Liver cancer: Description
Liver cancer is a malignant tumor disease of the liver. This organ fulfills many tasks in the body:
- The liver utilizes the nutrients absorbed from the intestine. For example, it stores excess sugar (glucose) in the form of glycogen. Certain vitamins and iron are also stored in the liver when the body does not need them.
- The organ is involved in controlling the sugar, protein and fat metabolism.
- The liver produces bile, which is necessary for the digestion of fat in the intestine.
- It produces the factors for blood clotting as well as the basic substances for the formation of sex hormones and the body’s own fats.
- As a central detoxification organ, the liver converts and breaks down harmful substances, drugs, alcohol and certain endogenous substances. The breakdown of old red blood cells also takes place here.
Different types of malignant liver tumors
Malignant tumors within the liver can have different origins. Accordingly, a distinction is made between primary and secondary liver tumors.
Primary liver tumors
A primary liver tumor has its origin directly in the liver – doctors refer to this as liver cancer. Depending on which cells degenerate, different forms of liver cancer result. These include, among others
- Liver cell cancer (hepatocellular carcinoma, HCC): In the vast majority of cases, primary liver tumors are hepatocellular carcinoma – i.e. a malignant tumor that arises from degenerated liver cells (hepatocytes).
- intrahepatic cholangiocarcinoma (iCC): This primary liver tumor develops from the bile ducts within the organ and is more common in women than in men. Incidentally, bile duct cancer can also develop from bile ducts outside the liver and is then called extrahepatic cholangiocarcinoma (eCC).
Secondary liver tumors
Secondary liver tumors are liver metastases, i.e. metastases (metastases) of a cancerous tumor in another part of the body. This original tumor (primary tumor) is often located in the lungs, breast, uterus, prostate or gastrointestinal tract. Individual cancer cells from the primary tumor can reach the liver via the blood and settle there. In Europe, such liver metastases are more common than liver cancer.
Only liver cancer is discussed below!
Frequency of liver cancer
Liver cancer is relatively rare in Europe: according to the World Health Organization (WHO), 58,079 men and 29,551 women were newly diagnosed with the disease in 2020. The disease mainly occurs at an older age.
Liver cancer: symptoms
You can find out about the symptoms of liver cancer in the article Liver cancer – symptoms.
Liver cancer: causes and risk factors
The exact causes of liver cancer are not yet fully understood. However, there are numerous known risk factors that promote the development of (primary) liver cancer. There are differences between the various types of primary liver cancer. Here are the most important ones:
Hepatocellular carcinoma – risk factors
Liver cirrhosis
In more than 80 percent of cases, hepatocellular carcinoma develops as a result of a shrunken liver (liver cirrhosis). The main causes of liver cirrhosis and thus hepatocellular carcinoma are
- chronic liver inflammation caused by hepatitis C or hepatitis B viruses
- Chronic alcohol consumption
- non-alcoholic fatty liver (develops mainly as a result of severe obesity and/or type 2 diabetes mellitus)
A chronic hepatitis B infection and a non-alcoholic fatty liver can also lead directly – without liver cirrhosis as a “detour” – to liver cancer.
Substances toxic to the liver (hepatotoxins)
Various toxins can also trigger liver cancer, for example aflatoxins. These are very potent, cancer-causing (carcinogenic) toxins that are produced by the mold fungus (Aspergillus flavus). The fungus often colonizes nuts and cereals if they grow under poor conditions (drought) and are subsequently stored in damp conditions. Liver cancer caused by mold toxins is much more common in tropical-subtropical countries than in Europe.
Other hepatotoxins that can promote hepatocellular carcinoma include the semi-metal arsenic and the toxic gas vinyl chloride (raw material for polyvinyl chloride, PVC).
Iron storage disease (haemochromatosis)
Intrahepatic cholangiocarcinoma (iCC) – risk factors
The risk of bile duct cancer inside (and outside) the liver increases primarily due to chronic inflammation of the bile ducts, which can have various causes. For example, bile duct cancer often occurs in patients with primary sclerosing cholangitis (PSC). This is a chronic, autoimmune-related inflammation of the bile duct.
