Imaging-based assessment of sarcopenia in liver transplant candidates: A systematic review

Table 1 Summary of study design, participant demographics, and methodological quality (Newcastle-Ottawa scale score) for the 17 studies

Ref.	Study design	Subjects (male/female)	Mean age (years)	Etiology (%)	MELD	Methods for the diagnosis of sarcopenia	Sarcopenia definition/cutoff	Imaging assessment time frame	NOS quality assessment
Woodward et al[22], 2021	Prospective	42 (36:6)	56	62 chronic hepatitis C; 12 ALD; 7 PSC; 19 others	14 ± 5	BIS, Tengvall; US, mid-forearm, mid-upper arm anteriorly, and mid-tight on the dominant side; CT, L3 SMI; DEXA, SMI	Male ≤ 8.50 kg/m2, female ≤ 5.75 kg/m2; male < 48.9 cm2/m2, female < 36.3 cm2/m2; male < 7.26 kg/m2, female < 5.45 kg/m2	Before LT	5
Molwitz et al[23], 2023	Retrospective	152 (109:43)	55 ± 10	35 ALD; 22 viral; 13 AIH; 6 NASH; 7 re-transplantation; 6 ALF; 12 cryptogenic or other	20 (12-30)	CT, L3 SMI, and muscle density	Male < 50 cm2/m2, female < 39 cm2/m2; mean MRA grouped patients, as BMI-based cutoffs may be biased by edema and ascites	Pre-LT, a short-term (11 months) and long-term (56 months) post-transplant follow-up	7
Forsgren et al[24], 2024	Prospective	18 (13:5)	58 ± 9.4	39 HCV; 33 ALD; 22 NASH; 6 HIV	15.3 ± 5.0	MRI, neck-to-knee, FFMV Z-score (AMRA®) and MFI	FFMV Z-score < 25th percentile and MFI > 75th percentile	LT waitlist	7
Carey et al[25], 2017	Retrospective	396 (277:119)	58 (51, 62)	48 HCV; 17 ALD; 12 NASH; 10 AIH/PBC/PSC; 5 HBV; 7 others	15.2 (11.0-20.6)	CT, superior aspect of L3, SMI	Male 50 cm2/m2, female 39 cm2/m2	Within 3 months post-listing	6
Quinlan et al[26], 2023	Prospective	57 (35:22)	55	48.7 ALD; 23 PSC; 10.2 PBC; 12.8 NASH; 5.2 Other	11.0 (5)	US, VL thickness, and quadriceps ACSA; MRI, L3, SMI, ACSA, mid-ACSA, PCSA, IMAT		LT waitlist	6
Golse et al[27], 2017	Retrospective	256 (196:60)	53 ± 10.5	45 ALD; 35 HCV; 7 HBV; 2 NASH; 2 AIH; 6 biliary; 2 others	19.3 ± 10.2	CT, L3/L4, PMA	Male < 1561 mm2, female < 1464 mm2	4 months before LT	7
Bot et al[28], 2023	Retrospective	169 (125:44)	54 ± 10	33.7 ALD; 14.2 cholestatic disease; 20.1 viral hepatitis; 11.8 HCC; 4.1 AIH; 16.0 others	13 ± 6	CT, L3, SMA, SMI, and MA		LT waitlist	7
Sinclair et al[29], 2019	Retrospective	420 (420:0)	55.4 (49.2, 59.4)	28.3 HCC; 24.3 HCV; 12.6 ALD; 10.2 PSC; 6.2 NAFLD; 18.3 others	16 (12-19)	DEXA, ALMI (ALM adjusted by height)	< 7.26 kg/m2	LT waitlist	7
Kappus et al[30], 2020	Retrospective	355 (232:123)	53.7 (12.0)	29 HCV; 3.3 HBV; 29.9 NASH/cryptogenic; 17.7 ALD; 5.1 AIH; 3.9 PBC; 8.7 PSC; 11.8 others	19.4 (8.3)	CT, L3, SMI	Male 50 cm2/m2, female 39 cm2/m2	LT waitlist	7
Lee et al[31], 2021	Retrospective	72 (52:20)	53.2 ± 8.7	72 HBV; 13 HCV; 1 HBV + HCV; 3 ALD; 11 others	21.1 ± 9.0	CT, L3, ΔSMI	Preoperative ΔSMI: ≤ -30% large decrease in skeletal muscle; > -30% small decrease or increase in SMI	1 year pre-LT, pre-LT (within 2 months), and post-LT	7
Kyselova et al[32], 2025	Prospective	134 (74:60)	59.6 (49.2, 65.3)		14 (11-17)	CT, L3, SMI; 31P MRS, gastrocnemius and soleus, βATP/Ptot, and intramyocellular pH	Male 50 cm2/m2, female 39cm2/m2; βATP/Ptot < 0.74; intramyocellular pH > 7.045	Pre- and post-LT (6, 12, and 24 months)	7
Chae et al[33], 2018	Retrospective	408 (286:122)	52.0 ± 9.0	57.6 HBV; 20.1 ALD; 7.6 HCV; 6.4 toxins and drugs; 3.2 AIH; 0.7 HAV; 4.4 cryptogenic	16 ± 1	CT, L3/L4, PMI	PMI change before LT to POD 7 cutoff ≤ 25th quartile/ < 11.7%	1 month before LT	7
Ebadi et al[34], 2018	Retrospective	353 (246:107)	56 ± 9	ESLD	16 ± 8	CT, L3, SMI and PMI	SMI: Male 50 cm2/m2, female 39 cm2/m2; PMI: Male 51cm2/m2, female 43 cm2/m2	3 months of listing	7
Alconchel et al[35], 2020	Retrospective	57 (49:8)	57 (35, 73)	35 HCC; 21 ALD; 26 HCV; 9 ALF (urgent); 6 other cirrhosis; 3 HBV	NA	CT, L3, PMI		1 month before LT	5
Hey et al[36], 2022	Retrospective	469 (338:131)	55.0 (47.4, 59.7)	29 viral hepatitis; 11 ALD	16 (12-20)	DEXA, APLM	Male < 7.26 kg/m2, female < 5.5 kg/m2	LT waitlist	8
van Vugt et al[37], 2018	Retrospective	224 (149:75)	56 (48, 62)	12.5 ALD; 3.1 HBV; 7.1 HCV; 29 PSC/PBC; 33.5 HCC; 0.5 cholangiocarcinoma; 3.1 NASH; 4 cryptogenic; 2.2 AIH; 5 others	16 (11-20)	CT, L3, SMI	Lowest sex-specific quartile	3 months from listing	9
Kuo et al[38], 2019	Retrospective	126 (80:46)	53 (46-59)	31 HCV; 25 ALD; 7 NASH/NAFLD; 13 AIH/PBC/PSC; 10 HBV; 15 others	32 (25-37)	CT, L3, SMI	Male < 48 cm2/m2	Pre-LT	7

