Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. It often develops in people with chronic liver disease and may not cause obvious symptoms in its early stages. HCC surveillance is periodic testing for people at increased risk; it aims to identify suspicious changes when there may be more treatment options.
This updated guide explains who may need regular surveillance, what U.S. and European guidelines recommend in 2026, and how ultrasound, alpha-fetoprotein (AFP), and follow-up imaging fit together. It is educational information, not an individualized medical recommendation.
What is hepatocellular carcinoma (HCC)?
HCC is cancer arising from hepatocytes, the liver's main functional cells. Long-term injury from viral hepatitis, alcohol-related liver disease, or metabolic dysfunction can promote fibrosis and cirrhosis (advanced scarring). Cirrhosis is a major risk factor for HCC, although certain people with chronic hepatitis B can develop HCC without cirrhosis. [1, 2]
HCC surveillance, sometimes called screening, is not the same as diagnosing cancer. Surveillance looks for an early warning sign. Confirming HCC generally requires characteristic findings on appropriate contrast-enhanced imaging or, in selected circumstances, tissue pathology.
Who should undergo HCC screening or surveillance?
Major professional guidance recommends ongoing surveillance for selected higher-risk groups, especially patients with cirrhosis who could benefit from HCC-directed treatment and certain people living with chronic hepatitis B. Eligibility depends on risk factors, liver function, life expectancy, and whether treatment could be offered if cancer were found. [1–4]
| Patient group | Guideline approach |
|---|---|
| Cirrhosis from most causes | Usually recommended when the patient could benefit from HCC-directed treatment. This includes many people with cirrhosis caused by hepatitis C, hepatitis B, alcohol-associated liver disease, or metabolic dysfunction-associated steatotic liver disease (MASLD). |
| Chronic hepatitis B without cirrhosis | Some patients qualify based on elevated HCC risk, including certain age/origin groups, family history, and validated risk scoring. Not everyone with hepatitis B requires the same surveillance approach. |
| Cirrhosis after hepatitis C cure | Continue surveillance when indicated; successful antiviral treatment reduces risk but does not necessarily remove it. |
| Fatty liver disease or advanced fibrosis without cirrhosis | Not automatically eligible. AASLD generally does not recommend routine HCC surveillance for advanced fibrosis without cirrhosis from MASLD or cured HCV. Individual specialist assessment may differ. |
| Severely decompensated cirrhosis | Surveillance generally offers limited benefit if curative treatment or transplant would not be possible. Transplant-eligible patients are an important exception. |
For people with chronic hepatitis B, the updated AASLD/IDSA guidance identifies risk groups without cirrhosis that may warrant surveillance. Examples include men from HBV-endemic countries older than 40, women from HBV-endemic countries older than 50, some people from Africa at younger ages, people with a family history of HCC, and patients with elevated validated risk scores such as PAGE-B. Separate recommendations address hepatitis D or HIV coinfection and some patients after loss of hepatitis B surface antigen. Your clinician can determine which criteria apply. [2]
How often should high-risk patients be screened?
For eligible patients, the AASLD recommends liver ultrasound plus serum AFP approximately every six months. The 2025 EASL HCC guidelines likewise recommend ultrasound every six months and consider adding AFP a reasonable option. Six-month surveillance is intended to be repeated even when the previous result was normal. [1, 3]
Which tests do the guidelines recommend?
1. Liver ultrasound
Ultrasound uses sound waves to look for suspicious liver lesions without radiation. It is the standard imaging method for routine HCC surveillance, but its ability to visualize the liver can be reduced in people with obesity, a markedly nodular liver, or other technical limitations. A poor-quality or limited ultrasound should be reported; the clinician may consider another imaging approach when surveillance visualization is unreliable. [1, 3]
2. Alpha-fetoprotein (AFP) blood testing
AFP is a protein that can rise in some patients with HCC. Used alongside ultrasound, AFP improves early-stage detection sensitivity compared with ultrasound alone, although it can also produce false positives. Normal AFP does not rule out HCC, and elevated AFP alone does not diagnose it. The meaning of any result depends on the patient's history and prior trend. [1]
3. CT and MRI when indicated
Multiphase contrast-enhanced CT or MRI is usually used to evaluate a suspicious lesion rather than as a default substitute for semiannual surveillance. If ultrasound detects a concerning lesion 1 cm or larger, or AFP is sufficiently elevated or rising, professional guidance calls for diagnostic evaluation with appropriate contrast-enhanced imaging. Subcentimeter lesions often lead to shorter-interval ultrasound and AFP follow-up, generally in about 3–6 months. [1]
Patients whose ultrasounds consistently do not visualize the liver adequately may be considered for alternative surveillance with MRI or multiphase CT, based on individual circumstances and clinical expertise.
