The Topic of This Month Vol.26 No.10(No.308)

Hepatitis E as of August 2005, Japan

(IASR 2005; 26 : 261-262)

Hepatitis E is an acute hepatitis caused by infection with hepatitis E virus (HEV), which belongs to the family Hepeviridae , genus Hepevirus . Hepatitis E shares many clinical characteristics with hepatitis A, including typical symptoms such as jaundice and the absence of chronic infection. However, the case-fatality rate is reportedly higher than that of hepatitis A, with 20% fatality among pregnant women. In developing countries, fecal-oral infection with viruses excreted in feces of infected patients commonly occurs, resulting in sporadic cases or outbreaks. However, large-scale outbreaks have occasionally been reported due to contaminated drinking water. On the other hand, in Japan and other countries, HEV infection has been identified in different animal species, leading to the recognition of hepatitis E as a zoonotic infectious disease (see IASR 193-194, 2005).

There are four known HEV genotypesiG1-G4j. G1 mainly circulates within human populations in developing countries. G2 has been reported in epidemics in Mexico, Namibia, and Nigeria, but has not been seen in recent epidemics. G3 and G4 infect both humans and animals. Only one HEV serotype is thought to exist.

In Japan, reporting of hepatitis E was mandatory within 7 days after diagnosis by a physician as an gacute viral hepatitish (category IV notifiable infectious disease), under the National Epidemiological Surveillance of Infectious Diseases (NESID) based on the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law, implemented in April 1999). Subsequently, in accordance with the law amendment in November 2003, ghepatitis Eh became an independent category IV notifiable infectious disease, with notification being required immediately after diagnosis.

Yearly and monthly incidence: Since April 1999, 118 cases reported as hepatitis E and confirmed as HEV infection have been recorded: 0 in 1999 (day of diagnosis during April-December), 3 in 2000, 0 in 2001, 16 in 2002, 30 in 2003, 37 in 2004, and 32 in 2005 (day of diagnosis during January-August) (reports as of September 8, 2005). Reports of cases presumed to have been infected in Japan (domestic cases) have increased sharply after 2002 (Fig. 1). At the same time, cases presumed to have been infected outside Japan (imported cases) have also increased since 2003. The increase in reports may reflect the fact that laboratory confirmation of infection through HEV gene detection by RT-PCR and IgM antibody detection by ELISA has recently become possible (see p. 263 of this issue). Dates of diagnosis by month are shown in Fig. 2. Seasonality has not been apparent. Hepatitis E was diagnosed within 10, 19, and 28 days of initial examination in 25%, 50%, and 75% of reported cases, highlighting the considerable time required in order to make the diagnosis.

Age and gender: Males overwhelmingly outnumbered females among both domestic and imported cases (101 total male cases: 71 domestic, 28 imported, 2 unknown; 17 total female cases: 15 domestic, 2 imported). Most of the domestic cases were of middle or advanced ages, with peaks in the latter 50fs for males and the latter 60fs for females, while imported cases were mainly in their 20fs to early 30fs (Fig. 3).

The laboratory diagnostic methods and genotypes: Of the 118 cases reported between April 1999 and August 2005, 33 cases were diagnosed by gene detection and 102 by antibody detection (figures include cases diagnosed by both methods). Virus genotypes were reported for 17 cases (including those determined after the initial report); G3 was detected in 12 domestic cases and 1 imported case (presumed to have acquired infection in Thailand), while G4 was detected in 4 domestic cases.

Presumed region of infection: Distribution of domestic cases by prefecture is shown in Fig. 4. During 2002-August 2005, cases were reported in 30 different prefectures. Cases from Hokkaido occur every year and account for about one third of all cases nationwide. The presumed areas of infection among imported cases were mainly in Asia, with China being the most identified followed by India (Table 1).

Foodborne infection: Of 86 domestic cases diagnosed during April 1999-August 2005, 16 were suspected to have been infected through pork liver consumption, 13 through wild boar liver and meat consumption, and seven by raw deer meat consumption. Recently reported foodborne outbreaks are described below.

1) In Hyogo Prefecture, four of eight members from five families who consumed frozen raw deer meat became ill in April 2003; HEV-IgM antibody and HEV genes were detected from acute-phase serum. The nucleotide sequences of HEV G3 detected in leftover wild deer meat were nearly identical to those from the cases (see p. 264 of this issue).

2) In Fukuoka Prefecture, one of 11 persons who ate wild boar meat developed disease in March 2005, with HEV G3 genetic sequences from serum of cases matching those detected in leftover wild boar meat (see p. 265 of this issue).

3) In Hokkaido, a patient developed illness in September 2004 and subsequently died of fulminant hepatitis the following month. Investigation and laboratory tests revealed that three of 14 family members and relatives who ate at a restaurant with the case, in addition one of nine individuals from a separate group that ate at the same restaurant, were confirmed to have been infected. Although food items were suspected as the source of the outbreak, no virus-contaminated food items could be implicated (see p. 266 of this issue). HEV G4 was detected in one case.

4) In Mie Prefecture, four sporadic cases were notified in late June 2005. Two strains of HEV G3 detected from three cases demonstrated high homology by phylogenetic analysis. Although consumption of undercooked meat was suspected as the cause, a common source of infection was not identified (see p. 267 of this issue).

HEV infections among animals (see p. 269 of this issue): HEV infection in pigs has been found at high frequencies in both developing and developed countries. In Japan, HEV genes have been detected in significant proportions from serum and feces of pigs 2-3 months of age. In addition, it is known that HEV is widely distributed among wild boars throughout the country. In contrast, while HEV has been detected in deer meat in Hyogo Prefecture, investigations have revealed no other HEV genetically-positive deer, with very few antibody-positive deer, in other prefectures.

Prevention of HEV infection: Given the fact that it has become evident that recent cases of HEV infection have been due to consumption of raw animal liver and meat, the Ministry of Health, Labour and Welfare has published a gCase study of hepatitis E virus infection through consumption of meat (hepatitis E Q&A)h on its homepage to promote awareness of HEV (Notice by the Inspection and Safety Division, Department of Food Safety, Pharmaceutical and Food Safety Bureau, November 29, 2004: http://www.mhlw.go.jp/topics/syokuchu/kanren/kanshi/041129-1.html). It is important to inform hunters, meat handlers and consumers to avoid eating raw meat or organs of pigs or other wild animals, and to consume these food items only after thorough cooking.

Furthermore, similar to the prevention of hepatitis A, it is important to pay attention to drinking water sources and to avoid eating undercooked food when traveling to endemic areas. Vaccines for hepatitis E are currently under development.

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