Apoptotic markers indicate nonalcoholic steatohepatitis in polycystic ovary syndrome

Abstract

Background: Polycystic ovary syndrome (PCOS) characterized by chronic anovulation and hyperan-drogenism is highly associated with obesity and insulin resistance (IR), two key features of non-alcoholic steatohepatitis (NASH).NASH often leads to cirrhosis, including portal hypertension, liver failure, and hepatocellular carcinoma as long-term complications. The caspase 3-cleaved fragment of cytokeratin 18 (CK18) emerging from ongoing cell death during apoptosis process has been established as a serum marker for NASH. This study was conducted to evaluate the prevalence of NASH in PCOS patients by caspase-cleaved CK18 measurement. Methods: In 192 PCOS patients [age, 29.0 ± 6.7 yr; body mass index (BMI), 31.5 ± 8.2 kg/m2] and 73 age-matched controls (age, 28.6 ± 8.0 yr; BMI, 24.1 ± 4.6 kg/m2), obesity and IR were determined by BMI and area under the curve of insulin response (AUCI), respectively. Apoptotic cell death was measured by M30 ELISA detecting caspase-cleaved CK18 only. Results: M30 levels were significantly elevated in PCOS patients after correction for BMI (304.7 ± 223.1 vs. 86.3 ± 165.6 U/liter; P < 0.001). M30 correlated significantly with BMI, AUCI, glucose secretion, low-density lipoprotein, low high-density lipoprotein, and free androgen index. AUCI turned out to be the only independent M30-determining factor in the multiple regression analysis with an effect size of 7.9%. Fifty-one of 186 (27.4%) PCOS patients showed M30 levels of at least 395 U/liter, indicating NASH. Conclusion: These data demonstrate elevation of apoptotic cell death, its correlation with IR, and a high prevalence of NASH in PCOS patients. Given this high prevalence, PCOS may be a risk factor for progressive hepatic sequelae. Incidence data are of strong interest. Copyright © 2010 by The Endocrine Society.