelectrical impedance analysis (BIA). We measured the lumbar skeletal muscle cross-sectional area by noncontrast CT scan at the L3 vertebra using the psoas muscle manually. All measurements were performed on the right psoas muscle. Lengths of major and minor axes of the psoas muscle were measured at the caudal end of the third lumbar vertebra. Psoas muscle area was calculated using the formula:
where a and b are the radii of the major and minor axes, respectively. The threshold for muscle volume loss (MVL) was defined as 800 cm2 for men and 380 cm2 for women in the present study.4
SARC-F Questionnaire
The SARC-F score constitutes five components: strength, assistance walking, rise from a chair, climb stairs, and falls. The SARC-F items indicate changes in health status associated with sarcopenia. Scores on the SARC-F scale range from 0 to 10 (0–2 points for each component; 0 = best to 10 = worst). Scores of ≥4 represent symptomatic status, whereas scores of 0–3 represent healthy status. Strength can be assessed by inquiring about the level of difficulty experienced when attempting to lift a weight of 10 pounds (0 = no difficulty, 1 = some, and 2 = a lot or unable to do). The evaluation of assistance walking involves inquiring about patients' level of difficulty when walking across a room and whether they rely on any form of assistance to accomplish this task (0 = no difficulty, 1 = some difficulty, and 2 = a lot of difficulty, use aids, or unable to do without personal help). The assessment of rising from a chair is conducted by inquiring about the level of difficulty experienced by patients while transitioning from a chair or bed and whether they rely on assistive devices or assistance from others to accomplish this task (0 = no difficulty, 1 = some difficulty, and 2 = a lot of difficulty, use aids, or unable to do without help). The assessment of stair-climbing ability involves the quantification of patients' perceived level of difficulty in ascending a set of 10 steps (0 = no difficulty, 1 = some, and 2 = a lot or unable to do). Participants who report that they have had falling incidents four or more times within the previous year are assigned a score of 2. Those who report falling incidents between one and three times within the previous year are assigned a score of 1. Participants who report no falling incidents within the previous year are assigned a score of 0.14
Statistical Analysis
The data were analyzed using SPSS 22 version software (IBM SPSS Statistics, Somers NY, USA). Continuous data were typically represented using the measures of central tendency, such as the mean, and the measure of dispersion, such as the standard deviation. The independent t-test was used to compare the means between two quantitative variables. Categorical data were represented using frequencies and proportions. The Chi-square test or Fischer's exact test (limited to 2 × 2 tables) was used as a statistical tool to determine the importance of qualitative data. Correlations were performed with Pearson correlation coefficient. A multvariate analysis was done using male gender, age, SARC-F score, MELD score, MAMC, and platelet count as variables. A P-value of less than 0.05 was deemed to be statistically significant, following adherence to all the principles of statistical testing.
RESULTS
The baseline clinical characteristics of patients are summarized in Table 1. Out of 100 patients, 86 were male and 14 females. Majority of the patients were in the 30–39-year age group (35%) and 40–49-year age group (33%). The most common etiology for cirrhosis was alcohol (80%) followed by hepatitis B (8%) infection, hepatitis C (8%) infection, and other etiologies (NASH/cryptogenic [4%]). Forty-two patients had CTP class B cirrhosis, 58 patients had CTP class C cirrhosis, whereas none of the patients had CTP class A cirrhosis. A SARC-F score of ≥4 was noted in 69 (69%) patients; MSD was noted in 74 (86%) males and 12 (85.7%) females, whereas MVL was noted in 54 (62%) males and 8 (57.1%) females. The mean BMI of patients was 21.3 (4.3) kg/m2, mean bilirubin: 4.6 (3.9) mg/dL, albumin: 2.8 (0.4) g/dL, international normalized ratio (INR): 1.7 (0.8), platelet count: 1.4 (0.8) × 105/μl, and ALT was 45.8 (29.9) U/L. (Table 1)
Table 1.
