Liver cancer

Liver cancer is a malignant tumor occurring in the liver. Medical practitioners refer to it as primary liver cancer.  

The majority of all liver cancers are hepatocellular carcinomas (HCC), which originate in liver cells. The primary liver tumors also include tumors in the bile ducts inside the liver (intrahepatic bile duct carcinomas) and more uncommon liver cancers such as sarcomas. Around 9,800 people get liver cancer every year in Germany.  

Often there are no symptoms indicating liver cancer to begin with. When someone has a complaint, it tends to be general: 

• pain and a sense of pressure in the upper stomach 
• general reduction in performance 
• loss of appetite 
• involuntary weight loss 

Sufferers usually get the liver cancer diagnosis at a late stage in the illness: a yellowing of the skin and eyes (jaundice), a much-enlarged liver (hepatomegalia), or a buildup of fluid in the abdomen (ascites) may then indicate a tumor in the liver.  

Bile duct cancer in the liver (also known as cholangiocarcinoma or biliary tract cancer) similarly only produces symptoms at a late stage. As well as the complaints already mentioned, dark urine, white-colored stools, and severe itching may also occur.   

General symptoms such as loss of appetite and general reduction in performance do not only occur in cases of cancer, but also often with benign illnesses. If these symptoms persist, a visit to the doctor is recommended. General Practitioners can already narrow down what is causing the symptoms and, if necessary, initiate further diagnostic steps with specialists.

The main risk factor for hepatocellular carcinoma is chronic liver damage, known as cirrhosis of the liver. In Germany it is most commonly linked to a chronic infection with the hepatitis C virus or high alcohol consumption.

Other risk factors include:

• a fatty liver: a liver disorder caused by overeating or a poor diet
• obesity (adiposity)
• diabetes mellitus
• a chronic hepatitis­ B or C­ infection
• certain congenital metabolic disorders
• smoking

The risk factors for bile duct carcinomas in the liver are largely the same as those for hepatocellular carcinoma. There are also additional risk factors, such as chronic inflammation of the bile ducts, protruding (cystic) enlargements of the bile duct outside of the liver or bile duct stones in the bile ducts of the liver.

In general, experts recommend a healthy lifestyle with a balanced diet and sufficient movement. These can help prevent liver disease.

By abstaining from alcohol and maintaining a healthy body weight, liver cancer in particular may be prevented.

Other preventive measures include:

• a hepatitis B vaccination in compliance with the guidelines issued by the Standing Committee on Vaccination (STIKO) at the Robert Koch Institute 
• treating those suffering from chronic infections with the hepatitis B or hepatitis C viruses
• giving up smoking
• drinking coffee in the case of chronic liver disease
• the drug metformin, which can reduce the risk of developing liver cancer in people with type 2 diabetes

In its early stage, liver cancer does not usually cause complaints that point to a tumor in the liver. For this reason, there is no statutory liver cancer screening program for the healthy population.

High-risk patients

Some people have a higher risk of getting liver cancer. These include patients with cirrhosis of the liver or hepatitis, caused by a chronic hepatitis B or hepatitis C infection or a fatty liver. Certain rare hereditary metabolic disorders also increase the risk of liver cancer. Experts recommend that these patients get regular ultrasound checks on their liver and, if necessary, have blood tests. Determining the fibrosis stage can also help doctors to better assess the risk of liver cancer for some high-risk patients. It indicates the extent to which the structures of the liver tissue have already changed.

Various methods are available to doctors to diagnose liver cancer.

An initial idea can be gained from an ultrasound scan (sonography) of the abdomen. To further clarify any suspect structure in the liver, doctors use imaging tests. To do this, they first inject a contrast agent into the patient’s vein. Images are then captured at specific time intervals. If liver cancer is present, doctors can usually identify the fact from the resulting sectional images.

The main contrast agent-enhanced imaging method for diagnosing liver cancer is magnetic resonance imaging (MRI). Other possible methods using contrast agents are computed tomography (CT) and sonography (CEUS).

