Transient elastography (TE) has received increasing attention as a means to evaluate disease progression in chronic liver disease patients. In this study, we assessed the value of TE for the prediction of fibrosis stage in a cohort of pediatric patients with nonalcoholic steatohepatitis. Furthermore, TE interobserver agreement was evaluated. TE was performed in 52 consecutive biopsy-proven nonalcoholic steatohepatitis patients (32 males, 20 females, age 13.6 ؎ 2.44 years). The area under the receiver operating characteristic curves for the prediction of "any" (>1), significant (>2), or advanced fibrosis (>3) were 0.977, 0.992, and 1, respectively. Calculation of multilevel likelihood ratios showed that TE values <5, <7, and <9 kPa, suggest the presence of "any" fibrosis, significant fibrosis, and advanced fibrosis, respectively. TE values between 5 and 7 kPa predict a fibrosis stage of 1, but with some degree of uncertainty. TE values between 7 and 9 kPa predict fibrosis stages 1 or 2, but cannot discriminate between these two stages. TE values of at least 9 kPa are associated with the presence of advanced fibrosis. The intraclass correlation coefficient for absolute agreement was 0.961. Conclusion: TE is an accurate and reproducible methodology to identify pediatric subjects without fibrosis or significant fibrosis, or with advanced fibrosis. In patients in which likelihood ratios are not optimal to provide a reliable indication of the disease stage, liver biopsy should be considered when clinically indicated. (HEPATOLOGY 2008;48:442-448.) N onalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, a cluster of abnormalities related to insulin resistance, which is frequently associated with obesity. Given the strong association of NAFLD with increased body mass index (BMI) and the considerable increase in the prevalence of overweight among children and adolescents, 1 NAFLD represents an emerging clinical problem affecting a substantial proportion of these subjects (2.6%-9.8%), 2-3 especially in the presence of obesity. 4 The high prevalence of NAFLD, and the likelihood of evolution to cirrhosis and its complications warrant increased attention toward this disorder. 5-9 Disease progression depends on the presence of hepatocellular damage, inflammation and fibrogenesis which define a pathological entity called nonalcoholic steatohepatitis (NASH).Currently, histopathological analysis of liver tissue represents the only means to assess fibrosis in NAFLD. 10 In the past decade, major efforts have been directed at identifying noninvasive methods for the assessment of liver fibrosis in different chronic liver diseases (CLD) including NAFLD. 11 These efforts assume a particular relevance in the pediatric setting, where the use of liver biopsy is perceived as bearing higher risks and is less acceptable than in adults.A noninvasive medical device based on transient elastography (TE) (Fibroscan; Echosens, Paris, France) has

DHA supplementation improves liver steatosis and insulin sensitivity in children with NAFLD.

Background: Liver fibrosis is a stage of non-alcoholic fatty liver disease (NAFLD) which is responsible for liver-related morbidity and mortality in adults. Accordingly, the search for noninvasive markers of liver fibrosis has been the subject of intensive efforts in adults with NAFLD. Here, we developed a simple algorithm for the prediction of liver fibrosis in children with NAFLD followed at a tertiary care center.

Congenital Hepatic Fibrosis (CHF) is a disease of the biliary epithelium characterized by bile duct changes resembling ductal plate malformations and by progressive peribiliary fibrosis, in the absence of overt necroinflammation. Progressive liver fibrosis leads to portal hypertension and liver failure, however the mechanisms leading to fibrosis in CHF remain elusive. CHF is caused by mutations in PKHD1, a gene encoding for fibrocystin, a ciliary protein expressed in cholangiocytes. Using a fibrocystin-defective (Pkhd1del4/del4) mouse, which is orthologous of CHF, we show that Pkhd1del4/del4 cholangiocytes are characterized by a β-catenin-dependent secretion of a range of chemokines, including CXCL1, CXCL10 and CXCL12, which stimulate bone marrow-derived macrophage recruitment. We also show that Pkhd1del4/del4 cholangiocytes, in turn, respond to proinflammatory cytokines released by macrophages by up-regulating αvβ6 integrin, an activator of latent local TGFβ1. While the macrophage infiltrate is initially dominated by the M1 phenotype, the profibrogenic M2 phenotype increases with disease progression, along with the number of portal myofibroblasts. Consistent with these findings, clodronate-induced macrophage depletion results in a significant reduction of portal fibrosis and portal hypertension as well as of liver cysts. Conclusion our results show that fibrosis can be initiated by an epithelial cell dysfunction, leading to low-grade inflammation, macrophage recruitment and collagen deposition. These findings establish a new paradigm for biliary fibrosis and represent a model to understand the relationship between cell dysfunction, parainflammation, liver fibrosis and macrophage polarization over time.