Baseline Clinical Characteristics of Patients.
| Characteristic | Number/mean (SD) |
|---|---|
| Age (years): 30–39:40–49:50–59:60–69 | 35:33:22:10 |
| Sex (n) male:female | 86:14 |
| Etiology (n) alcohol: HCV:HBV:others | 80:8:8:4 |
| CTP class (n) A:B:C | 0:42:58 |
| SARC-F score (n) <4:≥4 | 31:69 |
| Muscle volume loss—male:female (n) | 54 (62.8%):8 (57.1%) |
| Muscle strength decline—male:female (n) | 74 (86.1 %):12 (85.7 %) |
| Body mass index—kg/m2 | 21.3 (4.3) |
| Bilirubin, mg/dL | 4.6 (3.9) |
| Albumin, g/dL | 2.8 (0.4) |
| International normalized ratio | 1.7 (0.8) |
| Creatinine, mg/L | 1.2 (0.6) |
| Platelet count, 105/μl | 1.4 (0.8) |
| ALT, U/L | 45.8 (29.9) |
| AST, U/L | 49.7 (31.2) |
Abbreviations: ALT = alanine transaminase; AST = aspartate aminotransferase; HBV = hepatitis B virus; HCV = hepatitis C virus; SD = standard deviation.
There was no significant difference in mean age (44.9 ± 9.9 vs 40.8 ± 6.7; P = 0.13), gender distribution (males:females = 74:12 vs 12:2; P = 0.9), etiology of liver disease (alcohol:HCV:HBV:others = 68:8:8:2 vs 12:0:0:2; P = 0.9), CTP class (A:B:C = 0:36:50 vs 0:6:8; P = 0.9), INR (1.7 ± 0.9 vs 1.5 ± 0.5; P = 0.4), creatinine (1.2 ± 0.6 vs 1.1 ± 0.3; P = 0.5), and platelet count: 105/μlg (1.5 ± 0.8 vs 1.4 ± 0.8; P = 0.7) between patients with and without MSD. A total of 75.6% patients had a SARC-F score of ≥4 in patients with MSD as compared to 28.6% patients in those without MSD (P = 0.0002). MVL was more common in patients with MSD than in those without (69.8% vs 14.3 % respectively; P = 0.0006). As expected, the mean albumin level was significantly lower (P = 0.005) in patients with MSD. The mean alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were also lower in patients with MSD (40.5 ± 24.9 vs 76.3 ± 38.1; P =< 0.0001 and 45.4 ± 24.2 vs 81.8 ± 33.9; P =< 0.0001 respectively) than in patients without MSD (Table 2).
Table 2.
Comparison of Baseline Parameters Among Patients With and Without Muscle Strength Decline.
| MSD + (n = 86) | MSD (n = 14) | P value | |
|---|---|---|---|
| Age (years) | 44.9 (9.9) | 40.8 (6.7) | 0.13 |
| Gender (n) male:female | 74:12 | 12:2 | 0.9 |
| Etiology (n)- alcohol:HCV:HBV:others | 68:8:8:2 | 12:0:0:2 | 0.9 |
| CTP class (n) A:B:C | 0:36:50 | 0:6:8 | 0.9 |
| SARC-F score (n) <4:≥4 | 21:65 | 10:4 | <0.001 |
| Muscle volume loss male:female (n) | 52:8 | 2:0 | <0.001 |
| Body mass index kg/m2 male:female | 21.2 (4.5):19.2 (1.5) | 23.3(4.3):27.8(0.1) | 0.1; <0.001 |
| Total bilirubin, mg/dL | 4.2 (3.8) | 7.6 (4.2) | 0.002 |
| Albumin, g/dL | 2.8 (0.5) | 3.2 (0.4) | 0.005 |
| INR | 1.7 (0.9) | 1.5 (0.5) | 0.4 |
| Creatinine, mg/L | 1.2 (0.6) | 1.1 (0.3) | 0.5 |
| Platelet count, 105/μl | 1.5 (0.8) | 1.4 (0.8) | 0.7 |
| ALT, U/L | 40.5 (24.9) | 76.3 (38.1) | <0.001 |
| AST, U/L | 45.4 (24.2) | 81.8 (33.9) | <0.001 |
Abbreviations: ALT = alanine transaminase; AST = aspartate aminotransferase; CTP = Child–Turcotte–Pugh classification; HBV = hepatitis B virus; HCV = hepatitis C virus; SD = standard deviation; INR = international normalized ratio; MSD = muscle strength decline; SARC-F = (S) strength, (A) assistance while walking, (R) rise from a chair, (C) climb stairs, and (F) falls.
Bold numbers indicates statistically significant values.
