Costs and health outcomes of liver transplantation for hepatocellular carcinoma: a scoping review

Abstract

Background

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for 70–90% of all cases. Liver transplantation has demonstrated superior survival rates compared to surgery; however, there is a significant knowledge gap regarding the costs and outcomes across different healthcare settings and patient populations. This scoping review aimed to map the literature on the costs associated with hepatocellular carcinoma (HCC) and liver transplantation in patients with hepatocellular carcinoma (HCC).

Methods

We conducted a scoping review of studies published between 2019 and 2024 using PubMed, Embase, Scopus, LILACS, and Google Scholar. Data extraction focused on study characteristics, economic perspective, time horizon, discounting practices, cost components, data sources, and reported clinical outcomes. A qualitative descriptive synthesis was performed to characterize methodological approaches used to assess costs and outcomes.

Results

Fifteen studies were included, including 8 cost analyses and 7 cost-effectiveness studies. Study perspective was explicitly reported in 8 studies (53.3%), including 5 from the health system perspective and 3 from the payer perspective. Time horizons ranged from 3 years to lifetime. Among economic evaluations that reported discounting, annual discount rates ranged from 3% to 5%. Direct costs were assessed in 9 studies (60.0%), and institutional or hospital-based data sources were the most commonly used.

Conclusion

The included studies showed substantial methodological variation in perspective, time horizon, costing approach, and outcome definitions, which limited cross-study comparability. More standardized economic reporting is needed to strengthen future evidence on liver transplantation for HCC and support resource allocation decisions.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12962-026-00759-4.

Introduction

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for 70–90% of all cases [1, 2]. The global incidence doubled between 1990 and 2016, from 471,000 to 1,008,000 new diagnoses [3]. In 2022, approximately 20 million new cancer cases were registered globally, with HCC accounting for nearly 850,000 new diagnoses and 800,00 deaths [4, 5]. Mortality and disease burden projections indicate that liver cancer will be the tenth leading cause of death among low- and middle-income countries, accounting for 2.2% of all cancer deaths globally by 2030 [6].

HCC treatment encompasses a broad therapeutic spectrum, ranging from active surveillance to curative interventions, such as surgical resection, ablation, transarterial chemoembolization, and liver transplantation, the latter being considered the optimal treatment for selected patients with HCC [7, 8]. However, while evidence of the clinical effectiveness of these interventions has been widely documented, there is a considerable gap in the systematic understanding of the costs associated with HCC treatment, specifically with liver transplantation. The disease imposes a high economic burden on health systems [9–11].

Cost estimation shows high heterogeneity, marked in terms of methods, variables considered, and contexts studied, making it difficult to establish the main elements contributing to care costs, compare results, and make informed decisions. Therefore, we conducted a scoping review aimed at mapping the literature on the costs associated with hepatocellular carcinoma (HCC) and liver transplantation in patients with HCC. This synthesizes costs, identifies knowledge gaps, and provides a solid foundation for future systematic reviews and new primary research aimed at developing cost and cost-effectiveness models.

Materials and methods

This scoping review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The review question guiding this study was: What methodological approaches have been used to estimate the costs, clinical characteristics, and health outcomes of patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT)? The review specifically focused on methods for cost identification, measurement, and valuation, as well as the variables used to estimate costs and outcomes across different healthcare settings and populations.

Information sources and search strategy

We conducted an updated and systematic search of PubMed, Scopus, Embase, LILACS, and Google Scholar for studies related to HCC, liver transplantation, economic evaluation, and clinical outcomes. The search strategy was developed around three core concepts: (1) hepatocellular carcinoma, (2) liver transplantation, and (3) costs/economic evaluation. Controlled vocabulary terms (MeSH and Emtree, where applicable) and free-text terms were combined using Boolean operators and adapted to each database. The search strategy was developed and iteratively refined by the review team through pilot searches across databases. No formal consultation with a medical librarian or information specialist was undertaken.

