Liver fibrosis is a key prognostic determinant for clinical outcomes in non-alcoholic steatohepatitis (NASH). Current scoring systems have limitations, especially in assessing fibrosis regression. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses provides standardized evaluation of NASH features, especially liver fibrosis and collagen fiber quantitation on a continuous scale. This approach was applied to gain in-depth understanding of fibrosis dynamics after treatment with tropifexor (TXR), a non-bile acid farnesoid X receptor agonist in patients participating in the FLIGHT-FXR study (NCT02855164).
Unstained sections from 198 liver biopsies (paired: baseline and end-of-treatment) from 99 patients with NASH (fibrosis stage F2 or F3) who received placebo (n = 34), TXR 140 μg (n = 37), or TXR 200 μg (n = 28) for 48 weeks were examined. Liver fibrosis (qFibrosis®), hepatic fat (qSteatosis®), and ballooned hepatocytes (qBallooning®) were quantitated using SHG/TPEF microscopy. Changes in septa morphology, collagen fiber parameters, and zonal distribution within liver lobules were also quantitatively assessed.
Digital analyses revealed treatment-associated reductions in overall liver fibrosis (qFibrosis®), unlike conventional microscopy, as well as marked regression in perisinusoidal fibrosis in patients who had either F2 or F3 fibrosis at baseline. Concomitant zonal quantitation of fibrosis and steatosis revealed that patients with greater qSteatosis reduction also have the greatest reduction in perisinusoidal fibrosis. Regressive changes in septa morphology and reduction in septa parameters were observed almost exclusively in F3 patients, who were adjudged as ‘unchanged’ with conventional scoring.
Fibrosis regression following hepatic fat reduction occurs initially in the perisinusoidal regions, around areas of steatosis reduction. Digital pathology provides new insights into treatment-induced fibrosis regression in NASH, which are not captured by current staging systems.
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The Journal of Hepatology publishes original papers, reviews, case reports and letters to the Editor concerned with clinical and basic research in the field of hepatology. The Journal is published in English. Supplements may be accepted after editorial review.The full text of the Journal of Hepatology is available online via two sources: Institutional access: If your library has a subscription to ScienceDirect and has elected to include the Journal of Hepatology, you can access the journal online via www.sciencedirect.com.Please go to www.journal-of-hepatology.eu to access the Journal of Hepatology online.