Liver cancer is a malignant tumor characterized by the development of one or more cancerous nodules in the liver.
The liver is an organ essential to the functioning of the body and can not be supplemented. On the other hand, only a quarter of the liver is sufficient to ensure its main functions, and the liver has very high regenerative capacities which allow it to resume normal function from a reduced fraction of its mass. It is also possible to consider liver transplants.
In the vast majority of cases, these nodules develop in a diseased liver because of a chronic condition that has caused an overload of liver fat (“steatosis”) or generalized scarring (“cirrhosis”). These diseases can be alcoholism, steatosis during type 2 diabetes, chronic viral hepatitis or iron overload during hemochromatosis.
Liver cancer remains silent for a long time, that is, without causing clinical signs, making early diagnosis difficult. As a result, people in whom this cancer is eventually discovered often suffer from advanced forms that are more difficult to treat.
The number of liver cancers diagnosed each year is decreasing significantly, particularly because of the number of people treated for hepatitis C.
What are the different types of liver cancers?
- “Hepatocellular carcinoma”, or “hepatocarcinoma”, is the most common form of primary cancer of the liver (90% of primary liver cancers). It originates in the cells that form most of the liver (called “hepatocytes”). Hepatocellular carcinoma occurs most often in people who have a damaged liver, for example during alcoholic cirrhosis (scarring of the liver), viral or toxic. It can take the form of a single tumor that can become very large if it is not detected early. “Fibrolamellar carcinoma” is a variant that appears especially in women under 40 years of age.
- Other forms of primary liver cancer are more rare: When a cancer starts in a bile duct within the liver, it is referred to as “intrahepatic bile duct cancer” or “cholangiocarcinoma” . The bile ducts are the tubes that carry the bile, which contributes to the digestion of fat, from the liver to the small intestine.
- It is also possible to observe “soft tissue sarcomas” (“angiosarcoma”, “leiomyosarcoma”, “fibrosarcoma”, “malignant fibrous histiocytoma”, “rhabdomyosarcoma”), but also cancers developed from the cells of the vessels of the liver (“epithelioid hemangioendothelioma”), from endocrine cells (“neuroendocrine tumor”), from immune cells such as non-Hodgkin’s lymphoma.
- “Liver metastases”, which are secondary tumors of the liver, are much more common than primary liver cancer. Hepatic metastasis is a cancer that originates from a cancer that originated in another body organ and spread to the liver. In this case, the tumor that is in the liver is composed of cells of the type where the cancer originated, not liver cells. For example, colorectal cancer often spreads to the liver: it is called “colorectal cancer with liver metastasis,” and this secondary cancer would be treated as colorectal cancer, not as a primary cancer of the liver. Cancers that often “metastasize” to the liver are mainly cancers of the pancreas, breast, gallbladder and bile ducts, colorectal cancer, cancer of the stomach, esophagus, lung, skin (“Melanoma”), ovarian, eye, and neuroendocrine.
What are the signs of liver cancer?
At the beginning of the disease and for a long time, liver cancer causes no problem and there is no sign. The liver is indeed a bulky organ with large capacity for compensation and it can function normally even if it contains a large tumor.
The signs appear when the tumor grows and causes complications, for example if it obstructs the bile ducts.
In addition, the signs are not specific for liver cancer and other diseases, including cirrhosis, can cause the same signs as liver cancer. These include belly pain (which can radiate to the right shoulder), nausea and vomiting, loss of appetite, a feeling of “overeating,” even after a light meal (called premature satiety), diarrhea, constipation, weight loss, bulging under the right ribs, prominent swelling of the abdomen (caused by a build-up of fluid called “ascites”), swelling of the feet and legs caused by fluid buildup (called “edema”), fatigue with weakness.
What are the risk factors for liver cancer?
When the cells of the liver are attacked for a long time, they die and are replaced by fibrous tissue: this is “fibrosis”.
