20/21 - Hep A & B Flashcards
Pathophysiology of HAV
Mainly from Fecal-Oral Route > serum > saliva
could live in dried feces >4 weeks
from RAW seafood
does NOT cause CHRONIC DISEASE
HAV deographic distribution
HIGHEST in Africa / India
Mexico = south america = asia
anti-HAV IgM
Determines what?
Antibodies to Hep A IgM
Diagnoses ACUTE** **HAV
anti-HAV IgG
Determines what?
Past HAV Infection
or
- *Lifelong IMMUNITY** to HAV Vaccine
- may not need another dose*
Total anti-HAV
determines what?
Past HAV Infection
or
- *Lifelong IMMUNITY** to HAV Vaccine
- may not need another dose*
HBV Demographic Distriution
2 billion infected –> 257mil chronic
1 in 10 are ASIANS & PACIFIC ISLANDERS
HBV concentrations in Body fluids
HIGH:
BLOOD / SERUM / WOUND EXUDATES
Moderate:
semen / vaginal fluid / saliva
low / not detected:
urine / feces / sweat / tears / breast milk
HBV Transmission + Risk Factors
Blood + Infected Bodily fluids:
Percutaneous / SEXUAL / PERINATAL
Risk factors:
Vertical = perinatal/infants
Horizontal:
Children in day care , Sex > MM-Sex > Healthcare workers > travel
- *Parenteral**:
- *DIABETES** ( due to using the same meter / pen needles)
- *IV drug users** / Blood transfusion / tatoos / acupuncture
HBV GEOGRAPHIC Distribution
HIGHEST in AFRICA
> Asia/Northern china
Effect of AGE OF ACQUISITION of HBV
Getting ACUTE HBV when you are YOUNG
= GREATER RISK to develop into CHRONIC HBV
Adults have a LARGER chance to
eliminate the infection / less chance to develop CHRONICITIY
(perinatal / as a child)
Hepatitis B Development into Chronicity
Adult Acquired = 10-15% -> Chronic
- *Infant Acquired = 80-90% –> Chronic**
- Inactive carrier* = 50%
Mild/Moderate Hepatitis = 20-30%
Cirrhosis = 8-20%
EVEN WITHOUT CIRRHOSIS –> CAN DEVELOP TO LIVER CANCER
(HCC = hepatocellular carcinoma)
Which Hepatitis can develop into HCC
even WITHOUT symptoms or Cirrhosis?
HBV
HBsAg
HEP B surface antigen
What does this help diagnose?
GOLD STANDARD = Marker of INFECTION
1st serologic marker to appear
Shows in serum 1-9 weeks post exposure
>6 mos = chronic infection
Just tells if you if you have the infection,
does NOT tell if Chronic / Acute
anti-HBs
antibodies to HEP B surface antigens
What does this help diagnose?
If Positive & NO other markers = IMMUNITY/VACCINATED
Documents RECOVERY +/- IMMUNITY to HBV
Detectable after immunity conferred by HBV Vaccine
HBcAg
Hepatitis B CORE antigen
What does this help diagnose?
not useful in diagnosing active or chronic HBV
anti-HBc ( IgM )
antibody to hep B CORE IgM
What does this help diagnose?
ACUTE
HEPATITIS B INFECTION
IgM = ACUTE
M = making still
anti-HBc ( IgG )
Antibody to HEP B CORE IgG
What does this help diagnose?
can also be Total anti-HBc
- *PREVIOUS_ or _CHRONIC**
- *HBV**
HBeAg
Hep B ENVELOPE antigen
What does this help diagnose?
Indicates ACTIVE REPLICATION of HBV
is ABSENT in Pre-Core MUTANT HBV
anti-HBe
antibody to hep B envelope antigen
What does this help diagnose?
Indicates that:
Viral Replication has STOPPED or is DECREASING
patient can STILL be positive for HBsAg
HBV DNA
What does this help diagnose?
Use to ASSESS** & **QUANTIFY
HBV replication
HBV Genotyping
What does this help diagnose?
