qFibrosis: A fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients

Abstract

Background & Aims There is increasing need for accurate assessment of liver fibrosis/cirrhosis. We aimed to develop qFibrosis, a fully-automated assessment method combining quantification of histopathological architectural features, to address unmet needs in core biopsy evaluation of fibrosis in chronic hepatitis B (CHB) patients. Methods qFibrosis was established as a combined index based on 87 parameters of architectural features. Images acquired from 25 Thioacetamide-treated rat samples and 162 CHB core biopsies were used to train and test qFibrosis and to demonstrate its reproducibility. qFibrosis scoring was analyzed employing Metavir and Ishak fibrosis staging as standard references, and collagen proportionate area (CPA) measurement for comparison. Results qFibrosis faithfully and reliably recapitulates Metavir fibrosis scores, as it can identify differences between all stages in both animal samples (p <0.001) and human biopsies (p <0.05). It is robust to sampling size, allowing for discrimination of different stages in samples of different sizes (area under the curve (AUC): 0.93–0.99 for animal samples: 1–16 mm2; AUC: 0.84–0.97 for biopsies: 10–44 mm in length). qFibrosis can significantly predict staging underestimation in suboptimal biopsies (<15 mm) and under- and over-scoring by different pathologists (p <0.001). qFibrosis can also differentiate between Ishak stages 5 and 6 (AUC: 0.73, p = 0.008), suggesting the possibility of monitoring intra-stage cirrhosis changes. Best of all, qFibrosis demonstrates superior performance to CPA on all counts. Conclusions qFibrosis can improve fibrosis scoring accuracy and throughput, thus allowing for reproducible and reliable analysis of efficacies of anti-fibrotic therapies in clinical research and practice.

New classification of liver biopsy assessment for fibrosis in chronic hepatitis B patients before and after treatment

“…This relates, to some degree, to the relatively coarse assessment provided by a six‐point semiquantitative system. For example, as a reliable quantitative method in evaluation of liver fibrosis, collagen percentage area obtained from SHG analysis of tissue could show dynamic changes within single stages of Ishak classification that would therefore not register with Ishak assessments …”

“…Total collagen percentage area (CPA) was measured using second harmonic generation/two photon excitation fluorescence (SHG/TPEF) technology‐based microscope (Genesis200TM; HistoIndex Pte. Ltd, Singapore) . Image acquisition was performed by a 20 × objective on unstained liver biopsy samples with 512 × 512 pixel resolution of each 200 × 200 μm 2 tile.…”

Ultrasound Elastography and MR Elastography for Assessing Liver Fibrosis: Part 2, Diagnostic Performance, Confounders, and Future Directions

“…Because the location of collagen and the presence of remodeling contribute to the fibrosis stage, the fibrosis stage is not dictated solely by the total amount of collagen, and the relationship of fibrosis stage to total collagen content is not linear [21, 22]. Instead, as the fibrosis stage increases from stage 0 (no abnormal fibrosis) to higher stages, the total collagen content remains fairly stable until an advanced fibrosis stage is reached and then the total collagen content increases exponentially.…”

Asian-Pacific Association for the Study of the Liver (APASL) consensus guidelines on invasive and non-invasive assessment of hepatic fibrosis: a 2016 update

“…In addition, qFibrosis can differentiate late fibrosis stages on the Ishak scoring system, which suggests a potential to aid the monitoring of intra-stage cirrhosis changes. qFibrosis has demonstrated superior performance to CPA [63].…”