Liver cancer

Introduction and incidence

The liver is one of the largest organs in humans, located in the abdomen just below the diaphragm that separates it from the lungs. It consists of two larger lobes (right and left), and can be further divided into several segments. Some of its functions are the filtration of harmful substances for excretion in stool or urine, the production of bile, which is essential for the digestion of fats from food, the storage of glycogen (sugar), the production of proteins, and many others, and it is an organ without which life is impossible. It is more common in the male population, and according to data from the Croatian Cancer Registry from 2017, men accounted for 3% of all new cancer cases. There were about half as many cases in women. The two main types of liver cancer are hepatocellular carcinoma (HCC), which arises from altered liver cells, and cholangiocellular carcinoma, which arises from bile duct cells (ducts that transport bile). Of the primary liver tumors, metastases of other tumors that can spread to the liver are even more common.

Risk factors

Risk factors for the development of liver cancer include viral hepatitis (B and C), cirrhosis of the liver of any cause, excessive alcohol consumption, aflatoxin in food (more in Interesting facts at the end of the page), non-alcoholic steatohepatitis (a disease with the accumulation of fat in the liver), smoking, older age, and some genetic syndromes (hereditary hemochromatosis, alpha-1-antitrypsin deficiency, Wilson's disease, and others).​ You can read more about the risk factors for the development of cancer in a separate article.

Signs and symptoms

Liver cancer often occurs in a cirrhotic liver, and the symptoms may be masked by the symptoms of cirrhosis. Some of the signs of the disease may include a lump on the right side of the abdomen below the ribs, discomfort in the right upper abdomen, abdominal enlargement due to fluid accumulation (ascites), pain in the right shoulder or back, jaundice, bruising, fatigue and weakness, nausea and vomiting, loss of appetite and weight, white stools and dark urine, and fever.

Figure 1. Liver cancer is most common in Southeast Asia and sub-Saharan Africa due to the high prevalence of hepatitis B and C infections in these areas. (Source: Wikipedia)

Diagnosis

The basis is a detailed examination of the patient and a thorough medical history. Alpha-fetoprotein (AFP) is a tumor marker that may (but may not) be elevated in patients with liver tumors, and is analyzed from the blood. Liver function tests (enzymes) are also performed from the blood. Liver ultrasound can be used as an imaging test, but CT or MRI are more precise. If cirrhosis is present and the imaging test results clearly indicate HCC, a liver biopsy is not required to confirm the diagnosis. In addition to evidence of the disease, an assessment of liver function is also important because the possibility of applying certain types of therapy depends on it. In patients with impaired liver function, therapeutic options are significantly narrowed. You can read more about cancer diagnostics in a separate article.

Treatment

Liver cancer is treated depending on the type of tumor, liver function (child-Pugh score), and stage of the disease. There are several types of treatment that can be applied in these patients. Surgical treatment includes partial hepatectomy, which removes the part of the liver affected by the tumor. It is important that the remaining part of the liver is large and functional enough (for example, that it is not affected by cirrhosis) to take over the complete function of the organ. The remaining part of the liver can grow over time. Another option is transplantation, which completely removes the liver and replaces it with a new organ from another donor. Transplantation can only be performed if the disease is limited to the liver (no distant metastases), and while waiting for an organ, other forms of treatment can be performed so that the disease does not progress in the meantime. Ablation techniques are used to directly destroy the tumor, without its surgical removal. Special needles are usually used that are introduced through the skin to the liver lesion, and the techniques for destroying cells are diverse: radiofrequency ablation (high-energy radio waves cause intense heating and destruction of tissue), microwave therapy (microwaves that intensely heat tissue), percutaneous ethanol injection, cryoablation (destruction of tissue by freezing), and some others. Embolization techniques exploit the fact that most of the blood supply to tumor tissue comes from the hepatic artery, while healthy liver tissue is nourished mainly by the portal vein. By blocking (embolizing) the hepatic artery, the tumor tissue loses the nutrients it needs to grow. The procedure is performed by inserting a catheter (a thin, flexible tube) through the arteries in the groin all the way to the liver, and in addition to transarterial embolization (TAE), transarterial chemoembolization (TACE) can also be performed, in which chemotherapy is additionally injected into the hepatic artery before blocking it. The standard administration of chemotherapy via intravenous access (into a vein) in liver cancer is outdated and is not recommended. However, targeted therapy (including sorafenib, bevacizumab, lenvatinib, regorafenib) and immunotherapy (alone or in combination) are used as systemic treatments, which achieve excellent results in some patients. The use of radiotherapy in liver cancer is relatively limited. One option, especially for patients with advanced disease, is to enroll in a clinical trial.

Patients with early liver cancer are generally treated with one of the local techniques: surgery, transplantation in selected patients, or ablation techniques that can successfully replace surgery in smaller lesions with a rapid recovery of the patient.

In advanced disease, it is important to assess liver function as noted above, because if it is not satisfactory, the range of therapies that can be used is very limited, and it is not uncommon for liver function to be so damaged (e.g. cirrhosis) that no treatment is possible due to a direct threat to the patient's life. The most commonly used forms of treatment in these patients are embolization techniques, targeted therapy, and immunotherapy.

Additional interesting facts

Globally, liver cancer is most common in Southeast Asia and sub-Saharan Africa due to the high prevalence of hepatitis B and C infections in these areas. Data also show that the mortality rate from this disease is increasing significantly, and is currently growing faster than the mortality rate from any other malignant disease in the world!

Aflatoxins are a family of toxins produced by certain types of fungi that can be found on agricultural crops such as corn, peanuts and tree nuts. They are mainly produced by Aspergillus flavus and Aspergillus parasiticus, which are found in warm and humid regions of the world. These fungi can contaminate crops in the field, at harvest and (probably most often) during improper storage. Aflatoxins are known to be associated with an increased risk of liver cancer. People can be exposed to aflatoxins by eating contaminated plant products or by consuming meat or dairy products from animals that have eaten contaminated food. Farmers are also at risk by inhaling dust during their work. How to protect yourself? Buy trusted products (verified small producers or well-known brands) and do not consume nuts and other fruits that look moldy, discolored, or shriveled.

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