Hepatitis B Disease Background

Last updated: 07 August 2025

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Introduction

Content on this page:

Introduction

Introduction

Human hepatitis B virus (HBV) belongs to the family of Hepadnaviridae of small, enveloped, primarily hepatotropic DNA viruses. The virus replicates in the host and assembles exclusively in the hepatocytes, and the virions are released non-cytopathically through the cellular secretory pathway.  

Chronic hepatitis B is defined as chronic necroinflammatory liver disease that is due to persistent HBV infection. Chronic HBV infection is when the patient is hepatitis B surface antigen (HBsAg)- seropositive for more than 6 months.  

Hepatitis D Virus

Hepatitis D, also known as delta hepatitis, requires hepatitis B infection for its replication. The disease caused by hepatitis D can be acute or chronic, as a coinfection, or as a superinfection. Chronic hepatitis D is the most aggressive form of viral hepatitis because of its accelerated progression to liver cirrhosis or liver cancer. Acute HBV/HDV coinfection may resolve spontaneously. Superinfection can lead to rapid disease progression to liver cirrhosis and hepatic failure within 5-10 years in 70-80% or 1-2 years in 15% of patients with chronic HBV/HDV infection.  

Hepatitis D affects nearly 5% of patients with chronic HBV infection globally. A high prevalence rate for HDV infection was reported from countries in Western and Central Africa, Eastern and Southern Europe, Middle East, and East Asia.

Epidemiology

Hepatitis B affects 296 million people worldwide. It has an intermediate to high prevalence in Asia, representing three-fourths of chronic HBV-positive people worldwide. Nearly half of the people with chronic HBV infection globally are from the Western Pacific region (37 countries, including China, Japan, South Korea, Philippines, and Vietnam, according to the World Health Organization).  

The prevalence of HBV infection in Asia as of 2019 based on WHO reported that in East Asia, the prevalence was 2.95-10.47%, and the highest prevalence was in North Korea. In South-East Asia, the observed prevalence was 1.26-8.66%, with the highest prevalence from Lao People’s Democratic Republic). In South Asia, the prevalence was 1.12-2.93%, and the highest prevalence was in India.  In 2022, it is estimated that 254 million people were living with chronic hepatitis B infection. Hepatitis B can progress to severe liver diseases that include fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In Malaysia, a total of 35,861 cases were reported to the Ministry of Health in 2017 with an incidence rate of 12.65/100,000 population in 2015.

Chronic hepatitis B infection may develop in nearly half of the children infected with HBV before the age of 6 years and in <5% of individuals infected as adults. Hepatitis B coinfection with human immunodeficiency virus (HIV) affects 2.7 million people globally.

Pathophysiology

During the acute phase of infection, patients with HBV produce nucleocapsid proteins (HBcAg, or to a lesser extent HBeAg) on the cell membrane of hepatocytes which serve as viral antigens. These antigens are eventually recognized by cytolytic T-cells which try to eliminate the viral antigens but also end up causing damage to liver cells. Some patients recover from the acute infection, however, due to the differences or possible impairment in the cytolytic T-cell responsiveness or function along with the production of antiviral cytokines by such cells, some patients may progress to chronic hepatitis.

Classification

Phases of Chronic Hepatitis B

HBeAg-positive chronic HBV infection (immune-tolerant) is characterized by the following:

  • Presence of high amounts of HBsAg
  • Presence of serum HBeAg
  • Very high levels of HBV DNA (usually ≥107 IU/mL) 
  • ALT persistently within the normal range (<19 U/L for females and <30 U/L in males) or minimally elevated
  • Minimal or no liver necroinflammation or fibrosis
  • Occurs frequently and is prolonged in patients infected perinatally and is associated with preserved HBV specific T cell function at least until young adulthood
  • Patients at this stage are highly contagious because of the high levels of HBV DNA

HBeAg-positive chronic hepatitis B (immune-active HBeAg-positive) is characterized by the following:

  • Presence of high to intermediate amounts of HBsAg
  • Presence of serum HBeAg
  • High levels of HBV DNA (usually 104-107 IU/mL)
  • Elevated ALT
  • Moderate to severe liver necroinflammation and accelerated progression of fibrosis
  • Usually occurs in patients infected during adulthood
  • Patients may have HBeAg seroconversion and HBV DNA suppression that progress to HBeAg-negative infection phase while others may fail to control HBV and progress to the HBeAg-negative chronic hepatitis B phase for many years

HBeAg-negative chronic HBV infection (inactive carrier) is characterized by the following:

  • Presence of low amounts of HBsAg (usually <1,000 IU/mL)
  • Absence of serum HBeAg
  • Undetectable or low (<2,000 IU/mL) HBV DNA levels
  • Normal ALT
  • None or minimal liver necroinflammation and variable fibrosis as a result of previous hepatic injury during the HBeAg positive immune-active phase
  • Low risk of progressing to cirrhosis or HCC but progression to chronic hepatitis B may occur

HBeAg-negative chronic hepatitis B (HBeAg-negative immune reactivation) is characterized by the following:

  • Presence of intermediate amounts of HBsAg (usually >1,000 IU/mL)
  • Absence of serum HBeAg usually with detectable anti-HBe
  • Persistent or fluctuating moderate to high levels of serum HBV DNA (usually >2,000 IU/mL)
  • Fluctuating or persistently elevated ALT
  • Presence of liver necroinflammation and fibrosis
  • Associated with low rates of spontaneous disease remission

HBsAg-negative (occult HBV infection) is characterized by the following:

  • Serum negative HBsAg and positive antibodies to HBcAg with or without detectable antibodies to HBsAg
  • Normal ALT
  • Usually, but not always, undetectable serum HBV DNA
  • Liver has frequently detectable HBV DNA (covalently closed circular DNA [cccDNA])
  • Several studies have shown that almost all patients with occult HBV infection have normal liver biochemistry and minimal or no liver necroinflammation and fibrosis
  • However, it may still be associated with the development of liver cirrhosis and HCC