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Study Protocol

Costs and health outcomes of hepatocarcinoma and liver transplantation for hepatocarcinoma: Scoping review protocol

[version 1; peer review: 1 approved]
Uriel Palacios-Barahona
https://orcid.org/0000-0002-3740-0353
1,2, Luis Guillermo Toro-Rendón3, Yuli Agudelo-Berruecos3, Angelica Fonseca-Niño4, Diego Rojas-Gualdrón
https://orcid.org/0000-0002-2293-0431
5
Uriel Palacios-Barahona
https://orcid.org/0000-0002-3740-0353
1,2, Luis Guillermo Toro-Rendón3, [...] Yuli Agudelo-Berruecos3, Angelica Fonseca-Niño4, Diego Rojas-Gualdrón
https://orcid.org/0000-0002-2293-0431
5
PUBLISHED 08 Apr 2025
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OPEN PEER REVIEW
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Abstract

Introduction

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for 70–80% of cases. Liver transplantation has demonstrated superior survival rates compared to surgery; however, there is a significant knowledge gap regarding costs and outcomes across different healthcare settings and populations.

Objective

This scoping review aimed to map the literature describing the costs associated with hepatocellular carcinoma (HCC) and liver transplantation in patients with hepatocellular carcinoma (HCC).

Methodology

This review will search for studies published between 2019 and 2024 in the PubMed, Embase, Scopus, LILACS, and Google Scholar databases. Data extraction included the study characteristics, cost variables, clinical outcomes, and methodology. A qualitative analysis of the papers will identify and describe the different methods used to assess the costs and clinical outcomes.

Expected Results

This review provides a summary of the literature related to the cost estimation and clinical outcomes of HCC and liver transplantation.

Keywords

Hepatocellular carcinoma, liver transplantation, cost and cost analysis, outcome assessment

Corresponding author: Uriel Palacios-Barahona
Competing interests: No competing interests were disclosed.
Grant information: 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.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright:  © 2025 Palacios-Barahona U et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Palacios-Barahona U, Toro-Rendón LG, Agudelo-Berruecos Y et al. Costs and health outcomes of hepatocarcinoma and liver transplantation for hepatocarcinoma: Scoping review protocol [version 1; peer review: 1 approved]. F1000Research 2025, 14:417 (https://doi.org/10.12688/f1000research.163517.1) First published: 08 Apr 2025, 14:417 (https://doi.org/10.12688/f1000research.163517.1) Latest published: 08 Apr 2025, 14:417 (https://doi.org/10.12688/f1000research.163517.1)

Introduction

Hepatocellular carcinoma (HCC), also known as hepatocarcinoma, is the most common type of primary liver cancer, accounting for 70-80% of all cases.1 Globally, the incidence of HCC has increased by 114%, from 471,000 cases in 1990 to 1,008,000 in 2016.2 In projections of mortality and disease burden from 2002 to 2030, liver cancer is expected to become the tenth leading cause of death among middle- and low-income countries, representing 2.2% of cases worldwide.3

Among the most significant risk factors associated with the rising incidence of HCC, hepatitis B carriers have a 10–25% lifetime risk of developing HCC.4,5 The prevalence of cirrhosis in individuals with HCC is approximately 80% in autopsy series worldwide.6 The incidence of HCC in patients with known cirrhosis is 2.5% per year.7 The risk of liver cancer increases by approximately 2–4 times among individuals consuming more than 60–80 g/day of alcohol.8 Other identified factors include non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH).9

Curative treatment for HCC is based on surgical resection or liver transplantation, and diagnosis is made at an early stage of the disease. However, most patients with HCC present with advanced disease and underlying liver dysfunction, limiting their curative options. In such cases, surgery is feasible in only approximately 15% of HCC patients, and the 5-year survival rate after potentially curative resection ranges from 33% to 50%.10 In contrast, orthotopic liver transplantation (OLT) for HCC within the Milan criteria has demonstrated a 5-year survival rate exceeding 70% with a recurrence rate below 15%.7,11–13

Oncological research has primarily focused on the outcomes associated with pharmacological treatment and radiotherapy. This trend has created significant knowledge gaps, particularly regarding resource utilization, associated costs, and treatment outcomes in terms of survival within the context of routine clinical practice in middle- and low-income countries. In these settings, the technology available for managing HCC may differ significantly from that used in high-income countries, making it necessary to describe the variables and resources included in the cost estimation and cost-of-illness analyses.

Given the high heterogeneity present in cost studies related to liver transplantation in patients with HCC, this scoping review aims to identify the different methods used in cost estimation, the variables of interest considered, and the outcomes associated with this procedure across various contexts and populations. This scoping review provides a summary of the literature related to cost estimation, the structural characteristics measured, the selection of clinical outcome criteria studied, and the current landscape of HCC costs and liver transplantation in HCC patients. Additionally, it will serve as a foundation for future systematic reviews and inform primary research on the development of cost-estimation models and cost-effectiveness analyses in this context.

