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Hepatocellular carcinoma surveillance: a health economic evaluation

Qi-Feng Chen1,*, Xiong-Ying Jiang2,*, Song Chen3,*, Jiongliang Wang1,*, Ming Zhao1orcid
Clinical and Molecular Hepatology 2026;32(2):536-564.
Published online: January 9, 2026

1Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

3Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

Corresponding author : Ming Zhao Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong 510060, China Tel: +86-2087343272, Fax: +86-2087343392, E-mail: zhaoming@sysucc.org.cn

Joint first authors.


Editor: Ju Hyun Shim, University of Ulsan, Korea

• Received: September 19, 2025   • Revised: December 29, 2025   • Accepted: January 1, 2026

Copyright © 2026 by The Korean Association for the Study of the Liver

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Hepatocellular carcinoma (HCC) imposes a major health and economic burden worldwide, with disproportionate effects in low- and middle-income countries (LMICs). Surveillance in high-risk populations, typically using semiannual ultrasound and alpha-fetoprotein testing, has been shown to be cost-effective by enabling earlier detection and improving survival. Yet, its overall value is reduced by poor adherence and the limited sensitivity of ultrasound, particularly in patients with metabolic-associated steatotic liver disease. Emerging approaches—including abbreviated magnetic resonance imaging, multi-biomarker models (e.g., gender, age, AFP, AFP-L3, and DCP), and liquid biopsy assays such as methylated DNA markers—demonstrate greater diagnostic accuracy and potential economic advantages compared with conventional methods. Integration of artificial intelligence into imaging may further enhance efficiency and reduce downstream costs. Moving toward precision surveillance, guided by individualized risk stratification that incorporates etiology, fibrosis stage, and molecular profiles, can optimize allocation of resources and maximize cost-effectiveness at the population level. Interventions to improve adherence, including mailed outreach and behavioral economic incentives, have shown both clinical benefit and cost savings, underscoring the role of implementation science. Because socioeconomic disparities influence both access and outcomes, economic models must explicitly address equity to achieve sustainable impact. Future research should prioritize prospective trials that evaluate not only clinical performance but also the real-world cost-effectiveness of novel technologies and stratified surveillance strategies. For LMICs, adapting proven models into affordable, context-appropriate programs is essential. By combining prevention, precision risk assessment, innovative technologies, and equitable implementation, HCC surveillance can deliver both clinical and economic value, reducing the global burden of disease.
  • Keywords: Liver cancer; Surveillance; Cost-effectiveness; Abbreviated magnetic resonance imaging; Health economics
Liver cancer is a major public health challenge, being the sixth most common cancer and the third leading cause of cancer-related deaths globally, and hepatocellular carcinoma (HCC) accounts for approximately 75–85% of these cases [1]. Despite advancements in therapeutic modalities, its high mortality rate is largely attributable to the fact that most patients are diagnosed at an advanced stage when symptoms emerge, thereby missing the opportunity for curative treatment [2,3]. Consequently, regular surveillance of high-risk populations, such as individuals with cirrhosis, is a key strategy to enable early diagnosis, enhance treatment efficacy, and improve patient survival [4,5].
International guidelines widely recommend semiannual surveillance with ultrasound, with or without alpha-fetoprotein (AFP) testing (ultrasound±AFP) [6-11]. However, the implementation and widespread adoption of surveillance strategies are associated with significant healthcare resource utilization and economic costs, accounting for approximately 15–25% of annual liver disease management expenditures [12,13]. In recent years, the evolving etiological landscape of HCC—marked by a rising proportion of cases driven by metabolic-associated steatotic liver disease (MASLD, formerly non-alcoholic fatty liver disease [NAFLD], a 5–10% annual growth) and alcohol-related liver disease (ARLD) [14-18]—has presented new challenges to the effectiveness of traditional surveillance methods. Concurrently, the emergence of innovative tools such as advanced imaging technologies, novel biomarkers, and artificial intelligence (AI) offers the potential to optimize surveillance strategies but also necessitates careful evaluation of their economic value.
This study aims to provide a narrative assessment of the health economic issues surrounding HCC surveillance (Fig. 1). With a particular focus on cost-effectiveness, it aims to provide an evidence base for developing scientific, efficient, and equitable HCC prevention policies.
Disease burden: global trends and regional disparities
Understanding the global epidemiology of HCC is essential for assessing the cost-effectiveness of surveillance strategies. The disease imposes a significant global burden, with regional variations in incidence, mortality, and disability-adjusted life years (DALYs) (Fig. 2) [19,20]. The burden is particularly increasing among populations with high body mass index over 70, especially in low socio-demographic index regions [21]. Alcohol-related liver cancer is also rising in low- and middle-income countries (LMICs) with an approximate annual increase of 3% in associated mortality rates, where there is a severe lack of data on post-operative outcomes, particularly in Africa [22]. These global and regional disparities highlight the heterogeneous risk and varying cost-effectiveness of surveillance programs, with areas of higher incidence likely benefiting more from early detection strategies.
Direct and indirect economic costs
HCC’s economic impact includes both direct medical costs and indirect productivity losses. Medical expenditures increase sharply after diagnosis, with a median incremental cost of $50,110 in the first year post-diagnosis in the United States [23]. Early diagnosis significantly reduces costs, showing the incremental medical expenditures for earlystage HCC patients are approximately 40–50% lower than for those with late-stage disease [23-25], as demonstrated in France, where early surveillance of cirrhotic patients result-ed in a favorable incremental cost-effectiveness ratio (ICER) of $1,754 per life-year gained [13]. In Taiwan, the average medical expenditure per patient was $16,711, with even higher costs for liver transplantation, which can increase costs by 2 to 4-fold [24]. Indirect costs, particularly productivity losses from premature mortality, also contribute significantly to the economic burden, accounting for 50–70% of its total societal economic burden [26,27]. For example, productivity losses in Spain amounted to €12.88 billion from liver cancer deaths in the working-age population between 2013 and 2022 [28]. In Tianjin, China, years of life lost accounted for 99% of the DALYs, further underscoring the substantial economic impact of premature death [29].
The screening population involved in the surveillance strategies
Screening for HCC is recommended for patients with cirrhosis, particularly those who are considered candidates for curative-intent therapies such as liver transplantation, ablation or surgical resection. The current guidelines suggest that surveillance should be considered for all cirrhotic patients, especially those with Child–Pugh class A or B liver disease (Table 1), as these patients are more likely to benefit from early detection of HCC due to their eligibility for curative treatment options [6-11]. However, surveillance may not be indicated for patients with decompensated (Child–Pugh class C) cirrhosis who are ineligible for liver transplantation or other curative treatments. These patients generally have a poor prognosis due to non-HCC causes and would not benefit from early detection of HCC in terms of extending survival or improving outcomes. Furthermore, surveillance strategies may be less cost-effective for this group, given the limited therapeutic options available and the high risk of mortality from liver failure or other complications of cirrhosis [30]. These criteria for offering surveillance ensure that resources are directed toward patients who are most likely to benefit from early detection of HCC.
The foundational strategy: ultrasound±AFP
The use of ultrasound±AFP, is the foundational strategy for routine HCC surveillance recommended by major international guidelines (Fig. 3) [3,31]. Numerous health economic modeling studies have confirmed that this strategy is highly cost-effective compared to no surveillance, as the calculated ICER is consistently below the common willingness-topay threshold, for example, $50,000 per quality-adjusted life year (QALY) gained in the United States [4,13,32,33]. Empirical evidence supports its effectiveness: for example, a randomized controlled trial (RCT) in China indicated that biannual screening with AFP test and ultrasound examination reduced HCC mortality by 37%, compared with those who received no screening [34]. A study in Australia demonstrated that semiannual ultrasound surveillance for patients with cirrhosis had an ICER of AUD 28,423 per QALY compared with no surveillance, supporting the guideline recommendations [4]. Another study aimed to evaluate the cost-effectiveness of HCC surveillance, including both its benefits and harms. The results indicated that ultrasound plus AFP was the most cost-effective strategy in 80.1% of simulations at a willingness-to-pay threshold of $100,000 per QALY, compared with ultrasound alone or no surveillance in patients with compensated cirrhosis [35]. Consistently, an Australian model identified ultrasound plus AFP as the most cost-effective option, with ICERs falling below the willingness-to-pay threshold of $50,000 per QALY across all age ranges when compared to no surveillance [36].
The primary benefit of ultrasound±AFP surveillance lies in its ability to markedly increase the detection rate of earlystage HCC, achieving a 1.5 to 2.0-fold higher probability of detecting early-stage disease, thereby allowing more patients to undergo curative therapies and ultimately reducing mortality [4,5,13]. For example, a study in South Korea aimed to investigate the effectiveness of the National Liver Cancer Surveillance Program (NLCSP) in terms of survival benefits and cost. The results indicated that, in addition to survival benefits, the daily cost for the group participating in the NLCSP was 26% lower than the non-surveillance group [5]. Despite robust evidence, the effectiveness of conventional surveillance is challenged by inherent limitations, such as the reduced sensitivity of ultrasound in obese or MASLD patients, where it can drop as low as 20–30% [37,38], and the additional tests and potential harms resulting from falsepositive or indeterminate findings [35,39].
Economic considerations of surveillance frequency and starting/stopping ages
The frequency and age range of a surveillance program are key variables that determine its cost-effectiveness. The semiannual (6-month) interval widely recommended by international guidelines has been shown to be economically favorable in multiple studies [4,13,40]. However, the optimal frequency may vary based on the patient’s risk level. For example, a study on Chinese patients with chronic hepatitis B (CHB) who achieved virologic remission found that for those with advanced fibrosis or partial compensatory cirrhosis, annual surveillance, while slightly less effective than semiannual surveillance, was significantly less costly and thus more cost-effective (ICER $28,076/QALY) [41]. Similarly, in hepatitis C virus (HCV)-related cirrhosis, when assuming ideal adherence to surveillance and treatment, the surveillance interval could be extended from 3 or 6 months to 12 months and remain cost-effective [42]. The starting and stopping ages for surveillance also influence its economic value. For HCV patients who have achieved a sustained virologic response (SVR), it is recommended that surveillance for those with cirrhosis continue until age 70, and for those with stable advanced fibrosis, until age 60; beyond these ages, the economic benefit diminishes, as continuing surveillance in patients over 70 yields an ICER exceeding $150,000 per QALY [43].
Key influential factors in cost-effectiveness model
The cost-effectiveness of HCC surveillance is not static but is significantly influenced by several key factors:
HCC incidence rate: the annual incidence of HCC is a decisive parameter. The economic value of surveillance is directly proportional to the level of risk; surveillance is only cost-effective when the annual incidence in a population exceeds a certain threshold [35,44,45]. Notably, this threshold is dynamic and changes with advancements in treatment and shifts in cost. For instance, for patients with cirrhosis or advanced fibrosis who are virologically cured of HCV, the cost-effective annual HCC incidence threshold has decreased from the traditional 1.5% to as low as 0.7% [46].
Patient adherence: Real-world surveillance adherence rates are generally low, typically ranging from 20% to 40% [47-49], which undermines the overall benefit of surveillance programs [4,42]. Model analyses show that a strategy of ultrasound plus AFP is superior to no surveillance only when the semiannual adherence rate exceeds 19.5% [35]. Below that, the benefits may not outweigh costs. Therefore, improving adherence directly improves cost-effectiveness by increasing the proportion of early detections.
The diagnostic performance: The sensitivity of the surveillance modality influences outcomes. In obese or MASLD patients, the reduced sensitivity of ultrasound, which can drop to as low as 20–30% [2,37,38], can diminish the benefits of surveillance, a factor that future modeling studies must be factored in [38]. For instance, if a large subset has poor ultrasound visibility, supplementary or alternative modalities might be needed for surveillance to remain worthwhile.
Potential harms: Surveillance can lead to false positives and unnecessary procedures, such as additional imaging, invasive biopsies, and patient anxiety resulting from falsepositive results which also constitute a part of the economic cost [39]. Comprehensive evaluation of net benefit is needed—ideally surveillance strategies should maximize early detection while minimizing false positives (e.g., by combining modalities or risk stratification to avoid screening ultralow-risk individuals) [35].
The health economic evidence base for existing clinical guidelines

