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. 2025 Jan 30;7(5):101336.
doi: 10.1016/j.jhepr.2025.101336. eCollection 2025 May.

Evolving epidemiology of HCC in Spain

Margarita Sala  1   2 , Sonia Pascual  2   3 , Maria Rosa Rota Roca  4 , Ana María Matilla  5 , Marta Campos  2   6 , Manuel Delgado  7 , María Teresa Ferrer  8 , José Luís Montero  9 , Jesús Manuel González-Santiago  2   10 , Antonio Guerrero  2   11 , Carles Aracil  12 , Carlos Rodríguez-Lope  13 , Marta Romero-Gutiérrez  14 , Miguel Sogbe  15 , Sergio Vázquez-Rodríguez  16 , Javier Fuentes Olmo  17 , Beatriz Mínguez  2   18 , Luís Cortés-García  19 , Nicolau Vallejo-Senra  20 , Paloma Rendón Unceta  21 , Ariadna Clos  22 , Dácil Díaz-Bethencourt  23 , Araceli García Sánchez  24 , Raisa Quiñones Castro  25 , Javier Bustamante  26 , Christie Perelló  27 , Juan José Urquijo Ponce  28 , Hernán Andreu Serra  29 , Camilo Julio Llamoza-Torres  30 , Silvia Montoliu  31 , Cristina Fernández-Marcos  32 , Ana Guiberteau  33 , Manuel Hernández-Guerra  34 , Mercedes Vergara  2   35 , Alexia María Fernández-López  36 , María Paz Valer López-Fando  37 , María Luisa Gutiérrez-García  38 , Tánia Hernáez-Alsina  39 , Susana Coll  40 , Berta Cuyás  2   41 , María Julia Morillas  42 , Susana Rebolledo Olmedo  43 , Miguel Fernández-Bermejo  44 , Mercè Roget  45 , Irina Calvo Ramos  46 , Gemma Pacheco Del Río  47 , Raimon Rifà  48 , Pilar Conde Gacho  49 , Mónica Llorente Barrio  50 , Mariano Gómez-Rubio  51 , Irene Peñas  52 , Isabel Serra  1 , Alba Cachero  4 , María Reig  2   6 , Álvaro Giraldez  8 , Marta Guerrero  9 , José Xavier Segarra  10 , José Luis Lledó  2   11 , Álvaro Díaz-González  13 , Carolina Delgado  14 , Mercedes Iñarrairaegui  2   15 , María Milagros Rodríguez-González  16 , María Lázaro  17 , María Bermúdez-Ramos  18 , Alberto Lué  19 , Esther Molina  20 , Manuel Alberto Macías-Rodríguez  21 , Manuel Rodríguez  53 , Valentina Chiminazzo  54 , María Varela  53
Affiliations

Evolving epidemiology of HCC in Spain

Margarita Sala et al. JHEP Rep. .

Abstract

Background & aims: The epidemiological landscape of hepatocellular carcinoma (HCC) in Europe is evolving. This study aims to provide an updated description of the current epidemiology of liver cancer in Spain.

Methods: This multicenter prospective study collected demographic and clinical data on primary liver cancer between October 2022 and January 2023. We conducted descriptive and comparative analyses with data collected in 2008 and 2014.

Results: Of the 767 cases of primary liver cancer collected from 52 centers, 91% were diagnosed as HCC. The majority of patients were male (83.3%), average age 68 years, 80.7% had cirrhosis. The primary causes were alcohol (29.9% alone, 55% combined with other etiologies), liver disease related to metabolic syndrome (LDrMS, 23%) and hepatitis C (17.3%). Treatments included ablation (15.7%), systemic therapy (14.7%), and chemoembolization (14.6%). Data from 29 centers (n = 1,351) across three registries revealed a significant increase in LDrMS (from 4.9% to 24%) and HCC in non-cirrhotic livers (from 4.2% to 7.9%). Meanwhile, hepatitis C decreased sharply (from 43% to 17.5%). Alcohol-related cases remained stable. There was a slight increase in male patients and hypertension, diabetes, and obesity. Patients with cirrhosis diagnosed outside of screening programs presented with larger tumors and more advanced disease. This led to fewer evaluations for curative treatments.

Conclusions: Alcohol accounts for 30% of HCC cases and is the main etiology. The registry shows a decrease in hepatitis C-related HCC, an increase in LDrMS and HCC in non-cirrhotic livers. Surveillance was implemented in ∼80% of the recommended population. There is a need for improved screening and prevention strategies, particularly for alcohol abuse and LDrMS, to enhance HCC management.

