Time course alterations of virus sequences and immunoglobulin titers in a chronic hepatitis E patient

Abstract

Aim: 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.Methods: 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.Results: 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.Conclusions: 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.

Recent advances in hepatitis E virus research and the Japanese clinical practice guidelines for hepatitis E virus infection

“…Ribavirin treatment failure has occasionally been observed in association with HEV genomic RNA mutations. 150,153,354,358 Pegylated IFN can effectively treat chronic HEV infection following liver transplantation, although it is contraindicated in cases of kidney transplantation. 352 Administration of pegylated IFN, either alone or in combination with ribavirin, may be considered in some patients coinfected with HIV and HEV 359 or those with previous ribavirin treatment failure.…”