Clinical Correlates of Histopathology in Pediatric Nonalcoholic Steatohepatitis

Division of Gastroenterology, University of California, San Diego, San Diego, California 92103, USA.
Gastroenterology (Impact Factor: 16.72). 09/2008; 135(6):1961-1971.e2. DOI: 10.1053/j.gastro.2008.08.050
Source: PubMed


Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in American children. Noninvasive means to discriminate between NAFLD and nonalcoholic steatohepatitis (NASH) might diminish the requirement for liver biopsy or predict those at increased risk for progression.
Data obtained prospectively from children (age, 6-17 y) enrolled in the NASH Clinical Research Network were analyzed to identify clinical-pathologic correlates of pediatric NAFLD. All participants underwent liver biopsy within 6 months of clinical data that were reviewed by a central pathology committee.
A total of 176 children (mean age, 12.4 y; 77% male) were eligible for inclusion. By using ordinal logistic regression analysis, increasing aspartate aminotransferase (AST) level (odds ratio [OR], 1.017 per U/L; 95% confidence interval [CI], 1.004-1.031) and gamma-glutamyltransferase level (OR, 1.016 per U/L; 95% CI, 1.000-1.033) were associated independently with increasing severity of NASH. Increasing AST level (OR, 1.015 per U/L; 95% CI, 1.006-1.024), increasing white blood cell count (OR, 1.22 per 1000/mm(3); 95% CI, 1.07-1.38), and decreasing hematocrit (OR, 0.87 per %; 95% CI, 0.79-0.96) were associated independently with increasing severity of fibrosis. Area under the receiver operator characteristic curve for a model with AST and alanine aminotransferase was 0.75 (95% CI, 0.66-0.84) and 0.74 (95% CI, 0.63-0.85) for distinguishing steatosis from more advanced forms of NASH and bridging fibrosis from lesser degrees of fibrosis, respectively.
Certain components of routine laboratory tests are predictive of NAFLD pattern and fibrosis severity, but do not have adequate discriminate power to replace liver biopsy in evaluating pediatric NAFLD.

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Available from: Heather M Patton, Jan 06, 2014
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    • "When the adaptive mechanisms of the hepatocytes fail to accommodate the accumulated free fatty acids, lipotoxicity occurs, which induces oxidative stress and inflammatory changes that progress to nonalcoholic steatohepatitis (NASH). This condition causes injury to the hepatocytes, fibrosis, and subsequently, cirrhosis.[34] As such, oxidative stress is increasingly considered to be the therapeutic target in NAFLD management through the use of antioxidant agents. "
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    • "Non-alcoholic fatty liver disease (NAFLD) is usually suspected in case of fatty liver on ultrasound examination in an obese child [9] [10]. An elevated AST/ALT ratio may be indicative of non-alcoholic steatohepatitis (NASH), a progressive and more serious condition [11]. Nevertheless, NAFLD and NASH are diagnoses of exclusion even in obese children with elevated liver function tests, and a number of other diseases causing fatty liver (Table 3) should be excluded on the basis of patient age [4]. "
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    • "The AST/ALT ratio is a commonly used indicator of hepatic fibrosis because it is simple and easy to calculate; however, the diagnostic accuracy of an AST/ALT ratio>1 is very low in children with NAFLD, limiting its routine use as a hepatic fibrosis score18,24). "
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    ABSTRACT: Because nonalcoholic steatohepatitis can progress towards cirrhosis even in children, early detection of hepatic fibrosis and accurate diagnosis of nonalcoholic fatty liver disease (NAFLD) are important. Although liver biopsy is regarded as the gold standard of diagnosis, its clinical application is somewhat limited in children due to its invasiveness. Noninvasive diagnostic methods, including imaging studies, biomarkers of inflammation, oxidative stress, hepatic apoptosis, hepatic fibrosis, and noninvasive hepatic fibrosis scores have recently been developed for diagnosing the spectrum of NAFLD, particularly the severity of hepatic fibrosis. Although data and validation are still lacking for these noninvasive modalities in the pediatric population, these methods may be applicable for pediatric NAFLD. Therefore, noninvasive imaging studies, biomarkers, and hepatic fibrosis scoring systems may be useful in the detection of hepatic steatosis and the prediction of hepatic fibrosis, even in children with NAFLD.
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