This investigation utilized clinical and histological data obtained from the National Institutes of Health–funded Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), which is a multicenter collaborative established to

assess the natural history, pathogenesis, and treatment of NAFLD in the United States. 11-14 Between 2004 and 2008, the NASH CRN enrolled adults and children with the full spectrum of biopsy-proven NAFLD histology into an observational database study. Additionally, nondiabetic, noncirrhotic adults with NASH histology were given the opportunity to enroll selleck chemicals into an adult treatment trial of Pioglitazone Versus Vitamin E Versus Placebo for Treatment of Non-Diabetic Patients With NASH (PIVENS Trial; clinical trial no.: NCT00063622). 14 All participating centers’ institutional review boards and a data- and safety-monitoring board approved all NASH CRN study protocols. Studies were in compliance with good clinical practice guidelines for human research quality standards. Each participant enrolled in the NASH CRN provided written informed consent.

The current investigation LDE225 supplier included adults enrolled either in the observational Database or the PIVENS trial between 2004 and 2008. The following criteria were used for inclusion in our analyses (n = 1,026): (1) age ≥18 years; (2) liver histology data available within 6 months of enrollment; (3) no clinically significant history of alcohol consumption (definition of excessive alcohol use in the NASH CRN observational Database: >20 or >10 g/day for men and women, respectively; definition of excessive alcohol consumption in PIVENS: >30 or >20 g/day for men and women, respectively); and (4) no evidence of other etiologies of chronic liver disease. 13 The primary outcome of interest

in this study was NAFLD histological severity. Liver biopsies were categorized as either NASH or non-NASH NAFLD. We also modeled the outcome of fibrosis, categorized as either mild (stage 0-2) 上海皓元 or advanced (stage 3-4). Individuals with NASH had liver biopsies (within 6 months of enrollment into a NASH CRN study) demonstrating the following typical histological features of NASH: steatosis, hepatocyte ballooning and lobular inflammation, with or without fibrosis, and that the NASH CRN Pathology Committee read as being “definite” or “borderline” NASH (see below). Also included in the NASH group were individuals with NASH-induced cirrhosis. Non-NASH histology refers to individuals with histological evidence of NAFLD, but who did not meet histological criteria for NASH, as determined by the NASH CRN Pathology Committee. Non-NASH histology would include, for example, liver biopsies demonstrating steatosis alone or steatosis with mild, nonspecific inflammation.