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Obesity and related metabolic abnormalities play a key role in liver carcinogenesis. Non-alcoholic steatohepatitis (NASH), which is often complicated with obesity and diabetes mellitus, is associated with the development of hepatocellular carcinoma (HCC). Sodium alginate (SA), which is extracted from brown seaweeds, is marketed as a weight loss supplement because of its high viscosity and gelling properties. In the present study, we examined the effects of SA on the progression of NASH and related liver carcinogenesis in monosodium glutamate (MSG)-treated mice, which show obesity, diabetes mellitus, and NASH-like histopathological changes. Male MSG-mice were intraperitoneally injected with diethylnitrosamine at 2 weeks of age, and, thereafter, they received a basal diet containing high- or low-molecular-weight SA throughout the experiment (16 weeks). At sacrifice, control MSG-treated mice fed the basal-diet showed significant obesity, hyperinsulinemia, steatosis and hepatic tumor development. SA administration suppressed body weight gain; improved insulin sensitivity, hyperinsulinemia, and hyperleptinemia; attenuated inflammation in the liver and white adipose tissue; and inhibited hepatic lipogenesis and progression of NASH. SA also reduced oxidative stress and increased anti-oxidant enzyme levels in the liver. Development of hepatic tumors, including liver cell adenoma and HCC, and hepatic pre-neoplastic lesions was significantly inhibited by SA supplementation. In conclusion, oral SA supplementation improves liver steatosis, insulin resistance, chronic inflammation, and oxidative stress, preventing the development of liver tumorigenesis in obese and diabetic mice. SA may have ability to suppress steatosis-related liver carcinogenesis in obese and diabetic subjects.

The aim of this study was to determine whether skeletal muscle depletion predicts the prognosis of patients with hepatocellular carcinoma (HCC) that is being treated with sorafenib. We evaluated 40 consecutive HCC patients who received sorafenib treatment. The skeletal muscle cross-sectional area was measured by computed tomography at the third lumbar vertebra (L3), from which the L3 skeletal muscle index (L3 SMI) was obtained. The factors contributing to overall survival, sorafenib dose reduction, and discontinuation of sorafenib were analyzed using the Cox proportional hazards model. L3 SMI (p = 0.020) and log (α-fetoprotein (AFP)) (p = 0.010) were identified as independent prognostic factors in HCC patients treated with sorafenib. The initial dose of sorafenib (p = 0.008) was an independent risk factor for sorafenib dose reduction, and log (AFP) (p = 0.008) was the only significant risk factor for the discontinuation of this drug. L3 SMI was not a risk factor for either dose reduction (p = 0.423) or the discontinuation (p = 0.132) of sorafenib. A multiple linear regression analysis determined the following relationship between skeletal muscle mass (assessed as L3 SMI) and the explanatory factors: L3 SMI = -0.1896 × (Age) - 10.3441 × (Child-Pugh score) - 9.3922 × (log (AFP)) + 1.6139 × (log (AFP)) × (Child-Pugh score) + 112.9166. Skeletal muscle depletion is inversely associated with age, Child-Pugh score, and log (AFP). Moreover, it is an independent prognostic factor for HCC patients treated with sorafenib.

Hepatocellular carcinoma (HCC), which is a common malignancy worldwide, usually develops in a cirrhotic liver due to hepatitis virus infection. Metabolic syndrome, which is frequently complicated by obesity and diabetes mellitus, is also a critical risk factor for liver carcinogenesis. Green tea catechins (GTCs) may possess potent anticancer and chemopreventive properties for a number of different malignancies, including liver cancer. Antioxidant and anti-inflammatory activities are key mechanisms through which GTCs prevent the development of neoplasms, and they also exert cancer chemopreventive effects by modulating several signaling transduction and metabolic pathways. Furthermore, GTCs are considered to be useful for the prevention of obesity- and metabolic syndrome-related carcinogenesis by improving metabolic disorders. Several interventional trials in humans have shown that GTCs may ameliorate metabolic abnormalities and prevent the development of precancerous lesions. The purpose of this article is to review the key mechanisms by which GTCs exert chemopreventive effects in liver carcinogenesis, focusing especially on their ability to inhibit receptor tyrosine kinases and improve metabolic abnormalities. We also review the evidence for GTCs acting to prevent metabolic syndrome-associated liver carcinogenesis.

Background: Skeletal muscle depletion or sarcopenia has been identified as a poor prognostic factor for various diseases. The aim of this study is to determine whether muscle depletion is a prognostic factor for hepatocellular carcinoma (HCC)., Methods: We evaluated 217 consecutive patients with primary HCC. The skeletal muscle cross-sectional area was measured by computed tomography at the third lumbar vertebra (L3), from which the total body fat-free mass (FFM) and L3 skeletal muscle index (L3 SMI) were obtained. The factors contributing to overall survival (OS) were analyzed by univariate and multivariate Cox proportional hazards model., Results: In univariate analysis, FFM (P = 0.0422), Child-Pugh classification (P = 0.0058), serum albumin level (P < 0.0001), serum AFP level (P < 0.0001), serum proteins induced by vitamin K absence or antagonist-II level (P < 0.0001), cancer stage (P < 0.0001), and curability of the initial treatment (P < 0.0001) were significantly associated with the prognosis of HCC. 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. Sarcopenia was defined as an L3 SMI value of ≤29.0 cm(2)/m(2) for women and ≤36.0 cm(2)/m(2) for men, and 24 patients (11.1%) have sarcopenia. Sarcopenic patients showed a significantly lower OS than those without sarcopenia (P = 0.0043). Sarcopenic patients who were overweight (BMI >22) died earlier (P = 0.0129)., Conclusions: Skeletal muscle depletion is an independent prognostic factor. Intervention to prevent muscle wasting might be an effective strategy for improving the outcome of HCC.