The search period spanned from June 6, 2019, to June 12, 2024. This time restriction was prespecified in the review protocol and was intended to capture contemporary evidence reflecting current liver transplantation practices, recent allocation and reimbursement frameworks, and modern approaches to economic evaluation. Electronic searches were complemented by manual screening (snowballing) of reference lists from included studies and relevant specialized journals. The review protocol, including the detailed search strategy, was published previously [12].

Eligibility criteria and study selection

We included original research evaluating costs, economic outcomes, or clinical outcomes in adults (≥ 18 years) with HCC undergoing LT. Only full-text articles published in peer-reviewed journals were considered, with no restrictions on language or region. We excluded abstracts, conference proceedings, narrative reviews, systematic reviews, letters, editorials, and book chapters. Two reviewers independently screened titles, abstracts, and full texts (UPB, AF). Disagreements were resolved through discussion with a third reviewer (DRG).

Data charting

Two reviewers independently and in parallel charted data using a standardized extraction form. Because this was a scoping review, no single primary endpoint was prespecified for quantitative synthesis. Instead, we extracted a predefined set of methodological, economic, and clinical variables to map the range of approaches used across studies.

Extracted items included country, healthcare context, population characteristics, study type (cost analysis or economic evaluation), study perspective, cost components, clinical variables, time horizon, discounting practices, inflation adjustment, comparators, methods for valuing costs and effectiveness, modeling techniques, reported economic outcomes (mean cost, incremental cost-effectiveness ratios, cost per life-year or quality-adjusted life-year where available), clinical outcomes, and uncertainty analyses. Discrepancies were resolved through discussion with a third reviewer.

Synthesis of results

A qualitative descriptive synthesis was conducted to characterize the methodological approaches used to assess costs and clinical outcomes. Given the anticipated heterogeneity in study design, currencies, costing years, healthcare reimbursement systems, and analytical methods, we did not perform formal cost standardization or cross-country quantitative comparisons. Instead, these elements were extracted and synthesized descriptively in order to preserve contextual interpretation and align with the scoping review objective of mapping methodological variation rather than generating pooled estimates. Consistent with PRISMA-ScR guidance, risk of bias was not used as an exclusion criterion [13].

Ethics approval

As this study was based exclusively on data extracted from published literature and did not involve human participants or identifiable individual-level data, formal ethics approval was not required. Nevertheless, the project was reviewed and approved by the Ethics Committee of the Hospital San Vicente Fundación Rionegro (minutes 11-2023, April 2023).

Results

To improve interpretability in line with the scoping review objective, we organized the extracted data into three predefined domains: (1) study characteristics, including country, healthcare setting, population, intervention, and comparator; (2) methodological and economic characteristics, including type of economic study, perspective, time horizon, discounting, currency and costing year, cost categories, and analytical/modeling approach; and (3) reported economic and clinical outcomes, including total costs, cost-effectiveness outcomes (quality-adjusted life-years [QALYs] and incremental cost-effectiveness ratios [ICERs], when available), survival-related outcomes, and post-transplant outcomes.

Screening results

A total of 23 records were identified through database searching and supplementary methods. After screening and eligibility assessment, 15 studies were included in the final scoping review and data charting (Fig. 1). Of these, 8 (53%) were cost studies [10–17] and 47% were cost-effectiveness studies [22–28].

Fig. 1.

PRISMA flow diagram of study selection

The 15 included studies were conducted across multiple settings, most commonly in the United States (7/15, 46.7%), followed by Germany (2/15, 13.3%) and South Korea (2/15, 13.3%), with one study each from China, Spain, Brazil, and a multicountry European analysis (France, Italy, Spain, and the UK) (Table 1).

Table 1.

