The 2023 AASLD update on NAFLD/MASH (Rinella et al, Hepatology) made the non-invasive fibrosis panel mainstream. Liver biopsy stays the gold standard for ambiguous cases, but the 4-marker serum panel + FibroScan now do most of the day-to-day staging that biopsy used to be required for.
The four markers and what each adds
Hyaluronic acid (HA) — the single best marker for cirrhosis (F4) in NAFLD. Sinusoidal endothelial dysfunction reduces HA clearance, so it accumulates. AASLD-validated.
Type IV Collagen (Col IV) — basement membrane turnover marker. Released by activated hepatic stellate cells during ECM deposition. Predicts NASH-to-cirrhosis progression independent of AST/ALT.
Laminin — basement membrane glycoprotein. Tracks active fibrogenesis and correlates with portal hypertension. Useful as a "fibrosis is happening right now" signal.
PIIIP N-P (Type III procollagen N-terminal peptide) — Type III collagen predominates in early fibrosis (F1-F2), making PIIIP the best of the four for catching disease early.
Run together, the panel reaches >85% sensitivity for F3-F4 staging.
Where the ELF score fits
The Enhanced Liver Fibrosis (ELF) score combines HA + PIIIP + TIMP-1 into a single number. FDA-cleared in 2021. ELF >= 9.8 = clinically significant fibrosis. It's the cleanest single-number alternative to FibroScan when you don't have access to a vibration-controlled transient elastography machine, or when BMI / ascites limits FibroScan accuracy.
When biopsy is still the answer
- Discordance between FibroScan and 4-marker panel
- Suspected autoimmune hepatitis, PBC, or hemochromatosis on top of NAFLD
- Pre-liver-transplant evaluation
- Confirmation before starting resmetirom for MASH F2-F3 (the new FDA-approved antifibrotic)
Treatment implications
AASLD 2023 now lists resmetirom as the standard-of-care for MASH F2-F3. Identifying those patients requires either biopsy or a validated non-invasive panel. The 4-marker serum panel + FibroScan combination keeps the biopsy rate low while still giving the hepatologist enough confidence to initiate antifibrotic therapy.
Lab stocking
MME's Hepatic Fibrosis panel ships the full 4-marker set (HA, Col IV, Laminin, PIIIP N-P) plus Cholylglycine for hepatobiliary screening + ICP grading. Add ALT/AST/ALP/GGT from the standard chemistry menu for the full hepatology workup.