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Liver Cancer

Liver cancer is the fifth commonest cancer in Hong Kong. In 2019, there were 1 876 new cases of liver cancer, accounting for 5.3% of new cancer cases. Its crude annual incidence rate per 100 000 Hong Kong population was 25. Also, liver cancer is the third leading cause of cancer deaths in Hong Kong. A total of 1 530 people died from this cancer in 2019, accounting for 10.3% of all cancer deaths. Males are more susceptible to this disease than females, reflected by the male to female ratio for the incidence of 3.4 to 1 in 2019.

It is relatively difficult to cure liver cancer because the cancer is usually diagnosed in middle or late stage, which affects the cure rate. Prevention is always better than cure. We should get the hepatitis B vaccination, and people who carry hepatitis B should have regular follow-ups to check if there are signs of liver tumours development.

What is Liver Cancer?

The liver is the largest organ in the body and 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:

  • Produce and store of glucose for use when necessary.
  • Produce bile for digesting fats in food.
  • Detoxification of toxins and alcohol.
  • Produce proteins, blood-clotting components, antibodies and cholesterol.

Liver cancer will develop when the liver cells begin to mutate and divide uncontrolledly. Liver cancer can be classified into primary liver cancer and metastatic liver cancer. Primary liver cancer is a malignant tumour 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.

Who have higher chance of having Liver Cancer?

There are many causes of liver cancer. Factors posing higher risks include:

  • Hepatitis B infection

    55% of the 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 non-hepatitis B virus carriers. Hepatitis B is very common in Hong Kong. It is estimated that one tenth of citizens in Hong Kong either is hepatitis B virus carriers or had the infection. Among them, a quarter may develop cirrhosis, which may cause liver cancer.

  • Cirrhosis

    It will take 50 to 60 years to develop liver cancer after hepatitis B virus infection. People infected with hepatitis B virus may develop chronic hepatitis in about 10 years, which may then develop into cirrhosis in additional 21 years. After that, it will take 29 years for the cirrhosis to become liver cancer. The actual progress varies among people, depending on how active the hepatitis viruses are. Research shows that the more active the viruses are, the more quickly the liver cells are damaged, accelerating the development of cirrhosis or chronic hepatitis.

  • Hepatitis C infection

    The chance of chronic hepatitis B and hepatitis C carriers to get liver cancer is 150 times higher. However, liver cancers associated with hepatitis C infection are more common in Western countries.

  • Heavy alcohol consumption

    Excessive alcohol consumption may cause alcohol-related liver hardening, which may then develop into liver cancer. The chance of hepatitis B carriers with heavy alcohol consumption getting liver cell cancer is 2 times higher than 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.

  • Prolonged exposure to certain environmental and pollutant hazards

    For example, inhaling PVC used in plastics manufacturing factories.

  • Cholangitis or congenital choledochal cyst

    May lead to bile duct cancer.

What are the symptoms of Liver Cancer?

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. As a result, symptoms of a liver cancer at its early stage are not obvious. When the tumour grows, the patient can observe the following:

  • Pain in the right side of upper abdomen.
  • Pain in the right shoulder because the swollen liver stimulates the nerves of the diaphragm, which 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 and itchy skin because the bile duct is blocked by the tumour, resulting in the accumulation of the bile pigment in blood, leading to jaundice.
  • Tea-colour urine and light grey stools.
  • Ascites (collection of fluid in the abdomen).

Prevention

Major risk factors identified for liver cancer include chronic infection with hepatitis B virus (“HBV”) and hepatitis C virus (“HCV”), cirrhosis, alcohol consumption and ingestion of food contaminated with aflatoxin (a toxin found in some food, such as mouldy peanuts and grains), although other risk factors like diabetes, obesity, smoking and certain hereditary conditions such as haemochromatosis, glycogen storage disease and Wilson’s disease are also implicated. Locally, HBV vaccination has been given to all babies born since 1984 as an important preventive measure.

To reduce the chance of getting liver cancer, it is important to get vaccinated against HBV, avoid drinking alcohol and tobacco smoking. Avoidance of unprotected sexual intercourse, sharing needles and food possibly tainted with aflatoxins and maintaining healthy diet and body weight would also help reducing the risk of developing liver cancer.