Characteristics of the included studies

Study (year)	Country	Currency and year of cost analysis	Time horizon	Disease stage	Population	Perspective	Type of economic evaluation	Type of costs	Cost type description	Intervention	Comparator
Desai (2024) [14]	USA	USD, 2020	15 years	Patients with HCC	Adults (ages 18–64 years) with a new diagnosis of HCC	Not mentioned	Cost analysis	Direct and Indirect cost	Inpatient and outpatient costs	Not applied	Not applied
Gidwani-Marszowski (2019) [15]	USA	USD, 2014	Not mentioned	Patients with HCV + HCC	Veterans with HCV	Health care system	Cost analysis	Not applied	Outpatient and inpatient medial/surgery and behavioral health, HCV Rx cost, non-HCV Rx cost	Not applied	Not applied
Gundlach (2022) [16]	Germany	Euro, not mentioned a date exactly	9 years	Patient with HCC in waiting list with LTs (Milan criteria, such as within the UCSF criteria)	Patients with HCC in waiting list for LTs	Not mentioned	Cost analysis	Direct cost	Hospitalization, liver transplant	Not mentioned	labMELD and matchMELD
Harries (2019) [17]	Germany	Euro, not mentioned a date exactly	3 years	Not mentioned	Patients with HCC who received a LT	Perspective of the payer	Cost analysis	Not mentioned	Outpatient clinic care, inpatient hospital care and inpatient rehabilitation care; prescription of immunosuppression and of other medications	Not applied	Not applied
Pollock (2020) [21]	France, Italy, Spain, UK	Euro and GBP, 2018	3 years	patients with HCC stages B and C	Patients with unresectable HCC	Healthcare payer perspectives	Cost analysis	Direct cost	Costs divided across seven categories: implantable device costs (covering the cost of the SIR-Spheres Y-90 resin microspheres), hospital care and intervention room costs (covering the costs of the SIRT work-up and treatment), drug costs, adverse event costs, follow-up and drug administration costs, curative intent treatment costs, and end of life care costs	SIRT with SIR-SpheresY-90	TKIs
Skill (2019) [18]	USA	USD, september of 2017	Not mentioned	Not mentioned	Patients with HCV and HCC	Not mentioned	Cost analysis	Direct cost	Costs were categorized by radiology, surgery, interventional radiology, drugs (i.e., chemotherapy, immunosuppression), inpatient services, and other	LT	LR
Souza (2019) [19]	Brazil	USD, 9/June/2016, US$1.00 = R$3.38	Not mentioned	Patient with advanced liver disease for different causes such as: HCV, HCC, alcohol, HBV, fulminant hepatitis	patients who underwent deceased-donor LTx	Not mentioned	Cost analysis	Direct and indirect cost	Costs during hospitalization, discharge, death, and retransplantation (immediate pretransplant kit, specialized units (routine tests, specific procedures, specialized tests, physical therapy, immunosupression, transplant team fees), surgical unit, intensive care unit and inpatient unit)	Not applied	Not applied
Wong (2021) [20]	USA	USD, 2016	10 years	Any stage of NAFLD /NASH	Adults with NAFLD or NASH with or without LTs advanced liver diseases, CC, HCC, DCC	Not mentioned	Cost analysis	Direct and indirect cost	Inpatient and outpatient medical, and outpatient pharmacy claims, (costs were calculated from the adjudicated claims containing the provider-paid and patient-paid components (copayment, deductible, and coinsurance).	Not mentioned	Not applied
Hessheimer (2023) [23]	Spain	Euro, 2020	The lifetime of the patient	Patients with HCC who received LT treatment	Post-transplant HCC patients	National Healthcare System	Cost-effectiveness and Cost-utility Analysis	Direct cost	Outpatient clinic visits, laboratory analyses, medications, treatments, and surveillance	Surveillance	Non-surveillance (standard follow-up)
Kim H (2019) [24]	South Korea	KRW and converted to USD, 2 January 2018, $1 USD = 1,063.5 KRW	20 years	Patients with cirrhosis are at high risk of HCC. Any stage classified with BCLC system	Patients with compensated cirrhosis	Healthcare system	Cost-effectiveness and Cost-utility Analysis	Direct cost	Direct medical costs included hospitalization, consultation, medication, examination, and other treatment fees. Direct non-medical costs, which comprised transportation costs resulting from hospital visits, were included to reflect the total costs per patient	MRI	Liver US
Kim KD (2021) [25]	South Korea	KRW, 2018	17 years	Patients who underwent to LT	patients post-LTs receiving anti-HBc-positive grafts	Not mentioned	Cost-effectiveness analysis	Direct cost	Not mentioned	NAs	NAs and HBIG
Li (2021) [26]	China	USD, 2019, 1 USD = RMB 6.77	8 years	Patients with HCC	patients with any stage of HCC	Chinese health system	Cost-effectiveness analysis	Direct cost	Cost of the induction and subsequent treatments, examination (such as laboratory examination, computed tomography, and magnetic resonance imaging), hospitalization, hepatic artery catheterization, n hepatectomy, treatment for grade 3–4 severe adverse events (SAEs) and BSC	soraHAIC + FOLFOX	only soraHAIC
Parikh (2020) [27]	USA	USD, 2018	Lifetime horizon	Patients with cirrhosis	patients with compensated cirrhosis	No mentioned	Cost-effectiveness analysis	Not mentioned	Not mentioned	Three surveillance strategies were modelled: no surveillance, semi-annual US, and semi-annual US with AFP	Between strategies of surveillance
Patel (2023) [28]	USA	USD, 2021	5 years	Patients had unresectable early- to intermediate-stage HCC (BCLC stage A or B)	Patients with unresectable early- to intermediate-stage HCC	US healthcare perspective	Cost-effectiveness analysis	Direct cost	Costs to the hospital (e.g. device, drug acquisition costs, costs to treat adverse events and monitoring costs	TARE	cTACE and DEE-TACE
Wu (2023) [22]	USA	USD, 2022	5 years	Patients undergoing DS by LRT	Patients with any stage of HCC	Healthcare payer perspectives	Cost-effectiveness analysis	Direct cost	Cost of complications was assumed to be the mean cost of a hospital stay	TACE	TARE