MELD: Model for end-stage liver disease; NOS: Newcastle-Ottawa scale; ALD: Alcoholic liver disease; PSC: Primary sclerosing cholangitis; AIH: Autoimmune hepatitis; NASH: Non-alcoholic steatohepatitis; ALF: Acute liver failure; HCV: Hepatitis C virus; HIV: Human Immunodeficiency virus; PBC: Primary biliary cirrhosis; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HAV: Hepatitis A virus; ESLD: End-stage liver disease; NAFLD: Non-alcoholic fatty liver disease; NA: Not available; BIS: Bioelectrical impedance spectroscopy; US: Ultrasound; CT: Computed tomography; L3: Third lumbar vertebra; SMI: Skeletal muscle index; DEXA: Dual-energy X-ray absorptiometry; LT: Liver transplantation; MRA: Muscle radiodensity attenuation; BMI: Body mass index; FFMV Z-score: Fat-free muscle volume Z-score; MFI: Muscle fat infiltration; VL: Vastus lateralis; ACSA: Anatomical cross-sectional area; MRI: Magnetic resonance imaging; mid-ACSA: Mid-point anatomical cross-sectional area; IMAT: Intermuscular adipose tissue; PCSA: Physiological cross-sectional area; L4: Fourth lumbar vertebra; PMA: Psoas muscle area; ALMI: Appendicular lean mass index; ALM: Appendicular lean mass; ΔSMI: Change in skeletal muscle index; ³¹P MRS: Phosporus-31 magnetic resonance spectroscopy; PMI: Psoas muscle index; POD: Postoperative day; APLM: Appendicular lean mass; AMRA: Advanced magnetic resonance analytics; MA: Muscle attenuation; βATP: Beta adenosine triphosphate; Ptot: Total phosphorus metabolites; βATP/Ptot: Ratio of beta ATP to total phosphorus metabolites.

Table 2 Association between sarcopenia and waitlist mortality in end-stage liver disease: Summary of prevalence rates, effect measures, and outcomes from studies evaluating the impact of sarcopenia on waitlist mortality among patients with end-stage liver disease

Ref.	Prevalence of sarcopenia	Association with waitlist mortality	Effect measure	Result
Carey et al[25], 2017	45%, 42% male and 54% female	Significant	HR	HR per 1 cm2/m2 increase = 0.95 (95%CI: 0.92-0.98), P < 0.001, meaning a 5% risk reduction per unit increase in SMI; lower SMI indicates higher mortality risk
Sinclair et al[29], 2019	30, 9%	Significant	HR	HR per 1 kg/m2 increase in ALMI = 0.78 (95%CI: 0.62-0.98), P = 0.03. Indicates a 22% reduction in waitlist mortality risk with each unit increase in ALMI; sarcopenia is associated with increased risk
Kappus et al[30], 2020	17, 2%	Not significant	HR	HR = 0.98 (95%CI: 0.95-1.02), P = 0.41. No significant association between sarcopenia and waitlist mortality
Ebadi et al[34], 2018	22% (PMI-defined); 51% male/36% female (SMI)	Female: Both low SMI and PMI significant; male: Low SMI significant and PMI not significant	HR	Sarcopenia defined by SMI was significantly associated with increased waitlist mortality in both male (HR = 2.46, 95%CI: 1.38-4.39; P = 0.002) and female (HR = 2.05, 95%CI: 1.00-4.21; P = 0.05). Sarcopenia defined by PMI was significantly associated with mortality in females (HR = 2.47; 95%CI: 1.24-4.95; P = 0.01), but not in males (HR = 0.85; P = 0.09)
Alconchel et al[35], 2020	Not reported	Not significant	Not reported/no significant association	PMI was not representative of sarcopenia and failed to predict waitlist mortality

PMI: Psoas muscle index; SMI: Skeletal muscle index; HR: Hazard ratio; CI: Confidence interval; ALMI: Appendicular lean mass index.

