• branched-chain amino acids
• liver disease
• mTOR
• nutrition
• supplements

• Humans
• Amino Acids, Branched-Chain/metabolism
• Liver Diseases/metabolism
• Dietary Supplements
• Liver/metabolism
• Liver Cirrhosis/metabolism
• Liver Neoplasms
• Carcinoma, Hepatocellular/metabolism
• Non-alcoholic Fatty Liver Disease/metabolism
• Non-alcoholic Fatty Liver Disease/drug therapy
• Hepatic Encephalopathy/metabolism
• Hepatic Encephalopathy/drug therapy

• 2022ZFJH003 the Fundamental Research Funds for the Central Universities
• SKLID2024KF02 the opening foundation of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine

• Nutrition
• branched-chain amino acids
• cancer
• isoleucine
• leucine
• supplement
• valine

• Humans
• Amino Acids, Branched-Chain/therapeutic use
• Amino Acids, Branched-Chain/metabolism
• Dietary Supplements
• Neoplasms/chemically induced
• Neoplasms/drug therapy

• branched-chain amino acids
• cirrhosis
• hepatocellular carcinoma
• liver
• nutrition

• amino acids
• cancer
• cirrhosis
• hepatocellular carcinoma
• interventional radiology
• liver cancer
• nutrition
• supplements

Liver cancer is the sixth most commonly diagnosed cancer worldwide, with hepatocellular carcinoma (HCC) comprising most cases. Besides hepatitis B and C viral infections, heavy alcohol use, and nonalcoholic steatohepatitis (NASH)-associated advanced fibrosis/cirrhosis, several other risk factors for HCC have been identified (i.e. old age, obesity, insulin resistance, type 2 diabetes). These might in fact partially explain the occurrence of HCC in non-cirrhotic patients without viral infection. HCC surveillance through effective screening programs is still an unmet need for many nonalcoholic fatty liver disease (NAFLD) patients, and identification of pre-cirrhotic individuals who progress to HCC represents a substantial challenge in clinical practice at the moment. Patients with NASH-cirrhosis should undergo systematic HCC surveillance, while this might be considered in patients with advanced fibrosis based on individual risk assessment. In this context, interventions that potentially prevent NAFLD/ NASH-associated HCC are needed. This paper provided an overview of evidence related to lifestyle changes (i.e. weight loss, physical exercise, adherence to healthy dietary patterns, intake of certain dietary components, etc.) and pharmacological interventions that might play a protective role by targeting the underlying causative factors and pathogenetic mechanisms. However, well-designed prospective studies specifically dedicated to NAFLD/NASH patients are still needed to clarify the relationship with HCC risk.

• Nonalcoholic fatty liver disease
• Nonalcoholic steatohepatitis
• Hepatocellular carcinoma
• Risk stratification
• Lifestyle interventions
• Prevention

• Humans
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/etiology
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/epidemiology
• Liver Neoplasms/epidemiology
• Liver Neoplasms/etiology
• Liver Neoplasms/prevention & control
• Diabetes Mellitus, Type 2/complications
• Prospective Studies
• Liver Cirrhosis/complications
• Liver Cirrhosis/pathology
• Fibrosis

• Humans
• Carcinoma, Hepatocellular/prevention & control
• Carcinoma, Hepatocellular/surgery
• Liver Neoplasms/surgery
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/prevention & control
• Amino Acids, Branched-Chain/therapeutic use
• Prognosis
• Dietary Supplements

It is well known that the enzyme catalyzes the first step of branched-chain amino acid (BCAA) catabolism is branched-chain amino transferase (BCAT), which is involved in the synthesis and degradation of leucine, isoleucine and valine. There are two main subtypes of human branched chain amino transferase (hBCAT), including cytoplasmic BCAT (BCAT1) and mitochondrial BCAT (BCAT2). In recent years, the role of BCAT in tumors has attracted the attention of scientists, and there have been continuous research reports that BCAT plays a role in the tumor, Alzheimer’s disease, myeloid leukaemia and other diseases. It plays a significant role in the growth and development of diseases, and new discoveries about this gene in some diseases are made every year. BCAT usually promotes cancer proliferation and invasion by activating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway and activating Wnt/β-catenin signal transduction. This article reviews the role and mechanism of BCAT in different diseases, as well as the recent biomedical research progress. This review aims to make a comprehensive summary of the role and mechanism of BCAT in different diseases and to provide new research ideas for the treatment, prognosis and prevention of certain diseases.

• National Natural Science Foundation of China

• Aminoácidos de cadena ramificada
• Branched-chain amino acids
• Cirrhosis of the liver
• Cirrosis hepática
• Diet
• Dieta
• Estado nutricional
• Nutritional status

• Amino Acids, Branched-Chain/therapeutic use
• Diet
• Dietary Supplements
• Humans
• Liver Cirrhosis/diet therapy
• Nutrition Therapy/methods
• Nutritional Status

• Branched-chain amino acids
• Hepatocellular carcinoma
• Immunotherapy
• Molecular target therapies

Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids (BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis.

