Abstract

Non-alcoholic steatohepatitis (NASH) is the progressive form of non-alcoholic fatty liver disease (NAFLD) and is diagnosed by a liver biopsy. Due to the invasiveness of a biopsy, the majority of patients with NASH are undiagnosed. Additionally, the prevalence of NAFLD and NASH creates the need for a simple screening method to differentiate patients with NAFLD versus NASH. Non-invasive strategies for diagnosing NAFLD versus NASH have been developed, typically relying on imaging techniques and endogenous biomarker panels. However, each technique has limitations, and none can accurately predict the associated functional impairment of drug metabolism and disposition. The function of several drug metabolizing enzymes and drug transporters have been described in NASH that impacts drug pharmacokinetics. The aim of this review is to give an overview of the existing non-invasive strategies to diagnose NASH, and to propose a novel strategy based on altered pharmacokinetics using an exogenous biomarker whose disposition and elimination pathways are directly impacted by disease progression. Altered disposition of safe and relatively inert exogenous compounds may provide the sensitivity and specificity needed to differentiate patients with NAFLD and NASH to facilitate a direct indication of hepatic impairment on drug metabolism and prevent subsequent adverse drug reactions.

Significance Statement This review provides an overview of the main non-invasive techniques (imaging and panels of biomarkers) used to diagnose non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) along with a biopsy. Pharmacokinetic changes have been identified in NASH and this review proposes a new approach to predict NASH and the related risk of adverse drug reactions, based on the assessment of drug elimination disruption using exogenous biomarkers.