We also compared the baseline clinical characteristics among patients with SARC-F score ≥4 and those with SARC-F score <4. Mean age was found to be significantly higher in patients with a SARC-F score ≥4 (P = 0.0001). Other variables including gender, etiology of cirrhosis, and CTP class were similar in both the groups. As expected, the mean BMI in patients having a SARC F score ≥4 area was less than that of those with SARC-F score <4 in both males and females (20.7 ± 4.4 kg/m2 vs 22.59 ± 4.0 kg/m2; P = 0.04 in males and 19.3 ± 1.7 kg/m2 vs 22.4 ± 4.3 kg/m2; P = 0.0001 in females). The MAC, SFT, MAMC, and HG strength were all found to be significantly lower in patients with SARC-F score ≥4 than in those with SARC-F score <4 (P =< 0.05). Biochemical parameters including total bilirubin, albumin, ALT, AST, INR, and creatinine were similar in both the groups. Platelet count was significantly higher in patients with SARC-F score ≥4 than in those with SARC-F score <4 (Table 3).
Table 3.
Comparison of Various Parameters Among Patients With SARC-F Score ≥4 and SARC-F Score <4.
| SARC-F score ≥4 (n = 69) | SARC-F score <4 (n = 31) | P value | |
|---|---|---|---|
| Age (years) | 45.5 (1.1) | 42.1 (1.7) | 0.0001 |
| Gender (n) male:female | 60:9 | 26:5 | 0.7 |
| Etiology (n) alcohol:HCV:HBV:others | 56:7:6:0 | 24:1:2:4 | 0.6 |
| CTP class (n)- A:B:C | 0:26:43 | 0:16:15 | 0.19 |
| MVL—male:female [n (%)] | 42(70%): 8(88.9%) | 12(46.2): 0(0%) | 0.03; 0.002 |
| Body Mass Index—kg/m2 male:female | 20.7(4.4): 19.3 (1.7) | 22.6(4.0): 22.4(4.3) | 0.04; 0.0001 |
| MAC (inches) | 8.2 (1.5) | 9.3 (1.3) | <0.001 |
| Skin-fold thickness (mm) | 8 (5) | 13 (9) | <0.001 |
| MAMC (cms) | 17.8 (2.7) | 19.1 (1.7) | 0.01 |
| Hand-grip strength (Kg) | 9 (9) | 18 (11) | 0.0001 |
| Total bilirubin, mg/dL | 4.3 (3.8) | 5.3 (4.5) | 0.3 |
| Albumin, g/dL | 2.9 (0.5) | 2.8 (0.5) | 0.3 |
| INR | 1.8 (0.9) | 1.5 (0.5) | 0.1 |
| Creatinine, mg/L | 1.2 (0.6) | 1.2 (0.4) | 0.7 |
| Platelet count, 105/μl | 1.6 (0.8) | 1.1 (0.7) | 0.004 |
| ALT, U/L | 45 (30) | 48 (31) | 0.6 |
| AST, U/L | 49 (31) | 46 (29) | 0.6 |
CTP = Child–Turcotte–Pugh classification; MVL = muscle volume Loss; MAC = mid-arm circumference; MAMC = mid-arm muscle circumference; INR = international normalized ration; ALT = alanine transaminase; AST = aspartate aminotransferase; HBV = hepatitis B virus; HCV = hepatitis C virus; SARC-F = (S) strength, (A) assistance while walking, (R) rise from a chair, (C) climb stairs, and (F) falls.
Bold numbers indicates statistically significant values.
There was no significant difference in MVL (57.1% [n = 8/14] vs 62.8% [n = 54/86]; P = 0.8) and MSD (85.7% [n = 12/14] vs 86% [n = 74/86]; P = 1) in females and males respectively. There was significant correlation between MSD and MVL in males (P = 0.0004), whereas it was nonsignificant in females (P = 0.07). A total of 60 % (n = 48/80) of the alcohol-related cirrhosis had MVL, whereas all patients (n = 20/20) with HBV/HCV and other cause of cirrhosis had MVL (P = 0.0006). On receiver operating characteristic (ROC) curve analysis, the sensitivity and specificity of a SARC-F score ≥4 for MSD was found to be 75.6% and 71.4%, respectively, with a positive predictive value (PPV) of 94.2% and negative predictive value (NPV) of 32.3%. The sensitivity and specificity of SARC-F score ≥4 in males for MVL was 100% and 83.3%, respectively, and those for MSD were 75% and 100%, respectively. The sensitivity and specificity of SARC-F score ≥4 for MVL for females were 75% and 46.7%, respectively, and those for MSD were 77.8% and 71.4%, respectively. The sensitivity and specificity of SARC-F score for MVL with a cut-off ≥4 were found to be 80.7% and 50.0%, respectively (PPV: 72.5%, NPV: 61.3%). The sensitivity, specificity PPV, and NPV for combined MSD and MVL were 83.3%, 52.5%, 72.5%, and 67.7%, respectively. All the five variables of the SARC-F score were more common in patients having MVL compared to those with no MVL, with a statistically significant P-value of ≤0.05 (Table 4).
