Correspondence
Fulminant Hepatitis E in Japan
N Engl J Med 2002; 347:1456October 31, 2002
- Article
To the Editor:
Hepatitis E virus (HEV) is the leading cause of water-borne epidemics of hepatitis in many developing countries in Asia and Africa, where high mortality has been reported among infected pregnant women.1 Recently, it has become clear that sporadic hepatitis E occurs in persons in industrialized countries who have no evidence of exposure to HEV strains from countries where the infection is endemic.1-3 However, the contribution of HEV to the development of fulminant hepatitis in industrialized nations is unclear.
To investigate whether HEV might be a cause of fulminant hepatitis in Japan, we conducted a study involving 18 patients (6 men and 12 women; mean [±SD] age, 55±17 years) who had received a diagnosis of non-A, non-B, non-C fulminant hepatitis between 1992 and 2001. They had no history of traveling abroad. Three (17 percent) of them had positive tests for anti-HEV IgM by enzyme immunoassay and for HEV RNA by reverse-transcription polymerase chain reaction.4 The HEV viremia in the three infected patients persisted for 11 to 15 days after the onset of disease, and they died 16 to 54 days after its onset. The HEV isolates from the three infected patients differed from each other by 10 to 21 percent in the 412-nucleotide sequence (GenBank accession numbers, AB079762, AB079763, and AB079764). Two of the three isolates were most homologous to the known genotype IV isolate (T1) from China,5 with a nucleotide identity of 86 to 89 percent. The one remaining isolate had the highest identity (90 to 95 percent) with human and swine HEV isolates of genotype III (JRA1 and swJ570), which are considered indigenous to Japan.3,4
Our results indicate that HEV may play an important part in inducing fulminant hepatitis in patients in industrialized countries. All three of the infected patients were men and were older than 60 years; in contrast, rates of fulminant hepatitis in developing countries, where HEV generally affects young adults, are high among pregnant women. The origin of our variants of HEV is unclear. Our patients with fulminant hepatitis E did not report contact with pigs or rats, although zoonosis has been suggested as a source of HEV infection. We conclude that HEV should be considered a potential cause of non-A, non-B, non-C fulminant hepatitis in industrialized countries.
5 ReferencesKazuyuki Suzuki, M.D.
Iwate Medical University, Iwate 020-8505, JapanTatsuya Aikawa, M.D.
Aikawa Internal Clinic, Ibaraki 020-8505, JapanHiroaki Okamoto, M.D
Jichi Medical School, Tochigi 329-0498, Japan
hokamoto@jichi.ac. jp 1
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2
Schlauder GG ,Mushahwar IK . Genetic heterogeneity of hepatitis E virus. J Med Virol 2001;65:282-292
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Takahashi K ,Iwata K ,Watanabe N , et al. Full-genome nucleotide sequence of a hepatitis E virus strain that may be indigenous to Japan. Virology 2001;287:9-12
CrossRef | Web of Science | Medline4
Okamoto H ,Takahashi M ,Nishizawa T ,Fukai K ,Muramatsu U ,Yoshikawa A . Analysis of the complete genome of indigenous swine hepatitis E virus isolated in Japan. Biochem Biophys Res Commun 2001;289:929-936
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Wang Y ,Zhang H ,Ling R ,Li H ,Harrison TJ . The complete sequence of hepatitis E virus genotype 4 reveals an alternative strategy for translation of open reading frames 2 and 3. J Gen Virol 2000;81:1675-1686
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