Hepatitis E Virus Mixed Infection in Immunocompetent Patient

The Study

Conclusions

Acknowledgment

References

Figure

Suggested Citation

Donald B. Smith

, Jeff Vanek, Louise Wellington, Ingolfur Johannessen, Sandeep Ramalingam, and Peter Simmonds

Author affiliations: Author affiliations: University of Edinburgh, Edinburgh, Scotland, United Kingdom (D.B.S., P.S.); Royal Infirmary of Edinburgh, Edinburgh (J.V., I.J., S.R.); NHS Lothian, Edinburgh (L.W.)

Abstract

We detected 2 hepatitis E virus (HEV) strains in an acutely infected immunocompetent patient. Two populations of genotype 3 virus were observed in the hypervariable regions and open reading frames 2 and 3, indicating multiple infection with hepatitis E virus. Persons with mixed infections may provide the opportunity for virus recombination.

Most reports of multiple infection with different hepatitis E virus (HEV) variants can be ascribed to immunodeficiency of the host or to high frequencies of infection. For example, 2 different genotype 3 subtypes were detected in samples from an immunocompromised kidney transplant recipient (1), and virus from another immunocompromised patient contained an insertion of host-derived sequences or various deletions of this sequence (2). Multiple infection or co-circulation of closely related virus variants is not unexpected in such patients with chronic HEV infection (references in [3]). Few cases of multiple infection of immunocompetent persons have been reported; 2 different virus genotypes were isolated from a sushi chef in Japan (4), and 2 persons in Nepal were each infected by different genotype 1 subtypes (5). In the course of our study of the open reading frame (ORF) 1 hypervariable region (HVR) variability in acutely infected persons in Scotland (6), we described a person infected with 2 variants of HEV that encoded dramatically distinct HVR sequences. We report here a more complete investigation of this case.

The Study

The patient, a 55-year-old man, sought treatment at a hospital in the southeast of Scotland in April 2012 for nausea, vomiting, anorexia, jaundice, headache, and abdominal pain. At admission, the patient’s blood sample was positive for anti-HEV IgM and IgG and raised levels of alanine aminotransferase (ALT) (4,023 IU/L; reference range 5–60 IU/L) and bilirubin (91 μmol/L; reference range 3–17 μmol/L). Over the next 10 days, ALT declined steadily to 404 IU/L and returned to normal levels 1 month later. The patient’s abdominal pain had largely resolved by 6 weeks after seeking treatment, but fatigue and lethargy persisted for >8 weeks. There was no evidence that the patient was immunocompromised or was co-infected with other hepatitis viruses. The patient had unexplained jaundice at age 10 years and a history of alcohol abuse as an adult. Symptoms were relatively severe and required 6 days of hospitalization. Informed consent was provided by the patient for laboratory assessment of blood samples.
Virus RNA was extracted from 140 μL of serum and sequenced at limiting dilution in the HVR and ORF2 regions as described (6). Analysis of the ORF2/ORF3 overlap region used the primers 5′-CGGGTGGAATGAATAACATGT-3′ (outer sense nucleotides 5098–5118 relative to M73218), 5′-GCRGTYARCGGCGMRGCCCCAGCTG-3′ (outer antisense, 5481–5457), 5′-TYTGCCTATGCTGCCCGCGCCACCG-3′ (inner sense, 5184–5209) and 5′-GGCGCTGGGMYTGGTCRCGCCAAG-3′ (inner antisense, 5426–5403). Negative controls were included in all experiments. GenBank accession numbers for the ORF2 and ORF2/3 sequences described here are JX516004–JX516053 and for the HVR sequences are JX270882–JX270902.