Asia-Pacific guidelines

Given the high global burden of HCC in the Asia-Pacific region, surveillance strategies have been developed with strong consideration of both epidemiologic and economic efficiency. Across regional guidelines—including those issued by the Asian Pacific Association for the Study of the Liver (APASL), Korean Liver Cancer Association–National Cancer Center (KLCA–NCC), Japan Society of Hepatology (JSH), and the Chinese National Guidelines (CNLC)—a broad consensus supports semiannual ultrasound combined with serum AFP testing as the most cost-effective approach for high-risk individuals, such as those with cirrhosis or chronic hepatitis B virus (HBV)/HCV infection [8-11]. The APASL recommends ultrasound with AFP every six months as the optimal balance between diagnostic yield and healthcare expenditure, while reserving cross-sectional imaging for diagnostic confirmation [8]. In Korea, the National Liver Cancer Screening Program operationalizes these principles by providing biannual ultrasound and AFP testing for high-risk adults; national data demonstrate earlystage detection benefits and favorable cost-effectiveness [9]. The JSH 2021 guidelines introduce a risk-stratified framework, proposing intensified surveillance (every 3–4 months) for extremely high-risk patients and acknowledging the economic trade-offs associated with shorter intervals [10]. The CNLC similarly recommends semiannual ultrasound and AFP testing, with the incorporation of the age-Male-ALBI-Platelets (aMAP) risk score to allocate surveillance intensity more efficiently [11].
Collectively, these Asia-Pacific frameworks underscore that semiannual ultrasound-based surveillance remains the most economically optimal standard, while the progressive incorporation of risk-stratified intensity models—through biomarkers or validated risk scores—may further enhance cost-effectiveness and sustainability. This evolving paradigm reflects a shift toward precision surveillance, balancing early detection with equitable resource utilization—i.e., applying more intensive surveillance to higher-risk patients (even if cost per person is higher, the yield justifies it) and possibly extending intervals for lower-risk patients.

Western countries guidelines

Current mainstream hepatology societies in Western countries, such as the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver, recommend semiannual surveillance with ultrasound±AFP, for patients with cirrhosis and select high-risk CHB patients [3,31,50]. The development of these guidelines relies heavily on supporting evidence from health economic models [12,51]. A large body of cost-effectiveness analyses provides a solid theoretical foundation for existing guidelines, confirming that implementing surveillance in specific at-risk populations can yield significant health benefits—including higher early detection rates, increased opportunities for curative treatment, and extended survival—at an acceptable cost [4,13,36,52]. For example, a model that informed Australian clinical guidelines explicitly stated that 6-monthly ultrasound surveillance for cirrhotic patients is cost-effective [4]. Similarly, a French study showed that adhering to the “gold standard” surveillance recommended by guidelines, compared to non-standard “realworld” practices, yielded additional life-years at a low incremental cost [13].
It is important to recognize that this evidence is largely derived from simulation studies based on existing data rather than large-scale, prospective RCTs, which limits its evidence level [31,53]. Furthermore, these models often rely on idealized assumptions; real-world challenges like poor patient adherence and the limited sensitivity of ultrasound in certain populations can compromise the actual cost-effectiveness of guidelines in practice [2,38]. Western guidelines are increasingly acknowledging these caveats. In summary, Western guideline recommendations are economically justified on paper, but their real-world impact depends on addressing practical issues (which subsequent sections of our review discuss, like improving adherence and integrating better technologies for certain subgroups).
Cost-effectiveness of computed tomography and magnetic resonance imaging in surveillance
While ultrasound is the cornerstone of HCC surveillance, its limited sensitivity, approximately 47% for early-stage HCC detection, has spurred research into the value of imaging techniques like computed tomography (CT) and magnetic resonance imaging (MRI) (Fig. 4) [54]. CT and MRI offer higher diagnostic sensitivity than ultrasound, with reported estimates around 70% for CT and 80% for MRI, and can more effectively detect early-stage lesions [37,55]. Studies suggest that CT/MRI-based surveillance strategies may yield greater survival benefits compared to ultrasound, with MRI-based surveillance projected to provide 3–6 additional months of life expectancy [55,56]. However, the high cost of these technologies restricts their widespread use as firstline universal surveillance tools, and their cost-effectiveness in average-risk populations remains debatable [37,38,57].
Economic evaluations indicate that the value of imaging is closely tied to the risk level of the target population. In populations with a sufficiently high annual HCC incidence, such as cirrhotic patients with an annual risk exceeding 1.81% or 3%, MRI-based surveillance has been shown to be cost-effective [44,45]. That is, in very high-risk patients, the higher upfront cost of MRI is justified by significantly better early detection (thus better outcomes). Conversely, in lower-risk populations, the incremental benefit of MRI over ultrasound may not outweigh costs. This supports a riskstratified approach: reserving more accurate but expensive tests (like MRI) for the highest-risk patients, while using ultrasound for others. Such stratification can optimize resource allocation and overall cost-effectiveness of a surveillance program.

Economics of abbreviated MRI

Abbreviated magnetic resonance imaging (AMRI) is an emerging technique that aims to strike a balance between the accuracy of MRI and the accessibility of ultrasound by reducing scan sequences to shorten examination time and lower costs, while maintaining high diagnostic accuracy (Table 2) [37,44,45,58-72]. Multiple studies have demonstrated the immense potential of AMRI in HCC surveillance. Compared to conventional ultrasound, AMRI, particularly with contrast enhancement, shows superior sensitivity and specificity for HCC detection, achieving sensitivities of 84– 91% and specificities of 90–96% for HCC detection, compared to 47% sensitivity and 92% specificity with ultrasound alone [73].
Economic model analyses in Thailand and the United States have indicated that non-contrast AMRI (NC-AMRI) can be a cost-effective surveillance tool compared to ultrasound+AFP, especially in high-incidence populations [69]. Although some studies have noted the potentially limited sensitivity of NC-AMRI, reported in the range of 79–87% [73], its value in specific scenarios remains promising in specific scenarios. A more economically viable strategy is a tiered approach: for NAFLD cirrhotic patients with poor-quality conventional ultrasound images (e.g., ultrasound LI-RADS C), sequential use of AMRI as a supplementary test has been proven to be the most cost-effective surveillance plan [72].
Several recent prospective studies have reported that AMRI could be an optimal surveillance strategy for highrisk patients. A prospective, multicenter cohort study in Korea revealed that the sensitivity of annual NC-AMRI (71.0%, 22/31) was marginally higher than that of biannual US (45.2%, 14/31; P=0.077) [60]. Another prospective multicenter study in the United States demonstrated that more than one-third of participants with NAFLD cirrhosis had severe visualization limitations on US for HCC screening, compared with one-sixth in AMRI (P<0.0001) [74]. This suggests that AMRI is poised to become an important adjunct or alternative to conventional ultrasound surveillance, particularly in high-risk patients or those in whom ultrasound is technically limited.

The role and value of contrast-enhanced ultrasound

Contrast-enhanced ultrasound (CEUS) utilizes microbubble contrast agents to significantly improve the assessment of blood flow patterns in focal liver lesions, thereby enhancing diagnostic accuracy. The advantage of CEUS lies in its ability to perform both a conventional ultrasound scan and lesion characterization within a single session, avoiding the delays and inconvenience for patients who would otherwise need a separate CT or MRI for a suspicious finding [75]. A systematic review and cost-effectiveness analysis showed that for characterizing focal liver lesions, the diagnostic performance of CEUS is comparable to that of contrast-enhanced CT (CECT) and contrast-enhanced MRI (CEMRI). Furthermore, in the contexts of cirrhosis surveillance and characterizing incidentally found liver masses, CEUS was more cost-effective than CECT and CEMRI [76].
The establishment of CEUS-based HCC screening programs has also been proven feasible in semi-rural academic centers with relatively limited resources [75], expanding the geographic reach of high-quality surveillance. Therefore, CEUS is playing an increasingly important role as a diagnostic tool that balances efficacy and economy, especially for the rapid and accurate on-site characterization of suspicious lesions found on ultrasound.
Novel serum biomarkers: from traditional markers to molecular diagnostics
The traditional serum biomarker AFP is widely used in HCC surveillance, but its limited sensitivity and specificity, especially for early-stage or AFP-negative HCC, have spurred the search for more accurate and cost-effective novel biomarkers (Supplementary Table 1) [50,77]. Molecular diagnostics, particularly liquid biopsy, have opened new avenues for the early detection of HCC.

The potential of liquid biopsy technologies

Liquid biopsy, encompassing circulating tumor DNA, circulating tumor cells, tumor-derived extracellular vesicles, and others, represents an emerging non-invasive approach for the early detection and monitoring of HCC. Current evidence supports its potential utility in complementing conventional imaging and serologic markers to enhance surveillance sensitivity, particularly among high-risk populations [78-80]. However, robust data regarding cost-effectiveness and real-world applicability remain limited. The high cost of sequencing, lack of assay standardization, and uncertainty regarding clinical cut-off thresholds currently restrict its feasibility for routine use in population-based surveillance [78]. Therefore, future prospective studies integrating clinical and cost-effectiveness performance are warranted to define the role of liquid biopsy within HCC surveillance programs.

