SHG/TPEF-based image technology improves liver fibrosis assessment of minimally sized needle biopsies.

BACKGROUND AND AIMS: Sampling size variability of liver biopsy remains a major limitation in the assessment of liver fibrosis. We aimed to evaluate the diagnostic value of a fully quantitative method (second harmonic generation/two-photon excitation fluorescence, SHG/TPEF based) in "short" liver biopsy samples. METHODS: Liver biopsy samples from chronic hepatitis B (CHB) patients were constructed into "virtual" biopsies with different lengths. The original and "virtual" samples were measured by SHG/TPEF-based technology to obtain qFibrosis score, respectively. Here, ΔqFibrosis was defined as difference of qFibrosis between original biopsy and "virtual" biopsy. Equivalence test was used to compare ΔqFibrosis with the clinically acceptable error (deviation of 0.50) in each group. RESULTS: In real-world practice, qFibrosis score increased significantly with fibrosis progression in ≥ 1.5-cm-, 1.0-1.5-cm-, and 0.5-1.0-cm-long specimens (p < 0.05), compared with ≤ 0.5-cm-long specimens (p > 0.05). In virtual biopsy samples with specified length, the equivalence was confirmed in 0.5-1.0-cm- and 1.0-1.5-cm-long specimens (0.27 vs. 0.22, p < 0.001), whereas not in ≤ 0.5-cm-long specimens (0.53, p > 0.05). The number of cross-linked collagen fibers, the total and aggregated collagen proportionate area, and the collagen strings in number, length, width and perimeter showed excellent consistency with original biopsy samples in 0.5-1.0-cm- and 1.0-1.5-cm-long specimens (ICC > 0.90). CONCLUSIONS: The use of SHG/TPEF-based image technology may give useful suggestive information in evaluation of CHB-related liver fibrosis for the short sample (biopsy length > 0.5 cm).

Quantitative assessment of liver fibrosis (qFibrosis) reveals precise outcomes in Ishak "stable" patients on anti-HBV therapy.

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.

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

Liver fibrosis is the net result of dynamic changes between fibrogenesis and fibrolysis. Evidence has shown that antiviral therapy can reverse liver fibrosis or even early cirrhosis caused by hepatitis B virus. However, current evaluation systems mainly focus on the severity of, but not the dynamic changes in, fibrosis. Here, we propose a new classification to evaluate the dynamic changes in the quality of fibrosis, namely: predominantly progressive (thick/broad/loose/pale septa with inflammation); predominately regressive (delicate/thin/dense/splitting septa); and indeterminate, which displayed an overall balance between progressive and regressive scarring. Then, we used this classification to evaluate 71 paired liver biopsies of chronic hepatitis B patients before and after entecavir-based therapy for 78 weeks. Progressive, indeterminate, and regressive were observed in 58%, 29%, and 13% of patients before treatment versus in 11%, 11%, and 78% after treatment. Of the 55 patients who showed predominantly regressive changes on posttreatment liver biopsy, 29 cases (53%) had fibrosis improvement of at least one Ishak stage, and, more interestingly, 25 cases (45%) had significant improvement in terms of Laennec substage, collagen percentage area, and liver stiffness despite remaining in the same Ishak stage. CONCLUSION: This new classification highlights the importance of assessing and identifying the dynamic changes in the quality of fibrosis, especially relevant in the era of antiviral therapy.(Hepatology 2017;65:1438-1450).

Characterizing the Effects of Washing by Different Detergents on the Wavelength-Scale Microstructures of Silk Samples Using Mueller Matrix Polarimetry.

Silk fibers suffer from microstructural changes due to various external environmental conditions including daily washings. In this paper, we take the backscattering Mueller matrix images of silk samples for non-destructive and real-time quantitative characterization of the wavelength-scale microstructure and examination of the effects of washing by different detergents. The 2D images of the 16 Mueller matrix elements are reduced to the frequency distribution histograms (FDHs) whose central moments reveal the dominant structural features of the silk fibers. A group of new parameters are also proposed to characterize the wavelength-scale microstructural changes of the silk samples during the washing processes. Monte Carlo (MC) simulations are carried out to better understand how the Mueller matrix parameters are related to the wavelength-scale microstructure of silk fibers. The good agreement between experiments and simulations indicates that the Mueller matrix polarimetry and FDH based parameters can be used to quantitatively detect the wavelength-scale microstructural features of silk fibers. Mueller matrix polarimetry may be used as a powerful tool for non-destructive and in situ characterization of the wavelength-scale microstructures of silk based materials.

[Comparison of FibroTouch and FibroScan for the assessment of fibrosis in chronic hepatitis B patients].

OBJECTIVE: To perform a comparative assessment of the performance of FibroTouch and FibroScan in patients with hepatitis B. METHODS: A total of 211 patients with hepatitis B, including cases of chronic hepatitis B (CHB) and of compensated cirrhosis, were enrolled for study between June and November of 2013. The patients underwent FibroScan testing (group 1) and FibroTouch testing (group 3), after which the operator examined a time motion ultrasound image from the FibroScan test and located a specific liver portion for focused FibroTouch testing (group 2). The consistency between the two tests' results was investigated by Pearson's correlation analysis, and the difference of liver stiffness between CHB patients and compensated cirrhosis patients was investigated by the two independent samples t-test or Mann-Whitney U test. RESULTS: The values of liver stiffness were 5.30 (4.30,8.65) in group 1,6.10 (4.70,8.90) in group 2, and 5.70 (4.50, 8.00) in group 3 (all P < 0.05); the Pearson correlation coefficients were all more than 0.8 (P < 0.05) and there was no statistically significant difference found between the results from FibroScan and FibroTouch.The values of liver stiffness were significantly different between the CHB patients and the compensated cirrhosis patients (P < 0.05). The rates of successful detection were 100% for FibroTouch and 97% for FibroScan. CONCLUSION: FibroTouch and FibroScan have good consistency in the evaluation of the degree of liver fibrosis. FibroTouch has a higher rate of successful detection than FibroScan.