WEEK 12 - Hepatitis Virus Flashcards
Hepatitis virus INFO
What it is how many are there and how can it be transmitted
Hepatitis = infection of the liver
5 - hepatitis A, B, C, D and E
- a.k.a. HAV, HBV, HCV, HDV, HEV
- all are blood-borne viruses
- Hep B is the ONLY DNA virus
- other 4 are RNA viruses
TRANSMISSION:
- Faecal/oral (ingestion of contaminated food/water)
- Vertical (mother to child)
- Parenteral (unsterile injection)
Can be acute or chronic infections
- acute = < 6 months
Hepatitis A Virus (HAV) INFO
Cause, transmission, virus type, diagnostics
CAUSE: Picornaviridae
- up to 50 day incubation period
- most cases self-limiting, resolve within 2 months
- acute infections
TRANSMISSION: Faecal / oral
- sex / anal
- contact with contaminated inanimate objects, food, water
- travelling to endemic areas
Virus type: RNA
Diagnosis:
- IgG antibody presence = immunity
- have been exposed either naturally or via vaccine
- IgM antibodies = current or recent acute infection
- Liver function tests (ALT, AST)
NOTE:
- Only causes acute hepatitis
- Doesn’t cause HCC, cirrhosis or chronic hepatitis
HAV Pathogenesis
- Ingest contaminated food/ water
- Virus travels through GI tract, to liver then the hepatocytes
- Infected hepatocytes produce IL-15 = bystander CD8+ T cells activated = low level inflammation = liver damage
- Virus shreds in faeces
HAV Symptoms
Usually asymptomatic
Early symptoms:
- dark urine
- aches, pain
- nausea
Later symptoms:
- Jaundice
- damaged liver results in buildup of bilirubin (a product of broken down heme) ~ not excreted by liver
- bilrubin = dark pigmet
- Acute liver failure (ALF) = rare
Hep A: Vaccines
- Once exposed to HAV = LIFE LONG IMMUNITY
- via natural exposure or vaccine
Vaccine is NOT part of ROUTINE schedule
- Given if: at risk group or travelling
- Vaccine can be given on own or in combo. with HBV
- Can have symptomatic or asymptomatic HAV
- can result in ALF
- spontaneous recovery
- relapse HAV
Hep A: Treatment and Prevention
TREATMENT:
- No specific anti-viral treatment
- usually self-limiting
- Symptomatic relief e.g. rest, hydration, analgesia
PREVENTION:
- Lifestyle advice: avoid alcohol, healthy diet
- Infection control
AIM: prevent transmission + symtpomatic releif
HBV INFO
Cause, transmission, virus type, prevelance, diagnostics
CAUSE: Hepadnaviridae
- causes chronic and acute infections
- targets hepatocytes
TRANSMISSION: Faecal/oral
VIRUS TYPE: DNA
- can insert into human genome + cause insertial muttions
PREVALENCE:
- commonly seen in children < 5
- due to lack of adaptive immune response to virus
- lack CD8, CD4, B cells etc.