Screening

Two more widely-adopted tests for liver cancer screening are alpha-fetoprotein (“AFP”) test and abdominal ultrasonography (“USG”).  AFP test and abdominal USG have their limitations and they are not 100% accurate, because the blood AFP level is frequently normal during early stage and it could also be raised in conditions other than liver cancer, while the performance of abdominal USG is more operator dependent and could be affected by factors like abdominal fatness.

Asymptomatic individuals at average risk

Currently, routine liver cancer screening is not recommended for asymptomatic individuals at average risk.

Increased risk individuals

Individuals at increased risk of liver cancer (e.g. people with chronic HBV or HCV infection, or cirrhosis regardless of cause) should seek advice from doctors to determine their need for and approach of cancer surveillance.  Depending on certain criteria such as age, family history, presence of cirrhosis and other clinical parameters, periodic surveillance (e.g. every 6 to 12 months) with AFP and abdominal USG may be considered.

How to investigate and make diagnosis for Liver Cancer?

High-risk groups and those having the above-mentioned symptoms should consult doctors and 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:

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    Blood test

    Alpha-fetoprotein (AFP) is being used as a tumour marker for liver cancer, and can be used for screening of liver cancer in high risk groups such as patients with liver cirrhosis, chronic hepatitis B or C. It could also be helpful to determine prognosis, monitor response to therapy and detect recurrence.

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    Abdominal ultrasound

    Ultrasound is used to scan the structure of the liver to confirm the size and location of the tumour. It takes several minutes or longer for conducting the procedure.

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    Biopsy

    Doctors will use a fine needle to obtain tissue of the liver tumour through the skin on the right abdomen when the patient is under local anaesthesia. It is used for confirming the type of the tumour cells and examining whether they are benign or malignant. This test is usually performed together with ultrasound to ensure the needle is inserted at the precise position.

What are the treatments for Liver Cancer?

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

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    Surgery

    It is used to remove the tumour and the surrounding affected tissues. Removal by radical surgery suits 20% of liver cancer patients whose tumours affect only one of the liver lobes and their liver functions are normal. 3-year and 5-year survival rates are 62% and 50% respectively.

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    Injection of alcohol

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

    It suits patients whose tumour is smaller than 3cm or whose number of tumours is less than 3. As the injection can only wither the central part of the tumour, the neighbouring tissues still survive and keep growing. As a result, the patient has to get many injections to ensure the liver cancer cells are killed.

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    Liver transplant

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    Stereotactic body radiation therapy (SBRT)

    SBRT is an external radiation therapy that uses high energy radiation to destroy the tumour. It helps control the disease while sparing a sufficient amount of normal liver reserve. The treatment utilises multi-modality image registration, radiation treatment planning, breathing motion management and image guided radiation therapy. It has high delivery accuracy, allowing ablative doses of radiation to be delivered safely.

    The treatment suits patients who are not amenable to undergo surgery or local ablative therapies or have developed recurrence despite multiple courses of TACE. Cases with hepatocellular carcinoma whose tumours are less than 5 cm in diameter have 80-90% objective response rates while the rate is between 50-70% for those with larger cancers. Improved local control and survival have been seen in patients treated with higher doses.

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    Targeted therapy

    Targeted therapy interferes with specific targeted molecules (target) that are involved in cancer cell growth and survival, resulting in fewer side effects. Nonetheless, since some of the normal cells have similar target, targeted therapy can affect them too. Common side effects include rash, mouth sores, diarrhoea, etc.

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    Immunotherapy

    Immunotherapy helps the immune system to better act against cancer.

What are the complications of Liver Cancer?

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. This will lead to hepatic encephalopathy, which is the main cause of death from liver cancer.

  • Kidney failure

    The phenomenon of liver failure leads to kidney failure, which cripples the patient's ability to discharge waste from the body.

  • Metastasis of tumour

    It is common that tumour 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.

How do patients with Liver Cancer take care of themselves?

Patients need to pay attention to many things before and after surgery and during recovery. These include:

  1. Regular follow-ups

    To monitor the liver functions and symptoms of recurrence. If any new symptoms are found, the doctor should be notified as soon as possible.

  2. Diet

    Foods should be easy to digest and plenty of fruit and vegetables are recommended. Try to absorb proteins (milk, eggs and lean meat) and multivitamins and limit the intake of animal oil.

