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Liver Cancer

Liver

Introduction

Primary liver cancer are cancers which originate in the liver. An estimated 42,000 individuals will be diagnosed with liver cancer in 2024 and approximately 30,000 patients will die as a result of the disease.¹ The overall 5-year relative survival rate for liver cancer is 21.9% with survival rates varying by how far the cancer has spread including a 37.1% 5-year survival rate for localized pancreatic cancer, 12.7% for regional cancer, and 3.6% for distant liver cancer.²

There are several types of primary liver cancer based on where and how they originate. This includes.

Hepatocellular carcinoma (HCC) – HCC is the most common type of primary liver cancer accounting for approximately 75% to 85% of cases. HCC arise from the hepatocytes in the liver and typically occurs in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection, as well as conditions like alcoholic liver disease and nonalcoholic steatohepatitis (NASH).

Steps In the Development of Hepatocellular Carcinoma

Intrahepatic Cholangiocarcinoma (Bile Duct Cancer) is a cancer that originates in the bile ducts within the liver and accounts for 10% to 20% of primary liver cancers. Bile Duct Cancer begins in the cells lining the bile ducts (ducts that carry bile from the liver to the gallbladder and intestines) with primary sclerosing cholangitis, bile duct cysts, liver fluke infections, chronic liver disease being risk factors associated with its development.

Hepatoblastoma is a rare type of liver cancer that usually affects children under the age of 3 which arise from immature liver cells. Risk factors include premature birth, familial adenomatous polyposis (FAP), Beckwith-Wiedemann syndrome.

Angiosarcoma and Hemangiosarcoma are rare cancers which arise from endothelial cells lining the blood vessels of the liver. Risk factors include exposure to vinyl chloride, thorium dioxide, arsenic, and certain inherited conditions.

Fibrolamellar Hepatocellular Carcinoma (FLHCC), which is also known as fibrolamellar carcinoma (FLC) or eosinophilic glassy cell hepatoma, is a rare liver cancer that usually affects young adults and teens. It is characterized by a unique “lamellar” pattern of fibrous bands between tumor cells. FLHCC differs from HCC in that it occurs in people with healthy livers while primary liver cancers develop in individuals with damaged livers. FLHCC also has different clinical findings than HCC including normal alpha-fetoprotein levels less responsive to chemotherapy. Risk factors for the development of FLHCC are unknown and it is not typically associated with cirrhosis or hepatitis infections.

Staging

Staging of hepatocellular carcinoma (HCC) is crucial for determining the appropriate treatment and prognosis. Several staging systems are used, with the Barcelona Clinic Liver Cancer (BCLC) staging system being one of the most widely adopted due to its comprehensive approach that considers tumor characteristics, liver function, and patient performance status. Other systems include the TNM (Tumor, Node, Metastasis) staging system and the Okuda staging system.

Barcelona Clinic Liver Cancer (BCLC) Staging System

The BCLC Staging System classifies HCC into five stages:

Stage 0 (Very Early Stage):

Tumor Characteristics: Single tumor <2 cm

Liver Function: Child-Pugh A
Performance Status: 0 (fully active)
Treatment Options: Resection, ablation, or liver transplantation
Prognosis: Excellent with potential for cure

Stage A (Early Stage):

Tumor Characteristics: Single tumor or up to three nodules <3 cm

Liver Function: Child-Pugh A or B
Performance Status: 0
Treatment Options: Resection, liver transplantation, or ablation
Prognosis: Very good with high survival rates

Stage B (Intermediate Stage):

Tumor Characteristics: Multinodular (more than three nodules or a single tumor >3 cm without vascular invasion)

Liver Function: Child-Pugh A or B
Performance Status: 0
TreatmentOptions: Transarterial chemoembolization (TACE)
Prognosis: Moderate, with potential for long-term control

Stage C (Advanced Stage):

Tumor Characteristics: Portal invasion, extrahepatic spread

Liver Function: Child-Pugh A or B
Performance Status: 1-2 (restricted but ambulatory)
Treatment Options: Systemic therapy (e.g., sorafenib, lenvatinib)
Prognosis: Poor, with limited survival but improved with systemic therapy

Stage D (Terminal Stage):

Tumor Characteristics: Extensive tumor burden with poor liver function

Liver Function: Child-Pugh C
Performance Status: >2 (severely disabled)
Treatment Options: Best supportive care
Prognosis: Very poor, focusing on palliative care

TNM (Tumor, Node, Metastasis) Staging System

The TNM system, used by the American Joint Committee on Cancer (AJCC), classifies HCC based on the size and extent of the tumor (T), involvement of regional lymph nodes (N), and distant metastasis (M).

