Liver Cancer

The liver is the largest organ inside the body, and is a very important metabolic organ. It is found on the upper right of the abdomen, comprising the left lobe and the right lobe. The main functions of the liver include:

• The production and storage of glucose for use when necessary
• The manufacturing of bile for digesting fats in food
• The detoxification of toxins and alcohol for excretion
• The making of proteins, blood-clotting substances, antibodies and cholesterol

When the liver cells begin to mutate and uncontrolled divide, a liver cancer is formed.

Liver cancer can be classified into primary liver cancer and metastatic liver cancer. Primary liver cancer is a malignant tumor caused by liver cells, and the commonly known ones are "Hepatocellular Carcinoma" and "Cholangiocarcinoma". Metastatic liver cancer is a liver cancer caused by the spread of cancer cells from the other organs.

There are many causes of liver cancer and some of them are still being studied but factors posing higher risks are:

• Hepatitis B virus: Around 56% of the world’s liver cancer is caused by infection with hepatitis B virus (HBV). The chance of chronic hepatitis virus carriers getting liver cancer is 100 times higher than the non-hepatitis B virus carriers. Hepatitis B is very common in Hong Kong, and it is estimated that one tenth of the Hong Kong population are either hepatitis B virus carriers, or have been infected with the disease HBV. Among these chronic carriers, a quarter of them may develop cirrhosis, which may cause liver cancer.

 

• Cirrhosis: People infected with hepatitis B virus may develop chronic hepatitis in about 10 years, which may then develop into cirrhosis in another 21 years. It will take 29 years for the cirrhosis to become liver cancer. The actual progress of the disease varies among people and depending on how active the hepatitis viruses are. It is found in the studies that the more active the viruses are, the more quickly the liver cells are damaged, as a result of which, the patient will develop cirrhosis or chronic hepatitis soon. It will take 50 to 60 years to develop liver cancer after a patient infected with hepatitis B virus.

 

• Hepatitis C: The chance of chronic hepatitis B carriers and hepatitis C carriers to get liver cancer is 150 times higher. HCV-associated liver cancer is more prevalent in western countries.

 

• Heavy alcohol consumption: Having excessive alcohol may cause alcohol-related liver hardening, which may then develop into liver cancer. The chance of alcoholic hepatitis B carriers getting liver cell cancer is 2 times higher than the general virus carriers.

 

• Non-alcoholic fatty liver disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH): Obesity, diabetes mellitus, and other metabolic disorders may induce liver damage leading to cirrhosis and liver cancer.

 

• Toxic food consumption: Aflatoxins found in peanuts, corn, nuts and grains are proven to be a cause of liver cancer in animal experiments.

 

• Exposure to certain environmental and pollutant hazards for a long time (such as inhaling PVC used in plastics manufacturing factories)

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• Cholangitis or congenital choledochal cyst may lead to bile duct cancer

The following are ways of preventing liver cancer:

• Don't smoke
• Limit amount of drinking
• Regular work and rest, and eat more fruit and vegetables
• Avoid contracting hepatitis B:
  Should any member of a family be infected with hepatitis B, other members have to check whether they have got hepatitis viruses or if they have developed antibodies after contracting the viruses. If they have not yet been infected, they should take hepatitis B vaccine injections, which must be taken 3 times within 6 months.
• Use condom and don’t share needles:
  There are 8-10% and 0.5% of the Hong Kong population who are hepatitis B virus and hepatitis C virus carriers respectively. Both types of hepatitis can be transmitted through body fluids, so unprotected sexual intercourses or sharing needles can spread hepatitis B and hepatitis C.
• Store food properly and be cautious about rotten or contaminated food:
  Certain food such as peanuts, grains and corn may rot, and produce aflatoxins which increases the risk of getting liver cancer. These foods should be stored in places where it is cool and dry to avoid getting rotten.
• For those who are hepatitis virus carriers must remember to have regular follow-ups, which helps detect the disease at its early stage.

    The liver has the wonder of being able to self-repair. Even when only a small part of it remains, the liver can still function normally, so symptoms of a liver cancer at its early stage are not obvious. When the tumor grows larger, the patient can observe the following:

• Pain in the right side of upper abdomen
• Pain in the right shoulder: The swollen liver stimulates the nerves of the diaphragm, and the nerves here are connected to the nerves in the right shoulder.
• Loss of appetite and weight, nausea and drowsiness
• Lumps in the upper abdomen
• Yellow skin and eyes, itchy skin: The bile duct is blocked by the tumor, which causes the bile pigment to accumulate in the blood and thus jaundice is caused.
• Tea color urine and light grey stools
• Ascites (collection of fluid in the abdomen)

High-risk groups and those having the above-mentioned symptoms should consult family doctors to have examinations as soon as possible. The earlier the diagnosis and discovery of the disease, the higher the chance of cure. Relevant checks for liver cancer include the following:

Blood tests for alpha-fetoprotein: When liver cancer cells grow continuously, the numeral value of alpha-fetoprotein will be very high. Alpha-fetoprotein is an index for cancer and it helps diagnosis of liver cancer at its early stage. Abdominal ultrasound: Ultrasound is employed to scan the structure of the liver to confirm the size and location of the tumor. This test takes several minutes and the patient must stop drinking or eating four hours before the test. Computer scan: X-ray is used to scan the liver from different angles so as to get a detailed graph, which can display precisely the location and size of the tumor. The patient needs to drink a special contrast dye and the whole process takes more than 10 minutes. Angiogram: To observe the blood flow, the patient is injected with a contrast dye. This test can confirm the location of the tumor and the blood vessels that provide the tumor with nutrition. Magnetic resonance imaging: Magnetic field replaced X-ray to construct a cross-section image of the body so as to observe the location of the liver cancer tumor. Biopsy: The doctor will use a fine needle to obtain tissue of the liver tumor through the skin on his/her right abdomen when patient is under local anesthesia. This is for confirming the type of the tumor cells and deciding whether they are benign or malignant. This test is usually performed together with ultrasound to ensure the needle is inserted at the precise position. This test has small risk of bleeding.

    Once the patient is diagnosed to have liver cancer, doctor will consider the stage of the cancer, the malignancy of the cancer cells, and the patient's overall hralth condition to formulate the moste appropriate treatment plan. Generally, doctor will suggest the following treatments to the patient depending on the codition:

(1) Removal by surgery

• Rationale of treatment: To remove the tumor and the surrounding affected tissues.

• Suitable for: Removal by radical surgery is suitable for 20% of liver cancer patients whose tumors affect only one of the liver lobes and their liver functions are normal. 62% of them can survive 3 years while 50% of them can survive 5 years.

(2) Trans-arterial Chemoembolization (TACE)

• Rationale of treatment: This is to block the blood vessels, thus stopping them from providing the tumor with nutrition. This can stop the cancer tumor from growing, which can reduce its size. This can be achieved by injecting drugs into selected blood vessels which are for providing the tumor with nutrition through aorta. This is to block the artery, which monitors the liver cancer, to achieve treatment results and not to affect the normal liver tissues.

• Suitable for: This is suitable for a patient whose tumor has spread to both sides of the liver but has not yet metastasized to other organs, or a patient whose tumor is limited to one side of the liver but whose liver function, tumor location, tumor size, or tumor number is not suitable for surgery or local ablative treatment.

(3) Injection of alcohol

• Rationale of treatment: With the help of ultrasound or computer scan, the location of the tumor is confirmed. Then alcohol with 95% concentration is injected directly into the tumor with a thin needle through the skin. The highly concentrated alcohol will dry up the cells and thus kill them.

• Suitable for: It is suitable for a patient whose tumor is smaller than 3cm or whose number of tumors is less than 3. As the injection can only make the central part of the tumor to wither, which means the neighboring tissues still survive and keep growing, so the patient has to get many injections to ensure the liver cancer cells are killed.

(4) Radiofrequency ablation

• Rationale of treatment: This is to use localized thermal treatment technique, when temperature reaching 60∘C to destroy the tumor tissues. Depending on the location and size of the tumor, the surgery can be performed through percutaneous or laparotomy. Simultaneously ultrasonography is used to guide the electrode and to monitor the ablation level of the tumor.

• Suitable for: This is for those who are infected with primary liver cancer and metastatic liver cancer.

(5) Liver transplant

• Rationale of treatment: It is the best treatment for end-stage liver disease. The patient’s liver is removed and replaced by healthy liver tissue from a donor.  Usually, it is suitable for the patient either having a single tumor that is 5cm or smaller or having 3 or fewer tumors, all of which are smaller than 3cm. The liver is the only organ in the body that can replace lost or injured tissue (regenerate). The donor’s liver will grow back to normal size after surgery.

(6) Selective Internal Irradiation (SIRT)

• Rationale of treatment: SIRT is a radio-embolization technique in which radioactive microspheres are injected via intravascular catheters into the hepatic artery that supplies the tumor. These microspheres are tagged with Yttrium-90 which is capable of emitting short-distance radiation. Hence, SIRT allows preferential irradiation of the tumor to a high radiation dose without causing excessive damage to the normal liver function. 

• Suitable for: liver cancers that are not eligible for surgery or local ablative therapy. In contrast to TACE, some patients with portal vein thrombosis, a contraindication for TACE, appeared to tolerate SIRT favorably. 
• A prospective randomized trial comparison between SIRT and TACE suggested that these two procedures had similar efficacy.