  3. Exercise

    Appropriate exercise but avoid over-exertion.

  4. Avoid visiting crowded places to prevent infections of diseases

  5. Quit alcohol and avoid drugs and chemical substances that may add workload to the liver

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Liver Biopsy

  1. Introduction

    In patients with liver disease, accurate diagnosis of the cause of the disease can improve treatment. Although blood tests and ultrasound examination provide some clues, examination of the liver tissue provides much more valuable information for diagnosis. Liver biopsy involves the use of a special needle to obtain liver tissue through the skin. Patients with acute or chronic hepatitis, abnormal liver function tests, liver failure, cirrhosis, etc. may be candidates for liver biopsy. It can provide information for making the diagnosis, predicting the prognosis and formulating the treatment plan.

  2. Preparation before the procedure

    • Patients need to be fasted for at least 6 hours before the procedure.
    • If the patient has problem with blood clotting, it needs to be corrected first with transfusion of blood products.
    • Patients should inform the medical staff of any major medical problems including diabetes, hypertension and continue their medications as instructed.
    • Patients should also provide information concerning the current medications used especially antiplatelet and anticoagulation drugs and any allergic history. In patient using anticoagulation and antiplatelet drugs, they will be instructed to stop or modify the dosage of the medications.
  3. Procedure

    • Prior to the procedure, local anaesthetic is injected at the site of biopsy.
    • After the drug has taken effect, the doctor will make a small (about 1-2mm) incision on the skin. Doctor will ask the patient to hold the breath while piercing through the incision site with the biopsy needle into the liver to obtain tissue. About 1-2 cm of liver tissue will be obtained.
    • In general, the procedure takes 10-15 minutes.
  4. After the procedure

    • After the biopsy, the medical and nursing staff will closely monitor the pulse and blood pressure of the patient.
    • Patient may resume oral feeding when the condition is stable. Vigorous physical activity should be avoided within 2 weeks after the biopsy to prevent bleeding from the biopsy site.
    • Patients should attend the follow-up appointment as scheduled for the biopsy result. They should also follow the instructions of the medical staff regarding further use of medication.
  5. Risk and complication

    • After years of practice and research worldwide, liver biopsy has been shown to be safe and complications are uncommon. Studies showed that about 20% of the patients have mild pain in upper abdomen for several minutes to several hours after the procedure. A small number of patients have transient drop of blood pressure. About 1 in every 600 patients has minor internal bleeding and about 0.3-0.5% of patients has major bleeding that requires blood transfusion. In very rare circumstances (about 0.1-0.01%), the patient may die from severe bleeding.
    • Other complications include accidental injury of other organs like gallbladder, kidney, lung, intestine, etc. Serious complications may result in death. In case of complications, patients may need radiological or surgical intervention.
  6. Remarks

    For further information please contact your doctor.

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Transarterial chemoembolization (TACE)

  1. Introduction

    Transarterial chemoembolization (TACE) is a regional treatment for inoperable hepatocellular carcinoma. It is also indicated for patients with regional recurrence in the liver after previous resection of hepatocellular carcinoma. In some patients with critically inoperable tumour, the tumour size is reduced after repeated sessions of TACE, which then becomes resectable.

    TACE involves regional infection of chemotherapy drugs (Cisplatin + Lipiodol) to concentrate the drugs in the tumour area, enhancing the cytotoxic effect on the tumour cells. Gleform, a kind of sponge, is used to block the feeding vessels of the tumour and deprive nutrient and oxygen supply, causing tumour cell death and suppressing tumour growth.

