Patients with Polycystic Ovary Syndrome Expose Elevated Apoptosis Indicating Non-Alcoholic Steatohepatitis

Aims: Patients with polycystic ovary syndrome (PCOS) often exhibit also obesity and insulin resistance (IR), two key features of non-alcoholic steatohepatitis (NASH). NASH is associated with cirrhosis and can culminate in hepatocellular carcinoma and liver failure. Recent studies successfully determined NASH via serum concentration of caspase 3-cleaved cytokeratin 18 (CK18) fragments (M30), resulting from apoptotic cell death. This study aimed to determine the prevalence of NASH in PCOS patients by M30 serum levels. Methods: In 192 PCOS patients (age: 29.0±6.7 years, BMI: 31.5±8.2kg/m2) as defined by AESPCOS criteria and 73 age-matched controls (28.6±8.0 years, BMI: 24.1±4.6kg/m2), obesity was measured as body mass index (BMI) and IR was determined by area under the curve of insulin response during a 3-hour oral glucose tolerance test (AUCI). Apoptotic cell death was measured by M30 Apoptosense ELISA detecting caspase-cleaved CK18 only. Results: M30 levels were significantly increased in PCOS patients after correction for BMI (304.7±223.1 vs. 86.3±165.6 U/l; p<0.001). M30 exhibited significant correlation with BMI, AUCI, glucose secretion, LDL, low HDL and free androgen index. Multiple regression analysis determined AUCI as independent M30-determining factor with an effect size of 7.9%. 27.4% PCOS patients (51 of 186) exposed M30 levels ≥395U/l, which is regarded as indicator for NASH. Conclusion: PCOS patients in our cohort show a clear elevation of apoptotic cell death, which is correlated with IR, increased BMI and free androgen index. As PCOS seems to represent a metabolic risk state for developing NASH, clinicians should be aware of this interrelationship.