Cancer Atlas 2026 · Liver cancer

Liver Cancer (HCC) Biomarkers in 2026: AFP, Surveillance in Cirrhosis and New Blood Tests

Liver cancer is the third leading cause of cancer death worldwide. Its main type, hepatocellular carcinoma (HCC), usually arises in a liver already damaged by hepatitis, alcohol or fatty liver disease. That creates a defined high-risk group, which is watched with ultrasound and often a blood protein, alpha-fetoprotein (AFP). This article covers the burden, the surveillance evidence and the status of newer markers as of 1 October 2026.

By OncoFirm™ Scientific TeamPublished 1 Oct 2026Updated 1 Oct 2026Sources peer-reviewed, guidelines, regulators, linked

At a glance

Burden

843,045 new cases and 732,489 deaths worldwide in 2024; 42,340 new US cases expected in 2026.

Stage and survival

US five-year relative survival: 37.4% localized, 13.4% regional, 3.6% distant (SEER, liver and intrahepatic bile duct, 2016–2022).

Surveillance

Not for the general population. Ultrasound with or without AFP about every 6 months for people with cirrhosis and selected chronic hepatitis B.

Key biomarkers

AFP (add-on to ultrasound); AFP-L3 and DCP (US: risk assessment only); GALAD and GAAD scores (no FDA marketing authorization identified as of October 2026).

OncoFirm™ status

AFP is a future pipeline candidate; no OncoFirm™ AFP assay exists today. The platform is in development and for research use only.

On this page

Key numbers

Liver cancer in three numbers

843,045new liver cancer cases worldwide in 2024 (GLOBOCAN 2024)
37.4%US five-year relative survival at localized stage
3.6%US five-year relative survival at distant stage

Sources: IARC Global Cancer Observatory (GLOBOCAN 2024); SEER Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer (SEER 21, diagnoses 2016–2022), accessed 1 October 2026.

Burden

A cancer with nearly as many deaths as cases

In global statistics, liver cancer means cancer of the liver and of the bile ducts inside it. HCC, which starts in the main liver cells, is the most common type. GLOBOCAN 2024, from the International Agency for Research on Cancer (IARC), counts 843,045 new cases and 732,489 deaths in 2024: seventh among cancers for new cases and third for deaths. Deaths equal about 87% of new cases. Asia has 70.2% of cases. This page is part of the OncoFirm™ Cancer Atlas 2026.

Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) accounts for 21% to 55% of HCC. Other causes include aflatoxin (a mold toxin in food), alcohol, smoking, excess body weight, type 2 diabetes and MASLD (metabolic dysfunction-associated steatotic liver disease, a fatty liver condition). Rates are falling in several high-risk East Asian countries and rising in Europe, Northern America and other historically low-risk regions.

The American Cancer Society (ACS) expects 42,340 new US cases and 30,980 deaths in 2026. US incidence has tripled over four decades. It is still rising by nearly 2% per year in women and has stabilized in men. About 75% of US liver cancers are caused by risk factors that could be changed.

Why stage matters

Stage and survival: low at every stage, lowest when distant

Liver cancer: five-year relative survival by stage at diagnosisBar chart of five-year relative survival for Liver cancer by stage at diagnosis in the United States, 2016–2022: Localized 37.4% survival, 45% of cases; Regional 13.4% survival, 23% of cases; Distant 3.6% survival, 21% of cases. All stages combined: 21.9%. Source: SEER Cancer Stat Facts (liver and intrahepatic bile duct).LIVER CANCER · FIVE-YEAR RELATIVE SURVIVAL BY STAGE (US, 2016–2022)0%25%50%75%100%Localized45% of cases37.4%Regional23% of cases13.4%Distant21% of cases3.6%All stages combined: 21.9% · SEER Cancer Stat Facts (liver and intrahepatic bile duct)

Five-year relative survival by stage at diagnosis, United States, 2016–2022, with the share of cases at each stage (stage was unknown in a further 10%). SEER figures are for liver and intrahepatic bile duct cancer combined, not HCC alone. Source: SEER Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer, accessed 1 October 2026.

