Dr. Keith E. Stuart is a medical oncologist specializing in the study and treatment of cancers involving the gastrointestinal tract, with a special interest in tumors involving the liver. He was educated at Harvard University (graduating magna cum laude) and Albert Einstein College of Medicine and did his medical training at the New England Deaconess Hospital.
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
What are the population characteristics (epidemiology) of
liver cancer?
In the U.S., the highest frequency of liver cancer occurs in immigrants from Asian countries, where liver cancer is common. The frequency of liver cancer among Caucasians is the lowest, whereas among African-Americans and Hispanics, it is intermediate. The frequency of liver cancer is high among Asians because liver cancer is closely linked to chronic hepatitis B infection. This is especially so in individuals who have been infected with chronic hepatitis B for most of their lives (it is usually a childhood disease in Asia). If you take a world map depicting the frequency of chronic hepatitis B infection, you can easily superimpose that map on a map showing the frequency of liver cancer. On the other hand, in Japan, North America and Europe,
hepatitis C infection is a much more common cause; alcohol abuse is also an important contributing factor. All of these diseases cause continual damage to the liver, which can result in severe scarring (cirrhosis) that then can lead to cancer.
In areas where liver cancer is more common and associated with hepatitis B, the cancer usually develops in people in their 30s and 40s, as opposed to other areas of the world, where they are in their 60s and 70s. This is because it generally takes about 30 years of chronic damage to the liver before the cancer grows large enough to become obvious. Men are much more likely than women to have liver cancer, especially if they have hepatitis and cirrhosis. Regardless of the cause, patients with a history of alcohol abuse as well are much sicker when they initially develop the cancer. In North America, up to one-quarter of people with liver cancer have no obvious risk factors; they are generally healthier and do much better with treatment.
What are liver cancer causes and risk factors?
Hepatitis B infection
Hepatitis B can be caught from contaminated blood products or used needles or
sexual contact but is frequent among Asian children from contamination at birth
or even biting among children at play. 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 1970s in Taiwan involving male government employees over the age of 40.
In this study, the investigators found that the 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 infection.
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 viruses related to the hepatitis
B virus. 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, and very few
develop an ongoing (chronic active) infection, which happens as often as 15% of
the time in Asia.
Hepatitis C infection
Hepatitis C virus (HCV) infection is more difficult to get than hepatitis B. It usually requires direct contact with infected blood, either from contaminated blood products or needles. HCV 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%-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. Therefore, it has been argued 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. In fact, at autopsy, as many as half of alcoholics previously unsuspected to have cancer will have early evidence of cancer hidden within the liver. Many of these people are also infected with chronic hepatitis C virus. The usual setting is an individual with alcoholic cirrhosis who has stopped drinking for
10 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.
More importantly, if an alcoholic does not stop drinking, he or she is unlikely to live long enough to develop the cancer. Alcoholics 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 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 diagnostic imaging
studies,
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.
Liver cancer will develop in up to 30% of
patients with hereditary hemochromatosis (a disorder in which there is too much iron stored in the body, including in the liver). 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.
Diabetes and obesity
Over the past decade, the incidence of liver cancer in the United States has risen significantly, paralleling the rise in obesity. Although it is hard to separate the effects of diabetes from obesity on the liver, both conditions can cause chronic damage and accumulation of fat within the liver.. This is a disease called NASH (non-alcoholic steatohepatitis), which is present in up to 5% of North Americans. Fatty liver disease like this causes damage to the individual liver cells and may lead to cirrhosis in some people, thereby increasing the risk of liver cancer. Not only is the chance of developing the cancer enhanced, but patients with diabetes who undergo surgical removal of liver cancer have a higher chance of the cancer returning than do those without diabetes.
