Nonalcoholic fatty liver disease in severely obese subjects.
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) has been consistently associated with obesity and insulin resistance. Nonalcoholic steatohepatitis (NASH) is a histological entity within NAFLD that can progress to cirrhosis. The exact prevalence of NASH in severe obesity is unknown. It is unclear whether differences in insulin sensitivity exist among subjects with NASH and simple fatty liver.


OBJECTIVE
To evaluate the prevalence and correlates of NASH and liver fibrosis in a racially diverse cohort of severely obese subjects.


METHODS
Ninety-seven subjects were enrolled. Liver biopsies, indirect markers of insulin resistance, metabolic parameters, and liver function tests were obtained.


RESULTS
Thirty-six percent of subjects had NASH and 25% had fibrosis. No cirrhosis was diagnosed on histology. Markers of hyperglycemia, insulin resistance, and the metabolic syndrome but not body mass index were associated with the presence of NASH and fibrosis. Elevated transaminase levels correlated strongly with NASH and fibrosis but 46% subjects with NASH had normal transaminases. Subjects with NASH had more severe insulin resistance when compared to those with simple fatty liver. A signal detection model incorporating AST and the presence of diabetes predicted the presence of NASH while another incorporating ALT and HbA1C predicted the presence of fibrosis.


CONCLUSIONS
NAFLD is associated with the metabolic syndrome rather than excess adipose tissue in severe obesity. Insulin resistance is higher in subjects with NASH versus those with simple fatty liver. Statistical models incorporating markers of liver injury and hyperglycemia may be useful in predicting the presence of liver pathology in this population.
Gholam
Pierre M
PM
Division of Gastroenterology, St Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Flancbaum
Louis
L
Machan
Jason T
JT
Charney
Douglas A
DA
Kotler
Donald P
DP
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D005234:Fatty Liver / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000453:epidemiology; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D015995:Prevalence; D011379:Prognosis; D012307:Risk Factors; D012720:Severity of Illness Index; D014481:United States / Q000453:epidemiology
D001786:Blood Glucose