Hepatocellular carcinoma

https://doi.org/10.1016/S0168-8278(00)80428-6Get rights and content

Abstract

Hepatocellular carcinoma (HCC) is increasing in many countries as a result of an increase in hepatitis C virus (HCV) infection since World War II. The epidemiology of HCC varies with the global region. There have been conflicting observations from different parts of the world concerning the frequency of HCC in patients who in the distant past had post-transfusion non-A, non-B hepatitis. The genetic basis of hepatocarcinogenesis is still poorly understood. In hepatitis B virus (HVB) associated HCC, codon 249 mutation in the p 53 gene seems more related to exposure to aflatoxin B1 than to hepatocarcinogenesis itself. HCC that occurs in children in high HBV endemic regions could be associated with germ-line mutations, but little information is available; not much is known about chemical hepatocarcinogens in the environment other than aflatoxins. The X gene of HBV seems to play an important role in HBV-associated hepatocarcinogenesis. There are preliminary observations on the molecular mechanism of HCV-associated HCC, such as HCV core protein inducing HCC in transgenic mice and the NS3 genome transforming NIH 3T3 cells. Pathological distinction between preneoplastic and very early transformed lesions still depends on classical morphology, and a more genetically oriented differential diagnosis is required. Clinical diagnosis based on modern imaging has improved greatly, but is still unsatisfactory in the differential diagnosis of preneoplastic and early transformed nodules, because the vasculature changes that occur within the nodule are not accurately discerned with the current imaging. Use of sensitive des-γ-carboxy prothrombin (PIVKA II) assay, and lectin affinity chromatography separating HCC specific subspecies of AFP molecules with a more practical biochemical technique will further improve diagnosis. Early diagnosis and transplantation are the best treatment at the moment, but transplantation is not widely available because of the donor shortage. Despite successful resection, the remnant cirrhotic liver frequently develops new HCC lesions, seriously curtailing long-term survival. All-out efforts should be directed to the prevention of HCC, through prevention of viral hepatitis, prevention of acute hepatitis from becoming chronic, prevention of chronic hepatitis from progressing to cirrhosis, and prevention of the cirrhotic liver from developing HCC (chemoprevention). At the moment, very few such studies exist.

References (160)

  • M Arakawa et al.

    Emergence of malignant lesions within an adenomatous hyperplastic nodule in a cirrhotic liver. Observations in five cases

    Gastroenterology

    (1986)
  • M Sakamoto et al.

    Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma

    Hum Pathol

    (1991)
  • S Terasaki et al.

    Histological features predicting malignant transformation of nonmalignant hepatocellular nodules: a prospective study

    Gastroenterology

    (1998)
  • O Nakashima et al.

    Pathomorphologic characteristics of small hepatocellular carcinoma: a special reference to small hepatocellular carcinoma with indistinct margins

    Hepatology

    (1995)
  • F Mion et al.

    Adult cirrhotic liver explants: precancerous lesions and undetected small hepatocellular carcinomas

    Gastroenterology

    (1996)
  • T Takayama et al.

    Malignant transformation of adenomatous hyperplasia to hepatocelluar carcinoma

    Lancet

    (1990)
  • M Borzio et al.

    Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis; a prospective study

    Gastroenterology

    (1995)
  • M Borzio et al.

    Ultrasonography-detected macroregenerative nodules in cirrhosis: a prospective study

    Gastroenterology

    (1997)
  • K Ueda et al.

    Vascular supply in adenomatous hyperplasias of the liver and hepatocellular carcinoma: a morphometric study

    Hum Pathol

    (1992)
  • H Tsuda et al.

    Clonal origin of atypical adenomatous hyperplasia of the liver and clonal identity with hepatocellular carcinoma

    Gastroenterology

    (1988)
  • T Aihara et al.

    Clonal analysis of regenerative nodules in hepatitis C virus-induced liver cirrhosis

    Gastroenterology

    (1994)
  • S Kawai et al.

    Clonality in hepatocellular carcinoma: analysis of methylation pattern of polymorphic X-chromosome-linked phosphoglucerate kinase gene in females

    Hepatology

    (1995)
  • X Bosch et al.

    Epidemiology of primary liver cancer

    Semin Liver Dis

    (1999)
  • K Okuda et al.

    Changing incidence of hepatocellular carcinoma in Japan

    Cancer Res

    (1987)
  • SH Landis et al.

    Cancer statistics, 1998

    CA Cancer J Clin

    (1998)
  • HB El-Serag et al.

    Rising incidence of hepatocellular carcinoma in the United States

    N Engl J Med

    (1999)
  • K Okuda

    Liver cancer

  • K Ikeda et al.

    A multivariate analysis of risk factors for hepatocellular carcinoma: a prospective observation of 795 patients with viral and alcoholic cirrhosis

    Hepatology

    (1993)
  • MC Kew

    Hepatic tumors and cysts

  • V Mazzaferro et al.

    Liver transplantation for the treatment of small hepatocellular carcinoma in patients with cirrhosis

    N Engl J Med

    (1996)
  • LB Seeff et al.

    Long-term mortality after transfusion-associated non-A, non-B hepatitis

    N Engl J Med

    (1992)
  • LB Seeff et al.

    Long-term morbidity of transfusion-associated hepatitis (TAH) C

    Hepatology

    (1998)
  • MJ Tong et al.

    Clinical outcome after transfusion-associated hepatitis C

    N Engl J Med

    (1995)
  • K Kiyosawa et al.

    Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus

    Hepatology

    (1990)
  • GL Davis et al.
  • E Kenny-Walsh

    Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin

    N Engl J Med

    (1999)
  • J Cohen

    The scientific challenge of hepatitis C

    Science

    (1999)
  • K Okuda

    Hepatitis C virus and hepatocellular carcinoma

  • RA Weinberg

    Oncogenes, antioncogenes and the molecular bases of multistep carcinogenesis

    Cancer Res

    (1989)
  • T Sugimura

    Multistep carcinogenesis: a 1992 perspective

    Science

    (1992)
  • ER Fearon

    Molecular genetics of colorectal cancer

    Ann N Y Acad Sci

    (1995)
  • K Okuda

    Hepatocellular carcinoma: recent progress

    Hepatology

    (1992)
  • E Farber

    On the pathogenesis of experimental hepatocellular carcinoma

  • B Bressac et al.

    Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa

    Nature

    (1991)
  • IC Hsu et al.

    Mutational hot spot in the p53 gene in human hepatocellular carcinoma

    Nature

    (1991)
  • Y Kazachkov et al.

    p53 abnormalities in hepatocellular carcinoma from United States patients: analysis of all 11 exons

    Carcinogenesis

    (1996)
  • H Hayashi et al.

    The mutation of codon 249 in the p53 gene is not specific in Japanese hepatocellular carcinoma

    Liver

    (1993)
  • J Unsal et al.

    Genetic heterogeneity of hepatocellular carcinoma

    Proc Natl Acad Sci USA

    (1994)
  • C Challen et al.

    Analysis of the p53 tumor-suppressor gene in hepatocellular carcinoma from Britain

    Hepatology

    (1992)
  • M Volkman et al.

    p53 overexpression is frequent in European hepatocellular carcinoma and largely independent of the codon 249 hot spot mutation

    Oncogene

    (1994)
  • Cited by (0)

    View full text