HEALTH - LIVER CANCER (HEPATOCELLULAR - CARCINOMA - HEPATITIS)
What is Liver Cancer?
Liver cancer (hepatocellular carcinoma) is a cancer arising from the liver. It is also known as primary liver cancer or hepatoma. The liver is made up of different cell types (for example, bile ducts, blood vessels, and fat-storing cells). However, liver cells (hepatocytes) make up 80% of the liver tissue. Thus, the majority of primary liver cancers (over 90 to 95%) arises from liver cells and is called hepatocellular cancer or carcinoma.
When patients or physicians speak of liver cancer, however, they are often referring to cancer that has spread to the liver, having originated in other organs (such as the colon, stomach, pancreas, breast, and lung). More specifically, this type of liver cancer is called metastatic liver disease (cancer) or secondary liver cancer. Thus, the term liver cancer actually can refer to either metastatic liver cancer or hepatocellular cancer. The subject of this article is hepatocellular carcinoma, which I will refer to as liver cancer.
Hepatocellular carcinoma accounts for 80 - 90% of all liver cancers. This type of cancer occurs more often in men than women. It is usually seen in people ages 50 - 60. The disease is more common in parts of Africa and Asia than in North or South America and Europe.
Liver cancer is the fifth most common cancer in the world. A deadly cancer, liver cancer will kill almost all patients who have it within a year. In 1990, the World Health Organization estimated that there were about 430,000 new cases of liver cancer worldwide, and a similar number of patients died as a result of this disease. About three quarters of the cases of liver cancer are found in Southeast Asia (China, Hong Kong, Taiwan, Korea, and Japan). Liver cancer is also very common in sub-Saharan Africa (Mozambique and South Africa).
The frequency of liver cancer in Southeast Asia and sub-Saharan Africa is greater than 20 cases per 100,000 population. In contrast, the frequency of liver cancer in North America and Western Europe is much lower, less than five per 100,000 population. However, the frequency of liver cancer among native Alaskans is comparable to that seen in Southeast Asia. Moreover, recent data show that the frequency of liver cancer in the U.S. overall is rising. This increase is due primarily to chronic hepatitis C, an infection of the liver that causes liver cancer.
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Health: Risk Factors of Liver Cancer (Hepatocellular - Carcinoma)
Hepatitis B infection
The role of hepatitis B virus (HBV) infection in causing liver cancer is well
established. Several lines of evidence point to this strong association. As
noted earlier, the frequency of liver cancer relates to (correlates with) the frequency
of chronic hepatitis B virus infection. In addition, the patients with hepatitis
B virus who are at greatest
risk for liver cancer are men with hepatitis B virus cirrhosis (scarring of the liver) and a family
history of liver cancer.
Perhaps the most convincing evidence, however, comes from a prospective (looking forward in time) study done in the 1970's in Taiwan involving male government employees over the age of 40. In this study, the investigators found that the health risk of developing liver cancer was 200 times higher among employees who had chronic hepatitis B virus as compared to employees without chronic hepatitis B virus!
Studies in animals also have provided evidence that hepatitis B virus can cause liver cancer. For example, we have learned that liver cancer develops in other mammals that are naturally infected with hepatitis B virus-related viruses. Finally, by infecting transgenic mice with certain parts of the hepatitis B virus, scientists caused liver cancer to develop in mice that do not usually develop liver cancer. (Transgenic mice are mice that have been injected with new or foreign genetic material.)
How does chronic hepatitis B virus cause liver cancer? In patients with both chronic hepatitis B virus and liver cancer, the genetic material of hepatitis B virus is frequently found to be part of the genetic material of the cancer cells. It is thought, therefore, that specific regions of the hepatitis B virus genome (genetic code) enter the genetic material of the liver cells. This hepatitis B virus genetic material may then disrupt the normal genetic material in the liver cells, thereby causing the liver cells to become cancerous.
