Prevalence and outcome of sarcopenia in non-alcoholic fatty liver disease

Table 1 Baseline characteristics of the included studies showing the prevalence and outcome of sarcopenia in patients with non-alcoholic fatty liver disease

Ref.	Country, study design	Population and size	Age, in years, male sex, in %	Comorbidities	Definition of NAFLD	Definition and prevalence of sarcopenia	Outcome	Study quality
Lee et al[10], 2016	South Korea, retrospective	Korean National Health and Nutrition Examination Surveys 2008-2011, n = 2761	55.8 ± 14.3, 45%	BMI: 25.8 ± 3.1; MS: 81%; DM: 30%	NAFLD liver fat score	DEXA was used for the calculation of SI = ASM/BMI. Sarcopenia was defined using a cut-off point of SI < 0.789 in men and < 0.521 in women; n = 337 (12.2%)	Significant fibrosis was defined as FIB-4 ≥ 2.67. After adjusting for all covariates, a higher value of SI was associated with a lower risk of significant fibrosis with aOR: 0.67 (95%CI: 0.49-0.91)	Fair
Koo et al[11], 2017	South Korea, prospective	Boramae NAFLD registry, n = 240	53.3 ± 14.3, 48.7%	BMI: 27.4 ± 3.5; DM: 39.6%; HTN: 40.4%; smoking: 22.5%	≥ 5% macrovesicular steatosis on liver biopsy	BIA was used to calculate ASM, which was divided by weight = ASM%. ASM% < 29.0 in men or < 22.9 in women was considered as sarcopenia. n = 64 (26.7%) (21/117 in NAFLD and 43/123 in NASH)	Among patients with NAFLD, sarcopenia was associated with a higher risk of NASH (aOR: 2.59; 95%CI: 1.22-5.48). Sarcopenia was also associated with the presence of significant fibrosis (F2-F4) on liver biopsy (aOR: 2.21; 95%CI: 1.10-4.44)	Good
Petta et al[12], 2017	Italy, prospective	Consecutive patients with NAFLD at a single center, n = 225	48.3 ± 13.4, 62.7%	BMI: 30.3 ± 5.2; DM: 45.3%; HTN: 32.9%; obesity: 71.1%	≥ 5% macrovesicular steatosis on liver biopsy	BIA was used to calculate ASM, which was divided by weight × 100 = SMI. Sarcopenia was defined as an SMI ≤ 37 in males and ≤ 28 in females. n = 98 (43.6%)	Sarcopenia was also associated with the presence of advanced fibrosis (F3-F4) on liver biopsy (aOR: 2.36; 95%CI: 1.16-4.77). The prevalence of NASH was higher in the presence of sarcopenia (88.7% vs 76.3% in nonsarcopenic cases, P = 0.01)	Good
Kang et al[17], 2019	South Korea, retrospective	Adults undergoing comprehensive health screening at a single center from 2010-2017, n = 10711	47.9 ± 11.6, 52.8%	BMI: 23.9 ± 2.9; MS: 12.5%; DM: 5.9%; HTN: 11.6%; obesity: 34.1%	Abdominal ultrasound1	BIA was used to calculate ASM, which was divided by weight = ASM/BW%; ASM/BW% < 29.0 in men or < 22.9 in women was considered as sarcopenia; n = 615 (5.7%)	Advanced fibrosis was defined as NFS ≥ 0.676 and FIB-4 ≥ 2.670. Sarcopenia was also associated with the presence of advanced fibrosis (F3-F4) as defined by NFS with aOR: 2.68 (95%CI: 1.28-5.59), but not using FIB-4 (aOR: 1.58, 95%CI: 0.87-2.85)	Fair
Wijarnpreecha et al[18], 2019	United States, retrospective	Analysis of the third National Health and Nutrition Examination Survey (NHANES), conducted from 1988 to 1994, n = 4188	45.4 ± 0.42, 50.4%	BMI: 28.9 ± 0.22; HTN: 31.6%; DM: 7.5%	Abdominal ultrasound1	BIA was used to calculate ASM, which was divided by weight × 100 = SMI. Sarcopenia was defined as an SMI ≤ 37 in males and ≤ 28 in females; n = 2023 (48.3%)	Advanced fibrosis was defined as NFS ≥ 0.676; sarcopenia was significantly associated with advanced fibrosis (aOR: 2.39, 95%CI: 1.50-3.84)	Fair
Gan et al[19], 2020	China, prospective	Lanxi cohort, a community-based prospective cohort with a focus on obesity-related diseases, n = 1088	55.2 ± 11.5, 32.9%	BMI: 25.9 ± 2.9; MS: 59.5%; DM: 12.9%; HTN: 48.1%	Abdominal ultrasound1	DEXA was used for the calculation of SMI = total appendicular lean mass (ALM)/weight. The cut-off points for sarcopenia were 28.64% for men and 24.12% for women; n = 246 (22.6%)	-	Fair
Golabi et al[14], 2020	United State, retrospective	Analysis of the National Health and Nutrition Examination Survey (NHANES), from 1999 to 2004, n = 1351	50.7 ± 0.72, 60.0%	BMI: 32.5 ± 0.32; obesity: 60.6%; HTN: 68.4%; MS: 63.9%; DM: 20.7%	Fatty liver index (FLI) ≥ 30 based on age, race/ethnicity, waist circumference, GGT, activity, fasting insulin, and fasting glucose	DEXA was used to calculate SI = ASM/BMI. Sarcopenia was defined using a cut-off point of SI < 0.789 in men and < 0.521 in women. n = 239 (17.7%)	Sarcopenia was an independent predictor of mortality in NAFLD with aHR 1.78 (95%CI: 1.16-2.73)	Fair
Hsieh et al[13], 2021	Taiwan, prospective	Boramae NAFLD cohort, n = 521	52.0 ± 15.0, 50.9%	BMI: 27.8 ± 3.8; DM: 39.3%; HTN: 42.4%	≥ 5% macrovesicular steatosis on liver biopsy	Cross-sectional CT images at L3 was used to calculate SMI; Sarcopenia defined by L3-SMI < 50 cm2/m2 for men and < 39 cm2/m2 for women. n = 122 (23.4%)	Sarcopenia was also associated with the presence of significant fibrosis (F2-F4) on liver biopsy (aOR: 1.72; 95%CI: 1.05-2.84)	Good
Kang et al[15], 2020	South Korea, retrospective	Korean National Health and Nutrition Examination Surveys 2014-2016 with age 35-65 yr, n = 2092	45.6 ± 0.22, 42.4%	BMI: 23.8 ± 0.02; DM: 10.7%; HTN: 24.1%; obesity: 33.6%	HIS was calculated based on ALT, AST, BMI, DM, sex, NAFLD defined by HIS > 36	Hand grip strength was calculated using a dynamometer, and sarcopenia was defined for individuals in the 1st quartile (Q1) of muscle strength	Advanced fibrosis was defined as either a FIB-4 score ≥ 1.30 or a BARD score ≥ 2.00. Sarcopenia was also associated with the presence of advanced fibrosis as defined by BARD with aOR: 1.68 (95%CI: 1.07-2.62), but not using FIB-4 (aOR: 1.35, 95%CI: 0.75-2.45)	Fair
Park et al[20], 2020	South Korea, retrospective	Patients attending annual health examination at a single center, n = 747	48.9 ± 10.8, 68.1%	BMI: 24.9 ± 3.1	Abdominal ultrasound1	BIA was used to calculate ASM, which was divided by weight × 100 = SMI. ASM/BW% < 29.1 in men or < 23.0 in women was considered as sarcopenia. n = 66 (8.8%)	-	Fair
Seo et al[21], 2020	South Korea, retrospective	Seoul Metabolic Syndrome Cohort, n = 1278	55.8 ± 10.8, 53.6%	BMI: 26.5 ± 3.3; DM: 100%	Abdominal ultrasound1	BIA was used to calculate ASM, which was divided by weight = ASM/BW%. ASM/BW% < 29.0 in men or < 22.9 in women was considered as sarcopenia. n = 528 (41.3%)	-	Fair
