Chronic hepatitis E infection in children with liver transplantation
- Ugur Halac1,
- Kathie Béland1,
- Pascal Lapierre1,
- Natacha Patey2,
- Pierre Ward3,
- Julie Brassard3,
- Alain Houde3,
- Fernando Alvarez1
- 1Division of Gastroenterology, Hepatology and Nutrition, Department of, Pediatrics, CHU Sainte-Justine, Université de Montréal, Quebec, Canada
- 2Division of Pathology and Cellular Biology, CHU Sainte-Justine, Université de Montréal, Quebec, Canada
- 3Agriculture and Agri-Food Canada, Food Research and Development Centre, Saint-Hyacinthe, Quebec, Canada
- Correspondence to Dr Ugur Halac, Division of Gastroenterology, Hepatology and Nutrition, CHU Sainte-Justine, 3175 Côte Ste-Catherine, Montréal, Québec H3T 1C5, Canada;
Contributors UH helped in the conception and design of the study, collected clinical data, performed reverse transcription-polymerase chain reaction (RT-PCR) and ELISA experiments, analysed the data and wrote the manuscript. KB and PL helped in the conception and design of the study, in technical support (RT-PCR and ELISA experiments) and in critical revision of the manuscript. PL also performed the phylogenetic analysis and Genbank sequence submission. NP performed and analysed all the pathological data and helped to revise the manuscript. PW and JB contributed to viral load quantification and made helpful comments during revision of the manuscript. AH supervised the viral load quantification process and critically revised the manuscript. FA designed the study and critically revised the manuscript. All the authors approved the current version of the revised manuscript.
- Revised 30 September 2011
- Accepted 15 October 2011
- Published Online First 23 November 2011
Objective Chronic hepatitis E virus (HEV) infection has been described in immunosuppressed adult patients. A study was undertaken to establish the presence of HEV infection in children after orthotopic liver transplantation (OLT).
Methods Children undergoing liver transplantation between 1992 and 2010 with available serum were classified into two groups: group 1 (control group, n=66) with normal serum aminotransferases and group 2 (n=14) with persistently increased serum aminotransferases and histological features of chronic hepatitis. Patients were tested for HEV RNA by reverse transcription-polymerase chain reaction (RT-PCR). HEV amplicons were sequenced and compared with published sequences. Antibody titres (IgG and IgM) to 12 HEV immunodominant regions were measured by enzyme-linked immunosorbent assays.
Results In group 1 (control group), 15% of children were anti-HEV IgG-positive during follow-up. No anti-HEV IgM antibodies were detected in any of these children. After OLT, 86% of patients in group 2 had anti-HEV IgG compared with 36% pre-OLT. Thus, two-thirds of children acquired anti-HEV IgG after OLT. Seven anti-HEV IgG-positive patients (58%) were also anti-HEV IgM-positive more than once during follow-up after OLT. Eight years post-OLT, one girl presented with anti-HEV IgG and IgM that remained positive afterwards. In this patient, HEV RNA was found in five different annual samples from 10 years post-OLT, concomitantly with increased serum aminotransferases and cirrhosis development during that period. Phylogenetic analysis revealed two different HEV strains (detected 3 years apart) that were highly similar to swine genotype 3, suggesting a possible case of zoonotic re-infection.
Conclusion The diagnosis of HEV infection is technically challenging and should be made simultaneously with RT-PCR methods, viral load quantification and serological markers. In immunosuppressed children who develop chronic hepatitis, the prevalence of HEV is high and could explain the chronic liver inflammation potentially leading to cirrhosis. Re-infection by different HEV strains from zoonotic transmission can result in progressive liver disease in immunocompromised children.
Competing interests None.
Ethics approval Ethics committee approval was obtained from Sainte-Justine Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.