Nonalcoholic fatty liver disease (NAFLD) is present in up to one third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn, exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.

Nonalcoholic fatty liver disease.

NONALCOHOLIC FATTY LIVER DISEASE is emerging as the most common chronic liver condition in the Western world. It is associated with insulin resistance and frequently occurs with features of the metabolic syndrome. Disease presentation ranges from asymptomatic elevated liver enzyme levels to cirrhosis with complications of liver failure and hepatocellular carcinoma. Current treatment recommendations are limited to weight loss and exercise, although several promising medications are on the horizon. In this article we discuss the etiology, pathogenesis and diagnosis of nonalcoholic fatty liver disease as well as approaches to its management.

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Nonalcoholic fatty liver disease

OBJECTIVE.Fatty liver disease is diagnosed increasingly in children, but the prevalence remains unknown. We sought to determine the prevalence of pediatric fatty liver as diagnosed by histology in a population-based sample. METHODS.We conducted a retrospective review of 742 children between the ages of 2 and 19 years who had an autopsy performed by a county medical examiner from 1993 to 2003. Fatty liver was defined as 5% of hepatocytes containing macrovesicular fat. RESULTS.Fatty liver was present in 13% of subjects. For children and adolescents age 2 to 19 years, the prevalence of fatty liver adjusted for age, gender, race, and ethnicity is estimated to be 9.6%. Fatty liver prevalence increases with age, ranging from 0.7% for ages 2 to 4 up to 17.3% for ages 15 to 19 years. Fatty liver prevalence differs significantly by race and ethnicity (Asian: 10.2%; black: 1.5%; Hispanic: 11.8%; white: 8.6%). The highest rate of fatty liver was seen in obese children (38%). CONCLUSIONS.Fatty liver is the most common liver abnormality in children age 2 to 19 years. The presence of macrovesicular hepatic steatosis in 1 of every 10 children has important ramifications for the long-term health of children and young adults. The influence of the risk factors identified should be taken into consideration in the development of protocols designed to screen at-risk children and adolescents.

Prevalence of Fatty Liver in Children and Adolescents

AGA technical review on nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects a high proportion of the world's population. Insulin resistance and oxidative stress play a critical role in the pathogenesis of NAFLD. Clinical, biochemical and imaging studies are of value in the diagnostic evaluation of patients with NAFLD, but liver biopsy remains the most sensitive and specific means of providing important diagnostic and prognostic information. Simple steatosis has the best prognosis within the spectrum of NAFLD, but NAFLD has the potential to progress to steatohepatitis, fibrosis and even cirrhosis. No effective medical therapy is currently available for all patients with NAFLD. In patients with diabetes mellitus and hyperlipidemia, appropriate metabolic control is always recommended, but rarely effective in resolving the liver disease. Weight reduction, when achieved and sustained, may improve the liver disease, although the results with weight loss have been inconsistent. Pharmacological therapy aimed at the underlying liver disease holds promise. Several medications with different mechanisms of action and potential benefit are currently being evaluated in clinical trials. Liver transplantation is a life-extending therapeutic alternative for patients with end-stage NAFLD, but NAFLD may recur after liver transplantation.

Non-alcoholic fatty liver disease.

The prevalence of fatty liver in children is unknown and its relationship to obesity is poorly defined. The present study of 810 northern Japanese children (4-12 years old) determined the prevalence of fatty liver in the pediatric population and its relationship to obesity. Diagnosis of fatty liver was based on established real-time ultrasonographic criteria. The overall prevalence of fatty liver was 2.6% and was higher for boys (3.4%) than for girls (1.8%), although not statistically significant (P = 0.15). Fatty liver was found in children as young as 6 years of age. There was no significant association between the prevalence of fatty liver and height (physical growth). There was a strong positive correlation between fatty liver prevalence and established obesity indices: Rohrer's Index--chi 2 linear trend = 59.2, P < 0.0001; body mass index--chi 2 linear trend = 91.6, P < 0.0001; and age-gender-adjusted Japanese standard index of weight for height--chi 2 linear trend = 93.2, P < 0.0001. However, direct measurement of abdominal subcutaneous fat thickness by ultrasonography was the best predictor of fatty liver: chi 2 linear trend = 159, P < 0.0001. These results indicate that fatty liver may develop very early in life, and there is a direct relationship between degree of obesity and fatty liver in children.

John H. Kurata

Papers

Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey.