Polycystic Ovary Syndrome (PCOS) Is Associated With NASH Severity and Advanced Fibrosis

Monika Sarkar; Norah Terrault; Wesley Chan; Marcelle I. Cedars; Heather G. Huddleston; Caroline C. Duwaerts; Dana Balitzer; Ryan M. Gill


Liver International. 2020;40(2):355-359. 

In This Article


Study Design and Patient Population

This was a retrospective, single centre study of reproductive-aged women (ages 18–45 years) with biopsy-confirmed NAFLD between 2008 and 2019 (n = 110). PCOS was identified by chart review of corresponding ICD-9/10 diagnosis codes and confirmation of PCOS status by Rotterdam criteria.[7] Women with suspected PCOS without confirmed diagnosis by Rotterdam criteria were excluded. Metabolic comorbidities were captured from the most recent timepoint within 6 months before or after liver biopsy, including body mass index (BMI), fasting lipid panels (low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides), and diabetes history (types 1 or 2). Women with other causes of fatty liver were excluded, such as more than one alcoholic drink per day, human immunodeficiency virus, or use of tamoxifen, valproic acid, or diltiazem within 6 months prior to liver biopsy. PCOS-related medications including hormonal contraception or metformin were captured as 'ever' if any documentation of prior use, or 'recent' if at least 1 month of use within 6 months prior to liver biopsy.

NAFLD Assessment

Histologic assessment including presence and severity of NASH was determined by consensus between two independent pathologists blinded to PCOS status. The NAFLD Activity Score (NAS) which includes, a composite score ranging from 0 to 8 points composed of steatosis (0–3), hepatocyte ballooning (0–2) and lobular inflammation scores (0–3) was also determined.[8] Hepatocyte ballooning, lobular inflammation, and portal inflammation were also classified as 'severe' or 'not severe' based on highest grades for each respective histological category as detected low power magnification (ie with a 4x objective). Stage of fibrosis was assessed according to the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) methodology.[8]

Statistical Analysis

Group comparisons were performed by two-sided t tests, Mann-Whitney rank sum tests and Chi2[2] tests as appropriate. Results were reported as median (interquartile range, (IQR)). Logistic regression was used to assess the association of PCOS with presence of NASH or advanced fibrosis, although given similar proportion of patients with NASH by PCOS status, this model was not further pursued. As a post hoc analysis, the association of PCOS with severe hepatocyte ballooning was also evaluated given initial observed differences by PCOS status. A subgroup analysis was also performed among women with hyperandrogenic PCOS defined by Rotterdam criteria with either biochemical evidence (ever elevated androgen level above reference range) or clinical evidence of hyperandrogenism (androgenic alopecia or hirsutism)(n = 31).[9] Findings with P < .05 were considered statistically significant. Analyses were performed using Stata 15.0.