  2. Preparation before the procedure

    • Blood tests are needed on the day before the procedure to assess the liver function, complete blood count and the coagulation profile.
    • Patients with low platelet count or clotting deficiency require transfusion of platelet concentrate or fresh frozen plasma before the procedure.
    • Prophylactic antibiotics will be given before the procedure.
    • Fasting for 6 hours before the procedure.
    • A written consent is required.
  3. Procedure

    • The procedure is performed by an interventional radiologist.
    • Local anaesthesia will be applied. Intravenous sedation will be used if necessary.
    • The femoral artery in the groin will be punctured with a catheter and the catheter will be manipulated into the hepatic artery under imaging guidance. Contrast will be injected during the procedure to visualise the arteries.
    • After the catheter is manipulated into the target artery that feeds the tumour, a mixture of chemotherapeutic agent is injected.
    • In some cases, embolization may not be performed if the liver function or the catheter position is unfavourable.
    • After the procedure, the catheter is withdrawn and the groin wound is compressed to stop bleeding from the artery.
  4. After the procedure

    • Bed rest to avoid bleeding from the artery puncture site.
    • A course of antibiotics to prevent infection, and a course of medication to minimize the chance of peptic ulcer will be given.
    • Epigastric pain or fever will be commonly experienced and analgesics/antipyretics will be given if necessary.
    • Blood test will be performed the next day to check the liver function.
    • Most patients can be discharged the next day but some patients may have to stay longer for complications management.
  5. Risk and complication

    • Epigastric pain and fever are very common side effects of the procedure, which will subside with the use of medications in most cases.
    • About 20% of patients may develop more severe complications, which include:
      • Complications related to femoral artery puncture and catheterization of hepatic artery: bleeding, haematoma, dissection or thrombosis of artery and embolism of lower limb.
      • Complications related to chemoembolization that include acute cholecystitis, acute pancreatitis, liver failure renal failure, liver abscess, gastrointestinal bleeding, peptic ulcer. Some severe complications can be fatal in some cases.
      • The majority of patients with complication will recover with appropriate treatment. Patients who develop a severe complication or significant deterioration of liver function may have to discontinue the treatment.
  6. Remarks

    For further information please contact your doctor.

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Radiofrequency Ablation

  1. Introduction

    Radiofrequency ablation (RFA) is a local ablative treatment modality for liver tumours including primary and secondary liver cancer. It uses localised thermal treatment technique that causes tumour destruction by heating the tumour tissue to the temperature exceeding 60oC. The procedure can be performed through percutaneous and open approaches depending on the location and size of the tumours.

  2. Preparation before the procedure

    • Blood tests, liver function test, chest X-ray, ECG and CT scan are required.
    • Local anaesthesia is usually required for the percutaneous approach.
    • Patients can be admitted on the date of treatment.
    • Fasting for 6 hours before RFA.
    • A written consent is required.
    • For RFA through the open approach, patients need to be admitted one day before the procedure for anaesthetic work-up. The open RFA will be performed under general anaesthesia in operating theatre.
  3. Procedure

    • The procedure is performed by an interventional radiologist.
    • For accessible tumours, procedure is performed percutaneously under local anaesthesia with intraveneous sedation.
    • RFA is performed using a cool-tip probe. Either a single needle or a clustered probe will be used depending on tumour size. The aim is to obtain complete ablation of the tumour plus a 1-cm tumour-free margin.
    • For tumours that are located at the dome of the liver or close to adjacent structures e.g. diaphragm or colon, RFA will be performed by open surgery under general anaesthesia.
  4. After the procedure

    • Patients will stay in hospital during the initial post-operative period. Blood tests (liver function test) and other vital signs will be closely monitored.
    • A helical contrast CT scan is performed at one to two weeks after the ablative procedure to check for the completeness of ablation. Any residual tumours detected are treated with a repeat session of RFA.
    • Adequate pain control is given by anaesthetists.
    • Patients can resume a normal diet on the day after RFA.
    • Patients will be discharged if clinical condition is stable.
    • All patients who underwent RFA will be followed up in the specialist clinic by experienced hepatobiliary surgeons.
  5. Risk and complication

    • The complication rate is about 7%, including liver abscess formation, bleeding and visceral injury. The possibility of death is about 1%.
  6. Remarks

    For further information please contact your doctor.

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Radiotherapy (Selective Internal Radiation Therapy with Yttrium-90 Microspheres)

  1. Introduction

    Selective Internal Radiation Therapy (SIRT) using yttrium-90 (Y90) microspheres is an internal radiation therapy for liver tumours where curative resection is not possible.

    Treatment with SIRT-Y90 exploits a normal physiological process of 2 different blood supplies to liver to selectively target the tumour tissue. Following delivery via a hepatic artery catheter, Y90 microspheres become lodged in the micro-vessels of liver tumour where they have a local radiation effect. There may be some limited concurrent damage to healthy tissue caused by radiation that escapes tumour boundaries and from Y-90 microspheres that fail to become embedded in tumours. Following decay of the yttrium-90, the inert microspheres will be retained permanently in tissue.

