Metabolomic‐based noninvasive serum test to diagnose nonalcoholic steatohepatitis: Results from discovery and validation cohorts

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease worldwide and includes a broad spectrum of histologic phenotypes, ranging from simple hepatic steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). While liver biopsy is the reference gold standard for NAFLD diagnosis and staging, it has limitations due to its sampling variability, invasive nature, and high cost. Thus, there is a need for noninvasive biomarkers that are robust, reliable, and cost effective. In this study, we measured 540 lipids and amino acids in serum samples from biopsy‐proven subjects with normal liver (NL), NAFL, and NASH. Using logistic regression analysis, we identified two panels of triglycerides that could first discriminate between NAFLD and NL and second between NASH and NAFL. These noninvasive tests were compared to blinded histology as a reference standard. We performed these tests in an original cohort of 467 patients with NAFLD (90 NL, 246 NAFL, and 131 NASH) that was subsequently validated in a separate cohort of 192 patients (7 NL, 109 NAFL, 76 NASH). The diagnostic performances of the validated tests showed an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.88 ± 0.05, 0.94, and 0.57, respectively, for the discrimination between NAFLD and NL and 0.79 ± 0.04, 0.70, and 0.81, respectively, for the discrimination between NASH and NAFL. When the analysis was performed excluding patients with glucose levels >136 mg/dL, the area under the receiver operating characteristic curve for the discrimination between NASH and NAFL increased to 0.81 ± 0.04 with sensitivity and specificity of 0.73 and 0.80, respectively. Conclusion: The assessed noninvasive lipidomic serum tests distinguish between NAFLD and NL and between NASH and NAFL with high accuracy. (Hepatology Communications 2018;2:807‐820)

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

“…Satisfactory AUROC values were obtained for NAFLD vs. NL. Exclusion of patients with glucose > 136 mg/dL improved the sensitivity and specificity for NASH vs. NAFL [198]. As with all studies of this nature, there was considerable overlap between the three different clinical states in serum metabolite profiles.…”

Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis

“…To date, few analyses based on metabolomics have been carried out in plasma/ serum for the identification of biomarkers for liver diseases, including cancers and PSC. (20,21) The value of metabolomics, and particularly lipidomics, has been previously highlighted in the discovery of biomarkers for the diagnosis of NAFLD and NASH, (13,22,23) which are currently in clinical use. This technique allowed different metabolomics subtypes of NASH to be identified in animal models and patients.…”

Noninvasive Diagnosis of NAFLD and NASH

“…Performed on a small amount of plasma by a Liquid Chromatography (LC)-Mass Spectrometry (MS) system, it is a commercial test indicated for adults with BMI > 25 suspected of having NASH. In order to establish the risk of the patients to present NAFLD, NASH, or no NAFLD, this diagnostic method measures two panels of triglycerides in serum and performs a combined analysis with the relative intensities of those triglycerides and the body mass index (BMI) of the patients [47]. This test was initially performed in an original cohort of 467 patients with NAFLD (90 normal liver, 246 NAFL, and 131 NASH).…”