External validation of the fatty liver index and lipid accumulation product indices, using H-1-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals

Background and Aims. Simple clinical algorithms including the Fatty Liver Index (FLI) and Lipid Accumulation Product (LAP) have been developed as a surrogate marker for Non-Alcoholic Fatty Liver Disease (NAFLD). These algorithms have been constructed using ultrasonography, a semi-quantitative method. This study aimed to validate FLI and LAP as measures of hepatic steatosis, as measured quantitatively by proton magnetic resonance spectroscopy (1H-MRS). Methods. Data were collected from 168 patients with NAFLD and 168 controls who had undergone clinical, biochemical and anthropometric assessment in the course of research studies. Values of FLI and LAP were determined, and assessed both as predictors of the presence of hepatic steatosis (liver fat >5.5 %) and of actual liver fat content, as measured by 1H MRS. The discriminative ability of FLI and LAP was estimated using the area under the Receiver Operator Characteristic curve (AUROC). Since FLI can also be interpreted as a predictive probability of hepatic steatosis, we assessed how well calibrated it was in our cohort. Linear regression with prediction intervals was used to assess the ability of FLI and LAP to predict liver fat content. Results. FLI and LAP discriminated between patients with and without hepatic steatosis with an AUROC of 0.79 (IQR= 0.74, 0.84) and 0.78 (IQR= 0.72, 0.83), although quantitative prediction of liver fat content was unsuccessful. Additionally, the algorithms accurately matched the observed percentages of patients with hepatic steatosis in our cohort. Conclusions. FLI and LAP may be used clinically, and for metabolic and epidemiological research, to identify patients with hepatic steatosis, but not as surrogates for liver fat content

Polycystic ovary syndrome with hyperandrogenism is characterized by an increased risk of hepatic steatosis compared to nonhyperandrogenic PCOS phenotypes and healthy controls, independent of obesity and insulin resistance

Polycystic ovary syndrome (PCOS) affects up to 20% of women of reproductive age and is clinically characterized by irregular menstrual cycles, hyperandrogenism, infertility, or subfertility, frequently with a characteristic ovarian morphology on ultrasonographic examination. There is no consensus as to the most appropriate diagnostic criteria, which incorporate multiple possible phenotypes, but the critical difference between the criteria is whether hyperandrogenism is a prerequisite feature (1) or not (2). The etiology of PCOS is complex and not completely understood. Nevertheless, a central pathophysiological feature of PCOS is insulin resistance, which cannot be fully explained by the frequent association with obesity because PCOS women are more insulin resistant than healthy controls matched for body mass index (BMI) (3). Different distributions of body fat, for example increased abdominal fat in PCOS relative to controls matched for BMI, could potentially contribute to the insulin resistance in this patient group (4, 5). Visceral fat mass strongly correlates with the degree of insulin resistance and other aspects of the metabolic syndrome in women with PCOS (5, 6). Moreover, in healthy normal-weight and obese individuals, liver fat is also highly correlated with insulin resistance and other features of the metabolic syndrome (7, 8). There is some evidence of an increased prevalence of nonalcoholic fatty liver disease (NAFLD) in PCOS, using a variety of diagnostic and surrogate methods. NAFLD represents a disease spectrum, ranging from hepatic steatosis, characterized by deposition of triglycerides in the hepatocytes, through to nonalcoholic steatohepatitis (NASH), characterized by hepatocyte injury, inflammation, and fibrosis, which can in turn progress to cirrhosis (9). Using liver transaminases or ultrasonography to infer the presence of hepatic steatosis, a number of studies have demonstrated a high risk of hepatic steatosis in women with PCOS (10–13). Indirect methods have also been used to detect NASH, the intermediate stage in the NAFLD spectrum. Tan et al. (14) demonstrated a high prevalence of NASH in PCOS using levels of the apoptotic marker cytokeratin-18 as a surrogate index. Based on such literature, it has been suggested that women with PCOS should be screened for liver disease at an earlier age than is currently recommended for the general population (15). However, to our knowledge there have been no carefully controlled studies to address the clinically relevant question as to whether PCOS represents a specific risk factor for the development of NAFLD, or whether the increased risk of NAFLD in PCOS is mediated by the high prevalence of concomitant obesity. This latter possibility is suggested by the results of a small study in lean, insulin-resistant PCOS women demonstrating no increased risk of NAFLD (16). Using proton magnetic resonance spectroscopy (1H-MRS), a well-validated, noninvasive method for measuring liver fat content that correlates closely with liver fat determined histologically (17), it is possible to precisely determine liver fat rather than a more semiquantitative method such as ultrasonography. Thus, the aim of this study was to: 1) determine whether women with PCOS have increased liver fat, determined by 1H-MRS, compared with healthy controls of similar age and BMI; and 2) examine whether a specific phenotype of PCOS is more strongly associated with NAFLD than other phenotypes. We hypothesize that hyperandrogenic PCOS women will have increased liver fat independent of body composition