Background: Fatty liver (FL) is the most frequent liver disease in Western countries. We used data from the Dionysos Nutrition & Liver Study to develop a simple algorithm for the prediction of FL in the general population. Methods: 216 subjects with and 280 without suspected liver disease were studied. FL was diagnosed by ultrasonography and alcohol intake was assessed using a 7-day diary. Bootstrapped stepwise logistic regression was used to identify potential predictors of FL among 13 variables of interest [gender, age, ethanol intake, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase (GGT), body mass index (BMI), waist circumference, sum of 4 skinfolds, glucose, insulin, triglycerides, and cholesterol]. Potential predictors were entered into stepwise logistic regression models with the aim of obtaining the most simple and accurate algorithm for the prediction of FL. Results: An algorithm based on BMI, waist circumference, triglycerides and GGT had an accuracy of 0.84 (95%CI 0.81–0.87) in detecting FL. We used this algorithm to develop the "fatty liver index" (FLI), which varies between 0 and 100. A FLI < 30 (negative likelihood ratio = 0.2) rules out and a FLI ≥ 60 (positive likelihood ratio = 4.3) rules in fatty liver. Conclusion: FLI is simple to obtain and may help physicians select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies. Validation of FLI in external populations is needed before it can be employed for these purposes.

The prevalence of and the risk factors for fatty liver have not undergone a formal evaluation in a representative sample of the general population. We therefore performed a cross-sectional study in the town of Campogalliano (Modena, Italy), within the context of the Dionysos Project. Of 5,780 eligible persons aged 18 to 75 years, 3,345 (58%) agreed to participate in the study. Subjects with suspected liver disease (SLD), defined on the basis of elevated serum alanine aminotransferase (ALT) and γ-glutamyl-transferase (GGT) activity, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)-RNA positivity, were matched with randomly selected subjects of the same age and sex without SLD. A total of 311 subjects with and 287 without SLD underwent a detailed clinical, laboratory, and anthropometrical evaluation. Fatty liver was diagnosed by ultrasonography, and alcohol intake was assessed by using a 7-day diary. Multinomial logistic regression was used to detect risk factors for normal liver versus nonalcoholic fatty liver disease (NAFLD) and for alcoholic fatty liver (AFLD) versus NAFLD. The prevalence of NAFLD was similar in subjects with and without SLD (25 vs. 20%, P = .203). At multivariable analysis, normal liver was more likely than NAFLD in older subjects and less likely in the presence of obesity, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and systolic hypertension; AFLD was more likely than NAFLD in older subjects, males, and in the presence of elevated GGT and hypertriglyceridemia, and less likely in the presence of obesity and hyperglycemia. In conclusion, NAFLD is highly prevalent in the general population, is not associated with SLD, but is associated with many features of the metabolic syndrome. (Hepatology 2005.)

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. The prevalence of NAFLD in the general population of Western countries is 20–30%. About 2–3% of the general population is estimated to have non-alcoholic steatohepatitis (NASH), which may progress to liver cirrhosis and hepatocarcinoma. As a rule, the prevalence of NAFLD is higher in males and increases with increasing age, and it is influenced by the diagnostic method and the characteristics of the population, especially lifestyle habits. Population-based studies provide better estimates of the prevalence of NAFLD as compared to autoptic and clinical studies, but few such studies have been performed to date. The diagnosis of NAFLD in population studies is usually obtained by ultrasonography, which is known to underestimate the prevalence of fatty liver. The Dallas Heart Study and the Dionysos Study reported that 30% of the adults in the USA and 25% in Italy have NAFLD. In these studies, 79% and 55% of patients with NAFLD had normal aminotransferase levels, showing that liver enzymes are not surrogate markers of NAFLD in the general population. Noninvasive markers such as the fatty liver index obtained from the Dionysos Study may be useful to screen for NAFLD in the general population. The most important risk factors for NAFLD are male gender, age, obesity, insulin resistance and the cardiometabolic alterations that define the metabolic syndrome. The prevalence of NAFLD is 80–90% in obese adults, 30–50% in patients with diabetes and up to 90% in patients with hyperlipidemia. The prevalence of NAFLD among children is 3–10%, rising up to 40–70% among obese children. Moreover, pediatric NAFLD increased from about 3% a decade ago to 5% today, with a male-to-female ratio of 2:1. The incidence and natural history of NAFLD are still not well defined, but it is recognized that the majority of individuals with NAFLD do not develop NASH. The incidence of NAFLD is probably increasing in Western countries, strictly linked to lifestyle habits.

