Rapid tests for Hepatitis B

Hepatitis B virus biology

Hepatitis B virus (HBV) is the prototype for a family of viruses known as Hepadnaviridae. The family of hepadnaviruses comprises viruses isolated from a variety of animal species. Those that are most closely related to HBV include the woodchuck hepatitis virus (WHV), the ground squirrel hepatitis virus (GSHV), and the duck HBV.

HBV Virions, also sometimes referred to as Dane particles, are comprised of an outer lipoprotein coat (the hepatitis B surface antigen or HBsAg) that envelopes an icosahedral nucleocapsid protein core (the hepatitis B core antigen or HBcAg). This nucleocapsid encloses the DNA and a DNA polymerase. It is also notable that while not a retrovirus, the HBV polymerases exhibit reverse transcriptase activity.

Embedded in the outer envelope are proteins which are involved in viral binding of, and release into, susceptible cells. Virion shape is generally spherical with a diameter of 40 - 48 nanometers (nm). During replication an excess of the hepatitis B surface antigen (HBsAg) is produced by the infected cell. This results in tubular and spherical bodies of widely varying sizes that are missing both the core proteins and the viral DNA. These core-less particles are not infectious and are sometimes referred to as subviral particles or depending on their structure as a subviral sphere, subviral tube or subviral filament. These smaller HBsAg-only particles may outnumber the complete virions in the blood by a factor of 100 to 1000.

HBV also can also produce two proteins whose function is not yet clearly understood. One of these is the Hepatitis 'e' antigen (HBeAg). HBeAg is a non-structural peptide that is produced when the Hepatitis B virus is actively reproducing. However not all strain of HBV have the gene responsible for HBe production. There is some data to support that HBe may modulate the immune systems response to HBV infection. HBeAg is generally detectable at the same time as HBsAg and disappears before HBsAg. The presence of HBeAg in chronic infection is generally taken to indicate that HBV is actively reproducing and reflects a poor prognosis. Strains of HBV exist that replicate without producing HBeAg seem to be more virulent than HBe producing strains.

The second of these two proteins is the HBx protein. Little is know about this protein let alone its function. Recent studies indicate that the X protein contributes to the efficiency of HBV replication by interacting with different transcription factors, and is capable of stimulating both cell proliferation and cell death. HBxAg stimulates the cell cycle by a variety of different mechanisms and may contribute to the development of hepatocellular carcinoma (HCC).

The HBV DNA genome is not segmented but rather partially double-stranded. It contains two strand one long and one short. These strands overlap on about 240 nucleotides to form an open circle. The longer strand ranges from 3020-3320 nucleotides long, and the shorter is between 1700 and 2800 nucleotides in length.

It is estimated that 350 million people are infected with HBV, approximately 5% of the world's population. Chronic HBV infection can result in cirrhosis and hepatocellular carcinoma (HCC). HBV strains isolated worldwide have been classified into eight genomic groups according to the nucleotide sequence variations in the S gene sequence along with that of the entire genome. To date eight genotypes (A-H) have been classified. Along with this there are nine serological groups, called hepatitis B surface antigen (HBsAg) subtypes, have also been defined. These serotypes designations are based on antigenic epitopes on the envelope proteins. The serological designations are currently: adw2, adw4, adr, adrq−, ayw1, ayw2, ayw3, ayw4, and ayr.

It has been shown that each of the known HBsAg subtypes may belong to either one or several genotypes. In these instances it is the genotype, rather than the subtype, that is more likely to reflect the geographical origin of the strain. Different genotypes have distinct geographic distributions along with a direct impact on clinical outcome.

A- HBV genotype A appears to be the predominant genotype among patients with HBV infection in North America, Northwest Europe and Africa. Genotype A is more common among patients with chronic hepatitis B.

B- HBV genotype B is one of the predominant strains in Eastern Asia, specifically China and Japan. Genotype B is rarely associated with the development of HCC.

C- HBV genotype C is frequently found in China and Japan, Southeast Asia and across Oceania, including Australia. HBV genotype C is positively associated with the development of hepatocellular carcinoma (HCC).

D- HBV genotype D is prevalent in South Europe, Middle East and India. Genotype D is the most widespread strain in world and is the predominant genotype of the Mediterranean region. Studies have shown patients infected with genotype D usually present with acute, self resolving hepatitis.

E- HBV Genotype E is found in primarily in West Africa

F- HBV Genotype F is found mainly in the Central and South Americas. It is sometimes referred to as a New World genotype. However, in Brazil a country that is geographically divided into several regions and which has been colonized by people of different ethnic background the HBV genotype distribution is highly variable.

G- Genotype G was found recently in isolates from America and France but it has not yet been fully characterized and its particular clinical course is not yet elucidated.

H- Genotype H is highly predominant in HBV isolates of Mexico and Central America followed by genotypes G, A and D.

Coinfection with HBV of distinct genotypes is not infrequent and found in about 10% of infected individuals, and is responsible for a type of hybridization called intertypic recombination. Evidence is accumulating as to the influence of the different HBV genotypes and serotypes on the progression of chronic hepatitis B and their responses to antiviral therapies. HBV isolates even of the same genotype can differ in virological and clinical characteristics, usually expressed as regional difference of clinical presentation and outcomes. This likely reflects a need for HBV to be classified further into subtypes, particularly those that clinically significant.