“Cirrhosis” is the terminal phase of fibrosis and is the most important risk factor for liver cancer. It appears when the healthy tissue of the liver is replaced by scar tissue. The circulation of blood in the liver is then blocked, which prevents the organ from functioning normally. Cirrhosis is not only caused by alcoholism, but other factors can also cause it: chronic hepatitis B and C, the accumulation of fat in the liver related to obesity. The most recent studies show that anti-viral treatments, as long as they remove the hepatitis C virus from the bloodstream, reduce mortality and cancer liver risk, even with cirrhosis already in place.
In addition, smoking can be associated with other factors to increase the risk of liver cancer: most cancers are due to many risk factors.
Aflatoxin is a kind of “mycotoxin” (toxin produced by molds and fungi). It can contaminate different foods including cereals such as corn, rice and wheat, oilseeds like peanut, soybean and sunflower, spices such as chili pepper, black pepper and ginger, nuts like l almonds, nuts, pistachios and Brazil nuts or foods from animals fed aflatoxin-contaminated grain.
Vinyl chloride is used in the plastics industry to make polyvinyl chloride (PVC), which is used in many products. “Hemochromatosis” (iron overload) is an inherited disease in which the body stores a higher amount of iron than normal. This excess of iron accumulates in various tissues, especially in the liver. When the liver stores too much iron and the condition is not treated, the organ can be damaged (cirrhosis).
What are the complications of liver cancer?
- Hepatic encephalopathy occurs when the liver is not functioning properly and waste accumulates in the blood and various signs related to “brain intoxication” appear: mental confusion, drowsiness, change in personality or mood, nervousness and anxiety, slurred speech (trouble articulating), breath with a sweet or moldy smell, tremors or difficulty in controlling the movement of hands and arms, and finally, coma.
- Portal hypertension refers to an increase in blood pressure in the main vein that carries blood to the liver (the “portal vein”). This can happen when a liver tumor blocks the flow of blood in that vein, or in the presence of significant cirrhosis. Increased blood pressure causes large veins, or “varicose veins,” to form in the stomach and esophagus to allow blood to bypass the blockage. Varicose veins are very fragile and can easily bleed and the signs of portal hypertension include: a bump on the left side of the stomach (caused by swelling of the spleen or “splenomegaly”), fluid build-up in the abdomen (called “Ascites”), shortness of breath (caused by an accumulation of fluid around the lungs, called “pleural effusion”) and gastrointestinal bleeding, either minimal with blood in the stools (black and tarry color), or massive with vomiting of blood.
- When diagnosed late, liver cancer can be treated curatively (complete elimination) in about one third of patients. In other cases, treatments are possible but the recurrence rate is high (in 80 to 85% of cases five years after the first diagnosis).
- The five-year survival rate after a diagnosis of liver cancer varies greatly depending on the stage of cancer progression at the time of diagnosis: from 25% in the forms where the tumor is localized to less than 10% in the forms where the tumor is more extensive.
- When a liver transplant has been performed to treat cancer, the five-year survival rate is about 70%.
When should we talk about liver cancer?
When liver cancer occurs, it is most often on an already diseased liver, usually because of alcoholic cirrhosis or cirrhosis secondary to viral hepatitis. The discovery of liver cancer is often made during the follow-up of the initial liver disease.
Liver cancer can also be discovered in a healthy person, but the signs of the disease are most often late and not specific to the cancer: belly pains, especially if they radiate to the right shoulder, a bulge under right side ribs, nausea and vomiting, loss of appetite, feeling of overeating even after a light meal, diarrhea, constipation, weight loss or weight gain with swelling of the abdomen (“ascites”), edema of the feet and legs, fatigue with weakness.
How is liver cancer diagnosed?
In general, the diagnosis of liver cancer begins when an examination reveals that the liver may have a problem.
