Acute Hepatitis E

Definition, Etiology, PathogenesisTop

1. Etiologic agent: Hepatitis E virus (HEV), a Hepeviridae family virus in the Orthohepevirus A species. Eight genotypes are known in this group. Genotypes 1 and 2 cause human infections only and are transmitted in contaminated water sources by the fecal-oral route. Outbreaks tend to occur in areas with poor hygiene. Genotypes 3 and 4 are zoonotic, most commonly found in pigs (true primary host) and wild boars. Humans become infected when they consume infected meat. Genotypes 5 and 6 are found in wild boars and genotypes 7 and 8, in camels. Pathogenesis is not fully known. The primary site of viral replication is probably the gastrointestinal tract.

2. Incubation period: From 15 to 60 days.

3. Clinical features, natural history, and prognosis: In the majority of patients (up to 80%) HEV infection is asymptomatic. Manifestations of symptomatic HEV infection are as in other types of acute viral hepatitis. Jaundice is more common in patients with HEV genotype 1 or 2 infection. Cholestatic disease may occur. Overt acute hepatitis caused by HEV genotype 1 or 2 infection in endemic regions is most common in young adults (15-35 years), 2 to 5 times more frequent in men, and associated with estimated mortality rates of 0.2% to 4% (up to ~10% in children <2 years and 10%-25% in pregnant women due to obstetric complications and fulminant liver failure). In middle-aged and elderly men, acute infections with HEV genotype 3 or 4 are usually symptomatic, mild, and only rarely fatal. The antibodies that develop after HEV clearance are nonprotective and reinfections can occur. Chronic infections (only in the case of HEV genotype 3) may occur, particularly in immunosuppressed patients.

DiagnosisTop

Laboratory test results are the same as in other types of acute viral hepatitis. Diagnosis is usually based on the detection of serum anti-HEV antibodies (IgM antibodies appear in the prodromal period and are then replaced by IgG antibodies). The most reliable finding for hepatitis E is a positive serum HEV RNA test result, especially in immunocompromised patients (fecal tests are also performed but access is limited). Chronic infection is diagnosed in patients with serum HEV RNA persisting >3 months.

Differential diagnosis is as in hepatitis A.

ManagementTop

Treatment, monitoring, and effects on daily activities are as in hepatitis A. Probably the most common diagnostic omission is classification of liver disease caused by HEV infection as drug-induced.

Most cases of acute HEV infection are self-limiting and do not require antiviral therapy. In patients with severe acute HEV or acute-on-chronic liver failure, the use of ribavirin may be considered for 3 months. In addition, patients with primary liver disease infected with HEV genotype 3 and those receiving immunosuppressive drugs in doses that cannot be reduced or in whom dose reduction is ineffective may consider ribavirin 600 to 800 mg/d for ≥3 months as monotherapy or in combination with peginterferon alpha.

ComplicationsTop

Arthritis, aplastic anemia, mesangioproliferative or membranous glomerulonephritis, pancreatitis, peripheral neuropathies, polyradiculopathies, Guillain-Barré syndrome, ataxia, and Bell palsy. These manifestations may be the dominant clinical features and may not be attributed to HEV infection.

PreventionTop

1. In endemic regions improvement of hygiene standards, including water supply, is necessary. In developed countries preventive measures include appropriate disposal of sewage from animal farms, thermal processing of pork at 71 degrees Celsius for ≥20 minutes, and avoiding consumption of raw shellfish by immunocompromised persons. Hepatitis E vaccine against genotype 4 HEV is approved in China but does not provide immunity.

2. Disease reporting is subject to local regulations.