Detection of viral hepatitis E in clinical liver biopsies

Sandrine Prost, Claire L. Crossan, Harry R. Dalton, Robert A. De Man, Nassim Kamar, Janick Selves, Catharine Dhaliwal, Linda Scobie, Christopher O.C. Bellamy

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Abstract

Aims to determine the relative utility of in situ testing for hepatitis E virus (HEV) RNA and paraffin section PCR to diagnose HEV infection in paraffin-embedded clinical liver biopsies, and to correlate with clinico-pathological characteristics. Methods and results We evaluated in situ and quantitative PCR (qPCR)-based approaches to identifying HEV in clinical liver biopsies from infected patients from multiple centers, correlating with clinical setting (immunocompetent, allograft or immunosuppressed native liver) and histologic findings. 36 biopsies from 29 patients had histologic data, of which 27 and 23 biopsies had satisfactory material for in situ RNA testing and tissue qPCR respectively. Both approaches specifically identified HEV infection, but tissue qPCR was significantly more sensitive than in situ testing (P=0.035). In immunocompetent but not immunosuppressed patients the tissue qPCR yield correlated with the severity of lobular hepatitis (rho=0.94, P<0.001). qPCR viral yield was comparably high in allografts and immunosuppressed native livers and significantly greater than with native liver infection. Immunosuppressed patients showed reduced severity of hepatitis and cholestatic changes, compared with immunocompetent patients. Indeed, HEV-infected liver allografts could show minimal hepatitis for many months. In individual cases each technique was useful when serum was not available to retrospectively identify chronic infection (in biopsies taken 4-31 months before diagnosis), to identify persistent/residual infection when contemporary serum PCR was negative and to identify cleared infection. Conclusions qPCR is better than in situ RNA testing to identify HEV infection in paraffin-embedded liver biopsies and has diagnostic utility in selected settings.
Original languageEnglish
Pages (from-to)580-590
Number of pages11
JournalHistopathology
Volume71
Issue number4
Early online date24 May 2017
DOIs
Publication statusPublished - Oct 2017

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Hepatitis E
Hepatitis E virus
Biopsy
Polymerase Chain Reaction
Liver
Virus Diseases
Paraffin
Hepatitis
Allografts
RNA
Infection
Serum

Keywords

  • liver biopsy
  • hepatitis E
  • virology

Cite this

Prost, S., Crossan, C. L., Dalton, H. R., De Man, R. A., Kamar, N., Selves, J., ... Bellamy, C. O. C. (2017). Detection of viral hepatitis E in clinical liver biopsies. Histopathology, 71(4), 580-590. https://doi.org/10.1111/his.13266
Prost, Sandrine ; Crossan, Claire L. ; Dalton, Harry R. ; De Man, Robert A. ; Kamar, Nassim ; Selves, Janick ; Dhaliwal, Catharine ; Scobie, Linda ; Bellamy, Christopher O.C. / Detection of viral hepatitis E in clinical liver biopsies. In: Histopathology. 2017 ; Vol. 71, No. 4. pp. 580-590.
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Prost, S, Crossan, CL, Dalton, HR, De Man, RA, Kamar, N, Selves, J, Dhaliwal, C, Scobie, L & Bellamy, COC 2017, 'Detection of viral hepatitis E in clinical liver biopsies', Histopathology, vol. 71, no. 4, pp. 580-590. https://doi.org/10.1111/his.13266

Detection of viral hepatitis E in clinical liver biopsies. / Prost, Sandrine; Crossan, Claire L.; Dalton, Harry R.; De Man, Robert A.; Kamar, Nassim; Selves, Janick; Dhaliwal, Catharine; Scobie, Linda; Bellamy, Christopher O.C.

In: Histopathology, Vol. 71, No. 4, 10.2017, p. 580-590.

Research output: Contribution to journalArticle

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AU - Prost, Sandrine

AU - Crossan, Claire L.

AU - Dalton, Harry R.

AU - De Man, Robert A.

