Full‐genome characterization of the RIVM‐HAV16‐090‐like hepatitis A virus strains recovered from Japanese men who have sex with men, with sporadic acute hepatitis A

Abstract

Aim The major transmission mode of hepatitis A virus (HAV) in Japan is the fecal–oral route by contaminated foods. In contrast, HAV infection is well documented as a sexually transmitted disease in Europe and North America. The present study was undertaken to determine the full‐genome sequence of HAV and trace the transmission route of HAV in Japanese men who have sex with men (MSM). Methods In 2018, we encountered three Japanese MSM with acute hepatitis A co‐infected with HIV for 4–12 years. Serum samples obtained from these patients were used for HAV full‐genome analyses. Results Isolated HAV strains were segregated into subgenotype IA. The three HAV strains shared 100% identity within the 481‐nucleotide partial sequence. The entire nucleotide sequence showed that the three strains were 99.97% similar to each other with only two nucleotide substitutions. At the amino acid level, the three strains differed from each other by only one or two amino acids. All three strains obtained in the present study were >99.6% identical to the 66 reported strains isolated from Taiwan and European countries during 2015–2017. In addition, these 66 strains include the RIVM‐HAV16‐090 (EuroPride) strain, which has been involved in HAV outbreaks among MSM worldwide. Conclusions We determined for the first time the full‐genome sequence of HAV isolated from Japanese MSM with acute hepatitis A and found that the strains were identical to those from MSM worldwide. Thus, these HAV strains were imported to Japan from foreign countries through MSM.

Comparison of the Clinical Features of Hepatitis A in People Living with HIV between Pandemics in 1999–2000 and 2017–2018 in the Metropolitan Area of Japan

“…We, then, successfully cloned the HAV genome and sequenced the VP1 2A junction region. All the clones derived from these patients were very similar and belonged to genotype IA, the RIVM-HAV16-090 cluster (13), which was prevalent in Taiwan where the outbreak of HAV was observed prior to that in Japan (Fig. 1).…”

Assessing countermeasures during a hepatitis A virus outbreak among men who have sex with men

“…MSM sex tourism across national borders is recognized as an important avenue of introducing new outbreaks [11], and many outbreaks of hepatitis A occur among MSM. The timing of hepatitis A outbreaks has involved a certain time lag as they have moved across the globe, with a surge of patients occurring among MSM from 2015 to 2017 in Taiwan [12][13][14], from 2016 to 2017 in Europe [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29], from 2016 to 2018 in the United States [30,31], and in 2018 in Japan [11,32]. Spatial spread (e.g., from Taiwan and Europe to Japan) has been partly demonstrated via genome sequencing [11,32].…”

Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease

“…HAV infects humans through fecal–oral routes, when HAV-contaminated water and food are consumed. Among men who have sex with men (MSM), HAV is sexually transmitted [ 46 ], and HAV outbreaks have been observed [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. It is noteworthy that acute hepatitis A among MSM is one of the male-dominant diseases, although, in general, no gender difference exists in patients with an HAV infection caused by HAV-contaminated water and food.…”

“…In the United States, HAV infections also increased among MSM from 2016 to 2018 [ 54 , 136 , 137 ]. Since 2017, HAV infection has increased among MSM in Japan [ 34 , 37 , 52 ]. RIVM-HAV16-090-like hepatitis A virus strains, which were >99.6% identical to the 66 reported strains isolated from Taiwan and European countries from 2015 to 2017, were also recovered from Japanese MSM [ 52 ].…”

“…Since 2017, HAV infection has increased among MSM in Japan [ 34 , 37 , 52 ]. RIVM-HAV16-090-like hepatitis A virus strains, which were >99.6% identical to the 66 reported strains isolated from Taiwan and European countries from 2015 to 2017, were also recovered from Japanese MSM [ 52 ]. A recent outbreak of HAV infection was also reported in various countries, such as Brazil, Spain, and Italy [ 53 , 138 , 139 , 140 ].…”