Viral Hepatitis Flashcards

1
Q

Hepatitis Viruses: Overview

A

Hepatitis A* RNA No
Hepatitis B* DNA 10%
Hepatitis C RNA 70%

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2
Q

Hepatitis A: Review

A
  • Non-enveloped, RNA virus (picornavirus)
  • Transmission: fecal-oral; ingestion of contaminated food
    or water
  • Virus replicates and causes infection of hepatocytes
    – Immune response by cytotoxic T-cells is the likely cause of
    hepatocyte damage
    – Once the infection is cleared, hepatic damage is repaired
  • Infection may be asymptomatic or range in severity from
    mild illness lasting 1-2 weeks to severe disabling disease
    lasting several months
    – Children often asymptomatic versus adult
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3
Q

Hepatitis A: Clinical Course

A

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4
Q

Serology Interpretation

A

Anti HAV IgM Anti HAV IgG Possible Interpretation
- - No current or previous HAV infection
No immunity
- + No active infection
Immunity due to prior HAV infection
or vaccination
+ +/- Acute or recent HAV infection

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5
Q

Prevention HepA

  • Treatment
A
  • Proper hand washing and contact precautions
  • Sanitation
  • Avoid drinking contaminated water
  • Boil food/beverages that may be contaminated
  • Hepatitis A vaccination
  • Immunoglobulin

– Generally self-limiting
– Supportive care and symptomatic management

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6
Q

Hepatitis B: review

Pathophysiology

A

Partially double-stranded DNA virus of the family
Hepadnaviridae
* Enveloped
– Outer surface contains HBsAg
– Inner core contains HBcAg, HBeAg
* Several different genotypes have been identified

  • Hepatitis B virus attaches to the hepatocyte cell
    surface and then enters into the cell
  • Virus replicates
  • Immune system responds to virus
    – Strong immune response may clear virus (e.g., adults)
  • Patients do not become chronically infected
    – Weak immune response leads to chronic infection
  • Inflammatory response → Damage to hepatocytes →
    cirrhosis/hepatocellular carcinoma
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7
Q

Outcome of HBV Infection

A

Exposure &
Infection

Asymptomatic
Resolved
Immune
Chronic
infection
Asymptomatic
Cirrhosis
Liver cancer

Symptomatic acute hepatitis B
Resolved
Immune

Chronic
infection
Asymptomatic Cirrhosis
Liver cancer

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8
Q

Signs and symptoms

acute hep B
chronic hep B

A
  • Acute Hepatitis B
    – May be asymptomatic
    – Fever
    – Fatigue
    – Loss of appetite
    – N/V, abdominal pain
    – Grey-colored stool
    – Dark urine
    – Joint pain
    – Jaundice
  • Chronic Hepatitis B
    – May be asymptomatic
    – Fatigue, malaise
    – Anorexia, N/V
    – Ascites
    – Jaundice
    – Variceal bleed
    – Encephalopathy & seizures
    – Labs:
  • HBsAg positive > 6 months
  • intermittent ↑ ALT/AST
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9
Q

Serology Interpretation – Initial Tests

A

HBsAg Anti HBs Anti HBc Possible Interpretation
- - - No current or previous HBV
infection
No immunity
- + - Immunity due to vaccination
- + + Infection resolved, virus cleared
Immunity due to previous infection.
However if immunosuppressed,
virus can reactivate
+ - + Chronic infection

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10
Q

Goals of Therapy

preventionfor hep b

A
  • Prevent transmission
  • Prevent disease progression (e.g. fibrosis,
    development of hepatocellular cancer) and mortality
  • Suppress HBV-DNA replication (not curable…yet)
  • Vaccination
  • Passive immunity in post-exposure individuals
    – Hepatitis B immunoglobulin
  • Barrier protection (condom use)
  • Avoid sharing needles, razors, etc….
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11
Q

Populations disproportionately affected by HCV:
– Indigenous people, people who inject drugs, immigrants, homeless or
incarcerated populations, as well as those born between 1946-1965\

Burden of HCV in Canada

A

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12
Q

Transmission of HCV

A
  • Sharing drug-injection equipment
  • Unsterile tattooing or body piercing
  • Unsterile medical or dental procedures (where skin is pierced)
  • Blood product transfusion in Canada before 1992
  • Parent to child transmission during pregnancy or childbirth
    (Note: do not need to avoid pregnancy or breastfeeding)
  • Sexual transmission (where blood is present, even if trace)
  • Re-using someone else’s personal items that have blood on
    them (e.g., razors, nail clippers, toothbrushes)
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13
Q

