Hepatitis E

Background: Hepatitis E virus (HEV) is an enterically transmitted self-limited infection. It is spread by fecally contaminated water within endemic areas. Outbreaks can be epidemic and individual. It has many similarities with hepatitis A.

HEV was discovered during electron microscopy of feces contaminated with enteric non-A, non-B hepatitis. It is icosahedral and nonenveloped. It has a diameter of approximately 34 nanometers and contains a single strand of RNA approximately 7.5 kilobases long.

Because of similar physicochemical and biological properties, HEV currently is classified in the Caliciviridae family. However, the HEV genome is different from the other caliciviruses, and analysis suggests that its genomic sequences are more similar to rubella virus. Therefore, HEV eventually may be reclassified.

The Caliciviridae genus includes vesicular exanthema virus of swine and rabbit, hemorrhagic disease virus, and Norwalk-like viruses. The latter have been associated with human gastroenteritis.

Pathophysiology: The HEV genome contains 3 open reading frames (ORFs). The largest, ORF-1, codes for the nonstructural proteins responsible for viral replication. ORF-2 contains genes encoding the capsid. The function of ORF-3 is unknown, but the antibodies directed against ORF-3 epitopes have been identified

History: The incubation period ranges from 15 days to 60 days, and the course of infection has 2 phases termed prodromal and icteric.

• Prodromal-phase symptoms include the following:

• Myalgia

• Arthralgia

• Fever with mild temperature elevations (25-97%)

• Anorexia (66-100%)

• Nausea/vomiting (30-100%)

• Weight loss (typically 2-4 kg)

• Dehydration

• Right upper quadrant pain that increases with physical activity

• Icteric-phase symptoms include the following:

• Jaundice - May be difficult to see with some patients' natural skin color; serum bilirubin level is greater than 3 mg/dL; scleral icterus is present

• Dark urine

• Light-colored stools (20-40%)

• Pruritus (50%)

• Other features include the following:

• Urticarial rash
• Diarrhea
• Rapidly increasing serum amino transferase (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) levels that peak within 4-6 weeks of onset and gradually decrease to normal within 1-2 months
• Viral excretion in stool persisting 14 days from onset

• Symptoms of HEV are similar to other hepatitides and include the following:

• Abdominal pain (35-80% of patients)

• Jaundice
• Anorexia
• Hepatomegaly (10-85%)
• Malaise (95-100%)
• Vomiting

• When or how long the patient is infectious cannot be determined, but infectivity may relate to the presence of the virus in the stool.

Physical:

• Right upper quadrant tenderness

• Possible enlarged liver (palpable edges)

• Possible splenomegaly

• Possible transient spider angiomata

Lab Studies:

• A study involving human volunteers and nonhuman primates determined the typical serological course of HEV.

• Two humans ingested the virus and demonstrated liver enzyme elevations within 4-6 weeks that persisted for as long as 90 days.

• The virus was detectable in their stool approximately 1 month after ingestion and remained for another 2-4 weeks.

• Western blot and enzyme immunoassays detect anti-HEV antibodies by using the antigenic domains from ORF-2 and ORF-3. Assays of ORF-2 are more sensitive.

• Testing to detect anti-HEV immunoglobulin M (IgM) and immunoglobulin G (IgG) differentiates acute and chronic infection.

• The IgM titer falls rapidly after infection, becoming virtually undetectable within 6 months.

• Anti-HEV IgG persists for longer than 6 months, although its actual duration of positivity is unknown.

• IgG anti-HEV appears to afford protection against reinfection.
• HEV IgG AB testing is available through the Centers for Disease Control and Prevention (CDC).

• Serum, liver, and stool samples can be tested for HEV RNA with a polymerase chain reaction assay. These tests are not available commercially.

• Aminotransferase levels (AST, ALT) are elevated several days before the onset of symptoms but generally return to normal within 1-2 months after the peak severity of the disease has passed.

• Elevations can be associated with underlying liver disease or exposure to other hepatotoxins.

• Whether the magnitude of elevation correlates with the histological severity is not clear.

• Serum bilirubin elevations occur in both the total and direct fractions.

• Hemolysis is unusual.

• In most cases, bilirubin levels take longer to return to normal than aminotransferase levels.

• Many patients develop a mild leukocytosis.

• If associated with fever, bacteremia should be suspected.

• More commonly, WBC counts are decreased. Differential counts may show atypical cells and lymphocytosis.

Imaging Studies:

• Abdominal radiographs have no role in evaluating acute viral hepatitis unless the physical examination suggests a perforated viscus.

• Abdominal ultrasonography is recommended.

• It helps rule out biliary obstruction in cases with significant nausea, vomiting, or fever.

• It can demonstrate the presence of an enlarged liver; echo texture is heterogeneous and coarsened.

• It can demonstrate splenomegaly, if present.

Other Tests:

• Perform blood cultures if the patient is febrile and hypotensive with an elevated WBC count.

• Determine serum acetaminophen levels if overdose is suspected.

Procedures:

• Liver biopsy usually is not necessary.

• Typical pathological findings are included in Histological Findings.

Histologic Findings: The pathology picture is cholestatic, with stasis of canalicular bile and marked proliferation of intralobular bile ductules. The cholestasis is most notable within the centroacinar regions. Parenchymal changes are less severe and include swollen hepatocytes, foam cells, and acidophil bodies. Inflammatory infiltrate of mononuclear cells is present, resulting in expanded portal areas and possible piecemeal necrosis.

Medical Care:

• Therapy should be predominantly preventive, relying on clean drinking water, good sanitation, and proper personal hygiene.

• Travelers to endemic areas should avoid drinking water or other beverages that may be contaminated and should avoid eating uncooked shellfish. Care should be taken while preparing uncooked fruits or vegetables. Boiling water may prevent infection, but the effectiveness of chlorination is unknown.

• No immunoprophylaxis is available. Immunoglobulin from infected patients is not effective in preventing outbreaks or sporadic cases.

• Prototype vaccines are being developed using animal models. To date, this is hindered by an inability to maintain the virus in cell cultures.

• Once infection occurs, therapy is limited to support. Provide patients with adequate hydration and electrolyte repletion. Hospitalization is indicated only for patients unable to maintain oral intake.

Diet:

• The acute illness may result in anorexia, nausea, and vomiting, predisposing patients to dehydration.

• These symptoms tend to be worse in the afternoon or evening. Patients should attempt to ingest significant calories in the morning. As they improve, frequent small meals may be better tolerated.

• Hospitalization should be considered for patients with dehydration.

• Neither multivitamins nor specific dietary requirements are required.

Activity:

• Patients should be allowed to function at whatever levels they can tolerate.

• No evidence indicates that bedrest hastens recovery. It actually may retard recovery.

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Prognosis:

• No chronic cases of acute hepatitis E have been reported. The infection is self-limited.

• Whether protective immunoglobulins develop against future reinfection remains unknown

Дата добавления: 2015-10-29