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Transforming growth factor-α (TGFα) is an important autocrine growth factor of hepatocytes. The authors evaluated the roles of TGFα in chronic viral hepatitis (CVH) and hepatocellular carcinoma (HCC). The authors measured the amounts of TGFα mRNA in liver tissues from 18 patients with HCC, 31 patients with CVH, and 7 normal controls. “ Hot-start” reverse transcription-polymerase chain reaction (RT-PCR) using oligo-dT and specific primers detected TGFα mRNA in total cellular RNA extracted from liver tissues. The levels of TGFα mRNA were determined by the end point titers of serial, two-fold dilutions of cDNA. The amounts of hepatitis B virus RNA (HBV-RNA) in livers of patients with chronic hepatitis B also were measured by Northern blot hybridization. TGFα mRNA levels were extremely higher in patients with HCC compared with patients with CVH and normal controls, and the levels in patients with CVH also were elevated compared with normal controls. The levels of TGFα mRNA were overexpressed in the underlying livers of patients with HCC compared with patients with CVH, although they were lower than those found in HCC tissues. The levels of TGFα mRNA were higher in samples from patients with chronic hepatitis B than in samples from patients with chronic hepatitis C. The levels of TGFα mRNA were not correlated with serum alanine aminotransferase or HBV-RNA levels in liver tissues in patients with chronic hepatitis B. However, the expression of TGFα mRNA tended to be higher in the livers of patients with raised serum α-fetoprotein levels. The overexpression of TGFα mRNA in the liver seems to be associated with the regeneration of hepatocytes rather than hepatic necrosis or viral replication. Also, it may be related closely to the development or progression of HCC, especially in the livers of patients with chronic hepatitis B. Cancer 2000;89:977–82. © 2000 American Cancer Society.

Hepatocellular carcinoma (HCC) patients with major vascular involvement or extrahepatic metastasis are not good candidates for surgery or transarterial chemoembolization (TACE). In this study, the authors evaluated the efficacy of combined therapy with intraarterial cisplatin infusion and systemic administration of interferon-α (IFN-α) as a palliative treatment for these patients. Sixty-eight HCC patients with major portal vein thrombosis (n = 47) or distant metastasis (n = 27) were randomly allocated to 1 of 3 groups. Group I (n = 19) received combined therapy consisting of intraarterial cisplatin infusion and systemic IFN-α, Group II (n = 23) received intraarterial cisplatin infusion, and Group III (n = 26) was managed with only supportive care. Cisplatin 2 mg/kg was infused through the proper hepatic artery every 8 weeks, and IFN-α 3 million IU/m² was administered subcutaneously 3 times a week. The partial response (defined as a 50% or greater reduction in the product of the 2 longest perpendicular tumor measurements) rate of Group I was significantly higher than that of Group II (33% vs. 14%; P < 0.05). Also, the 1-year survival rate of Group I (27%) was higher than that of Group II (9%) or Group III (0%) (P < 0.05 and P < 0.01, respectively). The median survival period of Group I was 19 weeks, which was significantly longer than that of Group II (11 weeks) or Group III (5 weeks) (P < 0.05 and P < 0.01, respectively). These results suggest that combined therapy consisting of intraarterial cisplatin infusion and systemic IFN-α may be useful as a palliative treatment for HCC patients with major vascular involvement or extrahepatic metastasis. Cancer 2000;88:1986–91. © 2000 American Cancer Society.