Viral Hepatitis Flashcards
Where is HAV worst?
S America
Africa
Asia
Greenland
What type of Hepatitis is HAV?
Acute hepatitis IP 2-6 weeks
Often subclinical
Faecal-oral spread
Notifiable
How do the immunoglobulins change in HAV?
IgM rises first
IgG rises after
ALT spikes with IgM
HAV in stool just before and during infection
What is the molecular organisation of HBV?
- The family Hepadnaviridae
- Double-strained DNA with reverse transcriptase
- Enveloped virions
Where are the clades endemic for HBV?
10 genotypes (A-J) with distinctive geographic distribution
How is HBV spread?
- Sexual
- Vertical
- Blood products
What kind of infection is HBV?
- ACUTE and CHRONIC
- Chronic = 6 months or more
How does HBV antigens change over time?
What are the disease stages of HBV?
- Immune tolerant
- Immune reactive
- Inactive HBV carrier state
- HBeAg negative chronic HBV
- HBsAg negative phase
When might HBV cause cirrhosis?
When baseline HBV DNA is >10^6
What is the treatment of chronic HBV?
- Interferon alpha
- Lamivudine
- Adefovir
- Tenofovir
- Entecavir
- Emtricitabine
Where is HCV highest?
Parts of SA, Africa, Asia
What is Hep C?
- Flaviviridae
- Mainly blood product spread
- 60-80% chronicity
- Natural history
What enzymes does HCV use?
NS3/4 serine protease, RNA helicase
NS5A
NS5B RNA dependent RNA polymerase
What type of infection is HCV?
Acute 20-40%
Chronic 60-80%
Antibodies/ ALT in HCV?
ALT spikes and then anti HCV
How do you treat acute HCV?
Peginterferon alfa
Protease inhibitors:
telaprevir
boceprevir
simeprevir
asunaprevir
paritaprevir (ABT-450/r)
grazoprevir (MK5172)
vaniprevir
faldaprevir
deleoprevir
ledipasvir
daclatasvir
ombitasvir (ABT- 267)
elbasvir (MK-8742)
sofosbuvir
dasabuvir (ABT-333)
beclabuvir (BMS- 791325)
ABT-072
deleobuvir
Where to the DAAV act?
Where is HDV high?
Some parts of SA and Africa
What is the serological course for HDV superinfection?
What is the serological course for HDV superinfection?
Where is HEV worst?
Africa and Asia
What is the most common acute hepatitis?
HEV
What are the genotypes of HEV?
Genotype 1 and 2 – human, epidemic
Genotype 3 and 4 – swine and other
(humans accidental host = zoonosis)
Very little person to person spread
Case reports
Shellfish consumption, blood transfusion
Sausages, pig liver consumption
How do you treat HEV?
supportive ? ribavirin
What are the complications of HEV?
Incubation period 3-8 weeks
High mortality rate in pregnancy ( genotype 1)
RARE COMPLICATIONS
CNS disease – Bell’s palsy, Guillain Barre, other neuropathy
Chronic infection
Is there a Vx for HEV?
VACCINE – EFFECTIVE - trials with recombinant HEVg1
In Nepalese military and Chinese (100 000)
What is the serology of HEV?
What is the epidemiology of Hepatitis A?
- Approx. 1.5 millions of cases worldwide annually
- Developing countries with poor socio-economic conditions
- 300-500 cases annually in the UK
- Mostly among age 15-34 and non-travellers
- Outbreaks among MSM (2016/17) & IVDU (2001 & 2017)
What are the clinical manifestations of hepatitis A?
- Wide disease spectrum from asymptomatic to fulminant hepatitis
- Strong correlation with age: <10% symptomatic among children <6 years old versus 70% in adults
- Typical symptoms: fever, malaise, anorexia/nausea, abdominal discomfort, diarrhoea, jaundice
- Extra-hepatic diseases
- Acute presentation; 99% resolution
- NOT an aetiology for chronic hepatitis
What is the diagnosis and treatment of HAV?
•Diagnostics based on HAV serology
ØAcute infection: IgM reactive; unlikely if bilirubin level < 30umol/L
ØPast infection: IgM non-reactive, IgG reactive
•Supportive treatment
How do we alert public health for HAV?
•Notifiable disease in the UK – must alert HPT immediately upon diagnosis
•
- Infectious period of index case: two weeks before onset of first symptoms and until one week after the onset of jaundice
- Pre-exposure immunisation among population at risk
- Post-exposure prophylaxis
ØWithin 14 days of exposure to index case: HAV vaccine +/- HNIG (for 60 years and above, chronic liver diseases inc CHB/CHC, immunocompromised contact)
ØOver 14 days: HAV vaccine +/- HNIG (for chronic liver diseases inc CHB/CHC, immunocompromised contact)
What are the clinical manifestations of acute hepatitis?