Multi-biomarker-based diagnostic models (e.g., GALAD, GAAD)

To overcome the limitations of single biomarkers, researchers have developed diagnostic models that integrate multiple biomarkers and clinical variables to improve HCC detection. Among these, the GALAD score (gender, age, AFP, AFP-L3, and DCP) and its derivatives have demonstrated superior diagnostic value compared to single markers in clinical studies, with area under the receiver operating characteristic curve values ranging from 0.92–0.95, significantly higher than the 0.75–0.80 achieved by AFP alone [81]. Health economic evaluations are also beginning to confirm the economic advantages of these multi-biomarker models. A cost-effectiveness analysis conducted in the UK compared four surveillance strategies and found that using the GAAD algorithm (Gender, Age, AFP, and DCP) alone was more cost-effective than conventional ultrasound or ultrasound+AFP strategies, while the combination of GAAD+ ultrasound was clinically superior, increasing early-stage HCC detection rates by 10–13% [82]. Similarly, a study in Chinese CHB patients found that GAAD+ultrasound was the most cost-effective strategy for early HCC screening among all comparators [83].
Cost-effectiveness of AI in early lesion detection
AI technology, particularly deep learning algorithms, is rapidly advancing in the field of medical image analysis, offering promising solutions to enhance the efficiency and accuracy of early HCC detection. AI-assisted diagnostic systems can automatically identify and delineate suspicious lesions on MRI or CT images, and studies show they can improve radiologist’s performance, increasing sensitivity from 60–78% to 81–87% and specificity from 77–90% to 90–94% [84,85]. Beyond its technical advantages, the application of AI also demonstrates potential economic value.
A cost-effectiveness analysis conducted in the Italian healthcare system was the first to evaluate the economics of AI-assisted MRI for HCC surveillance in cirrhotic patients. The study constructed a decision-tree-Markov model to simulate lifetime health outcomes and costs, revealing that, compared to unaided radiology readings, the AI-assisted approach had an ICER of €9,888 per QALY, well below the common willingness-to-pay threshold in Italy (€33,000/QALY), suggesting the technology is highly costeffective [84]. Sensitivity analysis identified the cost of the AI tool and its diagnostic performance (sensitivity and specificity) as critical determinants of cost-effectiveness. As long as the AI software isn’t too expensive and maintains high accuracy, it markedly improves cost-effectiveness by catching more early cancers without proportionally increasing costs (due to avoiding advanced cancer treatments).
This Italian study provides initial confirmation that integrating cost-effective AI tools into clinical practice can improve patient outcomes while enhancing healthcare system efficiency [84]. A recent external validation study in China reported high detection accuracy for AI-assisted CT/MRI platforms in HCC, supporting the feasibility assumptions used in economic models [86]. Emerging advancements in AI-based HCC surveillance—particularly multimodal data integration, explainable AI, and real-time diagnostic applications—are reshaping the landscape of early HCC detection. These innovations hold great promise for improving diagnostic accuracy, workflow efficiency, and clinical decision-making, thereby enhancing the overall effectiveness and patient-centered impact of HCC surveillance programs [87]. However, we caution that most AI models haven’t been widely validated outside their development setting. Future studies should evaluate the cost-effectiveness of AIbased approaches for early HCC detection through multicenter prospective validation. Ensuring data harmonization and transparent reporting in accordance with TRIPOD-AI [88] and PROBAST-AI [89] guidelines will be essential to establish the generalizability, clinical utility, and economic sustainability of AI applications in HCC surveillance.
Surveillance strategies for high-risk populations with different etiologies
The risk of developing HCC varies significantly among populations with different underlying liver diseases. Therefore, developing risk-stratified surveillance strategies based on etiology is key to maximizing cost-effectiveness (Fig. 5).

Patients with cirrhosis related to viral hepatitis (HBV, HCV)

Viral hepatitis is a primary cause of HCC worldwide, accounting for approximately 70% of global HCC cases [90,91]. For patients with CHB, an HCC risk persists even in “inactive” carriers with virologic suppression. A modeling study in the United States population found that increasing surveillance rates from 37% to 90% and treatment rates from 59% to 80% was cost-saving. Building on this, if a patient’s annual HCC risk was ≥0.55%, adding semiannual ultrasound and AFP surveillance was also cost-effective [92]. In China, for CHB patients with advanced fibrosis or compensated cirrhosis who had achieved virologic remission, annual surveillance was found to be more cost-effective than semiannual surveillance [41]. For patients with HCV, the widespread use of direct-acting antivirals (DAAs) has enabled many to achieve a SVR, but their HCC risk is not entirely eliminated. Studies show that the cost-effectiveness threshold for post-SVR surveillance is much lower than traditional standards; for patients with cirrhosis or advanced fibrosis, semiannual surveillance is cost-effective as long as the annual HCC incidence exceeds 0.7% (versus the older ~1.5% threshold) [46]. This reflects improved outcomes and cheaper treatments in the DAA era. It suggests that even well-controlled viral hepatitis patients with residual risk warrant continued surveillance, albeit potentially with refined criteria.

Patients with MASLD and diabetes

With the global epidemics of obesity and diabetes, MASLD has become the fastest-growing cause of HCC, with an annual increase in incidence of 5–10% [14,15,93]. However, surveillance rates among patients with MASLD-related HCC are generally low, with 21.6% of eligible individuals receiving regular monitoring compared to 42.1% in non-MASLD individuals, leading to later-stage diagnosis and poorer outcomes [15,94]. This underlines that MASLD is both a huge atrisk population and one currently underserved by surveillance. Risk stratification is particularly crucial because MASLD encompasses a broad spectrum from simple steatosis to cirrhosis, with varying HCC risk.
A modeling study indicated that implementing routine surveillance for MASLD patients could reduce HCC-related mortality by 18.1% and is cost-effective in most subgroups, except for those with early-stage MASLD [14]. Essentially, surveillance appears justified (and economically reasonable) once MASLD patients have significant fibrosis, but not in those with mild disease due to low absolute risk. For the higher-risk subgroup of MASLD patients with comorbid type 2 diabetes (T2DM), surveillance strategies are even more economically favorable; economic evaluations show ICERs below $50,000 per QALY, with some scenarios even achieving cost savings. In fact, a Japanese study found that for diabetic patients who progressed to MASH cirrhosis, surveillance with gadoxetic acid-enhanced MRI was the most cost-effective strategy and could even be costsaving [95].
Preventive strategies also play a role: lifestyle interventions like weight loss effectively reduce the risk of MASLDrelated HCC and are cost-effective, as weight loss >10% is associated with a 25–50% reduction in HCC risk, and studies have shown that lifestyle programs offer good health economic value [14,96]. This implies that combining surveillance with preventive care (weight management in this case) can yield synergistic benefits for both health outcomes and costs in MASLD populations.
Moving forward, a key future research direction for this emerging high-risk group is how to operationalize risk stratification. One proposal is to screen all T2DM patients for liver fibrosis (with non-invasive tests) to identify those with advanced fibrosis who would benefit from HCC surveillance [97].

