What is the Life Cycle of the Hepatitis B Virus (HBV)?

The hepatitis B virus has an intricate life cycle, with some parts still unknown to science.

The virus seeks out liver cells called hepatocytes to infect. 80% of the liver is hepatocytes, and they handle the bulk of the functions of the liver.

The outside envelope of the virus is called the hepatitis B surface antigen (HBsAg), and the inner core is referred to as the hepatitis B core antigen (HBcAg).

HBV enters the core of the hepatocyte and converts the viral DNA into covalently closed circular DNA (cccDNA), which contains the instructions for viral replication. The newly augmented cell structure is now prepared to infect more cells and replicate.

If you have a robust immune system, your body may produce antibodies to control the viral load and clear an acute infection without treatment.

If you have a compromised immune system, your body may not be able to clear the virus on its own. If left untreated, the virus can corrupt the liver cells leading to serious complications, including cirrhosis and death.

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There are four stages associated with chronic HBV infection:

  • immune tolerance stage
  • immune or active clearance stage
  • inactive HBsAg carrier stage
  • reactivation stage

Some people with chronic hepatitis B may not experience all four stages of infection, and the transition between the phases can happen too fast to diagnose clinically.

Immune tolerance

Viral load is high during acute infection. HBV is highly contagious during this stage.

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) — two key enzymes — levels are typical or slightly elevated.

Immune active or clearance

The immune active phase is the immune system’s response to the virus once detected. AST/ALT increases as the body gets busy creating antibodies to destroy the infected cells.

Immunity to HBV is stronger during the immune active phase, leading to a decreased viral load.

You may experience an immune-mediated liver injury during this stage. Spontaneous flare-ups may increase your overall viral load.

Immune control

Reducing HBV to very low or undetectable levels can signal that your body’s in remission. The virus will remain inactive as long as your immune system stays healthy.

This is also called the “inactive carrier state.”

Reactivation

Reactivation can happen spontaneously, but it most commonly occurs when your immune system is compromised.

People receiving immunosuppressive therapies to treat cancer, an underlying autoimmune condition, or in the setting of an organ transplant are at an increased risk of HBV reactivation.

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HBV reactivation can happen even if you’ve recovered from HBV infection in the past. If the immune system cannot keep up with the needed antibodies, the viral load can increase, causing damage to the liver.