SEER, the US cancer registry program, reports liver and intrahepatic bile duct cancer together, so these figures are not for HCC alone. Relative survival compares patients with similar people in the general population. For 2016–2022, the five-year figure was 37.4% for localized disease (45% of cases), 13.4% for regional (23%) and 3.6% for distant (21%). It was 21.9% for all stages.

Stage changes survival about tenfold. Yet even localized disease has low survival, because many patients also have cirrhosis (scarring of the liver), which limits treatment and is itself life-threatening. In prostate cancer, by contrast, localized survival is 100.0%. US liver cancer survival has still improved, from 7% in the mid-1990s to 22%.

Surveillance

Surveillance in cirrhosis: ultrasound with or without AFP every 6 months

There is no screening program for the general population; the ACS states that screening is not recommended for most people. Guidelines instead advise surveillance, meaning regular testing of people at known high risk.

  • AASLD (US, 2023): ultrasound plus AFP about every 6 months for people with cirrhosis and for selected people with chronic hepatitis B. In the most advanced cirrhosis (Child-Pugh class C), only for those eligible for transplant.
  • EASL (Europe, 2025): ultrasound every 6 months. Adding AFP raises sensitivity, lowers specificity and is called a reasonable option.
  • When ultrasound views are poor: AASLD allows contrast MRI or CT in selected patients.
  • Not recommended: routine surveillance in MASLD with advanced fibrosis but no cirrhosis. Both bodies find too little evidence.

Performance is modest. AASLD cites sensitivity for early HCC of 53% for ultrasound alone and 63% with AFP added. At the usual cut-off of 20 ng/mL, AFP has about 60% sensitivity and 90% specificity. Ultrasound depends on the operator and works less well in people with obesity. Surveillance is also underused, even among patients seen by liver specialists.

What AFP is not. No protein tumor marker is recommended for general population cancer screening. AFP cannot diagnose HCC alone: some HCCs make no AFP, and AFP also rises in hepatitis, cirrhosis and pregnancy. See causes of high AFP and the early detection evidence hub.

Biomarkers

Serum markers by role: AFP, AFP-L3, DCP and the GALAD family

BiomarkerTypeUsed forNot used for
AFPOncofetal proteinAdd-on to ultrasound in surveillance; diagnostic aidGeneral population screening; diagnosis alone
AFP-L3%Glycoform of AFPHCC risk assessment in chronic liver disease (FDA cleared)Surveillance or diagnosis alone
DCP (PIVKA-II)Abnormal prothrombinHCC risk assessment (FDA cleared)Surveillance alone
GALADScore: gender, age, AFP-L3, AFP, DCPUnder validationRoutine surveillance
GAADScore: gender, age, AFP, DCPUnder validationRoutine surveillance

AFP is an oncofetal protein: made in fetal life, it can reappear in tumors. The current WHO reference material is the 2nd International Standard (NIBSC code 22/216, 2023). Intended use needs care in the US. For example, the Roche Elecsys AFP assay cleared in 2022 is indicated to aid in managing certain germ cell tumors, not for HCC surveillance. Our AFP guide has more.

AFP-L3 is a glycoform (a sugar-modified form) of AFP that binds a lentil lectin. It is reported as a percentage of total AFP, and 10% or more is considered elevated. The FDA database lists a 2011 clearance for an AFP-L3% test, as an aid in assessing HCC risk in chronic liver disease. DCP (des-gamma-carboxy prothrombin, also called PIVKA-II) has the same narrow US role. AASLD notes that both are authorized for risk stratification, not surveillance. AFP-L3 shows how a glycan-defined marker can reach the clinic; see tumor-associated antigens.

