Clinical characteristics and molecular epidemiology of hepatitis E in Shenzhen, China: a shift toward foodborne transmission of hepatitis E virus infection

Abstract

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in China. Recently, a shift in molecular epidemiology from hepatitis E genotype 1 (HEV-1) to hepatitis E genotype 4 (HEV-4) has been observed in Northern China, marking a switch from human-to-human transmission to zoonosis. However, similar data from cities in Southern China are lacking. This observational study of human hepatitis E cases in Shenzhen, a metropolitan city in the Pearl River Delta region, aimed to describe the clinical features and molecular epidemiology of hepatitis E in Southern China. Over a 55-month period, we identified 20 patients with acute hepatitis E. Most were middle-aged men, and 50% of patients had concomitant liver disease, of whom 70% were identified to have non-alcoholic fatty liver disease; such patients had a trend toward higher liver enzymes. Quantitative real-time RT-PCR using archived serum samples showed that 12 patients had hepatitis E viremia at presentation. Sequencing of the RNA-dependent RNA polymerase gene was performed for five of these patients, and phylogenetic analysis revealed that these five HEV isolates belonged to subgenotype 4b and were clustered with swine HEV isolates from Southern China. Combined with other studies showing similar findings, this suggests that the molecular epidemiology of hepatitis E in China is evolving toward low-level endemicity driven by foodborne transmission from seafood or pork products. The importance of concomitant liver disease, in particular non-alcoholic fatty liver disease, as a risk factor for severe hepatitis E requires further study.

Figure 1

Monthly variation in the incidence of acute hepatitis E cases.

Figure 2

Phylogenetic analyses of the partial RdRp region of the five human HEV isolates sequenced in this study (patients 1, 4, 5, 7 and 8 as per Table 2) and other HEV genotypes. The tree was constructed based on the maximum-likelihood method using the Kimura two-parameter model with invariant sites and gamma distributed with invariant sites (G+I). The bootstrap analysis was performed with 1000 replicates. Bootstrap values <70% are not shown. The analysis included 257 nucleotide positions (nucleotide position 4274–4530 numbered with reference to GenBank sequence M73218). GenBank accession numbers are shown in parentheses. The scale bar indicates the estimated number of substitutions per site. Hepatitis E virus (HEV).