In the patients with good liver functions and good performance status, aggressive treatment for HCC might improve the survival rate, even in the extremely elderly patients.

BackgroundCitrin, encoded by SLC25A13, is a component of the malate-aspartate shuttle, which is the main NADH-transporting system in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), which usually resolves within the first year of life. However, small numbers of adults with citrin deficiency develop hyperammonemic encephalopathy, adult-onset type II citrullinemia (CTLN2), which leads to death due to cerebral edema. Liver transplantation is the only definitive therapy for patients with CTLN2. We previously reported that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. Citrin deficiency may impair the glycolysis in hepatocytes because of an increase in the cytosolic NADH/NAD+ ratio, leading to an energy shortage. MCT administration can provide energy to hepatocytes and was expected to have a good effect on CTLN2.MethodsAn MCT supplementation therapy under a low-carbohydrate formula was administered to five patients with CTLN2. Four of the patients had episodes of hyperammonemic encephalopathy, and one patient had postprandial hyperammonemia with no symptoms.ResultsOne of the patients displaying hyperammonemic encephalopathy completely recovered with all normal laboratory findings. Others notably improved in terms of clinical and or laboratory findings with no hyperammonemic symptoms; however, the patients displayed persistent mild citrullinemia and occasionally had postprandial mild hyperammonemia most likely due to an irreversible change in the liver.ConclusionsAn MCT supplement can provide energy to hepatocytes and promote hepatic lipogenesis, leading to a reduction in the cytosolic NADH/NAD+ ratio. MCT supplementation under a low-carbohydrate formula could be a promising therapy for CTLN2 and should also be used to prevent CTLN2 to avoid irreversible liver damage.

Patients with chronic hepatitis C virus (HCV) infection often develop liver cirrhosis and hepatocellular carcinoma (HCC). The purpose of this study was to test the chemopreventive effect of alpha-tocopherol on hepatocarcinogenesis in patients with liver cirrhosis and a history of HCV infection. Eighty-three patients with liver cirrhosis and with positive history of HCV infection were divided at random into two groups. Forty-four patients were treated with alpha-tocopherol (Vit E group) while the other 39 were followed as controls. The clinical background (gender, age, and laboratory data) was similar in the two groups. Serum levels of alpha-tocopherol, albumin, alanine aminotransferase (ALT), and total cholesterol and platelet count were measured serially over a period of five years. The mean serum concentration of alpha-tocopherol was low in both groups at entry and was significantly higher in the Vit E group than in the control group one month after treatment. Platelet count, serum albumin, ALT, and total cholesterol were not different between the two groups during the five-year period. Cumulative tumor-free survival and cumulative survival rate tended to be higher in the Vit E group than in controls, albeit statistically insignificant. The serum level of alpha-tocopherol was low in patients with liver cirrhosis and positive for HCV. Although the administration of alpha-tocopherol normalized the level one month later, it could neither improve liver function, suppress hepatocarcinogenesis, nor improve cumulative survival. Patients treated with alpha-tocopherol tended to live longer without development of HCC but the difference was not statistically significant.

-This study evaluated the anti-apoptotic activity of fucoxanthin in carbon tetrachloride (CCl 4 )-induced hepatotoxicity. An in vitro study using the 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay clearly demonstrated an attenuation of CCl 4 -induced hepatotoxicity with fucoxanthin. This effect was dose-dependent; 25 μM was more effective than 10 μM of fucoxanthin for attenuating the hepatotoxicity induced by 5 mM of CCl 4 . Acute CCl 4 -hepatotoxicity in rats, with numerous cells positive for the terminal deoxynucleotidyl -transferase (TdT) -mediated deoxyuridine triphosphatedigoxigenin (dUTP) nick-end labeling (TUNEL) stain were seen in the pericentral area of the hepatic lobule. Oral pretreatment of CCl 4 -injected rats with fucoxanthin significantly reduced hepatocyte apoptosis. Fucoxanthin was immunohistochemically shown to increase heme oxygenase-1 expression in the cultured liver cells of Hc cells and TRL1215 cells. By oral pretreatment of CCl 4 -injected rats with fucoxanthin, the hepatic heme oxygenase-1 protein levels were significantly increased compared to those not pretreated with fucoxanthin. Heme oxygenase-1 mRNA expression after CCl 4 injection was higher in the CCl 4 +fucoxanthin group than in the CCl 4 group, although the difference was not significant. The findings suggest that fucoxanthin attenuates hepatocyte apoptosis through heme oxygenase-1 induction in CCl 4 -induced acute liver injury.

Clinical data and manifestations were more severe in the recent outbreak than in the past outbreak of acute hepatitis A. It is important to be aware of hepatitis A virus infection and to take into account the available vaccination against hepatitis A virus in Japan.