Kang et al[22], 2021	South Korea, retrospective	Patients undergoing carotid ultrasound at a single center, n = 683	49.1 ± 10.0, 86.1%	BMI: 26.4 ± 2.6; DM: 15.2%; obesity: 67.0%; HTN: 29.1%; MS: 43.6%	Abdominal ultrasound1	BIA was used to calculate SI = ASM/BMI. Sarcopenia was defined using a cut-off point of SI < 0.789 in men and < 0.521 in women. n = 75 (11.0%)	Sarcopenia was an independent predictor of increased intima-media thickness (OR: 2.26, (95%CI: 1.26-4.04) and carotid plaque (OR: 2.74, 95%CI: 1.30-5.78)	Fair
Kim et al[23], 2021	United States, retrospective	Analysis of the third National Health and Nutrition Examination Survey (NHANES), conducted from 1988 to 1994, n = 3773	45.5 ± 0.452, 50.5%	BMI: 29.0 ± 0.232; DM: 12.1%; HTN: 30.9%	Abdominal ultrasound1	BIA was used to calculate ASM, which was divided by weight × 100 = SMI. Sarcopenia was defined as an SMI ≤ 37 in males and ≤ 28 in females. n = 1822 (48.3%)	Sarcopenia was an independent predictor of mortality in NAFLD with aHR 1.44 (95%CI: 1.16-1.80)	Fair
Lee et al[24], 2021	South Korea, retrospective	Gangnam Severance Hospital Check-up (GSHC) dataset from 2016 to 2019, n = 4168	51.2 ± 11.5, 65.5%	BMI: 26.1 ± 3.5	Abdominal ultrasound1	n = 1288 (30.9%)	-	Poor
Lee et al[25], 2021	South Korea, retrospective	Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population data, n = 320	65.7 ± 7.6, 63.6%	BMI: 26.9 ± 2.9; DM: 67.9%; HTN: 60.5%	Abdominal ultrasound1	57 (39.6%), 107 (59.8%), and 148 (63.0%) participants had low muscle mass adjusted for height, BMI, and body weight in the NAFLD group, respectively	Appendicular muscle mass adjusted for body weight only was associated with hepatic fibrosis but not when adjusted for height and BMI	Fair
Linge et al[33], 2021	United Kingdom, retrospective	Participants of United Kingdom Biobank study, aged 40-69 yr at recruitment in 2006-2010, n = 1204	62.9 ± 7.4, 53.5%	BMI: 30.1 ± 4.8	MRI liver PDFF > 5%	Sarcopenia, defined as low hand grip strength [< 16/27 kg (females/males)] and low muscle quantity [MRI threshold of 3.0 and 3.6 L/m2 for thigh FFMV/height2 (females/males)]. n = 19 (1.6%)	-	Fair
Wang et al[26], 2021	China, prospective	Patients attending annual health examination at a single center in 2019, n = 154	67.8 ± 9.3, 19.5%	BMI: 24.9 ± 2.9	Abdominal ultrasound1	Sarcopenia, defined as low hand grip strength (< 18 kg in women and < 26 kg in men), a gait speed < 0.8 m/s, and DEXA-based ASM/height2 < 5.4 in women and < 7.0 kg/m2 in men. n = 25 (16.2%)	-	Fair
Almeida et al[27], 2022	Brazil, prospective	Consecutive patients with NAFLD at a single center, n = 57	52.7 ± 11.3, 24.6%	-	Abdominal ultrasound1	Probable sarcopenia, defined as low hand grip strength [< 16/27 kg (females/males)]. n = 15 (26.3%)	-	Fair
