world cancer report - iarc

tries is high (10-15%) and it can be estimated
that two-thirds of liver cancer
cases in developing countries are attributable
to this virus [7]. HBV is particularly
implicated in hepatocellular carcinoma in
Africa and Asia, and HCV in Japan and the
USA [4].
In developing countries, dietary ingestion
of aflatoxins (produced by the mould
Aspergillus flavus, which under hot and
humid conditions contaminates stored
grain), and specifically aflatoxin B1, is
causally associated with development of
hepatocellular carcinoma, and exposure
to aflatoxins may be synergistic with HBV
infection (Food contaminants, p43). In
developed countries, principal known risk
factors are smoking and chronic alcohol
abuse. The major clinical hepatocellular
carcinoma risk factor is cirrhosis; 70-90%
of hepatocellular carcinomas develop in
patients with macronodular cirrhosis.
Iron overload caused by untreated haematochromatosis
may provoke in some
patient series a risk of death of as much
as 45% from hepatocellular carcinoma
[8]. Hepatocellular carcinoma may occur
in 37% of patients with tyrosinaemia who
survive to two years old and may occur in
patients who have successfully undergone
liver transplant. Other metabolic disorders
which may carry an increased risk of
hepatocellular carcinoma or other liver
cancers include alpha-1-trypsin deficiency,
hypercitrullinaemia and glycogen storage
disease (Table 5.6).
Hepatic cholangiocarcinoma is rare in
most populations, the exception being in
the population of Northern Thailand where
it is associated with chronic infection by
the liver fluke Opisthorchis viverrini, which
is contracted through consumption of
infected raw fish.
Detection
Screening programmes by ultrasound
examination with or without pre-selection
on the basis of raised levels of alpha-fetoprotein
have not proved effective in reducing
mortality. Recent observations indicate
that free DNA originating from tumour cells
is detectable in the plasma of liver cancer
patients at an early stage. Detection of relevant
genetic changes in the plasma (such
as p53 mutation at codon 249 in the inhabitants
of high incidence areas and aberrant
methylation of CDKN2A in most parts of
the world) may soon become useful aids in
screening tests for hepatocellular carcinoma.
The availability of simple, genetic tests
would be an important contribution to
screening programmes.
Fig. 5.38 Age-specific incidence of liver cancer in men; rates are higher in young men in areas where viral
hepatitis is endemic.
204 Human cancers by organ site
Risk factors and predisposing
conditions
Hepatocellular carcinoma
Chronic infection with hepatitis B virus
Infection with hepatitis C virus
Chronic liver cirrhosis
Untreated haemochromatosis
Tyrosinaemia
Alcohol abuse
Aflatoxins
Long-term use of oral contraceptives
High dose anabolic steroids
Agents causing peroxisome proliferation
Cholangiocarcinoma
Liver fluke (Opisthorchis viverrini and
Clonorchis sinensis) infection (esp. certain
areas of China and South East Asia)
Hepatolithiasis
Thorotrast (no-longer used X-ray contrast medium)
Inflammatory bowel disease
Nitrosamines
Angiosarcoma
Vinyl chloride (polymer industry)
Table 5.6 Risk factors and predisposing conditions
for liver cancer.
Common symptoms of hepatocellular
carcinoma are abdominal pain, weight
loss, fatigue, abdominal swelling and
anorexia. Most patients, particularly in
sub-Saharan Africa, present with
hepatomegaly; other common signs are
ascites and jaundice. Hepatocellular
carcinoma which infiltrates a cirrhotic
liver often compromises the already
impaired hepatic function and thus
causes death before becoming very
large, as is the case in most Japanese
and American patients [8]. Intrahepatic
cholangiocarcinoma is characterized by
general malaise, mild abdominal pain
and weight loss, and by jaundice and
cholangitis at later stages [9]. The
majority of cases can be diagnosed by
computed tomography (CT) (Fig. 5.40)
and ultrasonography. A definitive diagnosis
may depend on histological analysis
via fine needle biopsy. Endoscopic
retrograde, transhepatic or magnetic
resonance cholangiography can identify
the level of biliary obstruction in the
case of intrahepatic cholangiocarcinoma.