Noninvasive Tests Do Not Accurately Differentiate Nonalcoholic Steatohepatitis From Simple Steatosis: A Systematic Review and Meta-analysis

Background & Aims Nonalcoholic fatty liver disease is a rapidly increasing health problem. Liver biopsy analysis is the most sensitive test to differentiate between nonalcoholic steatohepatitis (NASH) and simple steatosis (SS), but noninvasive methods are needed. We performed a systematic review and meta-analysis of noninvasive tests for differentiating NASH from SS, focusing on blood markers. Methods We performed a systematic search of the PubMed, Medline and Embase (1990–2016) databases using defined keywords, limited to full-text papers in English and human adults, and identified 2608 articles. Two independent reviewers screened the articles and identified 122 eligible articles that used liver biopsy as reference standard. If at least 2 studies were available, pooled sensitivity (sensp) and specificity (specp) values were determined using the Meta-Analysis Package for R (metafor). Results In the 122 studies analyzed, 219 different blood markers (107 single markers and 112 scoring systems) were identified to differentiate NASH from simple steatosis, and 22 other diagnostic tests were studied. Markers identified related to several pathophysiological mechanisms. The markers analyzed in the largest proportions of studies were alanine aminotransferase (sensp, 63.5% and specp, 74.4%) within routine biochemical tests, adiponectin (sensp, 72.0% and specp, 75.7%) within inflammatory markers, CK18-M30 (sensp, 68.4% and specp, 74.2%) within markers of cell death or proliferation and homeostatic model assessment of insulin resistance (sensp, 69.0% and specp, 72.7%) within the metabolic markers. Two scoring systems could also be pooled: the NASH test (differentiated NASH from borderline NASH plus simple steatosis with 22.9% sensp and 95.3% specp) and the GlycoNASH test (67.1% sensp and 63.8% specp). Conclusion In the meta-analysis, we found no test to differentiate NASH from SS with a high level of pooled sensitivity and specificity (≥80%). However, some blood markers, when included in scoring systems in single studies, identified patients with NASH with ≥80% sensitivity and specificity. Replication studies and more standardized study designs are urgently needed. At present, no marker or scoring system can be recommended for use in clinical practice to differentiate NASH from simple steatosis.