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The spectrum of histopathological findings after SVR to DAA for recurrent HCV infection in liver transplant recipients

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Abstract

Sustained virological response (SVR) to the treatment of recurrent HCV in liver transplant recipients has excellent clinical outcomes; however, little is known about the effects on allograft histology. The study aimed to assess the histology of the allograft liver. In this single-center, retrospective cohort study, patients with recurrent hepatitis C (HCV) in allograft liver who were cured with antiviral therapy between 2010 and 2016 were identified. Biopsies were reviewed by two liver pathologists blinded to the treatment and SVR status. Paired analysis was performed to compare pre- and post-treatment histological features. Of the 62 patients analyzed, 22 patients received PEGylated interferon/ribavirin (IFN) therapy, while 40 patients received direct-acting antiviral agents (DAA). The mean age was 57 years, 24% were female, and 79% were Caucasian. RNA in situ hybridization testing for HCV and HEV was negative in all the tested patients. Significant reduction in the inflammatory grade of post-treatment biopsy specimens was noted in all subjects (n = 57; p < 0.001) and in the IFN group (n = 21; p = 0.001) but not in the DAA group (p = 0.093). Of all subjects, 21% had worsening stage, 31% had improvement, and 48% had no change in stage. Of the treatment groups, 27% in the IFN and 17% in the DAA groups had worsening stage; however, the results were not statistically significant in all subjects or by treatment modality. Persistent inflammatory infiltrates and fibrosis was noted in allograft tissue of patients cured with DAA. Significant improvement in grade was noted in the IFN group, without a significant change in stage.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Abbreviations

DAA:

Direct-acting antiviral agents

EDTA:

Ethylenediaminetetraacetate

IFN:

Interferon

RNA-ISH:

Ribonucleic acid in situ hybridization

SVR:

Sustained virological response

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Authors and Affiliations

  1. Department of Gastroenterology, University of Mississippi Medical Center, Jackson, MS, USA

    Vedha Sanghi

  2. Department of Gastroenterology and Hepatology, Memorial Healthcare System, Hollywood, FL, USA

    Carlos Romero-Marrero

  3. Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, OH, USA

    Gianina Flocco & K. V. Narayanan Menon

  4. Department of Gastroenterology & Liver Pathology, Mayo Clinic, Rochester, MN, USA

    Rondell P. Graham

  5. Department of Critical Care Medicine/Transplant Hepatology, Cleveland Clinic Foundation, Abu Dhabi, United Arab Emirates

    Baraa Abduljawad

  6. Department of Gastroenterology, Hepatology and Nutrition, University of Iowa, Iowa City, IA, USA

    Fadi Niyazi

  7. Department of Gastroenterology, Hepatology and Nutrition, Augusta University, Augusta, GA, USA

    Mohammad M. Asfari

  8. Department of Surgery - Liver Transplantation, Cleveland Clinic Foundation, Cleveland, OH, USA

    Koji Hashimoto, Bijan Eghtesad & Federico N. Aucejo

  9. Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH, USA

    Rocio Lopez

  10. Department of Gastrointestinal and Hepatobiliary Pathology, Cleveland Clinic Foundation, Cleveland, OH, USA

    Lisa M. Yerian & Daniela S. Allende

Authors
  1. Vedha Sanghi
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  2. Carlos Romero-Marrero
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  3. Gianina Flocco
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  10. K. V. Narayanan Menon
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  11. Federico N. Aucejo
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  14. Daniela S. Allende
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Contributions

Vedha Sanghi, conception, design, data acquisition, interpretation of results, drafting and revising the article, and final approval; Carlos Romero-Marrero, conception, design, interpretation of results, critical revision for intellectual content, and final approval; Gianina Flocco, data acquisition and revising the article; Rondell P Graham, conception, data acquisition, interpretation of results, revising the article, and final approval; Baraa Abduljawad, design, data acquisition, and final approval; Fadi Niyazi, concept, design, data acquisition, and final approval; Mohammad M Asfari, data acquisition and final approval; Koji Hashimoto, conception, design, interpretation of results, critical revision for intellectual content, and final approval; Bijan Eghtesad, conception, design, interpretation of results, revising the article, and final approval; KV Narayanan Menon, conception, design, interpretation of results, revising the article, and final approval; Federico N Aucejo, conception, design, interpretation of results, revising the article, and final approval; Rocio Lopez, data analysis; Lisa M Yerian, conception, data acquisition, interpretation of results, revising the article, and final approval; Daniela S Allende, conception, design, data acquisition, interpretation of results, critical revision for intellectual content, and final approval.

Corresponding author

Correspondence to Daniela S. Allende.

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Conflict of interest

Dr. Allende has served as Advisory Board Member for Incyte.

The remaining authors declare no competing interests.

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Sanghi, V., Romero-Marrero, C., Flocco, G. et al. The spectrum of histopathological findings after SVR to DAA for recurrent HCV infection in liver transplant recipients. Virchows Arch 480, 335–347 (2022). https://doi.org/10.1007/s00428-021-03191-6

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  • DOI: https://doi.org/10.1007/s00428-021-03191-6

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