If the initial images fail to provide a definite diagnosis, the way forward depends on the size of the suspect area.

If imaging methods fail to provide a definite diagnosis twice in a row, the doctor will take tissue from the tumor (biopsy). This intervention is done from outside, through the abdominal wall. Patients are given a local anesthetic for this. The tissue removed is then examined under the microscope in the laboratory. This will secure the diagnosis.

Biopsies are a particular option if the liver lesions are small or if lesions are found in a cirrhosis-free liver.

Molecular pathology-based tests may also be useful in some cases, as they allow doctors to determine the properties of the tumor cells. This may help with planning future treatment.

Diagnosing bile duct carcinoma in the liver

The methods described above are used to diagnose bile duct carcinoma in the liver. Additional tests may also be required, such as:

• a three-dimensional image of the bile ducts using magnetic resonance imaging (MRI) and contrast agents
• an endoscopic method for showing bile ducts and possibly pancreatic ducts – this is called endoscopic-retrograde cholangio(pancreato)graphy, ERC(P)
• percutaneous transhepatic cholangiography (PTC), in which the bile ducts in the liver, guided by imaging, are punctured with a thin needle and shown using contrast agents
• an endoscopy of the abdominal cavity (laparoscopy) and removal of tissue samples

If it is not clear whether the issue is a primary liver or bile duct tumor or liver metastases, an endoscopy of the stomach and bowel may also be needed. This can be used to exclude a primary tumor that has come from those organs.

There is detailed information about the procedures and possible risks involved in imaging and surgical methods of diagnosing cancer on the website of the Cancer Information Service of the German Cancer Research Center (in German).

Which therapy is best for hepatocellular carcinoma depends on the stage of the disease. Doctors use a special system they call the Barcelona Clinic for Liver Cancer (BCLC) staging system to determine the stage. Key criteria in this system are:

• the number and size of tumors in the liver.
• the spread and location of the tumor: is the tumor restricted to the liver, locally advanced or are there metastases?
• the patient’s health: does the patient have chronic liver disease (cirrhosis of the liver) and how serious is it?
• the patient’s liver function.

If patients with hepatocellular carcinoma (HCC) also have a chronic hepatitis B or C viral infection, experts recommend that this be treated also.

Liver cell carcinoma – when a cure is possible

At an early stage of the disease, a cure is possible if doctors are able to completely remove the liver cancer. To do this, operations to remove part of the liver or a liver transplant are options.

If surgical removal is no longer an option at the stage the diagnosis is made or if the tumor is not in a favorable location for surgery, doctors may instead use various heat-based methods to destroy it locally.

In the period until a liver becomes available for a transplant, the patient often has to be tided over with other treatments. This is known as bridging.

A patient sometimes also receives treatment before surgery to reduce the size of the tumor. This is known as downstaging.

As an alternative to surgery – in particular if the location of the tumor is unfavorable – doctors may instead destroy the tumor locally using various methods. These include, in particular, thermal (heat-based) treatments such as radiofrequency ablation (RFA) and microwave ablation (MWA).

Liver cell carcinoma – when no cure is possible

If a cure is no longer possible there are therapeutic methods that can alleviate the patient’s discomforts. Specialists call this palliative therapy. These therapies can slow down the growth of the tumor and improve the quality of life.

If the liver cancer is between the early and advanced stages, less invasive treatments are an option. These include radiotherapy “from the inside” (internal radiotherapy) or chemotherapy targeted at the liver alone. These procedures act directly on the tumor. They cannot cure the cancer, but slow down its growth. Prerequisites are good patient health, good liver function, and no metastases.

Is the disease already advanced, has it spread to the surrounding tissue or dispersed to other organs? If so, a (systemic) treatment acting on the entire body makes more sense. In the case of systemic treatments, doctors use, for example, immunotherapy with immune checkpoint inhibitors or targeted therapy drugs – several drugs may also be used in combination.