    Normally the radiation from yttrium-90 microspheres retained inside the liver tumour will not be able to penetrate beyond the abdominal wall. However, when the total dose is higher than a certain limit, there is still some concern of potential harm to other people from the secondary radiation generated.

    According to Radiation Ordinance and the HA Code of Practice on Radiation Safety and Protection, the activity of yttrium-90 in a patient must be below 1.5 GBq before he/she is allowed to be discharged or travel by public transport. Therefore, all patients after receiving SIRT-Y90 must stay strictly in an isolation room to avoid radiation hazard to their family members or members of the public. Patients are forbidden to leave the isolation room until the radiation dose from their body was checked to fall below a safe limit. This may take a few hours up to a few days after SIRT-Y90, depending on the actual dose they received. In the event of death, cremation may be denied by health authorities or may be deferred for a period of time depending on residual radioactivity.

  2. Preparation before the procedure

    • Patients have to take note that radioactive substance can cause teratogenicity. During the course and within 2 months after treatment, both male and female patients (if applicable) should take contraceptive measures. Patients should not breastfeed during the first 2 weeks after treatment.
    • Before SIRT, patient is required to have a diagnostic hepatic angiogram (HAG) to establish the arterial anatomy of the liver and the tumour. At the same time a pretreatment simulation scan will be done with the injection of a radioactive tracer Tc-MAA, to predict the distribution of the microspheres in the body.
    • When necessary the feeding arteries to the stomach or duodenum will be embolised to prevent the flow of radioactive particles to these organs.
    • Only patient with suitable arterial supply and favourable result from the Tc-MAA scan can safely proceed to receive SIRT-Y90.
  3. Procedure

    • The procedure usually takes about 1-2 hours.
    • The doctor will puncture the femoral artery (at the groin) and inject the yttrium-90 microspheres through the hepatic angiographic catheter placed near the tumour-feeding artery.
    • The catheter will be removed after the procedure and pressure will be applied on the puncture site to stop the bleeding.
    • If the patient feels unwell anytime during the treatment period, please inform the staff.
  4. After the procedure

    • After the SIRT, all patients are required to stay strictly in an isolation room for a few hours up to a few days until the radiation from their body fall to a safe level.
    • As the patients can still emit low levels of radiation after discharge from the hospital (<1.5 GBq), they are advised to observe the instructions given by the instruction card.
    • Avoid close contacts with pregnant women or young children.
  5. Risk and complication

    • Side effects may include, but are not necessarily limited to the ones listed below. Each patient reacts differently and may experience none, some, or all of the complications to a varying degree of intensity.
      • Most patients may experience a mild post-embolization syndrome that include fever, abdominal pain, nausea, vomiting, diarrhoea and mild liver function test abnormalities which is usually self-limiting and will resolve in a few days. Painkiller and anti-sickness medication may be required.
      • Potential rare complications arising from the hepatic angiographic procedure include the risk of bleeding, damage to blood vessels with associated organ damage such as stroke, heart attack.
      • Very rarely radiation induced liver damage (radiation hepatitis) may occur, or some of the yttrium-90 microspheres may enter other organs and cause damage, including the lungs (radiation pneumonitis), stomach and duodenum (gastritis and duodenal ulcers), pancreas (acute pancreatitis), gallbladder (acute cholecystitis). Most of these complications can be prevented and treated but some can be fatal.
    • Radiation-induced tumours may occur, but this is rare.
    • It may be possible that the intended treatment outcome cannot be achieved, the disease may not be alleviated and it may recur or progress in the future.
    • Unpredictable and unpreventable adverse outcomes may occur after treatment. Patients should read and fully understand the content before deciding on undergoing the treatment.
  6. Follow-up

    • Recovery varies from person to person, some people can go back to work shortly after completion of treatment.
    • After completing the treatment, a follow-up appointment will be arranged to assess your response to the treatment and look for complications. Please attend your appointment as scheduled.
    • Patients must follow instructions strictly on taking medication as directed.
  7. Remarks

    For further information please contact your doctor.