GALAD combines gender, age, AFP-L3, AFP and DCP in one score. GAAD omits AFP-L3. Results depend on study design: studies that compare known cancer cases with controls tend to report higher sensitivity than studies that follow people in surveillance. A 2025 study in MASLD or alcohol-related cirrhosis found 87.2% sensitivity for early-stage HCC with both scores, at 68% to 69% specificity. EASL cites a pooled 73% sensitivity and 87% specificity for early HCC, and AASLD cites 65% and 82% from a cohort study. A prospective phase 3 validation of GALAD in cirrhosis was published in 2025. Neither guideline recommends the scores for routine surveillance. See multi-biomarker analysis.

Regulatory status as of October 2026. We identified no FDA marketing authorization (clearance, approval or De Novo) for GALAD or GAAD. Elecsys GALAD received FDA Breakthrough Device designation in March 2020. That designation speeds review; it is not an authorization. A search that finds nothing is not proof, so check the FDA database.

Emerging

Blood tests in studies: methylation plus proteins

Newer tests combine DNA methylation (chemical tags on tumor DNA shed into blood) with proteins; see liquid biopsy explained. Two US studies have reported results. The figures below come from company announcements.

  • HelioLiver (CLiMB study): 1,968 patients with cirrhosis at 42 US sites, judged against MRI. Sensitivity for HCC was 47.8% versus 28.3% for ultrasound, with specificity of 87.6% versus 93.9%.
  • Oncoguard Liver (ALTUS study): more than 3,000 participants. Sensitivity for early-stage HCC was 77% versus 36% for ultrasound, at 82% specificity. Peer-reviewed publication was described as planned.
  • Multi-cancer tests: Galleri reported 93.5% sensitivity for liver and bile duct cancer in a case-control study covering all stages. That is not the same as finding early HCC in surveillance. No multi-cancer early detection test is FDA approved as of 1 October 2026. An FDA panel backed Galleri on 23 September 2026 and the decision is pending. NHS-Galleri missed its primary endpoint.
  • Abbreviated MRI: a shorter scan with reported sensitivity of 80% to 90%, mostly from Asian cohorts. A randomized trial against ultrasound (PREMIUM) is under way.

The trade-off is specificity. A test with 82% to 88% specificity, repeated every 6 months, sends many people without cancer for extra scans. The sources we reviewed did not state an FDA authorization for either liver test. See emerging diagnostic technologies for the wider field.

Prevention

Prevention: HBV vaccination and treating hepatitis

Much HCC can be prevented. HBV vaccine has been introduced nationally in 190 countries, with 84% global coverage for the three-dose series. Coverage of the birth dose, given within 24 hours, is only 45%. It ranges from 80% in the WHO Western Pacific region to 18% in the WHO African region. AASLD recommends HBV vaccination for all newborns and high-risk adults, and notes that suppressing HBV and curing HCV lower HCC risk. Access is a wider theme of the global need for affordable diagnostics.

Open questions

Open research questions

  • Does surveillance with blood tests or abbreviated MRI improve early detection and survival, compared with ultrasound with or without AFP, in randomized trials?
  • Who should be watched among people with MASLD but no cirrhosis?
  • What specificity is acceptable for a test repeated every 6 months?
  • How can surveillance uptake be raised?
  • Do algorithms that track marker change over time beat fixed cut-offs?
  • How can the HBV birth-dose gap be closed?
  • Are glycan antigens beyond AFP-L3 useful? The Thomsen-Friedenreich (TF) antigen has been reported in HCC tissue studies, but this is research-stage. See causes of high TF antigen.

OncoFirm™ roadmap

Where OncoFirm™ fits: AFP as a future pipeline candidate

OncoFirm™ is developing a fluorescent lateral flow platform with a digital reader. Its lead assays are CEA and PSA. AFP is a future pipeline candidate: no OncoFirm™ AFP assay exists today. The assays, reader and software are in development, not cleared or approved by the FDA or any other regulatory authority, for research use only and not for sale. OncoFirm™ makes no screening or multi-cancer claims.

