Evidence mapPaperPMID 42499017Full record

ArticleLiver international : official journal of the International Association for the Study of the Liver2026

Cumulative Metformin Use and Hepatocellular Carcinoma Risk After HCV SVR: A Multicentre Cohort Study.

Henar Calvo-Sánchez, Lorena Jara-Fernández, Raquel Encijo-Heredia, Irene Villarino, Rubén Alvarado, Marta Quiñones-Calvo, María-Luisa Gutiérrez, Joaquín Miquel, Miguel Torralba, Myriam Catalá and 5 more

Abstract readMulticenter Study
In one paragraph

Article in Liver international : official journal of the International Association for the Study of the Liver, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Cumulative Metformin Use and Hepatocellular Carcinoma Risk After HCV SVR: A Multicentre Cohort Study.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Henar Calvo-SánchezService of Gastroenterology, University Hospital of Guadalajara, Guadalajara, Spain.ORCID https://orcid.org/0000-0002-1582-6521
Lorena Jara-FernándezService of Gastroenterology, University Hospital Fundación Alcorcón, Madrid, Spain.ORCID https://orcid.org/0009-0009-7281-4461
Raquel Encijo-HerediaTranslational Research Group on Cellular Immunology (GITIC), Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Guadalajara, Spain.ORCID https://orcid.org/0009-0000-3642-9480
Irene VillarinoService of Gastroenterology, University Hospital of Guadalajara, Guadalajara, Spain.ORCID https://orcid.org/0009-0008-5876-4579
Rubén AlvaradoService of Gastroenterology, University Hospital Fundación Alcorcón, Madrid, Spain.ORCID https://orcid.org/0000-0001-8724-2990
Marta Quiñones-CalvoService of Gastroenterology, University Hospital Fundación Alcorcón, Madrid, Spain.ORCID https://orcid.org/0000-0002-0138-6748
María-Luisa GutiérrezService of Gastroenterology, University Hospital Fundación Alcorcón, Madrid, Spain.ORCID https://orcid.org/0000-0002-0035-9211
Joaquín MiquelService of Gastroenterology, University Hospital of Guadalajara, Guadalajara, Spain.ORCID https://orcid.org/0000-0002-2367-8944
Miguel TorralbaService of Gastroenterology, University Hospital of Guadalajara, Guadalajara, Spain.ORCID https://orcid.org/0000-0003-2166-7405
Myriam CataláDepartment of Biology and Geology, Physics and Inorganic Chemistry, ESCET, Rey Juan Carlos University, Madrid, Spain.ORCID https://orcid.org/0000-0002-5114-6988
José GómezDepartment of Biology and Geology, Physics and Inorganic Chemistry, ESCET, Rey Juan Carlos University, Madrid, Spain.ORCID https://orcid.org/0000-0003-1758-4746
Sonia AlbertosGastroenterology Service, Alt Penedès-Garraf Sanitary Complex, Barcelona, Spain.ORCID https://orcid.org/0009-0001-4449-479X
Óscar Barquero-PérezDepartment of Signal Theory and Communications and Telematic Systems and Computing, Rey Juan Carlos University, Madrid, Spain.ORCID https://orcid.org/0000-0002-7235-3986
Conrado Fernández-RodríguezService of Gastroenterology, University Hospital Fundación Alcorcón, Madrid, Spain.ORCID https://orcid.org/0000-0002-1915-2157
Juan-Ramón LarrubiaService of Gastroenterology, University Hospital of Guadalajara, Guadalajara, Spain.ORCID https://orcid.org/0000-0002-6383-848X

Funding

Agencia Estatal de Investigación PID2022-136887NB-I00Instituto de Salud Carlos III PI15/00074
6 · The paper itself

Abstract

backgroundAlthough sustained virological response (SVR) after hepatitis C virus treatment reduces hepatocellular carcinoma (HCC) incidence, residual risk persists. Metformin has been associated with lower HCC risk, but whether cumulative metformin exposure (CME) lowers post-SVR risk remains unclear. We evaluated whether CME was associated with lower HCC risk after SVR.

methodsWe analysed a multicentre cohort of 1531 patients who achieved SVR after direct-acting antiviral therapy (median follow-up, 75.5 months). Metformin exposure was modelled as a time-updated cumulative variable in start-stop Cox models to control for immortal-time bias. Stabilised inverse probability weighting addressed confounding by indication and censoring. The overall model was sex-stratified and adjusted for FIB-4, clinically significant portal hypertension (CSPH), type 2 diabetes mellitus (T2DM) and smoking. A prespecified T2DM-restricted analysis used T2DM-specific IPTW plus IPCW, sex stratification and CSPH adjustment.

resultsDuring follow-up, 50 patients developed HCC. Crude incidence was highest among patients with FIB-4 > 3.25, CSPH and T2DM without metformin exposure (4.84 cases per 100 person-years). In the overall weighted model, CME was associated with lower HCC risk (HR, 0.46 per year; 95% CI, 0.27-0.77; p = 0.004). CSPH, T2DM, smoking and FIB-4 > 3.25 independently increased risk. In the T2DM-restricted model, each additional year remained associated with lower HCC hazard (HR, 0.49; 95% CI, 0.29-0.84; p = 0.009), whereas CSPH was associated with higher risk (HR, 6.04; 95% CI, 2.12-17.19; p < 0.001).

conclusionAfter SVR, CME was associated with lower HCC risk; this possible duration-dependent inverse association was clinically interpretable only among metformin-eligible patients with T2DM.

Indexed as

Antiviral AgentsCarcinoma, HepatocellularHepatitis C, ChronicHypoglycemic AgentsLiver NeoplasmsMetforminAgedDiabetes Mellitus, Type 2FemaleHumansHypertension, PortalIncidenceMaleMiddle AgedProportional Hazards ModelsRisk FactorsAntiviral AgentsHypoglycemic AgentsMetformincausal inferencehepatitis C treatmentinverse probability weightingportal hypertensionrisk stratificationtype 2 diabetes mellitus

Identifiers

PMID42499017
PMCPMC13400749

What Socratic holds

Texttitle and abstract
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.