Commentary by J. Michael Gonzalez-Campoy, MD, PhD, FACE
The prevalence of non-alcoholic fatty liver disease (NAFLD), a multifactorial condition that encompasses steatosis, non-alcoholic steatohepatitis, and advanced fibrosis, is on the rise.1 In fact, Salvatore Petta, MD, and colleagues found that women with polycystic ovary syndrome (PCOS) had a significantly higher risk for steatosis than women without the syndrome,2 according to findings published in PLoS One.
The growing number of patients presenting with non-alcoholic fatty liver disease, which raises the risk for hepatocellular carcinoma, may face the need for a liver transplant and cardiovascular complications.3,4 In women with PCOS, findings from observational studies have linked insulin resistance and hyperandrogenism as risk factors for steatosis and liver damage.5
To assess whether PCOS was a risk factor for steatosis and whether insulin resistance and hyperandrogenism played a role in steatosis and fibrosis, 202 women with PCOS were included in the study.2 These women were diagnosed with PCOS according to the Rotterdam criteria and exhibited at least 2 criteria of the clinical and/or biochemical symptoms.6 As a control, women who did not have a diagnosis of PCOS were included.5 Specifically, they had regular menstrual cycles, no clinical signs of hyperandrogenism and no polycystic ovarian morphology.5
A wide variety of tests were performed on each patient to collect clinical and anthropometric data.5 Steatosis was diagnosed using BMI, AST/ALT, gender, and diabetes, which are the parameters of the hepatic steatosis index (HSI).2,7 If the HSI > 36, patients were diagnosed with steatosis.7 Similarly, fibrosis was diagnosed using the FIB-4 score, which uses age, AST, ALT, and PLT.7 A FIB-4 > 2.67 indicated severe fibrosis.8
Among 202 patients with PCOS and 101 women in the control group, steatosis was observed in 59% of cases.2 However, in women who were diagnosed with PCOS, steatosis occurred at a significantly higher rate, 68.8%, compared to 33.3% in control subjects (P < 0.001).2 Steatosis was also significantly associated with higher body mass index (BMI) (P < 0.001), higher waist circumference (P < 0.001), and lower HDL cholesterol and triglyceride levels (P < 0.001).2
To assess which factors were associated with steatosis in patients with polycystic ovary syndrome, the researchers evaluated a variety of clinical and anthropometric data to see which factors were statistically different in patients with PCOS that had steatosis and those that did not. 5The factors that were significantly associated with steatosis were higher BMI (P < 0.001), higher WC (P < 0.001), higher fasting insulin (P < 0.001), higher free androgen index (P < 0.001), lower HDL cholesterol levels (P = 0.011) and lower sex hormone-binding globulin (SHBG) levels (P < 0.001).2
In addition, steatosis was observed in 80.6% of patients with PCOS who also presented with abdominal obesity (weight circumference > 88cm) as compared with 58.7% who did not.2
In the study,2 the authors concluded that “PCOS doubles the risk for steatosis and in PCOS patients, [insulin resistance] and hyperandrogenism are the two main determinants of steatosis and liver damage.” In addition, “the data clearly highlight that PCOS patients are at high risk for steatosis, so the identification of risk factor for fatty liver and for hepatic damage in this population is demanded,” they said. Dr. Petta did not respond to our queries about the study.
“The hepatic steatosis index is clearly higher in women with PCOS as compared to women without PCOS,” said J. Michael Gonzalez-Campoy, MD, PhD, who was not associated with the study, told EndocrineWeb, “We know that obesity increases the prevalence of steatosis in women with PCOS, and the free androgen index is strongly associated with steatosis in women who have polycystic ovary syndrome but not obesity, whereas insulin resistance is associated with fatty liver in women with PCOS regardless of their obesity status.”
“It seems clear that all women with PCOS should be assessed for steatosis, especially in the setting of obesity,” said Dr. Gonzalez-Campoy.
One particularly compelling finding is an apparent association between hyperandrogenism as a key risk factor for steatosis and fibrosis, particularly in non-obese patients.2 Dr. Gonzalez-Campoy said, “the most interesting finding is that high male hormone levels in women with PCOS who do not have obesity are more likely to develop liver damage (steatosis).”
The results of this study offer clinicians a strong indication that patients who are diagnosed with polycystic ovary syndrome is a risk factor for steatosis, and suggests that clinicians should be cognizant of this when caring for patients with PCOS, particularly those with insulin resistance and hyperandrogenism.
“This study documents associations between PCOS, obesity, and high androgen levels with hepatic steatosis. It opens the door to investigate what effect there may be on hepatic steatosis from androgen blockade. It also validates the ongoing use of insulin sensitizers to treat women with PCOS,” Dr. Gonzalez-Campoy said.