Assessment of Sarcopenia in Chronic Liver Disease: Indian Perspective

Abbreviations

ALM

appendicular lean mass

ASMI

appendicular skeletal muscle index

BIA

bioimpedance analysis

CT

computed tomography

DEXA

dual‐energy X‐ray absorptiometry

EWGSOP2

European Working Group on Sarcopenia in Older People, Second Meeting

HCC

hepatocellular cancer

HGS

handgrip strength

INASL

Indian National Association for Study of the Liver

L

lumbar vertebra

MRI

magnetic resonance imaging

SMI

skeletal muscle index

USG

ultrasonography

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Sarcopenia has consistently been recognized as a poor predictor of outcomes in chronic liver disease and is associated with higher mortality in patients with cirrhosis, patients with hepatocellular cancer (HCC), and patients on the transplant wait list. ¹ A worldwide consensus on the diagnostic criteria for sarcopenia is lacking and difficult to achieve because the diagnosis of sarcopenia inherently depends on the body composition, which differs among different ethnicities. Therefore, the diagnosis of sarcopenia in India has its challenges.

Ethnic Differences in the Body Composition

According to the World Health Organization global reports, the mean body mass index of Indians was 21.6 kg/m², similar to other Asian countries and much lower than the West. Previous studies have also shown that Asians and Indians have a higher percentage of body fat compared with age‐, sex‐, and body mass index–matched Caucasians. ² , ³ Therefore, for the same weight, the corresponding fat‐free mass (comprising mostly muscle) is expected to be lower in Indians. In a study involving 3087 healthy individuals without cirrhosis, Sidhu et al. ⁴ showed that the mean skeletal muscle index (SMI) at third lumbar vertebra (L3) for Indian men and women was 44.33 ± 6.56 and 41.25 ± 4.42 cm²/m², respectively, which was much lower than the L3‐SMI obtained from a healthy Caucasian population (60.9 ± 7.8 cm²/m² in men and 47.5 ± 6.6 cm²/m² in women). ⁵ Although these studies were done in different populations, they suggest that muscle mass is lower in Indians compared with Caucasians. Therefore, cutoff values to define sarcopenia in India cannot be based on normative values obtained from the West.

Estimation of Muscle Strength

Handgrip strength (HGS) is an inexpensive, reliable, noninvasive, and reproducible bedside tool for the assessment of nutritional status in patients with cirrhosis and is a predictor of transplant wait‐list mortality. ⁶ A low HGS is a prerequisite to define probable sarcopenia by the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. ⁷ HGS varies according to ethnicity and age. ⁸ HGS is lower in South East Asians compared with healthy individuals in Europe and North America. ⁹ Hence the HGS cutoffs for sarcopenia in patients with cirrhosis in the Indian population were based on normative values as obtained from a healthy representative population. ⁸ , ¹⁰

Diagnosis of Sarcopenia

The diagnosis of sarcopenia is based on three important premises: diagnostic criteria, modality, and cutoff (Fig. 1). Unfortunately, the enormous number of possible combinations has led to more confusion than clarity. Multiple cutoffs of sarcopenia have been used by authors worldwide (Table 1), and the prevalence of sarcopenia varies with the criteria chosen. The prevalence rate ranges between 5.9% and 82.1% in our cohort when various diagnostic criteria are applied to the same population, further emphasizing the need for a consensus. ¹¹

FIG 1.

Diagnosis of sarcopenia in patients with cirrhosis.

TABLE 1.

Various Diagnostic Definitions of Sarcopenia

Criteria	Muscle Strength (HGS)		Cutoff for Diagnosing Low Muscle Mass						Muscle Performance (4‐m Walking Speed)
			CT (SMI)		DEXA (ASMI)		BIA (ASMI)
	Male	Female	Male	Female	Male	Female	Male	Female
EWGSOP2 (2019)*	27 kg	16 kg	–	–	7.0 kg/m2	5.5 kg/m2	–	–	0.8 m/s
North American Expert Opinion (2019)	–	–	50 cm2/m2	39 cm2/m2	–	–	–	–	–
Asian Working Group for Sarcopenia (2019)*	26 kg	18 kg	–	–	7.0 kg/m2	5.4 kg/m2	7.0 kg/m2	5.7 kg/m2	1 m/s (6‐m walk)
International Group on Sarcopenia (2011)	–	–	–	–	7.23 kg/m2	5.67 kg/m2	–	–	1 m/s
Japanese Society of Hepatology (2016)	26 kg	18 kg	42 cm2/m2	38 cm2/m2	7.0 kg/m2	5.4 kg/m2	7.0 kg/m2	5.7 kg/m2	0.8 m/s
INASL consensus (2020)	27 kg	16 kg	42 cm2/m2	38 cm2/m2	7.0 kg/m2	5.4 kg/m2	7.0 kg/m2	5.7 kg/m2	0.8 m/s

^*Also includes other parameters for assessment of muscle strength and performance.