Other possible triggers of chronic bile duct inflammation and therefore a risk factor for bile duct cancer are chronic infections, for example with typhoid bacteria, hepatitis B or hepatitis C viruses, HIV or various parasites (such as the Chinese liver fluke).
Hemangiosarcoma of the liver – risk factors
Another risk factor for a cancerous tumor originating in the blood vessels is anabolic steroids, which are abused by some athletes and bodybuilders to build muscle.
Liver cancer: examinations and diagnosis
The right person to contact if you suspect liver cancer is your family doctor or a specialist in internal medicine and gastroenterology.
For people with certain risk factors for liver cancer (such as liver cirrhosis, chronic hepatitis B or C infection), regular examinations can be useful for the early detection of liver cancer.
Medical history and physical examination
To begin with, the doctor will take your medical history (anamnesis) in a detailed consultation. He will ask you to describe your symptoms in detail and ask you about your general state of health, your lifestyle and any underlying illnesses. Possible questions in this regard are, for example
- Do you have chronic inflammation of the liver (hepatitis) or cirrhosis of the liver?
- How much alcohol do you drink every day? Were there times in your life when you drank more?
- Do you have frequently changing sexual partners? (-> Increased risk of hepatitis B and C)
The interview is followed by a physical examination: in the case of liver cancer, the liver may be so enlarged that the doctor can feel it under the right costal arch. In the case of liver cirrhosis – the most important risk factor for liver cancer (more precisely: liver cell cancer) – the surface of the liver is typically bumpy and irregular. This can also be felt.
As a rule, the doctor also taps the abdomen with his fingers (percussion). This allows him to determine whether there is water in the abdomen (ascites). This is often the case with serious liver diseases such as liver cancer.
Based on the medical history and physical examination, the doctor can already roughly assess whether liver cancer is present. However, further examinations are always necessary for a reliable diagnosis.
Blood tests
The AFP value is more important for monitoring progress than for diagnosing liver cancer.
Various liver values are also measured in the blood as general parameters of liver function. These include liver enzymes (such as AST/GOT and ALT/GPT), liver synthesis parameters (vitamin K-dependent blood coagulation factors, albumin, cholinesterase) and values that are typically elevated in the case of bile stasis (gamma-GT, AP, bilirubin).
Imaging procedures
An ultrasound examination (sonography) provides an initial assessment of the condition of the liver. It can reveal structural changes in the organ and possibly a tumor. Clearer images can be obtained by administering a contrast agent (contrast-enhanced ultrasound, CEUS).
In addition, magnetic resonance imaging (MRI) and/or computer tomography (CT) are often used. They provide more detailed images than a normal ultrasound – especially if the patient is administered a contrast agent during the examination, as is usually the case.
The importance of the various imaging procedures depends on the individual case. For example, if liver cell cancer (hepatocellular carcinoma) is suspected in patients with liver cirrhosis, an MRI with contrast medium is recommended as a diagnostic imaging procedure.
If an MRI cannot be performed (e.g. in patients with a pacemaker) or if the findings are unclear, a computer tomography (CT) and/or a contrast-enhanced ultrasound examination (CEUS) is used as an alternative diagnostic procedure.
Biopsy
Sometimes liver cancer can only be diagnosed with certainty if a tissue sample is taken and examined microscopically in the laboratory. The tissue sample is taken by means of a puncture: the doctor inserts a fine hollow needle into the liver via the abdominal wall under ultrasound or CT guidance and extracts tissue from the suspicious area. The patient is given a local anaesthetic for the procedure so that they feel no pain.
Liver cancer: classification according to spread
TNM classification for liver cancer:
Tumor size (T):
- T1: A single (solitary) tumor that has not yet affected any blood vessels.
