What does the Liver Do?

The liver is an organ in the abdomen which is necessarily to live . It is mostly located behind the right ribcage, and when it becomes enlarged it protrudes below the right ribcage ("right costal margin"). It is composed of right and left "lobes", and a smaller "quadrate" lobe. Thegall bladder hangs down from the bottom of the liver, collecting greenish bile from it. The liver has as a major blood supply the "hepatic artery" which comes off of the aorta. The "hepatic vein" collects nutrients and drugs from the intestines and delivers them to the liver for processing. The liver drains blood via the large "inferior vena cava", directly into the heart. There is also a system of draining "lymph glands" around the liver which help to purify the blood. These lymph glands are connected via "lymph channels" which ultimately drain back into the bloodstream via the "left thoracic duct"; they are important as they may serve as conduits for spread of infections or cancer. The liver has a "capsule" around it which contains nerve endings, accounting for pain when the liver enlarges and stretches it's capsule. The damaged liver has an amazing ability to regenerate itself. The body needs only about 10% of the liver to live, and if a piece is cut out or injured, it can grow back. Sometimes, however, the liver gets chronic diseases which impair it's ability to regenerate. It can become infiltrated with fat ("steatosis"), shrink from chronic alcohol or viral exposure ("cirrhosis") or grow large from infection or a blocked blood drainage ("hepatomegly") . Any inflammation of the liver, whether caused by germs, drugs, or radiation, is called hepatitis . A damaged liver may heal, or may slowly fail and require liver transplant to save the patient's life The liver is an astounding laboratory sustaining metabolism. Among it's functions are purification of the blood, removing poisonous ammonia from proteins, detoxifying alcohol and drugs, controlling the body's sugar and cholesterol balance, making bile to digest fats, forming clotting factors for the blood and generating new blood cells. This myriad of functions makes clear why the liver is essential to life.


What is Liver Cancer?

The cells in the liver are meant to divide to replace those that die of injury or old age. Like all cell division in the body, this process is tightly controlled to proceed in an orderly manner, and controlled by the "genes" within each cell. Liver cancer starts within a single cell. Something changes the control mechanisms within this cell, and it starts dividing in a disorganized, uncontrolled manner. The abnormal cell makes millions of copies of itself, called "clones". They fail to perform the normal functions of liver cells, but are only intent on dividing to make more copies of themselves. Eventually these abnormal cells form a clump, ortumor. A tumor is merely a swelling, and isn't necessarily cancerous. A benign tumor just grows in it's local area, and although it may become very large it doesn't spread and isn't cancer. By contrast, a malignant tumor is cancer and has a capacity to spread to any area of the body. This process of spread is called metastasis . It is this capacity to spread to other vital organs that makes cancer so dangerous.


How Common is Liver Cancer?

Liver cancer is fairly uncommon in the U.S.A. with20,000 new cases and 15,000 deaths each year in the United States. It represents about 2% of all new cancers. About 3000 of the cases are in the liver itself, the remainder are in the Gall Bladder and bile drainage ducts. However, in Asia and Africa liver cancers are one of the most common cancers. Males are effected slightly more commonly than females, and the average patient is 50 years old. By contrast, benign liver tumors are more common in females and tend to occur at a younger age. Overall the death rate from liver cancer has dropped in the U.S.A. over the past 50 years. This is both from a decline in the number of cases, and better treatment for the disease.


What are the Types of Liver Tumors?

The most common types of benign liver tumors are hemangiomas (which are a cluster of abnormal blood vessels forming a swelling), and adenomas (which are clumps or knots of liver tissue). The most common malignant liver cancers are hepatocellular carcinoma (80% of cases) which arises from the liver cells themselves, and is also known as ahepatoma (a poor name for liver cancer, since it sounds benign). Cholangiocarcinoma (15% of cases) arises from bile ducts in the liver as they proceed down toward the gallbladder. A Klatskin tumor is a cholangiocarcinoma located at where the gall bladder meets the liver. Rare types of liver cancer include the angiosarcoma (which arises from the blood vessels in the liver), lymphomas (from the immune cells in the liver) and carcinoids (from hormone making liver cells). The liver is a very common place for cancers originating in other body organs to spread to; since it offers a soft, spongy blood-rich surface for metastatic "seeds" to grow. If their are multiple areas of cancer in the liver, the chances are much higher that it began in some other organ and then spread to the liver. Bowel, lung, breast, bladder, prostate and esophagus cancers have particular propensities for liver spread. These are not considered "primary" liver cancer, and their treatment upon spread is discussed in their particular transcripts.


