Hepatitis B (HBV)

Hepatitis B is an important vaccine-preventable infection with significant morbidity among those who develop chronic hepatitis. The prevalence of infection of hepatitis B in Australia is considered to be <0.5%. High-risk groups include Aboriginal and Torres Strait islanders, people born in Africa and the Asia Pacific region (where prevalence rates may be >10%) and institutionalised patients.

HBV is a parenterally transmitted virus that is acquired from:

The highest risk of transmission is during the perinatal period. If no prophylaxis is given to the infant, the baby of an HBeAg positive HBV infected mother has a 70–90% risk of infection, while the baby of an HBeAg negative HBV infected mother has a 5–20% risk of infection.

The high protective efficacy (95%) of neonatal vaccination suggests that infection occurs predominantly at or after birth. Caesarean section should not be routinely recommended for carrier mothers. Infants who have been vaccinated may be breastfed.

Approximately 60% of patients with acute hepatitis B have subclinical hepatitis, the rest develop jaundice. Fulminant hepatic failure is unusual, occurring in less than 1% of patients. A clinical picture of acute hepatitis occurs rarely in infants, in about 6% of infected children and one third of infected adults. The disease may be more severe in patients co-infected with HCV and/or HDV or with underlying liver disease.

A serum sickness-like syndrome may develop during the prodromal period, followed by anorexia, nausea, jaundice and right upper quadrant discomfort.

The symptoms and jaundice generally disappear after 1–3 months and for those with resolving infection, normalisation of serum aminotransferases (ALT, AST) usually occurs within 1–4 months.

The rate of progression from acute to chronic HBV infection is approximately 90% for perinatally acquired infection, 20–50% for infections between the age of 1–5 years and <5% for infection acquired as an adult. The risk of chronic infection is increased in patients whose ability to recognise and clear viral infections is reduced, for example, chronic haemodialysis patients, those with HIV co-infection, those immunosuppressed after organ transplantation or by cancer chemotherapy.

In chronic infection, HBsAg remains positive for six months or longer. Many patients with chronic hepatitis B are asymptomatic. Extrahepatic manifestations, for example, polyarteritis nodosa, glomerular disease, occur in 10–20% of those with chronic HBV infection. Patients with chronic HBV infection often have no history of an acute illness.

Prognosis is determined by the presence or absence of active viral replication and by the degree of histologic liver damage. Patients with chronic active hepatitis are at risk of developing cirrhosis (15–20%). Patients with chronic liver disease, particularly those with cirrhosis, are at risk for developing hepatocellular cancer (HCC).

HBsAg (hepatitis B surface antigen) indicates current HBV infection and appears in serum before the onset of symptoms or elevation of serum ALT. HBsAg usually becomes undetectable 4–6 months after infection acquired as an adult. Persistence of HBsAg for more than six months implies chronic infection. HBsAg loss occurs in 1–6% of chronically infected patients per year.

HBsAb (hepatitis B surface antibody). Antibody directed against HBsAg (anti-HBs) is detectable during resolution of acute hepatitis B, after HBsAg is no longer detectable. Anti-HBs is also present for around four months after giving HBIG and after a course of HBV vaccine. Coexistence of HBsAg and anti-HBs occurs in a small proportion of patients with chronic HBV infection. For this reason, testing anti-HBs alone to evaluate ‘immune status’ without measuring HBsAg is not advised.

HBcIgM (hepatitis B core IgM). Hepatitis B core antigen is an intracellular antigen that is expressed in infected hepatocytes. It is not detectable in serum. During acute infection, a serological response to this antigen, anti-HBcore IgM, appears around the same time as symptoms, if they occur.

The absence of anti-HBcore IgM in a person with HBsAg implies that infection has probably been present for more than six months and, therefore, infection is chronic.

As well as being detectable during primary infection, anti-HBcore IgM may be present during exacerbations of chronic hepatitis B or during reactivation of HBV infection (reappearance of active hepatitis in someone previously having inactive HBsAg carrier state or apparently resolved hepatitis B). This can make differentiating primary from chronic infection difficult in populations with a high prevalence of chronic infection (unless earlier HBV serology is available).

Anti-HBcore total antibody (largely IgG in the months after primary infection) is present, usually along with anti-HBs (HBsAb), in patients who recover from acute HBV infection, as well as in those with chronic HBV infection.

The presence of anti-HBcore total antibody in the absence of detectable HBsAg and anti-HBs has several possible explanations:

The likelihood of a false-positive anti-HBcore assay depends on the individual’s pre-test probability of HBV infection. The presence of anti-HBe supports previous HBV infection. Individuals with evidence of chronic liver disease should be tested for HBV DNA to exclude low level chronic HBV infection.

HBeAg (hepatits B early antigen) is generally a marker of HBV replication and infectivity. The presence of HBeAg is usually associated with high levels of HBV DNA in serum and higher infectivity. However, the absence of HBeAg does not necessarily correlate with lower infectivity. Some patients are HBeAg negative, yet continue to have high HBV DNA levels and active liver disease. Many of these patients harbour precore or core promoter HBV variants.

Seroconversion from HBeAg to anti-HBe (that is, development of anti HBe antibodies) is usually associated with a decrease in serum HBV DNA. However, some patients continue to have active liver disease and high levels of HBV DNA in serum after HBeAg seroconversion.

Vaccination is very effective at preventing hepatitis B. HBV vaccination is indicated for a number of at risk groups.

For information about hepatitis B vaccine and other groups who may benefit from vaccination, refer to the current Immunisation Handbook (see references).

Treatment of acute HBV is mainly supportive. Measures should be taken to prevent infection in exposed contacts and the local public health unit will assist with this. Depending on the likely mode of infection, screening for other blood-borne viruses and STIs may be appropriate. For patients with chronic HBV infection, regular surveillance for complications by measuring ALT and alfa-fetoprotein (AFP), usually six-monthly, is recommended.

Patients should be referred for specialist assessment if the ALT is elevated for more than six months or the patient has circulating Hepatitis B DNA beyond six months. Antiviral therapy may be indicated. Urgent referral is indicated if signs of liver failure develop, if the AFP is >100 ug/L (after pregnancy excluded) or if the AFP is between 21–100 ug/L for more than one month (after pregnancy is excluded).

Hepatitis B is a notifiable illness.

See Alpha fetoprotein (AFP); Hepatitis C (HCV); Hepatitis D (HDV)(‘hepatitis delta virus’); Liver function tests and liver disease; Occupational blood and body fluid exposure;