- T2: Solitary tumor with vascular involvement or several (multiple) tumors with a maximum diameter of five centimeters.
- T3: Multiple tumors with a diameter of more than five centimeters or tumors affecting a larger branch of the portal vein and the hepatic vein.
- T4: Tumor(s) with invasion of adjacent organs or tumor(s) with perforation of the peritoneum.
Lymph nodes (N):
- NX: Lymph node involvement cannot be assessed.
- N0: Lymph nodes are not affected by cancer cells.
- N1: Lymph nodes are affected by cancer cells.
Distant metastases (M):
- MX: Distant metastases cannot be assessed.
- M0: No distant metastases.
- M1: Distant metastases present (e.g. in the lungs).
UICC stages:
|
UICC stage |
TNM classification |
|
Stage I |
Up to T1 N0 M0 |
|
Stage II |
Up to T2 N0 M0 |
|
Stage III |
Up to T4 N0 M0 |
|
Stage IVa |
Any T N1 M0 |
|
Stage IVb |
Every T, every N and from M1 |
Liver cancer: Treatment
An operation offers the chance to cure the liver cancer patient by removing the diseased part of the liver (partial resection) or the entire liver. In the latter case, the patient receives a donor liver as a replacement (liver transplant).
In most cases, however, liver cancer is already too advanced for surgery at the time of diagnosis. Instead of an operation or to bridge the time until a liver transplant, local measures are then considered to destroy the tumor (local ablative therapy).
If liver cancer cannot be completely eliminated by surgery or local ablation, patients can be treated with transarterial (chemo or radio) embolization and/or medication. Sometimes high-precision radiation therapy (high-precision radiotherapy) is also considered. The aim of these treatments is to slow down tumor growth and prolong the survival time of those affected.
Surgery / liver transplant
If the liver cancer has spread to so many areas of the organ that a partial surgical resection is no longer possible, the entire organ may be removed and replaced with a donor liver. However, such a liver transplant is only an option for a small number of patients, as various conditions must be met. For example, the tumor must be confined to the liver and must not yet have formed metastases (liver cancer metastases) – for example in lymph nodes.
Local ablative procedures
There are various local ablative procedures for the treatment of liver cancer. Here are the most important ones:
In microwave ablation (MWA), the tumor tissue is also heated locally and thus destroyed. However, even higher temperatures (up to 160 degrees) are used than in radiofrequency ablation (RFA).
Another local ablative therapy method for liver cancer is percutaneous ethanol or acetic acid injection (PEI). In this procedure, the doctor injects alcohol (ethanol) or acetic acid through the abdominal wall into the affected area of the liver. Both substances cause the cancer cells to die. The surrounding healthy tissue is largely spared. The percutaneous ethanol or acetic acid injection is usually repeated in several sessions at intervals of several weeks.
Experts recommend radiofrequency or microwave ablation as a local ablative procedure for the treatment of liver cell cancer (hepatocellular carcinoma). Percutaneous ethanol or acetic acid injections have proven to be less effective than RFA, for example.
Transarterial (chemo)embolization (TAE/TACE)
The doctor advances a flexible cannula (catheter) to the hepatic artery via an access in the inguinal arteries under X-ray control. Each liver tumor is supplied with oxygen and nutrients via one or more branches of this artery. In the next step, the doctor injects small plastic particles into these vessels via the catheter, thereby sealing them off – the cancer cells, which are now cut off from the blood supply, die.
This therapy procedure is called transarterial embolization (TAE). It can be combined with local chemotherapy: For this purpose, the doctor also injects an active substance via the catheter into the vicinity of the tumor, which kills cancer cells (chemotherapeutic agent). This is known as transarterial chemo-embolization (TACE).
Transarterial radio-embolization (TARE)
Here too, a catheter is inserted into the hepatic artery via the groin. The doctor then uses this catheter to introduce numerous tiny radioactive beads into the vessels that supply the tumor. This has two effects: Firstly, the vessels are closed off so that the tumor is cut off from the blood supply. Secondly, the cancer cells are exposed to a high local dose of radiation, which kills them.