Blood Borne Pathogens – Relative
Risk of Transmission

A
  • Needlestick transmission rates:
    – HBV – 30 out of every 100
    – HCV – 3 out of every 100
    – HIV – 0.3 out of every 100
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14
Q

Pathophysiology hep
Hepatitis C virus life cycle

A

Belongs to the family flaviviridae
* Single stranded RNA virus
– 6 main genotypes (1 through 6) and many subtypes
* Replication occurs in the hepatocytes
– Chronic infection occurs due to rapid replication and continuous
cell-to-cell spread → chronic inflammation
– Frequent mutations

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15
Q

Clinical Presentation
hep c

Clinical Course of HCV - untreated

A
  • Usually asymptomatic
  • HCV detectable within 1-2 weeks + ↑ ALT
  • Fatigue, weakness
  • Anorexia, abdominal pain
  • Jaundice
  • Dark Urine

Acute HCV
infection
Death or transplantation
Resolution
Cirrhosis Hepatocellular
carcinoma

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16
Q

Preventing Transmission
hepc

Prevention

A
  • Avoid sharing personal care items contaminated with blood
    (e.g. razors, toothbrushes etc….)
  • Cover any bleeding wound
  • Do not share needles, syringes, or other equipment for
    injection drug use
  • Education on risk of sexual transmission and ways to reduce
    risk (e.g., condoms, lubricant etc)
  • https://www.catie.ca/prevention-in-focus/can-you-get-hepatitis-c-byhaving-sex-the-sexual-transmission-of-hepatitis-c
  • Clean blood spill (including dried blood) with 1 part bleach to
    10 parts water (use gloves)

Access to opioid agonist treatment and needle and
syringe programs (NSP) can reduce HCV incidence by
up to 80%

17
Q

Why screen and treat hepatitis C virus?

A
  • Associated with significant morbidity and mortality –
    lifetime cost to Canadian health system of $64 000
    per chronic infection
  • Disproportionately impacts key populations
  • New treatments (DAAs)– safe and effective (cure)!!
  • Treatment as prevention – population-level
    prevention (no vaccine currently available)
18
Q

Strategies to Eliminate HCV

A
  • Targets for Canada by 2030:
  • 80% decrease in new
    infections
  • 90% of people living with
    HCV will be diagnosed
  • 80% of people living with
    HCV will have initiated
    treatment

Priority Populations in Canada
Cascade of Care in Alberta (2009-2016)

19
Q

Who should primary care providers test
for HCV?

A
  • Current or history of injection drug use
  • Born or had medical/dental treatment in HCV endemic countries
  • Received healthcare where there is lack of universal precautions
  • Children > 18 months of age born to mothers with HCV
  • Received blood transfusions, blood products or organ transplant in Canada
    before 1992
  • History of incarceration
  • History of needle-stick injury
  • Patients with persistently elevated ALT
  • Other risk factors: high-risk sexual behaviours, homelessness, intranasal drug use,
    tattooing, body piercing, or sharing personal care items with someone who is HCVinfected
20
Q

Testing and Blood Work
(at least 3 months after exposure)

A

Initial screen of HCV antibodies (antibody EIA)
– If antibody positive -indicates acute, chronic or past
infection
* Qualitative HCV RNA assay (PCR)
– If antibody positive- ProvLab will automatically complete
reflex testing to confirm if RNA positive (current infection)
– If antibody positive, and RNA negative – HCV has cleared
(past infection)
* HCV is a notifiable disease in Alberta

21
Q

Pre-test Counselling

Barriers & Facilitators to HCV Testing

A
  • Reason for the test and why it is important
  • What a positive antibody test means
  • Next steps if antibody positive
  • Availability of curative treatment
  • Lack of knowledge, low perceived
    risk, fear of positive diagnosis,
    stigma and discrimination, and
    limited access to health care
    system commonly reported by
    patients
22
Q

Point of Care
(Rapid) Testing
– Approved in
Canada in 2017

A

step 1 collect sample
step 1b mix sample in buffer
step 2 insert device into buffer
step 3 read b/w 20-40min
non-reactive line in c zone
reactive line in c and t zones

23
Q

Point of Care Testing - HCV

pros
cons

A

Advantages
* Easy to perform (capillary
blood – finger prick)
* Results available at point of
care (~20 min)
* Very good sensitivity (96-
100%) and specificity (99-
100%)
* Easy to adapt to different
practice models and
settings
* “Low barrier” for testing

Disadvantages
* Requires confirmation (HCV
RNA)
* Results – not on Netcare
* Patients may be at risk for
HIV or other STIs
* Cost of testing?

