Brief introduction to hepatocellular carcinoma

Normal liver zones, microscopic Liver is divided histologically into lobules. The center of the lobule is the central vein. At the periphery of the lobule are portal triads. Functionally, the liver can be divided into three zones, based upon oxygen supply. Zone 1 encircles the portal tracts where the oxygenated blood from hepatic arteries enters. Zone 3 is located around central veins, where oxygenation is poor. Zone 2 is located in between.

Hepatocellular carcinoma, microscopic The malignant cells of this hepatocellular carcinoma (seen mostly on the right) are well differentiated and interdigitate with normal, larger hepatocytes (seen mostly at the left). Data source: Hepatic Pathology Index

Hepatocellular Carcinoma (HCC) involves the malignant tumor of the liver, and accounts for 80% to 90% of liver cancers.
It is a most common, and deadly, type of cancer. The World Health Organization (WHO) reports that at least 550,000 people
die each year from HCC. The incidence varies greatly with geographical location, sex, ethnic background, and age:

The cause of HCC is currently unknown, though it is possible for any kind of chronic inflammatory liver disease to develop
into HCC. Several risk factors, however, have been identified:

HCC symptoms also vary with geographical difference. In high-incidence regions, the symptoms are aggressive, involving bleeding,
hepatic rupture, hemoperitoneum; in low-incidence regions, the symptoms tend to be milder, including abdominal pain or tenderness,
malaise, weight loss, hepatomegaly, and jaundice (though rare).

A diagnosis of HCC begins with physical examination, searching for lumps in the abdomen, signs of liver enlargement, and noise caused
by suppressed blood vessels surrounding the tumor. What follows up is the AFP blood test (alpha-fetoprotein), done by measuring the
amount of protein present in the blood stream. A level of AFP exceeding 500 micrograms/L is a positive finding. Between 50% to 75% of
HCC patients suffer a high level of alpha-fetoprotein, yet this characteristic is shared by other cancer and hepatitis patients.
The more deterministic diagnosis methods are:

CT scan	CT Scan - Multiple X-rays are used to create a computerized 3D image of the internal organs. As shown in the left figure, the tumor is delineated by the dark area and shown by the arrow. This is in marked contrast to the normal gray color of the liver.
	Ultrasound - High frequency sound waves create an image of the internal organs on a monitor.
	MRI - Powerful magnets and radio signals create an image of the internal organs on a computer.
	Liver Scan - Radioactive isotopes are injected into the bloodstream. A scanner detects these isotopes, and produces a picture of their location. Under normal conditions, the isotopes would be evenly spread throughout the organ.

A liver biopsy remains the best way to discover HCC. A long needle is inserted into the liver to remove a small sample for HCC testing. This method is
extremely effective and safe, with a less than 0.5% possibility of inducing fatal hemorrhage.

Treatment for HCC:

	Surgery - Ridding the body of tumor or liver transplantation. The problem with the first approach is that more often than not, the cancer cannot be completely removed. Transplantation serves as a better way, but not all patients are eligible.
	Tumor Ablation or embolization - Ablation is the destruction of abnormal tissue without removing it. Examples include: high-energy radio waves to heat up liver tumors, tumors up to 4 cm. (or 2 in.) in diameter can be effectively destroyed with this technique; cyrosurgery, using sub-zero temperatures to freeze the tumor and let it be reabsorbed by the body; alcohol injection, injecting 100% absolute alcohol into tumors cause cells to dry our and cellular protein to disintegrate, leading to tumor cell death. Ablation is results in blood supply reduction, so it is unsuitable for hepatitis and cirrhosis patients.
	Chemotherapy - It is a treatment that works by drugs to interfere with the growth of cancer cells and promote them to die. Treatment of the entire body is called systemic chemotherapy, while treatment of localized areas is called regional chemotherapy. Liver cancer does not respond to most chemotherapy drugs. The only drugs that have been effective in shrinking tumors are doxorubicin, which is the most successful single drug, and cisplatin. In most studies, systemic chemotherapy has not helped patients to live longer.
	Radiation Therapy - Radiation therapy plays a relatively minor role in the treatment of liver cancer. Most primary tumors that metastasize to the liver are resistant to radiation therapy, while the healthy liver is highly susceptible to radiation damage. Radiation therapy is often used to treat patients who have tumors of the bile duct or gallbladder. Studies are going on to find out if using radiation along with certain chemotherapy drugs might work in treating liver cancer.
	Above is a CT scan of a patient with two liver tumors (depicted by arrows). The patient underwent an injection with DTI-0l5, which produced death of both tumors (depicted by the dark homogenous masses and two white arrows).

There is no perfect cure for the treatment of HCC, and the methods all have their potential side effects. This makes the prevention of HCC all the more essential. Nonspecific measures such as public health policies, clean sterile needles, stringent blood donation, good general hygiene, etc., have been under progress in all countries. Specific measures, such as universal hepatitis B vaccination for children, have proven to be a substantial aid in reducing HCC cases.

A new category of HCC-related information has been expanding rapidly recently involves the study of cancer genetics. Studies on gene mutation that is likely lead to HCC can serve as part of the screening process. Further understanding of genetic issues of HCC will contribute to the prevention, identification, and treatment of the disease.

Sites of hepatology associations:

AASLD - American Association for the Study of Liver Disease
EASL - The European Association for the Study of Liver

Sites of Journals:

Hepatology
Journal of Hepatology
Hepatology Research
Seminars in Liver Disease
Liver Transplantation

Others: