A serum “sweet-doughnut” protein facilitates fibrosis evaluation and therapy assessment in patients with viral hepatitis

TLDR

Liver fibrosis is a key marker of chronic hepatitis severity, yet no simple, accurate system exists to assess therapeutic impact. The authors aimed to create a glycan‑based immunoassay, FastLec‑Hepa, to fill this gap. FastLec‑Hepa rapidly detects a unique fibrosis‑related glyco‑alteration in serum hyperglycosylated Mac‑2 binding protein within 20 minutes. FastLec‑Hepa counts rise with fibrosis stage, distinguish all stages, sensitively quantify PEG‑interferon‑α/ribavirin treatment effects, reveal a −0.30 stage/year decline in sustained responders versus 0.01 stage/year in non‑responders, predict hepatocellular carcinoma when counts stay above a cutoff, and is currently the sole assay enabling clinically useful therapy evaluation.

Abstract

Although liver fibrosis reflects disease severity in chronic hepatitis patients, there has been no simple and accurate system to evaluate the therapeutic effect based on fibrosis. We developed a glycan-based immunoassay, FastLec-Hepa, to fill this unmet need. FastLec-Hepa automatically detects unique fibrosis-related glyco-alteration in serum hyperglycosylated Mac-2 binding protein within 20 min. The serum FastLec-Hepa counts increased with advancing fibrosis and illustrated significant differences in medians between all fibrosis stages. FastLec-Hepa is sufficiently sensitive and quantitative to evaluate the effects of PEG-interferon-α/ribavirin therapy in a short post-therapeutic interval. The obtained fibrosis progression is equivalent to -0.30 stages/year in patients with sustained virological response and 0.01 stages/year in relapse/nonresponders. Furthermore, long-term follow-up of the severely affected patients found hepatocellular carcinoma developed in patients after therapy whose FastLec-Hepa counts remained above a designated cutoff value. FastLec-Hepa is the only assay currently available for clinically beneficial therapy evaluation through quantitation of disease severity.