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Histological activity score on baseline liver biopsy can predict non-response to steroids in patients with severe alcoholic hepatitis

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Abstract

Baseline clinical and biochemical parameters fail to predict non-response to steroids in severe alcoholic hepatitis patients. Liver biopsy features have not been adequately assessed for predicting response to steroid therapy in severe alcoholic hepatitis. We aimed to identify histological parameters, which can predict steroid response in severe alcoholic hepatitis (SAH). We analyzed histological data of 107 SAH patients (71 in a derivative and 36 in a validation cohort) who presented within 4 weeks after inset of jaundice and were prospectively treated with steroids (40 mg/day). Histopathological parameters were semi-quantitatively scored in the pre-therapy biopsies in the derivative cohort, and a histological scoring system of SAH was developed which differentiated between steroid responders (Lille score < 0.45 at day 7) and non-responders. Seventeen of the 71 (24%) patients in the derivation cohort and 9 of 36 (25%) in the validation cohort were non-responders to steroids. In the derivation cohort, in comparison to responders, non-responders had higher severity of ballooning degeneration (BD) (mean 3.87 ± 0.91 versus 2.92 ± 1.33; p = 0.013) and density of Mallory-Denk bodies (MD) (mean 2.27 ± 0.79 versus. 1.69 ± 0.97; p = 0.028) on liver histology. A score derived using BD and MD (range 0–8) had high sensitivity (81%), specificity (64%), and negative predictive value (91%) in identifying patients who did not respond to steroids. The AUROC for a combined MD and BD score of > 5 for predicting steroid non-response was 0.731. Baseline histological parameters in SAH, ballooning degeneration, and Mallory-Denk bodies can reliably identify non-response to corticosteroids and help to stratify patients prior to introduction of therapy.

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Abbreviations

AH:

Alcoholic hepatitis

BD:

Ballooning degeneration

MD:

Mallory-Denk bodies

LI:

Lobular inflammation

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Authors and Affiliations

  1. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India

    Saggere Muralikrishna Shasthry, Rajan Vijayaraghavan, Vinod Arora, Manoj Kumar Sharma & Shiv Kumar Sarin

  2. Department of Hepatopathology, Institute of Liver and Biliary Sciences, New Delhi, India

    Archana Rastogi & Chhagan Bihari

Authors
  1. Saggere Muralikrishna Shasthry
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  2. Archana Rastogi
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  3. Chhagan Bihari
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  4. Rajan Vijayaraghavan
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  5. Vinod Arora
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  6. Manoj Kumar Sharma
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  7. Shiv Kumar Sarin
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Contributions

SMS, RV, VA, MS, and SKS did the patient enrollment, data collection, MS preparation, and correction; AR and CB did the histological scoring and grading,

Corresponding author

Correspondence to Shiv Kumar Sarin.

Ethics declarations

Institutional review board acceptance was sought before enrolling the patients and the current study is part of the registered trial NCT01820208.

Conflict of interest

The authors declare that they have no conflict of interest.

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Shasthry, S.M., Rastogi, A., Bihari, C. et al. Histological activity score on baseline liver biopsy can predict non-response to steroids in patients with severe alcoholic hepatitis. Virchows Arch 472, 667–675 (2018). https://doi.org/10.1007/s00428-018-2330-4

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  • DOI: https://doi.org/10.1007/s00428-018-2330-4

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