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Page 2 of 11 Puoti. Hepatoma Res 2018;4:57 I http://dx.doi.org/10.20517/2394-5079.2018.67

cirrhosis, often of viral [hepatitis B virus (HBV), hepatitis C virus (HCV)] or dysmetabolic origin; it means
that subjects with HCC suffer from three distinct diseases: the cancer, the cirrhosis and the virus, making
more difficult the clinical management of these people.

Indeed, it is known that the mechanisms of hepatocarcinogenesis result from the combination of several
causes, such as genetic, immunological, virus-related, environmental and host factors. Host-related factors
include male gender, age of at least 50 years, family predisposition, obesity, advanced liver fibrosis or cirrhosis
and co-infection with other hepatotropic viruses and human immunodeficiency virus. Environmental
[3]
factors include heavy alcohol abuse, cigarette smoking, and exposure to aflatoxin .

From a clinical point of view, it should be considered that these people, often critically ill individuals, often
elderly, may suffer from clinically relevant abnormalities of haemostasis, renal function and electrolyte
balance, and finally often suffer from systemic diseases (heart, lung).

[2]
At present HCC does represent the first cause of death of cirrhotic patients , while in the past morbidity
and mortality in cirrhosis were mainly determined by other complications of the disease, such as hepatic
encephalopathy, upper digestive bleeding from esophageal varices, spontaneous bacterial peritonitis and
hepatorenal syndrome. This is mainly due to both early diagnosis and optimized treatment of non-oncologic
complications, that increasing life expectancy might be in parallel with the increase of the HCC incidence.

This review is aimed at analyzing available data on the epidemiology and on the clinical aspects of HCC,
focusing on the current knowledge about the management of the disease.

EPIDEMIOLOGY
Available international epidemiological data show that primary liver cancer represents the 7th most common
tumor in males (4% of all cancers) and the 13th most common tumor in females (2.3% of all cancers), with a
[1,2]
prevalence of 53/100,000 in males and 22/100,000 in females (male-to-female ratio = 2:1) . The lifetime (up
to 74 years of age) risk of diagnosis of HCC is 17‰ in men (1/59) and 5‰ in women (1/199). Primary liver
cancer is the 5th cause of mortality in men (3rd in subjects 50-69 years old) and the 7th in women (4.5% of
[4,5]
malignancy-related mortality) .

Anyway, relevant geographical differences exist. In Chinese and in African populations, the mean age of
patients with the tumor is appreciably younger. This is in sharp contrast to Japan, where the incidence
of HCC is the highest in the cohort of men aged 70-79 years. The pattern of HCC occurrence has a clear
geographical distribution, with the highest incidence rates in East Asia, sub-Saharan Africa, and Melanesia,
where around 85% of cases occur. In developed regions, the incidence is low with the exception of Southern
[2]
Europe where the incidence in men is significantly higher than in other developed regions .

There is a growing incidence of HCC worldwide. Overall, the incidence and mortality rates were of 65,000
and 60,240 cases in Europe and 21,000 and 18,400 cases in the United States in 2008, respectively. It is
[2]
estimated that by 2020 the number of cases will reach 78,000 and 27,000, respectively .
Several factors are known to be associated with a higher incidence of HCC: (1) male gender; (2) increasing
age; (3) environmental and geographic factors; (4) metabolic and genetic factors (e.g., non-alcoholic
steatohepatitis (NASH), genetic hemochromatosis); (5) viral infection; (6) alcohol intake; (7) oncogenic
factors (e.g., aflatoxin); and (8) histological stage.

In the majority of the cases, HCC develops in patients with cirrhosis and thus the risk factors for HCC and