Non-invasive diagnosis for differentiating non-alcoholic steatohepatitis from simple steatosis: a meta-analysis and systematic review.Verhaegh P, Bavalia R, Winkens B, Masclee A, Jonkers D, Koek G. Clin Gastroenterol Hepatol. 2017 Aug 21. [Epub ahead of print]

BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is a rapidly increasing health problem. Liver biopsy is the most sensitive test to differentiate between non-alcoholic steatohepatitis (NASH) and simple steatosis (SS), but non-invasive diagnostics are warranted. We performed a systematic review on non-invasive tests for differentiating NASH from SS, focusing on blood markers.

METHODS:A systematic search in PubMed, Medline and Embase (1990-2016) using defined keywords, limited to full-text papers in English and human adults, resulted in 2608 hits. After screening by two independent reviewers, 122 eligible articles using liver biopsy as gold standard were identified. If at least 2 studies were available, pooled sensitivity (sensp) and specificity (specp) were determined using metafor in R.RESULTS:In total, 122 studies were identified, in which 219 different blood markers, either as single marker (n=107) or as part of scoring systems (n=112), and 22 other diagnostic tests were studied. Markers identified related to several pathophysiological mechanisms. Most extensively studied were alanine aminotransferase (sensp 63.5%, specp 74.4%) within routine biochemical tests, adiponectin (sensp 72.0%, specp 75.7%) within inflammatory markers, CK18-M30 (sensp 68.4%, specp 74.2%) within markers of cell death/proliferation and HOMA-IR (sensp 69.0%, specp 72.7%) within the metabolic markers. Two scoring systems could also be pooled, NASH test (NASH vs borderline NASH+SS sensp 22.9%, specp 95.3%) and the GlycoNASH test (sensp 67.1%, specp 63.8%).CONCLUSION:None of the pooled results revealed good sensitivity and specificity (≥80%), however, blood markers as part of scoring systems in single studies, showed promising results as non-invasive diagnostics for NASH. 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 SS.

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