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

Results

Of the 102 reproductive-aged women meeting study inclusion criteria, 36% (n = 37) had PCOS. Women with PCOS were younger (median age 33 vs 36 years P = .02), had higher median BMI (38 vs 33 kg/m2, P < .01), LDL levels (122 vs 102 mg/dL, P = .05) and numerically more diabetes (41% vs 31%, P = .3) (Table 1). Race/ethnicity and frequency of other metabolic comorbidities were similar between women with and without PCOS. Among women with PCOS, 68% (n = 25) had prior use of hormonal contraception, with 67% having at least 1 month of use within 6 months prior to biopsy. Prior metformin use was present in 65% of women with PCOS (n = 24), with 43% (n = 16) having at least 1 month of use during the 6 months prior to biopsy.

Histologic criteria for NASH (ie steatosis > 5%, ballooned hepatocytes and lobular inflammation) were met in 76% of women with PCOS vs 66% without PCOS (P = .3), and median NAFLD Activity Scores (NAS) were similar (Table 2). The proportion with severe steatosis and any ballooned hepatocytes was also similar, although more women with PCOS had evidence of severe hepatocyte ballooning (32% vs 13%, P = .02). Lobular and portal inflammation was similar between groups (P > .5). A numerically higher proportion of women with PCOS had hepatic fibrosis (84% vs 66%, P = .06) and advanced fibrosis, defined as stage 3 or 4 (16% vs 6%, P = .10). Importantly, among women with advanced fibrosis, the median age of those with PCOS was 5 years younger than women without PCOS (40 vs 45 years, P < .01).

On univariate analysis PCOS was associated with severe hepatocyte ballooning (OR 3.4, 95% CI 1.2–9.2, P = .02), which persisted after adjusting for age and BMI (OR 3.4, 95% CI 1.1–10.6, P = .03) (Table 3). On unadjusted analysis the association of PCOS with advanced fibrosis did not reach statistical significance (OR 3.0, 95% CI 0.78–11.2), P = .11), but was significant on adjusted analysis (AOR 7.1, 95% CI 1.3–39, P = .02) (Table 4). A sensitivity analysis comparing the 31 women with confirmed hyperandrogenic PCOS to women without PCOS was also performed. Women with hyperandrogenic PCOS had numerically more NASH (81% vs 67%, P = .12) and were more likely to have severe hepatocyte ballooning (29% vs 12%, P = .05). A higher proportion also had hepatic fibrosis (87% vs 66%, P = .03), with numerically more women with hyperandrogenic PCOS having advanced fibrosis (13% vs 6%, P = .26) (Supplemental Table 1). Estimates for severe hepatocyte ballooning were attenuated on adjusted analysis (OR 3.1, 95% CI 0.93–10.3, P = .07), although hyperandrogenic PCOS maintained a statistically significant association with advanced fibrosis on adjusted analysis (OR 9.5 95% CI 1.4–63, P = .02) (Supplemental Table 2).

Among women with PCOS, the proportion with severe hepatocyte ballooning was similar by ever (35% vs 25%), or recent hormonal contraception use (32% vs 25%), as well as ever (30% vs 38%), or recent metformin use (35% vs 29%), all P > .60. A numerically smaller proportion of PCOS patients had advanced fibrosis among those with ever (12% vs 25%), or recent hormonal contraception use (13% vs 25%), P > .32, while a higher proportion had advanced fibrosis with ever (26% vs 0%, P = .12), or recent metformin use (25% vs 10%, P = .21).

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