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Flashcards in Hepatitis viruses Deck (45)
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1

Hepatitis

General term referring to inflammation of liver

2

Causes

Infectious
-viral
-bacterial
-fungal
-parasitic
Non infectious
-alcohol
-drugs
-autoimmune
-metabolic diseases

3

Signs and symptoms of hepatitis

Malaise
Jaundice
Dark urine
Pale fatty stools
Serum & urine biochemistry, specific serological tests for HepA, B, C, D & E antibodies for viral hepatitis

4

Viral structure (DRAW)

Consist of a strand of nucleic acid, either DNA or RNA, surrounded by a protective protein coat (the capsid).
Sometimes they have a further membrane of lipid, referred to as an envelope, surrounding the protein.

5

Major hep viruses

HAV
-non-enveloped
-faecal-oral
HBV - DNA genome (rest RNA)
-lipid enveloped
-parenteral
HCV
-lipid enveloped
-parenteral
HDV
-lipid enveloped
-parenteral
HEV
-non-enveloped
-faecal-oral

6

Hep A

RNA, belongs to group
Picornavirus
Genotypes I - VII.
-four associated with human disease I-III & VII; most being I (80%) & III
Jejunum-blood-liver, bile faeces
2- week incubation followed by 4-10 day prodrome. Resolves in few weeks

7

Vaccine for Hep A

Formalin-killed virus

8

Recent Hep A outbreaks

San Diego
Manchester

9

Global distribution of Anti-HAV

Developing countries
Intermediate Russia and East Europe
High incidence in Greenland

10

Hep A epidemiology

1.5 million cases worldwide; 6-7000 cases reported p.a. in UK
Children (3-5 years) often asymptomatic
-important in spread (not very clean)
Severity > with age

11

IgM/IgG reminder

IgM is generally produced the first time a host is exposed to an antigen.
IgM will eventually decline, and then the host produces IgG, which lasts much longer.
Detection of IgM indicates acute or primary infection, IgG indicates past infection or immunity
MaGic

12

Serology of Hep A

First 2-3 weeks
-virus in faeces so can be spread
Present in blood during prodrome
->in HAV-specific IgM
HAV specific IgG after 5 weeks

13

Hep B

Hepatitis B virus (HBV)
Parenteral route of transmission
dsDNA virus, resides & multiplies in hepatocytes
Most patients recover in a few weeks

14

Carrier state of Hep B

2-5%
-chronic persistent hepatitis ('healthy carrier')
-chronic active hepatitis

15

Hep B virus (DIAGRAM)

3 forms
-'Dane particle' is whole virion, only infectious form
-Sphere form
-Filament/ tubular form
Made up of
-DNA polymerase enzyme
-core antigen HBcAg
-dsDNA

16

Breakdown product of HBcAg

Found in serum
HBeAg
Marker of active infection

17

HBV genes

S: preS1 --> preS2 --> surface antigen
C: preC --> core protein
P: polymerase
X: regulatory

18

HBc and HBe antigens

Hbe antigen is a soluble component released by the virus core, expressed on hepatocyte surface and targeted by host immune system
HBV is not directly cytopathic for liver cells, pathology is largely immune related: overactive immune response to HbeAg
Core gene transcribed --> core protein (c antigen, not secreted)
With signal peptide modification and protease cleavage: core protein with a bit of pre-core added (e antigen, secreted)
Both made at same time

19

Possible courses of HBV infection

Low viral replication rate: sub-clinical disease (Alt+-)
-elimination of virus; immunity or low HBsAg
Strong viral replication (HBeAG++)
-subclinical course (Alt+-) to persistent viraemia (chronic hep, HCC) --> low HBsAg
-or acute hepatitis (Alt++) --> fulminant hepatitis or elimination of virus; immunity
*Alt = enzyme found in liver cells, high levels mean that cells have lysed to release it, meaning liver is quite damaged*

20

Serology - acute HBV infection

HbeAg and HbsAg come up after 2-3 weeks then both decline
HbcAb and HbeAb, then HbcAb come up over months
Elevated for up to 10 months

21

Chronic HBV infection

HBS Antigen stays elevated against core antigen up to about 10 years
HBC and HBE antigen elevated until around 20 years

22

Lab diagnosis - serology - Hep B acute

Laboratory diagnosis of hepatitis B infection focuses on the detection of the hepatitis B surface antigen HBsAg.