The vast majority of liver cancer that is associated with chronic hepatitis B
virus occurs in
individuals who have been infected most of their lives. In areas where hepatitis
B virus is
not always present (endemic) in the community (for example, the U.S.), liver cancer is relatively
uncommon. The reason for this is that most of the people with chronic hepatitis
B virus in
these areas acquired the infection as adults.
However, liver cancer can develop in individuals who acquired chronic hepatitis B virus in adulthood if there are other risk factors, such as chronic alcohol use or co-infection with chronic hepatitis C virus infection.
Hepatitis C infection
Hepatitis C virus (HCV) infection is also associated with the development of
liver cancer. In fact, in Japan, hepatitis C virus is present in up to 75% of cases of liver
cancer. As with
hepatitis B virus, the majority of hepatitis C virus patients with liver cancer have associated cirrhosis (liver
scarring). In several retrospective-prospective studies (looking backward and
forward in time) of the natural history of hepatitis C, the average time to
develop liver cancer after exposure to hepatitis C virus was about 28 years.
The liver cancer occurred about eight to 10 years after the development of cirrhosis in these patients with hepatitis C. Several prospective European studies report that the annual incidence (occurrence over time) of liver cancer in cirrhotic hepatitis C virus patients ranges from 1.4 to 2.5% per year.
In hepatitis C virus patients, the risk factors for developing liver cancer include the presence of cirrhosis, older age, male gender, elevated baseline alpha-fetoprotein level (a blood tumor marker), alcohol use, and co-infection with hepatitis B virus. Some earlier studies suggested that hepatitis C virus genotype 1b (a common genotype in the U.S.) may be a risk factor, but more recent studies do not support this finding.
The way in which hepatitis C virus causes liver cancer is not well understood. Unlike hepatitis B virus, the genetic material of hepatitis C virus is not inserted directly into the genetic material of the liver cells. It is known, however, that cirrhosis from any cause is a risk factor for the development of liver cancer. It has been argued, therefore, that hepatitis C virus, which causes cirrhosis of the liver, is an indirect cause of liver cancer.
On the other hand, there are some chronic hepatitis C virus infected individuals who have liver cancer without cirrhosis. So, it has been suggested that the core (central) protein of hepatitis C virus is the culprit in the development of liver cancer. The core protein itself (a part of the hepatitis C virus) is thought to impede the natural process of cell death or interfere with the function of a normal tumor suppressor (inhibitor) gene (the p53 gene). The result of these actions is that the liver cells go on living and reproducing without the normal restraints, which is what happens in cancer.
Alcohol
Cirrhosis caused by chronic alcohol consumption is the most common
association of liver cancer in the developed world. Actually, we now understand that many
of these cases are also infected with chronic hepatitis C virus. The usual setting is an
individual with alcoholic cirrhosis who has stopped drinking for ten years, and
then develops liver cancer.
It is somewhat unusual for an actively drinking alcoholic to develop liver cancer. What happens is that when the drinking is stopped, the liver cells try to heal by regenerating (reproducing). It is during this active regeneration that a cancer-producing genetic change (mutation) can occur, which explains the occurrence of liver cancer after the drinking has been stopped.
Patients who are actively drinking are more likely to die from non-cancer related complications of alcoholic liver disease (for example, liver failure). Indeed, patients with alcoholic cirrhosis who die of liver cancer are about 10 years older than patients who die of non-cancer causes. Finally, as noted above, alcohol adds to the health risk of developing liver cancer in patients with chronic hepatitis C virus or hepatitis B virus infections.
Aflatoxin B1
Aflatoxin B1 is the most potent liver cancer-forming chemical known. It is a
product of a mold called Aspergillus flavus, which is found in food that has
been stored in a hot and humid environment. This mold is found in such foods as
peanuts, rice, soybeans, corn, and wheat. Aflatoxin B1 has been implicated in
the development of liver cancer in Southern China and Sub-Saharan Africa. It is thought
to cause cancer by producing changes (mutations) in the p53 gene. These
mutations work by interfering with the gene's important tumor suppressing
(inhibiting) functions.
