The Little Brother of Hepatitis B
Min Li
Andie Lee
Case Study – Mr SG
 35 year-old male
 Chronic HBV infection
 HIV




Diagnosed 2006, probably acquired 2001
Homosexual male, partner HIV positive
On antiretroviral treatment since diagnosis
HIV viral load undetectable, CD4 count 620
 Major depression
Case Study – Mr SG
 Presented in September 2008 with 3 weeks of:





Malaise, fatigue
Nausea, vomiting and diarrhoea
Jaundice
Dark urine and pale stool
No fever or abdominal swelling
Case Study – Mr SG
 Medications


Atripla (tenofovir/ emtricitabine/ efavirenz)
1 tablet po daily
Sildenafil 50mg po prn
 Previously worked as a graphic designer,
now on disability pension
 Smoker
 Crystal methamphetamine
Case Study – Mr SG
 Physical examination




Afebrile
Jaundiced
Spider naevi and palmar erythema
No abdominal tenderness,
hepatosplenomegaly or ascites
Case Study – Mr SG
Test
21.08.2008
24.09.2008
30.09.2008
Bilirubin (<18) μmol/L
6
62
334
ALP (30-130) U/L
71
123
135
GGT (<60) U/L
29
742
596
ALT (5-55) U/L
25
1245
3781
AST (5-55) U/L
24
470
3158
Albumin (38-48) g/L
46
39
39
-
1.0
1.6
178
170
116
INR (0.9-1.2)
Platelet count (150-400)
Case Study – Mr SG
 Hepatitis serology:
Hepatitis A IgM –ve, IgG +ve
 Hepatitis B cAb +ve, B sAg +ve, B eAg –ve
HBV concentration 8954 copies/mL (1210 IU/mL)
 Hepatitis C Ab –ve, HCV PCR –ve
 Hepatitis D total Ab +ve
 Hepatitis E IgM –ve, IgG –ve
 HDV superinfection
 Superinfection can lead to fulminant hepatitis
 Mortality rate for HDV infection is 2-20%

Case Study – Mr SG
 Symptoms and liver function tests improved
but ongoing fatigue
 June 2010 - Liver function tests remained
elevated probably due to chronic Hepatitis D
(HBV DNA negative)
Case Study – Mr SG
Test result
21.08.2008
24.09.2008
30.09.2008
16.06.2010
Bilirubin (<18) μmol/L
6
62
334
10
ALP (30-130) U/L
71
123
135
109
GGT (<60) U/L
29
742
596
185
ALT (5-55) U/L
25
1245
3781
372
AST (5-55) U/L
24
470
3158
218
Albumin (38-48) g/L
46
39
39
46
-
1.0
1.6
1.0
178
170
116
121
INR (0.9-1.2)
Platelet count (150-400)
Case Study – Mr SG
 Consideration for liver biopsy and treatment
with interferon therapy
 Treatment deferred
Min Li
Introduction
 Hepatitis is serious inflammation of the liver
caused by hepatitis viruses
 Most common – Hepatitis A, B, C
 Less common – Hepatitis D, E
 Liver – Inflammation - cirrhosis - cancer
Hepatitis Delta
Hepatitis D or Hepatitis Delta:
 Discovered by Dr Rizzetto in 1977
 Is a defective single stranded RNA virus
 It requires Hepatitis B virus for its own
replication
 It is the least common but most severe form
of viral hepatitis
What is HepD virus?
 36-43 nanometres in
diameter
 The genome of the
virus is very small and
consists of singlestranded RNA and
HD Ag
 HDV does not
synthesize its own
coat, it is enveloped
by Hepatitis B surface
antigen
 Its replication requires
helper functions
provided by HBsAg
HDV viral replication
release from
host cell as
Hep D virus
inserts its
genetic
material into
liver cells
HBsAg
outer coating
synthesizes its
own outer
protein coat
uses liver cell
resources to
replicate itself
genetic material is
assembled in the
host liver cell
Geographic distribution of HDV Infection
• Generally corresponds to
prevalence of chronic HBV
infection world wide. However,
distinct features have been
documented
• For those countries in which
the prevalence of chronic HBV
is low, distribution of HDV is
low among chronic HBV
carriers
• In these countries (like
Australia) HDV infection
commonly occurs among
intravenous drug users
Route of transmission
 Similar to those for HBV (except vertical transmission is





