Nutritional therapy for hepatocellular carcinoma

Table 1 Studies evaluating the association of nutritional status and prognosis in patients with hepatocellular carcinoma

Ref.	Population	Method of nutritional assessment and malnutrition prevalence	Outcomes
Faron et al[56], 2020	58 patients with HCC receiving Yttrium-radioembolization. (78% with cirrhosis). BCLC Stage n (%): A: 1 (2.0); B: 13 (25.5); C: 23 (45.1)	MRI derived fat-free muscle. Cut-off values: < 3582 mm2 in men. < 2301 mm2 in women. 50%	Patients with low FFMA showed significantly reduced overall survival (197 d vs 294 d, P = 0.024). Low FFMA (HR: 2.675, P = 0.011), estimated liver tumor burden (HR: 4.058, P = 0.001) and Eastern Cooperative Oncology Group performance status (1.763, P = 0.009) were independent predictors of OS on multivariate analysis
Fujita et al[57], 2019	179 patients with HCC receiving TACE (100% with cirrhosis). TNM Stage n (%): I: 14 (7.8); II: 70 (39.1); III: 71 (39.7); IVA: 17 (9.5); IVB: 7 (3.9)	Psoas mass index. Cut-off values: < 6.0 cm2/m2 in men. < 3.4 cm2/m2 in women. 44.7%	There were no significant differences in OS between groups with low and normal psoas mass index. Multivariate analysis showed that change in PMI per month during the TACE period was significantly associated with poor overall survival (HR: 1.884, P = 0.001)
Kobayashi et al[58], 2018	102 patients with HCC and transcatheter intra-arterial therapies. (100% with cirrhosis). TNM Stage n (%): I: 11 (10.8); II: 22 (21.6); III: 46 (45.1); IV: 23 (22.5)	SMI-L3. Cut-off values: 42 cm2/m2 in men. 38 cm2/m2 in women. 30.4%	Univariate analysis using a Cox proportional hazards model revealed no significant association between SMI-L3 and OS rate (HR: 1.405, 95%CI: 0.861–2.293, P = 0.174). Multivariate analysis revealed that skeletal muscle loss (HR: 1.675, 95%CI: 1.031–2.721, P = 0.037), serum AFP ≥ 20 ng/mL, and maximum tumor diameter ≥ 30 mm were independently predictive of poor overall survival
Nishikawa et al[59], 2017	232 patients with HCC treated with sorafenib. (100% with cirrhosis). TNM Stage n (%): I: 1 (0.6); II: 18 (7.6); III: 79 (34.1); IVA: 46 (19.8); IVB: 88 (37.9)	SMI-L3. Cut-off values: 36.2 cm2/m2 in men. 29.6 cm2/m2 in women. 65.1%	The median overall survival time was 174 d in the sarcopenia group and 454 d in the non-sarcopenia group (P < 0.0001). The median PFS was 77 d in the sarcopenia group and 106 d in the non-sarcopenia group (P = 0.0131). Multivariate analysis identified sarcopenia to be an independent predictor of OS (hazard ratio, 0.365, P < 0.0001)
Schütte et al[44] 2015	51 patients with HCC (82.4% with cirrhosis). BCLC Stage n (%): A: 12 (23.5); B: 13 (25.5); C: 23 (45.1); D: 3 (5.9)	Mini nutritional assessment 0% (37.3% risk for malnutrition). Nutritional Risk Screening 33.4%. BIA derived PhA 23.5%	Patients with a PhA of up to 4.8 had a median survival of 298 d (95%CI 229-367 d) while patients with a PhA > 4.8 had a median survival of 399 d (95%CI 351-446, P = 0.026). Multivariate Cox regression confirmed the PhA at a cut-off of 4.8 in addition to BCLC stage to significantly influence survival of patients
Levolger et al[60], 2015	90 patients with HCC undergoing surgical resection or radiofrequency ablation. (50% with cirrhosis). BCLC Stage n (%): A: 15 (16.7); B: 30 (33.3); C: 36 (40.0); D: 9 (10.0)	SMI-L3. Cut-off values: 52.0 cm2/m2 in men. 39.5 cm2/m2 in women. 57.8%	Sarcopenic patients had a limited overall survival (median: 33 mo vs non-sarcopenic median: 105 mo, P = 0.002). Sarcopenia was an independent predictor for overall survival in multivariate Cox-regression analysis (HR: 3.756, P = 0.001), major complications (32.7% vs 13.2%, P = 0.033) and treatment-related mortality (17.3% vs 2.6%, P = 0.029) were more frequent in sarcopenic patient
Iritani et al[61], 2015	217 patients with HCC. (100% with cirrhosis). Tumor stage n (%) (according to the Liver Cancer Study Group of Japan): I: 52 (24.0); II: 71 (32.7); III: 66 (30.4); IV: 28 (12.9)	FFM. Cut-off values: < 37.0 kg. 45.6%. SMI-L3. Cut-off values: < 36.0 cm2/m2 in men. < 29.0 cm2/m2 in women. 11.1%	Multivariate analysis indicated that FFM (P = 0.0499), albumin level (P = 0.0398), and curability of the initial treatment (P = 0.0008) were independent prognostic factors. Sarcopenic patients showed a significantly lower overall survival than those without sarcopenia (P = 0.0043)
Harimoto et al[62], 2013	186 patients with curative resection for HCC. (53% with cirrhosis). TNM Stage n (%): I: 29 (15.6); II: 95 (51.1); III: 49 (26.3); IV: 13 (7.0)	SMI-L3. Cut-off values: < 43.75 cm2/m2 in men. < 41.10 cm2/m2 in women. 40.3%	In patients with and without sarcopenia, the 5 yr overall survival rate was 71.0% and 83.7%, respectively. The 5 yr recurrence-free survival rate was 13% and 33.2% respectively. Multivariable analysis revealed that reduced skeletal muscle mass was predictive of an unfavorable prognosis

AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; BIA: Bioelectrical impedance analysis; CI: Confidence interval; FFM: Fat-free mass; FFMA: Fat-free muscle area; HCC: Carcinoma hepatocellular; HR: Hazard ratio; MRI: Magnetic resonance imaging; OS: Overall survival; PFS: Progression-free survival; PhA: Phase angle; PMI: Psoas mass index; SMI-L3: L3 skeletal muscle index; TACE: Transcatheter arterial chemoembolization; TNM stage: Classification of malignant tumors.