What is the pathophysiology of hepatocellular cancer?

Question

What is the pathophysiology of hepatocellular cancer?

Answer 1

Any chronic inflammatory liver disease has the potential to induce hepatocellular carcinoma, but the pathophysiologic process most commonly associated with the disease is cirrhosis, found in up to 80% of cases (1). However, knowledge of all possible sources is important, considering that 20% of cases are due to noncirrhotic, nonviral causes. Whether cirrhosis itself or the mechanism underlying cirrhosis is responsible for malignant transformation of hepatocytes is not known.

Certain viral, environmental, and hereditary causes of cirrhosis have a strong correlation with hepatocellular carcinoma. Chronic viral hepatitis as a cause of cirrhosis and hepatocellular carcinoma is well known. Hepatitis B virus infection is the leading cause of chronic liver disease and hepatocellular carcinoma around the world. About 350 million people worldwide have chronic hepatitis B, with the highest prevalence found in regions that have the highest rates of hepatocellular carcinoma (2). In the United States, hepatitis B virus infects about 1.2 million people and hepatitis C virus about 4 million people (3). Hepatitis C virus RNA is found in about 65% of patients who test negative for hepatitis B surface antigen at diagnosis of their hepatocellular carcinoma (4).

Alcohol use is also a common cause of cirrhosis, which can indirectly lead to hepatocellular carcinoma. However, a direct carcinogenic effect of alcohol on the liver has not been proved.

Certain substances derived from plants, industrial pollutants, and synthetic pharmaceutical agents have been found to cause hepatocellular carcinoma in animals and, as proved through epidemiologic studies, in humans. For example, when present in detectable levels, aflatoxin B (a mycotoxin in inappropriately stored grain) confers an odds ratio for hepatocellular carcinoma of 5.5 (5). Vinyl chloride is the most studied of the industrial carcinogens. Estrogens and androgens, as found in oral contraceptives and anabolic steroids, have been found to be carcinogenic in rodents.

Hemochromatosis carries a relative risk of more than 200 for hepatocellular carcinoma, which can occur without cirrhosis (6). Alpha1-antitrypsin deficiency and primary biliary cirrhosis are also associated with the disease.

Answer 2

pathophysiology of hepatocellular cancer

Incidence:
HCC represents ~ 5 % of all cancers.
Annual incidence in men averages 20-28/100'000 in Asia and Africa but only 5/100'000 in Europe and the US.
Annual incidence in cirrhosis from HBV, HCV and hemochromatosis is 2, 3-8 and 5 %, respectively.

Screening:

Ultrasound and determination of a-fetoprotein every 6 months in patients at risk
Nodules > 1cm need diagnostic work-up.
Nodules < 1cm: increase screening frequency to every 3 months
Ultrasound has a sensitivity, specificity and positive predictive value of 71, 93 and 14 %, respectively. The corresponding figures for a-fetoprotein are 39, 76 and 9 %.

Diagnosis:

Histology by FNP and or biopsy is advocated for tumors < 2 cm. (My opinion - cave seeding)
For lesions > 2 cm two coincident imaging techniques (US, spiral CT, MRI or angiography) showing arterial hypervascularization or one imaging technique showing arterial hypervascularization and a-fetoprotein > 400 ng/ml.
Extent of disease: spiral CT with fine liver slices. If OLT is considered include spiral CT of chest and bone scintigraphy. Lipiodol CT is obsolete and should not be used.

Answer 3

it has to do with the damage of hepatocellular genome due to either viral genome integration or toxic effect of ethanol metabolites. Both of them cause chirrosis, the pre-cancer stage. If u are interested I'll Have more details for u tomorrow