Cirrhosis
Individuals with most types of cirrhosis of the liver are at an increased
risk of developing liver cancer. In addition to the conditions described above (hepatitis
B, hepatitis C, alcohol, and hemochromatosis), alpha 1 anti-trypsin deficiency,
a hereditary 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. For example, liver cancer is rarely seen with the cirrhosis in Wilson's
disease (abnormal copper metabolism) or primary sclerosing cholangitis (chronic
scarring and narrowing of the bile ducts). It used to be thought that liver
cancer is
rarely found in primary biliary cirrhosis (PBC) as well. Recent studies,
however, show that the frequency of liver cancer in PBC is comparable to that in other
forms of cirrhosis.
Abdominal pain is pain in the belly and can be acute or chronic. Causes include inflammation, distention of an organ, and loss of the blood supply to an organ. Abdominal pain can reflect a major problem with one of the organs in the abdomen such as the appendix, gallbladder, large and small intestine, pancreas, liver, colon, duodenum, and spleen.
Cirrhosis of the liver refers to a disease in which normal liver cells are replaced by scar tissue caused by alcohol and viral hepatitis B and C. This disease leads to abnormalities in the liver's ability to handle toxins and blood flow, causing internal bleeding, kidney failure, mental confusion, coma, body fluid accumulation, and frequent infections. Symptoms include yellowing of the skin, itching, and fatigue.
Hepatitis C is an inflammation of the liver due to the hepatitis C virus (HCV), which is usually spread by
blood transfusion, hemodialysis, and needle sticks, especially with intravenous
drug abuse. Chronic hepatitis C may be treated with interferon, usually in combination with anti-virals.
Cholesterol is naturally produced by the body, and is a building block for cell membranes and hormones. Low-density lipoprotein (LDL) cholesterol is the "bad" cholesterol, conversely, high-density lipoprotein (HDL) cholesterol is the "good" cholesterol. High cholesterol treatment includes lifestyle changes (diet and exercise), and medications such as statins, bile acid resins, and fibric acid derivatives.
Jaundice is a yellowish staining of the skin and whites of the eyes (sclerae) with bilirubin, the pigment found in bile. Jaundice can be an indicator of liver or gallbladder disease, or it may result from the rupture of red blood cells (hemolysis).
Alcoholism is a disease that includes alcohol craving and continued drinking despite repeated alcohol-related problems, such as losing a job or getting into trouble with the law.
The hepatitis B virus is a unique, coated DNA virus belonging to the Hepadnaviridae family of viruses. The course of the virus is determined primarily by the age at which the infection is acquired and the interaction between the virus and the body's immune system. Successful treatment is associated with a reduction in liver injury and fibrosis (scarring), a decreased likelihood of developing cirrhosis and its complications, including liver cancer, and a prolonged survival.
Ascites, the accumulation of fluid in the abdominal cavity is most commonly caused by cirrhosis of the liver. Some of the other causes of ascites include portal hypertension, congestive heart failure, blood clots, and pancreatitis. The most common symptoms include increased abdominal girth and size, abdominal bloating, and abdominal pain. Treatment depends on the cause of ascites.
Polycythemia (elevated red blood cell count) causes are either primary (aquired or genetic mutations) or secondary (diseases, conditions, high altitude). Treatment of polycythemia depends on the cause.
Cancer is a disease caused by an abnormal growth of cells, also called malignancy. It is a group of 100 different diseases, and is not contagious. Cancer can be treated through chemotherapy, a treatment of drugs that destroy cancer cells.
Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease ranging from simple fatty liver (steatosis), to nonalcoholic steatohepatitis (NASH), to cirrhosis (irreversible, advanced scarring of the liver). All of the stages of NAFLD have in common the accumulation of fat (fatty infiltration) in the liver cells (hepatocytes).
Insulin resistance is the diminished ability of cells to respond to the action of insulin in transporting glucose (sugar) from the bloodstream into muscle and other tissues. Causes of insulin can include conditions such as stress, obesity, metabolic syndrome, and steroid use. Some of the risk factors for insulin resistance include fatty liver, heart disease, strokes, peripheral vascular disease, high cholesterol, and smoking. Treatment for insulin resistance are lifestyle changes and if necessary, medication.