Acute HBV infection is characterized by the presence of HBsAg and immunoglobulin M (IgM) antibody to the core antigen, HBcAg.
During the initial phase of infection, patients are also seropositive for hepatitis B e antigen (HBeAg). HBeAg is usually a marker of high levels of replication of the virus. The presence of HBeAg indicates that the blood and body fluids of the infected individual are highly contagious.

23

Lab diagnosis - serology - Hep B - chronic

Chronic infection is characterized by the persistence of HBsAg for at least 6 months (with or without concurrent HBeAg). Persistence of HBsAg is the principal marker of risk for developing chronic liver disease and liver cancer (hepatocellular carcinoma) later in life

24

Hep B epidemiology

UK carriage approx. 0.1%
Carriage in Africa and Asia approx. 5%
Transmission; vertical, parenteral, sexual
- >10^8 HBV/ml; 0.000001-0.00001ml blood;
Infection early in life > increased chance of chronicity
10% of chronic infection progress to chronic liver disease

25

Hep B epidemiology vaccine

Genetically engineered HBsAg

26

Hep D

Caused by a ‘defective’ RNA virus which coexists with HBV
-needs existence of hep B to live
Very small virus
Outer coat derived from HBsAg – cannot survive without HBV.
~5% HBV carriers are HDV positive

27

Hep D virus

HBsAg
RNA
Delta antigen (used for diagnosis)

28

Hep D infection co-incident with HBV (at the same time)

-HDV influenced by replication of HBV
-rarely progressive or chronic

29

Hep D: superinfection on HBV disease (already got Hep B, then get Hep D)

-ideal for rapid HDV replication
-commonly chronic

30

HDV cases worldwide

15 million
-mainly IV drug users in UK

31

Hep C virus (DRAW)

Small enveloped SSRNA virus
Core of genetic material (RNA), surrounded by an icosahedral capsid
Two viral envelope glycoproteins, E1 and E2, are embedded in the lipid envelope
Hepacivirus
Member of flavivirus
10 genes - transcribed as a polyprotein
Virus released by budding
-E1
E2 responsible for attachment via host cells scavenger receptor B1 and CD81

32

HCV epidemiology

180 million carriers worldwide
-5 million in Western Europe
-UK carriage ~0.08% (~40,000)
Transmission
-IV drug abuse needle sticks, tattoos, ear piercing
(80% iv drug users infected)
-previously
blood products, haemodialysis, transplantation
-minor routes - saliva; sexual; vertical

33

Hep C disease diagnosis

unreliable (antibody takes 6wk-6mnth) –
97% by 6mnth

34

Hep C mild disease

1% have acute illness with jaundice

35

Hep C chronic disease

50-85% become chronic
-50% fatigue (10y); 25% cirrhosis (20y); 5% HCC(30y)
-350 000 to 500 000 people die each year from hepatitis C-related liver diseases.

36

Hep C disease persistence

Relatively low replication replication rate
-no RNA repair mechanism
-variants selected by non-reactivity with antibody

37

Hep C disease treatment

Interferon alpha and Ribavirin

38

Hep C - new cures

In clinical trials, elbasvir-grazoprevir showed cure rates above 90% for people with genotypes 1 and 4.
Cure rate dependent on genotype, treatment history and presence of liver damage
Australia 2018: 20% drop in dying of liver failure/ cancer due to Hep C in last 2 years after new low cost treatment
-prevalrnce of 43% to 27% in IV drug users in 2 years

39

Hep C - financial burden in US

>17% of state prisoners have HepC, compared to 1% of general population
Cost $54-94,000 per person for 12 wks
$66 million spent in California p.a. on Hep C treatment in prisons

40

Prospects for HCV vaccine

11 major genotypes, ~ 40 subtypes
-multiple types in same individual
-types 1a & 1b in UK
Re-infection can occur (with same type)
-lack of neutralising antibody

41

Hep E

> 50% of hepatitis in some countries is not A,B or C
HEV is an RNA Hepevirus; 4 genotypes
Faecal-oral spread
Occurs in epidemics affecting young-middle aged adults

42

Hep E average incubation

6 weeks; high mortality in pregnancy (in India)

43

Table test

test yourself (slides)

44

The ABCs of viral hepatitis

A
B
C

45

Epidemiology Hep E

Poor sanitation, food hygiene
-most prevalent in developing countries