Nitta Sayuri, Takahashi Kazuaki, Kawai-Kitahata Fukiko, Tsuchiya Jun, Sato Ayako, Miyoshi Masato, Murakawa Miyako, Itsui Yasuhiro, Nakagawa Mina, Azuma Seishin, Kakinuma Sei, Watanabe Mamoru, Asahina Yasuhiro
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Medical Sciences, Tokyo-Shinagawa Hospital, Tokyo, Japan.
Hepatol Res. 2020 Apr;50(4):524-531. doi: 10.1111/hepr.13480. Epub 2020 Feb 5.
Hepatitis E virus (HEV) can cause chronic infection in immunocompromised hosts. However, the dynamics of HEV during persistent infection is not well understood. To elucidate time course alterations in virus sequences and anti-HEV antibodies during persistent infection, we analyzed the HEV sequences and titers of anti-HEV antibodies from a chronic hepatitis E patient.
Serum samples were obtained from a chronic hepatitis E patient under corticosteroid therapy for neurological disease. The titers of anti-HEV antibodies (immunoglobulin A, immunoglobulin M, and immunoglobulin G) in serum samples were detected by enzyme immunoassay. The full or near-full nucleotide sequences of HEV isolated from consecutive serum samples were identified and compared. Phylogenetic analysis was also performed.
Alterations of anti-HEV antibodies from a chronic hepatitis E patient were different from those previously reported in acute hepatitis E patients. The virus sequence was unchanged in the period without treatment, but nucleotide mutations were observed after ribavirin treatment was started. In addition, the sequence of this strain had extremely high identity to that isolated from swine liver in Japan.
Virus mutations in HEV emerged after ribavirin treatment was started. Sequence analysis may useful for deciding the treatment strategy for chronic hepatitis E patients who did not eliminate the virus with 3 months of RBV treatment and inferring the origin of the infection. This report provides insights into the chronicity of hepatitis E, and the impact of persistent infection and ribavirin treatment on the emergence of virus mutations.
