Liver cancer is the sixth most common malignant tumor in the world and the third most common cause of cancer-related deaths worldwide. More than 600,000 cases of liver cancer are diagnosed worldwide each year, and the number of new cases continues to grow. Men are three times more frequently affected than women. There are large differences in the geographical distribution of liver-cancer incidence. Well over half of cases are estimated to occur in China, with Japan in second place. Europe has more than three times as many liver-cancer patients as the United States. The most common form of liver cancer is hepatocellular carcinoma (HCC). It causes about 90 percent of primary cancer tumors in the liver.

The main risk factors for the development of liver cancer are chronic infections with hepatitis B and/or hepatitis C and cirrhosis of the liver; the latter is often associated with hepatitis but is also frequently caused by alcohol abuse. Other risk factors include obesity (fatty liver), diabetes, smoking, long-term intake of anabolics and long-term exposure to certain fungal toxins (aflatoxins).

Imaging techniques play a key role in liver diagnostics

In the diagnostic classification of liver lesions, a distinction is made between focal and diffuse lesions. Focal lesions affect a clear-cut area. They include benign and malignant tumors. Among the most important benign tumors are hemangiomas (sponge-like structures filled with blood), liver cysts, adenomas, and focal nodular hyperplasias. The most important malignant tumors are hepatocellular carcinomas and metastases from other primary tumors, such as colon cancer. Diffuse lesions, by contrast (e.g. fatty liver, liver cirrhosis), do not show clear boundaries.

The various liver lesions are characterized by different morphological structures, which are made visible in different ways using various imaging techniques. High diagnostic accuracy in the detection of focal liver lesions is based on a distinct contrast between healthy liver tissue (liver parenchyma) and focal lesions.

Three imaging techniques are used in liver diagnostics: ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI).

Ultrasound – Basic examination for a quick overview

Ultrasound is generally the first examination method used when liver results are ambiguous. As a basic examination liver sonography is fast, inexpensive and widely available. The procedure is very dependent on the experience of the physician, and the results are often difficult to reproduce. CT and MRI are more informative when it comes to localizing and characterizing liver lesions. Ultrasound is also used for controlling biopsies and operations.

Computed tomography – Broadly used in hospitals

CT is a commonly used procedure in liver diagnostics and enjoys broad clinical acceptance. The intrinsic contrast in a liver CT is inferior to that achieved by MRI, because the density difference between liver parenchyma and typical lesions is small. Using CT to detect focal liver lesions therefore requires optimal contrast enhancement. The rate of false positive lesions is higher than in MRI examinations. In particular, MRI is better at detecting very small lesions. One disadvantage of CT is that patients are exposed to radiation. In addition, some patients show an allergic reaction to the iodinated contrast media used.

MRI – Most informative in liver diagnosis

MRI has become established as a very effective method of detecting, localizing and characterizing focal liver lesions. A liver MRI is the most informative non-invasive diagnostic procedure. Another advantage is that the patients are not exposed to any radiation. Because of its diagnostic significance, the liver MRI is often the method of choice for clarifying unclear ultrasound findings.
For technical reasons, an MRI has the advantage that soft-tissue contrast is stronger compared to CT and ultrasound. MRI is better at characterizing liver lesions than CT because of its very specific signal characteristics. A liver MRI usually requires dynamic imaging after a bolus injection of contrast medium.

The introduction of liver-cell-specific contrast agents has further improved the contrast between the liver parenchyma and extrahepatic or malignant tissue in focal lesions. Furthermore, even very tiny lesions with a diameter of less than 1 cm can be detected (see Fig. 1). Bayer HealthCare Pharmaceuticals has developed a gadolinium-based contrast medium which – due to its structural properties – is taken up specifically by liver cells (hepatocytes) and thus accumulates in healthy liver tissue. Lesions with no, or only minimal, liver-cell functions, such as cysts, metastases and most hepatocellular carcinomas, are not enhanced. This increases contrast, making lesions easier to detect and locate compared to healthy liver tissue. In this way it contributes toward improved characterization, i.e. toward distinguishing between benign and malignant liver lesions and diagnosing the exact lesion type.

Fig.1: MR images of a liver before (left) and after administration) of contrast medium (right). Liver tumors (red arrows) become clearly visible after administration of a liver-specific contrast agent.

Treatment options for liver cancer

The options for treating liver cancer are limited and depend on what stage the cancer has reached. Liver cancer is usually detected late, because it typically only causes symptoms in advanced stages. Most patients therefore have a poor prognosis. There is hence a great need for reliable methods of early diagnosis and novel treatment options.

At present, the only chance for recovery is a surgical liver resection. However, only about 15 percent of patients are even operable. If the entire liver is removed, a liver transplant has to be subsequently performed. Patients who are not operable can receive treatment by radiation, chemotherapy or ethanol injection.

It was Bayer HealthCare Pharmaceuticals who firstly received the product approval for an oral cancer drug in the liver cancer indication in 2007. It is the only preparation so far that can significantly extend the overall survival rates of patients with HCC. The drug targets both the cancer cells and the tumor's vascular system. It is currently approved in more than 40 countries for the treatment of liver cancer.