This is the first report to demonstrate consistent and profound elevation of hs-CRP in cases of NASH compared with in cases of simple nonprogressive steatosis. Our results suggest that hs-CRP may be a clinical feature that not only distinguishes NASH from simple nonprogressive steatosis but also indicates the severity of hepatic fibrosis in cases of NASH.

Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.

Antiplatelet agents, especially cilostazol, offer the promise of becoming key agents for the treatment of NAFLD.

Major clinical parameters and histological observations were significantly improved by the treatment with ezetimibe. Our pilot study demonstrated the efficacy of ezetimibe for drug therapy of NASH and may lead to a large-scale clinical trial in the future.

OBJECTIVE -Until now, few clinical studies have reported on the association between the indexes of body fat distribution and serum ferritin, an indicator of body iron stores and a putative risk factor for insulin resistance. We investigated the association between serum ferritin concentrations and the indexes of distribution of adipose tissues in the body, such as the visceral fat area (VFA), the subcutaneous fat area (SFA), and the hepatic fat content in Japanese subjects.RESEARCH DESIGN AND METHODS -A total of 248 Japanese subjects (127 men and 121 postmenopausal women aged 57.8 Ϯ 13.9 years, BMI 25.7 Ϯ 4.6 kg/m 2 ; 140 subjects with type 2 diabetes and 108 nondiabetic subjects) were evaluated. Subjects with a history of alcohol intake were excluded from the study. We measured body height, body weight, and serum ferritin, as well as fasting plasma glucose and plasma insulin concentrations. We estimated insulin resistance by homeostasis model assessment. The fat distribution was evaluated by measuring the VFA and SFA by abdominal computed tomography at the umbilical level. To assess the hepatic fat content, the ratio of the computed tomography attenuation value of the liver to that of the spleen was calculated.RESULTS -Serum ferritin was significantly correlated with the various indexes of adiposity examined, such as the hepatic fat content (r ϭ Ϫ0.280, P Ͻ 0.0001), VFA (r ϭ 0.254, P Ͻ 0.0001), SFA (r ϭ 0.231, P ϭ 0.0005), and homeostasis model assessment (r ϭ 0.286, P ϭ 0.0008).CONCLUSIONS -This is the first report to directly demonstrate an association between serum ferritin and VFA and SFA. The results of this study suggest that the serum ferritin concentration may be a useful indicator of systemic fat content and degree of insulin resistance. Diabetes Care 28:2486 -2491, 2005P revious studies (1,2) have investigated the relationship between radiologically measured abdominal fat accumulation, hepatic fat content, and metabolic risk factors. It has been reported that both the visceral fat area (VFA) and the hepatic fat content are correlated with plasma triglyceride levels and glucose disposal (1,2). Elevation of serum ferritin concentrations has been suggested to be one of the components of the insulin resistance syndrome (3)(4)(5). In a population study of 1,013 eastern Finnish men (3), the serum ferritin concentrations were shown to be well correlated with the fasting plasma glucose and insulin concentrations. A subsequent study also revealed that circulating ferritin levels were related to the degree of insulin resistance (4). However, only a few studies have reported on the relationship between the serum ferritin concentrations and various indexes of adiposity. A study of Spanish subjects demonstrated no association between serum ferritin concentrations and the waist-to-hip ratio (4). On the other hand, a study of Norwegian men demonstrated independent associations between serum ferritin concentrations and the waist-to-thigh ratio and BMI (6). Gillum et al. also reported that the serum ferritin concentra...