What is Liver?
The liver is one of the largest organs in the body. It is located below the right lung and under the ribcage.
- The liver is located in the upper right-hand portion of the abdominal cavity, beneath the diaphragm (a sheet of muscle separating the chest and the abdomen), and on top of the stomach, right kidney, and intestines. The gall bladder is attached to the lower portion of the right side of the liver.Shaped like a cone, the liver is a dark reddish-brown organ that weighs about 1.2 kg.
- There are two distinct sources that supply blood to the liver:
- Oxygenated blood flows in from the hepatic artery
- Nutrient-rich blood flows in from the hepatic portal vein
- The liver holds about 500 ml (13 percent) of the body’s blood supply at any given moment.The liver consists of two main lobes – the right and the left, both of which are made up of thousands of lobules. These lobules are connected to small ducts that connect with larger ducts to ultimately form the hepatic duct. The hepatic duct transports the bile produced by the liver cells to the gallbladder and duodenum (the first part of the small intestine).
What does the liver do?
The liver regulates most chemical levels in the blood and excretes a product called “bile,” which helps carry away waste products from the liver. All the blood leaving the stomach and intestines passes through the liver. The liver processes this blood and breaks down the nutrients and drugs into forms that are easier to use for the rest of the body
The liver is the most complex and metabolically active organ in the body. It performs more than 500 vital functions. Some of the important ones are
- It provides immunity against infection. Hence if the liver is damaged, infections are more likely.
- It is the factory for manufacturing most of the important proteins in the body, and also cholesterol and special fat forms called lipoproteins in which all body fats are carried.
- It clears the blood of most chemicals, drugs and alcohol.
- It excretes bile into the intestine. Bile is vital for digestion of fats, and also serves to throw out body wastes.
- It regulates clotting of blood by manufacturing vital proteins
- It converts and stores extra sugar (glucose) in the form of starch (glycogen) which can be used in times of starvation.
What makes the liver unique?
All liver functions remain normal even if 70% of it is removed (provided the remaining 30% is healthy). Hence, in persons with cancer of the liver, large portions of cancerous liver can be removed without causing harm or compromise to liver function. Similarly, more than half the liver can be removed from the donor for transplantation purposes, without causing any derangement of liver function or any other serious harm to the donor.
The liver is the only organ in the body which can regenerate itself after large portions of it are removed. Small remnants of liver grow back to normal size within a few weeks. This is another reason why it is safe to remove large portions of liver from living donors and persons with liver tumours.
This is also why half livers transplanted into liver failure patients are very successful since they soon grow to normal size.
What is liver cancer?
Primary liver cancer (or hepatocellular cancer) is cancer that forms in the tissues of the liver.
Secondary liver cancer ( or metastatic liver cancer) is cancer that spreads to the liver from another part of the body. Cancers that commonly spread to the liver include colon, lungand breast cancers
Cancer can start within the liver (primary liver cancer or spread to the liver) from other sites, such as the colon. Cancer that starts in the liver is the fifth most common cancer in the world
Liver cancer is a bad cancer. It has frequently spread beyond the liver by the time it is discovered, and only 5% of patients with liver cancer that has begun to cause symptoms survive even five years without treatment. The only hope for patients who are at risk for liver cancer is regular surveillance so that the cancers can be found early.
What are liver cancer causes and risk factors?
1. 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.
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.
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.
2. 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 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..
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 has been suggested that the core (central) protein of hepatitis C virus is the culprit in the development of liver cancer.
Cirrhosis caused by chronic alcohol consumption is the most common association of liver cancer in the developed world
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, alcohol adds to the risk of developing liver cancer in patients with chronic hepatitis C virus or hepatitis B virus infections.
4. 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.
5. 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.
7. Diabetes and obesity
It is hard to separate the effects of diabetes from that of obesity on the liver as both conditions can cause chronic damage and accumulation of fat within the liver.. This is a disease called NASH (non-alcoholic steatohepatitis) 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.
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
What are symptoms and signs of liver cancer?
Primary cancer arises within the liver and in its early stages exists only within the liver. At an early stage, primary liver cancer may cause no symptoms at all. More advanced disease may cause loss of appetite, weight loss, fever, fatigue and weakness.
Secondary liver cancer is the term for cancer that originates in another organ, such as the colon, stomach, pancreas and breast, and then spreads to the liver. As the cancer grows, pain may develop in the upper abdomen on the right side and may extend into the back and shoulder. With advanced disease, the signs of liver failure appear, which include abdominal swelling and a feeling of fullness or bloating and jaundice, a condition in which the skin and the whites of the eyes become yellow and the urine becomes dark.
How do you diagnose liver Cancer ?
In making a diagnosis of liver cancer, your doctor will evaluate your medical history and perform a careful physical examination. Certain tests also will be recommended.
For people at increased risk of developing primary liver cancer, such as those with chronic viral hepatitis or cirrhosis, the current recommendation is to have an alpha-fetoprotein blood test and an ultrasoundexamination of the liver, at least annually. While not perfect, these tests increase the chances of detecting liver cancer at an early stage.
Certain blood tests like liver function test are used to see how well the liver is functioning.
