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In Utero Exposure to Mercury Is Associated With Increased Susceptibility to Liver Injury and Inflammation in Childhood
Author(s) -
Stratakis Nikos,
GoldenMason Lucy,
Margetaki Katerina,
Zhao Yinqi,
Valvi Damaskini,
Garcia Erika,
Maitre Léa,
Andrusaityte Sandra,
Basagana Xavier,
Borràs Eva,
Bustamante Mariona,
Casas Maribel,
Fossati Serena,
Grazuleviciene Regina,
Haug Line Småstuen,
Heude Barbara,
McEachan Rosemary R.C.,
Meltzer Helle Margrete,
Papadopoulou Eleni,
Roumeliotaki Theano,
Robinson Oliver,
Sabidó Eduard,
Urquiza Jose,
Vafeiadi Marina,
Varo Nerea,
Wright John,
Vos Miriam B.,
Hu Howard,
Vrijheid Martine,
Berhane Kiros T.,
Conti David V.,
McConnell Rob,
Rosen Hugo R.,
Chatzi Lida
Publication year - 2021
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.31809
Subject(s) - medicine , nonalcoholic fatty liver disease , interquartile range , cohort , toxicant , inflammation , liver disease , in utero , pregnancy , physiology , liver injury , proinflammatory cytokine , fatty liver , immunology , endocrinology , disease , fetus , biology , toxicity , genetics
Background and Aims Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant‐associated fatty liver disease. Approach and Results We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother–child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5‐8.7) from the European Human Early‐Life Exposome cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 μg/L; IQR, 1.1‐3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation‐related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating IL‐1β, IL‐6, IL‐8, and TNF‐α. Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up‐regulation of genes encoding these four cytokines and increased concentrations of IL‐8 and TNF‐α in the supernatants. Conclusions These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.