Patients with ARLD

ARLD is another major cause of HCC (15–30% of all HCC cases globally), and in some regions, its associated HCC burden is increasing (2–4% annual rise) [16,98]. ARLD patients often have worse surveillance adherence, with reported rates as low as 20.8%, leading to tumors being discovered at a later stage with worse prognoses (5-year survival rates range 14–17%) [16,99,100]. This highlights that proactively identifying and enrolling high-risk ARLD individuals into surveillance programs is critical.
Proactive liver fibrosis assessment in patients hospitalized for alcohol use disorder had the highest yield for detecting cirrhosis, with a cirrhosis detection rate of 10.8– 29.6%. This suggests that screening in such high-risk settings is a feasible and productive strategy [101]. Health economic models also support routine HCC surveillance for ARLD patients. Studies show that routine surveillance can reduce ARLD-related HCC mortality by 18.6% and is cost-effective [14].
Moreover, combining surveillance with alcohol cessation interventions can significantly improve patients’ quality-adjusted life expectancy, achieving a dual win for both health and economic outcomes. Some models show this combined approach is cost-effective or even cost-saving by preventing decompensations and other costs [14].
Risk stratification based on non-invasive liver fibrosis scores
In the pre-cirrhotic stage, especially among the vast noncirrhotic MASLD population estimated at 1.0–1.5 billion people globally, identifying high risk HCC individuals for targeted surveillance is a core health economics challenge. Non-invasive liver fibrosis scores based on routine blood tests, such as the fibrosis-4 (FIB-4) index, APRI (aspartate aminotransferase to platelet ratio index), and NAFLD fibrosis score (NFS), offer a simple and inexpensive tool for risk stratification.
A meta-analysis of nearly 380,000 non-cirrhotic MASLD patients confirmed that elevated FIB-4, APRI, and NFS values were significantly associated with an increased risk of developing HCC, with hazard ratios ranging from 6.57 to 23.90 [102]. More importantly, this study identified specific cutoff values for these scores, above which a patient’s annual HCC incidence would likely be high enough to make surveillance cost-effective. For instance, patients with a FIB-4 ≥5.91 or NFS ≥2.85 are projected to have an annual HCC incidence >1.5%, making it economically justifiable to initiate surveillance [102].
An Australian modeling study also simulated risk stratification of ARLD and MASLD populations using FIB-4 and transient elastography to guide surveillance, with results supporting the cost-effectiveness of such stratification [14]. This evidence indicates that using low-cost, non-invasive scores for initial risk screening can effectively identify highrisk individuals who should require imaging surveillance, thereby avoiding unnecessary and expensive surveillance in low-risk people and serving as a vital tool for precision surveillance on population scale.
Cost-effectiveness comparison: ‘precision surveillance’ vs. ‘one-size-fits-all’ strategies
The traditional “one-size-fits-all” surveillance strategy, which applies uniform semiannual ultrasound+AFP for all eligible cirrhotic patients, is the current mainstream practice [103]. However, this approach fails to account for the vast heterogeneity in HCC risk among patients, potentially leading to over-surveillance of low-risk individuals and undersurveillance of high-risk ones. With advancements in risk assessment tools and surveillance technologies, the concept of “precision surveillance” or “risk-stratified surveillance” has emerged as an alternative paradigm, aiming to tailor surveillance methods or frequencies to individual risk levels.
A pivotal cost-effectiveness analysis directly compared these approaches. The study modeled four strategies: no surveillance, universal ultrasound+AFP surveillance, “riskstratified” surveillance (yes/no to surveil based on risk level), and “precision surveillance” (both deciding whether to surveil and selecting modality/frequency based on risk tier). The results clearly demonstrated that the “precision surveillance” strategy was the most cost-effective option, with an ICER of $104,614/QALY, while the universal ultrasound+AFP and simple risk-stratified strategies were dominated (less effective and/or more costly) [103].
Precision surveillance achieved this by matching highersensitivity tests, albeit higher-cost tests (like MRI) to the highest-risk patients while sparing lower-risk patients from unnecessary surveillance. Precision surveillance strikes a balance between maximizing health benefits and minimizing potential harms/costs by using MRI for those who really need it and perhaps not surveilling those who won’t benefit.
We also note the future potential of machine learning to refine individual risk predictions dynamically (such as before and after SVR in HCV patients). This is considered a promising avenue for developing more cost-effective, customized surveillance plans, as models could continuously identify who moves into or out of a high-risk category [104].
This body of evidence (both modeling and conceptual) lead to the conclusion that shifting from “one-size-fits-all” to “precision” approaches is the inevitable path to enhancing the health economic value of HCC surveillance.
Interventions such as mailed outreach and patient navigators
High surveillance adherence is key to achieving cost-effective surveillance, since even the best surveillance strategy fails if people don’t participate. Studies showed that in model threshold analyses, a surveillance adherence of >19.5% bi-annually was necessary for ultrasound+AFP to be cost-effective compared to no surveillance [35]. Although HCC surveillance is proven to be effective, patient adherence rates in clinical practice remain persistently low, with typically only about 20% of eligible patients participating regularly. This severely diminishes the overall impact of surveillance programs [47,48].
Improving adherence is a critical bottleneck to translate the surveillance benefits into reality. Researchers have explored various interventions aimed at improving adherence and have evaluated their economic value (Fig. 6). Mailed outreach is a low-cost intervention, with an estimated cost of approximately $20–$35 per person, that has proven effective. An RCT demonstrated that mailing letters with presigned ultrasound orders to patients significantly increased surveillance completion rates within six months from 27.6% to 54.5% compared to usual care [105]. More importantly, a cost-effectiveness analysis using a microsimulation model found that a mailed outreach program for cirrhotic patients was not only cost-effective but was even cost-saving (a dominant strategy). The model predicted that the outreach program increased the number of early-stage HCC detections by 48.4%, yielding 300 QALYs, while the savings from reduced late-stage treatment costs were sufficient to offset the program’s expenses [106].
In addition to mailers, patient navigators are another effective method addressing patient-level barriers and guiding individuals through the surveillance process. The costeffectiveness of combining navigators with mailed invitations is currently being evaluated in a RCT called VIGILANT [47].
Application of behavioral economics to improve surveillance rates
Behavioral economics offers a new perspective for designing more effective adherence-boosting strategies by focusing on how to guide positive health behaviors through changes in choice architecture and by leveraging psychological biases. In a pragmatic RCT on HCC surveillance, researchers ingeniously applied an “opt-out framing”. They mailed patients a letter containing a signed ultrasound order, setting the default option to “participate in surveillance”; patients who did not wish to participate had to actively cancel. This design significantly lowered the action barrier for participation. The results showed that this strategy dramatically increased surveillance completion rates, performing significantly better than usual care [105].
Interestingly, the study also tested the effect of including an unconditional $20 cash incentive with the letter and found that this financial incentive did not further increase surveillance rates beyond the effect of the “opt-out” letter. This finding suggests that in the context of HCC surveillance, nudge-style interventions that simplify processes and reduce decision friction may be more powerful and more cost-effective than direct monetary incentives [105]. This provides important insights for designing low-cost, high-impact public health intervention programs in the future.
This finding provides important insights: low-cost behavioral “nudges” – like default scheduling – can double uptake, whereas paying patients did not further improve it, implying we should invest in reducing friction rather than necessarily paying people (which is cost to the system with no observed benefit in this case). From a cost-effectiveness perspective, the opt-out letter is very cheap and had a big effect (dominant in the model, as per 6.1), whereas adding $20 incentive adds cost with no added benefit, thus would be less cost-effective.
Integrating equity into health economic evaluation: conceptual framework and proposal
Conventional cost-effectiveness analyses of HCC surveillance frequently presuppose a homogeneous population, thereby neglecting the impact of socioeconomic determinants, including race, income level, and insurance status, on screening accessibility, compliance, and resultant health outcomes. This omission risks masking inequities and overestimating the efficiency of programs that primarily benefit advantaged groups. To address this gap, equity can be integrated into health economic modeling by stratifying populations according to key social determinants and incorporating subgroup-specific parameters—such as participation rates, diagnostic access, costs, and health utilities—into decision-analytic or Markov models. Such stratified modeling enables estimation of subgroup-specific ICERs and facilitates distributional cost-effectiveness analysis to jointly assess efficiency and fairness [107]. For instance, one can calculate not only overall QALYs gained, but also how those QALYs are distributed across income groups.
Quantitative tools, including the concentration index [108], can further capture inequality in health gains (e.g., QALYs) across socioeconomic strata. Embedding these approaches within HCC surveillance evaluation will help shift the field from asking “Is surveillance cost-effective?” toward “For whom is it cost-effective, and how can policies promote equitable benefit distribution?”—aligning health economic research with both efficiency and justice considerations is essential for truly sustainable policy.
Influence of race, socioeconomic status, and insurance on surveillance, treatment, and costs
Socioeconomic factors, including race, insurance status, and education level, are key determinants of health equity in HCC surveillance, treatment, and outcomes. These factors also directly shape the economic feasibility of surveillance strategies and health interventions (Fig. 7). Numerous studies, particularly those based on the United States populations, have documented significant health disparities. For example, African American patients have a 20– 30% lower likelihood of receiving curative treatment, often experience treatment delays, and have worse survival outcomes compared to White patients, especially in high-poverty communities [109-112]. Similarly, lower education levels and health literacy are linked to lower treatment uptake, reflected in a 15–25% reduction in the receipt of curative treatments, and poorer survival [109,113]. Insurance status plays a substantial role in HCC care. Patients with Medicaid or no insurance are 30–50% higher probability to present with advanced disease, and are less likely to receive curative treatments, thus leading to higher mortality rates [114-116]. These social determinants of health contribute not only to poorer health outcomes but also to higher medical costs. For instance, African American race, limited English proficiency, and living alone are all associated with higher postdiagnosis medical costs [109].
Therefore, health economic evaluations of HCC surveillance must incorporate these disparities to ensure the generalizability and fairness of cost-effectiveness models. Promoting health equity should be a core objective in designing and assessing surveillance strategies. Therefore, we argue that cost-effectiveness analyses must incorporate these disparities to ensure their conclusions are generalizable and equitable. We also assert that promoting health equity should be a core objective when designing and assessing surveillance strategies, which may require targeted interventions aimed at vulnerable populations to achieve equitable outcomes. These interventions might have additional costs, but they could improve overall cost-effectiveness by increasing participation in groups that would otherwise under-utilize surveillance.
Urban-rural disparities, geographic factors, and healthcare accessibility
Geography and healthcare accessibility are also key elements influencing the equity and effectiveness of HCC surveillance. In particular, urban-rural disparities are well documented: rural residents have lower surveillance rates and less access to medical resources, with surveillance uptake 10–30% lower than those observed in urban populations [117]. A study within the U.S. Veterans Affairs (VA) system demonstrated that travel distance to the nearest healthcare facility was a significant barrier to surveillance uptake, with patients living more than 30 miles away significantly less likely to undergo imaging. This geographic barrier increases healthcare complexity and may result in some patients seeking care outside the VA system [118].
In China, geographic disparities are also substantial, with liver cancer mortality and disease burden varying widely between regions, and rural areas often bear a heavier burden [119,120]. These regional differences reflect an uneven distribution of medical resources, variable economic development, and public health awareness gaps. For health economic evaluations, this means that a national average cost-effectiveness ratio may not be applicable across different regions. Therefore, surveillance policies should thus account for geographic diversity and consider targeted, cost-effective strategies for rural and under-resourced areas to ensure equitable access to HCC screening and treatment. For example, it might be cost-effective to implement telemedicine or mobile screening clinics in remote areas, even if those weren’t needed in cities.
Challenges and opportunities in LMICs
LMICs bear the heaviest global burden of HCC but often face substantial barriers to effective surveillance, early diagnosis, and treatment due to limited healthcare infrastructure, scarce resources, and high diagnostic costs [22,90,121,122]. In many LMICs (Table 3 and Supplementary Table 2) [41,45,57,69,95,123-131], viral hepatitis (HBV and HCV) remains the predominant etiological factor [90]; however, suboptimal vaccination coverage, insufficient screening, and limited access to antiviral therapy contribute to late-stage presentation and poor prognosis [122,132]. Advanced treatment modalities such as surgery or locoregional therapies are frequently inaccessible, further worsening outcomes [22,133].
Despite these challenges, emerging evidence underscores that cost-effective surveillance is feasible even in resource-constrained settings with creative approaches. For instance, in Egypt, a semiannual ultrasound+AFP surveillance program was shown to be highly cost-effective (ICER €800–€850 per QALY), with costs well below internationally accepted willingness-to-pay thresholds [134]. This likely reflects the relatively low cost of ultrasound and high HCC incidence in the population, yielding great value. Similarly, in India, a prospective evaluation of cirrhotic patients demonstrated that while six-monthly ultrasound+AFP surveillance was cost-effective from the hospital perspective ($280 per HCC case detected), costs increased markedly for patients outside major centers (up to $9,965), highlighting inequities in access and affordability [124]. This indicates that even if an intervention is cost-effective on average, rural patients might still face prohibitive costs, limiting realworld uptake.
In China, modeling among CHB patients identified a combined GAAD+ultrasound algorithm as the most costeffective strategy for early HCC detection (ICER $4,993– 26,691 per QALY), remaining below the 3× GDP per capita threshold [83]. However, real-world implementation remains inconsistent. Surveys across Asian LMICs (e.g., Indonesia, Malaysia, Thailand, Vietnam) indicate that although HCC surveillance programs are conceptually “widespread,” only 18% of physicians report that surveillance commonly identifies early-stage disease—reflecting gaps in program execution, patient engagement, and system-level followthrough [135]. This reflects gaps in program execution, patient engagement, and system follow-through—perhaps due to workforce shortages, irregular screening, or patients not returning for follow-up.
These findings collectively emphasize three recurring themes across LMICs: (1) inequities in access, as patients distant from specialized centers face higher costs and lower detection rates; (2) resource adaptation, wherein surveillance strategies must align with local capacity for imaging, biomarkers, and follow-up (e.g., annual vs. semiannual ultrasound when constrained); and (3) implementation challenges, where guideline awareness alone is insufficient without workforce training, robust referral networks, and patient education. Encouragingly, successful initiatives such as Rwanda’s national HCV elimination program demonstrate that with coordinated public health efforts, international collaboration, and strategic technology use, substantial progress is achievable in viral hepatitis control and HCC prevention at sustainable cost [136]. By analogy, robust programs targeting viral hepatitis and HCC in other LMICs could yield significant improvements if well-planned. Integrating such evidence from LMICs not only broadens the global perspective of HCC surveillance but also underscores the importance of equity-driven, context-specific strategies to mitigate the worldwide burden of this disease.
HCC imposes a tremendous dual burden of health and economic costs globally. Existing evidence clearly indicates that conventional surveillance for high-risk populations, such as individuals with cirrhosis, based on semiannual ultrasound±AFP, is a cost-effective strategy that can effectively increase early diagnosis rates, expand opportunities for curative treatment, and improve survival at an acceptable cost. However, the real-world effectiveness of this strategy is severely constrained by factors such as low patient adherence and the inadequate sensitivity of ultrasound in emerging high-risk groups, including those with MASLD.
To address these challenges, innovative surveillance technologies are showing great potential. Abbreviated MRI, multi-biomarker models (like GALAD), and liquid biopsy techniques (such as methylated DNA markers) promise to enhance diagnostic accuracy while maintaining favorable economics. The application of AI in medical imaging has also been initially shown to be cost-effective, heralding its broad prospects for integrating AI into future surveillance systems. More importantly, the field is moving away from a “one-size-fits-all” model toward “precision surveillance” based on individualized risk assessment. By integrating multi-dimensional information—including etiology, fibrosis stage, and molecular markers—to perform fine-grained risk stratification, we can match patients at different risk levels with the optimal surveillance tools and frequencies. This is the key to maximizing health benefits while minimizing resource waste and potential harms.
At the same time, strategies to improve surveillance adherence, such as mailed outreach and behavioral economic interventions, have not only been proven effective but may even be cost-saving, underscoring the central role of implementation science in translating the benefits of surveillance into real-world outcomes. Furthermore, profound socioeconomic inequities are an undeniable reality. Factors like race, insurance status, and geographic accessibility significantly impact surveillance coverage, access to treatment, and ultimate health outcomes. This requires that future health policies and economic models prioritize the promotion of health equity by incorporating targeted efforts to reach vulnerable populations as part of cost-effectiveness considerations.
Looking ahead, more prospective clinical trial evidence is needed to validate the clinical value and cost-effectiveness of novel surveillance technologies and to evaluate the effectiveness of risk-stratified strategies in real-world settings. For LMICs, it is imperative to adapt successful experiences and promote low-cost, high-impact surveillance and prevention programs tailored to local conditions. Future research should prioritize several key directions to further advance this field. First, prospective trials are needed to assess the real-world cost-effectiveness and clinical utility of AI-integrated surveillance platforms, ensuring that these innovations translate into meaningful outcome improvements. Second, the development of point-of-care risk stratification tools suitable for primary care and communitybased settings will be critical for expanding early detection beyond tertiary centers. Third, implementation studies focusing on scalable and sustainable approaches—such as mailed outreach programs and digital reminder systems—across diverse healthcare systems can provide valuable insights into improving surveillance uptake and equity. Ultimately, by integrating effective prevention, precision risk stratification, innovative surveillance technologies, and equitable implementation strategies, we will be better equipped to confront the global challenge of HCC (Fig. 8).