The doctor will question the person about the signs and will perform a clinical examination. He or she will also ask many questions about the medical history (cirrhosis, infection with the virus of the hepatitis B or C virus, consumption of alcohol, smoking, etc…).
Based on this initial review, he or she will refer the person to a specialist or prescribe tests to check for liver cancer. This period of diagnosis may seem long and worrisome, but we must not forget that other diseases can cause signs very similar to those of liver cancer. It is therefore important that the doctor eliminate any other possible cause before making a diagnosis of liver cancer.
Many complementary examinations make it possible to make a diagnosis of cancer and they also make it possible to determine “the stage”, that is to say the extent of the progression of the disease.
Blood tests measure the level of certain chemicals in the blood. Liver function tests are a set of biochemical blood tests that are often prescribed together. Although they do not diagnose liver cancer, they can tell the doctor that there may be a problem with the liver. Alkaline phosphatases are enzymes, that is, proteins that accelerate certain chemical reactions in the body. They are secreted by the liver and other tissues, but a high level of alkaline phosphatase may be a sign that the liver is damaged. Alanine aminotransferase (ALT) or SGPT is an enzyme that is detected in the liver and kidneys. High levels of ALT are often measured in the blood even before signs of liver damage appear. Aspartate transaminase (AST) or SGOT is an enzyme that is detected in liver, muscle and heart cells. When liver or heart cells are damaged, they also release SGOT in the blood.
The partial thromboplastin time (BP) is a measure of the time it takes a blood sample to form a clot in a test tube when certain chemicals are added to it. The coagulation time is very dependent on the coagulation proteins that are made by the liver.
Other biochemical blood tests can be done to find out if the liver is sick. A glucose test is a measure of the amount of glucose (sugar) in the blood. The liver releases glucose into the blood to maintain a normal blood glucose level. Low blood glucose (“hypoglycemia”) may indicate that the liver is damaged.
An ultrasound of the liver and bile ducts uses high-frequency sound waves to produce images of the liver structures and is used to test whether the liver is larger than normal or has thickened, or for determining if a mass in the liver is a solid tumor or is filled with fluid (such as a cyst).
The ultrasound can be supplemented with an abdominal ultrasound to see if there are lymph nodes and metastases.
Doctors can also use ultrasound to guide them to the liver tumor during a biopsy. During a biopsy, the doctor takes pieces of liver for analysis in the laboratory. The report from the laboratory confirms the presence or absence of cancer cells in the biopsy.
Doctors also use CT or MRI to obtain more precise information about the size, shape and location of the tumor, to decide if the liver tumor can be removed by surgery, and to detect signs of spread to neighboring organs. A scan of the chest, abdomen and pelvis can also confirm the diagnosis of liver cancer evoked by the results of the ultrasound. It can also identify other nodules and possible extensions of the tumor on other organs (ganglion, bone, lung, adrenal gland, peritoneum). An MRI can also be performed in addition to the scanner. MRI gives accurate images of the tumor and allows to see a possible extension to the blood vessels of the liver.
It is common to do a chest x-ray to see if the liver cancer has spread to the lungs, but the CT scan is more accurate. In some cases, bone scans and bone X-rays may be needed to investigate the spread of liver cancer to the bone.
Tumor markers are substances found in the blood, tissues and fluids taken from the body. An abnormal tumor marker may mean that someone has liver cancer. Tumor markers are also assayed to evaluate the response to cancer treatment. It can also be used to diagnose liver cancer. In the past, the tumor marker used for liver cancer was “alpha-fetoprotein” (AFP). Recent research has shown that AFP levels can also be higher than normal in the presence of other types of cancer, including intrahepatic bile duct cancer. Since this analysis does not specifically identify hepatocellular carcinoma, physicians no longer recommend it as a diagnostic test for liver cancer.
What can be confused with liver cancer?
A non-cancerous or “benign” liver tumor is a mass that does not spread to other parts of the body (no metastases). Non-cancerous tumors do not usually put life at risk. “Hemangioma” is composed of abnormal blood vessels and is the most common non-cancerous liver tumor.