Guo et al[35], 2022	China, prospective	Patients undergoing health checkup at a single center from 2020-2021, n = 1830	47.4 ± 10.5, 80.2%	BMI: 27.1 ± 3.0	Transient elastography with fat attenuation parameter > 240 dB/m	BIA was used to calculate ASM, which was divided by height × 100 = SMI. SMI gradually decreased in a stepwise manner as the severity of hepatic steatosis increased	LSM values > 7.3 kPa were classified as having liver fibrosis. Participants in the tertile 1 of SMI had significantly higher odds of liver fibrosis (aOR: 3.7, 95%CI: 2.6-5.3) compared to tertile 3	Good
Seo et al[36], 2022	South Korea, retrospective	Patients undergoing health checkup at a single center from 2017-2019, n = 3198	54.2 ± 9.6, 89.8%	BMI: 26.2 ± 2.9; HTN: 40.2%; DM: 20.1%	Transient elastography with controlled attenuation parameter > 248 dB/m	BIA was used to calculate ASM, which was divided by weight × 100 = SMI. ASM/BW% < 29.1 in men or < 23.0 in women was considered as sarcopenia. n = 517 (16.2%)	-	Poor
Song et al[37], 2023	South Korea, retrospective	Patients undergoing health checkup at a single center from 2007-2018, n = 1180	53.3 ± 10.3, 71.5%	BMI: 26.7 ± 3.67; DM: 20.7%	Transient elastography with fat attenuation parameter > 260 dB/m	BIA was used to calculate ASM, which was divided by weight × 100 = SMI. ASM/BW% < 30.0 in men or < 26.8 in women was considered as sarcopenia	LSM values ≥ 7.5 kPa (≥ F2) were classified as having liver fibrosis. Sarcopenia was not a predictor of fibrosis in NAFLD with aOR: 3.80 (95%CI: 0.86-16.75)	Good
Zhang et al[28], 2022	China, retrospective	T2DM patients with BMI < 25 kg/m2 were enrolled from a single center from 2017 to 2021, n = 1112	53.4 ± 10.7, 57.6%	BMI: 22.6; DM: 100%	Abdominal ultrasound1	BIA was used to calculate ASM, which was divided by weight × 100 = SMI. ASM/BW% < 32.2 in men or < 25.5 in women was considered as sarcopenia. n = 290 (26.1%)	-	Fair
Zhu et al[29], 2023	China, prospective	Participants of Shanghai Changfeng Study, a community-based prospective cohort study of multiple chronic diseases Jun 2009 to Dec 2012, with age > 45 yr, n = 1305	62.6 ± 8.9, 33.1%	BMI: 25.7 ± 3.2	Fatty liver was diagnosed when liver fat content by ultrasound exceeded the cut-off value of 9.15%	DEXA was used to calculate SI = ASM/height2. The cut-off SI for sarcopenia were 6.88 kg/m2 in male and 5.67 kg/m2 in female. n = 260 (19.9%)	Significant fibrosis was defined as FIB-4 ≥ 2.67. The presence of sarcopenia was associated with increased risk of carotid plaque (aOR: 2.22; 95%CI: 1.23-4.02) and liver fibrosis (aOR: 2.07; 95%CI: 1.24-3.44)	Fair
Cho et al[30], 2023	South Korea, retrospective	Patients with T2DM from the Seoul Metabolic Syndrome Cohort, n = 456	55.0 ± 9.4, 46.3%	BMI: 25.7 ± 2.8; DM: 100%; HTN: 36.0%	Abdominal ultrasound1	BIA was used to calculate ASM, which was divided by weight = ASM/BW%; ASM/BW% < 29.0 in men or < 22.9 in women was considered as sarcopenia. n = 123 (27.0%)	Sarcopenia was an independent predictor carotid plaque progression (OR: 2.02, 95%CI: 1.32-3.08)	Good
Choe et al[16], 2023	South Korea, retrospective	Korean Genome and Epidemiology Study (KoGES) Ansung-Ansan cohort, n = 1442	51.7 ± 8.5, 40.0%	BMI: 27.9 ± 2.5; DM: 28.4%; HTN: 34.7%; MS: 69.7%	Hepatic steatosis index (HSI) based on ALT, AST, BMI, DM, sex. NAFLD defined by HSI > 36	-	Fibrosis was defined as FIB-4 ≥ 1.3 and APRI ≥ 0.5. In the adjusted model, low muscle mass (lowest quartile) did not contribute to progression to hepatic fibrosis (HR: 1.02, 95%CI: 0.85-1.22)	Poor
