Background/Aims: Ultrasound is used to screen for hepatic steatosis, the most common liver disease in the United States. However, few studies have prospectively evaluated the accuracy of ultrasound to diagnose hepatic steatosis. Therefore, a double blinded prospective study was performed in consecutive patients undergoing liver biopsy to evaluate the accuracy of ultrasound to diagnose hepatic steatosis. Methods: Real time ultrasound was performed just prior to the biopsy by a single investigator masked to the clinical diagnosis. The liver biopsy was reviewed by a pathologist masked to the clinical indication or sonographic findings Results: Of 73 consecutive patients studied,macrovesicular steatosis of any severity on biopsy was found in 46 (63%) and micro vesicular fat found in 51 (69.9%). The overall impression of the sonographer for the presence of macrovesicular hepatic steatosis of any degree had a sensitivity of 60.9% and a specificity of 100%. The sensitivity increased to 100% and the specificity to 90% when there was ≥ 20% of fat. The zonular distribution of the fat did not alter the diagnostic accuracy of ultrasound. Ultrasound had a poor yield in the diagnosis of microvesicular fat with an overall sensitivity of 43% and a specificity of 73%. The combination of increased echogenicity and portal vein blurring on ultrasound had the greatest sensitivity in the diagnosis of hepatic steatosis. Conclusion: Real time ultrasound using a combination of sonographic findings has a high specificity but underestimates the prevalence of hepatic steatosis when there is less than ≥ 20% fat.

Background Nonalcoholic steatohepatitis (NASH) is common and severe in patients with diabetes mellitus. Although, there are no effective treatments for NASH in diabetic patients, preliminary reports suggest that polyunsaturated fatty acids (PUFA) may be beneficial in these patients. Aim A prospective, randomized, double blind placebo controlled study (NCT 00323414) was performed in NASH patients with diabetes. Methods 37 patients (50.6±9.8y) with well controlled diabetes (HbA1C<8.5%) were randomized to receive either PUFA containing eicosapentaenoic acid 2160 mg and docosahexaenoic acid 1440 mg daily or an isocaloric, identical placebo containing corn oil for 48 weeks under CONSORT guidelines. Clinical, demographics, biochemical laboratory tests, body composition using DEXA® and liver biopsy were done at randomization and at the end of treatment. Liver biopsy was scored by the NASH CRN criteria. An intention to treat analysis was performed. Results At inclusion, gender, age, body weight, biochemical tests, glucose control and liver histology were similar in the 2 treatment groups. There was no change in liver enzymes, body weight or body composition during the study in either group. At the end of treatment, hepatic steatosis and the activity score improved (p<0.05) and lobular inflammation worsened (p<0.001) with placebo but was unchanged with PUFA. At the end of treatment, insulin resistance (serum glucose and HOMA) worsened with PUFA but not placebo. Conclusions PUFA provided no benefit over placebo in NASH patients with diabetes. The effects of PUFA on histology and insulin resistance were inferior to placebo. These data provide no support for PUFA supplements in NASH.

Background Hypovitaminosis D is common in obesity and insulin resistant states. Increased fat mass in patients with non-alcoholic fatty liver disease (NAFLD) may contribute to hypovitaminosis D. Aims To determine the relation between plasma vitamin D concentration, severity of disease and body composition in NAFLD. Methods Plasma vitamin D concentration was quantified in 148 consecutive biopsy proven patients with NAFLD (non alcoholic steatohepatitis-NASH: n=81; and hepatic steatosis n=67) and healthy controls (n=39). NAFLD was scored using the NASH CRN criteria. Body composition was quantified by bioelectrical impedance analysis and abdominal CT image analysis. Results Plasma vitamin D concentration was significantly lower in NAFLD (21.2±10.4 ng/ml) compared to healthy controls (35.7±6.0 ng/ml). Higher NAFLD activity scores were associated with lower plasma concentration of vitamin D (r2=0.29; p<0.001). Subgroup analysis among patients with NAFLD showed that patients with NASH had significantly lower (p<0.01) vitamin D levels than those with steatosis alone (18.1±8.4 vs. 25.0±11.3 ng/ml). Low concentrations of vitamin D were associated with greater severity of steatosis, hepatocyte ballooning and fibrosis (p<0.05). On multivariate regression analysis, only severity of hepatocyte ballooning was independently associated (p=0.02) with low vitamin D concentrations. Plasma vitamin D (p=0.004) and insulin concentrations (p=0.03) were independent predictors of the NAFLD activity score on biopsy. Patients with NAFLD had higher fat mass that correlated with low vitamin D (r2=0.26; p=0.008). Conclusions Low plasma vitamin D concentration is an independent predictor of the severity of NAFLD. Further prospective studies demonstrating the impact of vitamin D replacement in NAFLD patients are required.