Although diet-induced weight loss is first-line treatment for patients with nonalcoholic fatty liver disease (NAFLD), long-term maintenance is difficult. The optimal diet for improvement in either NAFLD or associated cardiometabolic risk factors, regardless of weight loss, is unknown. We examined the effect of two ad libitum isocaloric diets (Mediterranean [MD] or low fat [LF]) on hepatic steatosis (HS) and cardiometabolic risk factors. Subjects with NAFLD were randomized to a 12-week blinded dietary intervention (MD vs. LF). HS was determined by magnetic resonance spectroscopy (MRS). From a total of 56 subjects enrolled, 49 completed the intervention and 48 were included for analysis. During the intervention, subjects on the MD had significantly higher total and monounsaturated fat, but lower carbohydrate and sodium, intakes compared to LF subjects (P < 0.01). At week 12, HS had reduced significantly in both groups (P < 0.01), and there was no difference in liver fat reduction between groups (P = 0.32), with mean (SD) relative reductions of 25.0% (±25.3%) in LF and 32.4% (±25.5%) in MD. Liver enzymes also improved significantly in both groups. Weight loss was minimal and not different between groups (-1.6 [±2.1] kg in LF vs -2.1 [±2.5] kg in MD; P = 0.52). Within-group improvements in Framingham Risk Score (FRS), total cholesterol, serum triglyceride (TG), and glycated hemoglobin (HbA1c) were observed in the MD (all P < 0.05), but not with the LF diet. Adherence was higher for the MD compared to LF (88% vs. 64%; P = 0.048). Conclusion: Ad libitum low-fat and Mediterranean diets both improve HS to a similar degree.

Background: Determining the stage of fibrosis by liver biopsy is important in managing patients with hepatitis C virus infection. We investigated the predictive value of the proprietary FibroTest score to accurately identify significant fibrosis in Australian hepatitis C patients. Methods: Serum obtained from 125 confirmed hepatitis C patients before antiviral therapy was analyzed for haptoglobin, α2-macroglobulin, apolipoprotein A1, bilirubin, and γ-glutamyltransferase activity, and the FibroTest score was computed. Liver fibrosis pathology was staged according to a defined system on a scale of F0 to F4. We used predictive values and a ROC curve to assess the accuracy of FibroTest scores. Results: The prevalence of significant fibrosis defined by liver biopsy was 0.38. The most useful single test for predicting significant fibrosis was serum α2-macroglobulin (cutoff value, 2.52 g/L; sensitivity, 75%; specificity, 67%). The negative predictive value of a FibroTest score &lt;0.1 was 85%, and the positive predictive value of a score &gt;0.6 was 78%. Although 33 of the 125 patients had FibroTest scores &lt;0.1 and were therefore deemed unlikely to have fibrosis, 6 (18%) had significant fibrosis. Conversely, of the 24 patients with scores &gt;0.6 who were likely to have significant fibrosis, 5 (21%) had mild fibrosis. Of the 125 patients in the cohort, 57 (46%) could have avoided liver biopsy, but discrepant results were recorded in 11 of those 57 (19%). Conclusion: The FibroTest score could not accurately predict the presence or absence of significant liver fibrosis.

Iron is implicated in the pathogenesis of liver injury and insulin resistance (IR) and thus phlebotomy has been proposed as a treatment for nonalcoholic fatty liver disease (NAFLD). We performed a prospective 6-month randomized, controlled trial examining the impact of phlebotomy on the background of lifestyle advice in patients with NAFLD. Primary endpoints were hepatic steatosis (HS; quantified by magnetic resonance imaging) and liver injury (determined by alanine aminotransaminase [ALT] and cytokeratin-18 ). Secondary endpoints included insulin resistance measured by the insulin sensitivity index (ISI) and homeostasis model of assessment (HOMA), and systemic lipid peroxidation determined by plasma F2-isoprostane levels. A total of 74 subjects were randomized (33 phlebotomy and 41 control). The phlebotomy group underwent a median (range) of 7 (1-19) venesection sessions and had a significantly greater reduction in ferritin levels over 6 months, compared to controls (2148 6 114 vs. 238 6 89 ng/mL; P < 0.001). At 6 months, there was no difference between phlebotomy and control groups in HS (17.7% vs. 15.5%; P 5 0.4), serum ALT (36 vs. 46 IU/L; P 5 0.4), or CK-18 levels (175 vs. 196 U/L; P 5 0.9). Similarly, there was no difference in end-of-study ISI (2.5 vs. 2.7; P 5 0.9), HOMA (3.2 vs. 3.2; P 5 0.6), or F2-isoprostane levels (1,332 vs. 1,190 pmmol/L; P 5 0.6) between phlebotomy and control groups. No differences in any endpoint were noted in patients with hyperferritinemia at baseline. Among patients undergoing phlebotomy, there was no correlation between number of phlebotomy sessions and change in HS, liver injury, or IR from baseline to end of study. Conclusion: Reduction in ferritin by phlebotomy does not improve liver enzymes, hepatic fat, or IR in subjects with NAFLD. (HEPATOLOGY 2015;61:1555-1564