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Introduction
Human hepatitis B virus 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 noncytopathically through the cellular secretory pathway.
Chronic hepatitis B is defined as chronic necroinflammatory liver
disease that is due to persistent hepatitis B virus infection. Chronic hepatitis
B virus infection is when the patient is hepatitis B surface antigen (HBsAg)-seropositive for more than 6 months.
Hepatitis D Virus
Hepatitis D 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. Acute hepatitis B virus/hepatitis D virus 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 hepatitis B virus/hepatitis D virus infection.
Hepatitis D affects nearly 5% of patients with chronic hepatitis B
virus infection globally. A high prevalence rate for hepatitis D virus
infection was reported from countries in Western and Central Africa, Eastern
and Southern Europe, Middle East, and East Asia.
Epidemiology
Hepatitis B affects 240 million people worldwide. It has an
intermediate to high prevalence in Asia, representing three-fourths of chronic
hepatitis B virus-positive people worldwide. Nearly half of the people with
chronic hepatitis B virus infection globally are from the Western Pacific
region (37 countries, including China, Japan, South Korea, Philippines, and
Vietnam, according to the World Health Organization [WHO]).
The prevalence of hepatitis B virus 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 Asia, the
prevalence was 1.12-2.93%, and the highest prevalence was in India.
In China, there is an estimated 70-80 million people with chronic
hepatitis B based on WHO. In Hong Kong, the crude prevalence of HBsAg-positive
patients among the general population was 7.8% while the age-and-sex-adjusted
prevalence was 7.2% according to a large seroprevalence study. In India, the
prevalence of HBsAg-positive patients was 1.1-12.2% and was estimated to
chronically infect 40 million people. In Korea, the prevalence of
HBsAg-positive patients dropped to 3% in 2008.
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.
Myanmar is one of the 28 priority countries for viral hepatitis prevention and
control according to WHO, with about 3.3 million people diagnosed with
hepatitis B. In the Philippines, hepatitis B is likewise highly prevalent
affecting approximately 16.7% of the general population or 7.3 million people
in 2013. In Vietnam, the prevalence of chronic hepatitis B was thought to be
8-25%. WHO estimated that the prevalence of hepatitis B in Vietnam was around
8.1% affecting at least 7.7 million people.
Chronic hepatitis B infection may develop in nearly half of the
children infected with hepatitis B virus 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.
Epidemiology-HK
The prevalence of hepatitis B virus 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 Asia, the prevalence was 1.12-2.93%, and the highest prevalence was in India.
In China, there is an estimated 70-80 million people with chronic hepatitis B based on WHO. In Hong Kong, the crude prevalence of HBsAg-positive patients among the general population was 7.8% while the age-and-sex-adjusted prevalence was 7.2% according to a large seroprevalence study.
Chronic hepatitis B infection may develop in nearly half of the children infected with hepatitis B virus 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.
Epidemiology-MY
The prevalence of hepatitis B virus 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 Asia, the prevalence was 1.12-2.93%, and the highest prevalence was in India. 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 hepatitis B virus 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.
Epidemiology-PH
The prevalence of hepatitis B virus 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 Asia, the prevalence was 1.12-2.93%, and the highest prevalence was in India. In the Philippines, hepatitis B is likewise highly prevalent affecting approximately 16.7% of the general population or 7.3 million people in 2013.
Chronic hepatitis B infection may develop in nearly half of the children infected with hepatitis B virus 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.
Epidemiology-VN
The prevalence of hepatitis B virus 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 Asia, the prevalence was 1.12-2.93%, and the highest prevalence was in India.
In Vietnam, the prevalence of chronic hepatitis B was thought to be 8-25%. WHO estimated that the prevalence of hepatitis B in Vietnam was around 8.1% affecting at least 7.7 million people.
Chronic hepatitis B infection may develop in nearly half of the children infected with hepatitis B virus 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 hepatitis B virus produce nucleocapside 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 hepatitis B virus infection (immune-tolerant)
is characterized by the following:
- Presence of serum HBeAg
- Very high levels of hepatitis B virus DNA
- 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 hepatitis B virus 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 serum HBeAg
- High levels of HBV DNA
- 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 hepatitis B virus infection (inactive carrier) is characterized by the following:
- Absence of serum HBeAg
- Undetectable or low (<2,000 IU/mL) HBV DNA levels
- Normal ALT
- 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 hepatocellular carcinoma (HCC) but progression to chronic hepatitis B may occur
HBeAg-negative chronic hepatitis B (HBeAg-negative immune reactivation) is characterized by the following:
- Absence of serum HBeAg usually with detectable anti-HBe
- Persistent or fluctuating moderate to high levels of serum HBV DNA
- Fluctuating or persistently elevated ALT
- Presence of liver necroinflammation and fibrosis
- Associated with low rates of spontaneous disease remission
HBsAg-negative (occult hepatitis B virus infection)
- 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 hepatitis b virus 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