Hepatitis%20a%20-and-%20e Diagnosis

Important Points in the Clinical History of Patients with Suspected Viral Hepatitis

• Contacts with jaundiced patients
• IV drug use
• History of blood transfusion
• Surgery or hospitalizations
• Family history of chronic liver disease
• Occupation
• Food and water sources

Serological Tests

Hepatitis A

• Anti-hepatitis A virus (HAV) IgM has high sensitivity and specificity and is a marker of acute infection
  
  • This test remains positive for ≥6 months

• Anti-HAV should be tested in patients <50 years

Hepatitis E

• IgM anti-hepatitis E virus (HEV), IgG anti-HEV in combination with HEV RNA indicate acute hepatitis E infection
• Detection of HEV antigen by enzyme immunoassays may also be used to diagnose both acute and chronic infections
• HEV genotype should be determined, if possible, in all HEV-infected persons prior to treatment to determine type and duration of therapy and chances of response; predominant genotypes worldwide are:
  • Genotype 1: Africa and Asia
  • Genotype 2: Mexico, West Africa
  • Genotype 3: Developed countries
  • Genotype 4: China, Taiwan, Japan

Tests to Rule Out Other Viral Hepatitis

• Hepatitis B: Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B e antigen (HBeAg)
• Hepatitis C: Anti-hepatitis C virus (anti-HCV) antibody, HCV RNA test, HCV core antigen
• Hepatitis D: Anti-hepatitis D virus (anti-HDV) antibody, HDV RNA test
• Please see Hepatitis B and Hepatitis C disease management charts for further information

Nucleic Acid Amplification Test (NAAT)

• Eg conventional reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, transcription-mediated amplification methods, genotyping for HAV RNA or HEV RNA may be considered
• HEV RNA is detected from serum and stool of infected patients by NAAT-based assays

Immunohistochemistry

• HEV ORF2 protein immunohistochemistry can be used to establish a histopathologic diagnosis of hepatitis E

Other Recommended Lab Tests in Patients Suspected of Viral Hepatitis

• Liver function tests (LFTs)
  
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
  • Serum bilirubin, alkaline phosphatase (ALP)
• Prothrombin time (PT), international normalized ratio (INR), complete blood count (CBC) with platelets, renal function tests
• Noninvasive tests such as the aminotransferase/platelet ratio index (APRI) or FIB4 may be used to assess the degree of hepatic fibrosis when resources are limited prior to initiating HCV therapy
  
  • Transient elastography may be an option for patients with contraindications to liver biopsy

Features of Hepatic Decompensation

• Mental dullness, hepatic encephalopathy, bilateral asterixis, ascites, clinical deterioration
• Serum bilirubin >2.5x upper limit of normal, PT is 3 seconds longer than control or INR >1.5

Biochemical or Clinical Improvement

• Repeat liver function test and serum/stool HEV RNA detection will show normalization if patient responded to treatment or infection subsided spontaneously
• Repeat anti-HAV IgM after 1 week may be used to determine if acute or recent infection has resolved
• Refer to a specialist if tests are still positive for infection and with disease persistence or progression

• Hepatitis B, C, D: Specific serologic testing identifies the different types of hepatitis
• Epstein-Barr virus, cytomegalovirus: Presents with liver function abnormalities, fever, fatigue, lymphadenopathy
• Yellow fever virus infection: Signs and symptoms (eg malaise, fever, jaundice) are similar to hepatitis A
• Herpes simplex virus infection: Usually severe and in immunocompromised patients
• Adenovirus infection: Gastrointestinal tract involvement overlaps with hepatitis A
• Human immunodeficiency virus (HIV) infection: Presents as nausea, diarrhea, and anorexia
• Alcoholic hepatitis: Presents as jaundice, anorexia, fever, tender hepatomegaly, right upper quadrant pain, epigastric pain, hepatic encephalopathy, signs of malnutrition, and increased AST/ALT
• Drug-induced liver injury (DILI): History of recent use may help in the diagnosis
• Budd-Chiari syndrome: Patient usually presents with acute or subacute liver disease or acute liver failure; diagnosis is made with the help of ultrasonography
• Autoimmune hepatitis: Nonspecific symptoms eg malaise, anorexia, nausea, abdominal pain, itching, arthralgia may be confused with hepatitis A and E; serologic testing and histologic findings may help with the diagnosis
• Wilson disease: Present as acute hepatitis, jaundice, abdominal pain, increased AST/ALT
• Bacterial infections: Malaria, leptospirosis, syphilis, Q fever

• More common in adults >50 years old
• Disease relapse may occur 6 months after resolution of acute illness

Hepatitis A

• Fulminant hepatitis may occur in patients with underlying hepatic disease or coinfection
  • Liver transplantation may be carefully considered in patients with fulminant hepatic failure and poor prognosis with medical management alone
• Cholestatic hepatitis
• Relapsing hepatitis
• Autoimmune hepatitis

Hepatitis E

• Neurologic manifestations: Acute meningoencephalitis, acute transverse myelitis, brachial plexus neuritis, Bell palsy, Guillain-Barré syndrome
• Hematologic manifestations: Severe thrombocytopenia, hemolytic anemia
• Acute pancreatitis
• Renal manifestations: Membranoproliferative glomerulonephritis, membranous glomerulonephritis