Authors’ contributions

Qi-Feng Chen: Writing – original draft, Visualization, Methodology, Investigation, Funding acquisition, Conceptualization. Xiong-Ying Jiang: Writing – original draft, Validation, Methodology, Investigation. Song Chen: Writing – review & editing, Validation, Supervision, Investigation. Jiongliang Wang: Writing – review & editing, Validation, Supervision, Conceptualization. Ming Zhao: Writing – review & editing, Validation, Supervision, Project administration, Funding acquisition, Conceptualization. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Acknowledgements

Supported by the National Natural Science Foundation of China (No. 82402403 and 82372061), and the GuangDong Basic and Applied Basic Research Foundation (No. 2025A1515011330).

Conflicts of Interest

The authors have no conflicts to disclose.

Supplementary material is available at Clinical and Molecular Hepatology website (http://www.e-cmh.org).
Supplementary Table 1.
Summary of emerging multi-biomarker-based surveillance technologies
cmh-2025-1060-Supplementary-Table-1.pdf
Supplementary Table 2.
Selected studies on the health economics of HCC screening outside Asia
cmh-2025-1060-Supplementary-Table-2.pdf
Figure 1.
Health economics of hepatocellular carcinoma (HCC) surveillance. Without surveillance, high-risk patients often present with late-stage HCC, limiting treatment options and survival. Semi-annual monitoring improves early detection and survival, supporting cost-effectiveness. Key economic and clinical considerations include shifting etiologies (e.g., MASLD, ARLD), advances in emerging technologies such as artificial intelligence and novel biomarkers, and the importance of adherence, costs, and equity in implementation. Six key aspects related to HCC surveillance were emphasized. ARLD, alcohol-related liver disease; MASLD, metabolic-associated steatotic liver disease.
cmh-2025-1060f1.jpg
Figure 2.
Global and socioeconomic burden of hepatocellular carcinoma (HCC). On the left, the epidemiology and disease burden of HCC are depicted through crude incidence and mortality rates (per 100,000 population) by region for 2022 on Globocan platform (gco. iarc.fr), highlighting the dominance of East Asia in both cases. It also identifies the rising burden in high body mass index elderly populations and the increasing incidence in low- and middle-income countries (LMICs), especially due to alcohol-related HCC. On the right, the socioeconomic burden is shown, including high medical costs driven by hospitalization and the significant productivity loss due to premature mortality (years of life lost). These factors emphasize the need for cost-effective prevention and surveillance strategies. DALYs, disability-adjusted life years.
cmh-2025-1060f2.jpg
Figure 3.
Surveillance strategies and cost-effectiveness drivers for hepatocellular carcinoma (HCC). The time intervals for monitoring include a 6-month standard period and 12-month intervals for specific subgroups, with surveillance stopping between the ages of 60 and 70 years. Key surveillance methods include alpha-fetoprotein (AFP) testing and ultrasound (US), aimed at increasing early-stage detection of HCC, facilitating more curative treatments, and reducing mortality. Key cost-effectiveness drivers are highlighted, including the annual incidence rate of HCC (>0.7%), patient adherence (target >19.5%), the sensitivity of ultrasound, especially in cases of obesity or metabolic-associated steatotic liver disease (MASLD), and the potential harms of false positives leading to additional tests. The clinical guidelines foundation from the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD), Asian Pacific Association for the Study of the Liver (APASL) and others provide the basis for these surveillance strategies.
cmh-2025-1060f3.jpg
Figure 4.
Advancements in hepatocellular carcinoma (HCC) surveillance technologies and their cost-effectiveness. Recent developments in HCC surveillance are emerging, concentrating on their diagnostic precision, cost-efficiency, and incorporation into clinical practice. On the left, various imaging technologies are shown, with magnetic resonance imaging (MRI)/computed tomography (CT) offering high sensitivity but high costs, abbreviated MRI (AMRI) providing a balanced approach of cost and accuracy, and contrast-enhanced US being a cost-effective method for lesion characterization. In the middle, novel biomarkers such as serum and molecular markers contribute to improved risk stratification, exemplified by multi-biomarker models (e.g., GAAD/GALAD). On the right, artificial intelligence (AI)-assisted detection is highlighted, demonstrating a cost-effective increase in diagnostic performance, with an incremental cost-effectiveness ratio of €9,888 per quality adjusted life year (QALY), suggesting significant potential for improving HCC diagnosis. GAAD, gender, age, AFP, and DCP; GALAD, gender, age, AFP, AFP-L3, and DCP.
cmh-2025-1060f4.jpg
Figure 5.
Transition from universal to risk-stratified precision surveillance for hepatocellular carcinoma (HCC). The customary “one-size-fits-all” approach to universal surveillance (left) is contrasted with a more effective, risk-stratified precision surveillance methodology (right). In the universal model, individuals from a heterogeneous at-risk population, including viral hepatitis, metabolic-associated steatotic liver disease (MASLD)/non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ARLD), and other risk factors, undergo the same surveillance process. This approach results in suboptimal cost-effectiveness. In contrast, risk-stratified surveillance uses tools like FIB-4, APRI, and NFS to categorize individuals into high, standard, and low-risk groups. This tailored approach allows for more targeted utilization of surveillance resources, employing MRI for high-risk individuals, and utilizing less expensive methods such as ultrasound or biomarkers for standard surveillance, with no surveillance for low-risk groups. The risk-stratified strategy achieves the most cost-effective outcomes, with an incremental cost-effectiveness ratio (ICER) of $104,614 per quality-adjusted life year (QALY). APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4 index; NFS, NAFLD fibrosis score.
cmh-2025-1060f5.jpg
Figure 6.
Improving surveillance adherence through outreach and behavioral economics interventions. The strategies to improve adherence to HCC surveillance and their associated cost-effectiveness. The central problem is low surveillance adherence, with only about 20% of patients following recommended screening protocols. Outreach and navigation interventions, including mailed outreach with presigned orders and patient navigator programs, significantly improve adherence. Behavioral economics interventions, such as “opt-out” framing (where patients are automatically enrolled unless they actively decline) further enhance participation. However, the elimination of financial incentives does not necessarily lead to increased participation. These strategies together result in over 50% adherence, leading to increased early detection, a cost-saving surveillance model, and substantial gains in quality-adjusted life years (QALYs).
cmh-2025-1060f6.jpg
Figure 7.
Socioeconomic barriers to equitable hepatocellular carcinoma (HCC) care. The key socioeconomic and geographic disparities that impede equitable access to hepatocellular carcinoma (HCC) care are illustrated. At the top, disparities in insurance status lead to later-stage tumor diagnoses in uninsured patients compared to those with insurance, who are more likely to be diagnosed at an earlier stage (~30% higher late-stage presentation in uninsured). Geographic barriers, such as the distance (>30 miles) between rural communities and medical centers, further exacerbate access to care, with urban residents having better access. The bottom section focuses on global disparities, particularly in low- and middle-income countries (LMICs), where challenges such as high burdens of hepatitis B virus (HBV) and hepatitis C virus (HCV), resource scarcity, and weak health systems hinder effective care. Solutions to these issues include international cooperation, price negotiations, and the implementation of cost-effective surveillance and public health programs, which are essential to improving care access in disadvantaged regions. At the bottom, a proposed framework for embedding equity considerations into health economic modeling of HCC surveillance is presented. The outputs can then be synthesized to assess how surveillance interventions perform in terms of both overall efficiency and equity across populations. ICER, incremental cost-effectiveness ratio.
cmh-2025-1060f7.jpg
Figure 8.
HCC surveillance: summary and future outlook. (A) The current challenges and future strategies for hepatocellular carcinoma (HCC) surveillance are illustrated. On the left, the limitations of standard surveillance methods—such as low patient adherence and reduced sensitivity, especially in populations with metabolic-associated steatotic liver disease (MASLD)—are highlighted. The central section presents the three pillars of future strategy: (1) advanced imaging technologies, (2) novel biomarkers, and (3) AI-assisted detection, all aimed at improving diagnostic accuracy and early detection. Below, implementation strategies, including adherence strategies such as outreach and nudges, and a focus on health equity, are emphasized to address socio-economic and geographic disparities. The right section shows the integrated future solution, which aims to maximize early detection, improve survival, and achieve optimal cost-effectiveness while ensuring equitable access to HCC surveillance globally. (B) A cost-effective surveillance protocol for HCC based on annual risk assessment, incorporating current evidence. The left side depicts a decision pathway for surveillance, while the right side provides four supplementary points to enhance the understanding of the protocol. AFP, alpha-fetoprotein; AI, artificial intelligence; AMRI, abbreviated magnetic resonance imaging; CT, computed tomography; HBV, hepatitis B virus; HCV, hepatitis C virus; MRI, magnetic resonance imaging; NAFLD, non-alcoholic fatty liver disease; US, ultrasound.
cmh-2025-1060f8.jpg
Table 1.
Surveillance modalities as per Western and Eastern guidelines
Table 1.
Characteristic West
 East
AASLD [6] EASL [7] APASL [8] KLCA [9] JSH [10] CNLC [11]
High-risk patients Child–Pugh A–B cirrhosis, any etiology Child-Pugh A–B cirrhosis, any etiology Cirrhotic hepatitis patients Chronic hepatitis B, chronic hepatitis C, or cirrhosis Cirrhosis, chronic hepatitis B, or chronic hepatitis C HBV and/or HCV infection, non-alcoholic steatohepatitis, cirrhosis from other causes, those who consume excessive amounts of alcohol, and/or those with a family history of liver cancer, especially males >40 years of age
 Hepatitis B Child–Pugh C cirrhosis, transplant candidate  HBV
 Hepatitis C (viremic or post-SVR)  HCV
 Alcohol associated cirrhosis Non-cirrhotic patients chronic HBV infection, at intermediate or high risk for HCC advanced fibrosis, regardless of the underlying etiology  NASH
 Nonalcoholic steatohepatitis  Genetic hemochromatosis
 Other etiologies  Primary biliary cirrhosis
Child–Pugh C cirrhosis, transplant candidate  A1AT deficiency
Non-cirrhotic chronic hepatitis B  Autoimmune hepatitis
 Man from endemic country* age >40 yr  Other etiologies
 Woman from endemic country* age >50 yr Chronic HBV carriers
 Person from Africa at earlier age†  Noncirrhotic (HBsAg positive)
 Family history of HCC  Asian females >50 yr
 PAGE-B score >10‡  Asian males >40 yr
Insufficient risk and in need of risk stratification models/biomarkers  Africans aged >20 yr
 Hepatitis C and stage 3 fibrosis  History of HCC in the family
 Noncirrhotic NAFLD
Modality Ultrasound+AFP Ultrasound Ultrasound+AFP Ultrasound+AFP Ultrasound+tumor marker Ultrasound+AFP
Interval (mo) 6 6 6 6 3–6 6

A1AT, alpha-1 antitrypsin; AASLD, American Association for the Study of Liver Diseases; AFP, alpha-fetoprotein; APASL, Asian Pacific Association for the Study of the Liver; CNLC, China Liver Cancer Staging; EASL, European Association for the Study of the Liver; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; JSH, Japan Society of Hepatology; KLCA, Korean Liver Cancer Association; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; PAGE-B, platelet, age, gender–hepatitis B score; SVR, sustained virologic response.

