Minireviews
Copyright ©The Author(s) 2021.
World J Gastrointest Oncol. Oct 15, 2021; 13(10): 1440-1452
Published online Oct 15, 2021. doi: 10.4251/wjgo.v13.i10.1440
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], 202058 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], 2019179 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], 2018102 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], 2017232 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] 201551 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], 201590 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], 2015217 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], 2013186 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
Table 2 Branched-chain supplementation in patients with hepatocellular carcinoma
Ref.
Type of study
Population
Intervention (BCAA amount, time of supplementation)
Outcomes
Tada et al[63], 2019Clinical trial (78 patients)BCAA group: 27 patients5.712 g of L-leucine, 2.856 g of L-isoleucine, 3.432 g of L-valine. 18 moBCAA therapy was independently associated with good prognosis in patients with HCC (HR: 0.317, 95%CI = 0.123–0.813, P = 0.017). Multivariate analysis using competing risks methods indicated that BCAA therapy is independently associated with reduction of disease-specific mortality (HR: 0.216, 95%CI = 0.068–0.689, P = 0.001)
Non-BCAA group: 51 Patients
Nojiri et al[64], 2016Randomized clinical trial (51 patients)Control: 26 patients. Diet: Energy: 30–35 kcal/kg; Protein: 1–1.3 g/kg per day420 kcal. 26.6 g of protein. 4.074 g of L-leucine. 3.845 g of L-isoleucine. 3.204 g of L-valine. 3 moEvent-free survival was significantly higher in the BCAA group, whereas the intrahepatic recurrence rate was significantly lower (P = 0.04 and 0.036, respectively). A significant improvement in the SF-8 mental component score was observed in the BCAA group only (P < 0.01)
Intervention: 25 patients. Diet + Supplementation
Ichikawa et al[65], 2013Randomized clinical trial (56 patients)Control: 30 patients. Standard diet1.144 g of L-isoleucine, 1.904 g of L-leucine, 0.952 g of L-valine. 2 wk before hepatic resection and 6 mo after. There was no significant difference in the overall survival rate between the two patient groups. Recurrence rate at 30 mo after surgery was significantly better in the BCAA group in comparison to the control group. Tumor markers such as AFP and PIVKA-II, significantly decreased at 36 mo after liver resection in the BCAA group in comparison to the control group
Intervention: 26 patients. Standard diet + BCAA
Saito et al[66], 2014Prospective cohort study (40 patients)Control: 13 patients. Standard diet2.856 g of L-isoleucine, 5.712 g of L-leucine, 3.432 g of L-valine. > 3 moSupplementation with BCAA granules improves energy metabolism after RFA. BCAA granules improve the liver function after RFA. Improvements in the residual liver function may result in consistently adequate treatment for HCC recurrence after RFA
Intervention: 27 patients. Standard diet + BCAA
Nishikawa et al[52], 2012Retrospective cohort study (99 patients)Control = 59 patients. Regular diet 2.856 g L-isoleucine, 5.712 g L-leucine, 3.432 g L-valine. > 3 moSerum albumin level and Child-Pugh score improved significantly in the BCAA group as compared with the control 3 and 6 mo after TACE (P < 0.05)
Intervention: 40 patients. BCAA treatment
Hayaishi et al[67], 2011Randomized clinical trial (211 patients)Control: 155 patients. Standard dietIntervention: 12 g/d BCAA (LIVACT Granules; Ajinomoto Co., Inc., Tokyo, Japan). > 6 moThe incidence of HCC was significantly lower in the BCAA group than in the control group (HR: 0.416, 95%CI: 0.216–0.800, P = 0.0085). Oral BCAA supplementation also seems to be effective in the prevention of liver-related complications in patients with Child-Pugh A cirrhosis.
Intervention: 56 patients. Standard diet + BCAA
Hachiya et al[68], 2020 Randomized clinical trial (156 patients)Control: 81 patients. Standard dietIntervention: 12 g/d BCAA (LIVACT Granules; Ajinomoto Co., Inc., Tokyo, Japan). 4 yrBCAA supplementation may reduce tumor recurrence in low-risk patients. BCAA may not reduce the risk of tumor recurrence after hepatic resection in HCC in high-risk patients
Intervention: 75 patients. Standard diet + BCAA