“Focal nodular hyperplasia” is the second most common non-cancerous liver tumor.
“Hepatic adenoma” is rare and can be in the form of a single tumor or numerous tumors distributed throughout the liver. It occurs more frequently in women of childbearing age and in women taking oral contraceptives with high doses of estrogen. The risk of hepatic adenoma is now lower because the dose of estrogen in oral contraceptives is lower.
“Hepatic cystadenoma” is a very rare type of non-cancerous liver tumor that occurs more often in women. This tumor is often observed in several regions of the liver (“multifocal” tumor) and can become cancerous (or “malignant”) if it is very large. That’s why doctors perform surgery to remove this tumor.
“Liver cysts” are bags filled with a liquid or semi-liquid substance. They can be there from birth (“congenital” cysts) or appear later. Most cysts grow very slowly and rarely cause problems. Doctors can drain them or perform surgery to remove them if they cause discomfort, such as pain.
How to classify a liver cancer?
The BCLC (Barcelona Clinic Liver Cancer) classification is the most recognized and most used staging system for hepatocellular carcinoma.
This BCLC classification takes into account the Child-Pugh classification (which measures the degree of hepatic involvement due to cirrhosis), tumor characteristics (including the number of tumors present in the liver), their size, the presence of signs and locations where the cancer has spread; and finally, the functional index, which is a measure of a person’s ability to perform routine tasks and daily activities. The latter is determined using the Eastern Cooperative Oncology Group (ECOG) scale (the higher a person’s score, the more difficult it is to perform daily activities).
|BCLC stage||Child-Pugh score||Characteristics of the tumor||ECOG score|
|0 (very early)||A||There is only 1 tumor of 2 cm or less that causes no signs. The tumor did not invade the blood vessels.|
|A (early)||A or B||There are up to 3 tumors that all measure less than 3 cm and do not cause any signs.|
|B (intermediate)||A or B||Tumors are present in several regions of the liver (multifocal disease), but they do not cause any signs.|
|C (advanced)||A or B||The tumor (or tumors) have invaded the blood vessels or the cancer has spread to other parts of the body. The tumor or tumors cause signs.||1 or 2|
|D (very advanced)||C||There are 1 or more tumors in the liver that can be of any size and cause signs. Tumors may have invaded the blood vessels or the cancer has spread to other parts of the body.||3 or 4|
What are the principles of liver cancer treatment?
Depending on the stage of liver cancer, one or more of the four types of liver cancer treatment can be performed: partial removal, liver transplantation, percutaneous tumor destruction, and chemotherapy.
Surgery is the first-choice treatment for liver cancer, either to remove the tumor (s) or to transplant a new liver. Unfortunately, at the time of diagnosis, surgery is only possible in about 15% of patients.
For others, it is possible to destroy the tumor or tumors through the skin (“percutaneous destruction”), to perform local chemotherapy, directly to the tumor (“chemoembolization”) or to administer a targeted therapy.
Percutaneous injection of ethanol is a treatment that involves injecting concentrated alcohol (ethanol) into a liver tumor with a needle. It is most effective when tumors are less than 2 cm.
External radiotherapy may be used to treat liver cancer that has spread to the bones.
The choice of treatment method depends on the severity of the cirrhosis, the appearance of the tumors (number, size, location, invasion of the blood vessels or bile ducts = stage) and the general condition of the person (his capacity to support the surgery).
What is liver cancer surgery?
Partial removal of the liver, or “liver resection” or “partial hepatectomy”, removes the tumor and a margin of healthy tissue all around. It is the main treatment when there is only one tumor, the tumor is less than 2 cm and the cancer has not spread to the lymph nodes or the blood vessels of the liver. In addition, it is proposed only if the tests show that the liver is healthy enough to function normally after surgery and that there is no increase in pressure in the portal vein.