LTs: liver transplant; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HBV: hepatitis B virus; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; CC: cirrhosis; DCC: decompensated cirrhosis; BCLC: Barcelona Clinic Liver Cancer; LRT: locoregional therapy; labMELD: laboratory values last transmitted to ET before organ offer, Model for End-Stage Liver Disease; matchMELD: the labMELD or standard/non-standard exceptional MELD applied in allocation, Model for End-Stage Liver Disease; AFP: alpha-fetoprotein; US: ultrasonography; MRI: magnetic resonance imaging; NAs: nucleotide analogues; HBIG: hepatitis B immunoglobulin; soraHAIC: 400 mg sorafenib twice daily for 21 days; TARE: transarterial radioembolization; cTACE: conventional transarterial chemoembolization; DEE-TACE: drug-eluting beads chemoembolization; SIRT: selective internal radiation therapy; SIR-Spheres Y-90: SIR-Spheres yttrium-90 resin microspheres; TKIs: tyrosine kinase inhibitors such as sorafenib and lenvatinib; TACE: transarterial chemoembolization; LR: liver resection; KRW: Korean won; GBP: pounds sterling; RMB: Renminbi; R: real; USD: US dollar; UNOS-DS criteria: (1) 1 lesion > 5 cm but ≤ 8 cm, (2) 2 or 3 lesions with at least 1 lesion > 3 cm, each lesion ≤ 5 cm, and total diameter ≤ 8 cm, or (3) 4 or 5 lesions each < 3 cm, total diameter ≤ 8 cm; DS: downstaging

Characteristics of the included studies

Variables and comorbidities

Clinical and population characteristics varied substantially across studies and included demographic variables, liver disease severity measures, transplant eligibility criteria, tumor burden indicators, and selected comorbidities. Commonly reported variables included age, sex, Model for End-stage Liver Disease (MELD)-related measures, waiting-list time, tumor size and number of lesions, and transplant eligibility according to Milan or University of California San Francisco (UCSF) criteria. Detailed clinical variables and comorbidity profiles are provided in the Supplementary Material.