Diagnostic Criteria

It is debatable whether the definition of sarcopenia should be based on low muscle mass alone (as suggested by the North American Expert Opinion statement) or a combination of low muscle mass and strength (as suggested by the EWGSOP2 and the Asian Working Group). Our results suggest that a combination of low HGS and low SMI is a better predictor of mortality in patients with cirrhosis compared with low SMI or low HGS alone. ¹¹ Other studies from India have also shown that HSG correlates with mortality in patients with cirrhosis, ¹² further validating the incorporation of low HGS in the diagnostic definition.

Diagnostic Modalities

Another major hurdle in arriving at a consensus definition is the lack of a uniform modality for quantifying muscle mass. Although it is accepted that cross‐sectional imaging modalities such as computed tomography (CT) provide the most accurate estimates of skeletal muscle mass, despite their limitations (Table 2), enormous heterogeneity exists in the literature regarding the level of assessment, muscles to be included, and the population used for standardization. However, the use of CT‐based SMI outside research settings is impractical, and there is an unmet need to develop other screening tools. Bioimpedance analysis (BIA) and dual‐energy X‐ray absorptiometry (DEXA) are available mostly in academic centers and are difficult to interpret in patients with ascites. Muscle ultrasound is easy and readily available, but its use for the diagnosis of sarcopenia is still in nascent stages.

TABLE 2.

Various Modalities for the Diagnosis of Muscle Mass in Patients With Cirrhosis

Modality	Advantages	Disadvantages
Ultrasound	Safe, inexpensive	Interobserver reliability
	No radiation exposure	Reproducibility not known
	Easily available
Bioelectrical impedance	Safe, inexpensive	Affected by ascites and physical activity
	No radiation exposure	Requirement of prediction equations
DEXA	Safe, less expensive	Low radiation
		Difficult to differentiate water from muscle
CT	Differentiates muscle, visceral, and subcutaneous adipose tissue	Cost
	Not affected by presence of ascites or edema	Radiation
MRI	No radiation	Cost
	Differentiates muscle, visceral, and subcutaneous adipose tissue
	Not affected by presence of ascites or edema

Diagnostic Cutoff

Previous studies have estimated sex‐specific SMI from healthy Indian individuals. ¹³ However, cutoffs that predict outcomes in patients with cirrhosis (mortality or need for liver transplantation) have been widely used by others and are a more practical alternative. ¹⁴ Normative values of appendicular lean mass estimated by BIA and DEXA are unavailable for the Indian population; therefore, cutoffs based on other Asian groups have been recommended. Considering these factors, the Indian National Association for Study of the Liver (INASL) has recommended an appropriate definition, incorporating low muscle strength and mass, and suggested optimum cutoffs for defining sarcopenia in Indian patients with cirrhosis. ¹⁰

Estimation of Physical Performance

Various methods have been validated as measures of muscle function in cirrhosis. These include gait speed, chair stand, timed up and go test, short physical performance battery, and 400‐m walk test. The inability to perform these tests suggests severe sarcopenia, which correlates with poor outcomes in cirrhosis. ¹² The INASL recommends a 4‐m usual walking gait speed of ≤0.8 m/s as an indicator of reduced physical performance.

Malnutrition and Sarcopenia

According to the national family health survey 2015‐2016, the prevalence of underweight among men and women in India was 19.6% and 22.4%, respectively. ¹⁵ These numbers are alarming and suggest that there is already a huge burden of malnutrition, and the high prevalence of sarcopenia in cirrhosis can partly be because of the underlying malnutrition. The prevalence of malnutrition in patients with cirrhosis ranges between 30% and 100%, depending on the method of assessment. ¹⁰ , ¹⁶ Various diagnostic tools are available for screening malnutrition in cirrhosis. ¹⁷ It is to be emphasized that sarcopenia and malnutrition are not synonymous. An assessment of malnutrition includes identifying nutritional deficiencies in the diet, anthropometry, body composition analysis, and functional status assessment. It is also important to realize that even in the absence of sarcopenia, patients with cirrhosis should always be screened for malnutrition.

Conclusion and Future Directions

Sarcopenia assessment and treatment should form a part of routine care in patients with cirrhosis. Identification of probable sarcopenia provides a therapeutic window where early interventions should be beneficial and lead to the reversal of changes. In addition to identifying the best definition that suits the population, it is equally essential to develop easily available screening tools for clinicians to identify the problem in the community, especially in resource‐constrained countries. There is a need for a uniform population‐based criterion to decrease heterogeneity among studies, identify pathophysiological mechanisms in similar patient subgroups, and develop therapeutic strategies.