5 Critical Facts About Liver Cancer

Liver cancer is a major cause of death worldwide, particularly in Asia. In the West, however, unlike many cancers, liver cancer incidence is increasing markedly. In the USA, the number of new liver cancer cases occurring each year has, since 1980, tripled. Between 2006-2015, the number of people diagnosed with the disease increased by approximately 3% per year. Men are 3 times more likely than women to develop liver cancer.

Türkiye 2020 Cancer Statistics reports that liver cancer is the 14th most common cancer in our country, with 5649 new cases annually, and the 7th leading cause of cancer death, with 5461 deaths.

Hepatocellular carcinoma (HepatoCellular Carcinoma = HCC) is the most common subtype of liver cancer and accounts for 75% of all liver cancers.

What Is Hepatocellular Carcinoma?

The main primary cancers, meaning cancers originating in the liver itself, are hepatocellular carcinoma, cholangiocarcinoma (bile duct cancer), angiosarcoma and fibrolamellar hepatocellular carcinoma. Hepatocellular carcinoma arises from hepatocytes, the main cells of the liver.

At diagnosis, more than half of patients with liver cancer are known to have inoperable or advanced disease, and according to US data, 5-year survival across all stages is 18.4%.

Hepatocellular carcinoma is an aggressive tumor that usually develops in the setting of chronic liver disease and cirrhosis. It is typically diagnosed late in its course, and median survival after diagnosis is approximately 6 to 20 months. Although surgical resection (removal of the tumor-bearing area by surgery) is the mainstay of treatment, most patients are not eligible for surgery because of tumor size or underlying liver dysfunction.

There are many treatment options for hepatocellular carcinoma:

• Liver transplantation (early stage)
• Radiofrequency ablation, microwave ablation and cryoablation (early stage)
• Percutaneous ethanol or acetic acid ablation (early stage)
• IRE, nanoknife: irreversible electroporation (early stage)
• Transarterial chemoembolization (TAKE) (early stage)
• Transarterial radioembolization (TARE, also known as radioembolization) (early stage)
• Radiation therapy and stereotactic radiation therapy (early stage)
• Systemic chemotherapy with cytotoxic agents and molecularly targeted therapies (advanced stage)
• Immunotherapy (advanced stage)
• Combination therapies (immunotherapy and targeted therapies) (advanced stage)

To help select the most appropriate treatment for hepatocellular carcinoma and better understand the disease, we compiled "5 critical facts you need to know about HCC" and hope they will be useful to anyone interested in HCC.

Cirrhosis Is the Greatest Risk Factor for Hepatocellular Carcinoma (HCC)

In 80-90% of patients, hepatocellular carcinoma (HCC) develops in the setting of cirrhosis. In addition, one-third of patients with liver cirrhosis will develop HCC in the future.

HCC screening every six months is recommended for high-risk groups of patients with cirrhosis. This frequency is recommended because HCC doubles in size, on average, in 6 months. For example, a tumor measuring 1 cm would be found on an ultrasound examination six months later to have doubled in size, reaching 2 cm. Ultrasound would be more effective at detecting a tumor of this size. At the same time, the tumor size criteria required for curative treatment options would also be met.

Although less common, HCC can also develop without cirrhosis. In the absence of cirrhosis, hepatitis B infection is known to lead to HCC. Advanced fibrosis and nonalcoholic steatohepatitis (nonalcoholic fatty liver disease) have also been associated with HCC occurring without cirrhosis.

Fatty Liver Is Considered the Main Cause of the Increase in HCC Cases

Large studies conducted in the USA and Europe have linked nonalcoholic fatty liver disease to HCC. In the US population, the proportion of people with fatty liver was found to be 25%, while the rate of nonalcoholic fatty hepatitis (liver disease) was 3% (in other words, fatty liver progressing to disease). Advanced fibrosis was found in 40% of patients with nonalcoholic fatty liver disease.

Although some studies have reported that liver cancer develops against a background of nonalcoholic fatty liver disease without cirrhosis, this rate has been reported to be only 0.1% per year.

Genetic factors, such as the presence of a PNPLA3 gene mutation, are also reported to be associated with greater susceptibility to nonalcoholic fatty liver disease and therefore to increase the risk of HCC.

Treatment for Chronic Hepatitis Infection Reduces HCC Risk

Treating chronic hepatitis C infection has been associated with a 71% reduction in HCC risk. This is the most effective way to reduce the risk of HCC developing in the future, particularly when advanced fibrosis is also present.

Patients with hepatitis C infection who have advanced liver fibrosis or cirrhosis need surveillance imaging before starting treatment and must continue this after treatment.

Patients who respond well to treatment for hepatitis C infection or HCC should undergo surveillance with CT or MRI every 3-6 months for an indefinite period because of the risk of HCC recurrence.

• Related topic: The 2020 Nobel Prize in Physiology or Medicine Was Awarded for the Discovery of the Hepatitis C Virus

A Biopsy Is Not Always Necessary to Diagnose Liver Cancer

When a liver tumor is identified, data from imaging techniques such as CT and MRI, together with the Liver Imaging Reporting and Data System, can be used to estimate the likelihood of HCC. This serves as an alternative diagnostic approach that can be used instead of a biopsy. In addition to these methods, various tumor markers, such as alpha-fetoprotein, may also be used.

Nevertheless, biopsy is the gold standard for diagnosis. A liver biopsy can also identify suspicious and indeterminate liver lesions, and genetic testing can be performed to assess eligibility for molecularly targeted cancer treatments.

There Are Many Subtypes - Fibrolamellar HCC, for Example

Fibrolamellar HCC is a subtype of hepatocellular carcinoma, a liver cancer. Liver cancer develops as a result of abnormal growth and development of liver cells. Fibrolamellar HCC is a rarer subtype of liver cancer and is usually seen in younger people. This cancer is characterized by fibrosis and lamellae (thin layers) in the liver tissue. The course of fibrolamellar HCC may be more favorable than that of other types of liver cancer. Various approaches, such as surgery, radiotherapy, chemotherapy or immunotherapy, may be used for treatment.

Completely Curative Treatments Are Possible With Early Diagnosis

Curative treatments for HCC include resection (surgical removal of the tumor), ablation (burning or freezing therapies) and liver transplantation.

Surgical resection is the preferred option for patients with early-stage cancer and preserved liver function, with a 5-year survival rate of 70%. The risks and benefits of this treatment are similar to those of local ablation therapies.

Ablation is an option for early-stage tumors that cannot be removed surgically. Radiofrequency ablation (RFA) is the most suitable and best-established option for this approach. Patients with lesions smaller than 2 cm who received this treatment had 5-year survival rates of 47-68%. Microwave ablation is a newer approach and may be more suitable for tumors in less favorable locations or with a diameter greater than 3 cm.

Systemic / palliative treatments (which extend life and improve quality of life) should be considered for patients with HCC who are not eligible for curative options. Palliative therapy may also be used for patients awaiting liver transplantation.

Until recently, the oral cancer drugs sorafenib (Nexavar) and sunitinib (Sutent) were the only systemic therapy options approved as suitable for HCC. However, many systemic treatment options, including immunotherapy, are now available for patients with HCC who are not eligible for resection.

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