*Endemic country as defined by AASLD hepatitis B virus guidance.

†Surveillance can be initiated as early as third decade of life given median age 46 years at HCC diagnosis.

‡Other risk calculators can be considered, although PAGE-B has been validated in Western populations on antiviral therapy.

Table 2.
Summary of AMRI for HCC surveillance
Table 2.
Characteristic Description
Strength [59,60] NC-AMRI:
 1. Most time- and cost-saving;
 2. No contrast related risk.
AMRI with gadoxetic acid:
 1. Shorter scan time than full MR.
DCE-AMRI:
 1. Shorter scan time than full MRl;
 2. Evaluation of vascular thrombus;
 3. No requirement of a recall test.
Weakness [59,60] NC-AMRI:
 1. Heavily dependent on DWI (prone to artifacts);
 2. Limited evaluation for vascular thrombus;
 3. Additional recall tests needed.
AMRI with gadoxetic acid:
 1. Additional recall tests needed;
 2. Contrast related risk.
DCE-AMRI:
 1. Contrast related risk.
Meta-analyses of diagnostic performance Author Year Number of studies Pooled sensitivity (%)** Pooled specificity (%)**
Gupta et al. [61] 2021 15 86 (84–88) 94 (91–96)
Kim et al. [62] 2021 10 86 (80–90) 96 (93–98)
Lu et al. [63] 2021 15 84 (78–88) 94 (90–95)
Kim et al. [64] 2021 4 87 (80–94) 94 (90–98)
Chan et al. [65] 2022 22 86.8 (83.9–89.4) 90.3 (87.3–92.7)
Maung et al. [66] 2024 27 86 (83–88) 92 (90–94)
Wang et al. [67] 2025 19 85 (83–87) 93 (91–94)
Ongoing cost-effectiveness trial FASTRAK: ClinicaTrials.gov (NCT05095714)*,[68]
Health-Economic recommendations AMRI used in patients at high risk of HCC (>1.8% per year)§,[44,45,69-71]
Ultrasound visualization score-based approach with AMRI∥,[72]

AMRI, abbreviated magnetic resonance imaging; DCE-AMRI, dynamic contrast-enhanced AMRI; DWI, diffusion-weighted imaging; HCC, hepatocellular carcinoma; NC-AMRI, non-contrast AMRI; T2DM, type 2 diabetes mellitus.

*The hypothesis posits that employing AMRI as a screening examination for patients with a high risk of HCC (greater than 3% per annum)could enhance the detection rates of tumors at an early stage, amenable to curative treatment, and further demonstrate its costeffectiveness within this demographic.

§Risk stratification shall be established and validated through future research, encompassing models that integrate clinical and laboratory assessments.

∥An investigation was conducted utilizing a Markov model to simulate the outcomes for adults diagnosed with compensated non-alcoholic fatty liver disease (NAFLD) cirrhosis in the United States who are subjected to HCC screening. The study compared various screening strategies, including the combination of ultrasound and visualization score, ultrasound alone, and the absence of surveillance. The analysis revealed that among patients with NAFLD cirrhosis, the strategy incorporating an ultrasound visualization score in conjunction with aMRI was the most cost-effective. This approach yielded an incremental cost-effectiveness ratio (ICER) of $59,005 in comparison to the strategy of no surveillance.

**95% confidence intervals.

Table 3.
Selected studies on the health economics of HCC screening in Asia
Table 3.
Year First author Origin Patients Surveillance method Model Cost-effectiveness results Cost-effectiveness conclusion
2008 Nouso et al. [123] Japan 45-year-old patients with Child–Pugh class A cirrhosis Ultrasound every 6 months Markov model The ICER was $29,900/QALY in a base-case analysis (annual HCC incidence=4%). The cost-effectiveness of HCC surveillance varies between patient subgroups and depends critically on the rate of incidental detection, HCC incidence, and adoption of liver transplantation.
2008 Paul et al. [124] India 194 cirrhotic patients 6-monthly ultrasound and AFP, yearly triple-phase CT Yes, not specific Cost per HCC case detected: $280 (hospital perspective). Direct medical cost (EASL protocol): $1,510/case. The cost of the HCC surveillance program is exorbitant for India and possibly other low/middle-income countries.
2012 Tanaka et al. [125] Japan HCV-related liver cirrhosis patients No surveillance, ultrasound, and contrast-enhanced ultrasound Markov model Compared to ultrasound surveillance, contrast-enhanced ultrasound had an ICER of $24,250/QALY. Both were cost-effective vs. no surveillance. Contrast-enhanced ultrasound surveillance is a cost-effective strategy for liver cirrhosis patients, even compared to standard ultrasound surveillance.
2014 Sangmala et al. [126] Thailand Thai chronic HBV patients Semi-annual ultrasound vs. semi-annual ultrasound+AFP Markov model ICERs vs. no program: ultrasound 118,796 Thai Baht/QALY; ultrasound+AFP 123,451 Thai Baht/QALY. Both ultrasound and ultrasound+AFP are cost-effective. Semi-annual ultrasound is recommended due to lower budget impact.
2016 Kuo et al. [127] Taiwan General population based cohorts in an area with high HCC incidence No surveillance, two-stage biomarker-ultrasound, and mass screening with ultrasound Markov model ICERs vs. no screening: Mass screening with ultrasound $39,825 per life-year gained; two-stage biomarker-ultrasound $49,733 per life-year gained. Mass screening using ultrasound is more cost-effective than two-stage biomarker ultrasound screening. Optimal strategy is biennial screening starting at age 50.
2019 Kim et al. [45] South Korea Patients with compensated cirrhosis (mainly HBV-associated) Semiannual surveillance using MRI with liver-specific contrast vs. ultrasound Markov model At 3% annual HCC incidence, MRI had an ICER of $25,202/QALY compared to ultrasound. ICER was 1.81%. Semiannual MRI surveillance may be more cost-effective than ultrasound in patients with compensated cirrhosis at sufficiently high HCC risk.
2021 Zhang et al. [128] China Simulated cohort of 40-year-old patients with chronic hepatitis B cirrhosis anti-tumor associated antigen autoantibody (TAAb)+AFP vs. ultrasound+AFP Markov model Compared with ultrasound+AFP, TAAb+AFP had an ICER of 127,635 yuan/QALY. It is cost-effective to use TAAb+AFP for early screening in the Chinese population with chronic hepatitis B cirrhosis.
2024 Tan et al. [57] Singapore Simulated 40-year-old at-risk patient cohort No surveillance, ultrasound, and non-contrast-enhanced MRI Markov model The ICER for non-contrast-enhanced MRI compared to ultrasound was SGD 9,479/QALY. Despite superior diagnostic accuracy, non-contrast-enhanced MRI is a less cost-effective strategy than ultrasound for HCC surveillance in the general at-risk population.
2024 Decharatanachart et al. [69] Thailand Cirrhotic patients in Thailand and the United States Non-contrast abbreviated MRI vs. ultrasound+AFP Markov model ICER for abbreviated MRI vs. ultrasound+AFP: $3,667/QALY in Thailand and $37,062/QALY in the United States. Non-contrast abbreviated MRI is a cost-effective strategy for HCC surveillance, especially in those with high HCC risks.
2024 Fang et al. [41] China Chronic hepatitis B patients with virological remission (cirrhosis or advanced fibrosis) Biannual vs. annual surveillance with ultrasound+AFP Markov model Annual surveillance was cost-effective for cirrhosis patients aged 55–70 (ICER $28,076/QALY) and for advanced fibrosis patients aged 40–75 (ICER $4,984/QALY). Annual surveillance was a more cost-effective option than biannual surveillance, providing substantial economic benefits for a slight reduction in effectiveness.
2024 Kowada [95] Japan 50-year-old diabetic patients with MASLD, risk-stratified Various methods including ultrasound, CT, and MRI Markov model In obese diabetic patients with MASH, gadoxetic acid-enhanced MRI was more cost-effective than no screening (ICER, $49,160 per QALY gained). For diabetic patients with MASH cirrhosis, gadoxetic acid-enhanced MRI yields the greatest cost-saving with the highest QALYs and averts the most HCC-related deaths.
2025 Decharatanachart et al. [129] Thailand MASLD patients in Thailand and the United States Using non-invasive tests (FIB-4, VCTE) to initiate HCC surveillance Markov model The FIB-4/VCTE strategy (ICER was $21,113/QALY) was the most cost-effective approach across all patient groups. Using FIB-4/VCTE to initiate HCC surveillance is cost-effective for MASLD patients. FIB-4 alone is a cost-effective alternative if VCTE is unavailable.
2025 Saeoui et al. [130] Thailand Patients with chronic hepatitis B Ultrasound+AFP vs. biomarker strategies (GAAD, GALAD, ASAP) Markov model ASAP every 6 months was the most cost-effective strategy, with an ICER of 76,447 Thai Baht/QALY vs. no surveillance. ASAP every 6 months is the most cost-effective HCC surveillance strategy for patients with chronic hepatitis B, especially for resource-limited settings.
2025 Chen et al. [131] China Chronic hepatitis B cohorts in China, risk-stratified Various active surveillance strategies vs. no surveillance Markov model All surveillance strategies, except quinquennial, were cost-effective for high-risk groups (ICER $28,448–$36,073/QALY). No strategy was cost-effective for the low-risk group. The cost-effectiveness of HCC surveillance in chronic hepatitis B patients varies by risk. A risk-stratified approach could optimize resource allocation.

Origins outside Asia are listed in Supplementary Table 2.

