LAUSR

The recently published article by Takyar et al. strongly suggests that nonalcoholic fatty liver disease (NAFLD) has emerged as a major public health problem in ethnically disparate population(s) in the postgenomic era. Healthy volunteers (disease-free controls) are indeed essential and/or critical for stringent, robust, and reliable biomedical research worldwide, including the Western world as well as the Asian Pacific region with a significant proportion of NAFLD patients. The cross-sectional study’s overall quality could have been enhanced with more meaningful interpretation of data if the investigators had maintained homogeneity in case and control numbers (3,160 subjects/149 trials: 101 noninterventional, 33 interventional, and 15 vaccine trials) and incorporated age-matched controls; a major study strength is the stratified/subgroup analysis in females and males with relevant statistical adjustments for clinical covariates/parameters (phosphorylated nuclear factor, alanine aminotransferase cut-off titers 20 for women or 31 for men and body mass index >25). Written informed consent is a core tenet of bioethics in good-practice research; healthy controls/volunteers and NAFLD cases in clinical trials should be explained the rationale of participation in the study by organizing a one-to-one interview and/or counseling/awareness lecture session. I wish to add that successful strategies utilizing meaningful participation of age-matched, healthy, disease-free controls of same ethnicity in a population-based disease management clinical research study protocol(s) are warranted in the near future so as to provide a broadspectral public health research model in terms of a cost-effective, patient-friendly, timeline-based global collaborative environment with pooled samples of diverse genetic landscapes. One of the major challenges in the hepatology research field is the relative paucity of clinically relevant predictive and prognostic biomarkers to identify and accordingly stratify susceptible individuals at risk of developing NAFLD; this demerit/drawback can be significantly diminished by recruiting age-matched, healthy controls of the same ethnicity as NAFLD cases so that the possibility of population admixture is ruled out. Furthermore, selective or combined use of different molecular computed tomography/magnetic resonance imaging diagnostic modalities in liver imaging (elastography, iron/fat deposition) is a promising strategy for monitoring livertissue–specific aberrations in disease progression in asymptomatic versus symptomatic study subjects. Targeting interrelated biochemical/metabolic pathways, especially transmembrane receptors and drug metabolizing enzymes/transporters, may be efficacious in unraveling the cellular/molecular mechanisms in NAFLD pathogenesis.