Important points in the clinical history of patients w/ suspected viral hepatitis

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

Serological Tests for Viral Hepatitis

Hepatitis A

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

• Anti-hepatitis A virus should be tested in patients <50 years

Hepatitis B

• Usually characterized by the presence of hepatitis B surface antigen (HBsAg) which suggests infectivity
  
  • Anti-HBs is produced following a resolved infection & is the only HBV antibody marker present after immunization

• Anti-HBc (anti-core antibody) is the first antibody to appear in the serum & is a marker of natural immunity
  
  • Presence of anti-HBc IgM is diagnostic for acute hepatitis B virus (HBV) infection but may occur during a flare of chronic hepatitis B
  • Its presence indicates an immune response against HBV within liver cells & is a specific marker of acute hepatitis B infection

• Hepatitis B e antigen (HBeAg) is a marker of active viral replication
  
  • This may be negative at the time that the patient is evaluated for acute hepatitis B since viral replication may have already ceased

• Patients w/ chronic hepatitis B should also be tested for co-infection w/ hepatitis C virus (HCV), hepatitis D virus (HDV) & human immunodeficiency virus (HIV), if they are at risk for these infections
• Depending on local health services, the following groups should be tested for chronic HBV infection:
  
  • Persons born in hyperendemic areas, men who have sex w/ men (MSM), IV drug users, dialysis patients, HIV-positive individuals, pregnant women & family members, household members & sexual contacts of HBV-infected persons, blood or organ donors, healthcare workers, patients needing chemotherapy
    
    • Individuals who are seronegative should be vaccinated against HBV
    • HBsAg-positive patients should be evaluated to assess progression of liver disease & need for antiviral therapy
    • Anti-HBs-positive patients have developed natural immunity & do not need to be vaccinated

Hepatitis C

• Anti-HCV antibodies are the first-line diagnostic test
• Acute hepatitis C cannot be reliably diagnosed by antibody tests since these often do not become positive until 3 months after infection
  
  • If the clinical suspicion is high, the patient should be tested for HCV RNA to establish the diagnosis
  • HCV RNA is used to determine acute or chronic infection

• Chronic hepatitis C should be confirmed w/ anti-HCV antibodies & HCV RNA
• Recombinant immunoblot assay (RIBA) may be used to establish the cause of a positive anti-HCV test in a person w/ undetectable HCV RNA
  
  • A negative RIBA indicates that a positive anti-HCV immunoassay result showed a false-positive result & no further testing is necessary
  • A positive RIBA & ≥2 subsequent tests in which HCV RNA cannot be detected suggest that HCV infection has resolved & no further testing is indicated
  • A positive anti-HCV & negative HCV RNA indicate no active HCV infection but should have HCV RNA retesting after 3 months to document recovery

• HCV RNA quantitative testing to determine baseline viral load is recommended before starting antiviral therapy
  
  • End of therapy is indicated by undetectable HCV RNA in a sensitive assay (<15 IU/mL) 12 & 24 weeks after therapy

• HCV genotype, including subtyping of genotype 1a/1b, should be determined, if possible, in all HCV-infected persons prior to treatment to determine type & duration of therapy & chances of response; predominant genotypes in Asia are:
  
  • Genotypes 1b & 2: East Asia (China, Taiwan, South Korea, Japan)
  • Genotype 3: South Asia (India & Pakistan)
    
    • Genotype 3 is considered difficult to treat & is associated w/ a poor prognosis
  • Genotypes 1 & 6: Southeast Asia (Vietnam, Cambodia, Laos, Indonesia, Myanmar, Malaysia, Philippines, Thailand)

• Liver biopsy may be done if it is thought that the results will influence clinical decision, but biopsy is not mandatory to start therapy in patients w/ genotypes 2 & 3
  
  • Liver biopsy may be obtained to provide prognostic information

• Depending on local health services, the following groups should be tested for chronic HCV infection:
  
  • Persons who have in the recent or remote past used illicit IV drugs
  • Persons w/ conditions associated w/ high prevalence of HCV infection
    
    • Positive HIV, hemophiliacs who received clotting factor prior to 1987, history of hemodialysis, persons who received blood/blood products or organ transplants prior to 1995, children born to HCV-infected mothers, healthcare workers after needle stick injury or mucosal exposure to HCV-positive blood, current sexual partners of HCV-infected persons

Hepatitis D

• Confirmed by positive anti-HDV antibody or HDV RNA test
• Hepatitis D occurs as a co-infection w/ Hepatitis B

Hepatitis E

• IgM anti-HEV, IgG anti-HEV & hepatitis E virus (HEV) RNA indicate acute hepatitis E infection
  
  • HEV RNA is detected from serum & stool of infected patients by PCR

Other lab tests that are recommended in patients suspected to have viral hepatitis:

• Liver function tests (LFTs)
  
  • Aspartate aminotransferase (AST) & alanine aminotransferase (ALT)
  • Serum bilirubin, alkaline phosphatase (ALP)

• Prothrombin time, international normalized ratio (INR)
• 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 w/ 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