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Background: The changes in nonalcoholic fatty liver disease (NAFLD) range over a wide spectrum, extending from steatosis to steatohepatitis (NASH). However, it has remained difficult to differentiate between NASH and nonprogressive NAFLD by clinical examination. We investigated the interrelationships between serum high-sensitivity C-reactive protein (hs-CRP) and the pathogenesis and progression of NASH., Methods: Hs-CRP was measured in 100 patients with histologically verified NAFLD (29 with steatosis and 71 with NASH), and a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to measure the intrahepatic mRNA expressions of CRP and interleukin (IL)-6., Results: The results of a multiple regression analysis revealed that in comparison with cases of steatosis, hs-CRP was significantly elevated (P = 0.0048) in cases of NASH. Furthermore, among patients with NASH, hs-CRP was significantly elevated in those with advanced fibrosis compared with that in those with mild fibrosis (P = 0.0384), even after adjustment for age, sex, presence of diabetes, body mass index, visceral fat area, subcutaneous fat area, homeostasis model assessment for insulin resistance, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol. The results of the RT-PCR analysis showed that intrahepatic mRNA expression of CRP, but not IL-6, was increased in patients with NASH compared with those with steatosis (P = 0.0228)., Conclusions: 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.

Background & Aims: Liver inflammation is a risk factor for the progression of nonalcoholic fatty liver disease (NAFLD). However, the diagnosis of liver inflammation is very difficult and invasive liver biopsy is still the only method to reliably detect liver inflammation. We previously reported that overexpression of CD14 in Kupffer cells may trigger the progression to nonalcoholic steatohepatitis (NASH) via liver inflammation following hyper-reactivity to low-dose lipopolysaccharide. Therefore, the aim of this study was to investigate the relationship between soluble type of CD14 (sCD14) and histological features in patients with NAFLD. Methods: Our cohort consisted of 113 patients with liver biopsy-confirmed NAFLD and 21 age-matched healthy controls. Serum sCD14 levels were measured by an enzyme-linked immunosorbent assay. Results: Serum sCD14 levels were significantly associated with diagnosis of NASH and the area under the receiver operator characteristic curve (AUROC) to distinguish between not NASH and NASH was 0.802. Moreover, serum sCD14 levels were significantly associated with the disease activity based on NAFLD activity score and hepatic CD14 mRNA expression, which is correlated with membrane CD14 (mCD14) expression, in patients with NAFLD. In multiple regression analysis, the serum sCD14 levels were independently associated with liver inflammation. The AUROC to distinguish between mild and severe liver inflammation in patients with NAFLD was 0.752. Conclusions: We found that serum sCD14 levels increased significantly with increasing liver inflammation grade in patients with NAFLD, reflecting increased hepatic CD14 expression. Serum sCD14 is a promising tool to predict the worsening of liver inflammation, and may offer a potential biomarker for evaluation of therapeutic effects in NAFLD. [ABSTRACT FROM AUTHOR]

Aim: Although non-alcoholic fatty liver disease (NAFLD) is now a common cause of chronic liver disease, discriminating between simple steatosis and non-alcoholic steatohepatitis (NASH), especially early-stage NASH, remains difficult. We investigated the clinical usefulness of measuring the spleen volume as a marker of early-stage NASH. Methods: We evaluated computed tomography (CT) images obtained in 84 patients with histologically diagnosed NAFLD (22 with simple steatosis, 62 with NASH with mild fibrosis [stages 1–2]). We defined the data obtained by the following formula as a spleen-body index (SBI): SBI = maximal CT axial section area of the spleen (cm2)/body surface area (BSA) (cm2) × 104. We compared the SBI between patients with simple steatosis and those with NASH with mild fibrosis. Results: The mean SBI of the simple steatosis group was 15.8 ± 3.9, while that of the NASH with mild fibrosis group was 18.7 ± 5.7. This difference between the two groups was significant ( P = 0.0314). A multiple logistic regression analysis showed that the SBI was significantly correlated with the discrimination of simple steatosis and NASH with mild fibrosis. The area under the receiver–operator curve was 0.661 for distinguishing between simple steatosis and NASH with mild fibrosis ( P = 0.026, 95% confidence interval = 0.532–0.789). Conclusion: Spleen enlargement may be a distinct feature of NASH, especially early-stage NASH. SBI might be a non-invasive and simple method of differentiating NASH and simple steatosis. [ABSTRACT FROM AUTHOR]

The changes in nonalcoholic fatty liver disease range over a wide spectrum, extending from simple steatosis to nonalcoholic steatohepatitis (NASH). We investigated the clinical usefulness of the type IV collagen 7s domain and hyaluronic acid for predicting the severity of fibrosis before progression to the cirrhotic stage in NASH patients. The type IV collagen 7s domain and hyaluronic acid were measured in 72 patients with histologically verified NASH. In a univariate analysis, marked elevation of hyaluronic acid and the type IV collagen 7s domain was observed in the NASH patients with advanced fibrosis compared with those with mild fibrosis ( P = 0.0028, P = 0.0006, respectively). For detection of NASH with advanced fibrosis, the area under the receiver-operating characteristic curves for type IV collagen 7s domain and hyaluronic acid were 0.767 and 0.754, respectively. However, multiple regression analysis revealed that the type IV collagen 7s domain, but not hyaluronic acid, was significantly elevated in patients with advanced fibrosis even after adjustment for age, sex, platelet count, prothrombin time, aspartate aminotransferase/alanine aminotransferase ratio, body mass index, and presence of underlying type 2 diabetes mellitus, all of which have previously been reported as useful predictors of advanced fibrosis in patients with NASH ( P = 0.0127, P = 0.2804, respectively). This is the first report to demonstrate a consistent and profound elevation of the type IV collagen 7s domain in NASH patients with advanced fibrosis (before progression to the stage of cirrhosis) compared with those with mild fibrosis. [ABSTRACT FROM AUTHOR]