Effects of Long-Term Oral Supplementation with Branched-Chain Amino Acids for Spontaneous Development of Hepatocellular Carcinoma in Long-Evans Cinnamon Rats

Branched-chain amino acids (BCAAs) are often used for nutritional support in patients with decompensated liver cirrhosis. However, the effect of long-term oral supplementation with BCAAs on the onset and progression of hepatocellular carcinoma (HCC) in patients with chronic liver disease is unknown. We investigated the effect of long-term oral supplementation with BCAAs for a model of spontaneous development HCC in Long-Evans Cinnamon (LEC) rats. The BCAA group (6 rats) and control group rats (6 rats), which were fed BCAA diet or control diet, were observed up to 12 months of age from at 6 months of age. There were no significant differences in serum albumin or liver function values between the two groups. Serum copper concentrations and transferrin levels were higher in the BCAA group than in the control group (p < 0.05). Fischer's ratio was higher in the BCAA group than in the control group, but the difference was not significant. The nodular lesions with HCC were observed on the liver surface in all rats in both groups. The severity of the nodular findings was moderate and severe in each of two rats in the control group, but only minimal or mild in all rats in the BCAA group. Histologically, BCAA group had less extensive tumor nodule formation per unit area and mild necroinflammatory changes in non-tumor areas. In the BCAA group, staining degree for iron and copper were mild in all rats compared to the control group. Long-term oral supplementation with BCAAs in LEC rats stimulated the release of copper into blood and inhibited the deposition of copper into hepatic tissue. BCAAs did not cause carcinogenesis, tumor growth, or tumor progression in LEC rats.