Drugs, medications, and chemicals
There are no medications that cause liver cancer, but female hormones (estrogens) and
protein-building (anabolic) steroids are associated with the development of
hepatic adenomas. These are benign liver tumors that may have the potential to
become malignant (cancerous). Thus, in some individuals, hepatic adenoma can
evolve into cancer.
Certain chemicals are associated with other types of cancers found in the liver. For example, thorotrast, a previously used contrast agent for imaging, caused a cancer of the blood vessels in the liver called hepatic angiosarcoma. Also, vinyl chloride, a compound used in the plastics industry, can cause hepatic angiosarcomas that appear many years after the exposure.
Hemochromatosis
Liver cancer will develop in up to 30% of
patients with hereditary hemochromatosis.
Patients at the greatest risk are those who develop cirrhosis with their
hemochromatosis. Unfortunately, once cirrhosis is established, effective removal
of excess iron (the treatment for hemochromatosis) will not reduce the risk of
developing liver cancer.
Cirrhosis
Individuals with most types of cirrhosis of the liver are at an increased
risk of developing liver cancer. In addition to the health conditions described above (hepatitis
B, hepatitis C, alcohol, and hemochromatosis), alpha 1 anti-trypsin deficiency,
a hereditary health condition that can cause emphysema and cirrhosis, may lead to liver
cancer.
Liver cancer is also strongly associated with hereditary tyrosinemia, a
childhood biochemical abnormality that results in early cirrhosis. Certain causes of cirrhosis are less frequently associated with liver cancer than are
other causes.
Health: Symptoms of Liver Cancer (Hepatocellular - Carcinoma)
Most people don't have symptoms in the early stages of liver cancer, which means the disease may not be detected until it's quite advanced. When symptoms do appear, they may include some or all of the following:
- Loss of appetite and weight
- Abdominal pain, especially in the upper right part of your abdomen, that may extend into your back and shoulder
- Nausea and vomiting
- General weakness and fatigue
- An enlarged liver
- Abdominal swelling (ascites)
- A yellow discoloration of your skin and the whites of your eyes (jaundice)
Health: Diagnosis of Liver Cancer (Hepatocellular - Carcinoma)
If you experience any of the symptoms of liver cancer, your doctor will ask you about your medical history and perform a physical exam. Tests and procedures used to diagnose liver cancer include:
- Ultrasound (ultrasonography). This test uses sound waves to produce a picture of internal organs, including the liver. Ultrasound is painless and usually takes less than 30 minutes. While you lie on a bed or examining table, a wand-shaped device (transducer) is placed on your body. It emits sound waves that are reflected from your liver and transformed into a computer image. Ultrasound provides information about the shape, texture and makeup of tumors.
- Computerized tomography (CT) scan. This test uses X-rays to produce cross-sectional images of your body. You may also have a variation of the test — known as a CT angiogram — in which contrast dye is injected into an artery in your liver. X-rays then track the dye as it flows through the blood vessels in your liver. A CT angiogram, which may take up to an hour to perform, can provide detailed information on the number and location of liver tumors, but a CT scan exposes you to more radiation than conventional X-rays do, and some people may experience an allergic reaction to the contrast dye.
- Magnetic resonance imaging (MRI). MRI creates images using a magnetic field and radio waves. Sometimes a contrast dye also may be used. The test can take from 15 minutes to an hour. Newer MRIs can show images of the ducts that transport bile from the liver to the upper part of the small intestine (duodenum) as well as of the arteries and veins within the liver.
- Liver biopsy. In this procedure, a sample of tissue is removed from your liver and examined under a microscope. Liver biopsy is considered the only definitive way to diagnose liver cancer. Your doctor may use a thin needle or a lighted instrument (laparoscope) to obtain the sample. Biopsy carries a health risk of bleeding, bruising and infection.