Hepatitis is most often viral, due to infection with one of the hepatitis viruses (A, B, C, D, E, F (not confirmed), and G) or another virus (such as those that cause infectious mononucleosis, cytomegalovirus disease). The main nonviral causes of hepatitis are alcohol and drugs. Many patients infected with hepatitis A, B, and C have few or no symptoms of illness. For those who do develop symptoms of viral hepatitis, the most common are flu- like symptoms including: loss of appetite, nausea, vomiting, fever, weakness, tiredness, and aching in the abdomen. Treatment of viral hepatitis is dependant on the type of hepatitis.
Hereditary hemochromatosis (iron overload) is an inherited disorder in which there is excessive accumulation of iron in the body. Individuals may have no symptoms or signs, or they can have severe symptoms and signs of iron overload. The most effective treatment for hemochromatosis is therapeutic phlebotomy.
Primary Biliary Cirrhosis is a chronic disease characterized by progressive inflammation and destruction of small bile ducts within the liver. The bile ducts transport bile from the liver to the intestine for the absorption of fat and elimination of waste products. The causes of Primary Biliary Cirrhosis may involve autoimmunity, infection, or genetic predisposition, acting alone or in combination. There are many medications and treatment options available for those with this and other associated diseases of Primary Biliary Cirrhosis.
The liver is the largest solid organ in the body, and is actually an gland. The liver has a wide variety of critical functions such as manufacturing proteins and metabolizing fats and carbohydrates. The liver also eliminates harmful biochemical waste products from the body (alcohol, drugs, toxins). The liver secretes bile that aids in digestion. Examples of diseases of the liver include cirrhosis, hepatitis, cancer, and fatty liver. Symptoms of liver disease include bleeding, easy bruising, edema, fatigue, and jaundice.
Mold exposure may cause symptoms in people who are sensitive to molds. Symptoms of mold allergy include sneezing, runny nose, wheezing, coughing, redness of the eyes, and rash. Prevent mold growth by keeping indoor humidity low, between 30%-50%, using bathroom fans when showering, repairing plumbing leaks quickly, and using an air conditioner during humid seasons.
Primary sclerosing cholangitis (PSC) is a chronic, progressive disease of the bile ducts that channel bile from the liver into the intestines. There is an association between primary sclerosing cholangitis and ulcerative colitis and Crohn's disease. Symptoms of primary sclerosing cholangitis include abnormal liver blood tests, itching, fatigue, and jaundice. Primary sclerosing cholangitis is treated with medications and in some cases, liver transplant.
Anabolic steroids are synthetic substances that are related to testosterone and promote skeletal muscle growth and the development of male sexual characteristics in both men and women. In the 1930s, it was discovered that anabolic steroids could promote skeletal muscle growth in lab animals, which lead to anabolic steroid abuse by bodybuilders and weight lifters.
Digestion is the complex process of turning food you eat into the energy you need to survive. The digestive process also involves creating waste to be eliminated, and is made of a series of muscles that coordinate the movement of food.
Alpha-1 antitrypsin deficiency is an inherited disorder that may cause liver and lung disease in adults. Signs and symptoms include shortness of breath, wheezing, weight loss, respiratory infections, fatigue, vision abnormalities. Advanced lung disease from alpha-1 antitrypsin deficiency include emphysema. Liver damage from alpha-1 antitrypsin deficiency causes a swollen abdomen, swollen legs or feet, and jaundice.
Hepatitis A and hepatitis B are the two most commnon viruses that infect the liver. Hepatitis A and Hepatitis B can be prevented and treated with immunizations (vaccinations) such as Havrix, Vaqta, Twinrix, Comvax, Pediarix, and hepatitis b immune globulin (HBIG).
Cancer RSS
Healthy Living Tips
This site complies with the