Hepatocellular carcinoma, or HCC, is the most common type of primary liver cancer, originating in the main liver cells known as hepatocytes. It is a leading cause of cancer-related deaths worldwide. The term “chronic” in this context is twofold; it describes the persistent nature of the cancer and the long-standing liver diseases that set the stage for its development.
A majority of HCC cases, between 80% and 90%, emerge from a liver already scarred by chronic disease, a condition called cirrhosis. This cancer rarely develops in a healthy liver. The progression to HCC is a multi-step process that begins with persistent injury to the liver, which leads to chronic inflammation. This state of damage and repair creates an environment where the genetic material within liver cells can change, eventually leading to cancerous growth.
The Link Between Chronic Liver Disease and HCC
The development of hepatocellular carcinoma is intricately tied to long-term liver damage. The most significant precursor to HCC is cirrhosis, an advanced stage of liver scarring that results from various chronic liver diseases. This scarring replaces healthy tissue with non-functional scar tissue, disrupting the liver’s normal function. Over time, this environment of constant cell death and regeneration can lead to genetic mistakes, giving rise to cancerous cells.
Several underlying conditions are primary drivers of the chronic liver injury that leads to cirrhosis and HCC. Chronic viral hepatitis, specifically infections with the Hepatitis B virus (HBV) and Hepatitis C virus (HCV), are a major cause. While HCV typically causes HCC through the gradual development of cirrhosis, HBV can sometimes directly integrate its genetic material into liver cells, causing cancer even before cirrhosis is established.
Beyond viral causes, alcohol-related liver disease from prolonged alcohol consumption is an established path to cirrhosis and HCC. More recently, metabolic conditions have emerged as a major risk factor, particularly non-alcoholic fatty liver disease (NAFLD) and its more severe form, non-alcoholic steatohepatitis (NASH). These conditions, often linked to obesity and type 2 diabetes, cause fat to accumulate in the liver, leading to inflammation and an elevated risk of developing HCC.
Diagnosis and Staging
Diagnosing hepatocellular carcinoma involves imaging, blood tests, and sometimes tissue samples. Because most HCC cases develop in individuals with known chronic liver disease, these patients are monitored through routine screening programs. The primary screening tool is a liver ultrasound, performed every six months. If an ultrasound detects a suspicious lesion, more detailed imaging is required for a definitive diagnosis.
Multiphase computed tomography (CT) scans and magnetic resonance imaging (MRI) are the most reliable imaging methods for diagnosing HCC. These scans are performed with a contrast agent that highlights blood flow. HCC tumors show a specific vascular pattern known as “wash-in,” where they rapidly absorb the contrast agent, followed by a “wash-out,” where the contrast fades more quickly from the tumor than the surrounding liver tissue. In patients with cirrhosis, these imaging features are often so clear that a biopsy is not needed for confirmation. A blood test for a protein called alpha-fetoprotein (AFP) can also support the diagnosis, as its levels are often elevated.
Once diagnosed, the cancer is staged to determine its extent and guide treatment decisions. The most widely used method is the Barcelona Clinic Liver Cancer (BCLC) staging system. This system considers tumor characteristics (size and number), the patient’s liver function, and their overall health (performance status). BCLC categorizes HCC into five stages: very early (0), early (A), intermediate (B), advanced (C), and terminal (D), which helps doctors recommend the most appropriate therapy.
Treatment Approaches for HCC
Treatment for hepatocellular carcinoma depends on the cancer’s stage, the patient’s underlying liver function, and their overall health. Therapies are categorized by their goal, whether it is to cure the cancer, control it within the liver, or manage it once it has spread.
For patients with early-stage disease (BCLC stages 0 and A), treatments with curative intent are the primary options. Surgical resection, which removes the portion of the liver containing the tumor, can be a cure for patients with a single tumor and well-preserved liver function. A liver transplant offers a dual benefit: it removes the cancer and replaces the diseased liver. Another curative approach is local ablation, where energy like radiofrequency or microwave heat is used to destroy small tumors.
When the cancer is at an intermediate stage (BCLC stage B), it is confined to the liver but is too widespread for curative treatments. The standard of care is often a localized therapy called transarterial chemoembolization (TACE). In this procedure, chemotherapy drugs are delivered directly to the tumor through its feeding artery, which is then blocked. Another option, transarterial radioembolization (TARE), uses tiny radioactive beads to deliver radiation directly to the tumor.
For advanced-stage HCC (BCLC stage C), where the cancer has invaded blood vessels or spread, systemic therapies are used. These treatments travel through the bloodstream to reach cancer cells throughout the body. Targeted therapy drugs, such as sorafenib and lenvatinib, work by interfering with pathways that cancer cells need to grow. Immunotherapy uses drugs called immune checkpoint inhibitors that help the body’s own immune system recognize and attack cancer cells, and is often used in combination with targeted drugs.
Long-Term Management and Surveillance
Managing hepatocellular carcinoma is a long-term process that extends beyond initial treatment. Even after successful curative therapy, there is a high risk that the cancer will return. This recurrence can happen as a metastasis from the original tumor or as a new tumor that develops in the damaged liver. Because of this high recurrence rate, which can exceed 60% within five years, continuous lifelong surveillance is a part of patient care.
Follow-up care involves a regular schedule of imaging, usually with CT or MRI scans, and blood tests to monitor AFP levels every three to six months. These checks are designed to detect any signs of recurrence as early as possible, when further treatment is most effective. Patients who remain cancer-free for five years are still advised to continue surveillance, as new tumors can develop later.
It is also important to manage the underlying chronic liver disease that created the conditions for HCC. This may involve antiviral therapy for hepatitis, lifestyle changes for alcohol-related or fatty liver disease, and management of cirrhosis complications. Addressing the health of the entire liver can reduce the risk of future tumor development and maintain better overall function.