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11/13/24, 7\:32 PM Guide | Hepatitis B serology

Hepatitis B serology

Table of contents

Introduction

Hepatitis B is an infection of the liver caused by the hepatitis B virus (HBV). Hepatitis B serological testing involves the
measurement of several di
chronic) and immunity (from vaccination or cleared infection). Therefore, the ability to interpret HBV serology is a crucial skill
to develop.

Background

Transmission

HBV is transmitted via parenteral routes, either via infected blood or bodily
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intercourse (vaginal or anal) or blood-to-blood contact (e.g. intravenous drug use, needlestick injuries). HBV may also be
acquired via vertical transmission (mother to infant during pregnancy or delivery).
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Clinical course

HBV infection results in a spectrum of clinical presentations, ranging from asymptomatic, self-limiting disease to a persistent
infected state with a subsequent high risk of developing hepatocellular carcinoma and decompensated liver failure.
Ultimately, the severity of illness is in
The incubation period of HBV ranges from 45 to 200 days, with an average time span of approximately 75 days. 2
This is a
clinically relevant period, as there is a notable gap between initial infection and the appearance of HBV viral antigens and
antibodies.
The likelihood of progression from acute to chronic infection depends on numerous factors, including the duration of infection
and immunocompetency.
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1
HBV is a member of the H e p a d n a v i r u s family and is a circular, partially double-stranded DNA virus. The virus contains three
surface antigens that are commonly tested for in clinical practice. These antigens will be discussed in the serology section.
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Figure 1. The structure of hepatitis B virus [3]

Clinical features

Acute hepatitis infection

Up to 50% of patients with acute HBV infection will experience subclinical or anicteric hepatitis (i.e. no associated jaundice).
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1
In the remaining patients, typical symptoms of acute HBV infection include \:
Constitutional symptoms (e.g. weight loss, fever, fatigue)
Nausea
Anorexia
Right upper quadrant pain
Jaundice

Chronic hepatitis infection

In chronic HBV infection, there are typically no physical signs unless complications of long-standing infection arise. Patients
with chronic infection may show signs of chronic liver disease or hepatocellular carcinoma.
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Serological testing

The serological markers of HBV infection include diagnostically relevant viral antigens, viral DNA and corresponding
antibodies.

Surface antigen and antibody

Hepatitis B surface antigen (HBsAg)
The hepatitis B surface antigen (HBsAg) is a protein found on the surface of HBV; it is the
following initial infection. Whilst it is the
days (average 75 days) between the
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HBsAg seroconversion is the development of antibodies against HBsAg (anti-HBs); it indicates the clearance of HBsAg and
the resolution of infection. 5
The presence of HBsAg always implies active infection, whilst persistence of HBsAg for more than
six months indicates chronic infection.
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Antibody to Hepatitis B surface antigen (anti-HBs)
Anti-HBs is the antibody produced by the host in response to HBsAg (HBsAg seroconversion). The presence of anti-HBs
without HBsAg indicates two possible scenarios\: either previous, cleared infection or vaccination against hepatitis B virus -
distinguishing between these two scenarios is possible with further serological testing. Anti-HBs remains in serum for life and
indicates immunity to HBV.

Core antigen and antibody

Hepatitis B core antigen (HBcAg)
The hepatitis B core antigen (HBcAg) is part of the nucleocapsid within HBV; it is not routinely measured in clinical practice;
however, the body produces a corresponding antibody to this antigen called hepatitis B core antibody (anti-HBc), which is
clinically relevant.
Antibody to Hepatitis core antigen (anti-HBc)\:
Anti-HBc is the antibody produced by the host in response to HBcAg; depending on which immunoglobulin type is present
indicates the time frame since infection. The presence of anti-HBc IgM indicates recent infection within the last six months.
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Over time, IgM is gradually replaced by anti-HBc IgG; therefore, anti-HBc is seen in patients with resolved infection and those
with chronic infection. 1
This is shown in Figure 2, as anti-HBc IgM acutely rises and falls, whilst total anti-HBc rises and plateaus
as IgG production predominates.
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Figure 2. Hepatitis B antigens and antibodies in chronic infection [6]

Envelope antigen and antibody

Hepatitis B envelope antigen (HBeAg)
The hepatitis B envelope antigen (HBeAg) is found between the core and lipid envelope within HBV and is present in both
acute and chronic infection. The presence of HBeAg in serum indicates active viral replication and a higher risk of
transmissibility. 1
HBeAg can be therefore used to distinguish between active chronic infection and inactive chronic infection.
Hepatitis B envelope antibody
HBeAg seroconversion is the development of antibodies against HBeAg (anti-HBe); it marks a transition from active disease
to an inactive ‘carrier’ state. 5
Anti-HBe remains in serum for life and indicates acquired, natural immunity (i.e. immunity from a
previous infection only).

Hepatitis B virus DNA (HBV-DNA)

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1
In patients with serological markers indicating infection, quanti
load is associated with an increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC). 1
In patients with
active chronic infection, a higher HBV-DNA viral load is expected.

Summary tables

The table below summarises the interpretation of hepatitis B serological tests.
Abbreviations\:
+ detectable in serum
- not detectable in serum
Table 1. Interpretation of all serological tests for hepatitis B
Hepatitis B
surface
antigen
(HBsAg)
Antibody to
Hepatitis surface
antigen (anti-HBs)
Hepatitis B
envelope
antigen
(HBeAg)
Anti
Antibody to Hepatitis
B envelope antigen
(anti-HBe)
-
HBc
IgM
+ - +- +-
Anti
-
HBc
IgG
Acute hepatitis B
infection
Chronic hepatitis B
infection (active)
+ - + - - +
Chronic hepatitis B
infection (inactive,
carrier)
+ - - + - +
Immunity
(following acute
infection)
- +- + - + -
Immunity
(following
vaccination)
- + - - - - -
It’s also important to consider hepatitis serology in context, by taking into account the e
1
Table 2. E
Transaminases
Acute hepatitis B infection Elevated
Chronic hepatitis B infection (active) Elevated
Chronic hepatitis B infection (carrier) Normal
Immunity (following acute infection) Elevated or normal
Immunity (following vaccination) Normal
HBV
DNA
+
+
(Hig
h)
+
(Low
)

Vaccination

In the UK, there are several hepatitis B vaccines licensed for use in children and adults in ‘high-risk groups’
; this includes people
at a high risk of exposure to HBV or subsequent complications from HBV infection.
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