• Hepatocellular carcinoma
• Liver cirrhosis
• Branched-chain amino acids
• Late evening snack
• Iron chelators
• Bone marrow cells

• Amino Acids, Branched-Chain/therapeutic use
• Animals
• Bone Marrow Transplantation
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/physiopathology
• Carcinoma, Hepatocellular/therapy
• Chemoprevention/methods
• Hepatitis, Viral, Human/complications
• Humans
• Liver/physiopathology
• Liver Neoplasms/etiology
• Liver Neoplasms/physiopathology
• Liver Neoplasms/therapy
• Neoplasm Recurrence, Local/prevention & control

Because the recurrence rate of hepatocellular carcinoma (HCC) is high, even after curative treatments such as hepatic resection and microwave ablation, chemopreventive agents that can effectively suppress HCC recurrence are required. Cyclooxygenase-2 (Cox-2) was recently found to be overexpressed in HCC. Therefore, Cox-2 inhibitors may offer a chemopreventive therapy for HCC. This randomised controlled trial (RCT) investigated the potential for meloxicam, a clinically used Cox-2 inhibitor, to prevent HCC recurrence after initial curative treatment.

A total of 232 consecutive patients underwent hepatic resection and/or microwave ablation as initial therapy for HCC at our institute between July 2008 and April 2011. Eight patients were excluded because of poor renal function, history of non-steroidal anti-inflammatory drug-related ulceration, or multiple cancers. The remaining 224 patients were randomised to a control group (n = 113) or a meloxicam group (n = 111). To patients in the meloxicam group, meloxicam was administered at 15 mg daily (5 mg three times a day) as long as possible. The overall survival (OS) and disease-free survival (DFS) rates were determined.

The 1-, 3-, and 5-year OS rates of the meloxicam group were 95.4, 82.4, and 70.1 %, respectively. Those of the control group were 98.2, 85.1, and 71.5 %, respectively (p = 0.9549). The corresponding DFS rates of the meloxicam group were 89.2, 53.9, and 44.0 % and those of control group were 86.5, 57.0, and 43.4 %, respectively (p = 0.6722). In the OS and DFS of subsets including patients with hepatitis B or C virus infection, we could not find significant differences between the meloxicam and control groups. However, in the subgroup of analysis of patients without viral hepatitis (NBNC-HCC), significant differences were observed in the DFS between the meloxicam group (1-year DFS, 92.3 %; 3-year DFS, 75.8 %; 5-year DFS, 70.4 %) and control group (1-year DFS, 83.3 %; 3-year DFS, 48.1 %; 5-year DFS, not obtained) (p = 0.0211).

Administration of the Cox-2 inhibitor meloxicam may have a possibility to suppress HCC recurrence after initial curative treatments in patients with NBNC-HCC.

• Chemoprevention
• Cox-2 inhibitor
• Hepatocellular carcinoma
• Recurrence

• prognostic factor
• radiofrequency ablation
• skeletal muscle
• surgical resection
• third lumbar skeletal muscle index

Most hepatocellular carcinoma (HCC) patients have complications, including cirrhosis and malnutrition. The efficacy of dietary supplementation with oral branched-chain amino acids (BCAAs) in HCC patients undergoing interventions has not been confirmed. Relevant publications on the efficacy and safety of oral BCAA supplementation for HCC patients undergoing anti-HCC interventions through September, 2014 were searched for identification in the PubMed, Embase, Web of Science, and the Cochrane Library databases. The pooled risk ratio (RR) and standardized mean difference (SMD) were used to assess the supplementation effects. A total of 11 eligible studies (974 patients in total) were evaluated and included in our analysis. Oral BCAA supplementation helped to maintain liver reserve with higher serum albumin (SMD = 0.234, 95 % CI: 0.033–0.435, P = 0.022), and lower rates of ascites (RR = 0.545, 95 % CI: 0.316–0.938, P = 0.029) and edema (RR = 0.494, 95 % CI: 0.257–0.952, P = 0.035) than in the control group. BCAA supplementation seemed to be effective in improving mortality, especially in Child-Pugh class B patients, but the efficacy was not confirmed. Apparent effects were not found in improving HCC recurrence, total bilirubin, ALT, or AST. BCAA supplementation was relatively safe without serious adverse events. BCAA supplementation may be clinically applied in improving liver functional reserve for HCC patients and further improving the quality of life.

• Acyclic retinoid
• Branched-chain amino acid
• Chemoprevention
• Hepatocellular carcinoma
• Obesity