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:
  55%of the world’s liver cancer is caused by infection with hepatitis B virus. 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. 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 Hepatosteatosis (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)
• 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)

    Once the patient is diagnosed to have liver cancer, doctor will generally suggest the following treatments depending on the cancer stage:

(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: This is for those who cannot undergo an operation for the removal of liver. They are patients whose livers function badly, and patients having undergone Transarterial Chemoembolization and injection of alcohol, provided that their tumors are no larger than 5cm. If the tumor has grown to a certain size, it is highly likely that the cancer cells have spread to other parts of the body. If then liver transplant is carried out, the cancer cell will reproduce themselves rapidly in the new liver, which will result in the recurrence of liver cancer.

(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. Various studies of SIRT in patients with advanced liver cancers reported response rates (RR) of 20-89%, and a median time-to-progression of 7-12 months.

• 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. Retrospective comparison between SIRT and TACE suggested similar efficacy, but there is no reported randomized controlled trials to compare SIRT and TACE face-to-face.

• 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. Technological advances in Stereotactic ablative body radiotherapy (SABR) through the use of multi-modality image registration, radiation treatment planning, breathing motion management and image guided radiation therapy have significantly increased treatment delivery accuracy and made it possible for ablative doses of radiation to be delivered safely to focally unresectable HCC.

• 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. Objective response rates are 80-90% in HCCs less than 5 cm in diameter, and in the range of 50-70% in larger cancers. Improved local control and survival have been seen in patients treated with higher doses.

(8) Sytemic therapy & Targeted therapy

• Before the development of sorafenib, first-line systemic therapies for the treatment of unresectable HCC were lacking. Many randomized-controlled trials had demonstrated that the use of systemic chemotherapy, hormonal compounds, octreotide and interferon in patients with unresectable HCC did not improve survival compared with no treatment.

• Sorafenib is currently the only targeted therapy approved by the US Food and Drug Administration to be used in patients with unresectable HCC, based on the survival advantage over best supportive care demonstrated in two randomized controlled trials. Sorafenib inhibits the following receptor tyrosine kinases: VEGFR-2, VEGFR-3, PDGFR-b, c-KIT, and Flt-3. Since Sorafenib has the potential to decrease blood flow in the tumor, studies have been initiated to investigate sorafenib as an adjuvant to potentially curative treatments such as resection or local ablation in resectable HCC, or the combination of sorafenib and TACE or SBRT in patients with unresectable HCC.

• Although sorafenib represents a palliative treatment option for patients with advanced HCC, it also produces toxicities that may significantly affect patients’ quality of life. High rates of dermatologic side effects (Hand foot syndrome), hypertension, fatigue and gastrointestinal discomfort have been reported. Other complications include cardiac ischemia, thyroid dysfunction, bowel perforation, bleeding and hepatitis.

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.

• 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.