- Blood tests. Doctors sometimes use a blood test that checks for the presence of alpha-fetoprotein (AFP) — a type of protein found in small amounts in adults — to detect liver cancer. But the test isn't perfect. Not all malignant liver tumors produce AFP, and those that do may be advanced by the time protein levels become elevated. In addition, other types of cancer and even some noncancerous liver diseases can raise AFP levels.
- Laparoscopy. A laparoscopy uses a thin, lighted tube to look at the liver and other internal organs. The tube is inserted through a small incision in the abdomen. The procedure is usually done under sedation and local anesthetic to numb the area; it doesn’t usually require a general anesthetic.
- Physical examination. If a person has symptoms of HCC, the doctor will feel the abdomen to check the liver, spleen, and other nearby organs for lumps, swelling, or other changes. The doctor will also look for an abnormal buildup of fluid in the abdomen and for signs of jaundice (yellowing of the skin and whites of the eyes).
Health: Staging of Liver Cancer (Hepatocellular - Carcinoma)
Staging tests help determine the size and location of cancer and whether it has spread. Liver cancer may be staged in different ways. One method uses the Roman numerals I through IV, with higher numbers indicating cancers that are more advanced. A stage I tumor is small and confined to one lobe of the liver. By stage IV, several tumors may exist in different lobes, or malignant cells may have spread to other parts of the body.
Doctors may also use the following stages to describe primary liver cancer in adults:
- Localized resectable. At this stage, the tumor is confined to one lobe of your liver and can be completely removed in an operation. The term "resectable" refers to a tumor that can be surgically removed.
- Localized unresectable. The cancer is found in only one part of your liver, but can't be completely removed, either because the noncancerous portion of your liver isn't healthy or because the cancer is located near your liver's main arteries, veins and bile ducts.
- Advanced. This stage of cancer has spread throughout the liver or to other parts of your body, particularly the bones or lungs. You're more likely to have advanced cancer if you also have cirrhosis or chronic hepatitis.
- Recurrent. This means the cancer has returned to your liver or to another part of your body after being treated.
Stages of primary cancer in children
Doctors use the following stages to describe childhood liver cancer:
- Stage I. At this stage, the cancer can be removed with surgery.
- Stage II. Most stage II liver cancers can be removed with an operation, but microscopic amounts of cancer remain in the liver after surgery.
- Stage III. At this stage, some of the cancer may be surgically removed, but some will remain in the lymph nodes or abdomen.
- Stage IV. This stage of cancer has spread to other parts of the body.
- Recurrent. This means the cancer has returned after it has been treated. It may recur in the liver or in another part of the body.
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Natural Alternative Treatment Options: NATURAL CANCER TREATMENT
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Health: Conventional Treatment of Liver Cancer (Hepatocellular - Carcinoma)
Treatments for primary liver cancer depend on the extent (stage) of the disease as well as your age, overall health, feelings and personal preferences. Discuss all of your options carefully with your treatment team or health care provider.
The goal of any treatment is to eliminate the cancer completely. When that isn't possible, the focus may be on preventing the tumor from growing or spreading. In some cases palliative care only is appropriate. Palliative care refers to treatment aimed not at removing or slowing the disease but at helping relieve symptoms and making you as comfortable as possible.
Treatments for primary liver cancer in adults
- Surgery. The best treatment for localized resectable cancer is usually an operation known as surgical resection. In some cases, the area of the liver where the cancer is found can be completely removed. You aren't a candidate for surgical removal of liver tumors if you have cirrhosis or only a small amount of healthy liver tissue. Even when resections are successful, there is a chance the cancer can recur elsewhere in the liver or in other areas within a few years.