DIAGNOSTICS:
- ALT (transaminases) ~ LFT
- Surface antigens
- HBV / DNA levels
- HBeAg - secreted by liver cells
- sign of viral replication
NOTES:
- slow process, occurs over 10-30 years = hard to diagnose
- causes HCC, liver cirhossis and fibrosis
HBV Pathogenesis
- HBV produces dane and sub-viral particles when in the body
- dane particles have viral genome
- sub-viral have no genome = decoy for host immune system
- Presence of sub-viral particles = constatnt activation + production of HBV specific T cells / other innate immune cells
- Constant actiavtion wears immune system down
- Activation leads to host-mediated liver inflammation
HBV: Vaccination
Hep B vaccine is part of routine vaccination schedule
- vaccine is admisntered in childhood
- virus is prevalent in <5
- vaccine ↓ risk of chronic infections
Vaccine composition:
- Prepared using yeast cells
- take DNA from HBV and yeast cells produce HBsAg
- Recombinant vaccine
- Inactiavted vaccine
HBV: Prevention
- Vaccine (part of routine schedule)
- Reduce transmission (HBV can survuve for 7 days outside body)
- Hep B Immunoglubulin
Hep B Immunoglobulin (HBIG)
Prevention
HBIG are obtained from plasma of immunised human donors (outisde UK)
- Induces passive immunity
- immediate BUT temporary potection - Given at same time as HBV vaccine
- gives rapid protection until vaccine protection kicks in
- reduces vertical transmission to child - SC or IM injection
HBV: Treatment
- Anti-virals
- Immunomodulator
AIMS:
- Prevent transmission
- Prevent progression to cirrhosis or HCC
- Suppress viral replication
- Reduce liver inflammation
Explain the MoA of anti-retrovirals
e.g. Tenofovir or Entecavir (NRTIs)
Both LIFE LONG TREATMENTS
- take OD
- well tolerated
- NRTIs = inhibit reverse transcriptase
- inhibit RNA polymerase = viral DNA synthesis inhibited - Antivirals ↓ viral load
- aim for undetectable HBV DNA levels
Explain the MoA immunomodulator
e.g. Peg interferon
Boost immune repsonse to HBV:
1. Activate NK cells and macrophages
2. Enhance presentation of viral antigens to T cells
3. Inhibits HBV transcription, translation, replication
DURATION of Treatment:
- Only given for 48 weeks
- S/C Injection weekly
- Delay need for life-long oral therapy
- Has SE = assess tolerability
- Not successful against all HBV types (↓ response rates)
Liver Cirrhosis and HCC
Caused by Hep B, C and D
CAUSE: ongoing low-grade liver inflammation
- inflammation occuring over 10-30yrs
Chronic hep infections lead to fibrosis → cirrhois → HCC
Activation of T cells = chemokine and cytokine production in hepatocytes
= host cell mediated inflammation
HCC = hepatocellular carcinoma
HDV INFO
Hep D virus can not occur without Hep B infection
- requires HBV to infect and replicate
- Hep D is a co-infection
- Having both HBV and HDV = worst case outcomes
- ↑ risk of developing liver cirrhosis and HCC
HDV: Prevention and Treatment
PREVENTION:
- HBV vaccine (as hep D co-exits with this virus / requires it to replicate)
TREATMENT:
- Immunomodulaters ~ Peg interferon
- Antivirals (Bulevirtide)
- inhibitd HDV from enetering hepatocytes
AIMS: same as HBV
HCV INFO
Cause, transmission, virus type, diagnostics
CAUSE: Flaviviridae
TRANSMISSION:
- Parenteral e.g. people who inject drugs
- Unprotected sex
- Blood, organ, tissue transplants
- Unsterile needles
- Vertical
VIRUS TYPE: RNA
DIAGNOSTICS:
- Hard to diagnose as damage occurs of 10-30 years = need to actvely look for people who present risk factors
NOTE:
- causes HCC, liver cirhossis and fibrosis
- Once cured can be re-infected
- have no immune memory
HCV: Pathogenesis
- HCV uses claudin 1 and occludin to enter host cells
- Virus uncoats + uses host machinery to generate viral proteins, assemble proteins
- uses endoplasmic reticulum, golgi appartus
- Virus leaves hepatocyte + infects other hepatocytes
How to clean up blood spillage after an injury
- Put on a pair of rubber household or disposable gloves
- Clean up blood with disposable paper towels
