Natural History

What Is Hepatitis B?

Hepatitis B is the most common serious liver infection in the world. It is caused by the hepatitis B virus that attacks and injures the liver.

240 million people are living with a chronic hepatitis B infection, worldwide. Each year up to 1 million people die from hepatitis B despite the fact that it is preventable and treatable.

1 in 35 Singaporeans are Hepatitis B carriers. Hepatitis B is the leading cause of liver complications and liver cancer in Singapore.

Hepatitis B is a “silent epidemic” because most people do not have symptoms when they are newly infected or chronically infected. Most people who are infected with viral Hepatitis don’t even know they have the disease, and may unknowingly spread it to others. The virus is spread through contact with the blood or other body fluids of an infected person putting those closest to Hepatitis B carriers, like family members, and healthcare workers at risk.

The good news is that hepatitis B is preventable and treatable. There is a safe vaccine to prevent hepatitis B. There are effective drug therapies that can manage a chronic hepatitis B infection. And a cure is within sight.

Natural History

Most Hepatitis B is acquired during birth or childhood and remain asymptomatic for long periods. It is estimated that between 25-50% of Hepatitis B virus carriers can expect to die prematurely, either as a result of chronic liver inflammation, liver failure or the development of liver cancer.

4 phases of HBV infection have been described: immune tolerance, immune clearance, the inactive carrier state, and reactivation. These consecutive phases are much more likely to be apparent in patients with acquisition of
chronic hepatitis B early in life.

The immune tolerance phase is often the earliest phase to be recognized when there is a history of infection at birth or the first few years of life. It is characterized by HBeAg positivity, high levels of HBV DNA, low or normal levels of serum aminotransferases, and minimal or no necroinflammation or fibrosis in the liver. During this phase, the rates of HBeAg loss are low.  Perinatal transmission of HBeAg is considered to be one of several potential mechanisms.

The immune active phase often begins after several decades of HBV infection and is characterized by elevated serum aminotransferase levels, lower HBV DNA levels than in the immune tolerance phase, and histologic evidence of chronic hepatitis. Continued efforts by the host immune system against the virus may result in HBeAg seroconversion (loss of HBeAg with the development of anti-HBe in serum). The mean annual rate of spontaneous HBeAg seroconversion generally ranges from 8% to 15% in older children or adults with elevated serum ALT levels; however, the rate is considerably lower among Asian children and immunocompromised persons. HBeAg seroconversion does not always indicate quiescent disease, however. As many as 30% of persons who undergo HBeAg seroconversion enter into a subsequent phase of active disease.

The Inactive HBV carrier stage is characterized by normalization of serum ALT and low or nondetectable serum HBV DNA levels. Over time, hepatic necroinflammation and fibrosis subside. The inactive HBsAg carrier phase may last a lifetime, but some patients ultimately develop reactivation, which may occur spontaneously.

Reactivation is defined by the reappearance of high levels of HBV DNA in serum, with or without HBeAg seroreversion, and often a noticeable rise in serum ALT levels. If the immune active phase of hepatitis B remains untreated, cirrhosis can be anticipated to develop in at least 20% of cases.

Clinical Outcomes

Hepatitis B infection may either be acute (last less than 6 months) or chronic (6 months or longer).

Acute Hepatitis B refers to a short-term infection that clears within the first 6 months after someone is infected with the virus.

The age at which a person becomes infected with HBV is a principal determinant of the clinical outcome. Perinatal exposure leads to the chronic HBV carrier state in as many as 95% of persons. By contrast, children exposed during the first 5 years of life have a 30% chance of developing chronic HBV. Only 2% to 5% of adults with an intact immune system become chronically infected.

Chronic Hepatitis B refers to a lifelong infection with the Hepatitis B virus. Over time, this can cause serious health problems, including liver damage, cirrhosis, liver cancer, and even death.

Progressive liver disease (including cirrhosis and HCC) can be expected to develop in 1/4 to 1/3 of people who
acquire infection in the first few years of life. An estimated 15% to 25% of predominately middle-aged or older male patients with acquisition of infection early in life ultimately die of liver-related causes.

Hepatitis B infection is a gateway to numerous life-threatening complications if not managed properly.