Chun et al[31], 2023	South Korea, retrospective	Patients undergoing health checkup at a three center from 2014-2020, n = 23889	50.0 ± 11.0, 69.5%	BMI: 25.9 ± 3.3; DM: 14.4%; HTN: 37%; obesity: 56.9%; MS: 47.1%	Abdominal ultrasound1	BIA was used to calculate ASM, which was divided by weight = ASM/BW%; ASM/BW% < 29.0 in men or < 22.9 in women was considered as sarcopenia. n = 3092 (12.9%). Sarcopenia was defined using a cut-off point of ASM/BMI = SI < 0.789 in men and < 0.521 in women. n = 1577 (6.6%)	-	Fair
Harring et al[38], 2023	United States, retrospective	Analysis of the third National Health and Nutrition Examination Survey (NHANES), from 2017 to 2018, n = 1056	41.9 ± 0.422, 54.8%	BMI: 33.5 ± 0.372; obesity: 78.7%; DM: 18.1%; HTN: 53.9%; MS: 64.8%	Transient elastography with fat attenuation parameter > 263 dB/m	DEXA was used to calculate SI = ASM/BMI. Sarcopenia was defined using a cut-off point of SI < 0.789 in men and < 0.512 in women. n = 303 (28.7%)	-	Good
Lu et al[32], 2023	China, retrospective	Patients diagnosed with obesity during health checkup at a single center from 2020-2021, n = 476	51.0 ± 13.7, 52.7%	BMI: 27.9 ± 3.3; obesity: 100%	Abdominal ultrasound1	BIA was used to calculate SMI = appendicular skeletal mass/height2. Sarcopenia defined as SMI ≤ 7.0 kg/m2 for males and ≤ 5.7 kg/m2 for females; n = 261 (54.8%)	-	Fair
Zhou et al[34], 2023	China, prospective	Consecutively enrolled subjects who underwent BIA at a single center, between May 2017 and July 2022, n = 1123	37.8 ± 10.6, 58.7%	BMI: 28.9 ± 5.1; DM: 17.6%	MRI liver PDFF > 5%	BIA was used to calculate the appendicular skeletal mass (ASM). Sarcopenia was defined as ASM/height2 or ASM/weight or ASM/BMI less than 2 SD. n = 50 (4.4%)	The MAFLD patients with lower quartiles of ASM/W had a higher risk OR for insulin resistance, both in male and female (OR: 2.14, 95%CI: 1.16-3.97), and OR: 4.26, 95%CI: 1.29, 14.02) for Q4 vs Q1	Fair

¹Abdominal ultrasound showing at least two of the following three abnormal findings: (1) Diffusely increased echogenicity in liver near field (‘bright liver’) with greater liver echogenicity than kidney or spleen; (2) vascular blurring; and (3) poor visualization of the posterior portion of the right lobe because of deep attenuation.

²Standard error.

ALT/AST/GGT: Alanine transaminase/aspartate transaminase/gamma-glutamyltransferase; aOR: Adjusted odds ratio; 95%CI: 95% confidence interval; ASM: Appendicular skeletal muscle mass; BIA: Bioelectrical impedance analysis; BMI: Body mass index; BW: Body weight; DM/HTN/MS: Diabetes mellitus/hypertension/metabolic syndrome; DEXA: Dual X-ray absorptiometry; LSM: Liver stiffness measurement; MRI-PDFF: Magnetic resonance imaging proton density fat fraction; SMI: Skeletal muscle mass index; HIS: Hepatic steatosis index; FIB-4: Fibrosis-4; NASH: Nonalcoholic steatohepatitis; NAFLD: Nonalcoholic fatty liver disease.