Electrochemical biosensors for MMP-9 in hepatitis B liver inflammation

Chronic hepatitis B (CHB) currently lacks a rapid and objective inflammatory marker. However, matrix metalloproteinase-9 (MMP-9) is a biomarker for necroinflammation and fibrosis, as it is mechanistically linked to these processes. This review summarizes the data supporting the association between circulating MMP-9 and hepatic necroinflammation and assesses the use of electrochemical biosensors for quantification at the point of care (POC). MMP-9 is found in several molecular forms, including pro-MMP-9 (∼92 kDa) and active (∼82-83 kDa), with different clinical implications. Active MMP-9 represents the ongoing matrix remodelling whereas total MMP-9 represents the summed expression (r = 0.81 zymography vs enzyme-linked immunosorbent assay (ELISA)). However, a direct comparison of these forms in terms of histology and outcomes has not been performed. Treatment dynamics provide a good clinical background: serum MMP-9 drops 40-60 % in 6 months of antiviral therapy with normalization of MMP-9 4-8 weeks before alanine aminotransferase (ALT) making MMP-9 an early treatment response marker (≥50 % reduction predicts good outcome whereas ≤30 % predicts failure). Conformity to clinical needs requires Total Allowable Error (TEa) analysis with clinical decision limits for significant inflammation (≥G2) being ∼150-180, advanced fibrosis (F2) ∼200-220, and cirrhosis (F4) ∼300 ng/mL. Multi-platform standardization includes commuted secondary reference materials for CHB with stable pro/active ratios and external quality assessment programs that confirm multi-laboratory interoperability. As such, it is suggested that a four-step framework of validation that combines clinical thresholds, commutable reference materials, and EQA-harmonized reporting be employed to ensure reliable MMP-9 biosensing for monitoring hepatitis B worldwide.