rare)
Percutaneous
Contaminated drug use equipment
Transfusion of infected blood and blood products
Permucosal
Sexually transmitted, although less efficient than HBV
Who is at Risk of HDV infection?
 Chronic HepB carrier
 Anyone at risk for HBV
 Injecting drug users
 Haemophiliacs/haemodialysis patients
 Homosexuals and heterosexuals with multiple sex
partners
 It has been estimated that 15 million people with
Hepatitis B are infected with Hepatitis D
 In Australia, over the last 6 years, 20-30 cases reported
each year
HDV infection clinical features
Coinfection
HDV
Superinfection
HBV
HDV
Healthy individual
3-4%
Fulminant
Hepatitis
Death
90%
HBV Carrier
Rare
Recovery
with immunity
7-10%
Chronic
HBV/HDV
Cirrhosis
Fulminant
Hepatitis
Death
10-15%
80%
Acute, severe Chronic
disease
HBV/HDV
Recovery
Death
Symptoms of HDV infection
Similar to Hepatitis B






loss of appetite
nausea and vomiting
tiredness
pain in the liver (upper, right side of abdomen)
muscle and joint pain
jaundice (yellowish eyes and skin, dark urine
and pale-coloured faeces)
Diagnosis of Hepatitis D
 Detection of HDV RNA by PCR :
sensitive method can detect 10-100 copies of

HDV genome in infected serum
 HD Ag detection by EIA

The finding of HD Ag in the serum indicating
acute HDV infection and early stage of
infection
 Anti –HD IgM, IgG detection by EIA

The serological response to HDV infection.
Provides supplemental evidence for HDV
infection.
RPAH Serology Section
 Testing algorithm
 Normally would not test for HDV unless HBV
surface antigen present


Sometimes patient history is not provided when a
request for HDV is received
Testing requests for HDV are almost
exclusively by specialists

HDV RNA requests uncommon, though requests
received are from experienced specialists
 Crucial window between RNA presence and HDV-Ab
presence
 These requests are forwarded to VIDRL
RPAH Serology Section
 Qualitative HDV detection conducted by detecting total
antibodies to HDV antigen (anti-HD)

Dia Sorin ETI-AB-DELTAK-2 (P2808)
1. Well coated with recombinant HD Ag.
2. Anti-HD from sample or control.
3. Enzyme tracer: anti-HD antibodies (human) conjugated to horseradish
peroxidase (H R P).
RPAH Serology Section
 Dia Sorin EIA
 Performed fortnightly
 Manual test
 Samples tested in duplicate
 One blank, positive and negative controls / run
 External controls periodically tested and monitored
 Results are calculated manually
 Interpreted via cut-off values derived from positive and
negative controls
 All initial positives are repeated before reporting
Anti-HDV total anti-bodies (RPA)
120
100
80
Total samples
60
Pos
40
20
0
2005
2006
2007
2008
2009
2010
Treating Hepatitis D
There is no antiviral therapy specifically for
chronic hepatitis D
Individuals with chronic HDV and HBV infection
should follow HBV therapy
Research indicates using Pegylated interferon
demonstrates some benefit in people with
hepatitis D
Liver transplantation may be considered for
end-stage chronic hepatitis D
Prevention of Hepatitis D
 No vaccine specific for HDV
 Since HDV is dependent on HBV for
replication, preventing HDV through HBV
vaccination can be effective
 In HDV superinfection, education to reduce
risk behaviours and reduce exposure to
infectious blood
Australian Society for Microbiology
NSW-ACT Branch
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