Hepatitis E Virus

Epidemiology

HEV infection manifests in two distinct clinicoepidemiologic patterns, mainly related to viral genotype. In hepatitis E epidemics, HEV (genotype 1 or 2) is transmitted primarily by the fecal-oral route. Fecally contaminated drinking water is the most commonly documented vehicle of transmission, and outbreaks usually occur during the rainy season and sometimes affect thousands of people. HEV infection also accounts for most cases of acute sporadic viral hepatitis in both children and adults in endemic countries. Risk factors for sporadic hepatitis E have not been well defined.

In the past, hepatitis E cases in the US and Western Europe have been reported among travelers returning from HEV genotype 1–endemic areas. Although outbreaks of hepatitis E do not commonly occur in the US and Western Europe, increasing numbers of autochthonous cases unrelated to travel have been reported over the past 2 decades. ^, The HEV strains isolated from patients with autochthonous hepatitis E belong to HEV genotype 3 and 4 and have close genetic resemblance to the swine HEV strains isolated from local farms. ^, Identification of IgG anti-HEV in animal species in many regions of the world provides indirect evidence that HEV is a zoonotic agent. ^, Cross-species transmission studies found that human HEV genotypes 1 and 2 can be transmitted to non-human primates but not to other animals. In contrast, HEV genotype 3 has been experimentally transmitted from pigs to nonhuman primates and vice versa. Zoonotic reservoirs for HEV genotype 3 and 4 have been identified and include domestic pigs, wild boars, deer, rabbits, rats, mongoose, trout, ferrets, chicken, and molluscan shellfish. HEV can be transmitted by food, as evidenced by disease following consumption of uncooked offal from wild boar and sika deer in Germany and Japan, and after consumption of raw figatelli, a traditional pig liver sausage, in France. To date, there has been no confirmation of direct HEV transmission through contaminated produce, although its presence in irrigation waters, berries, green leafy vegetables, salads, pepper, and bay leaf powder has been reported. ^,

Vertical transmission of HEV from infected mother to fetus is common. In epidemic settings, person-to-person transmission can contribute to significant transmissions. Nosocomial transmission, presumably by person-to-person contact and by transmission through blood transfusion, has been reported.

The worldwide distribution of hepatitis E has not been fully determined, in part because of lack of well-standardized serological tests and lack of surveillance for hepatitis E. ^, However, HEV infection appears to be endemic globally. Large outbreaks of HEV have been documented over a wide geographic area, primarily in developing countries with inadequate environmental sanitation.

Clinical Manifestations

HEV infection can be asymptomatic or can result in clinically evident disease. The incubation period ranges from 15–60 days (mean, 40 days). Typical acute hepatitis E signs and symptoms are indistinguishable from those of other types of viral hepatitis and consist of jaundice, malaise, anorexia, nausea, vomiting, abdominal pain, dark urine, fever, and hepatomegaly. ^{, , , ,} Other less common signs and symptoms are diarrhea, arthralgia, pruritus, and urticarial rash. The period of infectivity after acute HEV infection has not been determined, but virus excretion in stool has been demonstrated beginning approximately 2 weeks before elevation of serum hepatic enzyme levels and ending by the time liver enzyme levels return to normal. ^, In most outbreaks, the highest rates of clinically evident disease have occurred in young to middle-aged adults; lower disease rates in younger age groups could be the result of anicteric or subclinical infections. ^{, , ,} In contrast, most autochthonous HEV infections occur among men aged >40 years. No evidence of chronic HEV infection has been detected in long-term follow-up of otherwise healthy people and people infected with HEV genotypes 1 and 2. However, chronic HEV infection occurs among adult recipients of solid organ transplants, people with immunological disorders including acquired immunodeficiency syndrome, and people with hematologic malignant diseases. Association of autochthonous HEV infection with neurologic signs and symptoms including Guillain-Barré syndrome is recognized increasingly. ^, Cases of chronic HEV infection that rapidly progressed to cirrhosis have been reported among children who received bone marrow transplants for hematologic malignant diseases and among liver transplant recipients. ^, HEV superinfection causes severe hepatic decompensation in patients with preexisting chronic liver disease. ^,

The mortality rate observed during hepatitis E epidemics is approximately 0.1%–4%. However, fulminant hepatitis occurs more frequently among pregnant women, particularly in the third trimester, and case-fatality rates can reach 25%. The reason for the high mortality rates among pregnant women is unknown; causes of death include hepatic encephalopathy and disseminated intravascular coagulation. ^, In a prospective study of 26 pregnant women with HEV infection, 15 patients had fulminant hepatic failure and 11 patients had nonfulminant disease. Five mothers died undelivered, two aborted, four delivered prematurely, and 15 delivered full-term infants. Fifteen (79%) of the 19 live born infants had evidence of HEV infection at birth (12 had IgM anti-HEV and 10 had HEV RNA detected). Neonates had icteric hepatitis (N=7), anicteric hepatitis (5), and jaundice with normal hepatic enzymes (3). In the first week of life, seven infants died, one of prematurity and six of HEV infection; five of six mothers of infants who died had fulminant hepatic failure. Vertical transmission of HEV to the fetus with poor perinatal outcome has occurred in 30%–100% of pregnant women with HEV infection. Mortality rates in young children can be high. ^,