X-rays of the chest and abdomen, angiograms or X-rays of blood vessels; CT scans, or X-rays put together by computer; and magnetic resonance images (MRIs), created by using a magnetic field, may be part of the diagnostic process.
If there is uncertainty about the diagnosis, the presence of liver cancer may be confirmed with a biopsy. Tissue from the liver is removed through a needle or during an operation and checked under a microscope for the presence of cancer cells.
Your doctor also may look at the liver with an instrument called a laparoscope, which is a small tube-shaped instrument with a light on one end. For this procedure, a small cut is made in the abdomen so that the laparoscope can be inserted. Your doctor may take a small piece of tissue during the laparoscopy. A pathologist then examines the tissue under the microscope to see if cancer cells are present.
Once primary liver cancer is found, more tests will be performed to determine if cancer cells have spread to other parts of the body.
Staging of liver cancer
The following stages are used for adult primary liver cancer:
Localized resectable — Cancer is found in one place in the liver and can be completely removed by surgery.
Localized unresectable — Cancer is found only in one part of the liver, but the cancer cannot be totally removed.
Advanced — Cancer has spread through much of the liver or to other parts of the body.
Recurrent — Cancer has come back or recurred after it was treated.
What are the treatment options for liver cancer?
- The best possible treatment a liver cancer is surgery wherein the affected portion of the liver is removed (“hepatectomy”).
- If surgery is performed at a time when the cancer is confined to a removable portion of the liver and has not spread elsewhere, there is a high chance of cure. .
- Two unique features of the liver help in good recovery of patients. One is the tremendous reserve due to which liver function remains normal even if upto 70% liver is removed as long as the remaining liver is not diseased. The second is the power of regeneration due to which the liver recovers its original weight within few weeks after removal of up to 60-70% of liver.
- In some suitable cases, especially those where the liver has cirrhosis along with cancer, liver transplantation is also possible. This procedure can treat both liver cirrhosis and cancer at the same time.
Treatment without operation
If an operation is not possible or safe, there are now several other treatment options available.
- Alcohol injection and radiofrequency thermoablation (RFA, burning the tumour with a special probe without operation) are two excellent options. Both these procedures destroy the tumour without any significant harm to the rest of the liver or the body and can be done on an outpatient basis without the need for admission to hospital. However, their major limitation is that they are only effective for cancers less than about 2 inches in size and fewer than three in number.
- Injection of chemotherapy drugs through the liver arteries (transarterial chemotherapy or TAC) can be done if the cancer is widespread within the liver. This way the drugs are delivered directly to the tumour greatly enhancing their effectiveness and at the same time, markedly reducing their side effects on the rest of the body.
- Another method by which liver surgeons can deal with large or multiple tumours that are confined to one side of the liver is by blocking the blood supply of the cancerous area of the liver with chemotherapy impreganted material (transarterial chemo-embolization or TACE) resulting in death of tumour cells. All above treatments can and should only be carried out in specialized liver centres by experienced liver surgeons, physicians and radiologists.
Radiofrequency Ablation (RFA) as Liver Cancer Treatment
Radiofrequency ablation, is a technique of heating up liver cancers with probes inserted into the cancers. The probe is hooked to a machine which drives current in a high frequency alternating—back and forth–path which results in heating the liver tissue to the level of 90 to 100 degrees Centigrade (100 degrees C=212 degrees Fahrenheit).
This temperature cooks the tissues around it. A straight needle like probe will cook the tissues around it in a limited elliptical fashion which will not kill or “ablate” all of the cancer it is put in, except for the very smallest cancers.
Chemoembolization is also known as TACE, standing for transarterial chemoembolization.
In this technique an interventional radiologist injects a chemotherapeutic agent directly into the arteries supplying a tumor within the liver. Frequently lipiodol is also injected since lipiodol, which is actually poppyseed oil, will hold the chemical there within the injected artery for a longer time
Chemoembolization may be superior to bland embolization, which is the injection of agents to cause the artery to clot off, without adding chemotherapy drugs along with the clotting agents
This treatment method is used more frequently in the patient with hepatocellular carcinoma than in the patient with metastasis from a cancer of the colon or rectum.
A post-embolization syndrome does occur in many patients after TACE that makes them sick for several days post-procedure.
TACE is a second line therapy that should only be considered after ablation or resection have been ruled out.
- The most commonly used systemic chemotherapeutic agents are doxorubicin (Adriamycin) and 5-fluorouracil (5 FU).
How can you prevent liver cancers?
Prevention of liver cancer is possible at two levels.
- The first level of prevention is to avoid alcohol abuse and to prevent the occurrence of Hepatitis B or Hepatitis C. These are acquired from infected individuals via blood or rarely other secretions, by sharing of infected needles among drug addicts, or by the sexual route. Their transmission can be avoided by use of disposable needles in hospitals, by strict and universal screening of all blood donors in blood banks and refusing donations from infected persons. The spread of Hepatitis B can be curbed by universal vaccination of all newborns and the rest of the non-infected population.
- The second level of prevention is in patients who have liver cirrhosis. A significant proportion of them will develop cancer. This can be avoided if they undergo a timely liver transplant and the diseased liver can be removed. All those with cirrhosis should see a liver specialist to find out if a liver transplant is suitable for them.