What about new blood-based molecular tests?
Researchers are studying DNA-, RNA-, and other biomarker-based blood tests that could supply information different from AFP. MoleculeDx's Liver Cancer Fusion Predictor is based on research involving cell-free cancer-associated fusion-transcript signals in blood and multi-marker analysis. Published MoleculeDx-associated work has investigated these signals in HCC study populations. [5]
However, the AASLD does not currently recommend replacing ultrasound and AFP surveillance with other blood biomarkers as routine standard-of-care surveillance. Research findings from selected cohorts should not be interpreted as guaranteed test performance in all patients. Any molecular result must be interpreted with clinical history and appropriate imaging. [1, 4]
A positive blood-based molecular screening result is not an HCC diagnosis. A negative result is not a reason to stop guideline-recommended surveillance. Decisions about whether an additional test is useful should be discussed with a qualified healthcare professional.
Why is early detection important?
HCC discovered at an earlier stage may be eligible for potentially curative treatments such as surgical resection, local ablation, or liver transplantation in selected patients. Advanced HCC often requires a different mix of liver-directed or systemic treatments. Surveillance therefore aims to increase the likelihood of detecting HCC when treatment options may be broader. Early detection is an opportunity—not a guarantee of cure. [1, 3]
What should you do after an abnormal screening result?
An abnormal ultrasound, rising AFP, or concerning molecular test result warrants discussion with the ordering clinician. Depending on the finding, the next step may be repeat surveillance at a shorter interval, contrast-enhanced CT or MRI, or a liver-specialist consultation. Do not attempt to determine whether cancer is present from a single marker result.
Frequently asked questions
Does every person with hepatitis B need HCC surveillance?
No. Surveillance is recommended for some people with chronic HBV even without cirrhosis, but recommendations depend on risk factors such as origin, age, family history, liver condition, and coinfections. A clinician should review the individual risk.
Is screening every six months enough?
Approximately every six months is the usual surveillance interval for eligible patients. Additional tests or shorter-interval follow-up may be needed after concerning findings or a technically limited ultrasound.
Should I continue surveillance after hepatitis C has been cured?
Often yes if cirrhosis is already present and the person remains eligible for treatment. Viral cure lowers but does not completely remove HCC risk. The need for surveillance with lesser degrees of fibrosis is different.
Can liver cancer be present when AFP is normal?
Yes. Some HCCs do not produce an AFP elevation. A normal AFP result cannot exclude HCC.
Can a blood test alone diagnose HCC?
No. Diagnosis relies on appropriate imaging criteria and/or pathology interpreted by a qualified clinician; biomarkers alone are insufficient.
Does everyone with fatty liver disease need screening?
No. HCC risk varies. Cirrhosis is a particularly important threshold for routine surveillance recommendations, and people with fatty liver disease without cirrhosis should not automatically assume they qualify.
Can MoleculeDx replace my ultrasound appointments?
No. MoleculeDx's research-based blood testing should not be represented as a substitute for guideline-recommended ultrasound and AFP surveillance. Discuss all testing decisions and follow-up with your healthcare professional.
References and clinical guidance
- Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78:1922–1965. DOI: 10.1097/HEP.0000000000000466.
- Ghany MG, Pan CQ, Lok AS, et al. AASLD/IDSA Practice Guideline Update on Treatment of Chronic Hepatitis B. Published November 4, 2025. Read guideline.
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol. 2025;82:315–374. PMID: 39690085.
- American Gastroenterological Association. Clinical Practice Update on Risk Stratification and Emerging Surveillance Strategies for Hepatocellular Carcinoma. Gastroenterology. 2026. PMID: 42017860.
- Yu YP, Liu S, Geller D, Luo JH. Serum Fusion Transcripts to Assess the Risk of Hepatocellular Carcinoma and the Impact of Cancer Treatment through Machine Learning. Am J Pathol. 2024. DOI: 10.1016/j.ajpath.2024.02.017.
Learn about MoleculeDx's blood-based research
Learn how MoleculeDx studies fusion-transcript signals and discuss whether additional testing may be relevant with your clinician. Routine guideline-based HCC surveillance should continue regardless of any separate molecular screening test result.