Defining plastic-induced liver injury (PILI)

Do plastics make liver disease worse? Exploring their interaction with alcohol, diet and inflammation

Defining plastic-induced liver injury (PILI)

Do plastics make liver disease worse? Exploring their interaction with alcohol, diet and inflammation

Title: Defining Plastic-Induced Liver Injury (PILI)

Funded by: University of Plymouth

Dates: October 2025 – ongoing

Project partners: Southwest Liver Unit, University Hospitals Plymouth NHS Trust; Roger Williams Institute of Liver Studies, King’s College London

University of Plymouth PI:

Professor Shilpa Chokshi

University of Plymouth staff: Dr Paula Boeira , Dr Valentin Tastet ; Namrata Pandey ; Dr Kieran Smith ; Dr Dhanushan Gnanendran ; Professor Richard Thompson OBE FRS ; Professor Jamie Lead ; Professor Mathew Upton

Overview

Human liver tissue has been found to contain micro- and nanoplastics (MNPs), with evidence that hepatic MNP accumulation has significantly increased over the last 10 years, prompting critical questions regarding their potential causal role in liver disease.

In cell-based and murine models, MNP exposure can trigger oxidative stress, fibrogenesis, and inflammation – pathological features that resemble those of advanced liver disease and cirrhosis, suggesting shared mechanistic pathways. Furthermore, the capacity for MNPs to act as 'Trojan horses' for microbial pathogens, antimicrobial resistance, endocrine-disrupting chemicals and carcinogenic additives may have important implications for liver pathology. Currently, major knowledge gaps remain regarding the mechanistic pathways, causal links, and clinical relevance of MNP exposure in liver health.

The PILI project investigates how plastics and their associated chemicals, alcohol and dietary lipids interact to injure the liver and accelerate the progression of alcohol-related liver disease and metabolic dysfunction associated steatotic liver disease.

Using human relevant new approach models, including precision cut liver slices, hepatic organoids, patient-derived liver organoids and gut–liver microphysiological systems, this project defines the cellular and molecular events triggered by plastic exposure under healthy and disease relevant conditions. Integrated multi-omics profiling, spatial imaging and bioinformatics will reveal how plastics alter hepatocyte function, disrupt the gut barrier, activate inflammation and promote fibrosis.

Objectives

To define the mechanisms by which micro- and nanoplastics, along with their associated chemicals, induce hepatotoxicity under alcoholic, obesogenic, and inflammatory conditions using advanced 3D human liver models.
To investigate the role of micro- and nanoplastics and associated contaminants as a 'second hit' in patient-derived hepatic organoids and precision cut liver slices from individuals with established metabolic dysfunction associated steatotic liver disease and alcohol related liver disease.
To determine the impact of micro- and nanoplastic exposure on intestinal barrier integrity and gut–liver axis communication using intestinal organoids and gut–liver microphysiological systems.
To delineate conserved and model-specific mechanisms of toxicity through integrated multi-omics profiling, spatial imaging and advanced bioinformatics approaches to inform biomarker discovery and translational risk assessment.

With plastic pollution escalating at an unprecedented rate and liver disease rates rising worldwide, this project aims to address critical questions about how MNPs impact liver health. Using human-relevant models, we will generate meaningful insights and deepen our understanding of the consequences of real-world plastic exposure.

Dr Paula Boeira
Post Doctoral Research Fellow

Context of the issue

Micro- and nanoplastic exposure is increasing through contaminated food, water and air. These particles and their associated chemical additives and endocrine-disrupting chemicals can interfere with liver metabolism, immune responses and tissue repair. At the same time, alcohol-related liver disease and metabolic dysfunction associated steatotic liver disease are rising globally, creating a convergence of environmental and lifestyle driven insults to the liver.

How the project addresses the issue

PILI uses human-derived liver and gut models to simulate real-world exposure scenarios and investigate how plastics and chemical co-exposures drive liver injury. This work reflects a shift towards human-relevant mechanistic toxicology, aligned with European efforts to reduce animal use, improve chemical risk assessment and understand the health impacts of emerging pollutants.

Diagram showing the effects of plastics on the liver

Centre of Environmental Hepatology

The Centre of Environmental Hepatology (CEH) brings together scientists, clinicians and environmental researchers to generate mechanistic, clinically grounded evidence that can inform prevention, improve patient outcomes, and support policies that reduce harmful exposures.

Our mission is to transform understanding of liver health in a changing world and to ensure that research translates into meaningful impact for patients, communities, and future generations.

Discover more research from the Centre of Environmental Hepatology