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Inicio Gastroenterología y Hepatología (English Edition) mTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results...
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Vol. 46. Issue 10.
Pages 764-773 (December 2023)
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Vol. 46. Issue 10.
Pages 764-773 (December 2023)
Original article
mTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results from the prospective collaborative CHES study (Chronic Hepatitis EScreening in patients with immune impairment and increased transaminases levels)
Los inhibidores de mTOR como potencial factor predisponente para la hepatitis crónica E: resultados del estudio prospectivo colaborativo CHES (Chronic Hepatitis E Screening in patients with immune impairment and increased transaminases levels)
Mar Riveiro-Barcielaa,b,c, Luisa Roadea,c, Joan Martínez-Campreciosa,c, Judit Vidal-Gonzáleza,c, Basilio Rodríguez-Diezd, Manel Perellóe, Guillermo Ortíf, Virginia Robles-Alonsob,g, Cristina Berasteguih, Jordi Navarroi, Fernando Martínez-Vallej,c, Itxarone Bilbaob,k, Lluis Castellsa,b,c, Meritxell Ventura-Cotsa,b,c, Jordi Llanerasa,c, Ariadna Rando-Segural, Xavier Fornsb,m, Sabela Lensb,m, Martín Prietob,n, María García-Elizn..., Arkaitz Imazo, Francisco Rodríguez-Fríasb,p, Maria Butia,b,c,
Corresponding author
mbuti@vhebron.net

Corresponding author.
,
Rafael Estebana,cVer más
a Liver Unit, Internal Medicine Department, Hospital Universitario Vall d’Hebrón, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
b Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
c Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain
d Rheumatology Department, Hospital Universitario Vall d’Hebrón, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
e Nephrology Department, Hospital Universitario Vall d’Hebrón, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
f Department of Hematology, Hospital Universitario Vall d’Hebrón, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
g Digestive System Research Unit, Hospital Universitario Vall d’Hebrón, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
h Pneumology Department, Hospital Universitario Vall d’Hebrón, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
i Infectious Diseases Department, Hospital Universitario Vall d’Hebrón, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
j Systemic Autoimmune Diseases Unit, Internal Medicine Department, Hospital Universitario Vall d’Hebrón, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
k Liver Transplant Unit, Hospital Universitario Vall d’Hebrón, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
l Microbiology Department, Hospital Universitario Vall d’Hebrón, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
m Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Spain
n Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
o Infectious Diseases Department, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain
p Liver Pathology Unit, Departments of Biochemistry and Microbiology, Clinical Laboratories, Vall d’Hebron University Hospital, Spain
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Tables (3)
Table 1. Baseline characteristics of the overall cohort and according to the presence of detectable HEV-RNA.
Table 2. Anti-HEV IgG, IgM and HEV RNA according to the main cause for immunosuppression.
Table 3. Multivariate analysis of factors associated with detectable HEV-RNA.
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Additional material (2)
Abstract
Background

Chronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes.

Patients and methods

CHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey.

Results

Three hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model.

Conclusions

Despite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E.

Keywords:
Hepatitis E virus
Solid-organ transplant
Immunosuppression
Liver cirrhosis
HIV infection
mTOR inhibitors
Chronic hepatitis E
Resumen
Introducción

La infección crónica por el virus de la hepatitis E (VHE) en personas con disfunción inmunitaria tiene un curso progresivo conllevando una rápida progresión a cirrosis hepática. Sin embargo, los datos prospectivos a este respecto son escasos. El objetivo de este estudio fue determinar la prevalencia y factores de riesgo para la infección crónica VHE en sujetos con disfunción inmunitaria y elevación de enzimas hepáticos.

Pacientes y métodos

CHES es un estudio prospectivo multicéntrico que incluyó adultos con transaminasas elevadas durante al menos 6 meses y alguno de estos factores: receptores de trasplante, infección por VIH, hemodiálisis, cirrosis hepática o tratamiento inmunosupresor. En todos los sujetos se realizaron IgG/IgM anti-VHE (Wantai Elisa) y ARN-VHE por una técnica super sensible (Roche Diagnostics). Además, todos los participantes contestaron una encuesta epidemiológica.

Resultados

381 pacientes fueron incluidos: 131 trasplantados, 115 cirróticos, 51 infectados por VIH, 87 bajo inmunosupresores, 4 hemodiálisis. En total, 210 sujetos recibían inmunosupresores. La IgG anti-VHE fue positiva en 94 (25,6%) sujetos, con tasas similares en todas la causas de disfunción inmunitaria. El ARN-VHE fue positivo en 6 (1,6%) pacientes, todos ellos trasplantados, siendo la tasa de infección crónica VHE en receptores de órgano sólido del 5,8%. En la población de trasplantados, solo el tratamiento con inhibidores de mTOR se asoció de forma independiente a la hepatitis crónica VHE, mientras que los niveles de ALT impactaron en el modelo general.

Conclusiones

A pesar de los niveles anormales de transaminasas, solo se objetivó hepatitis crónica VHE en trasplantados de órgano sólido. En esta población, la tasa de hepatitis crónica VHE fue del 5,8% y solo el tratamiento con inhibidores de mTOR se asoció de forma independiente a la hepatitis crónica E.

Palabras clave:
Virus de la hepatitis E
Trasplante de órgano sólido
Inmunosupresión
Cirrosis hepática
Infección por VIH
Inhibidores de mTOR
Hepatitis crónica E

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