Abstract
Current widely used semiquantitative histological assessment methods are insensitive to identify subtle changes of liver fibrosis. Therefore, to precisely assess therapeutic efficacy on chronic hepatitis B (CHB), we explored the utility of qFibrosis (a fully-quantitative morphometric method employing second harmonic generation/two photon excitation fluorescence) in liver fibrosis evaluation. Fibrosis changes were evaluated by Ishak fibrosis scoring and qFibrosis in CHB patients with paired liver biopsies before and after 78 weeks’ antiviral therapy. A total of 162 patients with qualified paired biopsies were enrolled. Ishak fibrosis scoring revealed that 42.6% (69/162) of the patients achieved fibrosis regression (≥1-point decrease), 51.9% (84/162) remained stable, and 5.5% (9/162) showed progression (≥1-point increase). qFibrosis showed similar trends in the groups of regression and progression patients as evaluated by Ishak. However, in Ishak stable patients, qFibrosis revealed hitherto undetected changes, allowing for further subcategorization into regression (“Regression by qFibrosis”; 40/84, 47.6%), stable (29/84, 34.5%), and progression (“Progression by qFibrosis”; 15/84, 17.9%) groups. These newly fine-tuned categories were supported by changes of morphological parameters of fibrosis, collagen percentage area, and liver stiffness measurements. In conclusion, qFibrosis can be used to quantitatively identify subtle changes of liver fibrosis in CHB patients after antiviral therapy.
Highlights
Current widely used semiquantitative histological assessment methods are insensitive to identify subtle changes of liver fibrosis
All specimens were assessed by Ishak modified histology activity index (HAI) grading and fibrosis staging and SHG/TPEF-based qFibrosis (Fig. 1)
In this study based on a well-characterized cohort of chronic hepatitis B (CHB) patients on antiviral therapy with paired liver biopsies, we evaluated fibrosis regression by both semiquantitative histological fibrosis scoring (Ishak) and fully automated quantitative method
Summary
Current widely used semiquantitative histological assessment methods are insensitive to identify subtle changes of liver fibrosis. Fibrosis changes were evaluated by Ishak fibrosis scoring and qFibrosis in CHB patients with paired liver biopsies before and after 78 weeks’ antiviral therapy. In Ishak stable patients, qFibrosis revealed hitherto undetected changes, allowing for further subcategorization into regression (“Regression by qFibrosis”; 40/84, 47.6%), stable (29/84, 34.5%), and progression (“Progression by qFibrosis”; 15/84, 17.9%) groups. These newly fine-tuned categories were supported by changes of morphological parameters of fibrosis, collagen percentage area, and liver stiffness measurements. The entecavir study showed 88% (50/57) of patients achieving at least a 1-point improvement in Ishak fibrosis scores after 5 years of treatment[4]. In the era of potent anti-HBV treatment, relatively coarse assessment provided by the 6-point semiquantitative system may not suffice to evaluate progression or regression of fibrosis[2]
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