Hepatitis E is a serious liver disease caused by hepatitis E virus. Hepatitis E virus is a cause of waterborne hepatitis, especially in developing countries. Hepatitis E virus is a small non- enveloped with a diameter of 27-34nm, positive sense ss RNA icosahedral virus with 7.5 kb genome. The genome of hepatitis E virus contains 3′ poly A tail and short 5′and 3′ noncoding region (NCR). It encodes three open reading frames that are used to express different proteins. ORF 1 that encodes a polyprotein that undergoes post translational cleavage into multiple non-structural proteins required for viral replication, ORF2 that encodes the capsid protein, ORF3 that encodes a small immunogenic amino acid phosphoprotein. The proteins encoded by ORF2 and ORF3 are produced from a bicistronic subgenomic (SG) mRNA. A junction region (JR) is present between ORF1 and the start site of the subgenomic coding region. Therefore, the coding region for ORF2 overlaps with ORF3, but neither overlaps with ORF1. The 5′ end of the HEV genome contains a 7-methylguanosine cap structure, and the genome is organized as 5′ NCR-ORF1-JR-ORF3/ORF2-3′ NCR. Two cis-reactive elements (CRE) have been identified in the genome. The first CRE is essential for HEV replication and overlaps with both the 3′ end of ORF2 and the 3′ NCR. The second CRE is located in the junction region, and both the sequence and structure of the stem–loop in the junction region are crucial for HEV replication. Furthermore, the second CRE may be the promoter for the 2.0-kb SG mRNA.
Reservoir: Human and some primates act as reservoir.
Hepatitis E is an important enteric infection causing large scale outbreak in many part of the world. The earliest outbreak occurred in Kanpur city, Utter Pradesh, India in 1991 where over 79000 clinical cases were reported. Epidemics of Hepatitis E have been reported in Southeast and Central Asia, northern and western Africa and Mexico.
The highest prevalence of infection occurs in regions where low standards of sanitation promote the transmission of the virus. High case fatality rate upto 20% in pregnant women affected in their third trimester of pregnancy.
Hepatitis E is found worldwide and different genotypes of the hepatitis E virus determine differences in epidemiology. For example, genotype 1 is usually seen in developing countries and causes community-level outbreaks while genotype 3 is usually seen in the developed countries and does not cause outbreaks.
Globally, 70,000 deaths and 3.4 million cases of acute hepatitis E are attributable to infection with hepatitis E virus genotypes 1 and 2
Epidemiology in Nepal
In Nepal Hepatitis E is a major public health concern, and the Kathmandu is the hyper-endemic area of the Hepatitis E virus infection, common cause of jaundice and acute liver failure in 2006-2007. Recent Hepatitis E outbreaks occurred in the Biratnagar City, Nepal on May, 2014 where over 6000 were infected, 9 were died, 80 were in critical condition and 35 were receiving treatment in intensive care unit in different hospitals. The disease was caused by the water distributed by the Nepal Water Supply Corporation, without prior testing.
Hepatitis E is transmitted mainly through faecal-oral route due to fecal contamination of drinking water. Other transmission routes are:
- Food borne transmission from ingestion of products from infected animals
- Transfusion of infected bloods
- Vertical transmission from pregnant woman to fetus
Outbreaks are associated with contaminated water in countries with poor sanitation. The ingestion of raw or uncooked shellfish has also been identified as the source of sporadic cases in endemic areas.
In monkeys, viral replication apparently causes liver damage. The immune response successfully eliminates viraemia. Seroconversion marks the clearing of virus from feces and blood. Severe or fulminant cases may show sub massive and massive hepatic necrosis.
Pathogenesis of hepatitis E virus is not completely understood.
The incubation period of Hepatitis E virus ranges from 3-8 weeks with mean of 40 days.
The sign and symptoms of Hepatitis E virus include:
- Jaundice (yellow discoloration of the skin and sclera of the eye, dark urine and pale stool)
- Abdominal pain and tenderness
- Nausea and Vomiting
- Joint pain
The ratio of symptomatic to asymptomatic infection in outbreak is range from 1:2 to 1:13.
- People in overcrowded, unsanitary areas
- Young adults aged 15-40 years
- Pregnant women
- Children but generally asymptomatic
Cases of hepatitis E are not clinically distinguishable from other types of acute viral hepatitis. Diagnosis can be confirmed by the detection of specific IgM and IgG antibodies to Hepatitis E virus but commercial test kits are not available. Additional tests include reverse transcriptase polymerase chain reaction (RT-PCR) to detect hepatitis E virus RNA in blood and/or stool.
Hepatitis E is usually self-limiting. There is no specific antiviral drug available. Treatment is only based on supportive therapy.
Hospitalization is required for people with fulminant hepatitis and should be considered for symptomatic pregnant women.
A vaccine based on recombinant viral proteins has been developed and recently tested in a high- risk population (military personnel of a developing country).The vaccine appeared to be effective and safe, but further studies are needed to assess the long-term protection and the cost- effectiveness of hepatitis E.
Prevention of Hepatitis E depends on:
- Good sanitation and the availability of clean drinking water.
- Establishing proper disposal systems to eliminate sanitary wastes.
- Avoiding drinking water of unknown purity.
- Maintaining hygienic practices such as hand washing with safe water, particularly before handling food.
Miss Pratiksha Pokhrel
St. Xavier’s College, Kathmandu, Nepal
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