Investigations
1st investigations to order
serum antibody to HEV
Test
Request antibody to HEV (anti-HEV) IgM in all immunocompetent patients as part of the initial evaluation.[2][15][56]
Definitive diagnosis of HEV infection in endemic areas is usually based on serum anti-HEV IgM antibody detection in immunocompetent patients.[15][56] Anti-HEV IgM is usually detectable from 1 week to 2 months after exposure to the virus and typically persists for 3-4 months.[2][56] Positive HEV IgM suggests recent HEV infection. However, anti-HEV IgM tests can also be negative in acute infection (i.e., in people who are immunosuppressed due to delayed or impaired humoral response).
Some organisations, such as the European Association for the Study of the Liver (EASL), also recommend anti-HEV IgG screening alongside anti-HEV IgM.[2] Bear in mind, however, that anti-HEV IgG positivity may reflect past infection. Anti-HEV IgG is detectable later in the clinical course than anti-HEV IgM; the titre increases throughout the illness, and can persist for many years.[2]
Result
may be positive
HEV RNA nucleic acid amplification techniques (NAATs)
Test
If the patient is immunosuppressed, use NAATs such as reverse transcriptase polymerase chain reaction (RT-PCR) for hepatitis E virus RNA detection in serum and stool (note that these tests require specialised testing facilities).[2][15][25][41][56] Antibody detection is unreliable in transplant recipients and other people who are immunosuppressed, due to delayed or impaired humoral response (which may lead to false negative results).[2][25][41][56][57] HEV RNA testing may also be helpful for diagnosis in areas where HEV infection is less common, and to detect chronic HEV infection.[15]
HEV RNA present in serum or stool indicates HEV infection and is often the only positive test in immunosuppressed patients with chronic HEV infection.[56]
HEV RNA is detectable around 3 weeks after onset of infection and may persist for several weeks after infection has cleared.[2][17][47]
Chronic HEV infection is defined by the persistence of HEV RNA for 3 or more months.[2][4][5]
In practice, serum HEV RNA testing is often used in preference to stool analysis due to availability and ease of testing; however, stool testing may be useful following treatment of chronic infection as a negative stool HEV RNA is helpful to confirm treatment success.
Result
positive for HEV
serological tests for other causes of viral hepatitis
Test
Request serological tests for hepatitis A infection, hepatitis B infection, and hepatitis C infection in all patients as part of the initial evaluation to exclude other viral causes of hepatitis. See Hepatitis A, Hepatitis B, Hepatitis C.
Result
negative
liver biochemistries
Test
Request in all patients as part of the initial evaluation:
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Alkaline phosphatase (alk phos)
Total bilirubin (direct and indirect)
Albumin.
In acute infection ALT and AST may be >1000 IU/mL. In chronic infection ALT and AST may only be mildly elevated. Bilirubin level may be elevated and albumin may be low in patients with decompensated cirrhosis.
Result
ALT, AST, alk phos, bilirubin: may be elevated; albumin: may be low
FBC
Test
Request in all patients as part of the initial evaluation:
Haemoglobin/haematocrit
White cell count and differential
Platelet count.
All parameters of the FBC may be decreased in patients with cirrhosis and portal hypertension.
Result
may be low (particularly platelet count) or normal
urea and electrolytes
Test
Request in all patients as part of the initial evaluation:
Electrolytes
Urea
Creatinine.
In patients with cirrhosis and ascites there may be electrolyte disturbances including hyponatraemia. Metabolic parameters may be deranged in severe acute infection, including infection in patients with underlying cirrhosis.
Result
may be normal or hyponatraemia and/or high urea
coagulation profile
Test
Request in all patients as part of the initial evaluation:
Prothrombin time (PT) and INR.
In patients with acute liver failure or cirrhosis, levels may be elevated, indicative of liver synthetic dysfunction.
Result
may be normal or elevated
Investigations to consider
abdominal ultrasound
Test
Consider abdominal ultrasound as a first imaging test in patients who may have underlying liver disease, are immunocompromised, or have chronic infection, to evaluate the liver for the presence of fibrosis, cirrhosis, and portal hypertension, and to exclude hepatocellular carcinoma.
Ultrasound may be normal. In patients with cirrhosis, the liver may look coarsened with irregular contours and there may be signs of portal hypertension (which may include increased spleen longitudinal diameter, oesophageal varices, or mild ascites).
Result
may reveal coarsened appearance of the liver with irregular contours and signs of portal hypertension, or hepatocellular carcinoma
CT/MRI
Test
Consider triphasic contrast CT scan or contrast MRI of the abdomen in patients with advanced fibrosis or cirrhosis.
Result
may demonstrate cirrhotic liver morphology and evidence of portal hypertension
liver biopsy
Test
Histological examination following biopsy is not routinely obtained in cases of hepatitis E infection but may be required if there is a diagnostic dilemma.
Result
may demonstrate inflammation or fibrosis
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