• Targeted therapy drugs attack the biological properties of tumor cells that are important for the cancer’s progression.
• Immunotherapy stimulates certain of the body’s natural defensive cells to fight the cancer cells themselves.

Every 6 to 12 weeks, doctors use imaging scans to determine whether the treatment is effective and whether the tumor is responding to the drugs.

In the final stage of the disease, and when they have discomfort, patients receive a supportive treatment. The aim of supportive therapy is to alleviate tumor-related symptoms and improve the sufferer’s quality of life. This means that the measures taken are aimed at the patient’s symptoms.

Bile duct carcinomas in the liver

In early stages doctors remove bile duct tumors in the liver by operating, along with parts of the liver. Which part of the liver the surgeon removes depends on the vessels and bile ducts affected. The neighboring lymph nodes are usually taken out, too. Experts do not recommend a liver transplant outside of studies.

A supportive treatment may follow on after the operation. It is intended to lower the risk of the cancer returning. Doctors tend to favor chemotherapy in these cases. Specialists call this treatment phase “adjuvant therapy”. Patients may also receive localized treatments as an alternative to surgery. For example, heat may be used to destroy the tumor.

If the disease is already well advanced, the treatment is based on the patient’s general condition. The aim of this palliative therapy is not to cure, but to check the disease and maintain the quality of life:

• When a tumor is well advanced or metastasized, medication is an option. Doctors usually then favor chemotherapy.
• To alleviate discomfort, a patient can also be given in situ therapies that destroy the tumor.
• Depending on the individual situation, targeted therapies are also an option.
• A supportive treatment can alleviate the sufferer’s onerous symptoms.

Liver cell carcinoma or bile duct carcinoma – what happens if the tumor comes back?

If a tumor grows back again following successful treatment, medical practitioners refer to this as a relapse. Another operation may be possible, provided that the tumor is limited to the liver. Otherwise, localized treatments will be considered.

What should be considered when it comes to operations? What are the procedures for chemotherapy and targeted therapies and what side effects do they have? There is detailed additional information on the website of the Cancer Information Service of the German Cancer Research Center (in German).

Medical rehabilitation (rehab) after a cancer therapy is aimed at helping patients deal with the consequences of their illness and treatment as well as possible. A medical rehab program thus focuses on the personal medical history and existing limitations. 

A medical rehab program after liver cancer therapy may include: 

• psychological support 
• nutritional advice 
• re-integration into working and social life 

The website of the Cancer Information Service of the German Cancer Research Center has the addresses of cancer advisory services and psycho-oncologists who provide outpatient psychotherapy. There is also a list of the main contacts for any questions relating to social law. 

Aftercare examinations help to quickly identify, and treat, any relapse or complications arising from the treatment.  

When a tumor has been completely removed, patients are regularly examined, first at short, then at longer intervals. Aftercare monitoring can stretch over a period of 5 years.  

If the cancer is incurable, regular follow-up checks will help to identify and treat any adverse symptoms at an early stage. For example, a doctor can prescribe medication for nausea, vomiting and fatigue. 

Doctors with different specializations work closely together to treat liver cancer. Hospitals that are particularly experienced in treating patients with liver cancer can get certification to prove this. The German Cancer Society (DKG) regularly checks their compliance with certain professional requirements.  

You can find the addresses of the certified liver cancer centers on the OncoMAP website.

In relation to the quality of the surgical clinic/department, the German Society for General and Visceral Surgery (Deutsche Gesellschaft für Viszeralchirurgie) maintains a list of certified centers for surgical liver diseases.

Do you have further questions about dealing with the condition in everyday life and additional support options? You can find information about this on the website of the Cancer Information Service of the German Cancer Research Center (in German).

For all questions about liver cancer, you can also make direct contact with Cancer Information Service doctors by dialing the freephone number (0800) 420 30 40 or by sending an e-mail to krebsinformationsdienst@dkfz.de.