Yes—blood tests can detect signals associated with liver cancer, but a blood test alone usually cannot confirm or rule out hepatocellular carcinoma (HCC). For people at increased risk, blood biomarkers can help clinicians decide whether closer investigation is needed. Imaging and clinical evaluation remain important for diagnosing a liver lesion.
HCC is the most common primary liver cancer. Because early HCC may cause no symptoms, people who meet risk-based criteria may be offered ongoing surveillance rather than waiting for symptoms to appear.
Quick answer: can liver cancer be detected in blood?
Blood tests measure biological signals associated with cancer. The familiar alpha-fetoprotein (AFP) blood test measures a protein. Investigational approaches can examine DNA methylation patterns or cancer-associated RNA fusion transcripts. Each provides different information and has limitations; an abnormal result calls for clinical follow-up, not an automatic cancer diagnosis.
What blood tests are used or studied for liver cancer?
1. Alpha-fetoprotein (AFP)
AFP is a well-established serum marker used in liver cancer surveillance. Some patients with HCC, particularly those with smaller tumors, do not have substantially elevated AFP. AFP may also increase with noncancerous liver inflammation or regeneration. Consequently, an AFP result must be interpreted in clinical context.
2. AFP-L3
AFP-L3 refers to a particular fraction of AFP. It has been investigated as a liver cancer risk marker, often in combination with other information. AFP-L3 is not equivalent to a confirmed diagnosis, and its utility depends on the clinical situation.
3. Cell-free DNA methylation testing
DNA methylation is a chemical modification that affects how genes are regulated. Researchers have evaluated methylation patterns in circulating cell-free DNA to distinguish HCC from noncancer conditions. A 2024 multicenter validation study reported encouraging results for a specific methylation assay, but those results cannot be generalized to all blood tests or treated as proof of clinical replacement for established surveillance.
4. Circulating RNA fusion-transcript testing
Some cancers contain chromosomal rearrangements that generate abnormal RNA fusion transcripts. Research has examined whether selected transcripts can be measured in serum and used to flag molecular patterns associated with HCC. This differs from relying on a single protein-marker concentration.
Fusion-detect™ is MoleculeDx's proprietary multivariable blood-testing approach developed for the Liver Cancer Fusion Predictor. The specific biomarkers and prediction algorithm are proprietary and are not disclosed here.
How do the approaches differ?
| Approach | Signal evaluated | Important limitation |
|---|---|---|
| AFP | Protein concentration | Can be normal in HCC and elevated without HCC |
| AFP-L3 | AFP fraction | Must be assessed in clinical context; not a stand-alone diagnosis |
| DNA methylation | Epigenetic patterns in cell-free DNA | Performance is assay- and population-specific |
| Fusion-detect™ (internally validated) | Proprietary multivariable blood-based signals | Performance may vary across patient populations and requires clinical interpretation |
Who should discuss HCC surveillance with a clinician?
Surveillance is especially relevant for many people with cirrhosis and certain individuals with chronic hepatitis B. Risk may also be influenced by the cause and severity of liver disease, age, and family history. Not everyone with fatty liver disease, prior hepatitis, or abnormal liver tests qualifies for the same screening program. A clinician can determine whether surveillance is indicated and which schedule is appropriate.
What symptoms should prompt evaluation?
Early HCC often causes no obvious symptoms. Persistent or worsening upper abdominal pain, unexplained weight loss, loss of appetite, abdominal swelling, jaundice or significant fatigue warrant medical attention. These symptoms have many possible causes and are not specific for liver cancer.
How accurate are blood tests for liver cancer?
Accuracy depends on the individual assay, the population studied and the reference method used to determine whether HCC is present. Sensitivity describes the proportion of cancer cases detected; specificity describes the proportion of people without cancer correctly classified. A high sensitivity does not mean every early cancer will be detected, and a positive result is not the same as a diagnosis.
In a peer-reviewed 2024 study published in The American Journal of Pathology, investigators assessed circulating serum fusion transcripts and multivariable prediction models for HCC. One evaluated research model achieved 95% classification accuracy in the testing cohort. This is a model-specific research result—not a guaranteed performance figure for every commercial test configuration or a demonstration that a blood test can replace ultrasound-based surveillance.
Early detection of small HCC remains an important research goal. Results in small tumor subgroups can be encouraging, but a small number of confirmed cases does not establish screening specificity, positive predictive value or survival benefit in a general at-risk population.
What do positive and negative Fusion-detect™ results mean?
A positive surveillance result suggests that the assay identified a pattern associated with HCC. It should prompt clinician-guided review and appropriate diagnostic evaluation, potentially including contrast-enhanced MRI or multiphasic CT. It is not a pathologic diagnosis.
A negative result means the measured pattern was not detected in that sample. It may be reassuring, but it does not completely exclude HCC and should not be used to abandon follow-up recommended by a healthcare professional.
Could an advanced blood test replace AFP or ultrasound?
MoleculeDx is pursuing evaluation of a proposed surveillance indication under which the Liver Cancer Fusion Predictor, alone or in combination with ultrasound, could replace the usual surveillance approach involving AFP. This is an intended future use subject to FDA review, not an already-authorized replacement indication or established proof of superiority.
For eligible at-risk patients, the 2023 AASLD guidance recommends ultrasound plus AFP at approximately six-month intervals. Until an alternative approach has suitable evidence and authorization for its specific use, patients should follow their treating clinician's current surveillance plan.
Why does earlier detection matter?
Identifying HCC while the tumor remains treatable may increase eligibility for options such as surgical resection, ablation or liver transplantation in selected patients. Although the promise of blood-based screening is important, an individual assay's ability to reduce HCC-related deaths must be evaluated rather than assumed.
Frequently asked questions
Can a blood test detect liver cancer before symptoms?
Some tests can detect concerning biological signals in people without symptoms, but performance varies. A positive result generally leads to imaging and clinical review.
Can AFP be normal when a person has HCC?
Yes. A normal AFP value does not exclude HCC.
Does a positive molecular result mean cancer is confirmed?
No. A positive molecular finding requires appropriate diagnostic evaluation.
Can a negative test replace future surveillance?
No single negative blood test rules out future HCC. A clinician should determine the follow-up schedule according to risk.
Conclusion
Blood-based HCC screening is evolving from protein markers such as AFP to molecular signals measured in serum or plasma. These developments offer promising research directions, but different methods answer different questions. MoleculeDx's Fusion-detect™ approach is part of that research and development effort; results should be interpreted alongside clinical assessment and any necessary imaging.
Medical information: This article is for general education, not personal medical advice or a substitute for current clinical surveillance and diagnostic evaluation. It makes no claim of FDA marketing authorization for the proposed replacement indication.
References
- Singal AG, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78:1922–1965. Full text.
- 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;194:1262–1271. DOI.
- Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: a multicentre cohort study. Clin Transl Med. 2024. Full text.