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

Abstract

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.

Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection

“…7 Perhaps the most important finding of the present study is that the incidence of HCC development was significantly reduced in the IFN-treated patients. Similar to the observation in patients with hepatitis C virus and cirrhosis, 12,14-17 a beneficial effect of IFN therapy on the prevention of HCC in HBV patients with cirrhosis was observed in a few nonrandomized controlled studies, [11][12][13] which could be biased because the untreated patients might have more advanced disease and thus not be suitable or contraindicated for IFN therapy. 14 To the best of our knowledge, this could be the first randomized controlled study that shows that IFN therapy reduces HCC development in HBV patients with or without cirrhosis.…”

“…5,6 However, long-term follow-up data are limited. [7][8][9][10] Although several studies have suggested that IFN therapy may reduce the risk of HCC in patients with HBV or hepatitis C virus-related cirrhosis, [11][12][13][14][15][16][17] evidence derived from randomized controlled studies is still lacking. Therefore, the effect of IFN on the prevention of HCC in patients with chronic HBV infection still remains to be clarified or confirmed.…”

Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis

“…Soon after trial approval, the protocol was amended to use IFN-␣2b (Intron A; Schering-Plough, Kenilworth, NJ) rather than lymphoblastoid IFN-␣. 16,17 In the treatment arm, IFN-␣ was started within 6 weeks of surgery and was given subcutaneously (3 million units 3 times every week for 48 weeks). Adverse events during treatment were rated as mild, moderate, severe, or life-threatening as previously described.…”

Impact of Interferon Therapy after Curative Treatment of Hepatocellular Carcinoma

“…In 1995, a small randomized controlled trial (RCT) of IFN treatment showed a decrease in the incidence of HCC in patients with hepatitis C virus (HCV) cirrhosis compared with that in untreated controls [25]. Following this study, several others, including controlled trials [26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42], have been performed, mostly in patients with HCV infection. Other retrospective cohort studies of a relatively small size have shown a marked degree of heterogeneity, making it difficult to assess the actual level of benefit obtained by IFN treatment.…”