Hu, H. (Howard)

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    In utero exposure to mercury is associated with increased susceptibility to liver injury and inflammation in childhood
    (2021) Papadopoulou, E. (Eleni); García, E. (Erika); Wright, J. (John); Haug, L.S. (Line Smastuen); Chatzi, L. (Lida); Vos, M.B. (Miriam B.); Hu, H. (Howard); Robinson, O. (Oliver); Bustamante, M. (Mariona); Sabidó, E. (Eduard); Golden-Mason, L. (Lucy); Roumeliotaki, T. (Theano); Conti, D.V. (David V.); Vafeiadi, M. (Marina); Maitre, L. (Léa); Rosen, H.R. (Hugo R.); Heude, B. (Barbara); Gómez-Urquiza, J. (José); McEachan, R.R.C. (Rosemary R. C.); McConnell, R. (Rob); Casas, M. (Maribel); Meltzer, H.M. (Helle Margrete); Fossati, S. (Serena); Grazuleviciene, R. (Regina); Valvi, D. (Damaskini); Basagana, X. (Xavier); Margetaki, K. (Katerina); Vrijheid, M. (Martine); Borrás, E. (Eva); Berhane, K.T. (Kiros T.); Stratakis, N. (Nikos); Andrusaityte, S. (Sandra); Zhao, Y. (Yinqi); Varo-Cenarruzabeitia, M. N. (Miren Nerea)
    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 mu g/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-1 beta, IL-6, IL-8, and TNF-alpha.