•Age related presentation & prognosis in acute hepatitis B
ØNeonates & children: mostly asymptomatic or anicteric; 90% HBV-infected neonates develop CHB, and 30% among children age <5 years
ØAdult: 30-50% icteric hepatitis; 10% become CHB
- 0.1-0.05% risk of fulminant hepatitis; related to co-infection with HCV/HDV
- Maternal HBeAg/Ab status & HBV viral load
ØHBeAg as the most important risk predictor for vertical transmission
What are the clinical manifestations of chronic hepatitis B?
- Definition: persistence of HBsAg for 6 months or more after acute HBV infection
- Complications
ØCirrhosis: 8-20% untreated CHB in 5 years;
ØHepatocellular carcinoma: the annual risk of 2-5% among CHB cirrhotic patients; affected by host (e.g. alcohol abuse) and viral factors (e.g. high HBV viral load & qHBsAg)
What is the epidemiology of hepatitis B?
Approximately 296 million people are living with CHB worldwide; CHB-related mortality at roughly 820,000 people per year
How do you interpret HBV serology?
- HBsAg: infection
- HBsAb: immunity through either immunisation or past infection
- HBcAb: exposure
ØIgM: acute infection
- HbeAg: replication activity
- HBeAB
What is the prevention/public health for HBV?
- Acute hepatitis B: a notifiable disease
- Pre-exposure prophylaxis
ØRoutine childhood immunisation in the UK since 2017
ØHigh risk population
•Post-exposure prophylaxis
ØNeonate born to mother living with hepatitis B
ØSexual partner: HBV vaccine +/- HBIG (within one week from the contact)
ØNeedle stick injury
What is HDV?
- Single-stranded, circular RNA genome
- A defective virus that relies on HBV for propagation
- Blood-borne transmission
- Incubation period: 3-6 weeks
What is the HBV/ HDV co-infection?
•HBV/HDV simultaneous co-infection
ØSimilar to classic acute hepatitis B; mostly self-limited
Ø<5% chronic infection
•HDV super-infection in CHB
Ø80% chronic infection
ØIncreased risk of cirrhosis and HCC than CHB alone
What is the diagnosis/ treatment/ prevention of HDV?
- Anti-HDV serology; other HDV investigations rarely used
- PEG-interferon alpha licensed for HDV superinfection in CHB
- Pre-exposure HBV immunisation
- Acute HDV infection: notifiable disease
What is Hep C?
- The family Flaviviridae, genus Hepacivirus
- Single-stranded, positive sense RNA genome
- Blood borne transmission
- Incubation period: 2-6 weeks
- 58 million people living with chronic hepatitis C worldwide
- 1.5 million new cases every year
What is the clinical manifestations of Hep C?
•Acute infection
Ø30% spontaneous clearance
Ø70% become chronic hepatitis C (CHC)
- Hepatic versus extra-hepatic manifestation
- Cirrhosis (15-30% in 20 years) & HCC as complication of CHC
What is the antibodies for HCV?
What is the treatment of HCV?
- Revolutionised the treatment for acute/chronic HCV infection
- Any HCV cases should be considered
- 8 or 12 weeks
- Sustained virological response (SVR) at week 12
- Pan-genotypic regimen
- Single-tablet regimen
- Drug-drug interaction
What is the prevention/ public health of Hep C?
- Acute hepatitis C: notifiable disease in the UK
- Nil vaccine available
- Nil post-prophylaxis available
- Active HCV screening
- Risk reduction (e.g. safe handling and disposal of sharps, protected sex)
What is HEV?
•The family Hepeviridae, genus Orthohepevirus; species A strains (8 genotypoes) infect humans
ØG1 & G2: obligate human pathogens
ØG3 & G4: zoonotic; pigs & wild boar are natural hosts
- Single-stranded, positive sense RNA genome
- Quasi-enveloped HEV
- Faeco-oral versus blood-borne transmission
- Incubation period: 15-60 days
- Approximately 20 million new HEV cases worldwide annually
- 3.3m symptomatic hepatitis E
- 44,000 mortality annually
- UK is a HEV G3 endemic country
What are the clinical manifestations of Hep E?
- Mostly self-limited; advised against alcohol during the course
- At risk population
ØPregnant women: G1; fulminant hepatic failure and obstetric complications (e.g. eclampsia and haemorrhage); 25% maternal mortality & high perinatal infant mortality
ØChronic liver disease patients
ØImmunocompromised patients: may develop chronic hepatitis E (G3 & G4)
•Hepatic versus extra-hepatic manifestations
How do you diagnose HEV?
- Immunocompetent: HEV serology
- Immunocompromised: HEV PCR
What is the treatment and prevention of HEV?
- Only indicated in chronic hepatitis E as most acute HEV infection are self-limited
- Acute HEV infection: a notifiable disease
- HEV patient should avoid prepping food during the first 2 weeks
- Immunocompromised and chronic liver disease patients should avoid consumption of undercooked meat (pork, wild boar and venison) and shellfish
ØHEV vaccination: only licensed in China
