Non-alcoholic steatohepatitis in children

Obesity has emerged as a significant new health problem in the pediatric population. Non-alcoholic steatohepatitis (NASH) is an entity in the spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from fat in the liver - simple steatosis, NASH/ steatohepatitis - fat with inflammation and/or fibrosis to advanced fibrosis and cirrhosis when fat may no longer be present. NASH is associated with obesity, diabetes, insulin resistance (IR), and hypertriglyceridemia. While majority of individuals with risk factors like obesity and IR have steatosis only a minority develop steatohepatitis, possible mechanisms have been discussed. Clinical experience with pediatric NASH is limited. Children generally present in the prepubertal age group, have a male predominance with a higher incidence in children of Hispanic origin. Body mass index (BMI) of 25-29.9 is considered to be overweight and that greater than or equal to30 obese. Acanthosis nigricans as a marker of IR should be looked for. As NASH is a diagnosis of exclusion, other causes of chronic liver disease must be excluded. Increased echogenicity in the liver is noted on ultrasound. Liver biopsy is considered the gold standard in establishing the diagnosis. Histopathological lesions thought to be necessary for diagnosis of NASH include steatosis (macrovesicular > microvesicular), mixed mild lobular inflammation and hepatocyte ballooning. A system of grading depending on degree of steatosis and/or inflammation and staging depending on the extent of fibrosis has also been proposed. Although there is no consensus for the treatment for NASH, effort needs to be made to prevent development of fibrosis, which results in cirrhosis and portal hypertension. Slow, consistent weight loss has been shown to be effective in childhood NAFLD, based on improvement of serum aminotransferases or liver sonogram. A low glycemic index diet has been shown to be more effective than a low fat diet in lowering BMI. Family based behavioral intervention may also enhance success with diet. Several pharmacological agents have been used including ursodeoxycholic acid, vitamin E, betaine, n-acetyl cysteine, and insulin sensitizing agents like metformin, rosiglitazone, and pioglitazone. Transplantation for overt NASH is rare, accounting for <1% of liver transplantations in the USA. The disease can recur after liver transplantation. A strong association exists between the presence of steatosis in a donor liver and poor graft function. As a result, cadaveric donor livers with macrovesicular steatosis >40% are not used routinely. Prognosis in NASH is dependent not only on severity and number of risk factors but also on the degree of histological damage. Clinical trials are needed to identify an effective treatment that halts the progression of NAFLD to NASH in both pretransplantation and post-transplantation patients.