What is Hepatocellular Carcinoma (HCC)?

Primary liver cancer—that is, cancer that starts in the liver—is called hepatocellular carcinoma, or HCC for short. HCC almost always happens to people who have had liver disease for many years. In the United States the most common causes are infection with the hepatitis C virus or from excessive alcohol intake; around the world, hepatitis B is the leading cause of liver cancer. Around 800,000 people get HCC every year, making it the fifth most common cancer worldwide. Compared to most other cancers treatment is more difficult, though, so nearly 750,000 people die of HCC each year, making it number two, behind only lung cancer as the leading cancer killer.

Whatever the underlying disease, it takes many years of continual liver damage before HCC develops; in most cases cirrhosis, a hardening of the liver due to built-up scar tissue, is already present. HCC usually grows slowly in its early stages; as a result HCC can usually be cured if discovered early enough.

Screening for HCC

People with any type of cirrhosis are at risk to develop HCC; when cirrhosis is due to hepatitis B or C, the risk is especially high—up to five percent every year. Since we know who is at risk, HCC is a perfect target for screening and surveillance, and doing scans every six months has been proven to save lives. While guidelines recommend ultrasound for this purpose because it is cheap and widely available, up to 30 percent of early cancers can be missed by ultrasound. For this reason, at Mount Sinai, as at many centers where effective treatments like liver resection and transplantation are available to treat early HCC, we use more sensitive methods for screening like CT scan or MRI.

Diagnosis of HCC

For most types of cancer, a biopsy (a sample of the tumor tissue) is necessary to establish the diagnosis. This is not the case, though, for HCC. In a person who has cirrhosis, finding a mass in the liver with a rich blood supply that it lights up in a characteristic way on CT or MRI scan after dye injection is accepted around the world to be as good as a biopsy. Not every HCC has the typical appearance, and occasionally HCC develops in someone who has no known liver disease; in such cases biopsy may still be necessary. Now that we have entered the era of personalized medicine where treatments are being developed that can target the specific genetic abnormalities in a particular person’s cancer, the role of biopsy to provide tissue for genetic analysis is likely to increase.

Staging of HCC

Cancer staging is a way of classifying people with cancer based on the extent of the cancer and other relevant factors into groups with roughly similar prognosis; in some instances staging is directly linked to treatment. For most cancers staging is according to guidelines produced by the American Joint Commission on Cancer (AJCC). The AJCC system includes three things: the extent of the tumor in the liver (T), whether it has spread to nearby lymph nodes (N), and whether it has spread, or metastasized, to more distant places (M). For most people with cancer surgery is the primary treatment, and AJCC staging is primarily focused on them; in fact, HCC staging according to AJCC can only be done on people who have had surgery since it depends on things the pathologist finds on examining the part of the liver that was removed. This is a problem for HCC, since as a result of the underlying liver disease many people cannot undergo surgery even though they have early HCC, and as a result most doctors who treat HCC don’t rely on the AJCC system.

The Barcelona Clinic Liver Cancer staging system (BCLC) was developed to enable staging of all people with HCC. A key feature of BCLC is that it links the stage of HCC to the recommended treatment based on critical analysis of medical evidence. BCLC staging has been adopted in guidelines both in the U.S. and in Europe as the best staging system, and it is how we stage HCC at Mount Sinai. People with a single small (less than 2cm) HCC are at the earliest stage that can be detected; they are called BCLC class 0. BCLC class A comprises people with HCC that is potentially curable and includes people with a single HCC up to 5cm in diameter or 2-3 nodules of HCC up to 3cm in diameter and without invasion of blood vessels or spread outside of the liver based on scans. It also includes people with single HCC larger than 5cm, if their liver function is normal and they can undergo surgical resection.

Treatments for BCLC classes 0 and A HCC include resection, transplantation, and thermal ablation. People with HCC beyond the limits that define BCLC class A but that is still confined to the liver without invasion of blood vessels or distant spread are in BCLC class B. The treatment for BCLC class B HCC is chemoembolization. HCC that has invaded large blood vessels that can be identified on scans or has spread outside of the liver is considered BCLC class C as long as the liver function and general condition of the person affected remains good enough that treatment is possible. According to BCLC the treatment for class C is the drug called sorafenib, though many centers including Mount Sinai also add direct treatment of the tumors in the liver when the extent of blood vessel invasion or spread outside the liver is limited. When HCC is advanced to the point where the liver (and the person) can no longer function well enough to tolerate treatment it is considered BCBC class D, and the recommended treatment is supportive care.

Treatments for HCC

Hope for a cure for HCC depends on removing or in some other way destroying the tumor before it spreads. The fact that most people with HCC have cirrhosis greatly complicates matters; what is good from the standpoint of treating the cancer may be bad from the standpoint of the liver. Only with an interdisciplinary team made up of transplant and cancer surgeons, hepatologists (medical liver specialists), radiologists, and oncologists working together can the best decisions be made and treatments—both surgical and nonsurgical—can be carried out.