Hepatitis E in Singapore: A Case-Series and Viral Phylodynamics Study

Abstract

Abstract. The incidence of hepatitis E in Singapore appears to be increasing. A retrospective case-series study of patients diagnosed with hepatitis E in a tertiary hospital from 2009 to 2013 was conducted. Of 16 cases, eight (50%) were solid-organ transplant recipients (SOTRs), and 14 (88%) were found infected by genotype 3 hepatitis E virus (HEV-3). Bayesian inferences based on HEV subgenomic sequences from seven cases suggest that HEV-3 strains were introduced to Singapore as two principal lineages. Within limitations of the study, it can be inferred that one lineage, in the 3efg clade, emerged about 83 years ago, probably originating from Japan, whereas the other, in the 3abchij clade, emerged about 40 years ago, from the United States. Establishment and subsequent transmissions of strains from these two lineages likely contribute to the current endemicity of hepatitis E in Singapore.

Seroepidemiology and genotyping of hepatitis E virus in Singapore reveal rise in number of cases and similarity of human strains to those detected in pig livers

“…A small minority of HEV genotype 3 strains were from the 3efg clade (4/59, 7%; Figure a). Of these strains, two sequences shared the same ancestor as a genotype 3e strain from Japan (3e_Sw_Japan_AB248521) while two others belonged to the same lineage as that of a previously reported strain in Singapore (KT447527) which was believed to have originated from the United States (Teo et al, ). All but four genotype 3 strains were from Chinese persons—two genotype 3a strains were detected from Indian individuals, one strain was from a Caucasian and one was from an individual of unknown race.…”

“…Molecular analyses of sequences in our study of human sera revealed genotype 3 to be distinctly the most prevalent (121/143, 84.6%), with genotype 3a as the main circulating strain. Although Teo et al () and Zhu et al () have previously described the identification of genotype 3a in Singapore, the number of their cases (3 and 15, respectively) was small. Our study detected genotype 3a in 44 of 59 patient samples with concatenated ORF1 and ORF2 sequences (74.6%).…”

“…The rise in the rate and the almost 10‐fold increase in the number of positive HEV IgG cases over 10 years among residents are similar to findings in Europe (European Centre for Disease Prevention & Control, ), which is suggestive of a growing hepatitis E burden in Singapore. This rise in the number of HEV cases and recent reports of chronic HEV in solid organ transplant recipients (Teo et al, ) and immunocompromised patients (Zhu et al, ) raise considerable concerns. A pertinent question would be whether blood donors in Singapore should be screened for hepatitis E.…”

“…The phylogenetic trees were constructed using concatenated sequences from ORF1 and ORF2. Genotypes of HEV reference strains (Lu, Li, & Hagedorn, 2006;Smith et al, 2016), selected strains previously reported in Singapore (Teo et al, 2017;Zhu et al, 2019) and selected reference strains from previous studies (Nishizawa et al, 2017) were downloaded from GenBank (Clark, Karsch-Mizrachi, Lipman, Ostell, & Sayer, 2016). Males formed the majority of hepatitis E-infected persons among both residents (56%-70%, Figure 1c) and non-residents (72%-100%, Figure 1d).…”

“…A study of 29 cases in 2015 showed that genotype 3 ( n = 12/25) was detected among the indigenous cases while genotypes 1 ( n = 2/4) and 3 ( n = 1/4) were found among the imported cases; the genotypes of the remaining indigenous and imported cases could not be determined (Ministry of Health, ). In a separate report of 16 cases, genotype 3 appeared to belong to two lineages, one originating from Japan and the other, the United States (Teo et al, ). Another study of 15 immunocompromised patients suggested genotype 3a to be a locally circulating strain (Zhu et al, ).…”