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

Disclosures

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

In This Article

Abstract and Introduction

Abstract

Background: Polycystic ovary syndrome (PCOS) affects 10% of reproductive-aged women, and is marked by irregular menses and high androgens. PCOS is a known risk factor for imaging-confirmed steatosis, and we now aim to evaluate whether PCOS influences histologic severity of non-alcoholic fatty liver disease (NAFLD).

Methods: Retrospective study of women ages 18–45 years with biopsy-confirmed NAFLD between 2008 and 2019. Metabolic comorbidities were captured within 6 months of biopsy. Histologic features of non-alcoholic steatohepatitis (NASH) were independently evaluated by two pathologists blinded to PCOS status.

Results: Among 102 women meeting study criteria, 36% (n = 37) had PCOS; median age was 35 years; 27% were white, 6% black, 19% Asian and 47% reported Hispanic ethnicity. Women with PCOS had higher LDL (122 vs 102 mg/dL, P = .05) and body mass index(BMI) (38 vs 33 kg/cm2, P < .01). NASH was present in 76% of women with PCOS vs 66% without PCOS (P = .3), and a higher proportion with PCOS had severe ballooning (32% vs 13%, P = .02), presence of any fibrosis (84% vs 66%, P = .06) and advanced fibrosis (16% vs 6%, P = .10). Adjusted for age and BMI, PCOS remained associated with severe hepatocyte ballooning (OR 3.4, 95% CI 1.1–10.6, P = .03) and advanced fibrosis (OR 7.1, 95% CI 1.3–39, P = .02). Among women with advanced fibrosis, median age was 5 years younger in those with as compared to those without PCOS (40 vs 45 years, P = .02).

Conclusion: Polycystic ovary syndrome is independently associated with more severe NASH, including advanced fibrosis. Hepatologists should routinely inquire about PCOS in reproductive-aged women with NAFLD, and evaluate for more severe liver disease in this population.

Introduction

Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting ~10% of reproductive-aged women.[1] Most women with PCOS have insulin resistance and elevated androgens, such as high testosterone levels.[2] Other metabolic comorbidities are also more common in women with PCOS, including dyslipidaemia and obesity.[2] This aberrant metabolic and hormonal milieu appears to increase their risk for non-alcoholic fatty liver disease (NAFLD), which presents in 40–50% of women with PCOS.[3–5] Indeed, PCOS is now recognized as a distinct at-risk group for NAFLD.[6]

Whether PCOS is also associated with the more clinically relevant manifestations of NAFLD, including non-alcoholic steatohepatitis (NASH) and NASH-associated fibrosis is not clear. We therefore aimed to evaluate whether PCOS was associated with more severe NAFLD histology as compared to reproductive-aged women without PCOS. If identified, such differences would support the need for more routine inquiry of PCOS in reproductive-aged women presenting with NAFLD, as well as need to evaluate for more severe liver disease in these young women. Such findings would also support efforts to evaluate NASH treatments in this hormonally and metabolically distinct risk group.

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