Insulin resistance and hyperandrogenism drive steatosis and fibrosis risk in young females with PCOS.

Nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) recognize obesity and insulin resistance (IR) as common pathogenic background. We assessed 1) whether PCOS is a risk factor for steatosis, and 2) the impact, in PCOS patients, of IR and hyperandrogenism on steatosis and fibrosis.We considered 202 consecutive Italian PCOS nondiabetic patients and 101 age-matched controls. PCOS was diagnosed applying the Rotterdam diagnostic criteria. Steatosis was diagnosed if hepatic steatosis index (HSI) >36, while fibrosis by using the FIB-4 score. As surrogate estimate of insulin sensitivity we considered the insulin sensitivity index (ISI). Free androgen index (FAI) was calculated as estimate of biochemical hyperandrogenism.In the entire population, steatosis was observed in 68.8% of patients with PCOS, compared to 33.3 of controls (p<0.001), this association being maintained after adjusting for metabolic confounders (OR 3.73, 95% CI 1.74-8.02; P = 0.001). In PCOS patients, steatosis was independently linked to WC (OR 1.04, 95% CI 1.01-1.08; P = 0.006) and ISI Matsuda (OR 0.69, 95% CI 0.53-0.88; P = 0.004), not to free androgen index (OR 1.10, 95% CI 0.96-1.26; P = 0.14). Notably, ISI Matsuda was confirmed as independently associated with steatosis in both obese (OR 0.42, 95% CI 0.23-0.77, P = 0.005) and nonobese (OR 0.69, 95% CI 0.53-0.91, P = 0.009), patients, while FAI (OR 1.45, 95% CI 1.12-1.87; P = 0.004) emerged as an independent risk factor only in nonobese PCOS. Similarly, higher FIB-4 was independently associated with higher FAI (p = 0.02) in nonobese and with lower ISI Matsuda (p = 0.04) in obese patients.We found that PCOS is an independent risk factor for steatosis, and that, IR and hyperandrogenism, this last especially in nonobese patients, are the key players of liver damage in PCOS

Multivariate linear regression analyses of factors associated with FIB-4 in the entire population of PCOS, and in sub-groups according to presence/absence of abdominal obesity.

<p>Multivariate linear regression analyses of factors associated with FIB-4 in the entire population of PCOS, and in sub-groups according to presence/absence of abdominal obesity.</p

Univariate and multivariate logistic regression analyses of factors associated with steatosis (HSI>36) in the entire population of PCOS and controls.

<p>Univariate and multivariate logistic regression analyses of factors associated with steatosis (HSI>36) in the entire population of PCOS and controls.</p

Multivariate logistic regression analyses of factors associated with steatosis (HSI>36) in the entire population of PCOS, and in sub-groups according to presence/absence of abdominal obesity.

<p>Multivariate logistic regression analyses of factors associated with steatosis (HSI>36) in the entire population of PCOS, and in sub-groups according to presence/absence of abdominal obesity.</p

Prevalence of steatosis—defined as hepatic steatosis index > 36—according to presence of polycystic ovary syndrome (PCOS) and/or abdominal obesity.

<p>Prevalence of steatosis—defined as hepatic steatosis index > 36—according to presence of polycystic ovary syndrome (PCOS) and/or abdominal obesity.</p

The presence of white matter lesions is associated with the fibrosis severity of nonalcoholic fatty liver disease

We tested whether nonalcoholic fatty liver disease (NAFLD) and/or its histological severity are associated with vascular white matter lesions (WML) in patients with biopsy-proven NAFLD and in non-NAFLD controls. Data were recorded in 79 consecutive biopsy-proven NAFLD, and in 82 controls with normal ALT and no history of chronic liver diseases, without ultrasonographic evidence of steatosis and liver stiffness value 45 years (OR 3.09, 95% CI: 1.06-9.06, P=0.03; and OR 11.1, 95% CI: 1.14-108.7, P=0.03), and F2-F4 fibrosis (OR 3.36, 95% CI: 1.29-8.73, P=0.01; and OR 5.34, 95% CI: 1.40-20.3, P=0.01) were independently associated with WML (mostly of mild grade) by multivariate analysis. Among NAFLD, the prevalence of WML progressively increased from patients without (1/18; 5.5%), or with 1 (1/17, 5.8%), to those with 2 (9/30; 30%) and further to those with 3 (12/14; 85.7%) risk factors. The presence of WML is not associated with NAFLD, but with metabolic diseases in general, and fibrosis severity of NAFLD. Clinical implications of this issue need to be assessed by longitudinal studies

Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study

Abstract Background No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. Aim of the study We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. Materials and methods The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (RHI). The mini-mental state examination (MMSE) was administered to test cognitive performance. Results 80 consecutive patients with biopsy-proven NAFLD and 83 controls without fatty liver disease. NAFLD subjects showed significantly lower mean RHI, higher mean arterial stiffness indexes and lower mean MMSE score. Multivariable analysis after correction for BMI, dyslipidaemia, hypertension, sex, diabetes, age and cardiovascular disease showed that BMI, diastolic blood pressure and RHI are significantly associated to NAFLD. Simple linear regression analysis showed among non-alcoholic steatohepatitis (NASH) subjects a significant negative relationship between ballooning grade and MMSE and a significant positive association between Kleiner steatosis grade and augmentation index. Conclusions Future research will be addressed to evaluate the relationship between inflammatory markers and arterial stiffness and endothelial function indexes in NAFLD subjects. These study will evaluate association between cardiovascular event incidence and arterial stiffness, endothelial and cognitive markers, and they will address the beneficial effects of cardiovascular drugs such as statins and ACE inhibitors on these surrogate markers in NAFLD subjects