Regarding comorbidities, 13.3% of studies included: cardiovascular problems, kidney disease, and diabetes mellitus [14, 15], 6.65% included personal history of seizures, psychosis, mental illness, and heart failure [15]; 6.65% included presence of hepatic encephalopathy and portal hypertension [16], 60% did not mention comorbidities within their target population [17–22, 25], 6.65% mentioned presence of hepatitis B virus [24], and two studies mentioned being over 65 years old as a comorbidity [14, 28] (Supplementary material).

Interventions evaluated

Among the different interventions evaluated, we identified: two studies on surveillance of transplanted patients [23, 27], performing liver ultrasound vs. contrast-enhanced liver MRI for early detection of HCC [24], use of soraHAIC alone vs. soraHAIC plus FOLFOX [26], performing liver ultrasound and alpha-fetoprotein (AFP) [27], use of transarterial radioembolization (TARE) vs. conventional transarterial chemoembolization (cTACE), and drug-eluting bead chemoembolization (DEE-TACE) [22, 28], performing liver transplant vs. liver resection [18], SIRT (selective internal radiation therapy) with SIR-Spheres yttrium-90 (Y-90) resin microspheres vs. TKIs (tyrosine kinase inhibitors) such as sorafenib and lenvatinib [21].

In cost-effectiveness studies, the studied population consisted of patients with hepatocellular carcinoma [22, 26], post-transplant, patients with compensated and uncompensated cirrhosis [20, 24, 27], transplanted patients [25], patients with unresectable HCC [28]. Cost studies analyzed patients with new diagnosis of HCC [14], patients with HCC and hepatitis C [15, 18], patients on waiting list or who received liver transplant [16, 17, 19] unresectable HCC [21].

Methodological results

Methodological and economic characteristics were heterogeneous across the included studies. In 8 studies, the study perspective was identified; in 5 studies, the perspective was from the health system [15, 23, 24, 26, 28], and in others the payer’s perspective [17, 21, 22]. These studies evaluated time horizons from three years to the lifetime horizon and discount rates between 3% and 5%. No study explicitly reported the use of micro-costing methods or standardized costing instruments. The type of costs evaluated in 60% (9/15) were direct costs [16, 18, 21–26], these included medical consultations, laboratories, medications, treatments, use of medical devices, chemotherapy and immunosuppressive medications, interventional radiology, diagnostic imaging (CT scan, MRI, US, etc.); 3 studies report mixed costs (Direct and indirect) [14, 19, 20] (Fig. 2).

Fig. 2.

Methodological characteristics of included studies

For cost-effectiveness studies, the statistical methods used and the measurement of QALYs were obtained from the literature. The analytical method used was a Markov model with Monte Carlo simulation. Regarding probability distributions, the beta distribution was used for the estimation of utilities, disutilities, and proportions, and the estimation of utilities in each health state [23, 24, 26–28]; cost: gamma distribution [23, 24] and triangular distribution [27]; survival: Weibull distribution [21, 26], Gompertz [21], and others (exponential, log-logistic, lognormal) [21, 28]. In descriptive analyses and regression models: Chi-square, Wilcoxon test, Kruskal-Wallis [14, 17, 25]; generalized estimating equations [15]; Kaplan–Meier analysis followed by a log-rank test or Cox regression [16, 25]; logistic regression análisis [16, 25]; generalized linear model [20]. The cost and cost-effectiveness results are shown in (Supplementary material).

