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VIRAL HEPATITIS SEROLOGIES

To diagnose hepatitis A virus infection (there is only acute or recurrent infection, a chronic infectious state does not exist), a positive IgM anti-HAV titer is the preferred test.

IgM anti-HAV: This test is indicative of acute or recent infection. This test becomes positive around 10 days before symptoms and becomes negative after approximately six months. In acute infection, patients will be symptomatic and display a marked transaminasemia.

Total (IgM and IgG) anti-HAV: Indicative of past infection or prior vaccination. A positive level indicates immunity to infection.

Stool HAV: HAV is found in stool samples during active infection or if patients who have had a recent infection develop recurrent symptoms, a positive stool sample would indicate recurrence of infection.

Hepatitis B Virus (HBV)

To diagnose acute HBV infection, the patient will display symptoms of acute hepatitis and have a marked transaminasemia on laboratory testing. The presence of HepBsAg or IgM anti-HepB core antibody is indicative of acute infection. Chronic infections are diagnosed when Hep BsAg persists in the serum for greater than six months after acute infection.

Hepatitis B surface antigen (HepBsAg): This test is indicative of active infection with the hepatitis B virus. Acute infection is marked by concomitant symptoms and a significant transaminasemia with levels greater than 10 times normal and often with levels over 1,000. In acute infection, the level returns to undetectable by about six months. Chronic infection is diagnosed if HepBsAg positivity persists for greater than six months after acute infection, or if the patient is asymptomatic with normal or mildly elevated transaminases and has a positive HepBsAg.

IgM anti-HepB core Ab: This is indicative of acute infection. It is used when acute infection is suspected but the HepBsAg is negative. This part of acute infection is termed the window phase (HepBsAg negative and IgM anti-HepB core Ab positive).

Total anti-Hep B core Ab: This becomes positive after acute infection and is indicative of prior infection.

IgG anti-Hep BsAg Antibody: Indicates past infection with resultant immunity to further infection or immunity from prior vaccination series.

Hep B e Antigen (Hep BeAg): This is seen in chronic hepatitis B infection and indicates active viral replication and is associated with more aggressive liver destruction. This antigen is detected in patients with chronic hepatitis B infection in either the immune tolerance or immune clearance phases.

Anti-HepB e Antibody (Hep BeAb): Appears upon clearance of the e antigen. It is associated with better outcomes and is often the target of therapy. In chronic hepatitis B, its presence is seen in the inactive carrier or reactivation phases.

Hepatitis B virus DNA (HBV DNA): This is indicative of ongoing infection. High levels (greater than 20,000 IU/mL) are seen with the immune tolerance and immune clearance phases. Lower levels are seen in the reactivation phase and even lower levels (less than 2,000 IU/mL) are seen in the inactive carrier phase.

Hepatitis C Virus (HCV)

Acute infections are often asymptomatic and therefore not pursued aggressively. Chronic infection is now epidemic and the HCV Ab is used as a screening test with patients displaying a positive test being subjected to HCV RNA testing. The presence of HCV RNA is indicative of infection.

Hepatitis C virus antibody (HCV Ab): This is indicative of past infection or ongoing chronic infection. Since acute infection is often not diagnosed, patients with HCV Ab and a positive HCV RNA have chronic infection and those with a positive HCV Ab but a negative HCV RNA have had past infection but have cleared the virus from their system. Since multiple genotypes of HCV exist, prior infection does not confer immunity. Immunosuppressed patients may have a false negative HCV Ab; therefore, HCV RNA testing should be done even though the HCV Ab is negative if the pretest probability is high. Children born to HCV-positive women may be screened with HCV Ab testing but only after the age of one secondary to passive immunity with maternal anti-HCV antibodies.

HCV RNA: Indicates ongoing infection. The level of viremia does not predict symptoms, histologic stage of disease, or prognosis. Quantitative levels indicate ongoing infection and the level of viremia (levels under 600,000 IU/mL indicate low level viremia and a more favorable outcome to treatment). Qualitative levels only reveal if HCV RNA is present or not. The benefit of qualitative levels is that they are more sensitive and may detect infections associated with a low level of viremia which may have been missed by quantitative assays. However, newer quantitative assays using real-time PCR have a sensitivity of 10-50 IU/mL which may make qualitative assays unnecessary. Children born to HCV-positive women may be screened with HCV RNA after birth in order to establish the presence of infection.

HCV genotype: Determines the type of virus (genotypes 1-4). Genotype 1 is the most common in the United States and has a worse response to treatment and therefore requires a longer course of therapy. Genotypes 2 and 3 respond more favorably to treatment and therefore are treated for a shorter course of therapy.

Hepatitis Delta Virus (HDV)

Total anti-HDV antibody (HDV Ab): This virus requires the patient to have infection with the hepatitis B virus. If infection occurs simultaneously, then a positive HDV Ab level indicates coinfection. If the patient has chronic hepatitis B infection and then is infected with HDV, a positive HDV Ab is indicative of super infection. Coinfection has a better prognosis than super infection.

HDV RNA: Indicates ongoing hepatitis delta virus infection. It is also used to document a sustained virologic response or treatment failure six months after therapy.

Hepatitis E Virus (HEV)

IgM anti-HEV Antibody (anti-HEV Ab): Indicates acute infection. The level appears around the third week of infection and becomes negative around week 13 of infection.

Total anti-HEV Antibody: Indicates past infection and remains positive throughout the life of the patient.