Cancer Glossary & Scientific Reference

Liver cancer and cholangiocarcinoma

Liver cancer

compiled by Healing Cancer Naturally from material © 1994-2000 Encyclopædia Britannica, Inc.

Liver diseases

A variety of agents, including viruses, drugs, environmental pollutants, genetic disorders, and systemic diseases, can affect the liver. The resulting disorders usually affect one of the three functional components of the liver: the hepatocyte (liver cell) itself, the bile secretory (cholangiolar) apparatus, or the blood vascular system. Although an agent tends to cause initial damage in only one of these areas, the resulting disease may in time also involve other components. Thus, although viral hepatitis (inflammation of the liver) predominantly affects hepatocytes, it commonly leads eventually to canalicular damage.

Most acute liver diseases are self-limited, and liver functioning returns to normal once the causes are removed or eliminated. In some cases, however, the acute disease process destroys massive areas of liver tissue in a short time, leading to extensive death (necrosis) of hepatic cells and often to death of the patient. Hepatitis may result from viral infections or toxic damage from drugs or poisons. When acute hepatitis lasts for six months or more, a slow but progressive destruction of the surrounding liver cells and bile ducts occurs, a stage called chronic active hepatitis. If hepatocellular damage is severe enough to destroy entire acini (clusters of lobules), they are often replaced with fibrous scar tissue. Bile canaliculi and hepatocytes regenerate in an irregular fashion adjacent to the scar tissue and result in a chronic condition called cirrhosis of the liver. Where inflammatory activity continues after the onset of cirrhosis, the disorderly regeneration of hepatocytes and cholangioles may lead to the development of hepatocellular or cholangiolar cancer.

Liver cancer & cholangiocarcinoma

Cancer of the liver is a disease whose incidence varies widely; in African countries such as Nigeria and Benin and among Chinese in Singapore, Taiwan, and Hawaii the incidence is high, while in the continental United States and in western Europe primary cancer of the liver is relatively rare. Environmental factors appear to play an important role; the disease is linked to infectious hepatitis B virus (prevalence of chronic viral hepatitis or the chronic presence of viruses in the blood [viremia] caused by hepatitis B), to malnutrition, and to natural chemical carcinogens such as aflatoxin B1, toxic alkaloids from plants used to brew certain native teas, and nitrosamines. Chronic alcohol abuse, which leads to cirrhosis (scarring) of the liver*, is a significant risk factor, especially in the Western world, since it appears to predispose a person to the development of liver cancer. Long exposure to certain environmental poisons, such as vinyl chloride or carbon tetrachloride, has also been shown to lead to hepatic cancer.

Primary cancers of the liver are carcinomas arising from liver cells, the major cellular component of liver (hepatocellular carcinomas), or, more rarely, from a minor cellular component of liver, bile duct cells (cholangiocarcinomas). Both types of carcinoma tend to spread extensively within the liver; and the hepatocellular carcinomas also grow into the veins of the liver, from which they may spread to more distant sites, such as the lungs. Cancer of the liver may be successfully treated surgically if the tumour has not spread widely within the liver or beyond it.

Cancer originating in the liver, usually in hepatocytes and less frequently in cells of bile duct origin, as mentioned is rare in the West and is almost always associated with active cirrhosis, particularly the form found in patients with chronic hepatitis.

* There are of course types of cirrhosis (eg Primary Biliary Cirrhosis, an autoimmune disease, or hepatic cirrhosis due to ingestion of arsenic) which are not caused by intentional drinking and can occur in persons abstaining from alcohol.

Hepatitis B virus

In recent years certain DNA viruses have been strongly implicated as causal agents for a variety of cancers in humans. These include human papillomavirus (HPV) as a cause of genital cancers in both sexes worldwide, the Epstein-Barr virus (EBV) for childhood lymphoma in Africa and cancer of the nose and throat in Asia and Africa, and the hepatitis viruses B and C that cause liver cancer worldwide with the highest incidence in Asia and Africa. However, at present only one type of human cancer, the rare adult T-cell leukemia, has been solidly linked to infection with an RNA virus, the human T-cell leukemia virus (HTLV-1). While much experimental and clinical evidence supports the carcinogenic role of the above-mentioned viruses in humans, additional research suggests that other factors also may be required. Observations that support the multifactorial nature of viral carcinogenesis include the continuous but not neoplastic growth of human cells infected in culture with HPV, the restricted geographic distribution of cancers induced by EBV, and the lack of either an oncoprotein (protein product produced by an oncogene) for HBV or evidence of consistent integration of the virus near a proto-oncogene encoding for a growth-regulatory protein. Thus far, oncogenic viruses have not been shown to induce DNA mutations directly in human cells; rather, their contribution seems to lie in promoting and hastening the process of mutation.

Infection with hepatitis B virus (HBV) is endemic in populations that also have a high incidence of liver cancer. This has led some researchers to conclude that the virus is the cause of liver cancer. Cancer, however, is a multifactorial disease, and liver cell cancer is an excellent example. HBV infection invariably leads to the augmented growth of liver cells, which renders them exquisitely sensitive to carcinogens. Since populations plagued by a high incidence of liver cancer are also chronically exposed to numerous toxic substances, some of which are carcinogenic for the liver, it is difficult to dissect the interactions of virus and carcinogen with sufficient precision to either indict or exonerate HBV as a liver oncogen. Thus, HBV must be considered only as a possible carcinogen. HBV may well be considered a cocarcinogen, however; it may so increase the sensitivity of liver cells to carcinogens that it decreases the latent period during which the cells undergo malignant transformation and increases the number of tumors that ultimately develop.

Metastatic cancer in the liver

Cancers arising elsewhere in the body, particularly in abdominal organs, lungs, and lymphoid tissue, commonly lead to metastatic cancer in the liver and are by far the most frequent type of hepatic malignancy. Usually, when such metastases are found, the primary tumor has advanced beyond the stage where it can be removed surgically.

Benign tumors and cysts

Various benign types of tumors and cysts arise from certain components of the liver, such as the hepatocytes (adenomas) or blood vessels (hemangiomas). While the cause of these lesions is not always clear, hepatic adenomas are associated with the prolonged use of female sex hormones (estrogens). Symptoms of benign tumours depend mainly on their size and their position in relation to the surface of the liver. If they enlarge significantly, patients may note pain or sensations of heaviness in the upper abdomen. When benign tumors are located close to the surface of the liver, they may rupture through the capsule and bleed freely into the abdominal cavity. Surgery is then required.

Benign cysts (tissue swellings filled with fluid) in the liver may occur as congenital defects or as the result of infections from infestation of the dog tapeworm (Echinococcus granulosus). Abscesses on the liver result from the spread of infection from the biliary tract or from other parts of the body, especially the appendix and the pelvic organs. Specific liver abscesses also result from infections with the intestinal parasite Entamoeba histolytica. Abscesses usually respond well to treatment with specific antibiotics, although surgical drainage is required in some cases.

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