Discussion

In this scoping review, 15 cost and cost-effectiveness studies related to hepatocarcinoma (HCC) and liver transplantation were identified. 53% (8/15) were cost studies, and 47% (7/15) were cost-effectiveness evaluations. Most of these studies (40%) were conducted in the United States, followed by Germany and South Korea (13.3% each). Analyses predominantly used the health system or payer perspective, and 60% of studies only estimated direct costs related to medical care, with horizons ranging from three years to lifetime and discount rates of 3–5%. The cost ranges were broad; liver transplantation presented median costs between €30,300 and €43,500 per procedure [16]. Similarly, a pattern of increased costs associated with liver disease progression was observed. Gidwani-Marszowski et al. simulated how annual costs increase as patients progress from non-advanced fibrosis (US $17,556) to advanced fibrosis (US $20,791), hepatocellular carcinoma (US $46,089), liver transplant (US $261,959), and post-transplant (US$ 18,643 per year) [15].

From a methodological perspective, the included studies show the predominant use of Markov models, which are appropriate for chronic pathologies such as hepatocarcinoma, as they allow representation of transitions between mutually exclusive clinical states, incorporation of costs and outcomes in each cycle, and application of appropriate temporal discounting [29]. The choice of specific distributions to characterize parameter uncertainty reinforces this rigor: beta for probabilities bounded between 0 and 1, gamma or triangular for positive and asymmetric costs, and parametric models such as Weibull or Gompertz for time-to-event, as recommended by the NICE guidelines for survival extrapolation [30]. These choices ensured the mathematical coherence of the inputs and facilitated probabilistic sensitivity analyses that supported the external validity of the results.

Similarly, the combination of Kaplan-Meier curves, log-rank tests, and Cox regression constitutes the standard for describing and comparing oncological survival, while generalized linear models (GLM) and GEE allow the estimation of covariate impact on costs, appropriately handling the skewed and heteroscedastic distribution of these data [31]. The integration of non-parametric tests (Wilcoxon, Kruskal-Wallis) and logistic regression has been widely used in cost and outcome estimations, capturing both bivariate and multivariable associations.

Regarding the results, a cost increase was observed as the disease progressed, from US $17,556 in non-advanced fibrosis to US $261,959 at the transplant stage, with subsequent reduction to US$ 18,643/year post-transplant. Similarly, studies reported a median liver transplantation cost in Germany of €30,300 − 43,500 [16], post-transplant surveillance in Spain showed a mean increase of €988 with a marginal gain of 0.026 QALY and an ICUR of 37,548 €/QALY, not cost-effective at the threshold of 25,000 €/QALY (17), surveillance with MRI vs. ultrasound was cost-effective only when the annual HCC incidence exceeded 1.81% (20), and TARE was dominant against cTACE (saving US $15,779 and + 0.33 QALY at 5 years) and cost-effective against DEE-TACE (ICER US $41,474/QALY) [28]. Economic evaluations have shown that locoregional interventions with higher initial costs (TARE) can be efficient in the medium term when they improve the quality of life or prolong survival. In surveillance, cost-effectiveness critically depends on HCC incidence and the local payment threshold, highlighting the need to contextualize models for each health system. These findings show a substantial and heterogeneous economic burden of HCC over the clinical course.

The strong cost increase when moving from advanced fibrosis to transplantation reflects the complexity of management during the terminal phases. However, the subsequent reduction suggests that transplantation can stabilize annual expenses, aligning with its potentially curative profile. Wong et al.‘s results on the percentage increase in costs according to liver disease progression (69% for NAFLD/NASH without advanced disease, 39% for compensated cirrhosis, 159% for decompensated cirrhosis, 172% for liver transplant, and 145% for hepatocarcinoma) provide evidence to prioritize preventive and early detection interventions that could mitigate this cost escalation [20].

In terms of clinical and public health implications, studies by Gundlach et al. and Harries et al. noted that factors such as elevated labMELD score (OR 1.042), need for reoperations (p < 0.001), infections with multidrug-resistant organisms (p = 0.020), need for dialysis (p = 0.017), prolonged surgical time (p = 0.012), and transfusions (p < 0.001) significantly increased transplant costs. On the labMELD scale, the cost increased by approximately €580 per additional point, highlighting the importance of considering this parameter for resource planning. These aspects are important for health systems seeking to optimize resource use in patients with HCC, especially those on transplant waiting lists. The median cost of liver transplantation varied between €30,300 (€17,200–€395,900) for patients with matchMELD and €43,500 (€17,800–€185,000) for patients with labMELD. Efficient management of nosocomial infections or prevention of complications can significantly reduce liver transplantation costs and improve both health outcomes and health system efficiency [16, 17].

