OCCULT HEPATITIS B INFECTION :

AN OVERVIEW

Dr. Arifa Akram MBBS MD (Virology)

IEDCR, DGHS compoundMohakhali,DHAKA

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INTRODUCTIONThe hepatitis B virus (HBV) represents a worldwide public health problem; According to EASL , about one-third of the world’s populations have serological evidence of past or present HBV infection. However, this rate may in fact be higher due to occult hepatitis B virus infection.

In 2008 (EASL) defined occult hepatitis B virus infection (OBI) as “the presence of HBV DNA in the liver tissue of individuals who test negative for HBsAg, by currently available assays, regardless of the detection of HBV DNA in the serum. When detectable, the level of HBV DNA in the serum is usually very low (<200 IU/mL)”

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Current evidence suggests that OBI maintains its carcinogenic potential, favoring the progression of fibrosis and cirrhosis of the liver & can contribute to the establishment of HCC. Implementation of HBV DNA screening has the potential to significantly reduce the WP and to reveal OBI or HBV carriage.

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*Allain reported OBI in several clinical contexts including:

recovery from past infection indicated by the presence of hepatitis B surface antibody (anti-HBs);

chronic hepatitis with surface gene escape mutants that are not recognized by current assays;

chronic carriage without any marker of HBV infection other than HBV DNA (referred to as “seronegative”); and

most commonly in endemic areas, chronic carriage stage with HBsAg too low to be detected and recognized by the presence of anti-HBc.

*Allain JP. Occult hepatitis B virus infection. Transfus Clin Bio l2004; 11: 18-25

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HBV VIROLOGY

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The HBsAg is a peptide with 226 amino acids with a single major antigenic determinant. The 1 major antigenic determinant is called the “a” determinant and is located in the amino acid positions between 100 and 160 (boxed area).

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SEROLOGICAL PATTERN OF OCCULT HEPATITIS B INFECTION

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MOLECULAR MECHANISMS LEADING TO OCCULT HBV INFECTION

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HBV induces expression of cellular DNA methyl transferases (DNMTs)

Methylation of dinucleotides in the HBV genome

Hyper methylation impairs HBV replication, virion production, and HBV protein levels

Epigenetic Mechanisms

Methylation

Leading to occultHBV infection

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Host Immune Responses and

Occult HBV Infection:

Host immune responses are involved in-

viral clearance, viral persistence, and immunopathogenesis of

HBV infection.

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EVALUATION OF DIFFERENT OBI DIAGNOSTIC TECHNIQUES

Liver biopsy: Detection of HBV DNA is the Best way for diagnosis of OBI.

HBsAg

Anti-HBc testing: anti-HBc alone might reflect an occult HBV infection. Furthermore the absence of this antibody does not exclude OBI (seronegative OBI).

HBV DNA testing: The gold standard test for detection of OBI is the amplification of HBV DNA(from liver or blood).

Anti-surface antibody: This is the last antibody to appear (about three months after acute phase), and it is able to neutralize the virus. This antibody can be used with anti-HBc to study the serological status of patients with a probable OBI.

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•chronic hepatitis C especially those with flare in liver enzymes•solid organ, hematopoietic stem cell transplantation, and blood transfusion.

TARGET POPULATIONS FOR INVESTIGATING THE PRESENCE OF OBI

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CLINICAL SIGNIFICANCE

OBI infectivity by transfusion:

transmission associated with extremely low levels of HBV DNA (only< 20 IU/mL) or blood collected during the very early phase of acute infection (eclipse phase) in which neither HBsAg nor HBV DNA is detectable.

OBI in blood donors:

transmissible in HBV-naive recipients. Addition of anti-HBc testing for donor screening, leading to rejection of a large number of donor units,

definitely eliminate help in reducing HBV transmission.

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OBI and organ transplantation: Reactivation possible in liver transplant recipients with of past exposure to hepatitis B (anti-HBc positive) as a consequence of immunosuppression after transplantation. The risk of occult HBV transmission is very low after kidney, heart or bone marrow transplantation.

OBI and immune suppression:Patients are at risk of HBV reactivation.

OBI and chronic liver diseases:long-lasting persistence of virus in liver may provoke necroinflammation.

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HBV DNA can persist in the hepatocytes both integrated into the host genome and as free episome.

OBI may exert direct pro-oncogenic effects through the activation of the same oncogenic mechanisms that are activated in the course of an HBsAg-positive infection.

The persistence of very low viral replicative activity during OBI may induce mild liver necro inflammation continuing for life.

thus favoring the progression toward cirrhosis & can contribute to hepato cellular transformation.

OBI and hepatocellular carcinoma

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Accumulated evidence indicates that occult HBV can be both a source of virus contamination in blood and organ donations, as well as the reservoir from which full blown hepatitis can arise.

For detection of OBI - HBV DNA nucleic acid testing should be implemented even if anti-HBc and anti-HBs are negative especially in endemic area.

CONCLUSION

Cont….

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Advanced progress in molecular biology techniques helps in early detection of OBI and paves the way for implementing a detecting strategy to eliminate post-transfusion occult HBV infection, with consideration for the immune status of blood recipients.

Further studies examining this issue need to be conducted in the future.

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