Table 3 Association between sarcopenia and post-transplant survival in end-stage liver disease: Summary of sarcopenia prevalence, statistical associations, and survival outcomes reported in studies assessing post-liver transplantation prognosis in end-stage liver disease patients

Ref.	Prevalence of sarcopenia	Association with post-LT survival	Effect measure	Result
Molwitz et al[23], 2023	Pre-LT: 61%. Post-LT prevalence not reported in %	Significant (only myosteatosis, not muscle mass)	HR = 0.945 (95%CI: 0.903-0.990), P = 0.016	Myosteatosis predicted worse survival: 3 months (72% vs 95%), 1 year (63% vs 90%), 5 years (54% vs 84%), P = 0.001. SMI decreased post-LT but was not associated with survival
Golse et al[27], 2017	22%	Significant	Survival probabilities (Kaplan-Meier)	Sarcopenia, defined by psoas muscle area (cutoffs: < 1561 mm2 for male, < 1464 mm2 for female), was associated with lower post-LT survival, 1-year survival 59% vs 94%, and 5-year survival 54% vs 80% (log-rank P < 0.001)
Lee et al[31], 2021	1 year pre-LT: 77.8%. Pre-LT: 98.6%. Post-LT: 100%	Significant	HR	A large preoperative decrease in SMI (ΔSMI ≤ -30%) was significantly associated with reduced post-LT survival, HR = 0.284 (95%CI: 0.102-0.789), P = 0.016
Kyselova et al[32], 2025	44.7% in LT candidates; 47.6% in transplanted patients	Sarcopenia not significant; abnormal 31P MRS and myosteatosis linked to worse survival	HR	Abnormal 31P MRS (HR = 3.40; 95%CI: 1.50-7.71, P = 0.003) and myosteatosis (HR = 2.78; 95%CI: 1.14-6.78, P = 0.025) predicted poor long-term survival and perioperative complications better than sarcopenia
Chae et al[33], 2018	25% with high muscle loss (≤ 11.7%)	Significant	HR	High psoas muscle loss was independently associated with worse overall survival after liver transplantation: HR 1.87 (95%CI 1.07-3.25), P = 0.03
Kuo et al[38], 2019	Male 46%	Significant	HR	Male with sarcopenia had significantly higher post-LT mortality at 1 and 3 years. Sarcopenia was independently associated with increased risk of mortality after adjustment for MELD and liver disease etiology (univariable HR = 3.65, 95%CI 1.29-10.28, P = 0.01; multivariable HR = 4.39, P = 0.007)

LT: Liver transplantation; HR: Hazard ratio; CI: Confidence interval; SMI: Skeletal muscle index; ΔSMI: Change in skeletal muscle index; ³¹P MRS: Phosporus-31 magnetic resonance spectroscopy; MELD: Model for end-stage liver disease.

Table 4 Association between sarcopenia and intensive care unit/hospital length of stay in end-stage liver disease: Summary of effect measures and findings from studies assessing the relationship between sarcopenia and the duration of intensive care unit and hospital stays in liver transplant candidates

Ref.	Prevalence of sarcopenia	Association with length of ICU and hospital stays	Effect measure	Result
Bot et al[28], 2023		SMI: Significant with hospital stay; not significant with ICU stay. MA: Not significant	OR	Length of ICU stay > 3 days was not significantly associated with SMI (OR = 1.44; 95%CI: 0.48-4.36; P = 0.518) or MA (OR = 0.45; 95%CI: 0.15-1.27; P = 0.155). Total hospital stays > 3 weeks was significantly associated with higher SMI (OR = 0.21; 95%CI: 0.06-0.73; P = 0.014), but not with MA (OR = 0.41; 95%CI: 0.13-1.27; P = 0.122)
Hey et al[36], 2022	Male 28%, female 15%	Upper limb lean mass: Significant (male), not significant (female); sarcopenia (APLM cutoffs): Not significant	τb	Upper limb lean mass was inversely associated with ICU stay (τb = -0.090, P = 0.015) and hospital stay (τb = -0.10, P = 0.0078). Sarcopenia based on gender-specific cutoffs showed no significant association with length of ICU or hospital stays

SMI: Skeletal muscle index; ICU: Intensive care unit; MA: Muscle attenuation; OR: Odds ratio; APLM: Appendicular lean mass index; τb: Tau-b de Kendall.