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Hepatobiliary system (DEN 303) > Hepatitis viruses > Flashcards

Hepatitis viruses Flashcards

1
Q

Hepatitis

A

General term referring to inflammation of liver

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2
Q

Causes

A 
Infectious
-viral
-bacterial
-fungal
-parasitic
Non infectious
-alcohol
-drugs
-autoimmune
-metabolic diseases
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3
Q

Signs and symptoms of hepatitis

A 
Malaise
Jaundice
Dark urine
Pale fatty stools
Serum & urine biochemistry, specific serological tests for HepA, B, C, D & E antibodies for viral hepatitis
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4
Q

Viral structure (DRAW)

A

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.

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5
Q

Major hep viruses

A 
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
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6
Q

Hep A

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

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7
Q

Vaccine for Hep A

A

Formalin-killed virus

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8
Q

Recent Hep A outbreaks

A

San Diego

Manchester

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9
Q

Global distribution of Anti-HAV

A

Developing countries
Intermediate Russia and East Europe
High incidence in Greenland

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10
Q

Hep A epidemiology

A

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

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11
Q

IgM/IgG reminder

A

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

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12
Q

Serology of Hep A

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
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13
Q

Hep B

A

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

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14
Q

Carrier state of Hep B

A

2-5%

  • chronic persistent hepatitis (‘healthy carrier’)
  • chronic active hepatitis
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15
Q

Hep B virus (DIAGRAM)

A 
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
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16
Q

Breakdown product of HBcAg

A

Found in serum
HBeAg
Marker of active infection

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17
Q

HBV genes

A

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

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18
Q

HBc and HBe antigens

A

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

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19
Q

Possible courses of HBV infection

A

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
Q

Serology - acute HBV infection

A

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
Q

Chronic HBV infection

A

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

22
Q

Lab diagnosis - serology - Hep B acute

A

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
Q

Lab diagnosis - serology - Hep B - chronic

A

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
Q

Hep B epidemiology

A

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
Q

Hep B epidemiology vaccine

A

Genetically engineered HBsAg

26
Q

Hep D

A

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
Q

Hep D virus

A

HBsAg
RNA
Delta antigen (used for diagnosis)

28
Q

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

A
  • HDV influenced by replication of HBV

- rarely progressive or chronic

29
Q

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

A
  • ideal for rapid HDV replication

- commonly chronic

30
Q

HDV cases worldwide

A

15 million

-mainly IV drug users in UK

31
Q

Hep C virus (DRAW)

A

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
Q

HCV epidemiology

A 
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
Q

Hep C disease diagnosis

A

unreliable (antibody takes 6wk-6mnth) –

97% by 6mnth

34
Q

Hep C mild disease

A

1% have acute illness with jaundice

35
Q

Hep C chronic disease

A

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
Q

Hep C disease persistence

A

Relatively low replication replication rate

  • no RNA repair mechanism
  • variants selected by non-reactivity with antibody
37
Q

Hep C disease treatment

A

Interferon alpha and Ribavirin

38
Q

Hep C - new cures

A

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
Q

Hep C - financial burden in US

A

> 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
Q

Prospects for HCV vaccine

A 
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
Q

Hep E

A

> 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
Q

Hep E average incubation

A

6 weeks; high mortality in pregnancy (in India)

43
Q

Table test

A

test yourself (slides)

44
Q

The ABCs of viral hepatitis

A

A
B
C

45
Q

Epidemiology Hep E

A

Poor sanitation, food hygiene

-most prevalent in developing countries

Hepatobiliary system (DEN 303) (3 decks)

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