Pilot Clinical Trial of the Use of Alpha-tocopherol for the Prevention of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

Abstract

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.

Oxidative stress modulation in hepatitis C virus infected cells

“…Based on the multiple oxidant and antioxidant activities performed in vivo and in vitro systems during viral infections, and the variable ability of antioxidants to cross cell membranes, the systematic use of antioxidants as antiviral therapies had been limited [40] . On the other hand, HCV is potentially lymphotropic, because it can invade and propagate in cells of the [47,48] 400-544 IU/d or 600 mg 1 Vitamin C [48] 500 mg-10 g N-acetylcysteine [78] 600 mg or 1800 mg/d 1 Mitoquine Q [65,66] 40 or 80 mg/d α-tocopherol [79] 600 mg, 500 mg/d, 800 IU/d Glycyrrhizin [40,42,53,54] 500 mg, 120 mg Different mechanisms Silymarin (Silibinin A, Silibinin B, etc.) [40,64,[80][81][82] 250 mg or 5-20 mg/kg 1 S-adenosylmethionine [69] 1600 mg/d 1 Acetylsalicylic acid [73] 4 mmol/L (in vitro) Gallic acid 300 mg/mL (in vitro) 1 Combined treatment with interferon.…”

Development of a tomato-based food for special medical purposes as therapy adjuvant for patients with HCV infection

“…This evidence supported the use of vitamin E therapy (500 mg/die) for the prevention of disease progression in patients with HCV, who follow the ribavirin pharmacological therapy (Ota et al, 2004). On the other hand, it has also been reported that a-tocopherol failed in preventing hepatocellular carcinoma in patients with liver cirrhosis and positive history of HCV infection (Takagi et al, 2003). Moreover, Kugelmas et al (2003) demonstrated that supplementation with 800 IU vitamin E daily dose for 12 weeks in overweight non-alcoholic steatohepatitis patients did not cause statistically significant improvement in liver enzyme levels beyond weight loss alone (Von Herbay et al, 1997).…”

Hepatocellular Carcinoma with Peritoneal Dissemination which was Regressed during Vitamin K2 and Vitamin E Administration

“…Vitamin E is also known to be an apoptotic agent for tumor cells and prevents hepatocarcinogenesis in animal models (7,8). It is reported that administration of vitamin E for patients with liver cirrhosis and hepatitis C virus (HCV) infection resulted in a lower rate of development of HCC and a higher cumulative survival without development of HCC (8).…”

“…Vitamin E was also used for chemoprevention of HCC using the same dosage for the treatment of peripheral nerve impediment and there were no adverse effects (8) …”