Table 4.
Sensitivity, Specificity, PPV, and NPV of SARC-F Score With Cut-off ≥4 for MVL and MSD.
| Sensitivity | Specificity | PPV | NPV | |
|---|---|---|---|---|
| MVL | 80.7% | 50.0% | 72.5% | 61.3% |
| MSD | 75.6% | 71.4% | 94.2% | 32.3% |
| Combined MVL and MSD | 83.3% | 52.5 | 72.5% | 67.7% |
| MVL (males:females) | 100%:75% | 83.3%:46.7% | – | – |
| MSD (males:females) | 75%:77.8% | 100%:71.4% | – | – |
MSD = muscle strength decline, MVL = mMuscle volume loss; PPV = positive predictive value; NPV = negative predictive value; SARC-F = (S) strength, (A) assistance while walking, (R) rise from a chair, (C) climb stairs, and (F) falls.
Bold numbers indicates statistically significant values.
The area under the ROC curve (AUC) for SARC-F as predictor of sarcopenia was 0.74 ([95% confidence interval {CI} = 0.65 to 0.83], P =< 0.001). AUC for each variable of SARC-F score was also found to be significant (P =< 0.05) (Figure 1) The Pearson paired correlation plot suggested a significant inverse correlation noted between SARC-F score and MSD and SARC-F score and MVL. Low MAMC, low HG strength, and high SARC-F score could predict sarcopenia (MVL) (Figure 2).
Figure 1.
Receiver-operator characteristics curve for individual parameters of SARC-F score as a predictor of Muscle volume Loss. AUC = area under the receiver operating characteristic curve; CI = confidence interval.
Figure 2.
Pearson paired correlation plot of different variables among each other. Variables are shown along the diagonal boxes. The boxes in the upper right corner of the matrix display the Pearson correlation coefficient between each variable. The boxes in the left lower corner display the scatterplot between each pair of variables (∗∗∗ indicates significant correlation.; ∗∗ indicates near significant correlation; Negative values indicated inverse correlation).
A univariate analysis was done using age, sex, BMI, bilirubin, albumin, creatinine, PTI/INR, SARC-F score, platelet count, MELD score, and MAMC. The SARC-F score, creatinine, and platelet count directly correlated with MVL, whereas BMI, bilirubin, and MAMC correlated inversely with MVL (Table 5). We then used all statistically significant variables from the univariate analysis to be included in the multivariate analysis with adjustment for age and sex. A high SARC-F score (≥4) and low MAMC were found to be predictive of MVL in patients with cirrhosis (Table 5).
Table 5.
Univariate and Multivariate Analysis of Various Factors to Predict the Risk for Sarcopenia (MVL).
| Univariate analysis |
Multivariate analysis |
|||||
|---|---|---|---|---|---|---|
| Odds ratio | 95% CI | P value | Odds ratio | 95% CI | P value | |
| Age | −0.02 | −0.06 to 0.02 | 0.4 | 0.95 | 0.88–1.01 | 0.1 |
| Sex | 0.24 | −0.75 to –1.19 | 0.7 | 3.95 | 0.55–33.51 | 0.2 |
| BMI | −0.14 | −0.23 to 0.06 | 0.01 | 0.96 | 0.82–1.13 | 0.6 |
| Bilirubin | −0.10 | −0.20 to 0.02 | 0.05 | 1.01 | 0.87–1.17 | 0.9 |
| Albumin | −0.37 | −1.02 to 0.26 | 0.3 | – | – | – |
| Creatinine | 1.22 | 0.49–2.08 | 0.01 | 3.72 | 1.64–37.38 | 0.06 |
| INR | 0.86 | 0.21–1.68 | 0.06 | – | – | – |
| SARC-F | 0.47 | 0.28–0.68 | 0.01 | 1.63 | 1.20–2.36 | 0.004 |
| Platelet count | 0.54 | 0.10–1.02 | 0.05 | 1.07 | 0.52–2.21 | 0.9 |
| MELD | 0.05 | −0.01 to 0.1 | 0.2 | – | – | – |
| MAMC | −0.43 | −0.63 to 0.25 | <0.001 | 0.65 | 0.42–0.95 | 0.03 |
BMI = body mass index; INR = international normalized ratio; MELD = Model for End-stage liver disease; MAMC = mid-arm muscle circumference; CI = confidence interval.
