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

INR (0.9-1.2) - 1.0 1.6

Platelet count (150-400) 178 170 116

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

INR (0.9-1.2) - 1.0 1.6 1.0

Platelet count (150-400) 178 170 116 121

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 single-stranded 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

inserts its genetic

material into liver cells

uses liver cell resources to

replicate itself

genetic material is assembled in the

host liver cell

outer coating synthesizes its

own outer protein coat

release from host cell as Hep D virus

HBsAg

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 Superinfection

HDV HBV HDV

Healthy individual HBV Carrier

3-4% 90% Rare 7-10% 10-15% 80%

Fulminant Recovery Chronic Fulminant Acute, severe Chronic

Hepatitis with immunity HBV/HDV Hepatitis disease HBV/HDV

Death Cirrhosis Death 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)

0

20

40

60

80

100

120

2005 2006 2007 2008 2009 2010

Total samples

Pos

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 MicrobiologyNSW-ACT Branch

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