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The Topic of This Month Vol.35 No.1 (No.407)

Hepatitis E, 2005-2013, Japan

(IASR 35: 1-2, January 2014)

Hepatitis E is an acute hepatitis caused by infection with hepatitis E virus (HEV), which belongs to the family Hepeviridae, genus Hepevirus.  It shares many clinical characteristics with hepatitis A including jaundice.  Asymptomatic infection is quite common as in hepatitis A.  The incubation period is average 6 weeks; the prodromal symptoms are systemic and quite variable depending upon the case, include anorexia, nausea, vomiting, fatigue, malaise and low grade of fever.  The case fatality rate is found in 1-2% of HEV cases, which is 10 times higher than in HAV (0.1%).  Though HEV infection rarely becomes chronic, chronic conversion was reported among immunocompromised individuals recently (see pp. 3 & 13 of this issue).  HEV infection has been identified as an important zoonotic infection in the world including in Japan (see p. 4 of this issue).  In developing countries where HEV is endemic and water-mediated large-scale outbreaks are common, however, feco-oral infection through drinking of water contaminated by HEV patients’ feces is an important infection route.

There are four known HEV genotypes (G1-G4) all belonging to one serotype.  In developing countries, G1 is the major genotype detected in the local epidemics.  In developed countries, G3 and G4 from pigs and wild boars are commonly detected though G3 and G4 are detected from sporadic HEV cases.

In April 1999, HEV was classified as category IV infectious disease under the Infectious Diseases Control Law, and notification became mandatory as “acute hepatitis” of all the cases within 7 days after diagnosis.  Subsequently, with the law amendment in November 2003, “hepatitis E” became one of the independent category IV notifiable infectious diseases that mandates immediate reporting after diagnosis (reporting criteria are found in http://www.niid.go.jp/niid/images/iasr/35/407/de4071.pdf).

Incidence:  From January 2005 to November 2013, 626 cases were reported under the National Epidemiological Surveillance of Infectious Diseases (as of 27 November, 2013, Table 1).  While 42-71 cases were reported annually in 2005-2011, more than 100 cases have been reported since 2012 (the increase being attributable to IgA test added to the notification criteria in 2013; see below).  The domestic cases occupied 71-79% of all the cases in 2005-2008, while 86-94% since 2009 (Fig. 1).

Age and gender:  As in previous years (IASR 26: 261-262, 2005), male patients outnumbered female patients irrespectively of place of infection.  There were 502 male cases (infection in Japan: 425 cases, infection abroad: 68 cases; place of infection unknown: 9 cases) in contrast to 124 female cases (infection in Japan 107: cases; infection abroad: 13 cases; place of infection unknown: 4 cases). 

As for age distribution, among those infected in Japan, the most frequent age was middle-aged and older, while the ages of those infected abroad varied widely (Fig. 2).

The laboratory diagnostic methods and genotypes (see p. 3 of this issue):  Of the 626 cases reported in 2005-2013, 303 cases (48%) were laboratory diagnosed by RT-PCR; 228 cases (36%) and 171 cases (27%), respectively, by IgM and IgA antibody detections using ELISA (the above figures include overlaps due to use of more than one diagnostic methods in a single case) (Table 1).  In October 2011, medical insurance started covering diagnosis based on the IgA tests.  The rate of diagnosis based on the IgA test was increased since 2012.  IgA positive was added to the notification criteria in 2013.

Virus genotypes were identified for 86 cases; there were 2 G1 cases (1 domestic; 1 abroad); 39 G3 cases (36 domestic; 3 unknown for place of infection); 45 G4 cases (40 domestic; 5 abroad) and zero G2 case.

Suspected places of infection:  From 2005 to November 2013, 42 prefectures reported HEV cases, whose distribution are shown in Fig. 3.  Hokkaido, reporting every year, reported the largest number of cases, about 34% of all the domestic cases (see pp. 5 & 7 of this issue), which was followed by Tokyo (14%).  The place of infection abroad were mainly Asia, China being the top (42%) followed by India (17%) and Nepal (9.9%) (Table 2). 

Infection routes:  Of 626 cases reported from 2005 to November 2013, information on the infection routes was available for 250 cases infected in Japan and 17 cases infected abroad.  Among the 250 domestic cases, 88 cases (35%) consumed pork (including liver), 60 cases (24%) wild boar meat, 33 cases (13%) deer meat, 10 cases (4.0%) horse meat, 11 cases (4.4%) shellfish (including oyster) and 37 cases (15%) meat and 24 cases (9.6%) liver of unidentified animals (raw or grilled) (figures include overlaps of counting).  There were 4 cases without history of meat consumption that appeared to have been infected through dissection, burial, preparation or cooking.  Among the 17 cases infected abroad, 6 cases (35%) were attributable to drinking of unboiled water, 4 cases (24%) to consumption of pork, and 4 other cases (24%) to consumption of meat of unknown animals.  

HEV infections among animals:  High prevalence of HEV infection in pigs has been reported from many countries including Japan.  In Japan, HEV genes have been detected at high frequencies from feces of pigs 2-3 months of age, and more than 90% of pigs 6 months of age placed on market had anti-HEV antibody.  HEV gene was detected from pig livers placed on the market (see pp. 4 & 8 of this issue).  While the antibody prevalence being reportedly lower than that in pigs, HEV is widely distributed among wild boars throughout the country (34%). 

While deer has been claimed to be infected by HEV, Kumamoto Prefectural Public Health Institute was unable to find any deer whose liver, blood or muscle specimens were HEV genome positive (see p. 9 of this issue).  As also for cattle, sheep and goats, HEV-genome positive cases have not been reported (see p. 10 of this issue).  More recently, several novel HEV variants have been detected in rats, rabbits, bats, and ferrets, but its infectivity to humans is unknown (see p. 10 of this issue).  

Prevention of HEV infection:  As HEV infection due to consumption of raw animal liver and meat continues, the Ministry of Health, Labour and Welfare (MHLW) has published a “Case study of hepatitis E virus infection through consumption of meat (hepatitis E Q&A)” 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).  MHLW continuously recommends hunters, meat handlers and consumers to avoid eating raw meat or liver of pigs or other wild animals, and to consume these foods only after thorough cooking. 

When traveling to endemic areas in abroad, as in case of hepatitis A, drinking of unboiled water and eating of undercooked food should be avoided.  The Japanese public should be more aware of the risks of HEV infections.  Vaccines for hepatitis E are currently under development in Japan.

Copyright 1998 National Institute of Infectious Diseases, Japan

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