Bold numbers indicates statistically significant values.
DISCUSSION
The present study demonstrates that a simple bedside questionnaire, SARC-F score, has good sensitivity for detection of sarcopenia in patients with cirrhosis. The SARC-F score showed high sensitivity for detection of MVL alone (80.7%) and MVL and MSD combined (83.3%). Besides, SARC-F score had significant inverse correlation with MSD and MVL. Presence of a high SARC-F score and low MAMC predicts the presence of sarcopenia in these patients.
Despite being an important prognostic marker, sarcopenia is often ignored in routine clinical practice. Patients with cirrhosis are prone to muscle mass loss and muscle strength loss, leading to a poor prognosis. While MAMC, HG strength, and more specialized equipment such as CT, DXA, and BIA can be utilized to evaluate muscle mass and strength, a convenient and reliable bedside tool is required to diagnose sarcopenia. Recently, the European working group on sarcopenia in older people (EWGSOP2) also recommended the use of SARC-F score as the first step for sarcopenia evaluation.15 SARC-F score was originally validated in African American Health study, Baltimore Longitudinal Study of Aging, and National Health and Nutrition Examination Survey, which included participants more than 60 years age.1
In the present study, SARC-F and MAMC were predictive of MVL in cirrhosis patients. Though, the higher mean age in patients with a SARC-F score ≥4 could have contributed to higher MVL, the absolute difference of age was only three years. Besides, on multivariate analysis, a high SARC-F score was found to be an independent predictor for MVL after adjustment for age. The low specificity for MVL (50%) could be due to significant overlap between malnutrition, sarcopenia, and frailty in cirrhosis patients. Recently, Hiraoka et al. studied the sensitivity and specificity of SARC-F score in 383 patients, where 86.9% patients had either chronic hepatitis or CTP class A cirrhosis, and 13.1% had CTP class B/C cirrhosis.16 The sensitivity and specificity for MSD detection were noted to be 17.6% and 97.8%, respectively, whereas theyy were 75.6% and 71.4%, respectively, in the present study. The higher sensitivity of SARC-F score for MSD in the present study could be attributed to the higher percentage of patients having advanced cirrhosis. MAMC has been found to be have a strong correlation with DXA-measured lean body mass and survival in a prospective study of 792 maintenance hemodialysis patients.17 Similarly, a meta-analysis of 12 prospective cohort studies showed higher all-cause mortality in patients with lower MAMC.18
Interestingly, significantly higher platelet counts were observed in patients with SARC-F score ≥4. The mechanism by which platelet count contributes to sarcopenia is not fully understood, but platelets contribute to subclinical inflammation and oxidative stress by secreting inflammatory cytokines, thus contributing to sarcopenia.19, 20, 21 A study of 3671 geriatric individuals by Liaw et al. found elevated platelet-to-lymphocyte ratio significantly associated with sarcopenia.22 Similarly, in a large cross-sectional study of 10,092 individuals, higher platelet count was independently associated with sarcopenia with an odds ratio (95% CI) of 1.62 (1.20–2.19).20
The role of alcohol as an independent contributing factor for sarcopenia in cirrhosis patients needs further research. Excess alcohol intake increases myostatin levels, which impairs muscle protein synthesis and inhibits mTORC1 stimulation, thus causing autophagy,23, 24, 25 but in a large meta-analysis of 13,155 individuals, alcohol consumption was not found to be a risk factor for development of sarcopenia. The odds ratio (95% CI) for sarcopenia among alcohol drinkers was found to be 0.77 (0.67–0.88), though the authors accepted huge ambiguities in diagnosing sarcopenia across the studies.26 MVL was significantly lower in patients with alcohol-related cirrhosis than in other etiologies (60% vs 100%; P = 0.0006) in the present study, though 80 % of the patients had alcohol as etiology of liver disease.
