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Background & AimsNoninvasive methods have been evaluated for the assessment of liver fibrosis and steatosis in patients with nonalcoholic fatty liver disease (NAFLD). We compared the ability of transient elastography (TE) with the M-probe, and magnetic resonance elastography (MRE) to assess liver fibrosis. Findings from magnetic resonance imaging (MRI)−based proton density fat fraction (PDFF) measurements were compared with those from TE-based controlled attenuation parameter (CAP) measurements to assess steatosis.MethodsWe performed a cross-sectional study of 142 patients with NAFLD (identified by liver biopsy; mean body mass index, 28.1 kg/m2) in Japan from July 2013 through April 2015. Our study also included 10 comparable subjects without NAFLD (controls). All study subjects were evaluated by TE (including CAP measurements), MRI using the MRE and PDFF techniques.ResultsTE identified patients with fibrosis stage ≥2 with an area under the receiver operating characteristic (AUROC) curve value of 0.82 (95% confidence interval [CI]: 0.74−0.89), whereas MRE identified these patients with an AUROC curve value of 0.91 (95% CI: 0.86−0.96; P = .001). TE-based CAP measurements identified patients with hepatic steatosis grade ≥2 with an AUROC curve value of 0.73 (95% CI: 0.64−0.81) and PDFF methods identified them with an AUROC curve value of 0.90 (95% CI: 0.82−0.97; P < .001). Measurement of serum keratin 18 fragments or alanine aminotransferase did not add value to TE or MRI for identifying nonalcoholic steatohepatitis.ConclusionsMRE and PDFF methods have higher diagnostic performance in noninvasive detection of liver fibrosis and steatosis in patients with NAFLD than TE and CAP methods. MRI-based noninvasive assessment of liver fibrosis and steatosis is a potential alternative to liver biopsy in clinical practice. UMIN Clinical Trials Registry No. UMIN000012757.

Background and Aim: Recent studies have implicated several important hepatic cellular processes and signaling pathways that are affected by abnormal lipid metabolism, resulting in specific biochemical, histological, and clinical changes associated with NAFLD. We established highly sensitive and specific analysis of serum biomarkers for comprehensive view of the change in cholesterol and fatty acid metabolism by HPLC-ESI-MS/MS. By using this method, we monitored lipid metabolism in NAFLD patients before and during administration of pitavastatin. Materials and Methods: Serum samples were obtained from patients with NAFLD enrolled in multicenter case control study (n=15) at baseline, 3 months (mo), and 12 mo from initiation of pitavastatin treatment(1~2mg/day). Sex and age matched control (CTL) samples were obtained from 36 healthy volunteers with none of obesity, hyperlipidemia, and liver dysfunction. Internal standards were added to 10μL of serum. After extraction and derivatization, the samples were analyzed by LC-MS/MS equipped with reversed C18 column. Results: Markers of intestinal cholesterol absorption, serum sitosterol (CTL vs. NAFLD: 4.04±1.79 vs 1.69±0.68 ng/mL, P

Backgrounds/Aims: Bach1 is a transcriptional repressor of heme oxygenase-1 (HO-1). HO1 has cytoprotective activities through its antioxidant and anti-inflammatory properties. In this study, we investigated the effect of bach1 knockout on an animal model of NASH. Methods: Ten-week old male C57BL/6J mice (WT) and bach1 deficient mice (KO) were pair-fed either a chow or methionine/choline deficient (MCD) diet for 8 weeks (n=15 each). At fixed periods, mice were sacrificed, and livers and blood were collected. Histological findings were assessed by HE and Azan-Mallory staining. Serum transaminases were analyzed enzymatically. Hepatic mRNA expression of HO-1, TGF-β1, αSMA, peroxisome proliferator activated receptor α (PPARα) and microsomal triglyceride transfer protein (MTP) were analyzed by real-time PCR. Hepatic content of triglycerides (TG) was analyzed enzymatically. As the determination of hepatic oxidative stress generation, hepatic malondialdehyde (MDA) content was analyzed enzymatically. Results: Whereas MCD diet promoted significantly greater weight loss (chow -15%; MCD -40%, P < 0.05), significant change was not observed between WT and KO mice on each diet. At 8 weeks on MCD diet, liver inflammation and steatosis were pathohistologically significantly attenuated in KO mice when compared with WT mice, but changes found in the serum level of ALT were not significant. The expression of hepatic HO-1 mRNA was increased in KO mice when compared with WT mice (6.1fold). Upregulation of hepatic MDA content by MCD diet (4.2-fold) was inhibited in KO mice thoroughly. MCD diet feeding increased hepatic content of TG in WT mice (6.1-fold). But, in KO mice, such change was repressed significantly. In WT mice, MCD diet reduced hepatic PPARα and MTP mRNA expression significantly, whereas such a change was not observed in KO mice. Hepatic expression of TGF-β1 and αSMA mRNA was expressed at higher levels in WT mice after 1 and 4 weeks on the MCD diet when compared to KO mice. Such changes were not observed in WT and KO mice on chow diet. Conclusions: Up-regulation of HO-1 induced by Gene ablation of bach1 improved steatosis, at least in part, through themechanism of hepatic secretion of TG associated with PPARα-MTP pathway. HO-1 also inhibited ROS generation in the liver and suppressed the activation of hepatic stellate cells, suggesting its causal relation to liver fibrosis. We speculate that HO-1 plays a protective role in the development of NASH through its cytoprotective and anti-oxidant activities.