Objectives

The objective of this scoping review was to map the literature describing the costs associated with HCC and liver transplantation in patients with HCC, specifically, to describe the methodologies used to estimate the cost of liver transplantation for HCC, characterize the clinical population investigated in the studies, and provide an overview of the factors or variables used in cost estimation models and outcomes. For the purposes of this scoping review, cost studies are defined as studies that analyze the costs of healthcare interventions, including cost descriptions, cost-of-illness studies (economic burden of the disease),14 and cost effectiveness analysis.

Methods

Stage 1. Planning and development

The guiding question for this scoping review is as follows: What are the methodologies used in cost estimation, clinical characteristics, and health outcomes measured in patients with hepatocellular carcinoma and liver transplantation for hepatocellular carcinoma?

  • • Population: Patients with hepatocellular carcinoma (HCC) and patients with HCC who underwent liver transplantation.

  • • Concept: Methodologies used in cost estimation, variables included in the analysis, clinical characteristics, and measured health outcomes.

This review focuses on the methodologies used in cost measurement, as well as the variables of interest employed in both cost and outcome estimations. Additionally, the context (healthcare settings, such as high-, middle-, and low-income countries) and population (different patient populations, such as those with various stages of HCC, underlying liver disease, and comorbidities) will be considered.

Stage 2. Evidence search

A search will be conducted in bibliographic databases, such as PubMed, Scopus, Embase, LILACS, and Google Scholar. Relevant search terms for HCC, transplantation costs, and clinical outcomes were also used. The search will be complemented by manual searches (snowballing) in specialized journals and by reviewing the references of the selected studies. The search period covered information from 2019 to June 06, 2024.15

Stage 3. Study selection and eligibility

Studies were selected based on the following inclusion criteria:

  • • Patients with hepatocellular carcinoma (HCC).

  • • Liver transplantation for hepatocellular carcinoma.

  • • Costs and clinical outcomes associated with HCC and liver transplantation for HCC.

  • • Original articles only (abstracts, conference summaries, posters, reviews, letters, editorials, and books were excluded).

  • • Publications in indexed journals.

  • • There were no language or regional restrictions.

  • • Population aged ≥ 18 years.

Studies will be independently selected by two reviewers. In cases of disagreement, a third reviewer was consulted.

Stage 4. Data extraction

The following data were extracted from the selected studies14:

  • • Countries.

  • • Context (hospital, outpatient, surgery).

  • • Analyzed population (population characteristics).

  • • Study perspective (Health System, Ministry of Health, Insurer, Service Provider, etc.).

  • • Cost and clinical variables of the study.

  • • Time horizon and discounting.

  • • Compared interventions.

  • • Methods for evaluating cost outcomes.

  • • Methods for evaluating effectiveness and utility outcomes.

  • • Modeling or calculation of the analysis.

  • • Economic and health outcomes (mean cost, years of life gained, and number of deaths avoided).

  • • Uncertainty (e.g., deterministic and probabilistic sensitivity analyses, scenarios, and subgroup analyses).

Data were independently extracted by two reviewers. In case of disagreement, a third reviewer will be consulted.

Stage 5. Analysis, synthesis, and reporting of results

The data were analyzed qualitatively. Various methods used to evaluate the costs and clinical outcomes associated with hepatocellular carcinoma will be identified and described. Since our approach is broad and aims to describe and map the available evidence, the risk of bias in the studies will not be a criterion for excluding the identified articles. In scoping reviews, it is common to omit this aspect because the primary objective of a scoping review is to describe and map a body of literature in terms of characteristics and factors detailed by the review's objectives, questions, and inclusion criteria.16

Study limitations

Our search excluded preprint studies available in databases such as medRxiv/bioRxiv or conference abstracts. We opted to exclude the latter because it is unlikely that they would provide all the necessary information to accurately complete the proforma. We restricted our search to PubMed, Scopus, Embase, and LILACS, which are four online databases likely to include the most significant published works in this area. Studies from the NHS EED database were only updated until 2015 and, therefore, will not be included in the search.

Ethical considerations

This research was approved by the Ethics Committee of the Hospital San Vicente Fundación Rionegro, minutes 11-2023 from April 2023. However, it is essential to clarify that, as this is a scoping review of the literature, this study does not directly involve human subjects. Therefore, according to Colombian Law 8430 of 1993, this study is classified as risk-free research. The findings of this scoping review will be disseminated through peer-reviewed publications and conference presentations.

Consent statement

This study did not require patient consent to participate.

Data availability

Underlying data

No data are associated with this article.

Extended data

Zenodo: Search strategy: Costs and health outcomes of hepatocarcinoma and liver transplantation for hepatocarcinoma: Scoping review protocol, 10.5281/zenodo.15079691.15

This project contains the following underlying data:

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

Acknowledgments

Ministry of Science, Technology and Innovation of Colombia for funding the project. Hospital San Vicente Fundación Rionegro for allowing the project's execution at the hospital. Hospital Universitario Mayor Méderi for the support in publishing the study protocol.

