Risk of chemotherapy-associated liver injury (CALI) in PNPLA3 p.148M allele carriers: Preliminary results of a transient elastography-based study.

Abstract

BACKGROUND AND AIMS:

Liver steatosis is one of the side effects of chemotherapy. The PNPLA3 p.I148M, TM6SF2 p.E167K and MBOAT7 p.G17E variants represent genetic determinants for progressive liver diseases. Here, we investigate their association with chemotherapy-associated steatosis.

PATIENTS AND METHODS:

Prospectively, we recruited 87 patients undergoing systemic chemotherapy for gastrointestinal cancers. Hepatic fat (controlled attenuation parameter, CAP) and liver stiffness (LSM) were measured non-invasively before the initiation of chemotherapy (T0) and after at least two (T1) and four cycles (T2). Genetic variants were genotyped using allelic discrimination assays.

RESULTS:

In the final dataset (n = 60) patients demonstrated the following CAP values: T0 - 215.0 ± 55.7 dB/m, T1 - 223.3 ± 53.6 dB/m, T2 - 223.4 ± 56.7 dB/m, consistent with mild steatosis. Initial CAP correlated with BMI (P < 0.01) and serum triglyceride concentrations (P = 0.03). Whereas at T0 none of the variants was associated with CAP or LSM, carriers of the prosteatotic PNPLA3 p.148M allele showed significantly (P = 0.008) higher steatosis at T1 as compared to patients carrying the homozygous wild-type genotype [II].

CONCLUSIONS:

Our preliminary results show that patients carrying the PNPLA3 p.I148 M risk allele might be prone to hepatic fat accumulation during chemotherapy. Further studies are be needed to validate the clinical value of these findings.

• Authors: Markus Casper, Simone Zimmermann, Susanne N Weber, Anita Arslanow, Frank Lammert, Marcin Krawczyk
• Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (Dig Liver Dis) Vol. 52 Issue 1 Pg. 102-106 (01 2020) ISSN: 1878-3562 [Electronic] Netherlands
• PMID: 31669075 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Membrane Proteins
• TM6SF2 protein, human
• Triglycerides
• Acyltransferases
• MBOAT7 protein, human
• Lipase
• adiponutrin, human

Topics

• Acyltransferases (genetics)
• Aged
• Alleles
• Antineoplastic Agents (adverse effects)
• Elasticity Imaging Techniques
• Fatty Liver (chemically induced, genetics)
• Female
• Genetic Predisposition to Disease
• Heterozygote
• Humans
• Lipase (genetics)
• Liver (pathology)
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Polymorphism, Genetic
• Prospective Studies
• Triglycerides (blood)