Hepatitis B and C
The liver is the largest organ in the abdominal cavity and the most complex. It consists of a myriad of individual microscopic functional units call lobules. The liver performs a variety of functions including the removal of endogenous and exogenous materials from the blood, complex metabolic processes including bile production, carbohydrate homeostasis , lipid metabolism, urea formation, and immune functions.

The liver arises from the ventral mesogastrium and only the upper posterior surface is outside of that structure. The ligamentum teres and falciform ligament connect the liver to the anterior body wall. The lesser omentum connects it to the stomach and the coronary and triangular ligaments to the diaphragm. The liver is smooth and featureless on the diaphragmatic surface and presents with a series of indentations on the visceral surface where it meets the right kidney, adrenal gland, inferior vena cava, hepatoduodenal ligament and stomach (Figure 4).

Figure 5. Causes of hepatocellular carcinoma.

Cirrhosis
Cirrhosis, irrespective of its etiology , is a risk factor for the development of hepatocellular carcinoma. The risk is 3–4 times higher in patients with cirrhosis compared to those with chronic hepatitis in a given population. An increase in hepatocellular proliferation may lead to the activation of oncogenes and mutation of tumor suppressor genes. These changes, in turn, may initiate hepatocarcinogeneses . In low-incidence areas, more than 90% of patients with hepatocellular carcinoma have underlying cirrhosis. However, the presence of cirrhosis is less (approximately 80%) in high-incidence areas, which is probably related to vertical transmission of hepatitis B virus in these areas (Figure 5).

Other Factors
Other etiological factors affecting disease incidence include aflatoxins, alcohol, hemochromatosis , and anabolic steroid use (Figure 5). Exposure to dietary carcinogenic aflatoxins, produced by Aspergillus parasiticus and Aspergillus flavus, is common in certain regions of Southeast Asia and sub-Saharan Africa. Hepatitis B is also common in these areas. The relative contribution of aflatoxins and the hepatitis B virus to the pathogenesis of hepatocellular carcinoma in these parts of the world are poorly understood. In patients with hepatitis C viral infection, alcohol has been found to be another contributing factor. Whether this is related to a more aggressive disease due to a combination of hepatitis C virus and alcohol, or whether alcohol is an independent factor remains unknown. The incidence of hepatocellular carcinoma in patients with hemochromatosis can be as high as 45%, and often the tumor is multifocal.