[1619] Fatty Acid Synthase: A Potential Serum Marker for Non-Alcoholic Steatohepatitis (NASH)

Z Maleki, M Torbenson, S Medghalchi, WF Han, FP Kuhajda. Johns Hopkins University School of Medicine, Baltimore, MD; FASgen Inc, Baltimore, MD

Background: Non-alcoholic fatty liver disease (NAFLD) is a clinically silent condition most commonly occurring in obese individuals. Left undiagnosed and untreated, a subset of individuals with NAFLD will develop steatohepatitis (NASH) with an increased risk of cirrhosis. Since elevated expression of fatty acid synthase (FAS), the enzyme responsible for de novo fatty acid synthesis, has been reported in the liver of patients with NAFLD, we hypothesized that serum FAS levels are increased in the blood of patients with NASH and may be a useful serum marker to identify individuals at greater risk for NASH.
Design: FAS was measured in presurgical serum from 101 bariatric surgery patients using a human anti-FAS monoclonal sandwich ELISA assay (FASgen Inc, Baltimore, MD). Intraoperative liver biopsy was performed on 77 patients and semiquantitatively scored with a NASH activity score (0-2 steatosis, 3-5 mild NASH, 6-7 marked NASH). Age, gender, body mass index (BMI), serum ALT, AST and alkaline phosphatase values were collected. Hepatic FAS expression was assessed with immunohistochemistry. Serum FAS was also measured in 119 healthy controls.
Results: Of the 77 patients with both serum FAS and liver biopsy, FAS ranged from 1-88 ng/mL (avg 15.2). Biopsy results showed: 43 steatosis, 28 mild NASH, and 6 marked NASH. BMI ranged from 34-88 (avg 50). Increased serum FAS levels were associated with NASH by linear regression (p=0.007) or 1-way ANOVA (p=0.025). The table shows the data when FAS levels were categorized.

Serum FAS and NAFLD
Serum FAS ng/mL0-45-10>10
Steatosis (%)19/25 (76)10/18 (56)14/34 (41)
Mild NASH (%)6/25 (24)7/18 (39)15/34 (44)
Marked NASH (%)01 (5)5/34 (15)
p=0.0027 (regression)

Increasing FAS levels were associated with the severity of liver disease (p=0.0027, regression). FAS levels > 10 ng/mL identified 5/6 patients with marked NASH. Neither liver function tests nor clinical data were significantly associated with NASH. Serum FAS in the 119 healthy controls averaged 0.97 ng/mL (0.18 std. error). Immunoreactive FAS was identified in the liver of patients with either steatosis or NASH.
Conclusions: Serum FAS levels are elevated in morbidly obese subjects compared to healthy controls. Among bariatric surgery patients, FAS levels were significantly associated with NASH. FAS may prove to be a useful marker for detection of NAFLD in obese subjects.
Category: Liver & Pancreas

Monday, March 22, 2010 1:45 PM

Platform Session: Section D, Monday Afternoon


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