Hepatitis viruses Flashcards
Hepatitis
General term referring to inflammation of liver
Causes
Infectious -viral -bacterial -fungal -parasitic Non infectious -alcohol -drugs -autoimmune -metabolic diseases
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
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.
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
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
Vaccine for Hep A
Formalin-killed virus
Recent Hep A outbreaks
San Diego
Manchester
Global distribution of Anti-HAV
Developing countries
Intermediate Russia and East Europe
High incidence in Greenland
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
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
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
Hep B
Hepatitis B virus (HBV)
Parenteral route of transmission
dsDNA virus, resides & multiplies in hepatocytes
Most patients recover in a few weeks
Carrier state of Hep B
2-5%
- chronic persistent hepatitis (‘healthy carrier’)
- chronic active hepatitis
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
Breakdown product of HBcAg
Found in serum
HBeAg
Marker of active infection
HBV genes
S: preS1 –> preS2 –> surface antigen
C: preC –> core protein
P: polymerase
X: regulatory
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
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
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
Chronic HBV infection
HBS Antigen stays elevated against core antigen up to about 10 years
HBC and HBE antigen elevated until around 20 years
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.
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
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
Hep B epidemiology vaccine
Genetically engineered HBsAg
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
Hep D virus
HBsAg
RNA
Delta antigen (used for diagnosis)
Hep D infection co-incident with HBV (at the same time)
- HDV influenced by replication of HBV
- rarely progressive or chronic
Hep D: superinfection on HBV disease (already got Hep B, then get Hep D)
- ideal for rapid HDV replication
- commonly chronic
HDV cases worldwide
15 million
-mainly IV drug users in UK
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
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
Hep C disease diagnosis
unreliable (antibody takes 6wk-6mnth) –
97% by 6mnth
Hep C mild disease
1% have acute illness with jaundice
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.
Hep C disease persistence
Relatively low replication replication rate
- no RNA repair mechanism
- variants selected by non-reactivity with antibody
Hep C disease treatment
Interferon alpha and Ribavirin
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
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
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
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
Hep E average incubation
6 weeks; high mortality in pregnancy (in India)
Table test
test yourself (slides)
The ABCs of viral hepatitis
A
B
C
Epidemiology Hep E
Poor sanitation, food hygiene
-most prevalent in developing countries