24
Q

Dried blood spot
testing

pros cons

A

Advantages Disadvantages
* Easy to perform
* Very good sensitivity and specificity
* Can detect HCV RNA
* Can test for multiple infections (HIV, HBV
syphilis etc)
* Easy to adapt to different practice models
and settings
* “Low barrier” for testing
* Not widely available at public health labs
* Results are not immediate

25
Q

Counselling Adults with HCV Infection
(to reduce liver damage)

A
  • Reduce/avoid (if possible) alcohol consumption
  • Smoking cessation (to reduce risk of hepatocellular
    carcinoma)
  • Hepatitis A and B vaccinations (if non-immune)
  • Maintain healthy weight
  • Eat healthy diet
  • Avoid/limit hepatotoxic agents/drugs
26
Q

Bloodwork to Order in
Patients with HCV Infection

A
  • Additional bloodwork:
    – Anti-Hep A IgG antibody, Hep B surface antigen, anti-Hbc
    antibody, anti-Hbs antibody & HIV antibody
    – AST, ALT, CBC (platelets), creatinine
  • Will help assess if patient appropriate to treat in
    primary care or if needs referral to specialist
27
Q

Assess Liver Fibrosis

A

Liver fibrosis and risk of cirrhosis
* https://www.mdcalc.com/fibrosis-4-fib-4-
index-liver-fibrosis
– If FIB-4 > 3.25 – refer to specialist
– If FIB-4 < 3.25 – seek advice (phone or written)
from specialist

28
Q

Who should be treated?
hcv

A
  • Treatment is recommended for all patients with
    chronic HCV infection
    – Exception: those with severe comorbidities and short life
    expectancy unrelated to HCV infection
  • Adults with HCV who do not have cirrhosis and have
    not previously received hepatitis C treatment are
    eligible for simplified treatment
29
Q

Goals of therapy hcv

A
  • Eradicate infection (virologic cure)
    – Achieve sustained virological response (SVR) – absence of detectable
    HCV RNA at least 12 weeks after completion of therapy
    – SVR is a marker for ‘cure’ of HCV infection
    – Will continue to have HCV antibodies but HCV RNA no longer
    detectable in serum or liver tissue
  • Prevent disease progression
  • Improve survival
  • Improve patient specific symptoms
  • Prevent transmission
30
Q

Before Starting Treatment

A

Assess medication coverage
– https://www.ab.bluecross.ca/dbl/pdfs/60022.pdf
* Complete medication reconciliation
– Assess potential for drug interactions
* Pregnancy testing and counselling about risks
(individuals of childbearing potential)
* Education on adherence, benefits and risks of
treatment

31
Q

Oral direct acting agents (DAA)

A
  • NS3/4A protease inhibitor (-previr)
    – simeprevir, paritaprevir, grazoprevir, asunaprevir,
    glecaprevir, voxilaprevir
  • NS5B polymerase inhibitors (-buvir)
    – sofosbuvir, dasabuvir
  • NS5A inhibitors (-asvir)
    – ledipasvir, ombitasvir, daclatasvir, elbasvir,
    velpatasvir, pibrentasvir
32
Q

Pan-genotypic Regimens

A

Sofosbuvir/velpatasvir
(Epclusa®)
12 weeks duration
>95%
1 pill daily +/- food
eGFR>30
avoid PPI, penytoin, rifampin, carbmazepine, St John’s wort

Glecaprevir/pibrentasvir
(Maviret®)
8wks
>95%
3 pill daily +/- food
no eGFR or dialysis restriction
avoid Ethinyl estradiol, atorvastatin,
phenytoin, rifampin,
carbamazepine, St. John’s wort

33
Q

Pharmacokinetic Properties (DAA)
Drug interactions:
Pan-genotypic Regimens

A

slide 53
Most interactions linked to CYP450-3A4 metabolism or
hepatic/intestinal transporters [organic anion-transporting
polypeptide (OATP) and p-glycoprotein (P-gp)]
* Lower risk of interactions with more recently approved agents
* Most common real-word interactions with
sofosbuvir/velpatasvir:
– pantoprazole, omeprazole, carvedilol
* Most common real-word interactions with
glecaprevir/pibrentasvir:
– cyclosporine, tacrolimus, carvedilol, pravastatin

34
Q

Monitoring
role of pharm

A

Week 12 after end of therapy (SVR 12):
– HCV RNA, AST, ALT

Disease prevention and screening
– Education/awareness
– Harm reduction (e.g. clean needles, OAT)
– Screening (esp. HCV POCT)
* Linkage to care
* Treatment Initiation and Monitoring