AU - Kamar, Nassim

AU - Selves, Janick

AU - Dhaliwal, Catharine

AU - Scobie, Linda

AU - Bellamy, Christopher O.C.

N1 - Acceptance email in SAN AAM: 12m embargo Note AAM is online first at 24-5-17 before VoR - ET Note on webpage: 'This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record'.

PY - 2017/10

Y1 - 2017/10

N2 - Aims to determine the relative utility of in situ testing for hepatitis E virus (HEV) RNA and paraffin section PCR to diagnose HEV infection in paraffin-embedded clinical liver biopsies, and to correlate with clinico-pathological characteristics. Methods and results We evaluated in situ and quantitative PCR (qPCR)-based approaches to identifying HEV in clinical liver biopsies from infected patients from multiple centers, correlating with clinical setting (immunocompetent, allograft or immunosuppressed native liver) and histologic findings. 36 biopsies from 29 patients had histologic data, of which 27 and 23 biopsies had satisfactory material for in situ RNA testing and tissue qPCR respectively. Both approaches specifically identified HEV infection, but tissue qPCR was significantly more sensitive than in situ testing (P=0.035). In immunocompetent but not immunosuppressed patients the tissue qPCR yield correlated with the severity of lobular hepatitis (rho=0.94, P<0.001). qPCR viral yield was comparably high in allografts and immunosuppressed native livers and significantly greater than with native liver infection. Immunosuppressed patients showed reduced severity of hepatitis and cholestatic changes, compared with immunocompetent patients. Indeed, HEV-infected liver allografts could show minimal hepatitis for many months. In individual cases each technique was useful when serum was not available to retrospectively identify chronic infection (in biopsies taken 4-31 months before diagnosis), to identify persistent/residual infection when contemporary serum PCR was negative and to identify cleared infection. Conclusions qPCR is better than in situ RNA testing to identify HEV infection in paraffin-embedded liver biopsies and has diagnostic utility in selected settings.

AB - Aims to determine the relative utility of in situ testing for hepatitis E virus (HEV) RNA and paraffin section PCR to diagnose HEV infection in paraffin-embedded clinical liver biopsies, and to correlate with clinico-pathological characteristics. Methods and results We evaluated in situ and quantitative PCR (qPCR)-based approaches to identifying HEV in clinical liver biopsies from infected patients from multiple centers, correlating with clinical setting (immunocompetent, allograft or immunosuppressed native liver) and histologic findings. 36 biopsies from 29 patients had histologic data, of which 27 and 23 biopsies had satisfactory material for in situ RNA testing and tissue qPCR respectively. Both approaches specifically identified HEV infection, but tissue qPCR was significantly more sensitive than in situ testing (P=0.035). In immunocompetent but not immunosuppressed patients the tissue qPCR yield correlated with the severity of lobular hepatitis (rho=0.94, P<0.001). qPCR viral yield was comparably high in allografts and immunosuppressed native livers and significantly greater than with native liver infection. Immunosuppressed patients showed reduced severity of hepatitis and cholestatic changes, compared with immunocompetent patients. Indeed, HEV-infected liver allografts could show minimal hepatitis for many months. In individual cases each technique was useful when serum was not available to retrospectively identify chronic infection (in biopsies taken 4-31 months before diagnosis), to identify persistent/residual infection when contemporary serum PCR was negative and to identify cleared infection. Conclusions qPCR is better than in situ RNA testing to identify HEV infection in paraffin-embedded liver biopsies and has diagnostic utility in selected settings.

KW - liver biopsy

KW - hepatitis E

KW - virology

U2 - 10.1111/his.13266

DO - 10.1111/his.13266

M3 - Article

VL - 71

SP - 580

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Prost S, Crossan CL, Dalton HR, De Man RA, Kamar N, Selves J et al. Detection of viral hepatitis E in clinical liver biopsies. Histopathology. 2017 Oct;71(4):580-590. https://doi.org/10.1111/his.13266