Nonalcoholic Fatty Liver Disease: Its Mechanisms and Complications

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disorder in which fat accumulates excessively in the liver. The disease affects between 10% to 30% of the general population and up to 90% in obese patients [1]. Fatty liver, the first step of NAFLD, is linked with insulin resistance, a well-known condition that predisposes to the development of metabolic disorders such as diabetes and obesity. Although NAFLD may be asymptomatic, the development of nonal-coholic steatohepatitis (NASH) results in hepatic fibrosis, cirrhosis, and ultimately might evolve to liver cancer. While substantial progress has been made in understanding the disease , the mechanisms governing the development of hepatic steatosis and fibrosis are still unclear, and their effects on metabolism need to be clearly understood. NAFLD has been associated with metabolic disorders, and many confounders such as hyperlipidemia, hypertension, diabetes, and obesity make research in the field very difficult to conduct. To understand the impact of NAFLD on the development of cardiovascular disease (CVD), H. Lu et al. performed a meta-analysis on 4 cross-sectional and 2 prospective cohort studies in European and Asian populations. After adjustments for confounders (age, sex, HbA1c, plasma lipid and liver enzyme levels, and metabolic syndromes), NAFLD significantly predicted CVD suggesting the prime role of the liver steatosis on the development of metabolic syndrome. The association between NAFLD and metabolic diseases has also been reported in children [2]. Here, L. Pacifico et al. further investigated the association between NAFLD and thyroid function in childhood obesity. In this Italian cohort of 402 overweight/obese children (age 10–12 years old), eighty-eight children (21.9%) had TSH above the normal range (>4.0 mIU/L). High TSH was associated with many metabolic variables such as hepatic steatosis, hypertriglyc-eridemia, elevated total cholesterol, and insulin resistance after adjustment for age, gender, pubertal status, and BMI. Stepwise multivariate regression analysis showed a significant association between hyperthyrotropinemia and hepatic steatosis (OR = 1.96). Other covariates independently associated with hepatic steatosis were hypertriglyceridemia (OR = 2.73) and insulin resistance (OR = 2.37). This study clearly demonstrated the complexity of metabolic disorders even in children. Given the growing population in obese children, it is important to understand how metabolic comorbidities develop in children in order to prevent earlier metabolic derangements. A review from H. Rodríguez-Hernández et al. " Obesity and Inflammation: Epidemiology, Risk Factors, and Markers of Inflammation " tries to understand the causal role of low-grade inflammation on the development of …