Hepatitis B Virus (HBV)

HBV and hepatitis

HBV specifically replicates in the liver cells (hepatocytes). This does not cause direct damage to the liver cells, but the body's immune system mounts an attack against infected liver cells which then causes the hepatitis (liver inflammation).

HBV infection in adults

Healthy adults who get infected by HBV are able to clear the infection normally (acute HBV) without medical intervention and will not get chronic infection. Here HBV is transmitted much the same way as HIV is, via sexual contact (increased risk with men who have sex with men) or sharing needles.

Note though even a person who contracted and cleared HBV as an adult, a loop of HBV DNA (cccDNA see picture) remains in the hepatocytes afterwards (not detectable), and they are at risk of reactivation if started on immunosuppressants later in life.

HBV infection in infants - perinatal transmission and chronic HBV

If HBV is transmitted to an infant or a young child, their immunity is not fully developed and they are unable to clear the virus. These individuals have a high risk of going on to have life-long chronic HBV infection. Here transmission is typically from a mother who has chronic HBV infection to her newborn baby, this is called peri-natal transmission, or vertical transmission. Perinatal transmission occurs due to prolonged contact between mother and infant. It is the main way chronic HBV is transmitted.

There is a high prevalence of perinatal transmission and chronic HBV in China. Other areas with high prevalence are Central and East Asia, sub-Saharan Africa and Pacific regions.

Peri-natal transmission can be prevented by giving the infant Hepatitis B vaccination at birth as well as Hepatitis B immunoglobulin (antibody) infusion. All Hong Kong born babies receive Hepatitis B vaccinations at birth whether their mothers have HBV or not.

Hep B vaccination

Hepatitis B vaccination involves three injections of Hepatitis B surface antigen (not the whole virus) to trigger anti-HBV antibody production. It is a is safe, highly effective and long lasting vaccine with minimal side effects.

Genotypes

There are 8 HBV genotypes, each has interesting characteristics such as epidemiology, aggressiveness, and responsiveness to certain types of therapy.

Liver cirrhosis and cancer

In chronic HBV if there is persistent and chronic hepatitis this prolonged long term damage causes liver cirrhosis.

If untreated, liver cirrhosis occurs in 40% of chronic HBV patients, of which 30% may go on to develop liver carcinoma. Chronic HBV is one of the leading causes of liver cancer, and liver cancer is one of most common causes of death world wide.

Often HBV infection is asymptomatic until there is liver cirrhosis, detection is via screening.

Phases of chronic HBV

Chronic HBV infection in a person can transition between phases of activity and inactivity, possibly several times in a lifetime depending on their immune system and whether they are having treatment. Liver damage occurs during active phases.

Immunotolerance and inactive disease

It is possible to have chronic HBV with high levels of HBV DNA but minimal liver inflammation due to management by the immune system, this is termed immunotolerance and is often seen in patients who were infected at birth up until 30-40 + years old. Then interestingly (provided their immunity remains good) at around 30-40 years old, their HBV DNA levels drop right down, this is termed inactive disease. 60-80% of individuals remain in this phase indefinitely

Drug treatment is not required for patients who are in either inactive phase.

Active phases

Liver damage occurs during active phases.

Patients can go from immunotolerance to immunoactive disease, where the immune system dips and there is liver damage.

Patients can go from inactive disease to reactivation, where DNA levels were low, and then come back up again due to a reactivation trigger such as immunosuppressants.

Drug treatment is required whenever there is active disease and hepatitis, in order to control liver damage.

Determining the phase

Biomarkers (Tests) used to determine the HBV status:

• Presence or absence of HB antigen and anti-HB antibodies
• HBV DNA levels
• ALT levels (LFT) - sensitive marker for liver inflammation
• Biopsy to determine presence or absence of liver damage and fibrosis (fibrosis is scarring)

HBV cure

Hepatocytes (liver cells) are hardy. HBV enters the hepatocyte, triggering inflammation. But after the inflammation stops and the cell returns to normal, a loop of inactive HBV remains in the hepatocyte, which enables HBV to reactivate at a later date, so complete virological cure is not possible in practice.

It is possible to get a functional cure, which is where HBsAg and HBV DNA levels drop to undetectable levels for a sustained period of time.

Reactivation

Because a loop of HBV DNA remains in the hepatocytes after the infection is cleared, reactivation may occur even with patients who only had acute HBV infection in adulthood.

Chronic HBV patients who were in inactive disease phase are at risk of reactivation if exposed to immunosuppression.