High-precision radiotherapy
In high-precision radiotherapy, a high dose of radiation is directed very precisely from the outside onto a precisely defined area of the body – the tumor or a metastasis. The procedure is also known as stereotactic body radiotherapy (SBRT). It is considered when other local therapy methods for the treatment of liver cancer are not possible.
Drugs
Targeted drugs
In addition to sorafenib, other enzyme inhibitors (multi-kinase or tyrosine kinase inhibitors) are now available for liver cancer therapy, including regorafenib and lenvatinib.
For certain patients with hepatocellular cancer, combination therapy with the artificially produced monoclonal antibodies atezolizumab and bevacizumab is an option. Atezolizumab inhibits a protein produced by the cancer cells (PD-L1), which ensures that the body’s own immune system does not attack the tumor cells. By blocking PD-L1, atezolizumab can remove this “brake” on the immune defense, allowing the body to take more effective action against the malignant cells.
Bevacizumab specifically inhibits the growth factor VEGF. This is produced by tumors in order to stimulate the formation of new blood vessels – for a better supply to the tumor. By inhibiting VEGF, bevacizumab can therefore reduce the supply and thus the growth of the malignant tumor.
Treatment with targeted drugs is only considered for selected patient groups.
Systemic chemotherapy
Doctors use systemic chemotherapy (= chemotherapy that affects the whole body) to treat many cancers – i.e. drugs that generally inhibit the growth of rapidly dividing cells (such as cancer cells).
However, such chemotherapy is not used as standard for adults with liver cell cancer because it generally has little effect here. However, it can be considered in individual cases, for example in the final stage of liver cancer as a pain-relieving (palliative) measure. Although it cannot stop the progression of liver cancer completely, it can at least slow it down.
In contrast to adults, children and adolescents with hepatocellular cancer respond well to systemic chemotherapy in almost half of all cases. This is why it is standard treatment for this patient group.
Liver cancer: course of the disease and prognosis
However, the malignant tumor is often only discovered at an advanced stage. The therapeutic options are then limited. As with most tumor diseases, life expectancy and chances of recovery are poor in the case of liver cancer if it is diagnosed late. By this time, the cancer cells have already spread to other organs and formed metastases (liver cancer metastases). In the most common form of liver cancer – hepatocellular carcinoma (liver cell cancer) – an average of 15 percent of affected men and women are still alive five years after diagnosis (five-year survival rate).
Liver cancer: prevention
If you want to prevent liver cancer, you should avoid the known risk factors (see above) as far as possible:
- Only drink alcohol moderately or, in the case of chronic liver disease (cirrhosis, chronic hepatitis, etc.), avoid alcohol altogether. This stimulant can cause massive damage to the liver and lead to liver cirrhosis within years – a significant risk factor for the development of liver cancer.
- Do not eat any moldy food (such as cereals, corn, peanuts or pistachios). These should be thrown away – just removing visibly affected parts is not enough. The mold has already formed long, invisible threads that run through the food.
- It is also advisable to avoid tobacco. The consumption of cigarettes etc. is also associated with an increased risk of liver cancer.
- People with chronic liver disease should drink coffee because it can counteract the progression of scarring (fibrosis) of the liver in these patients and reduce the risk of liver cancer (more precisely: liver cell cancer). The effect appears to be most noticeable with three or more cups of coffee a day.
- In addition, proper treatment of chronic liver diseases (such as cirrhosis, hepatitis B or C) is important to reduce the risk of liver cancer.
- There is currently no vaccination to prevent hepatitis C. However, other measures (e.g. not sharing drug equipment such as syringes) can reduce the risk of hepatitis C infection and thus liver cancer.
- If possible, patients with non-insulin-dependent diabetes should be treated with the blood sugar lowering drug metformin. It reduces the risk of liver cancer (more precisely: liver cell cancer) in those affected.