Why AFP is a candidate

Total AFP is the one serum marker with a guideline role in HCC surveillance, as an add-on to ultrasound with a 20 ng/mL cut-off. That use needs a quantitative result. See the AFP guide.

One reader, growing menu

The platform follows a one reader, one strip design, so analytes could be added over time. Any AFP assay would need its own full validation.

Glycoform tests are harder

An AFP-L3-type assay must tell sugar forms apart, typically with a lectin. OncoFirm™ TF antigen assay concepts are concept-stage; see the role of peanut agglutinin.

Honest limits

A point-of-care AFP result would inherit AFP’s limits: modest sensitivity and benign causes of elevation. It would not replace ultrasound. Research groups can ask about collaboration.

OncoFirm™ assays, reader and software are in development, have not been cleared or approved by the FDA or any other regulatory authority, are for research use only and are not for sale. Designed ranges and result times are development targets, not validated performance claims.

FAQ

Frequently asked questions

Is there a screening test for liver cancer?

Not for the general population. Guidelines recommend surveillance only for people at high risk, mainly those with cirrhosis and some people with chronic hepatitis B. Surveillance uses ultrasound, with or without an AFP blood test, about every 6 months.

What does a high AFP mean?

AFP is a protein that can rise in hepatocellular carcinoma and some germ cell tumors. It also rises in hepatitis, cirrhosis and pregnancy, and some liver cancers make no AFP. A high AFP is a reason for further tests, not a diagnosis.

What are AFP-L3 and DCP?

AFP-L3 is a sugar-modified form of AFP, and DCP (also called PIVKA-II) is an abnormal form of the clotting protein prothrombin. In the US both are cleared to help assess HCC risk in people with chronic liver disease. They are not authorized for surveillance on their own.

Is the GALAD score FDA approved?

We identified no FDA marketing authorization for GALAD or GAAD as of October 2026. Elecsys GALAD received Breakthrough Device designation in March 2020, which is not an approval. Neither AASLD nor EASL recommends these scores for routine surveillance.

Can a blood test replace ultrasound for surveillance?

Not yet. In company-reported US studies, two methylation-plus-protein blood tests found more HCC than ultrasound but had lower specificity. Whether this improves survival has not been shown in randomized trials.

Does OncoFirm™ offer an AFP test?

No. AFP is a future pipeline candidate for the OncoFirm™ platform, which is in development and for research use only. Nothing is cleared or approved by the FDA or any other regulatory authority, and nothing is for sale.

