Long-term survival following treatment of hepatocellular carcinoma in Singapore: evaluation of Wellferon in the prophylaxis of high-risk pre-cancerous conditions.

The present paper reviews several studies performed between 1977 and 1986 in Singapore on the 10-year survival outcome of treatment for stage I and II hepatocellular carcinoma (HCC). Of 801 HCC patients evaluated, only 2 survivors (0.3%) remained in complete remission for 13 and 14 years, respectively. One had received four weekly cycles of prednisolone, Adriamycin, vincristine and 5-fluorouracil for an inoperable HCC with a 10-cm diameter, and the other had received localised synchronised hepatic irradiation and Adriamycin. As follow-up, the use of localised hepatic irradiation consisting of 131I-labeled (30 mCi) iodised oil in lipiodol infused via the hepatic artery appeared to benefit patients with small residual tumours but did not affect larger tumours measuring 2 cm in diameter. Prophylactic, intermittent long-term administration of lymphoblastoid interferon-alpha (Wellferon) was carried out in pre-cancerous, high-risk hepatitis B surface antigen (HBsAg)-positive patients with cirrhosis, in immediate male relatives of liver cancer patients, and in persons who had undergone hepatic resection. In the untreated group, 10/162 (6%) cirrhotics, 3/18 (17%) male family members, and 6/10 (60%) post-resection cases developed single or multiple HCCs within 1 year of screening done at 3-month intervals on the basis of alpha-fetoprotein (AFP) levels and real-time hepatic ultrasonography. In contrast, none of the Wellferon-treated group consisting of 518 cirrhotic patients, 82 male relatives of HCC patients and 20 post-resection cases developed HCC. Two HBsAg-positive individuals who had not been treated with interferon (IFN) developed hepatic nodules which that showed dysplasia, AFP elevation and chromosomal changes. These studies demonstrate the poor results of late diagnosis and show that early intervention and prophylaxis with Wellferon can reduce the incidence of HCC in high-risk persons. In addition, transhepatic chemoembolisation and liver resection are suitable methods for treating small HCCs (single or multiple) that are detected by screening. However, some of these early-detected HCCs remain highly malignant. Prophylactic treatment of pre-cancerous conditions appears to be a better option as a long-term programme for HCC.