Hepatitis B

Hepatitis B virus (HBV) is an enveloped DNA virus of the family Hepadnaviridae. The aetiology of ‘‘serum hepatitis’’, as it was known for many years, was not identified, until the discovery of the (...) continue »

Hepatitis B virus (HBV) is an enveloped DNA virus of the family Hepadnaviridae. The aetiology of ‘‘serum hepatitis’’, as it was known for many years, was not identified, until the discovery of the so-called Au antigen by Blumberg et al. in 1965 [Blumberg et al., 1965] led to the identification of viral particles by Dane et al. several years later [Dane et al., 1970].

Hepatitis B (HB) has a long incubation period of 45 to 160 days (average: 120 days). The length of incubation period is related to the amount of virus in the inoculum, the mode of transmission and host factors.

The appearance of symptoms under acute HB is inversely related to age: less than 1% of newborns and 30%–50% adults develop symptoms. Those who do get symptoms, which are similar for all types of viral hepatitis, usually suffer from tiredness, loss of appetite, abdominal discomfort, nausea, vomiting, fever and jaundice. In less then 1 % of cases, especially in the elderly, fulminating HB develops, which is mostly fatal due to acute hepatic necrosis.

The acute HB often resolves spontaneously after a 4-8 week illness. Otherwise, the infection can last for six months or more. This condition is known as chronic HB.
More than 90 % of infected infants, 25–50 % of children infected between 1 and 5 years of age, and 6–10 % of acutely infected older children and adults develop chronic infection. As a result, more than 350 million people in the world today are estimated to be persistently infected with HBV.

In a considerable number of patients, chronic HB may lead to liver cirrhosis and hepatocellular carcinoma. Cirrhosis affects around one in five people with chronic hepatitis B. Of all causes of cirrhosis, approximately one third can be attributed to chronic HBV infection.

Transmission occurs by percutaneous and permucosal (through broken skin) exposure to such infective body fluids as blood, vaginal and menstrual fluids, and semen. The main ways of transmission include: vertical - from an infected mother during delivery (rate of transmission around 50%); sexual; horizontal - household contact with an infected person (for example, contact of infected blood with cutaneous scratches), sharing of contaminated injection drug equipment by injection drug users, or unhygienic injection procedures in health-care institutions.

To date, 8 genotypes (A-F) were isolated, basing on the differences within HBV genome. As a result of the antigenic heterogeneity of the main immunogenic determinant, HBsAg, 9 serological subtypes were identified. Point mutations at several positions within S gene represent molecular basis for the existence of subtypes. In Ukraine, genotype D, subtypes ayw2 and ayw3 are predominant.

There are remarkable differences in the clinical characteristics between the patients with different genotypes. In Europe, most of the patients with genotype A have chronic hepatitis, while most patients with genotype D have acute hepatitis.

HB occurs worldwide. Countries with high endemicity are those, where the level of chronicity is greater than 8 percent (sub-Saharan Africa; east and southeast Asia); countries with intermediate endemicity are those, where the level of chronicity is 2–7 percent (southern parts of eastern and central Europe; the Middle East; the Indian subcontinent; and those with low endemicity are those, where the level of chronicity is less than 2 percent (most developed countries).

Among seven known HBV proteins, 5 are structural proteins of mature virus particles (S, M, and L proteins of virus envelope; core protein; virus polymerase); one protein, designated X protein, is a non-structural one; and another one protein, E protein, could be found only in blood where it is secreted. S and M proteins are also included in the envelope of non-infectious viral particles, lacking viral DNA, which are present in 10 000 to 1 000 000 - fold excess over mature ones.

All HBV proteins are immunogenic and able to elicit production of antibodies. Despite this fact, only two HBV proteins and 3 diagnostic markers are traditionally [Blumberg, 1976] used in serodiagnostics:
• Circulating S protein in serum (HbsAg) - an ultimate marker of disease, acute or chronic;
• Antibodies to S protein (anti-HBs) - markers of vaccine-induced immunity or recovery;
• Antibodies to C protein (anti-HBc) - marker of exposure to virus, recent or past (IgG) or acute infection (IgM).

The first serologic markers to become detectable in persons with acute HBV infection are HBsAg and antibodies to HBV core antigen. These markers appear in incubation period, 3-6 weeks after infection. IgG and IgM anti-HBc antibodies appear later and almost simultaneously. In persons who recover from HBV infection, HBsAg is gradually eliminated from blood, and anti-HBs develops during convalescence, approximately 6 months after infection. In the same period, immunoglobulin M antibodies to hepatitis B core antigen become also undetectable. IgG antibodies to hepatitis B core antigen persist for life. Most persons who recover from natural infection will be also positive for anti-HBs, but anti-HBs becomes undetectable in some (20%) over time.

A significant number of patients with acute self-limited primary HBV infection never have detectable HBsAg in blood. In these patients anti-HBs is the first marker of HB already during the first weeks after infection. Anti-HBc appear several weeks later and in lower titres. The level of both antibodies reaches plateau at approximately 15th week after infection, remains stable in the first year, and then decreases gradually, remaining detectable for life.

Unlike persons who recover from acute HBV infection, persons with chronic HBV infection do not develop anti-HBs, and HBsAg typically persists for decades.
Despite the introduction of molecular methods, serological tests remain the mainstay in the diagnostics of HB infection. Biochemical probes, especially those measuring elevation in serum transaminase (aminotransferase) activity, could provide an auxiliary information. According to the definition of World Health Organization, diagnosis of hepatitis B is confirmed by HbsAg positive or anti-HBc IgM positive, and anti-HAV IgM negative tests. The quality of the serological test used is crucial for the firm diagnosis of infection. Countries without ready access to such tests as ELISA or radioimmunoassay tests may choose inexpensive methods to detect HBV such as reverse passive haemagglutination (RPHA) or latex bead technology.

Serodiagnostics is useful in following main cases:
• For pregnant women – to determine need for vaccination (prenatal screening). Babies born to mothers found to be infected with hepatitis B need to be given a dose of the hepatitis B vaccine within 24 hours of their birth, followed by further doses at 1, 2 and 12 months old;
• For groups at risk (blood recipients, haemodialysis patients, persons who abuse drugs)-to determine need for vaccination;
• For blood donors. Routine screening of blood donors for HbsAg was mandated in 1972 (USA).
• For newborns at 12 months old born to mothers infected with hepatitis B-to check if they have become infected with the virus;
• For monitoring the course of acute HB;
• To check the efficacy of the vaccine. An initial anti-HBs titre of >10 IU/l is regarded as being protective;
• To monitor treatment of chronic HB;
• For epidemiological purposes.

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