Liver transplantation is the gold standard treatment for people with severe cirrhosis whose remaining part of the liver would not function normally after surgery to remove the tumor. Liver transplantation is systematically considered in cases of liver cancer with terminal cirrhosis. The transplant helps treat the cancer and chronic liver disease by replacing the liver with a healthy liver. However, it is not necessary for the cancer to spread outside the liver to other parts of the body and only 5% of patients with liver cancer can be transplanted. The number of available grafts is limited and the contraindications of the graft are numerous. In people who are eligible for a liver transplant, treatments are often put in place while waiting for the availability of a graft.
What is chemoembolization?
Chemotherapy can slow the development of cancer when it is not possible to remove the tumor. This treatment consists of blocking the blood supply of the hepatic tumor and administering chemotherapy directly into the tumor: in the case of the liver, chemotherapy is rarely administered in a general way.
During “chemoembolization”, a chemotherapy drug is injected as close to the tumors as possible, via a catheter into the hepatic artery or into one of its branches, together with a substance called an “embolization agent” (a greasy substance or a solution of microscopic plastic beads). The embolization agent thickens the blood and allows the chemotherapy drug to stay in contact for as long as possible with the cancer cells that form the tumor. In addition, the embolization agent decreases the flow of oxygenated blood into the tumor, which suffocates the cancer cells and makes them more susceptible to chemotherapy.
Chemoembolization is proposed when the tumor can not be treated with surgery and the cancer has not spread to the main blood vessels of the liver, lymph nodes or other parts of the body. It is only considered if hepatic function is good, no fluid has accumulated in the abdomen (ascites) and no problem affects the main vein of the liver (called portal vein).
What is radiofrequency ablation?
Percutaneous radiofrequency tumor destruction is an alternative to surgery, depending on the size and location of the tumor in the liver. This technique uses heat to destroy the tumor by passing through the skin.
Radiofrequency ablation uses a high-frequency electric current to release heat that will destroy the cancer cells. Ablation destroys cancer cells in the liver while trying to damage as little of the nearby liver tissue as possible. Ablation is offered to people with liver cancer who can not undergo surgery when hepatic tumors are no more than 2.5 cm tall and when there are no more than 3 tumors.
What is targeted therapy?
Targeted treatment involves using drugs to target specific molecules (such as proteins) on the surface of cancer cells that serve as targets. These molecules help send signals that tell cells to grow or divide.
By targeting these molecules, the drugs stop the growth and spread of cancer cells while limiting damage to normal cells. Targeted therapy is used to treat advanced liver cancer when the person can not have surgery or the cancer is no longer responding to other treatments.
Living with liver cancer
In most cases, liver cancer is at an advanced stage when diagnosed. “Advanced cancer” refers to a cancer that is unlikely to heal. The goal of the treatment is to relieve the signs, slow the progression of the cancer and improve the quality of life.
People with liver cancer are often in poor health because their liver is not functioning properly. The care team has solutions to manage pain, ascites, nausea and vomiting and loss of appetite.
Supportive care for people living with liver cancer
Supportive care enables people with liver cancer to overcome the various barriers caused by cancer.
This care is an important component of the care provided to people with this disease. Many programs and services help meet the needs and improve the quality of life of these individuals and their loved ones, especially once treatment is complete.
Recovery after liver cancer and adaptation to life after treatment differ for each person. Recovery depends on the stage of the disease, the type of treatment given, and many other factors. The end of cancer treatment can trigger shared emotions. Even if the treatment is succesful, there may be other issues that need to be addressed, such as adjusting to long-term side effects.
How to prevent liver cancer
- Prevention measures for liver cancer are those that prevent fibrosis and cirrhosis of the liver:
- Consume alcoholic beverages in moderation,
- Vaccinate against hepatitis B,
- Avoid overweight and obesity by eating a balanced diet and exercising regularly,
- Perform a test for hepatitis C and avoid becoming HIV positive