• SIRT is contraindicated in patients who have poor liver function or uncontrolled ascites. Pre-treatment assessment with hepatic angiogram and Technetium MAA scan is necessary to evaluate the amount of microspheres uptake in lung, liver, and gastrointestinal tract. Inadvertent delivery of SIR- microspheres to the gastrointestinal tract or pancreas will cause acute abdominal pain, acute pancreatitis, cholecystitis, or peptic ulceration. Excessive shunting to the lung may lead to radiation pneumonitis. Excessive radiation to the normal liver parenchyma may result in radiation hepatitis.

(7) Stereotactic ablative body radiotherapy (SABR)

• Rationale of treatment: External beam irradiation for HCC was rarely used in the past because of the low radiation tolerance of liver. The risk of radiation induced liver disease (RILD) increases with poor baseline liver function. With growing experience, it is now known that disease control can be possible if high radiation dose can be delivered to the tumor while sparing a sufficient amount of normal liver reserve.
• Suitable for: patients who are not amenable to undergo surgery or local ablative therapies. It is also indicated in patients who have developed recurrence despite multiple courses of TACE. Patients with portal vein thrombosis who are not suitable for TACE can also be treated with SABR.

(8) Targeted therapy & Immunotherapy

• Target therapy is systemic treatment targeting cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. It blocks the growth and spread of cancer cells effectively and limits damage to healthy cells. Side effects may include high blood pressure, back pain, headaches, changes in taste, fatigue, diarrhea, appetite loss, joint and muscle pain, weight loss, abdominal pain, rash, redness, itching or peeling of the skin on the hands and feet, hoarseness, bleeding, change in thyroid hormone levels, and nausea.

• For first-line treatment, for patients with unresectable or metastatic liver cancer, doctors may prescribe bevacizumab (anti-angiogenesis targeted therapy given intravenously) with atezolizumab (immunotherapy, taken as pill), Lenvatinib (anti-angiogenesis targeted therapy, taken as pill) or sorafenib (taken orally as pill).

• For patients who already received sorafenib as previous treatment, cabozantinib (oral pill) or regorafenib (oral pill), may be prescribed

• Immunotherapy fights cancer by improving the immune system's ability. Immune checkpoint inhibitor is a common one, to help the immune system to better find and attack the cancer cells. Immunotherapy can cause side effects. Many side effects happen when the immune system that is revved-up to act against the cancer also acts against healthy cells and tissues in the body. Common side effects include skin reactions, flu-like symptoms, diarrhea, and weight changes from retaining fluid.

• Doctors will choose drugs based on the clinical judgement and patients' condition. Patients may consult the doctor-in-charge for advice on medication treatment. HA has implemented its Drug Formulary with a view to ensuring equitable access by patients to cost effective drugs of proven safety and efficacy through standardization of policies on drugs and drug utilization in all public hospitals and clinics. HA has mechanisms in place to conduct ad hoc and regular reviews of the HA Drug Formulary. The review process follows an evidence-based approach, having regard to the safety, efficacy and cost-effectiveness of drugs while taking into account the latest international practice as well as views of professionals and patient groups.

Common complications observed among liver cancer patients include:

• Liver failure: Cancer tissues cause serious damages to a patient's liver, which results in the liver being unable to removed toxins from the body and this will lead to hepatic encephalopathy which is the main cause of death from liver cancer.
• Kidney failure: The phenomenon of liver cancer leads to kidney failure which cripples the patient's ability to discharge waste from the body.
• Metastasis of tumor: It is common that tumor cells metastasize to lungs and bones. When it metastasizes to the peritoneum, ascites is caused. Thus the liver cancer near the diaphragm infiltrates directly to the diaphragm and pleura, which may lead to bloody pleural fluid.

Patients need to pay attention to a lot of things before and after surgery and during recovery. The more they understand the disease, the more positive they will become when dealing with the disease.

• Regular follow-ups: Regular follow-ups will be arranged to monitor the liver functions and symptoms of recurrence. Should any new symptoms be found, the doctor should be notified as soon as possible.

• Diet: To improve appetite and encourage eating

  • Try to absorb proteins (milk, eggs and lean meat) and multivitamins and limit the intake of animal oil.

  • Foods should be easy to digest and plenty of fruit and vegetables are recommended.

  • Cancer treatment might weaken the immune system. Immunocompromised patient is advised to avoid to eat raw or undercooked meat, poultry, eggs, seafood, raw or unpasteurized dairy products, and ready-to-eat raw vegetables.

• Exercise: Appropriate exercise but avoid over-exertion.

• Activities: Avoid visiting crowded places to prevent infections of diseases.

• To quit alcohol and avoid drugs and chemical substances that may add workload to the liver.