References

  • 1.  El-Serag HB, Rudolph KL: Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007; 132(7): 2557–2576. Publisher Full Text
  • 2.  Liu Z, Jiang Y, Yuan H, et al.: The trends in incidence of primary liver cancer caused by specific etiologies: Results from the Global Burden of Disease Study 2016 and implications for liver cancer prevention. J. Hepatol. 2019; 70(4): 674–683. PubMed Abstract | Publisher Full Text
  • 3.  Mathers CD, Loncar D: Projections of Global Mortality and Burden of Disease from 2002 to 2030. PLoS Med. 2006; 3(11): e442. PubMed Abstract | Publisher Full Text | Free Full Text
  • 4.  Fattovich G, Stroffolini T, Zagni I, et al.: Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004; 127(5 Suppl 1): S35–S50. Publisher Full Text
  • 5.  Crissien AM, Frenette C: Current Management of Hepatocellular Carcinoma. Gastroenterol. Hepatol. 2014; 10(3): 153–161. PubMed Abstract
  • 6.  Simonetti RG, Cammà C, Fiorello F, et al.: Hepatocellular carcinoma. A worldwide problem and the major risk factors. Dig. Dis. Sci. 1991; 36(7): 962–972. Publisher Full Text
  • 7.  Bruix J, Sherman M: Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatol. Baltim. Md. 2005; 42(5): 1208–1236. Publisher Full Text
  • 8.  Hassan MM, Hwang LY, Hatten CJ, et al.: Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatol. Baltim. Md. 2002; 36(5): 1206–1213. Publisher Full Text
  • 9.  Carrilho FJ, Paranaguá-Vezozzo DC, Chagas AL, et al.: Epidemiology of Liver Cancer in Latin America: Current and Future Trends. Semin. Liver Dis. 2020; 40(02): 101–110. PubMed Abstract | Publisher Full Text
  • 10.  Roxburgh P, Evans TRJ: Systemic therapy of hepatocellular carcinoma: are we making progress? Adv. Ther. 2008; 25(11): 1089–1104. Publisher Full Text
  • 11.  Bruix J, Sherman M: American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatol. Baltim. Md. 2011; 53(3): 1020–1022. PubMed Abstract | Publisher Full Text | Free Full Text
  • 12.  European Association For The Study Of The Liver, European Organisation For Research And Treatment Of Cancer: EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J. Hepatol. 2012; 56(4): 908–943. PubMed Abstract | Publisher Full Text
  • 13.  Kudo M, Izumi N, Kokudo N, et al.: Management of hepatocellular carcinoma in Japan: Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig. Dis. Basel Switz. 2011; 29(3): 339–364. Publisher Full Text
  • 14.  Mandrik O(L), Severens JL(H), Bardach A, et al.: Critical Appraisal of Systematic Reviews With Costs and Cost-Effectiveness Outcomes: An ISPOR Good Practices Task Force Report. Value Health. 2021; 24(4): 463–472. PubMed Abstract | Publisher Full Text
  • 15.  Palacios-Barahona U, Toro-Rendón LG, Agudelo-Berruecos Y, et al.: Search strategy: Costs and health outcomes of hepatocarcinoma and liver transplantation for hepatocarcinoma. Scoping Review Protocol. Zenodo. 2025. Publisher Full Text
  • 16.  Peters MDJ, Godfrey C, McInerney P, et al.: Best practice guidance and reporting items for the development of scoping review protocols. JBI Evid. Synth. 2022; 20(4): 953–968. PubMed Abstract | Publisher Full Text

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Palacios-Barahona U, Toro-Rendón LG, Agudelo-Berruecos Y et al. Costs and health outcomes of hepatocarcinoma and liver transplantation for hepatocarcinoma: Scoping review protocol [version 1; peer review: 1 approved]. F1000Research 2025, 14:417 (https://doi.org/10.12688/f1000research.163517.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
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Reviewer Report 14 Aug 2025
Dima Malkawi, University of Colorado Denver, Denver, Colorado, USA 
Approved
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https://doi.org/10.5256/f1000research.179881.r395892
These authors present a protocol to conduct a review of the literature describing costs associated with HCC and the cost of OLT in HCC, with a focus on middle to low income countries. The proposed protocol provides a thorough explanation ... Continue reading
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Malkawi D. Reviewer Report For: Costs and health outcomes of hepatocarcinoma and liver transplantation for hepatocarcinoma: Scoping review protocol [version 1; peer review: 1 approved]. F1000Research 2025, 14:417 (https://doi.org/10.5256/f1000research.179881.r395892)
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https://f1000research.com/articles/14-417/v1#referee-response-395892
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
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  1. Dima Malkawi, University of Colorado Denver, Denver, USA

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    Alongside their report, reviewers assign a status to the article:
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    Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
    Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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