Viral Hepatitis Flashcards
Hepatitis Viruses: Overview
Hepatitis A* RNA No
Hepatitis B* DNA 10%
Hepatitis C RNA 70%
Hepatitis A: Review
- 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
Hepatitis A: Clinical Course
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Serology Interpretation
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
Prevention HepA
- Treatment
- 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
Hepatitis B: review
Pathophysiology
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
Outcome of HBV Infection
Exposure &
Infection
Asymptomatic
Resolved
Immune
Chronic
infection
Asymptomatic
Cirrhosis
Liver cancer
Symptomatic acute hepatitis B
Resolved
Immune
Chronic
infection
Asymptomatic Cirrhosis
Liver cancer
Signs and symptoms
acute hep B
chronic hep B
- 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
Serology Interpretation – Initial Tests
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
Goals of Therapy
preventionfor hep b
- 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….
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
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Transmission of HCV
- 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)
Blood Borne Pathogens – Relative
Risk of Transmission
- Needlestick transmission rates:
– HBV – 30 out of every 100
– HCV – 3 out of every 100
– HIV – 0.3 out of every 100
Pathophysiology hep
Hepatitis C virus life cycle
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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Clinical Presentation
hep c
Clinical Course of HCV - untreated
- 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
Preventing Transmission
hepc
Prevention
- 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%
Why screen and treat hepatitis C virus?
- 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)
Strategies to Eliminate HCV
- 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)
Who should primary care providers test
for HCV?
- 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
Testing and Blood Work
(at least 3 months after exposure)
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
Pre-test Counselling
Barriers & Facilitators to HCV Testing
- 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
Point of Care
(Rapid) Testing
– Approved in
Canada in 2017
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
Point of Care Testing - HCV
pros
cons
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?
Dried blood spot
testing
pros cons
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
Counselling Adults with HCV Infection
(to reduce liver damage)
- 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
Bloodwork to Order in
Patients with HCV Infection
- 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
Assess Liver Fibrosis
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
Who should be treated?
hcv
- 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
Goals of therapy hcv
- 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
Before Starting Treatment
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
Oral direct acting agents (DAA)
- 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
Pan-genotypic Regimens
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
Pharmacokinetic Properties (DAA)
Drug interactions:
Pan-genotypic Regimens
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
Monitoring
role of pharm
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
