Related Experiment Video

Updated: Sep 10, 2025

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

4.7K

Impact of PNPLA3 I148M on Drug-Induced Hepatocellular Liver Injury: A Systematic Review and Meta-Analysis

Alexandra Gatzios1, Lorna Marchandise1, Hannes Hagström2,3

  • 1In Vitro Liver Disease Modelling Team, Department of In Vitro Toxicology & Dermato-Cosmetology, Faculty of Medicine & Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.

Liver International : Official Journal of the International Association for the Study of the Liver
|August 25, 2025
PubMed
Abstract

Insights

The PNPLA3-I148M variant shows little evidence of increasing susceptibility to drug-induced liver injury (DILI). However, it may amplify transaminase elevations in specific drug treatments for metabolically impaired individuals.

Area of Science:

  • Hepatology
  • Pharmacogenomics
  • Genetics

Background:

  • The patatin-like phospholipase domain-containing protein 3 (PNPLA3)-I148M variant's role in drug-induced liver injury (DILI) is not well understood.
  • This study aimed to systematically review and meta-analyze the association between PNPLA3 I148M carriage and hepatocellular DILI.

Purpose of the Study:

  • To investigate if the PNPLA3 I148M variant increases the risk of developing hepatocellular DILI.
  • To assess the impact of PNPLA3 I148M on drug-induced transaminase elevations.

Main Methods:

  • Systematic review and meta-analysis of published studies up to January 31st, 2025.
  • Inclusion criteria: studies reporting serum transaminase elevations in response to drug treatment, with assessment of DILI using Hy's law.
  • Meta-analysis focused on transaminase elevations compared to baseline levels.

Main Results:

  • Eight articles (13 studies, 8235 patients) were reviewed; 5 studies (3480 patients) were included in the meta-analysis.
  • No conclusive evidence found for increased hepatocellular DILI occurrence based on PNPLA3 I148M carriage.
  • Meta-analysis indicated amplified transaminase elevations with adomeglivant and basal insulin peglispro in metabolically impaired PNPLA3-IM/MM individuals (OR=1.53).

Conclusions:

  • Limited evidence suggests PNPLA3 I148M carriage does not confer susceptibility to clinically relevant hepatocellular DILI.
  • The variant may potentiate drug-induced transaminase elevations for specific drugs in metabolically impaired individuals.
Keywords:
chemical and drug induced liver injurygeneticshepatotoxicitypatatin‐like phospholipase domain‐containing protein 3transaminases

More Related Videos

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen09:44

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen

Published on: November 27, 2019

10.3K
Investigating the Protective Effects of Platycodin D on Non-Alcoholic Fatty Liver Disease in a Palmitic Acid-Induced In Vitro Model08:20

Investigating the Protective Effects of Platycodin D on Non-Alcoholic Fatty Liver Disease in a Palmitic Acid-Induced In Vitro Model

Published on: December 2, 2022

1.9K

Related Concept Videos

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
79
Hepatic Drug Excretion: Influencing Factors01:16

Hepatic Drug Excretion: Influencing Factors

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
216
Hepatic Drug Clearance: Effect of Protein Binding01:09

Hepatic Drug Clearance: Effect of Protein Binding

Hepatic clearance is influenced by protein binding based on the drug's extraction ratio. Drugs with high extraction ratios are considered flow-limited and remain unaffected by protein binding during hepatic clearance. On the other hand, drugs with low extraction ratios may be impacted by plasma protein binding, although the extent of this influence depends on the fraction of the drug bound.
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
284