Evidence map›Paper›PMID 41455979›Full record

ReviewBiology of sex differences2025

The importance of sex dimorphism in liver metabolism and progressive liver diseases.

Eva Kočar, Kaja Blagotinšek Cokan, Tinkara Kreft, Tadeja Režen, Damjana Rozman

Abstract readReview
In one paragraph

Review in Biology of sex differences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. 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

5 authors.

Eva KočarCentre for Functional Genomics and Bio-Chips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.ORCID 0009-0009-1962-2698
Kaja Blagotinšek CokanCentre for Functional Genomics and Bio-Chips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.ORCID 0000-0002-7779-8036
Tinkara KreftCentre for Functional Genomics and Bio-Chips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.ORCID 0009-0001-4735-2025
Tadeja ReženCentre for Functional Genomics and Bio-Chips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.ORCID 0000-0001-6210-7370
Damjana RozmanCentre for Functional Genomics and Bio-Chips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. damjana.rozman@mf.uni-lj.si.ORCID 0000-0002-6501-2163

Funding

The Slovenian Research and Innovation Agency J3-4513The Slovenian Research and Innovation Agency P1-0390
6 · The paper itself

Abstract

The liver is a central metabolic organ with pronounced sex-specific differences shaped by sex hormones, sex chromosome-linked gene expression, ageing, and circadian rhythm. These factors influence disease susceptibility, progression, and treatment response, with notable differences between females and males in the prevalence, severity, and clinical outcomes of metabolic dysfunction-associated steatotic liver disease. This condition represents a growing global health burden that can progress to hepatocellular carcinoma, the second leading cause of cancer-related death worldwide. Despite this impact, sex remains an underexplored variable in liver research, and the molecular mechanisms by which sex influences disease development remain poorly understood. In this review, we examine the key determinants of sex differences in liver pathogenesis. We highlight the protective role of estrogen signaling in female liver metabolism, the increased vulnerability to disease progression after menopause, and the contribution of circadian regulation to sex-specific outcomes. We further discuss how the lack of systematic inclusion of both sexes in preclinical and clinical studies limits the identification of biomarkers and the development of effective therapeutic interventions. Incorporating sex as a biological variable is therefore essential to improve mechanistic understanding, translational relevance, and the personalization of treatment approaches. Particular emphasis is placed on animal models that reflect sex-specific liver physiology and pathophysiology, as these provide valuable frameworks for studying disease progression and testing targeted interventions. In summary, recognizing and integrating sexual dimorphism in liver metabolism is crucial to advancing prevention, diagnosis, and treatment strategies. Addressing sex differences is critical for developing accurate diagnostic tools and personalized therapeutic approaches, ultimately improving outcomes for both women and men with liver disease.

Indexed as

LiverLiver DiseasesSex CharacteristicsAnimalsDisease ProgressionFemaleHumansMaleAnimal modelsFibrosisHCCLiverMASHMASLDSexual dimorphism

Identifiers

PMID41455979
PMCPMC12853960

What Socratic holds

Textmetadata
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.