What Causes or Increases Risk for Liver Cancer?

As for any cancer, the exact reason why any one person gets liver cancer and another doesn't remains unknown . However, several things have been noted which increase the risk, called"risk factors":

1. Chronic Hepatitis can lead to changes in the liver cells associated with the most common type of liver cancer, hepatocellular carcinoma (HCC).
a)Hepatitis B -- evidence of prior infection is found in 75% of liver cancer patients worldwide. It can lead to cirrhosis, below. The more common Hepatitis A (spread by feces) isn't associated with liver cancer.
b)Carcinogens (chemicals inducing cancer) such as aflatoxin food contamination (used by Iraq on the Kurds) and nitrosamines.

2. Cirrhosis of the liver (the liver can shrink up and become fibrous and fatty in response to chronic irritation). Causes of cirrhosis include:
a) Alcoholism-- alcoholic cirrhosis leads to 5% of liver cancer.
b)Hemochromatosis is an overload of iron in the liver. 20% of patients who get cirrhosis from the overload may develop HCC.
c)Alpha1- antitrypsin deficiency is a rare condition where a necessary enzyme is lacking to break down waste products in the liver and lung. HCC can develop in 40% of patients who get this type of cirrhosis.

3. Miscellaneous irritants to the liver including:
a) Polyvinyl Chloride (PVC) is linked to angiosarcoma.
b)Liver flukes are linked with bile duct cancer in China.
c) Thorotrast is a contrast dye for radiology studies no longer used after being linked to angiosarcoma.
d)Radiation Exposure can lead to liver sarcomas, sometimes as long as 5 decades after the exposure.The common thread to liver cancer risk factors is chronic irritation, which causes the liver cells to divide more quickly than they ordinarily would to repair perceived damage. The more often cells divide, the more the chance for a genetically abnormal one to arise, with the gene changes leading to it's becoming cancerous.


What are the symptoms of Liver Cancer?

The most common symptoms of liver cancer are from a massive tumor growing in the liver, or even liver failure. A very early cancer will have no symptoms, since it is too small to cause any. As it enlarges, common symptoms include:
1.Pain in the right upper abdominal area caused by stretching of the liver's capsule, which is rich in nerves. The liver may then extend below the righ costal margin ("hepatomegaly") and be painful to probe.
2. Weight Loss and loss of appetite; the liver is a digestive organ.
3. Swelling of the abdomen (called "ascites" pronounced a-site-ees) from the liver failing to produce the protein required to hold the blood's fluid in the blood vessels, so it migrates out to fill the abdomen, scrotum and limbs.
4. Cirrhosis signs like breast swelling in males (from the liver failing to break down estrogens) and little spider shaped veins (angiomata) seen on the skin. Another sign of liver failure is very red palms ("palmar erythema").
5. Blood clotting problems leading to intestinal bleeding and bruises on the skin. The liver normally uses vitamin K from the diet and intestinal bacteria sources to synthesize the clotting factor ("prothrombin") necessary for life.
6.Fatigue and eventually coma from buildup of ammonia in the body.
7. Jaundice and light stools, from blockage of the bile draining system. Also looser and smellier stools may be seen, ("steatorrhea") indicating poor breakdown of fats in the digestive tract. Jaundice normally produces itching (pruritis) when it becomes marked. The first area notable for jaundice, caused by theliver's failure to clear bilirubin, is the whites of the eyes ("scleral icterus").
8. Paraneoplastic syndromes means unusual symptoms caused by chemical alterations in the body either from the liver failing or secretions from the tumor cells themselves. These include elevated blood calcium, low blood sugar, anemias, precocious puberty in children, intense flushing, and other metabolicdisturbances. These syndromes often will be alleviated with cancer shrinkage.
9. Signs of Distant Spread include bone pain, neurological symptoms from brain involvement, and intestinal blockage. These all indicate advanced disease.


How is Liver Cancer Diagnosed and Evaluated?

