Promising diagnostic biomarkers of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: From clinical proteomics to microbiome

Abstract

Fatty liver has been present in the lives of patients and physicians for almost two centuries. Vast knowledge has been generated regarding its etiology and consequences, although a long path seeking novel and innovative diagnostic biomarkers for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is still envisioned. On the one hand, proteomics and lipidomics have emerged as potential noninvasive resources for NAFLD diagnosis. In contrast, metabolomics has been able to distinguish between NAFLD and NASH, even detecting degrees of fibrosis. On the other hand, genetic and epigenetic markers have been useful in monitoring disease progression, eventually functioning as target therapies. Other markers involved in immune dysregulation, oxidative stress, and inflammation are involved in the instauration and evolution of the disease. Finally, the fascinating gut microbiome is significantly involved in NAFLD and NASH. This review presents state-of-the-art biomarkers related to NAFLD and NASH and new promises that could eventually be positioned as diagnostic resources for this disease. As is evident, despite great advances in studying these biomarkers, there is still a long path before they translate into clinical benefits.

Bile acids and sphingolipids in non-alcoholic fatty liver disease

“…Despite NAFLD being one of the fastest growing diseases, continued research is needed to elucidate the biological mechanisms underlying NAFLD to develop novel therapeutic interventions [24] . Multiple recent reviews have summarized the potential therapeutic and diagnostic value in targeting components of bile acid and sphingolipid metabolism [15,23,72–75] . Therapeutics which target different components of bile acid metabolism can have unanticipated effects on glucose homeostasis or lipid metabolism, but adverse side effects are mostly isolated to gastointestinal dysregulation [76] .…”

“…[24] Multiple recent reviews have summarized the potential therapeutic and diagnostic value in targeting components of bile acid and sphingolipid metabolism. [15,23,[72][73][74][75] Therapeutics which target different components of bile acid metabolism can have unanticipated effects on glucose homeostasis or lipid metabolism, but adverse side effects are mostly isolated to gastointestinal dysregulation. [76] However, bile acid pathways appear to be a sensible pharmacologic target.…”

Diagnostic scores and scales for appraising Nonalcoholic fatty liver disease and omics perspectives for precision medicine

“…These techniques include proteomics, transcriptomics, metabolomics, genomics and other novel markers such as the bacterial microbiome involving metagenomics [22 ▪▪ ]. Recent studies have shown that there are differences in protein expression between patients with NAFLD and healthy controls [48]. Also, specific genetic markers such as circulating microRNAs (miR-122 and miR-34, among others) seem to be a potential and attractive biomarker under study for NAFLD severity [31,49 ▪▪ ].…”

“…In this context, one of the most recent efforts to use ‘-omics’ approaches has been devoted to identify new biomarkers of NAFLD, NASH and advanced fibrosis [48]. These techniques include proteomics, transcriptomics, metabolomics, genomics and other novel markers such as the bacterial microbiome involving metagenomics [22 ▪▪ ].…”

Predictive Power of Tissue and Circulating Biomarkers for the Severity of Biopsy-Validated Chronic Liver Diseases

“…Although a liver biopsy should be still considered the gold standard for diagnosing and monitoring liver disease, the costs and invasiveness make such a procedure eligible only to selected cases. In the last decade, non-invasive diagnostic biomarkers, the use of transcriptomics, proteomics, and metabolomics to predict liver disease severity, progression, and response to lifestyle changes and pharmacological treatment has been developed [ 4 ]. Another area of research consists in characterizing genetic and epigenetic markers, which are useful in evaluating disease progression.…”