Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis?

Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are associated with obesity, insulin resistance, metabolic syndrome, cardiovascular disease, cirrhosis, and liver tumors. On these grounds, we have hypothesized that NAFLD and PCOS occur more frequently than expected by chance alone. We have tested this hypothesis by reviewing the clinical and biological evidence that supports a significant association between NAFLD and PCOS. PubMed was extensively searched for articles published through March 2015 using the keywords "nonalcoholic fatty liver disease" or "fatty liver" combined with "PCOS." Several cross-sectional and case-control studies have consistently demonstrated that the prevalence of NAFLD is remarkably increased in young women with PCOS, independent of overweight/obesity and other coexisting metabolic syndrome features, and that these women are more likely to have the more severe forms of NAFLD (non-alcoholic steatohepatitis, advanced fibrosis, and cirrhosis). Accumulating evidence suggests that NAFLD, especially its necro-inflammatory form, may exacerbate hepatic and systemic insulin resistance and releases multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators that may play important roles in the pathophysiology of PCOS. These findings call for more active and systematic search for NAFLD among women with PCOS. Conversely, gastroenterologists/hepatologists need to be aware of the presence of PCOS among female patients with NAFLD and compatible clinical features. Finally, all these patients should undergo regular follow-up not only for liver-related complications but also for cardio-metabolic diseases.