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A 45-year-old woman with chronic hepatitis B underwent partial hepatectomy for hepatocellular carcinoma (HCC). However, the HCC recurred 2 months after surgery and rapid progression of the disease resulted in her death. Immunohistochemistry showed that transforming growth factor-alpha (TGFalpha) was barely expressed in the liver specimens obtained at hepatic resection, whereas autopsy specimens were strongly stained with anti-TGFalpha antibody in the cytoplasm of both non-tumourous and tumourous liver cells. A higher level of Ki67 expression, a proliferating marker, was observed in the recurrent HCC, similar to that of TGFalpha. Thus, we speculate that the partial hepatectomy increased the level of TGFalpha leading to recurrence and progression of HCC through an autocrine/paracrine mechanism.

It is known that iron acts as a co-factor to catalyze lipid peroxidation (LP) induced by an hepatotoxic compound, such as alcohol. To investigate the role of iron in the pathogenesis of alcoholic liver disease (ALD), we developed a new experimental rat model. Male Sprague-Dawley rats were pair-fed ad libitum a liquid high-fat diet containing ethanol (36% of total calories) or isocaloric carbohydrate with or without dietary carbonyl iron (0.5% w/v) for 12 weeks. Serum alanine aminotransferase (ALT) levels were greatly elevated in rats fed a highfat diet containing both ethanol and iron (EtOH-Fe). Morphologically, slight fibrosis with fatty infiltration and occasional iron deposits were found in the liver of rats fed EtOH-Fe. Moreover, type 4 collagen was definitely stained in the liver of the EtOH-Fe-fed group. However, no evidence of fibrosis was seen in the liver of rats other than the EtOH-Fe-fed group. Furthermore, there was no evidence of secondary hemochromatosis in the rat fed EtOH-Fe or a high-fat diet containing iron. The hepatic content of hydroxyproline (HP) was significantly increased in EtOH-Fe-fed rats as compared to rats other than the EtOH-Fe-fed group. Similarly, microsomal malondialdehyde (MDA) levels were relatively elevated in EtOH-Fe-fed rats. These results demonstrate the evidence of a synergistic effect between alcohol and iron in producing alcoholic liver fibrosis through the enhancement of LP. This new rat model (Fukudai Model) may be useful for further studies in the pathogenesis of ALD.