Tumor (T) Staging:

T1: Single tumor without vascular invasion
T2: Single tumor with vascular invasion or multiple tumors, none >5 cm
T3a: Multiple tumors, at least one >5 cm
T3b: Tumor(s) involving a major branch of the portal or hepatic vein
T4: Tumor(s) with direct invasion of adjacent organs or with perforation of the visceral peritoneum

Node (N) Staging:

N0: No regional lymph node involvement
N1: Regional lymph node involvement

Metastasis (M) Staging:

M0: No distant metastasis
M1: Distant metastasis present

Risk Factors

Several risk factors are associated with the development of liver cancer, particularly hepatocellular carcinoma (HCC), the most common type of primary liver cancer. Understanding these risk factors can help in the prevention, early detection, and management of the disease. Key risk factors include:

Chronic Viral Hepatitis

Hepatitis B Virus (HBV): chronic HBV infection is a significant risk factor for HCC. The virus can cause long-term liver inflammation and damage, leading to cirrhosis and HCC. Vaccination against HBV can reduce the risk.
Hepatitis C Virus (HCV): Chronic HCV infection can lead to liver cirrhosis and HCC. Effective antiviral treatments can reduce the risk by curing HCV infection.

Cirrhosis – A condition where healthy liver tissue is replaced by scar tissue, impairing liver function.

Causes include:

Chronic viral hepatitis (HBV, HCV)
Alcoholic liver disease
Nonalcoholic steatohepatitis (NASH)
Genetic diseases like hemochromatosis and Wilson’s disease

Fatty Liver Disease – risk factors include obesity, type 2 diabetes, metabolic syndrome

Nonalcoholic Fatty Liver Disease (NAFLD) resulting from fat accumulation in the liver without alcohol use.
Nonalcoholic Steatohepatitis (NASH): a more severe form of NAFLD with liver inflammation and damage, which can progress to cirrhosis and HCC.

Alcohol Consumption – chronic and heavy alcohol consumption can cause liver damage, leading to cirrhosis and an increased risk of HCC.

Aflatoxin Exposure – toxins produced by fungi found on agricultural crops like maize and peanuts. Contaminated food can lead to liver damage and increase HCC risk.

Genetic and Metabolic Diseases

Hemochromatosis: Excess iron accumulation in the liver
Wilson’s Disease: Excess copper accumulation in the liver
Alpha-1 Antitrypsin Deficiency: Leads to liver disease and cirrhosis
Glycogen Storage Diseases: Affects liver function

Other Risk Factors

Smoking: Increases the risk of many cancers, including HCC.
Family History: A family history of liver cancer can increase individual risk.
Gender and Age: Males and older adults are at higher risk.
Environmental Exposures: Certain chemicals and toxins, such as vinyl chloride and thorium dioxide, can increase HCC risk.

Click here for more detailed information on risk factors associated with the development of liver cancer.

Treatment

The treatment of liver cancer depends on various factors, including the stage of the cancer, the location of the tumor, the patient’s overall health, and individual preferences. Liver cancer is often diagnosed at an advanced stage, and treatment may involve a combination of approaches. Common treatments include surgery, including liver transplantation, systemic therapies, radiation, and/or interventional procedures.³

The figure below represents the 2022 update to the BCLC staging and treatment algorithm.⁴ The BCLC system establishes a prognosis in accordance with the five (5) stages that are linked to first-line treatment recommendation. Detailed information on each of these treatment options can be found in the modules listed below.

References

Cancer Facts & Figures 2024, American Cancer Society (ACS), Atlanta, Georgia, 2024.
SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. [Cited 2024 June 9].
National Comprehensive Cancer Network®. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatocellular Carcinoma. Version 1.2024 — April 9, 2024.
Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022 Mar;76(3):681-693. doi: 10.1016/j.jhep.2021.11.018.