Complementarily, Harries et al. found that the total median cost in their study population was €144,424 (range: €16,162–€887,418), with 75% of patients reaching treatment costs of €242,157, which was defined as the threshold for high-cost cases. For hospital care, a median of €94,902 (range: €12,486–€616,857) was recorded. Factors significantly associated with higher hospital costs were an elevated labMELD score (OR 1.042), subsequent retransplantation (OR 7.16), and patient mortality (OR 3.6). Additionally, each waiting day for transplantation had a significant impact on high treatment costs (OR 1.001), and patients with viral cirrhosis and hepatocarcinoma presented significantly higher medication costs (OR 21.62 and 7.43, respectively) [17].

Souza et al. reported that the mean cost of liver transplantation was US$17,367 ± 9,935, distributed by specialty unit: Surgical Unit and Specialized Units represented 31.9% (US$4,609) and 26.4% (US$4,296) of the total transplant cost, respectively, followed by 25.3% for ICU, 15% for hospitalization unit, and 1.4% for pre-transplant kit [19].

Regarding patient survival, Gundlach et al. found no significant differences in overall survival among patients according to transplant criteria used (p = 0.759) [16]. However, Kim et al. observed that the survival of patients transplanted with anti-HBc-positive grafts was comparable to that of those with anti-HBc-negative grafts, with 5-year survival rates of 73.5% and 77.4%, respectively [25]. Similarly, Li et al. analyzed the survival of patients treated with FOLFOX combined with sorafenib, showing an increase of 0.89 life years over the standard treatment with sorafenib, highlighting the potential of combining therapies to improve outcomes in patients with advanced HCC [26]. Skill et al., reported that average post-resection survival was 652 days, while post-transplant survival was 524 days [18]. Although the costs of transplantation are significantly higher, this procedure remains a crucial option for prolonging the lives of patients with HCC.

These findings highlight the importance of identifying key clinical characteristics, such as elevated labMELD scores or nosocomial infections, to inform prevention and management strategies in patients with HCC and potentially reduce long-term costs. Evidence on the cost-effectiveness of surveillance and treatment modalities may support resource-allocation decisions, including reserving MRI surveillance for high-incidence populations and prioritizing transarterial radioembolization over other locoregional therapies. From a health policy perspective, although liver transplantation entails substantial upfront costs, the associated reduction in long-term expenditures suggests potential economic benefits that should be considered in coverage and financing decisions. However, these conclusions should be interpreted with caution, as this scoping review was not designed to critically appraise study quality, underscoring the need for future systematic reviews with formal critical appraisal.

The variability in costs between different regions and health systems, as evidenced by the difference between transplant costs in American studies (US $261,959 according to Gidwani-Marszowski et al.) [15], European (€30,300 - €43,500 according to Gundlach et al.) [16] and Latin American (US $17,367 ± 9,935 according to Souza et al.) [19], highlights the need to develop local economic studies that reflect specific realities, as direct extrapolation of results between different contexts may not be appropriate.

Several methodological limitations affect the interpretability and policy relevance of the findings. Only 40% of studies incorporated indirect costs, likely underestimating the societal economic burden of hepatocellular carcinoma by prioritizing direct medical costs from a payer perspective. Considerable heterogeneity was observed in costing approaches and utility estimation methods, limiting the comparability of cost and cost-effectiveness results across studies. In addition, the predominance of retrospective designs raises concerns about selection bias and incomplete long-term cost capture. These limitations have important implications for decision-making, as country-specific costing methods and willingness-to-pay thresholds restrict cross-country comparisons, underscoring the need for future economic evaluations to adopt standardized reference case methodologies to improve comparability and support resource-allocation decisions [32].