AFP, alpha-fetoprotein; ASAP, age, sex, AFP, and PIVKA-II; CT, computed tomography; EASL, European Association for the Study of the Liver; FIB-4, fibrosis-4 index; GAAD, gender, age, AFP, and DCP; GALAD, gender, age, AFP, AFP-L3, and DCP; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; ICER, incremental costeffectiveness ratio; MASH, metabolic dysfunction–associated steatohepatitis; MASLD, metabolic-dysfunction associated steatotic liver disease; MRI, magnetic resonance imaging; PIVKA-II, protein induced by vitamin K absence or antagonist-II; QALY, quality-adjusted life year; TAAb, tumor-associated antigen autoantibody; VCTE, vibration-controlled transient elastography.

AFP

alpha-fetoprotein

AASLD

American Association for the Study of Liver Diseases

AI

artificial intelligence

AMRI

abbreviated magnetic resonance imaging

APASL

Asian Pacific Association for the Study of the Liver

ARLD

alcohol-related liver disease

CHB

chronic hepatitis B

CNLC

Chinese National Guidelines

CT

computed tomography

DAAs

direct-acting antivirals

DALYs

disability-adjusted life years

EASL

European Association for the Study of the Liver

FIB-4

fibrosis-4 index

HCC

hepatocellular carcinoma

JSH

Japan Society of Hepatology

KLCA–NCC

Korean Liver Cancer Association–National Cancer Center

LI-RADS

liver imaging reporting and data system

LMICs

low- and middle-income countries

MASLD

metabolic-associated steatotic liver disease

MRI

magnetic resonance imaging

NAFLD

non-alcoholic fatty liver disease

NFS

NAFLD fibrosis score

PIVKA-II

protein induced by vitamin K absence or antagonist-II

QALY

quality-adjusted life year

RCT

randomized controlled trial

SVR

sustained virologic response

T2DM

type 2 diabetes

US

ultrasound

VA

Veterans Affairs
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Hepatocellular carcinoma surveillance: a health economic evaluation
Clin Mol Hepatol. 2026;32(2):536-564.   Published online January 9, 2026
DOI: https://doi.org/10.3350/cmh.2025.1060
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Hepatocellular carcinoma surveillance: a health economic evaluation
Clin Mol Hepatol. 2026;32(2):536-564.   Published online January 9, 2026
DOI: https://doi.org/10.3350/cmh.2025.1060
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Hepatocellular carcinoma surveillance: a health economic evaluation
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Figure 1. Health economics of hepatocellular carcinoma (HCC) surveillance. Without surveillance, high-risk patients often present with late-stage HCC, limiting treatment options and survival. Semi-annual monitoring improves early detection and survival, supporting cost-effectiveness. Key economic and clinical considerations include shifting etiologies (e.g., MASLD, ARLD), advances in emerging technologies such as artificial intelligence and novel biomarkers, and the importance of adherence, costs, and equity in implementation. Six key aspects related to HCC surveillance were emphasized. ARLD, alcohol-related liver disease; MASLD, metabolic-associated steatotic liver disease.
Figure 2. Global and socioeconomic burden of hepatocellular carcinoma (HCC). On the left, the epidemiology and disease burden of HCC are depicted through crude incidence and mortality rates (per 100,000 population) by region for 2022 on Globocan platform (gco. iarc.fr), highlighting the dominance of East Asia in both cases. It also identifies the rising burden in high body mass index elderly populations and the increasing incidence in low- and middle-income countries (LMICs), especially due to alcohol-related HCC. On the right, the socioeconomic burden is shown, including high medical costs driven by hospitalization and the significant productivity loss due to premature mortality (years of life lost). These factors emphasize the need for cost-effective prevention and surveillance strategies. DALYs, disability-adjusted life years.
Figure 3. Surveillance strategies and cost-effectiveness drivers for hepatocellular carcinoma (HCC). The time intervals for monitoring include a 6-month standard period and 12-month intervals for specific subgroups, with surveillance stopping between the ages of 60 and 70 years. Key surveillance methods include alpha-fetoprotein (AFP) testing and ultrasound (US), aimed at increasing early-stage detection of HCC, facilitating more curative treatments, and reducing mortality. Key cost-effectiveness drivers are highlighted, including the annual incidence rate of HCC (>0.7%), patient adherence (target >19.5%), the sensitivity of ultrasound, especially in cases of obesity or metabolic-associated steatotic liver disease (MASLD), and the potential harms of false positives leading to additional tests. The clinical guidelines foundation from the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD), Asian Pacific Association for the Study of the Liver (APASL) and others provide the basis for these surveillance strategies.
Figure 4. Advancements in hepatocellular carcinoma (HCC) surveillance technologies and their cost-effectiveness. Recent developments in HCC surveillance are emerging, concentrating on their diagnostic precision, cost-efficiency, and incorporation into clinical practice. On the left, various imaging technologies are shown, with magnetic resonance imaging (MRI)/computed tomography (CT) offering high sensitivity but high costs, abbreviated MRI (AMRI) providing a balanced approach of cost and accuracy, and contrast-enhanced US being a cost-effective method for lesion characterization. In the middle, novel biomarkers such as serum and molecular markers contribute to improved risk stratification, exemplified by multi-biomarker models (e.g., GAAD/GALAD). On the right, artificial intelligence (AI)-assisted detection is highlighted, demonstrating a cost-effective increase in diagnostic performance, with an incremental cost-effectiveness ratio of €9,888 per quality adjusted life year (QALY), suggesting significant potential for improving HCC diagnosis. GAAD, gender, age, AFP, and DCP; GALAD, gender, age, AFP, AFP-L3, and DCP.
Figure 5. Transition from universal to risk-stratified precision surveillance for hepatocellular carcinoma (HCC). The customary “one-size-fits-all” approach to universal surveillance (left) is contrasted with a more effective, risk-stratified precision surveillance methodology (right). In the universal model, individuals from a heterogeneous at-risk population, including viral hepatitis, metabolic-associated steatotic liver disease (MASLD)/non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ARLD), and other risk factors, undergo the same surveillance process. This approach results in suboptimal cost-effectiveness. In contrast, risk-stratified surveillance uses tools like FIB-4, APRI, and NFS to categorize individuals into high, standard, and low-risk groups. This tailored approach allows for more targeted utilization of surveillance resources, employing MRI for high-risk individuals, and utilizing less expensive methods such as ultrasound or biomarkers for standard surveillance, with no surveillance for low-risk groups. The risk-stratified strategy achieves the most cost-effective outcomes, with an incremental cost-effectiveness ratio (ICER) of $104,614 per quality-adjusted life year (QALY). APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4 index; NFS, NAFLD fibrosis score.
Figure 6. Improving surveillance adherence through outreach and behavioral economics interventions. The strategies to improve adherence to HCC surveillance and their associated cost-effectiveness. The central problem is low surveillance adherence, with only about 20% of patients following recommended screening protocols. Outreach and navigation interventions, including mailed outreach with presigned orders and patient navigator programs, significantly improve adherence. Behavioral economics interventions, such as “opt-out” framing (where patients are automatically enrolled unless they actively decline) further enhance participation. However, the elimination of financial incentives does not necessarily lead to increased participation. These strategies together result in over 50% adherence, leading to increased early detection, a cost-saving surveillance model, and substantial gains in quality-adjusted life years (QALYs).
Figure 7. Socioeconomic barriers to equitable hepatocellular carcinoma (HCC) care. The key socioeconomic and geographic disparities that impede equitable access to hepatocellular carcinoma (HCC) care are illustrated. At the top, disparities in insurance status lead to later-stage tumor diagnoses in uninsured patients compared to those with insurance, who are more likely to be diagnosed at an earlier stage (~30% higher late-stage presentation in uninsured). Geographic barriers, such as the distance (>30 miles) between rural communities and medical centers, further exacerbate access to care, with urban residents having better access. The bottom section focuses on global disparities, particularly in low- and middle-income countries (LMICs), where challenges such as high burdens of hepatitis B virus (HBV) and hepatitis C virus (HCV), resource scarcity, and weak health systems hinder effective care. Solutions to these issues include international cooperation, price negotiations, and the implementation of cost-effective surveillance and public health programs, which are essential to improving care access in disadvantaged regions. At the bottom, a proposed framework for embedding equity considerations into health economic modeling of HCC surveillance is presented. The outputs can then be synthesized to assess how surveillance interventions perform in terms of both overall efficiency and equity across populations. ICER, incremental cost-effectiveness ratio.
Figure 8. HCC surveillance: summary and future outlook. (A) The current challenges and future strategies for hepatocellular carcinoma (HCC) surveillance are illustrated. On the left, the limitations of standard surveillance methods—such as low patient adherence and reduced sensitivity, especially in populations with metabolic-associated steatotic liver disease (MASLD)—are highlighted. The central section presents the three pillars of future strategy: (1) advanced imaging technologies, (2) novel biomarkers, and (3) AI-assisted detection, all aimed at improving diagnostic accuracy and early detection. Below, implementation strategies, including adherence strategies such as outreach and nudges, and a focus on health equity, are emphasized to address socio-economic and geographic disparities. The right section shows the integrated future solution, which aims to maximize early detection, improve survival, and achieve optimal cost-effectiveness while ensuring equitable access to HCC surveillance globally. (B) A cost-effective surveillance protocol for HCC based on annual risk assessment, incorporating current evidence. The left side depicts a decision pathway for surveillance, while the right side provides four supplementary points to enhance the understanding of the protocol. AFP, alpha-fetoprotein; AI, artificial intelligence; AMRI, abbreviated magnetic resonance imaging; CT, computed tomography; HBV, hepatitis B virus; HCV, hepatitis C virus; MRI, magnetic resonance imaging; NAFLD, non-alcoholic fatty liver disease; US, ultrasound.