- Alcohol injection. In this procedure, pure alcohol is injected directly into tumors, either through the skin or during an operation. Alcohol dries out the cells of the tumor and eventually the cells die. Each treatment consists of one injection, although you may need a series of injections for the best results. Alcohol injection has been shown to improve survival in people with small hepatocellular tumors. It may also be used to help reduce symptoms in cases of metastatic liver cancer. The most common side effect is leaking of alcohol onto the liver or into the abdominal cavity.
- Radiofrequency ablation. In this procedure, electric current in the radiofrequency range is used to destroy malignant cells. Using an ultrasound or CT scan as a guide, your surgeon inserts several thin needles into small incisions in your abdomen. When the needles reach the tumor, they're heated with an electric current, destroying the malignant cells. Radiofrequency ablation is an option for people with small, unresectable hepatocellular tumors and for some types of metastatic liver cancers. Although the procedure has a somewhat higher risk of serious complications than alcohol injection does, it appears to provide better outcomes.
- Chemoembolization. Chemoembolization is a type of chemotherapy treatment that supplies strong anti-cancer drugs directly to the liver. Chemoembolization isn't curative, but it can shrink tumors in a certain percentage of people, which may provide symptom relief and improve survival. During the procedure, the hepatic artery — the artery from which liver cancers derive their blood supply — is blocked, and chemotherapy drugs are injected between the blockage and the liver. The idea is that by targeting the tumor directly, doctors can use potent doses of drugs without creating as many side effects as occur with systemic chemotherapy. But the fact is that chemoembolization causes many of the same side effects as other forms of chemotherapy, including abdominal pain, nausea and vomiting. Chemoembolization is less likely to cause some side effects such as lowered blood cell counts or hair loss.
- Cryoablation (cryosurgery or cryotherapy). This treatment uses extreme cold to destroy cancer cells. Cryoablation may be an option for people with inoperable primary and metastatic liver cancers. It may also be used in addition to surgery, chemotherapy or other standard treatments. During the procedure, your doctor places an instrument (cryoprobe) containing liquid nitrogen directly onto liver tumors. Ultrasound images are used to guide the cryoprobe and monitor the freezing of the cells. Side effects include damage to the bile ducts and major blood vessels, leading to bleeding or infection.
- Radiation therapy. This treatment uses high-powered energy beams to destroy cancer cells and shrink tumors. Radiation may come from a machine outside your body or from radiation-containing materials inserted into your liver. Radiation may be used on its own to treat localized unresectable cancer. Or you may have radiation therapy following surgical removal of a tumor to help destroy any remaining malignant cells. Radiation side effects may include fatigue, nausea and vomiting.
- Chemotherapy. This treatment uses powerful drugs to kill cancer cells. Chemotherapy may be systemic — meaning it travels throughout your body in your bloodstream — or regional. Systemic chemotherapy is generally not effective in treating liver cancer, but may be a treatment option in certain cases.
- Liver transplantation. In this surgical procedure, a diseased liver is removed and replaced with a healthy, donated organ. Liver transplantation may be an option for some people with small, early-stage liver tumors and for certain people with bile duct tumors. In other cases, especially when tumors are larger or blood vessels are involved, a transplant may not improve long-term outlook because the cancer may recur outside the new liver.
- Sorafenib (Nexavar). Sorafenib was approved by the Food and Drug Administration in 2007 for use in advanced inoperable liver cancer. Sorafenib is a targeted therapy designed to interfere with a tumor's ability to generate new blood vessels. Sorafenib has been shown to slow or stop advanced liver cancer from progressing for a few months longer than with no treatment. More studies are needed to understand how targeted therapies may be used to control advanced liver cancer.
Treatments for primary liver cancer in children
Liver cancer in young people is rare. As a result, most children with
the disease are treated at centers that specialize in childhood
cancers. In general, the treatments available for children are the same
as for adults, and the best approach depends on the stage and type of
cancer as well as the child's age and overall health.
