Assessment of non-alcoholic fatty liver disease (NAFLD) severity with novel serum-based markers: A pilot study

Abstract

Background/Aims Non-alcoholic fatty liver disease (NAFLD) represents a significant public health issue. Identifying patients with simple steatosis from those with non-alcoholic steatohepatitis (NASH) is crucial since NASH is correlated with increased morbidity and mortality. Serum-based markers, including adipokines and cytokines, are important in the pathogenesis and progression of NAFLD. Here we assessed the usefulness of such markers in patients with NAFLD. Methods This prospective, cross-sectional study included 105 adult patients with varying severity of NAFLD. Twelve serum-based markers were measured by 3 biochip platforms and 2 enzyme-linked immunosorbent assay (ELISA) methods. We also developed a NAFLD individual fibrosis index (NIFI) using the serum-based markers mostly correlated with fibrosis severity. Results Sixty-one out of 105 patients were male (58.1%) with mean age was 53.5 years. Higher Interleukin-6 (IL-6) increased (p = 0.0321) and lower Matrix Metalloproteinase-9 (MMP-9) serum levels (p = 0.0031) were associated with higher fibrosis as measured by Fibroscan® in multivariable regression analysis. Using receiver-operating characteristic (ROC) curve analysis for the NIFI, area under the curve for predicting Fibroscan values ≥ 7.2 kPa was 0.77 (95%CI: 0.67, 0.88, p<0.001), with sensitivity of 89.3%, specificity of 57.9% and a positive likelihood ratio of 2.8. Conclusions Increasing fibrosis severity in NAFLD is associated with differential expression of IL-6 and MMP-9. NIFI could be valuable for the prediction of advanced NAFLD fibrosis and potentially help avoid unnecessary interventions such as liver biopsy in low-risk patients.

Investigation of the potential mechanism of the Shugan Xiaozhi decoction for the treatment of nonalcoholic fatty liver disease based on network pharmacology, molecular docking and molecular dynamics simulation

“…MMP9 has a vital role in modulating and degrading gelatins, collagens and other ECM compounds ( D’Amico et al, 2010 ; Lachowski et al, 2019 ). A decreased level of MMP9 is associated with more advanced fibrosis and serum liver injury indexes in NAFLD patients ( Goyale et al, 2021 ). GRP78 (HSPA5) is a chaperone heat shock protein playing the central role in maintaining ER proteostasis under excessive stress ( Pobre, Poet & Hendershot, 2019 ).…”

“…MMP9 performs a vital role in modulating and degrading gelatins, collagens, and other ECM compounds ( D’Amico et al, 2010 ; Lachowski et al, 2019 ). A decreased MMP9 level is associated with more advanced fibrosis and serum liver injury indexes (AST, GGT) in NAFLD patients, while increased MMP9 activity could precede the clearance of the fibrotic matrix ( Goyale et al, 2021 ; Trojanek et al, 2020 ).…”

Key Genes Associated With Non-Alcoholic Fatty Liver Disease and Polycystic Ovary Syndrome

“…MMP9 was shown to be overexpressed in PCOS and involved in the pathogenesis of PCOS ( Ranjbaran et al, 2016 ). MMP9 could increase fibrosis severity in NAFLD and be involved in the development and progression of human HCC metastasis ( Shi et al, 2010 ; Goyale et al, 2021 ). TREM1 is expressed on myeloid lineage cells and played an important role in maintaining homeostasis and the normal immune responses.…”

Contribution of organokines in the development of NAFLD/NASH associated hepatocellular carcinoma

“…Since serum IL-6 levels are greater in NAFLD and NASH patients it has been considered as a potential biomarker for these liver pathologies. 319,346 IL-6 signaling in liverparenchymal cells suppresses hepatic inflammation and improves systemic insulin action in mice. 347 It is known to promote liver regeneration and is protective against several forms of liver damage including toxins, alcohol, ischemia and reperfusion.…”

“…It plays an important role in energy homeostasis and development of IR, which is a major factor in genesis of NAFLD. Since serum IL‐6 levels are greater in NAFLD and NASH patients it has been considered as a potential biomarker for these liver pathologies 319,346 . IL‐6 signaling in liver‐parenchymal cells suppresses hepatic inflammation and improves systemic insulin action in mice 347 .…”