Impact and implications: Our study showcases the involvement of numerous reference centers across Spain and examines over 1,300 patients to track the changing epidemiology of hepatocellular carcinoma (HCC) over 14 years. In patients with known liver cirrhosis, more than 80% of HCC diagnoses were made through screening leading to early-stage identification and curative treatment opportunities. Notably, there has been a shift in HCC etiology within the registries from hepatitis C to liver disease related to metabolic syndrome, with an increase in cases without cirrhosis. Findings indicate a need for the prevention and early detection of HCC, particularly focusing on alcohol and liver disease related to metabolic syndrome, along with greater involvement of health authorities, to improve the participation of at-risk patients in screening programs.

Keywords: Etiology; Liver cancer; Surveillance; Treatment.

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Conflict of interest statement

MS: travel expenses and congress registrations Roche, Astra-Zeneca; SP: conferences for Roche, Astra-Zeneca, consultant for Astra-Zeneca, Roche, travel expenses and congress registrations Roche; AM: conferences for EISAI-MSD, Roche, Boston, Sirtex, consultant for Roche, EISAI-MSD; MC: consultant for Roche; MTF: Gilead (Grant), conferences for Gilead, EISAI, consultant for EISAI, travel expenses and congress registrations Gilead, Roche, EISAI; JLM: consultant for Roche, EISAI, Advance, Gilead, Abbvie; AGue: conferences for Roche, Astra-Zeneca, travel expenses and congress registrations Roche; BM: Laboratorios Viñas (Grant), conferences for Merck-EISAI, Roche, Astra-Zeneca, consultant for Merck-EISAI, Roche, Astra-Zeneca, travel expenses and congress registrations Astra-Zeneca, Roche, Merck-EISAI; LC-G: conferences for Roche, EISAI, consultant for EISAI, travel expenses and congress registrations EISAI, Gilead, Chiesi; NV-S: travel expenses and congress registrations Gilead; AC: travel expenses and congress registrations Astra-Zeneca; CP: conferences for Roche; JJUP: conferences for EISAI, Gilead, Roche, travel expenses and congress registrations Roche, Gilead, Abbvie; CJL-T: conferences for EISAI, MSD, Roche, travel expenses and congress registrations EISAI, MSD, Roche; SM: travel expenses and congress registrations Roche, EISAI; AGui: conferences for EISAI, Roche; MV: conferences for EISAI, Roche, consultant for Astra-Zeneca, travel expenses and congress registrations Roche, Gilead; AMF-L: Gilead, Abbvie, Roche, Astra-Zeneca (Grants), conferences for Abbvie, travel expenses and congress registrations Gilead, Abbvie, Roche, Astra-Zeneca, Salvat; TH-A: travel expenses and congress registrations Roche, Astra-Zeneca; SC travel expenses and congress registrations Roche; SR: Abbvie, Gilead, EISAI, Roche (Grants), conferences for Gilead, travel expenses and congress registrations Gilead, Abbvie, ESAI, Roche, SESCAM; GP: travel expenses and congress registrations Roche; RR: travel expenses and congress registrations Roche; PCG: travel expenses and congress registrations Roche; MLB: travel expenses and congress registrations Norgine; MG-R: conferences for EISAI, Merck, travel expenses and congress registrations Roche, EISAI, Merck; MR: Bayer, IPSEN (Grants), conferences for Astra-Zeneca, Bayer, BMS, Eli Lilly, Gilead, Roche, Biotoscana Farma, consultant for Astra-Zeneca, Bayer, MSD, Eli Lilly, Geneos, IPSEN, Merck, Roche, Universal DX, Boston, Engitix Therapeutics, Parabilis Medicines, travel expenses and congress registrations Astra-Zeneca, Roche, Bayer, BMS, Lilly, Ipsen; ÁG: travel expenses and congress registrations EISAI; JLL: conferences for Roche, Astra-Zeneca, EISAI, consultant for Roche, Astra-Zeneca and EISAI, travel expenses and congress registrations Roche; AL: conferences for Astra-Zeneca, Advanz Pharma, EISAI, Roche, travel expenses and congress registrations Roche; Manuel Rodríguez conferences for Gilead, travel expenses and congress registrations Gilead, Abbvie; MV: conferences for Boston, Roche, Astra-Zeneca, consultant for Astra-Zeneca, Roche, Boston, travel expenses and congress registration Astra-Zeneca, Roche. Please refer to the accompanying ICMJE disclosure forms for further details.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Flow chart of patients included in the third registry (n = 767) and geographic distribution of the participating hospitals (n = 52).
Fig. 2
Fig. 2
Flow chart of HCC diagnosis in patients with cirrhosis (n = 560). CCA, cholangiocarcinoma; HCC, hepatocellular carcinoma; HCC-CCA, mixed hepatocellular carcinoma.
See this image and copyright information in PMC

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