Key facts
Introduction
An estimated 350 million persons worldwide are chronically infected with HBV. Carriers of HBV are at increased risk of developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Although most carriers will not develop hepatic complications from chronic hepatitis B, 15% to 40% will develop serious sequelae during their lifetime. The outlook of the chronic carriers has improved over the years as our understanding of the natural history of HBV infection and the available potential therapies of the resultant disease have improved.
Natural history
The natural history of CHB can be schematically divided into five phases, which are not necessarily sequential.
(1) The ‘‘immune tolerant” phase is characterized by HBeAg positivity, high levels of HBV DNA with normal levels of aminotransferases, mild or no liver necroinflammation and no or slow progression of fibrosis. Treatment is not required in this phase.
(2) The ‘‘immune reactive phase” is characterized by HBeAg positivity, increased or fluctuating levels of aminotransferases with moderate or severe liver necroinflammation on biopsy. There is risk of progression of fibrosis during this phase. If spontaneous HBeAg seroconversion does not occur within 3 months with persistent ALT > 2x ULN treatment should be considered.
(3) The ‘‘inactive HBV carrier state” may follow seroconversion from HBeAg to anti-HBe antibodies. It is characterized by very low or undetectable serum HBV DNA levels and normal aminotransferases.
(4) ‘‘HBeAg-negative” chronic hepatitis B (CHB) represents a later phase in the natural history of CHB. It is characterized by periodic reactivation with a pattern of fluctuating levels of HBV DNA and aminotransferases and active hepatitis. There is a high risk of progression to advanced hepatic fibrosis, cirrhosis and subsequent complications such as decompensated cirrhosis and HCC.
(5) In the ‘‘HBsAg-negative phase” after HBsAg loss, low-level HBV replication may persist with detectable HBV DNA in the liver but not in the serum. This is associated with improvement of the outcome with reduced risk of cirrhosis, decompensation and HCC. However the patient remains at risk of reactivation if immunosuppressed (e.g. during chemotherapy).
When to see a doctor?
All HBV carriers require long term regular review. 15% to 40% of HBV carrier will develop complication as a result of the infection. Patients in the immune tolerant state and the inactive HBV carrier state do not require treatment. However the patient may progress to the immune reactive or HBeAg negative phase which may require treatment. Hence the recommendation is to review the patients at least once every 6 months with a set of liver function test. The patients should be referred to a hepatologist once the transaminase becomes abnormal. Early referral should be considered in patients who has a very strong family history of HCC or has developed cirrhosis despite normal transaminase.
Indications for treatment.
The indications for treatment in the various guidelines published in the Asia Pacific region, Europe and America are generally the same for both HBeAg-positive and HBeAg-negative CHB. This is based mainly on the combination of three criteria:
(1) Serum HBV DNA levels.
(2) Serum aminotransferase levels.
(3) Evidence of liver damage.
Treatment options
There are currently 7 licensed antivirals available to treat HBV. This has enabled us to change the natural history of this illness and in a small percentage of patients benefiting from losing the HBsAg. One important aspect of long term management of these patients is the screening for HCC. Screening appropriate patients with ultrasound scan and AFP every 6 months have been shown to safe lives.
- Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease.
- The virus is transmitted through contact with the blood or other body fluids of an infected person.
- About 600 000 people die every year due to the consequences of hepatitis B
- Hepatitis B is preventable with the currently available safe and effective vaccine.
Introduction
An estimated 350 million persons worldwide are chronically infected with HBV. Carriers of HBV are at increased risk of developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Although most carriers will not develop hepatic complications from chronic hepatitis B, 15% to 40% will develop serious sequelae during their lifetime. The outlook of the chronic carriers has improved over the years as our understanding of the natural history of HBV infection and the available potential therapies of the resultant disease have improved.
Natural history
The natural history of CHB can be schematically divided into five phases, which are not necessarily sequential.
(1) The ‘‘immune tolerant” phase is characterized by HBeAg positivity, high levels of HBV DNA with normal levels of aminotransferases, mild or no liver necroinflammation and no or slow progression of fibrosis. Treatment is not required in this phase.
(2) The ‘‘immune reactive phase” is characterized by HBeAg positivity, increased or fluctuating levels of aminotransferases with moderate or severe liver necroinflammation on biopsy. There is risk of progression of fibrosis during this phase. If spontaneous HBeAg seroconversion does not occur within 3 months with persistent ALT > 2x ULN treatment should be considered.
(3) The ‘‘inactive HBV carrier state” may follow seroconversion from HBeAg to anti-HBe antibodies. It is characterized by very low or undetectable serum HBV DNA levels and normal aminotransferases.
(4) ‘‘HBeAg-negative” chronic hepatitis B (CHB) represents a later phase in the natural history of CHB. It is characterized by periodic reactivation with a pattern of fluctuating levels of HBV DNA and aminotransferases and active hepatitis. There is a high risk of progression to advanced hepatic fibrosis, cirrhosis and subsequent complications such as decompensated cirrhosis and HCC.
(5) In the ‘‘HBsAg-negative phase” after HBsAg loss, low-level HBV replication may persist with detectable HBV DNA in the liver but not in the serum. This is associated with improvement of the outcome with reduced risk of cirrhosis, decompensation and HCC. However the patient remains at risk of reactivation if immunosuppressed (e.g. during chemotherapy).
When to see a doctor?
All HBV carriers require long term regular review. 15% to 40% of HBV carrier will develop complication as a result of the infection. Patients in the immune tolerant state and the inactive HBV carrier state do not require treatment. However the patient may progress to the immune reactive or HBeAg negative phase which may require treatment. Hence the recommendation is to review the patients at least once every 6 months with a set of liver function test. The patients should be referred to a hepatologist once the transaminase becomes abnormal. Early referral should be considered in patients who has a very strong family history of HCC or has developed cirrhosis despite normal transaminase.
Indications for treatment.
The indications for treatment in the various guidelines published in the Asia Pacific region, Europe and America are generally the same for both HBeAg-positive and HBeAg-negative CHB. This is based mainly on the combination of three criteria:
(1) Serum HBV DNA levels.
(2) Serum aminotransferase levels.
(3) Evidence of liver damage.
Treatment options
There are currently 7 licensed antivirals available to treat HBV. This has enabled us to change the natural history of this illness and in a small percentage of patients benefiting from losing the HBsAg. One important aspect of long term management of these patients is the screening for HCC. Screening appropriate patients with ultrasound scan and AFP every 6 months have been shown to safe lives.