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Second-harmonic generation (SHG) microscopy and hepatic venous pressure gradient-based validation of a novel histological staging system for alcoholic hepatitis

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Abstract

Alcoholic hepatitis (AH) lacks specific histological staging. A novel fibrosis staging that encompasses perisinusoidal fibrosis and cirrhosis sub-stages, substantiated by Hepatic venous pressure gradient (HVPG) and automated fibrosis quantification, is imperative. To correlate novel histological staging system of AH with second-harmonic generation microscopy (SHG)-based q-fibrosis, HVPG, and activated hepatic stellate cells (HSCs). Liver biopsies of AH (n = 175) were staged semi-quantitatively as F0, F1, F2, F3A and F3B and Laennec substages of cirrhosis 4A, 4B and 4C. Stages were correlated with SHG q-fibrosis parameters, HVPG and HSCs. Mean age 41.2 ± 9.4 years, 96.6% males, bilirubin 20.58 ± 8.0 mg/dl and Maddrey’s discriminant function 78.9 ± 36.7 displayed advanced fibrosis in 98.6%. With increasing histological stages, an increase in q-fibrosis indices and mean HVPG (p < 0.0001) were recorded; stage 4C showed the most significant difference from other stages (p < 0.000). Stages 3A and 3B were comparable with the stages 4A and 4B, respectively, for q-fibrosis (p = 1) and HVPG (p = 1). HSCs (> 30%) were significantly higher in stage 3 (75%) compared with 4 (49%) and 2 (59%), p = 0.018. Overall agreement for histological staging was excellent for all stages (0.82). SHG quantified fibrosis and HVPG corroborates the novel histological staging of AH. Expansive PCF matches with collagen content and clinical severity to early sub-stages of cirrhosis. This highlights the need for an accurate quantification and inclusion of PCF as a separate stage. SHG-based quantification can be a useful adjunct to histological fibrosis staging systems.

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Authors and Affiliations

  1. Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India

    Archana Rastogi, Nayana Patil, Rakhi Maiwall, Chhagan Bihari, Ananda Soshee & Shiv K. Sarin

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  1. Archana Rastogi
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  2. Nayana Patil
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  3. Rakhi Maiwall
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  4. Chhagan Bihari
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  6. Shiv K. Sarin
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Contributions

All authors contributed to the study conception and design. Data collection and analysis were performed by Archana Rastogi, Nayana Patil, Rakhi maiwall, Ananda Soshee and Chhagan Bihari. Data interpretation and compilation were performed by Archana Rastogi, Nayana Patil, Rakhi maiwall and Ananda Soshee. The first draft of the manuscript was written by Archana Rastogi and Nayana Patil, and all authors commented on the versions of the manuscript. Final draft was critically assessed for important intellectual content by Shiv K Sarin. All authors read and approved the final manuscript.

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Correspondence to Archana Rastogi.

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The study protocol was approved by the Institutional Ethics Committee/ Institutional Review Board (IEC/2019/71/MA06) dated 02.11.2019.

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Rastogi, A., Patil, N., Maiwall, R. et al. Second-harmonic generation (SHG) microscopy and hepatic venous pressure gradient-based validation of a novel histological staging system for alcoholic hepatitis. Virchows Arch 479, 493–506 (2021). https://doi.org/10.1007/s00428-021-03089-3

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