Background. Most hepatocellular carcinomas (HCC) arise in patients with cirrhosis, in whom its incidence is high. The prevention of HCC in patients with cirrhosis is important. Methods. A prospective, randomized, nonblind controlled study was performed to evaluate the preventive effect of Sho‐saiko‐to (TJ‐9) on HCC development. TJ‐9 is a Chinese herbal medicine that contains crude extracts of seven herbs; it has anti tumor effects in experimental animals. Two hundred sixty patients with cirrhosis were randomly assigned to two groups, matched for age, sex, presence of hepatitis B surface antigen, and the severity of liver damage. The patients in the trial group were given TJ‐9 at a daily oral dose of 7.5 g in addition to the conventional drugs given to the control patients. The patients were prospectively monitored for 60 months and the cumulative incidence of HCC and the survival rate in the two groups were calculated. Results. The cumulative incidence curve for 5 years of the trial group was lower than that of the control group (P = 0.071). For the patients without HBs antigen, the difference was significant (P = 0.024). The survival curve for 5 years of the trial group was higher than that of the control group (P = 0.053). For the patients without HBs antigen, the difference was significant (P = 0.043). Conclusions. TJ‐9 helped to prevent the development of HCC in patients with cirrhosis, particularly in patients without HBs antigen.

The usefulness of measurements of serum alpha-fetoprotein elevation for diagnosis of the development of hepatocellular carcinoma was evaluated by a prospective study of 260 patients with cirrhosis. Hepatocellular carcinoma was found in 55 patients during the 5-yr follow-up, excluding 7 found to have hepatocellular carcinoma in the first 6 mo. The cumulative incidence of hepatocellular carcinoma was 26% in the 185 patients who had alpha-fetoprotein levels below 20 ng/ml at the time of entry and 46% in the 68 patients who had alpha-fetoprotein levels of 20 ng/ml or more but below 200 ng/ml. In 169 of the patients, serum levels of alpha-fetoprotein were assayed regularly for at least 2 yr. The incidence of hepatocellular carcinoma development in the 36 patients who had repeated transient increases in alpha-fetoprotein to above 100 ng/ml was 36%. This was significantly higher than the incidence in the 99 patients who had alpha-fetoprotein levels consistently below 20 ng/ml. Thus patients who had alpha-fetoprotein levels of 20 ng/ml or more, who had transient increases in alpha-fetoprotein or who had both should be treated as being in a super-high-risk group for hepatocellular carcinoma. Frequent and careful examination by ultrasonography of such patients is recommended.

When a small amount of Gram-negative lipopolysaccharide was intravenously injected into mice which had been injected with heat-killed Propionibacterium acnes 7 days before, massive hepatic cell necrosis was induced and most of the mice died 24 hr later. However, when prostaglandin E1 was administered with lipopolysaccharide, remarkable improvements in the survival rate and in the histological changes of the liver were observed. In order to find out how prostaglandin E1 suppressed the induction of massive hepatic cell necrosis in this experimental model, we studied the effects of prostaglandin E1 on the activation of liver adherent cells, from which the cytotoxic factor is released, and on the protection of hepatocytes from the cytotoxic factor. As a result, prostaglandin E1 not only inhibited the activation of liver adherent cells and suppressed the release of the cytotoxic factor, but it also directly affected the hepatocytes and protected them from the cytotoxic factor.

A comparative study of three different high-dose regimens of interferon-alpha-2b (IFN) was conducted in patients with chronic hepatitis C to determine which was better at obtaining a sustained remission. A total of 126 patients were assigned randomly to one of three groups: group A was given 10 million international units (MIU) of IFN six times a week for eight weeks; group B was given 10 MIU IFN six times a week for four weeks followed by three times a week for an additional eight weeks; group C was given 10 MIU IFN six times a week for two weeks followed by three times a week for 12 weeks. The total dose administered to each group was 480 MIU/patient. Only the dosing schedule varied among the three groups. Among 98 efficacy-evaluable patients, a sustained alanine aminotransferase (ALT) response, defined as persistent normalization of the ALT for greater than six months after the termination of treatment, was achieved in 21.2% (7/33) of group A, 42.3% (11/26) of group B, and 54.5% (18/33) of group C patients. Similarly, a sustained loss of measurable serum hepatitis C virus RNA was observed in 28.6% (8/28) of group A, 40.9% (9/22) of group B, and 48.3% (14/29) of group C patients. Based upon these data, it can be concluded that 10 MIU of IFN administered six days a week for two weeks followed by three times a week for an additional 12 weeks produces the highest rate of both biochemical and virological responses to IFN therapy in patients with chronic HCV.