Advanced HCC
Advanced HCC is cancer that has spread throughout the liver and to other parts of the body. At this stage, the goal of treatment is typically not to cure the cancer, but to slow the disease’s growth and make the patient more comfortable. Therapy for advanced HCC may include chemotherapy (including sorafenib, see Targeted therapy above), radiation therapy, or both. Palliative care can reduce pain, control symptoms, and make the patient’s quality of life better.
Clinical trials
Because standard treatments often aren't effective in treating liver
cancer, you may want to consider participating in a clinical trial — a
research study that tries to improve current treatments or find new
treatments. This can give you access to experimental therapies that
might not otherwise be available. There are no guarantees with clinical
trials, however, and you should fully understand the potential risks as
well as possible benefits before taking this step.
Health: Prevention of Liver Cancer (Hepatocellular - Carcinoma)
In many cases it's not possible to prevent the spread of cancer from another site to the liver. And it may not always be possible to prevent primary liver cancer. But you can greatly reduce your risk by taking steps to protect yourself from hepatitis B and C, cirrhosis and other liver diseases.
Get vaccinated
The single most effective way to prevent hepatitis B is to receive the
hepatitis B vaccine, which provides more than 90 percent protection for
both adults and children. Protection lasts years and may even be
lifelong. The vaccine can be given to almost anyone, including infants,
older adults and those with compromised immune systems. Infants often
receive the vaccine in the first year of life — typically at 2, 4 and 9
months of age.
Take measures to prevent hepatitis C
Because no vaccine for hepatitis C exists, the following measures can play a key role in protecting your health:
- Educate yourself and others. Make sure you understand what viral hepatitis is and how it's transmitted.
- Know the health status of any sexual partner. Don't engage in unprotected sex unless you're absolutely certain your partner isn't infected with HBV, HCV or any other sexually transmitted disease. If you don't know the health status of your partner, use a new latex condom every time you have vaginal or anal sex. If you don't have a male condom, use a female condom.
- Don't use IV drugs, but if you do, use a clean needle. The best way to protect yourself from HCV is not to inject drugs. But if that isn't an option for you, make sure any needle you use is sterile, and don't share it. Contaminated drug paraphernalia is responsible for about half of all new hepatitis C cases. Take advantage of needle exchange programs in your community and consider seeking help for your drug use.
- Avoid body piercing and tattooing. Needles that may not be properly sterilized can spread the virus.
- Be cautious about blood products in certain countries. Most Americans with HCV became infected through blood transfusions received before 1992 — the year improved blood-screening tests became available. Although the blood supply is now well screened in the United States, this isn't always the case in other countries. If an emergency requires that you receive blood or blood products in another country, get tested for HCV and HBV as soon as you return home.
- Avoid or limit alcohol. Alcohol speeds the progression of any liver disease you may have and is the leading cause of cirrhosis — a key factor in primary liver cancer.
- Avoid medications that may cause liver damage. Your doctor can advise you about these medications, which may include over-the-counter medications as well as prescription drugs. Avoid mixing alcohol and acetaminophen (Tylenol, others) — a combination known to cause liver damage.
- Avoid exposure to environmental toxins. Your liver filters every substance you ingest, inhale or apply to your skin. For that reason, avoid unnecessary chemical exposure.
- Certain patients may benefit from hemochromatosis screening.
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Disclaimer: This information is not presented by a medical practitioner. Therefore any content of this site is strictly intended for educational and informational purpose only. Any access to this site is strictly on a voluntary basis and at the sole discretion of the user. No content of this site is intended as a substitute for medical advice, diagnosis or treatment, nor constitute the practice of any medical profession or health care provider. The information provided on this site is here to educate visitors on health issues that may affect their lives. Otherwise, always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition. And never disregard professional medical advice or delay in seeking it because of something you have read.
Sources: NIH News In Health/National Institutes of Health/National Library of Medicine/Dept of Health and Human Services_______________________________________________________________________________________________________
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