Despite the prognostic importance of sarcopenia in patients with cirrhosis, its assessment is currently hampered by the lack of safe, inexpensive, and easily available tests for clinical use. This study ascertains the role of SARC-F score for screening of sarcopenia in patients with cirrhosis. Based on the available literature, SARC-F score and/or MAMC should be used as the initial screening test followed by HG strength. Patients having a normal SARC-F score, MAMC, or HG strength should be rescreened later on follow-up visits. Sarcopenia should be confirmed by muscle quantity usingCT, MRI, DXA, or BIA. The severity of sarcopenia can be graded using 6-m walk test, gait speed, and short physical performance battery (Figure 3).
Figure 3.
Flowchart depicting algorithm for screening, confirming and assessing the severity of sarcopenia in patients with cirrhosis (S-A-C-S). MAMC = mid-arm muscle circumference; CT = computed tomography; MRI = magnetic resonance imaging; DXA = dual-energy X-ray absorptiometry; BIA = bioelectrical impedance analysis; SPPB = short physical performance battery.
Cirrhosis is a predisposing condition for malnutrition, sarcopenia, and frailty. Although there is some overlap observed among these three disorders in clinical practice, it is crucial to comprehend each as distinct entities. This understanding is essential in order to facilitate the development of customized behavioral interventions and targeted pharmacotherapies for each of these conditions.27 While sarcopenia refers to the degenerative condition characterized by the decline in both muscle mass and functionality, frailty on the other hand encompasses the presence of multisystem impairments, rendering individuals more susceptible to stressors. The components of the SARC-F score have a significant correlation with impaired muscular function, hence facilitating the assessment of sarcopenia. Since sarcopenia and frailty have overlapping features, SARC-F score correlates well with the Fatigue, Resistance, Ambulation, Illness, and Loss of weight (FRAIL) score, a score used to evaluate frailty.1 Despite the fact that definitions of malnutrition, sarcopenia, and frailty exist in the published domain outside of the field of hepatology, they are multiple, yet complimentary. We believe that various hepatology societies should come forward to establish a consensual definition for these in patients with cirrhosis.
This is the first study as per our knowledge validating the SARC-F score in Indian population. We agree that the results of this study might not be generalizable to all patients with cirrhosis as majority of patients had alcohol as etiology of liver disease, and there were no patients with CTP class A besides lack of external n. Another limitation of this study is the overlap of frailty and sarcopenia, which might have contributed to the SARC-F score in some patients. Further studies with large sample size are required that might help to generate more substantial results. This might require combining the SARC-F score with other bedside tests such as HG strength and mid-arm muscle circumference.
In conclusion, the SARC-F score has good sensitivity to be used as a bedside screening tool for sarcopenia in patients with cirrhosis. Presence of a high SARC-F score and low MAMC in patients with cirrhosis indicates the presence of muscle volume loss and warrants further evaluation for sarcopenia.
Credit authorship contribution statement
Conceptualization: NS, BRK, RM.
Data curation: NS, PI.
Formal analysis: NS, PI.
Funding acquisition: NS, PI, BRK, RM.
Investigation: NS, PI, BRK, RM.
Methodology: NS, PI, BRK, RM.
Project administration: NS, PI, BRK, RM.
Resources: NS.
Software: NS, PI.
Supervision: NS, PI, BRK, RM, DNR.
Validation: NS, PI, BRK, RM.
Visualization: NS, PI, BRK, RM.
Writing-original draft: NS, PI.
Writing-review and editing: NS, PI, BRK, RM, DNR.
Conflicts of interest
All authors have none to declare.
Acknowledgements
Thanks to my wife Dr. Khayati Singla for her relentless support throughout this study.
Funding
None.
Data availability statement
Raw data were generated at Osmania Medical College and Hospital, Hyderabad. Derived data supporting the findings of this study are available from the corresponding author [NS] on request.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jceh.2023.101318.
Appendix A. Supplementary data
The following are the supplementary data to this article:
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Raw data were generated at Osmania Medical College and Hospital, Hyderabad. Derived data supporting the findings of this study are available from the corresponding author [NS] on request.