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

Pauline Verhaegh, Roisin Bavalia, Bjorn Winkens, Ad Masclee, Daisy Jonkers, Ger Koek*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

21 Citations (Web of Science)

Abstract

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 (sens(p)) and specificity (spec(p)) 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 (sens(p), 63.5% and spec(p), 74.4%) within routine biochemical tests, adiponectin (sens(p), 72.0% and spec(p), 75.7%) within inflammatory markers, CK18-M30 (sens(p), 68.4% and spec(p), 74.2%) within markers of cell death or proliferation and homeostatic model assessment of insulin resistance (sens(p), 69.0% and spec(p), 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% sens(p) and 95.3% spec(p)) and the GlycoNASH test (67.1% sens(p) and 63.8% spec(p)).

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.

Original languageEnglish
Pages (from-to)837-861
Number of pages25
JournalClinical gastroenterology and hepatology
Volume16
Issue number6
DOIs
Publication statusPublished - Jun 2018

Keywords

  • ALT
  • Diagnostic Accuracy
  • NAFLD Severity
  • Sensitivity and Specificity
  • FATTY LIVER-DISEASE
  • MORBIDLY OBESE-PATIENTS
  • POLYPEPTIDE SPECIFIC ANTIGEN
  • CLINICAL SCORING SYSTEM
  • IV COLLAGEN 7S
  • BARIATRIC SURGERY
  • BIOMARKER PANEL
  • PREDICTING STEATOHEPATITIS
  • ALANINE AMINOTRANSFERASE
  • PLASMA CYTOKERATIN-18

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