Use of noninvasive tests (NITs) to diagnose and follow non-alcoholic steatohepatitis (NASH) with liver fibrosis patients treated with resmetirom

Background: MAESTRO-NASH (NCT03900429) is an ongoing 54-month, randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy of resmetirom in patients with biopsy-confirmed NASH and fibrosis. 966 patients with biopsy-confirmed NASH were randomized 1:1:1 to resmetirom 80 mg, resmetirom 100 mg, or placebo once daily. Dual primary endpoints at Week 52 were achieved with both resmetirom 80 mg and 100 mg: NASH resolution with no worsening of fibrosis (NR) or≥1-stage improvement in fibrosis with no worsening of NAS (FI). Both Week 52 liver biopsy endpoints, NR and FI, were achieved. Resmetirom was recently approved for the treatment of adult patients with noncirrhotic NASH and liver fibrosis consistent with F2 to F3 stages.

Objectives: Expert guidances recommend treatment with resmetirom based on staging fibrosis using FibroScan VCTE.

EASL recommends stratifying patients using FIB-4. Most guidelines recommend using VCTE cutoffs lower than 10-<15 kPa for treatment.

Methodology: We assessed results from baseline noninvasive tests (FIB-4, VCTE) against biopsy results inlogy MAESTRO-NASH to measure how well they diagnosed noncirrhotic patients with NASH (consistent with F2-F3 stages at baseline). We assessed the utility of a lower VCTE cutoff (8.5 to<10 kPa) in capture of F2 and F3 patients who otherwise would be missed. Also evaluated was the addition of MRE/MRI-PDFF or ELF to FibroScan VCTE to assess diagnostic utility.

Results: FIB-4 poorly predicted patients in the non-cirrhotic fibrosis stages: F2 (60% patients fell into low-risk) and F3 (40% fell into low-risk). Including a lower cutoff of VCTE (8.5 to<10 kPa) captured F1B (34% 8.5-<10 kPa) and many F2 (25% 8.5-<10 kPa) and F3 patients (19% 8.5-<10 kPa). The addition of MRE/MRI-PDFF to FibroScan VCTE increased diagnostic accuracy for F2/F3 to 68% and F4 to 81%. The addition of the ELF to the FibroScan VCTE suggested that a low ELF result paired with high VCTE may warrant a VCTE repeat.

Conclusion: Identification of patients with NASH F2 to F3 was achieved with FibroScan and VCTE.

F1B are F2 equivalent (F1B is moderate fibrosis on biopsy). Patients with fibrosis stage F4 were effectively ruled out. In addition to FibroScan VCTE, practitioners may consider expanded noninvasive criteria (ELF, MRE) to help refine fibrosis staging.