Diagnostic and interventional circulating biomarkers in nonalcoholic steatohepatitis

Abstract

Nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent forms of chronic liver disease with a global prevalence of approximately 25% among adults. 1 NAFLD is the broad umbrella term that encompasses the spectrum of FLD. Histologically, NAFLD is categorized into nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH). 2-4 To meet diagnostic criteria for NAFL, individuals must have ≥5% hepatic steatosis without evidence of hepatocellular injury. Alternatively, NASH is defined by the presence ≥5% hepatic steatosis with lobular inflammation and hepatocyte injury (ballooning) with or without hepatic fibrosis. 2 It is estimated that approximately 20% of individuals with NAFLD have NASH. 1,2,5 Clinical practice guidelines from both the American and European liver societies currently recommend liver biopsy as the gold standard for diagnosing and staging NASH. 2,6 Enrolment in NASH clinical trials and definition of therapeutic response to novel pharmacologic agents for NASH are also largely defined using histologic criteria. 7

Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted 1H-NMR Metabolomics

“…Increasing BCAAs have been noted in liver tissue in NAFLD progression [18,52], and comparing serum and tissue levels of BCAAs in NAFLD could help to better understand their trends in NAFLD. Given the consistent rates of obesity and diabetes between the groups in Table 1, which are also supported by BCAA/AAA levels not changing significantly, the increasing hba1c trend in this work is attributed to NAFLD progression and is consistent with the use of hba1c as a reporter on NAFLD [27].…”

“…Subjects were classified on assessment of liver sections, which is the gold standard for determining NAFLD progression. The progression of NAFLD in the groups in Table 1 is also illustrated by insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and waist circumference, which were observed to vary significantly across the groups and have known associations with NAFLD [26][27][28].…”

“…Importantly, markers often associated with T2D can also be affected by NAFLD progression. Notably, Hba1c and insulin levels are incorporated into diagnostic models of NAFLD [27]. Given the evidence that T2D did not change across the groups, the Hba1c and insulin levels are more likely to report on NAFLD progression in this work.…”

Primary care and referring physician perspectives on non-alcoholic fatty liver disease management: a nationwide survey

“…14 The role for screening will continue to evolve based on optimization of non-invasive methods to diagnose and risk stratify patients, and as the treatment landscape improves. 15,16 Our study also highlighted the low uptake of recommendations to use non-invasive serum and imaging biomarkers to risk stratify patients. In Finally, our study reinforced the ongoing challenges in primary care regarding uptake and maintenance of first-line therapy for NAFLD, lifestyle interventions.…”

Mitochondrial Mutations and Genetic Factors Determining NAFLD Risk

“…Metabolic abnormalities can be detected in peripheral cells and used as biomarkers to estimate the NAFLD/NASH stage and liver status. The levels of OS and pro-inflammatory cytokines are the main markers to monitor NAFLD severity and progression [ 39 ]. Additionally, there are several metabolic pathways completely or partly localized to the mitochondria, such as citric acid and urea cycles.…”