In 1978 there was a vast epidemic of icteric viral hepatitis in the Kashmir Valley involving 52000 cases with 1650 fulminant forms and 1560 deaths.Since serology for hepatitis A and B in these patients was negative and the clinical course and the epidemic type of its spread were not those of post-transfusional non-A non-B hepatitis, MS Khuroo in 1980 suggested that this epidemic of hepatitis might have been caused by another virus.(Am J Med 68:818-23,1980).In 1983 Balayan demonstrated that this virus, at difference of non-A non-B virus, is transmitted by fecal-oral route. He himself ingested fecal suspensions from affected patients and contracted the disease.(Intervirology 20:23-31,1983).By transmitting the disease to monkeys the virus was recovered and its morphology and genome were identified only 12-13 years later in the early nineties.

The virus
Fig.128 -The viral particle is round, spiky, without envelope. The genome is a single stranded RNA containing about 75 kb. The particles resemble caliciviruses. It cannot be cultivated in vitro but can be propagated in cynomolgus monkeys and can be recovered from their bile. Capsomere proteins are not characterized.
Clinical features
Fig.129 - The infection causes an acute viral hepatitis. Incubation period is between 15 and 50 days, average 6 weeks. In a typical case the preicteric phase may last 10 days and consists of nausea, vomiting and epigastric pain. The jaundice will last an average of 10 days. Recovery will occur within one month.
Children below 14 and adults above 55 are prone to develop a subclinical form without jaundice. The clinical course of hepatitis E is similar to hepatitis A, however, the fatality rate which is due to fulminant hepatitis is much higher: 1-2/1000 in hepatitis A, 1-2/100 in hepatitis E. In pregnant women fatality rate could be up to 22% occurring exclusively in the third trimester. These patients develop an unusual form of DIC (diffuse intravascular coagulation) besides fulminant hepatitis. Chronicization of this infection does not appear to exist.
Laboratory data:
Bilirubin, up to 8-10 mg/dl. ALT, high up to 1000 deceasing to normal values in 3-4 months. Virus in blood and feces at the beginning of the jaundice for a brief period of 15-20 days. Large amounts of IgM antibodies from the pick of the jaundice and for over 25 weeks. IgG antibodies appear in the jaundice but are of low-titer. They seem to persist for long time, 14 years in a report from Kashmir, and appear to offer protection against subsequent infections.

Liver Histology
There are the classical changes of acute viral hepatitis without specific features. In 50% of cases, the hepatitis is "cholestatic type": lobular cholestasis with bile thrombi in bile canaliculi, cytoplasmic cholestasis, absence of diffuse lobular inflammation and degeneration but rather focal lobular necrosis and portal triditis. The New Dehli epidemic of 1955 was of this type. The cholestatic type was not observed in experimental animals.

The most practical and convenient test is Enzyme Immuno Assay (EIA) which detects IgM and IgG antibodies to HEV. Other tests, although less convenient and practical are:
-Immuno Electron Microscopy to detect viral particles in stool and serum.
-Immunofluorescence to detect viral antigen in liver tissue. Not practical.
-Polymerase Chain Reaction to detect viral genome in serum, feces, and liver tissue.

Fig.130 -The virus is endemic In a broad region of Asia, Nord Africa and only Mexico in the American continent. The vast Asiatic region involves India, southeast Asia and central Asia from Turkey to south Russia and China. There is low endemic also in Europe(Netherlands, Italy and Spain). Major epidemics with icteric cases and an average of 3% mortality occurred in:
New Delhi, 1955, 2900 cases due to contamination of drinking water.
Kirghiz Republic (Soviet Union), 1955, 11000 cases.
Nepal, 1973,
Ahmedabad, 1975, 2500 cases, due to contaminated water.
Kanpur, 1991, 79000 cases.
Xinjiang Uygur region, 186-1988, 12000 cases.
In the West, the incidence of Hepatitis E is sporadic and among travelers but it may be an important cause of hepatic failure in these non-endemic areas.

Prophylaxis and treatment
Protective antibodies after the infection are apparently effective to prevent reinfection even with strains from distant regions but the duration of this protection in humans is still questioned. Immune serum globulin will considerably reduce mortality in the 3rd trimester of pregnancy but will not block incidence of infection on contact. A vaccine is not yet available.

TF Bader, Viral hepatitis, H&H Publishers, 1995
Khuroo M, Ann. Saudi Medicine 16(3):308-319, 1996
Rizzetto M, in Oxford Textbook of Clinical Hepathology
Oxford University Press, 1991 p.617