Many cancers metastasise to the liver, whereas primary liver cancer (cancer that arises in the liver) is not very common. Liver cancer is found twice as frequently in men than in women. This is due to reasons such as different alcohol drinking habits. The most common type of primary liver cancer is liver cell carcinoma, or hepatocellular carcinoma (HCC). Less common are bile duct carcinomas, or cholangiocarcinomas, which originate in the bile ducts inside the liver. What these cancers have in common is that they usually appear in a liver that is already damaged by liver cirrhosis or a chronic bile duct disease. Bile duct carcinomas are discussed in connection with gallbladder cancer.

HCC may metastasise to other parts of the liver, but it seldom spreads outside the liver to other organs such as the bones or lungs, and only at an advanced stage of the disease. At the early stage, the tumor often grows and progresses very slowly. Advanced liver cancer may cause internal bleeding, ascites or liver failure.

Risk of disease

In Western countries, most cases of HCC are caused by liver cirrhosis and other liver diseases. Globally, liver cancer is most often secondary to chronic Hepatitis B virus infection. In African and Asian countries, the frequency of Hepatitis B and C is high. As a result, liver cirrhosis and liver cancer are also common in these countries. In Finland and other Western countries, excessive use of alcohol is the most common cause of liver cirrhosis. However, liver cirrhosis is not always caused by alcohol; it may also be a consequence of rare liver diseases that are not associated with alcohol at all. Obesity is an increasing health concern in Western countries. It leads to metabolic syndrome and hepatic steatosis (fatty liver), which increase the risk of HCC. This is an issue in the United States in particular, but increasingly in other countries as well.

Haemochromatosis is another condition that causes liver cirrhosis and liver cancer. It is a disorder of iron metabolism and leads to excessive amounts of iron being stored in the liver, pancreas and other organs. Untreated haemochromatosis increases the risk of HCC to approximately 200-fold. If haemochromatosis is treated early, before liver cirrhosis develops, the risk of HCC is virtually nonexistent.

Furthermore, diabetes, advanced age and smoking slightly increase the risk of HCC.

Symptoms

Most HCC patients remain symptom-free for a long time, which delays the diagnosis. Usually, patients do not experience symptoms until the cancer has penetrated through the fibrous capsule of the liver or spread to nearby organs. In addition, HCC mainly presents general symptoms that can be caused by a number of other reasons. Cancer does not always come to mind.

Common liver cancer symptoms include tiredness, a feeling of fullness in the upper part of the stomach and loss of appetite. If the tumor causes pain and is palpable on the upper abdomen, it has probably grown quite large already. Later symptoms include weight loss and possibly fever, jaundice and vomiting. The jaundice is caused by the liver’s inability to continue to eliminate bilirubin from the blood. Liver cancer symptoms may also include itching, caused by changes in the bile acid content of the blood.

Diagnosis

In a suspected HCC case, the first examinations usually include blood tests such as liver function tests. Blood test results are nearly always abnormal if the patient has HCC.

CT and MRI scans provide accurate images of the liver, which makes it easier to reach a diagnosis. CT scanning shows whether the tumor has spread to the surrounding area and blood vessels. In connection with the imaging studies, a sample is taken of the tumor to determine whether it is cancerous or not. Analysis of the sample is the most reliable way of determining whether the lesion found in the liver is benign or malignant. However, hepatocellular cancer sometimes appears so recognisable in a CT scan that the scan alone is sufficient grounds for a diagnosis.

In addition, various lab tests are performed when HCC is suspected. The alpha-fetoprotein (AFP) level in blood is clearly elevated in up to 80 % of HCC patients. Increasing AFP levels in successive blood samples are strongly indicative of cancer, and together with typical imaging results, these findings are diagnostic. The functioning of the liver is often disturbed due to the underlying liver disease. Liver function blood tests are performed when considering the choice of treatment for HCC. The prognosis for severe cirrhosis of the liver may be worse than that for cancer, making treatment challenging or even impossible.

Treatment

The treatment of liver cancer is planned individually. The choice of treatment depends on the stage of the cancer, the functioning of the liver and the patient’s general physical condition. In addition, the patient’s other possible diseases and medication affect the decision. The operability of the tumor depends on its location in relation to critical blood vessel and bile duct structures and the size and number of tumors.

The following treatment methods can be used alone or in combinations:

  • surgery (including liver transplantation)
  • other local treatment
  • embolisation therapies (TACE and SIRT) administered directly into the blood circulation of the liver
  • radiotherapy
  • chemotherapy

Surgical resection is an effective treatment method for liver cancer. However, the tumor must be relatively small and located in a section from which it can be removed. Furthermore, the rest of the liver must be relatively healthy. Approximately 25 per cent of the entire liver tissue can be safely removed, providing that liver insufficiency is not too far advanced. If the liver is healthy, as much as 70–80 per cent of it can be removed. However, the liver is often already seriously damaged by liver cirrhosis.

If the hepatic cancer has not significantly spread (1–3 small cancerous tumors in the liver) but some other existing medical condition of the liver prevents surgical operation, a liver transplant may be considered. However, the availability of suitable transplants poses a challenge. If a patient has developed liver cirrhosis as a result of excessive alcohol consumption, they must commit to complete abstinence from alcohol in the long term before a liver transplant can be considered.

In the event that surgery can not be accomplished, it is often possible to reduce the size of the tumor or slow down its development with other treatments.  If there is just a single tumor or only a few of them, local treatments, such as thermal ablation, may sometimes come into question. In this treatment, a needle-like probe is guided into the middle of the tumor. It transmits radiofrequency radiation that briefly heats the area of the tumor to a high temperature, destroying both sick and healthy cells.

In TACE therapy (transcatheter arterial chemoembolisation), chemotherapeutic agents are injected directly into the vessels of a hepatic cancer tumor. At the same time, vessels supplying the tumor with blood are blocked with an embolising agent. In some rare cases, TACE therapy may decrease the size of the tumor so much that it can actually be operated on. Sometimes, tiny microspheres of radioactive material may be used that attach to the capillary network of the tumor and radiate, causing an internal radiation therapy effect (SIRT, selective internal radiation therapy).

In general, hepatic cancer is treated with external radiotherapy only in case no other local treatment is viable. Healthy liver tissue is easily damaged by radiotherapy, which limits its use.

Pharmacotherapy is applied to patients with advanced hepatic cancer that has spread so far it cannot be treated with local methods such as surgery, thermal ablation or embolisation. The most frequently used form of pharmacotherapy is sorafenib, a targeted drug which clinical trials have found to extend the average life span of cancer patients. Recently, the use of another targeted drug called lenvatinib has increased. If a patient’s cancer has spread during sorafenib treatment, the use of a third targeted drug, regorafenib, may be considered. New pharmacological treatments for hepatic cancer are constantly being developed and the availability of drugs may improve over the coming years. For example, while hepatic cancer is not as of yet an official subject for immunological treatment in the EU, studies on it have yielded positive preliminary results.

Our hospital provides pharmacotherapy for advanced cancer with high professional skill and expertise.

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