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World J Diabetes. Dec 15, 2014; 5(6): 917-923
Published online Dec 15, 2014. doi: 10.4239/wjd.v5.i6.917
Nonalcoholic steatohepatitis and insulin resistance in children
Mikage Arata, Junya Nakajima, Shigeo Nishimata, Tomomi Nagata, Hisashi Kawashima
Mikage Arata, Junya Nakajima, Shigeo Nishimata, Tomomi Nagata, Hisashi Kawashima, Department of Pediatrics, Tokyo Medical University, Tokyo 160-0023, Japan
Author contributions: Arata M and Kawashima H conceived and wrote the manuscript, and contributed equally to this manuscript; Nakajima J, Nishimata S and Nagata T investigated the studies on cytokines and pathological studies, and assisted in designing the figures and tables.
Correspondence to: Hisashi Kawashima, MD, PhD, Department of Pediatrics, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. hisashi@tokyo-med.ac.jp
Telephone: +81-03-33426111 Fax: +81-03-33440643
Received: August 20, 2014
Revised: October 7, 2014
Accepted: November 7, 2014
Published online: December 15, 2014
Processing time: 114 Days and 21.3 Hours
Abstract

Various pathological conditions can cause fatty liver in children. Nonalcoholic steatohepatitis (NASH) in children has been known since 1983. However, NASH diagnosed in childhood does not have a favorable outcome. The pathological characteristics of NASH are significantly different between children and adults. Nonalcoholic fatty liver disease (NAFLD)/NASH is accompanied by insulin resistance, which plays a pivotal role in its pathophysiology in both children and adults. In NASH, a “two-hit” model involving triglyceride accumulation (first hit) and liver damage (second hit) has been accepted. Insulin resistance was found to correlate with changes in fat levels; however, it did not correlate with fibrosis or NAFLD activity score in children. Therefore, insulin resistance may be important in the first hit. Because there is obvious familial clustering in NASH, genetic predisposition as well as environmental factors including diet might be the second hit of NAFLD/NASH.

Keywords: Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Insulin resistance; Homeostasis model assessment as an index of insulin resistance; Obesity

Core tip: The pathological characteristics of nonalcoholic steatohepatitis (NASH) are significantly different between children and adults. Nonalcoholic fatty liver disease is accompanied by insulin resistance, which plays a pivotal role in its pathophysiology in both adults and children. In NASH, a “two-hit” model involving triglyceride accumulation (first hit) and liver damage (second hit) has been accepted. Insulin resistance was found to correlate with changes in fat levels; however, it did not correlate with fibrosis in children. Insulin resistance may be important in the first hit. Genetic predisposition as well as environmental factors might be the second hit in children.