Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis
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BACKGROUND & AIMS: Society guidelines differ in their recommendations for surveillance to detect early-stage hepatocellular carcinoma (HCC) in patients with cirrhosis. We compared the performance of surveillance imaging, with or without alpha fetoprotein (AFP), for early detection of HCC in patients with cirrhosis. METHODS: Two reviewers searched MEDLINE and SCOPUS from January 1990 through August 2016 to identify published sensitivity and specificity of surveillance strategies for overall and early detection of HCC. Pooled estimates were calculated and compared using the DerSimonian and Laird method for a random effects model. The study was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. RESULTS: Thirty-two studies (comprising 13,367 patients) characterized sensitivity of imaging with or without AFP measurement for detection of HCC in patients with cirrhosis. Ultrasound detected any stage HCC with 84% sensitivity (95% confidence interval [CI] 76%-92%), but early-stage HCC with only 47% sensitivity (95% CI 33%-61%). In studies comparing ultrasound with vs without AFP measurement, ultrasound detected any stage HCC with a lower level of sensitivity than ultrasound plus AFP measurement (relative risk [RR] 0.88; 95% CI 0.83-0.93) and early-stage HCC with a lower level of sensitivity than ultrasound plus AFP measurement (RR 0.81; 95% CI 0.71-0.93). However, ultrasound alone detected HCC with a higher level of specificity than ultrasound plus AFP measurement (RR 1.08; 95% CI 1.05-1.09). Ultrasound with vs without AFP detected early-stage HCC with 63% sensitivity (95% CI 48%-75%) and 45% sensitivity (95% CI 30%-62%), respectively (P = .002). Only 4 studies evaluated computed tomography or magnetic resonance image-based surveillance, which detected HCC with 84% sensitivity (95% CI 70%-92%). CONCLUSIONS: We found ultrasound alone has a low sensitivity to detect early stage HCC in patients with cirrhosis. Addition of AFP to ultrasound significantly increases sensitivity of early HCC detection in clinical practice.
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Ultrasound-based surveillance has low sensitivity for detection of hepatocellular carcinoma at an early stage, particularly in adults with MASLD-related cirrhosis and obesity.
“As ultrasound-based surveillance has a low sensitivity for detection of hepatocellular carcinoma at an early-stage, particularly in adults with MASLD-related cirrhosis and obesity, alpha-fetoprotein (AFP) measurement can be combined with ultrasound in individuals at high risk ( LoE 3, open recommendation, consensus ).”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [250]
The Results report low pooled sensitivity (47%) for detecting early HCC with ultrasound. The Discussion reports lower ultrasound sensitivity in patients with obesity or non-alcoholic steatohepatitis, but says the meta-analysis could not evaluate these patient subgroups directly; its implication for NAFLD-related cirrhosis is framed as a suggestion rather than an established subgroup finding. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIndividuals with MASLD have increased odds of persistent poor visualisation with a pooled sensitivity of 45% for ultrasound alone and increased risk of false positive or indeterminate results.
“However, individuals with MASLDhaveincreasedoddsofpersistentpoorvisualisation with a pooled sensitivity of 45% for ultrasound alone and increased risk of false positive or indeterminate results. 250,251”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [250]
The Results (Ultrasound with AFP for HCC Detection; page not provided) report 45% pooled sensitivity for ultrasound alone in early HCC detection, but not specifically among people with MASLD. The Discussion reports lower-quality imaging in patients with non-alcoholic steatohepatitis and mentions false-positive and indeterminate ultrasound results; it does not establish increased odds of persistent poor visualisation or an increased risk of those results in people with MASLD. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCombined use of AFP and ultrasound increases sensitivity for detection of early HCC from 45% to 63%.
“Inameta-analysisof13,367individuals,thecombined useofAFPandultrasoundwasreportedtoincreasethesensitivity for detection of early HCC from 45% to 63%. 250”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [250]
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McMahon, B., Cohen, C., Brown Jr, R. S., El-Serag, H., Ioannou, G. N., Lok, A. S., Roberts, L. R., Singal, A. G., & Block, T. (2023) · JNCI Cancer Spectrum · doi:10.1093/jncics/pkad034 · Cited by 44 · see citing works
Self-citationHughes, D. M., Berhane, S., Emily de Groot, C. A., Toyoda, H., Tada, T., Kumada, T., Satomura, S., Nishida, N., Kudo, M., Kimura, T., et al. (2021) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2020.04.084 · Cited by 39 · see citing works
Authors, & Collaborators: (2022) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1880-2388 · Cited by 30 · see citing works
- Authors
- Tzartzeva, K., Obi, J., Rich, N. E., Parikh, N. D., Marrero, J. A., Yopp, A., Waljee, A. K., & Singal, A. G.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Michigan (US)
- Corresponding author
- Singal, Amit G.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 154
- Issue
- 6
- Pages
- 1706-1718.e1
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC5927818
- OpenAlex
- W2786099441
- Cited by
- 1,207
- References
- 71
- Citations by year
- 2026: 153 · 2025: 170 · 2024: 168 · 2023: 180 · 2022: 180 · 2021: 141 · 2020: 112 · 2019: 76 · 2018: 25
- FWCI
- 12.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Gastroenterology (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (U01CA230694, R01CA212008, R01CA222900)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007745)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Keywords
- hepatocellular carcinoma, liver cirrhosis, cancer surveillance, alpha-fetoprotein, ultrasonography, early cancer detection, sensitivity and specificity, computed tomography, magnetic resonance imaging
- MeSH terms
- Adult, Aged, alpha-Fetoproteins, Female, Carcinoma, Hepatocellular, Humans, Liver Cirrhosis, Liver Neoplasms, Magnetic Resonance Imaging, Male, Middle Aged, Sensitivity and Specificity, Tomography, X-Ray Computed, Ultrasonography, Early Detection of Cancer
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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