PNPLA3 and TM6SF2 exacerbate the impact of alcohol and metabolic dysfunction on liver fibrosis
Our findings indicate that fibrosis progression in steatotic liver disease is mediated by an interaction of environmental risk factors (obesity, insulin resistance, alcohol consumption) and genetic risk variants, such as <i>PNPLA3</i> and <i>TM6SF2</i>, but not by genetic variants alone. This highlights the importance of acknowledging these gene-environment interactions for patient counselling and risk stratification.
Authors
- Camilla Dalby Hansen (ORCID: https://orcid.org/0000-0002-5704-2485)
- Elmar Aigner (ORCID: https://orcid.org/0000-0003-0310-0536)
- K. Bech (ORCID: https://orcid.org/0000-0002-3760-0689)
- Paul Thöne (ORCID: https://orcid.org/0009-0001-1618-476X)
- Mads Israelsen (ORCID: https://orcid.org/0000-0001-9443-5846)
- Bernhard Wernly (ORCID: https://orcid.org/0000-0003-4024-0220)
- Aleksander Krag (ORCID: https://orcid.org/0000-0002-9598-4932)
- Christian Datz (ORCID: https://orcid.org/0000-0001-7838-4532)
- Stephan Zandanell (ORCID: https://orcid.org/0000-0002-0223-0323)
- Nikolaj Torp (ORCID: https://orcid.org/0000-0002-4378-6256)
- Maja Thiele (ORCID: https://orcid.org/0000-0003-1854-1924)
- Sophie Gensluckner
- Georg Semmler (ORCID: https://orcid.org/0000-0002-0411-166X)
- Mattias Mandorfer (ORCID: https://orcid.org/0000-0003-2330-0017)
- Michael Straßer (ORCID: https://orcid.org/0000-0002-0913-7949)
- Lorenz Balcar (ORCID: https://orcid.org/0000-0002-6708-3061)
- Laura Maarit Pikkupeura (ORCID: https://orcid.org/0000-0003-4430-8552)
- Helle Lindholm Schnefeld (ORCID: https://orcid.org/0009-0009-6566-9681)
- Torben Hansen (ORCID: https://orcid.org/0000-0001-8748-3831)
- Jan Embacher
Institutions
- University of Copenhagen (DK)
- University of Southern Denmark (DK)
- Paracelsus Medical University (AT)
- Novo Nordisk Foundation (DK)
- Odense University Hospital (DK)
- Krankenhaus Oberndorf (AT)
- Medical University of Vienna (AT)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-10-30
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101649
- Citations
- 1
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.35
Funders
- Universität Wien
- Novo Nordisk
- Odense Universitetshospital
- Medizinische Universität Wien
- Syddansk Universitet
- Faculty of Health and Medical Sciences, University of Western Australia
- Novo Nordisk Fonden
- Novo Nordisk Foundation Center for Basic Metabolic Research
- Paracelsus Medizinische Privatuniversität
- Ludwig Boltzmann Gesellschaft
- Det Sundhedsvidenskabelige Fakultet, Københavns Universitet