Since liver cancer is unusual, and it's symptoms mimic many other conditions, there is commonly a delay in making the diagnosis while the cancer grows larger. Unfortunately, most patients have advanced disease by the time the diagnosis is made. Important steps to diagnosing liver cancer include:
1. A high"index of suspicion" in patients with a history of chronic hepatitis, alcoholic cirrhosis, toxin exposure, or the rare genetic diseases which increase risk.
2. A Complete Physical Exam especially looking for signs of a tumor in the upper right abdomen and signs of liver failure like body swelling and bruising. Other organs (i.e. rectum, prostate, breast) are examined to see if a primary tumor has arisen there, and possibly spread to the liver.
3. Blood Tests including a complete blood count (CBC) to look for anemia or infection, and a blood chemistry panel(SMA) which tells about liver function and general metabolism. The most commonly elevated blood tests with liver damage are AST, ALT, GGT and alkaline phosphatase . These are all enzymes that are released into the bloodstream when liver cells die. Also, a hepatitis panel is appropriate. Blood clotting studies (PT/PTT) are gotten both to assess liver function and a part of a pre-surgical screen if surgery is a possibility. There is a "tumor marker" to help diagnosis liver cancer. In HCC patients, especially younger ones, the "alpha-fetoprotein" (AFP) blood test is elevated in over 50% but it may represent some other malignancy besides liver cancer. If it is elevated, it will usually return to normal with successful treatment.
4. Radiologic Tests, include standard Chest X-ray to look for infection or tumor in the lungs. Ultrasound (US) remains useful for looking at the shape of the liver, identifying a tumor, and tracking the progress of therapy. Ultrasound doesn't use any radiation (just sound waves) and is very safe in children and pregnant women. However, the results are very dependent upon the skill of the technician performing the test, and if something is found then a CT scan will be ordered anyway. A CT scan is very accurate for detecting tumors larger than 1 cm, it does use radiation like a series of multiple X-rays which are joined together. If contrast is injected into an arm vein for a CT scan, the blood vessel of the liver will be more clearly visible. It is best to ask for "omnipaque" or equivalent contrast, which is more expensive but less likely to cause an allergic reaction. The The CT scan isn't technician dependent, and is very good for showing extension of the tumor into nearby organs and enlarged lymph glands in the vicinity of the tumor, which can represent spread to them. Other tests to visualize cancer are arteriography, where some contrast dye is injected and special X-rays are taken that show the shape of the tumor's blood vessels. Another test is the MRI scan which uses no radiation, shows the organs in the abdomen very clearly and is excellent for showing local spread and imaging nearby lymph glands. The MRI can also be given with contrast ("gadolinium") to better show the blood vessels. However, it is expensive ($1000) and requires the patient to lie almost perfectly still for an hour to be accurate. These tests are gotten to evaluate a patient for possible surgery or check their response to therapy. Other more exotic tests, such as bone scans, liver-spleen scans, or CT scans of the brain are only gotten if their are symptoms is these particular areas, and the therapy will be changed depending upon the results of these tests.5. The only way to absolutely diagnose any cancer is by getting a piece of it fo analysis, that is a biopsy of the tumor. This biopsy may be obtained by a fine needle under local anesthesia, in the radiology department using ultrasound or CAT scan to guide the needle into the tumor. Several samples are usually taken for accuracy. Risks of biopsy include spilling the tumor or bleeding the from puncturing blood vessels in the tumor, this may require an emergency operation to stop bleeding. Overall fine-needle biopsy is safe and effective; i is a very common procedure in hospital Interventional Radiology Departments The biopsy material is examined by a pathologist, a physician who specializes in diagnosing diseases from tissue samples. If cancer is detected, he will specify the particulartype, and the grade (I,II or III) which tells how aggressive the cancer is likely to be. Higher grade cancers (III ) look more "malignant" under the microscope, with numerous cell divisions and cells scantly resembling normal liver tissue. They tend to be more aggressive (likely to grow very quickly and spread). On the other hand, low grade (I ) tumors have fewer cell divisions and look much like the normal liver tissue they arose from. They are considered more "indolent" (slow growing) and less likely for early spread. Grade II tumors are considered intermediate in appearance and behavior.There can be more than one grade (or even type) of cancer in a given specimen, this is called a "mixed tumor" . If there is any doubt, more than one pathologist should review the biopsy material, since pathologists do not always agree on the diagnosis. Pathologist's themselves (obviously) know this andwill normally request a review upon any biopsy they are unsure of. It is also obviously important for the pathologist to state whether the tumor has arisen from the liver primarily, or has spread there from some other organ. Occasionally it is strongly felt the tumor did not arise in the liver, since it does not have a resemblance to liver tissue. On the other hand, it may be difficult or impossible to say just where it originated. This is called "cancer of unknown primary" and is thoroughly investigated with emphasis on re-examining the liver biopsy.

The liver is a digestive organ necessary for life. Besides helping produce bile for digestion, it produces clotting factors for the blood, essential protiens, regulates cholesterol and detoxifies drugs and poisons. The liver is very resilient, but when it develops cancer can fail quickly, leading to rapid demise of the patient.