Introduction
NAFLD, Obesity, Digestive, non-alcoholic steatohepatitis, macrovesicular steatosis, fatty liver, panacinar or periportal macrovesicular steatosis, inflammation, cirrhosis, fibrosis, lobular inflammation, abdominal obesity, NASH, portal lymphocytic inflammation, NAFL, Diabetes, NALFD
OBESITY, FATTY LIVER, NON-ALCOHOLIC STEATOHEPATITIS, INFLAMMATION, LIVER FIBROSIS, FIBROSIS, NON-ALCOHOLIC FATTY LIVER, NON-ALCOHOLIC FATTY LIVER DISEASE, CIRRHOSIS, KIDNEY DISEASES, INSULIN RESISTANCE, NON-ALCOHOLIC FATTY LIVER DISEASE, DIABETES, REGRESSION, METABOLIC SYNDROME
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty liver change, including non-alcoholic steatohepatitis (NASH), that can be considered to represent a hepatic manifestation of metabolic syndrome. Obesity, specifically abdominal obesity, and insulin resistance increase risk for NAFLD and NASH in children. NASH is defined by presence of > 5% macrovesicular steatosis, hepatocyte ballooning, and lobular inflammation and typically also has portal lymphocytic inflammation. This typical (type 1) pattern is observed in most adults, whereas in children an alternate (type 2) pattern, consisting of severe panacinar or periportal macrovesicular steatosis and portal-based fibrosis and inflammation is recognized. NALFD is an umbrella term that includes NASH and non-alcoholic fatty liver (NAFL), which has much lower risk for progression to liver fibrosis, cirrhosis, and eventual liver transplantation than NASH, though NAFL with lobular inflammation may confer some increased risk of fibrosis over NAFL without lobular inflammationFactors associated with fibrosis progression to cirrhosis and from NAFL to NASH are not well delineated, particularly in pediatric patients. Furthermore, NASH in children may manifest with a type 1 or type 2 pattern, or show transition from one type to another (typically from type 2 to type 1), particularly in older children and adolescentsRecent studies have focused on the potential role of telomeres, the non-coding DNA sequences that protect chromosomes from damage and degradation, specifically hepatocyte telomeres as playing a potential role in the process of liver aging that is associated with NAFLD, specifically NASH and fibrosis processesUsing data collected from the National Institute of Diabetes and Digestive and Kidney Diseases sponsored Treatment of Non-alcoholic Fatty Liver Disease in Children Trial (TONIC) (NCT00063635), we evaluated the relationship between leukocyte telomere length (LTL) in children with NAFLD and NASH in TONIC. We additionally assessed the potential role of LTL as a predictive biomarker of NASH progression and regression using data points from this trial over 96 weeks of follow-up. As there was detailed liver biopsy characteristics on each child at two time points, we sought to understand the role that LTL might be play to help elucidate the process of NAFLD progression in children.