Summary: Background: Gut microbiota modifiers may have beneficial effects of non‐alcoholic fatty liver disease (NAFLD) but randomised controlled trials (RCT) are lacking in children.Aim: To perform a double‐blind RCT of VSL#3 vs. placebo in obese children with biopsy‐proven NAFLD.Methods: Of 48 randomised children, 44 (22 VSL#3 and 22 placebo) completed the study. The main outcome was the change in fatty liver severity at 4 months as detected by ultrasonography. Secondary outcomes were the changes in triglycerides, insulin resistance as detected by the homoeostasis model assessment (HOMA), alanine transaminase (ALT), body mass index (BMI), glucagon‐like peptide 1 (GLP‐1) and activated GLP‐1 (aGLP‐1). Ordinal and linear models with cluster confidence intervals were used to evaluate the efficacy of VSL#3 vs. placebo at 4 months.Results: At baseline, moderate and severe NAFLD were present in 64% and 36% of PLA children and in 55% and 45% of VSL#3 children. The probability that children supplemented with VSL#3 had none, light, moderate or severe FL at the end of the study was 21%, 70%, 9% and 0% respectively with corresponding values of 0%, 7%, 76% and 17% for the placebo group (P < 0.001). No between‐group differences were detected in triglycerides, HOMA and ALT while BMI decreased and GLP‐1 and aGLP1 increased in the VSL#3 group (P < 0.001 for all comparisons).Conclusions: A 4‐month supplement of VSL#3 significantly improves NAFLD in children. The VSL#3‐dependent GLP‐1 increase could be responsible for these beneficial effects. Trial identifier: NCT01650025 (www.clinicaltrial.gov)

Background: The study of the relationship between anthropometry and visceral adipose tissue (VAT) is of great interest because VAT is associated with many risk factors for noncommunicable diseases and anthropometry is easy to perform in clinical practice. The studies hitherto available for children have, however, been performed on small sample sizes. Design: Pooling of the data of studies published from 1992 to 2004 as indexed on Medline. Aims: To assess the relationship between anthropometry and VAT and subcutaneous adipose tissue (SAT) as measured by magnetic resonance imaging (MRI) in children and to analyze the effect of age, gender, pubertal status and ethnicity. Subjects and methods: Eligible subjects were 7–16 year-old, with availability of VAT and SAT, gender, ethnicity, body mass index (BMI) and waist circumference (WC). A total of 497 subjects were collected from seven different investigators and 407 of them (178 Caucasians and 229 Hispanics) were analyzed. Results: Despite ethnic differences in MRI data, BMI, WC and age, no difference in VAT was found between Caucasians and Hispanics after correction for SAT and BMI. Univariate regression analysis identified WC as the best single predictor of VAT (64.8% of variance) and BMI of SAT (88.9% of variance). The contribution of ethnicity and gender to the unexplained variance of the VAT–WC relationship was low (⩽3%) but significant (P⩽0.002). The different laboratories explained a low (⩽4.8%) but significant (P<0.0001) portion of the unexplained variance of the VAT–WC and SAT–BMI relationships. Prediction equations for VAT (VAT (cm²)=1.1 × WC (cm)−52.9) and SAT (SAT (cm²)=23.2 × BMI (kg/m²)−329) were developed on a randomly chosen half of the population and crossvalidated in the remaining half. The pure error of the estimate was 13 cm² for VAT and 57 cm² for SAT. Conclusions: WC can be considered a good predictor of VAT as well as BMI of SAT. The importance of ethnicity and gender on VAT estimation is not negligible.

Summary: Background  Recent studies suggest a role of n‐3 long‐chain polyunsaturated fatty acids (n‐3 PUFA) as peroxisome proliferator‐activated receptor‐α ligands in improving non‐alcoholic fatty liver disease (NAFLD) in rodents. However, data in humans are still lacking.Aim  To evaluate the efficacy of prolonged PUFA supplementation in patients with NAFLD.Methods  Fifty‐six patients with NAFLD were enrolled. Among the overall eligible patients, 42 assumed n‐3 PUFA 1‐g capsule daily for 12 months, whereas 14 refused the treatment and were analysed as controls. All patients underwent haematochemical and ultrasound follow‐up.Results  Polyunsaturated fatty acid supplementation significantly decreased serum aspartate transaminase (P = 0.003), alanine transaminase (P = 0.002), γ‐glutamyl transpeptidase (P = 0.03), triglycerides (P = 0.02) and fasting glucose (P = 0.02) in comparison with controls. Circulating arachidonate and n‐6/n‐3 fatty acid ratio was reduced (P = 0.0002, and P = 0.0001 respectively) in treated patients. Moreover, ultrasonography demonstrated improvement of liver echotexture after PUFA (P = 0.0001), and increase of Doppler perfusion index (P = 0.001), whereas no significant changes occurred in controls.Conclusions  Supplementation with n‐3 PUFA improves biochemical, ultrasonographic and haemodynamic features of liver steatosis. Our study supports the efficacy of n‐3 PUFA as a new therapeutic approach in the treatment of NAFLD.