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Hepatocellular carcinoma surveillance: a health economic evaluation
Characteristic West
 East
AASLD [6] EASL [7] APASL [8] KLCA [9] JSH [10] CNLC [11]
High-risk patients Child–Pugh A–B cirrhosis, any etiology Child-Pugh A–B cirrhosis, any etiology Cirrhotic hepatitis patients Chronic hepatitis B, chronic hepatitis C, or cirrhosis Cirrhosis, chronic hepatitis B, or chronic hepatitis C HBV and/or HCV infection, non-alcoholic steatohepatitis, cirrhosis from other causes, those who consume excessive amounts of alcohol, and/or those with a family history of liver cancer, especially males >40 years of age
 Hepatitis B Child–Pugh C cirrhosis, transplant candidate  HBV
 Hepatitis C (viremic or post-SVR)  HCV
 Alcohol associated cirrhosis Non-cirrhotic patients chronic HBV infection, at intermediate or high risk for HCC advanced fibrosis, regardless of the underlying etiology  NASH
 Nonalcoholic steatohepatitis  Genetic hemochromatosis
 Other etiologies  Primary biliary cirrhosis
Child–Pugh C cirrhosis, transplant candidate  A1AT deficiency
Non-cirrhotic chronic hepatitis B  Autoimmune hepatitis
 Man from endemic country* age >40 yr  Other etiologies
 Woman from endemic country* age >50 yr Chronic HBV carriers
 Person from Africa at earlier age†  Noncirrhotic (HBsAg positive)
 Family history of HCC  Asian females >50 yr
 PAGE-B score >10‡  Asian males >40 yr
Insufficient risk and in need of risk stratification models/biomarkers  Africans aged >20 yr
 Hepatitis C and stage 3 fibrosis  History of HCC in the family
 Noncirrhotic NAFLD
Modality Ultrasound+AFP Ultrasound Ultrasound+AFP Ultrasound+AFP Ultrasound+tumor marker Ultrasound+AFP
Interval (mo) 6 6 6 6 3–6 6
Characteristic Description
Strength [59,60] NC-AMRI:
 1. Most time- and cost-saving;
 2. No contrast related risk.
AMRI with gadoxetic acid:
 1. Shorter scan time than full MR.
DCE-AMRI:
 1. Shorter scan time than full MRl;
 2. Evaluation of vascular thrombus;
 3. No requirement of a recall test.
Weakness [59,60] NC-AMRI:
 1. Heavily dependent on DWI (prone to artifacts);
 2. Limited evaluation for vascular thrombus;
 3. Additional recall tests needed.
AMRI with gadoxetic acid:
 1. Additional recall tests needed;
 2. Contrast related risk.
DCE-AMRI:
 1. Contrast related risk.
Meta-analyses of diagnostic performance Author Year Number of studies Pooled sensitivity (%)** Pooled specificity (%)**
Gupta et al. [61] 2021 15 86 (84–88) 94 (91–96)
Kim et al. [62] 2021 10 86 (80–90) 96 (93–98)
Lu et al. [63] 2021 15 84 (78–88) 94 (90–95)
Kim et al. [64] 2021 4 87 (80–94) 94 (90–98)
Chan et al. [65] 2022 22 86.8 (83.9–89.4) 90.3 (87.3–92.7)
Maung et al. [66] 2024 27 86 (83–88) 92 (90–94)
Wang et al. [67] 2025 19 85 (83–87) 93 (91–94)
Ongoing cost-effectiveness trial FASTRAK: ClinicaTrials.gov (NCT05095714)*,[68]
Health-Economic recommendations AMRI used in patients at high risk of HCC (>1.8% per year)§,[44,45,69-71]
Ultrasound visualization score-based approach with AMRI∥,[72]
Year First author Origin Patients Surveillance method Model Cost-effectiveness results Cost-effectiveness conclusion
2008 Nouso et al. [123] Japan 45-year-old patients with Child–Pugh class A cirrhosis Ultrasound every 6 months Markov model The ICER was $29,900/QALY in a base-case analysis (annual HCC incidence=4%). The cost-effectiveness of HCC surveillance varies between patient subgroups and depends critically on the rate of incidental detection, HCC incidence, and adoption of liver transplantation.
2008 Paul et al. [124] India 194 cirrhotic patients 6-monthly ultrasound and AFP, yearly triple-phase CT Yes, not specific Cost per HCC case detected: $280 (hospital perspective). Direct medical cost (EASL protocol): $1,510/case. The cost of the HCC surveillance program is exorbitant for India and possibly other low/middle-income countries.
2012 Tanaka et al. [125] Japan HCV-related liver cirrhosis patients No surveillance, ultrasound, and contrast-enhanced ultrasound Markov model Compared to ultrasound surveillance, contrast-enhanced ultrasound had an ICER of $24,250/QALY. Both were cost-effective vs. no surveillance. Contrast-enhanced ultrasound surveillance is a cost-effective strategy for liver cirrhosis patients, even compared to standard ultrasound surveillance.
2014 Sangmala et al. [126] Thailand Thai chronic HBV patients Semi-annual ultrasound vs. semi-annual ultrasound+AFP Markov model ICERs vs. no program: ultrasound 118,796 Thai Baht/QALY; ultrasound+AFP 123,451 Thai Baht/QALY. Both ultrasound and ultrasound+AFP are cost-effective. Semi-annual ultrasound is recommended due to lower budget impact.
2016 Kuo et al. [127] Taiwan General population based cohorts in an area with high HCC incidence No surveillance, two-stage biomarker-ultrasound, and mass screening with ultrasound Markov model ICERs vs. no screening: Mass screening with ultrasound $39,825 per life-year gained; two-stage biomarker-ultrasound $49,733 per life-year gained. Mass screening using ultrasound is more cost-effective than two-stage biomarker ultrasound screening. Optimal strategy is biennial screening starting at age 50.
2019 Kim et al. [45] South Korea Patients with compensated cirrhosis (mainly HBV-associated) Semiannual surveillance using MRI with liver-specific contrast vs. ultrasound Markov model At 3% annual HCC incidence, MRI had an ICER of $25,202/QALY compared to ultrasound. ICER was 1.81%. Semiannual MRI surveillance may be more cost-effective than ultrasound in patients with compensated cirrhosis at sufficiently high HCC risk.
2021 Zhang et al. [128] China Simulated cohort of 40-year-old patients with chronic hepatitis B cirrhosis anti-tumor associated antigen autoantibody (TAAb)+AFP vs. ultrasound+AFP Markov model Compared with ultrasound+AFP, TAAb+AFP had an ICER of 127,635 yuan/QALY. It is cost-effective to use TAAb+AFP for early screening in the Chinese population with chronic hepatitis B cirrhosis.
2024 Tan et al. [57] Singapore Simulated 40-year-old at-risk patient cohort No surveillance, ultrasound, and non-contrast-enhanced MRI Markov model The ICER for non-contrast-enhanced MRI compared to ultrasound was SGD 9,479/QALY. Despite superior diagnostic accuracy, non-contrast-enhanced MRI is a less cost-effective strategy than ultrasound for HCC surveillance in the general at-risk population.
2024 Decharatanachart et al. [69] Thailand Cirrhotic patients in Thailand and the United States Non-contrast abbreviated MRI vs. ultrasound+AFP Markov model ICER for abbreviated MRI vs. ultrasound+AFP: $3,667/QALY in Thailand and $37,062/QALY in the United States. Non-contrast abbreviated MRI is a cost-effective strategy for HCC surveillance, especially in those with high HCC risks.
2024 Fang et al. [41] China Chronic hepatitis B patients with virological remission (cirrhosis or advanced fibrosis) Biannual vs. annual surveillance with ultrasound+AFP Markov model Annual surveillance was cost-effective for cirrhosis patients aged 55–70 (ICER $28,076/QALY) and for advanced fibrosis patients aged 40–75 (ICER $4,984/QALY). Annual surveillance was a more cost-effective option than biannual surveillance, providing substantial economic benefits for a slight reduction in effectiveness.
2024 Kowada [95] Japan 50-year-old diabetic patients with MASLD, risk-stratified Various methods including ultrasound, CT, and MRI Markov model In obese diabetic patients with MASH, gadoxetic acid-enhanced MRI was more cost-effective than no screening (ICER, $49,160 per QALY gained). For diabetic patients with MASH cirrhosis, gadoxetic acid-enhanced MRI yields the greatest cost-saving with the highest QALYs and averts the most HCC-related deaths.
2025 Decharatanachart et al. [129] Thailand MASLD patients in Thailand and the United States Using non-invasive tests (FIB-4, VCTE) to initiate HCC surveillance Markov model The FIB-4/VCTE strategy (ICER was $21,113/QALY) was the most cost-effective approach across all patient groups. Using FIB-4/VCTE to initiate HCC surveillance is cost-effective for MASLD patients. FIB-4 alone is a cost-effective alternative if VCTE is unavailable.
2025 Saeoui et al. [130] Thailand Patients with chronic hepatitis B Ultrasound+AFP vs. biomarker strategies (GAAD, GALAD, ASAP) Markov model ASAP every 6 months was the most cost-effective strategy, with an ICER of 76,447 Thai Baht/QALY vs. no surveillance. ASAP every 6 months is the most cost-effective HCC surveillance strategy for patients with chronic hepatitis B, especially for resource-limited settings.
2025 Chen et al. [131] China Chronic hepatitis B cohorts in China, risk-stratified Various active surveillance strategies vs. no surveillance Markov model All surveillance strategies, except quinquennial, were cost-effective for high-risk groups (ICER $28,448–$36,073/QALY). No strategy was cost-effective for the low-risk group. The cost-effectiveness of HCC surveillance in chronic hepatitis B patients varies by risk. A risk-stratified approach could optimize resource allocation.
Table 1. Surveillance modalities as per Western and Eastern guidelines

A1AT, alpha-1 antitrypsin; AASLD, American Association for the Study of Liver Diseases; AFP, alpha-fetoprotein; APASL, Asian Pacific Association for the Study of the Liver; CNLC, China Liver Cancer Staging; EASL, European Association for the Study of the Liver; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; JSH, Japan Society of Hepatology; KLCA, Korean Liver Cancer Association; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; PAGE-B, platelet, age, gender–hepatitis B score; SVR, sustained virologic response.

Endemic country as defined by AASLD hepatitis B virus guidance.

Surveillance can be initiated as early as third decade of life given median age 46 years at HCC diagnosis.

Other risk calculators can be considered, although PAGE-B has been validated in Western populations on antiviral therapy.

Table 2. Summary of AMRI for HCC surveillance

AMRI, abbreviated magnetic resonance imaging; DCE-AMRI, dynamic contrast-enhanced AMRI; DWI, diffusion-weighted imaging; HCC, hepatocellular carcinoma; NC-AMRI, non-contrast AMRI; T2DM, type 2 diabetes mellitus.

The hypothesis posits that employing AMRI as a screening examination for patients with a high risk of HCC (greater than 3% per annum)could enhance the detection rates of tumors at an early stage, amenable to curative treatment, and further demonstrate its costeffectiveness within this demographic.

Risk stratification shall be established and validated through future research, encompassing models that integrate clinical and laboratory assessments.

An investigation was conducted utilizing a Markov model to simulate the outcomes for adults diagnosed with compensated non-alcoholic fatty liver disease (NAFLD) cirrhosis in the United States who are subjected to HCC screening. The study compared various screening strategies, including the combination of ultrasound and visualization score, ultrasound alone, and the absence of surveillance. The analysis revealed that among patients with NAFLD cirrhosis, the strategy incorporating an ultrasound visualization score in conjunction with aMRI was the most cost-effective. This approach yielded an incremental cost-effectiveness ratio (ICER) of $59,005 in comparison to the strategy of no surveillance.

95% confidence intervals.

Table 3. Selected studies on the health economics of HCC screening in Asia

Origins outside Asia are listed in Supplementary Table 2.

AFP, alpha-fetoprotein; ASAP, age, sex, AFP, and PIVKA-II; CT, computed tomography; EASL, European Association for the Study of the Liver; FIB-4, fibrosis-4 index; GAAD, gender, age, AFP, and DCP; GALAD, gender, age, AFP, AFP-L3, and DCP; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; ICER, incremental costeffectiveness ratio; MASH, metabolic dysfunction–associated steatohepatitis; MASLD, metabolic-dysfunction associated steatotic liver disease; MRI, magnetic resonance imaging; PIVKA-II, protein induced by vitamin K absence or antagonist-II; QALY, quality-adjusted life year; TAAb, tumor-associated antigen autoantibody; VCTE, vibration-controlled transient elastography.

Table 1.

Table 2.

Table 3.

Clin Mol Hepatol : Clinical and Molecular Hepatology
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