Hepatocellular Carcinoma: Recent Progress

Abstract

HCC is not a major killer among malignant diseases in Western countries, and until recently few Western hepatologists were interested in this cancer. After the demonstration of an etiologic role for HBV infection in hepatocarcinogenesis, interest surged even in lowincidence countries, particularly among molecular biologists and oncologists. A large body of literature now exists dealing with molecular mechanism in HBVrelated human HCC and hepadnavirus-induced HCC in animals. The recent identification and cloning of hepatitis C virus (HCV) has focused interest on chronic C hepatitis which, under the name of non-A, non-B (NANB) hepatitis, had for some time been suspected as another etiological factor for HCC in certain areas of the world. It did not take long before well-documented evidence linked HCV to HCC. Imaging diagnosis of small-mass lesions in the liver has progressed remarkably in recent years, as emphasized in a previous review in this JOURNAL (1). In countries where detection and resection of small HCCs in cirrhotic livers are common practice, pathologists are discussing how to differentiate large, benign, hyperplastic nodules; adenomatous hyperplastic nodules with potential to transform; and early HCC lesions histopathologically. Radiologists are attempting to make similar diagnostic distinction by imaging alone with limited success. This review attempts to update the recent progress made in the basic study of HCC. EPIDEMIOLOGY AND ETIOLOGYAccording to Muiioz and Bosch (2), no clear indication of a change has appeared in the incidence rate of HCC in developed Western countries in the past 20 yr or so as far as cancer registry data are concerned. However, in Japan, incidence of HCC began to increase about 20 yr ago; the increase was accounted for by non-HBV-related cases, and an etiologic role of chronic NANB hepatitis was suspected in the early 1980s (3). All cancer registries in Japan have clearly shown significant increases in HCC because of non-HBV-related cases. HBsAgpositive patients accounted for more than 40% of all HCC cases in the early 1970s, when testing was by the immunoprecipitation techniques. This figure is currently less than 20% as tested by the much more sensitive methods (4). At the autopsy table, the numbers of patients with HCC and of those with cirrhosis alone were about the same in early 1960s, but HCC now far exceeds cirrhosis in number. The frequency of complicating HCC among all cirrhotic livers autopsied used to be 20% to 40% and is currently about 80% (5). A similar trend of increase has been observed among autopsies in northern Italy (6) and the United States (7). A number of studies in Japan have shown that the frequency with which HCC develops in cirrhotic patients during follow-up is more than 6%/yr (8) among all cirrhotic patients. In a recent study in northern Italy, HCC developed in 29 (7%) of 417 patients with cirrhosis (62% viral) during follow-up periods averaging 33 mo (9).Shortly after the identification of HCV by the group at Chiron Laboratories and the developmen...

Aberrant FHIT transcripts in hepatocellular carcinomas

“…The precise aetiology of HCC is not yet clear, however it is well known that HCC is frequently associated with a background of chronic liver disease (Beasley et al, 1981). Predisposing factors include hepatitis B virus or hepatitis C virus infection and aflatoxin BI exposure (Okuda, 1992;Wright et al, 1992;Chen, 1993). Hepatocarcinogenesis is therefore considered as a multifactorial and multistep process that includes the activation of oncogenes and the inactivation of tumour-suppressor genes (Ding and Habib, 1994;Sugimura, 1992).…”

“…Hepatocellular carcinoma (HCC) is one of the most common human malignancies in the world, especially in areas such as China and sub-Saharan Africa (Okuda, 1992;Wright et al, 1992). It usually carries a grave prognosis.…”

Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery

“…Hepatocellular carcinoma (HCC), representing the most prevalent histological form, develops in around 90% of cases with a background of chronic active hepatitis and cirrhosis. 1,2 This in turn has two major implications: an apparently isolated, small tumor nodule is in fact surrounded by a number of liver cell clones which have the potential to evolve into tumor nodules. In addition, due to the underlying chronic liver disease, any treatment should take into consideration the risk of inducing severe liver failure.…”

CpG methylation of MGMT and hMLH1 promoter in hepatocellular carcinoma associated with hepatitis viral infection

“…A correlation between the promoter methylation status and viral infection, although it was weak, intimated that hepatitis viral infections could play a role in the CpG methylation of the MGMT promoter. Keywords: CpG methylation; MGMT; hMLH1; hepatocellular carcinoma; hepatitis viral infection; urea/bisulphite sequencing Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies and a major cause of cancer-related deaths worldwide (Okuda et al, 1992). Most HCCs exhibit characteristics compatible with chronic hepatitis and cirrhosis caused by persistent infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) (Okuda et al, 1992).…”

“…Keywords: CpG methylation; MGMT; hMLH1; hepatocellular carcinoma; hepatitis viral infection; urea/bisulphite sequencing Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies and a major cause of cancer-related deaths worldwide (Okuda et al, 1992). Most HCCs exhibit characteristics compatible with chronic hepatitis and cirrhosis caused by persistent infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) (Okuda et al, 1992). Both chronic hepatitis and cirrhosis associated with viral infection are considered as precancerous conditions (Paradis et al, 1998).…”