Sources

References

  1. IARC Global Cancer Observatory. Liver and intrahepatic bile ducts fact sheet, GLOBOCAN 2024. gco.iarc.who.int/media/globocan/factsheets/cancers/11-liver-and-intrahepatic-bile-ducts-fact-sheet.pdf
  2. Sung et al. Global cancer statistics 2024: GLOBOCAN estimates for 34 cancers in 186 countries. CA Cancer J Clin. 2026. acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.70090
  3. American Cancer Society. Cancer Facts & Figures 2026. www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2026/2026-cancer-facts-and-figures.pdf
  4. American Cancer Society. Cancer statistics report 2026, press release. 13 January 2026. pressroom.cancer.org/cancer-statistics-report-2026
  5. National Cancer Institute. SEER Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer. Accessed 1 October 2026. seer.cancer.gov/statfacts/html/livibd.html
  6. Singal et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78:1922–1965. journals.lww.com/hep/fulltext/2023/12000/aasld_practice_guidance_on_prevention,_diagnosis,.27.aspx
  7. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on hepatocellular carcinoma. J Hepatol. 2025;82:315–374. www.journal-of-hepatology.eu/article/S0168-8278(24)02508-X/fulltext
  8. Hepatocellular carcinoma surveillance: current challenges. Annals of Hepatology. 2025. www.elsevier.es/en-revista-annals-hepatology-16-articulo-hepatocellular-carcinoma-surveillance-current-challenges-S1665268125001607
  9. PREMIUM trial design: abbreviated MRI plus AFP versus ultrasound plus AFP in cirrhosis. 2025. www.sciencedirect.com/science/article/pii/S2589555925003490
  10. Association of Clinical Biochemists in Ireland. Guidelines for the Use of Tumour Markers, 5th edition. 2018. acbi.ie/wp-content/uploads/2022/12/1644913336-1602832758-Tumour-markers-5th.pdf
  11. Mayo Clinic Laboratories. Test catalog entry L3AFP (AFP-L3%). www.mayocliniclabs.com/test-catalog/overview/88878
  12. NIBSC. Alpha-fetoprotein, human, 2nd WHO International Standard, code 22/216. Instructions for use. 2023. nibsc.org/documents/ifu/22-216.pdf
  13. US Food and Drug Administration. 510(k) K220176, Elecsys AFP. 2022. www.accessdata.fda.gov/cdrh_docs/pdf22/K220176.pdf
  14. US Food and Drug Administration. 510(k) K100464, uTASWako AFP-L3. Decision 23 February 2011. www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K100464
  15. Fujifilm Healthcare. AFP-L3 test (manufacturer information). healthcaresolutions-us.fujifilm.com/products/in-vitro-diagnostics/hcc-risk-biomarkers/afp-l3-test/
  16. Roche. Investor update: FDA Breakthrough Device Designation for the Elecsys GALAD score. 4 March 2020. www.roche.com/investors/updates/inv-update-2020-03-04
  17. GAAD and GALAD for HCC detection in MASLD and alcohol-related cirrhosis. Cancers. 2025;17:3835. www.mdpi.com/2072-6694/17/23/3835
  18. Marsh et al. GALAD prospective phase 3 validation in cirrhosis. Gastroenterology. 2025. www.gastrojournal.org/article/S0016-5085(24)05460-X/fulltext
  19. Helio Genomics. CLiMB study of HelioLiver versus ultrasound, press release. 6 May 2026. www.prnewswire.com/news-releases/landmark-climb-study-demonstrates-superior-sensitivity-of-helioliver-a-multi-analyte-blood-test-over-ultrasound-for-early-detection-of-hepatocellular-carcinoma-302764194.html
  20. Exact Sciences. ALTUS study results for Oncoguard Liver, press release. 7 November 2025. www.exactsciences.com/news-events/press-releases/exact-sciences-announces-breakthrough-results-from-landmark-study
  21. GRAIL. Galleri test performance (manufacturer information for health care professionals). www.galleri.com/hcp/galleri-test-performance
  22. Targeted Oncology. FDA panel report on the Galleri multi-cancer early detection test. September 2026. www.targetedonc.com/view/fda-panel-galleri-multi-cancer-early-detection-test
  23. Study of MUC1, TF, Tn and sialosyl-Tn antigen expression in hepatocellular carcinoma and preneoplastic lesions. Virchows Arch. 1999. link.springer.com/article/10.1007/s004280050375

About this article. Compiled from public sources read on 1 October 2026. Guideline text was read from hosted copies, and the newer blood test figures come from company press releases. Regulatory status may change after that date. Part of the OncoFirm™ Cancer Atlas 2026, written by the OncoFirm™ Scientific Team from the sources linked above and reflecting public information as of 1 October 2026. It is for education and is not medical advice. OncoFirm™ has no affiliation with the companies or tests named. OncoFirm™ assays are in development, have not been cleared or approved by the FDA and are not available for sale.

Collaborate on the next edition

Clinicians, laboratories, researchers and industry partners can contribute data, corrections or validation studies. Collaboration inquiry · Investor inquiry

[email protected]+1 516.900.2606Port Washington, NY