Conclusion

This scoping review highlights considerable methodological variation across studies evaluating costs and outcomes in hepatocellular carcinoma and liver transplantation, particularly with respect to study perspective, time horizon, costing methods, and outcome definitions, thereby limiting direct comparability across settings. Although the included studies suggest that clinical and disease-related characteristics may influence both costs and outcomes, the available evidence remains heterogeneous in design and reporting. Greater standardization in cost identification, measurement, valuation, and outcome reporting is needed to improve the methodological consistency of future studies and to better support evidence-informed resource allocation in this field.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

HCC

Hepatocellular carcinoma

LT

Liver transplantation

QALY

Quality-adjusted life year

NASH

Non-alcoholic steatohepatitis

UCSF

University of California, San Francisco

sora-HAIC

Sorafenib plus hepatic arterial infusion chemotherapy

HCV

Hepatitis C virus

HBV

Hepatitis B virus

NAFLD

Nonalcoholic fatty liver disease

NASH

Nonalcoholic steatohepatitis

CC

Cirrhosis

DCC

Decompensated cirrhosis

BCLC

Barcelona Clinic Liver Cancer

LRT

Locoregional therapy

MELD

Model for End-Stage Liver Disease

labMELD

Laboratory values last transmitted to ET before organ offer, Model for End-Stage Liver Disease

matchMELD

The labMELD or standard/non-standard exceptional MELD applied in allocation, Model for End-Stage Liver Disease

AFP

Alpha-fetoprotein

US

Ultrasonography

MRI

Magnetic resonance imaging

NAs

Nucleotide analogues

HBIG

Hepatitis B immunoglobulin

TARE

Transarterial radioembolization

cTACE

Conventional transarterial chemoembolization

DEE-TACE

Drug-eluting beads chemoembolization

SIRT

Selective internal radiation therapy

SIR-Spheres Y-90

SIR-Spheres yttrium-90 resin microspheres

TKIs

Tyrosine kinase inhibitors such as sorafenib and Lenvatinib

TACE

Transarterial chemoembolization

LR

Liver resection

KRW

Korean won

GBP

Pounds sterling

RMB

Renminbi

R

Real

USD

US dollar

DS

Downstaging

Author contributions

Conceptualization: UPB, LGTR, YAB, AF, DRG. Data curation: UPB, LGTR, DRG. Formal analysis: YAB, AF, DRG. Investigation: UPB, LGTR, YAB, AF, DRG. Methodology: UPB, LGTR, YAB, AF, DRG. Project administration: UPB, YAB. Resources: UPB, LGTR, YAB. Supervision: DRG. Writing – original draft: UPB, LGTR, YAB, AF, DRG. Writing – review & editing: UPB, LGTR, YAB, AF, DRG.

Funding

This study was funded by the Ministry of Science, Technology and Innovation of Colombia (Project Code 98605, Call No. 934–2023). The funder had no role in the study design, execution, or decision to submit this manuscript.

Data availability

This study did not generate any primary individual-level data. All data used were obtained from previously published articles identified through the literature search. The aggregated data supporting the findings of this scoping review are included in this article and its supplementary material. The protocol for this review has been published previously and is publicly available: Palacios-Barahona U, Toro-Rendón LG, Agudelo-Berruecos Y, Fonseca-Niño A, Rojas-Gualdrón D. Costs and health outcomes of hepatocarcinoma and liver transplantation for hepatocarcinoma: scoping review protocol. F1000Research. 2025; 14:417.

Declarations

Ethics approval and consent to participate

This study is a systematic (scoping) review based exclusively on published and publicly available data; therefore, it did not require individual informed consent. The review forms part of a broader research project approved by the Ethics Committee of the Hospital San Vicente Fundación Rionegro (minutes 11-2023, April 2023).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.