HCC, or hepatocellular carcinoma, is the most common type of primary liver cancer. It starts in the main cells of the liver (hepatocytes) and accounts for roughly 75% to 85% of all liver cancers. Globally, about 906,000 people are diagnosed with liver cancer each year, and HCC makes up the vast majority of those cases.
How HCC Develops
HCC doesn’t usually appear out of nowhere. It follows a pattern: ongoing liver injury leads to chronic inflammation, which causes scarring (fibrosis), which can progress to cirrhosis, and cirrhosis creates the conditions for cancer to develop. This process typically unfolds over years or decades. Along the way, key protective genes stop working properly, allowing liver cells to lose their normal identity and begin dividing uncontrollably.
The progression involves multiple biological breakdowns at once: abnormal activation of growth signals, new blood vessel formation that feeds tumor growth, and immune system dysfunction that allows cancer cells to evade detection. This is why HCC is so closely tied to conditions that cause long-term liver damage.
Leading Risk Factors
Chronic viral hepatitis (hepatitis B and C) remains the most common cause of HCC worldwide, responsible for about 32% of cases in well-studied populations. Heavy alcohol use, which causes its own form of chronic liver disease, accounts for roughly 18%.
The fastest-growing risk factor is metabolic dysfunction-associated steatotic liver disease, or MASLD (previously called non-alcoholic fatty liver disease). This condition, linked to obesity, type 2 diabetes, and metabolic syndrome, may now be responsible for up to 35% of HCC cases globally. In Sweden, MASLD overtook hepatitis C as the leading cause of HCC in 2017 and has remained the top cause since. Similar trends are emerging in the United States, the United Kingdom, and China.
Other risk factors include inherited liver conditions like hemochromatosis and primary sclerosing cholangitis, as well as exposure to aflatoxins, which are toxins produced by molds that contaminate certain grains and nuts in tropical regions.
Symptoms: Often Silent Until Advanced
Early-stage HCC rarely causes noticeable symptoms. Most people feel fine when the tumor is small, which is why the cancer is often found during routine screening of high-risk patients or incidentally on imaging done for other reasons.
As the tumor grows, symptoms can include:
- A feeling of fullness or a hard lump under the ribs on the right side (from an enlarged liver)
- Yellowing of the skin and eyes (jaundice)
- Abdominal swelling from fluid buildup
- Loss of appetite or feeling full after eating very little
- Unexplained weight loss
- Nausea, vomiting, or persistent itching
By the time these symptoms appear, the cancer is often at an intermediate or advanced stage, which significantly limits treatment options.
How HCC Is Diagnosed
Unlike most solid cancers, HCC can often be diagnosed with imaging alone, without a biopsy. This is possible because HCC tumors have a distinctive blood supply pattern that shows up on contrast-enhanced CT or MRI scans.
The hallmark finding is a tumor that lights up brightly during the arterial phase of a contrast scan (when dye first flows through the liver’s arteries) and then fades, or “washes out,” in later phases. Radiologists use a standardized system called LI-RADS to categorize suspicious liver lesions on a scale. A lesion 2 cm or larger that shows this characteristic pattern receives the highest suspicion rating, which carries a 94% positive predictive value for HCC. No biopsy is needed in those cases.
Blood tests play a supporting role. Alpha-fetoprotein (AFP) is a protein that can be elevated in HCC, and it’s commonly used for screening in high-risk patients. At a cutoff of 20 ng/mL, it catches about 60% of cancers with roughly 90% specificity. The tradeoff is clear: raising the threshold to 50 ng/mL increases confidence that a positive result is real (96% specificity) but misses more than half of cancers. Notably, about 42% of people with confirmed HCC have completely normal AFP levels, so a normal result does not rule out the disease.
Staging and What It Means for Prognosis
Doctors use the Barcelona Clinic Liver Cancer (BCLC) system to stage HCC, which is unique because it considers not just tumor size and spread but also how well the liver is functioning and the patient’s overall physical condition. This matters because a damaged liver limits which treatments are safe to use.
The stages range from very early (stage 0, a single small tumor in a liver that still works well) through early (stage A), intermediate (stage B, multiple tumors but preserved liver function), advanced (stage C, cancer that has invaded blood vessels or spread beyond the liver), and end-stage (stage D, where the liver or the patient’s health is too compromised for cancer-directed treatment).
Five-year survival varies dramatically by how far the cancer has progressed. Localized HCC, confined to the liver, has a five-year survival rate of about 38%. Once it reaches nearby lymph nodes (regional spread), that drops to around 13%. If it has spread to distant organs, the five-year survival rate falls to roughly 4%. Without any treatment, intermediate-stage disease carries a median survival of about 9 months, and advanced-stage disease about 3 months.
Treatment Options by Stage
Surgery and Transplant for Early Disease
For patients with very early or early-stage HCC, the most effective options are surgical removal of the tumor or a liver transplant. Surgery to remove part of the liver works best when there’s no cirrhosis or the cirrhosis is mild, with good liver function and no significant pressure buildup in the liver’s blood vessels.
Liver transplant is the only treatment that addresses both the cancer and the underlying liver disease. Eligibility traditionally follows the Milan criteria: a single tumor no larger than 5 cm, or up to three tumors with none exceeding 3 cm, and no cancer in blood vessels or other organs. Patients who meet these criteria have five-year survival rates above 70% after transplant. Some centers now use expanded criteria that allow slightly larger or more numerous tumors while still achieving good outcomes.
For small tumors where transplant isn’t being pursued, ablation (destroying the tumor with heat, cold, or microwave energy) is an alternative that can be equally effective for very early-stage disease.
Locoregional Therapy for Intermediate Disease
When the cancer involves multiple tumors but hasn’t spread beyond the liver, treatments delivered directly to the tumor through the liver’s blood vessels are the standard approach. The most common is transarterial chemoembolization (TACE), which delivers chemotherapy drugs directly into the tumor’s blood supply while simultaneously blocking that blood supply. Radiation-based approaches that target the tumor’s arterial supply are also used.
Systemic Therapy for Advanced Disease
For HCC that has spread into blood vessels, lymph nodes, or other organs, immunotherapy-based combinations have transformed outcomes. The current first-line standard pairs two drugs: one that helps the immune system recognize cancer cells and another that cuts off the tumor’s blood supply. In clinical trials, this combination extended median survival to 19.2 months compared to 13.5 months with older targeted therapy alone, and it shrinks tumors in about 30% of patients.
Patients whose cancer progresses on first-line treatment have several second-line options available, though response rates are lower. At the most advanced stage, when liver function has significantly deteriorated or the patient’s overall health is poor, the focus shifts to comfort and symptom management regardless of tumor characteristics.
Who Should Be Screened
Because early detection dramatically improves outcomes, guidelines recommend regular screening for people at high risk. This typically includes anyone with cirrhosis from any cause, people with chronic hepatitis B (even without cirrhosis in some cases), and increasingly, patients with advanced fibrosis from MASLD. Screening usually involves a liver ultrasound and AFP blood test every six months. The goal is to catch tumors while they’re still small enough for curative treatment, since early-stage HCC has nearly ten times the survival rate of cancer that has already spread.