- Use bleach or Milton Fluid to cover the area and leave to soak
- Clean the item that caused the cut (e.g. kitchen knife) in the same way
- Clean up the bleach + place disposable towels into bin
If you cut yourself, you should:
1. Wash your hands with soap under warm running water
2. Hold the cut under running water and clean the wound with soap
3. Dry hands using a disposable paper towel + throw towel into bin
4. Cover cut immediately with waterproof dressing
HCV: Prevention and Treatment
PREVENTION:
- No current vaccines
- National HCV elimination programme
- Not sharing personal hygiene products e.g. razors, clippers, toothbrush
- Avoid sharing needles, piercied jewelery e.g. earrings
TREATMENT:
- Direct acting antivirals (DAAs)
- Use 2 or 3 in COMBINATION
- Ribavarin
AIM:
- Prevent transmission
- Prevent long term liver damage e.g. cirrhosis, HCC
- Cure HCV (= sustained virological response)
Explain the MoA DAAs
HCV Treatment
Target specific steps in HCV life cycle, resulting in viral clearance
DAAs target non-structural (NS) proteins
- e.g. inhibit NS3/4A protease, NS5B polymerase, NS5A
DAA choice depends on:
- HCV genotype
- presence of cirrhosis
DAA Treatment:
- OD, for 8-12 weeks
- Well tolerated, limited SE
-
Explain the MoA Ribavarin
HCV Treatment
- Added to DAA regime if have cirrhosis
- Boosts response rate
MoA not fully understood:
- Inhibits viral RNA synthesis
- Inhibits RNA polymerase
- Immunomodulation
HEV INFO
Cause, transmission, virus type, diagnostics
CAUSE:
- casues acute infections (not chronic)
- 4 genotypes (2 human, 2 zoonotic)
TRANSMISSION: Faecal / oral
- ingesting contaminated water / food
VIRUS TYPE: RNA
DIAGNOSTIC:
NOTE:
- Doesnt cause chronic hep, liver cirrhosis or HCC
- Usually asymtpomatic
- Re-infection is possible (no long lasting immunity)
HEV: Pathogenesis
- HEV endocytosed into hepatocytes
- HEV multiples inside cell using host machinery
- machinery reads viral RNA + generates viral proteins - Viral proteins assembled + are released from cell = infect other hepatocyes
HEV: Treatment and Prevention
TREATMENT:
- Spontaneous recovery, self-limitng (within few weeks)
- Non-specific anti-virals (if immunocompromised only)
- given ribavirin
- immunocompromised may not be able to mout response against HEV
- Symptomatic relief = rest, hydration
PREVENTION:
- Infection control
- sanitation + hygiene practices
- Vaccines (not available in UK)
- Avoid consuming undercooked meat
AIM:
- Symtomatic releif
- Prevent transmission
- Management in high risk indiviuals
Which hepatitis viruses have vaccines
2 viruses
Hep A
inactivated IM vaccine
- have diff. Types
- not part of uk schedule (given if “at risk “ group or travel
Hep B
- Inactivated
- Part of UK childhood routine schedule
Which hepatits can be cured
1 virus
Hep C Virus
- cured using direct acting anti-virals
What needs to be considered when managing drug therapy for patients with viral hepatitis
- Liver function
- fibrosis or cirrhosis presence
- compensated or decompensated
- Co-morbidites
- HIV
- Diabetes
- Pregnancy, immunocompromised
- Taking other medications = interactions
- need to review patients regularly
- e.g. statins, anti-epileptics
- ADRs
- Adherence + advice
What ADRs may occur in hepatitis management
- renal toxicity
- bone mineral density reduction (TAF)
- flu-like symptoms (PEG)
- depression, anxiety, insomnia, visual disturbances (PEG)
- Fatigue, headache, rashes, nausea (DAAs / ribavarin)
- Anaemia, tetrogenic (ribavarin)
How might pharmacist’s contribute to patient care and improve outcomes in viral hepatitis
- Prevention via vaccinations and education
- on transmission, risk factors, infection control
- Screening and testing for HCV
- Harm reduction for Hep B, C, D
- safe injecting advice + needle exchange
- Offer advice and referals
- inc. ADRs and DDIs advice
- treatment advice - Support adherence
- Appropriate prescribing, monitoring
- Obtaining funding for patients treatment
- completing paperwork