Helps determine the SEVERITY of the liver disease
&
Helps determine RESPONSE to IFN Therapy
HBV Genotypes, comparison of B vs C
A-J
A B C = Most Common
vary by location, B&C mainly in ASIA
B > C
in terms of IFN RESPONSE
&
BETTER in other ways
remission / preogression to cirrhosis / chronicity
Serological Test Chart for HBV
HDV Transmission
NEED TO HAVE HBV before you can get HDV
transmission is the same as HBV
Percutaneous = Injecting drug use
Permucosal = Sex
but RARE in vertical transmision
HDV CO-infection
You can be infected with
HBV & HDV
AT THE SAME TIME
most will recover,
<5% develop chronicity
may develop fulminant liver failure –> DEATH
HDV SUPERINFECTION
Already infected w/ HBV –> Acquire HDV LATER IN LIFE
more common than Co-infection:
Usually leads to
MORE SEVERE LIVER DISEASE / 70-90% Develop CIRRHOSIS
HEV
Distribution / Pathophysiology
Also found in the FECES** / **STOOL
Usually a SELF-LIMITING ACUTE Illness
HIGH mortality in pregnant women
& seen in Immunocompromised patients
4 genotypes, mainly in ASIA & AFRICA
CHINA has a HEV Vaccine
HGV Information
Transmission through BLOOD & SEXUAL CONTACT
found from blood donors
Liver is NOT a significant site of replication
May PREVENT cirrhosis in HIV patients
being researched
Agents for PREVENTION of HAV
HAND WASHING!
Immune Globulin = IG
gives passive TEMPORARY immunity, for post/pre-exposure
- *Hep A VACCINE**
- *active & LONG-TERM** immunity, also for post/pre-exposure
- some may have HYPERSENSITIVITY to vaccine components = NEOMYCIN*
Immune Globulin = IG
for HAV
for PRE-Exposure = TRAVEL
for up to <1 Month of Travel, 1 dose
or 2+ months of Travel, greater dose / can REPEAT
for POST-exposure
1 dose weight based 0.1mL/kg
HAV Vaccines
Dose / Names
HAVRIX
2 Doses, 2nd dose between month 6 - 12
INTERCHANGABLE
VAQTA
2 doses, 2nd dose between month 6 - 18
think 18 is greater & V>H
When to give PRE-Exposure HAV
IG or HAV Vaccine
Healthy Traveler 1-40 years old
International Travel - Africa / Asia
Based on: AGE & TRAVEL TIME
HAV VACCINE ONLY
given ANYTIME prior to travel
When to give PRE-exposure HAV
IG or HAV Vaccine
For traveler LEAVING < 2 WEEKS
International Travel - Africa / Asia
Based on: AGE & TRAVEL TIME
> 40 Years Old or Immunocompromised or Chronic Disease (+liver)
BOTH IG & HAV VACCINE
When to give PRE-exposure HAV
IG or HAV Vaccine?
Traveler can NOT recieve HAV vaccine
International Travel - Africa / Asia
Based on: AGE & TRAVEL TIME
< 12 months old
(NOT approved for this age group)
ALLERGIC to vaccine / Choose NOT to
IG ONLY
When to give POST-exposure HAV
IG / HAV Vaccine
Persons recently exposed to HAV & have NOT been VACCINATED
Give WITHIN 2 WEEKS AFTER exposure
HAV Vaccine
ONLY for Healthy 12mo - 40y/o
IG
<12 mo & >40 y/o
Immunocompromised & Chronic Liver Disease
can give HAV vaccine INSTEAD, if they can NOT obtain IG
HAV Vaccine FACTS
- *VERY GOOD RESPONSE**
- *97-100%** 1st dose –> 100% after 2nd dose
do NOT need routine vaccination
Recommended in specific circumstances:
Injection Drug Users
High Prevelance of HAV
PREVENTION of HBV
Mainly from SEX / BLOOD / Vertical Transmission
HBV IG = HBIG
Immunoglobulin = PASSIVE immunity
- *HBV Vaccine**
- *Engerix-B / Recombivax HB**
HBV Vaccine Dosing Schedule
Recombivax HB or Engerix B
both have same schedule
3 DOSE REGIMEN
0 / 1 / 6-12
months
Limitations of HBV Vaccines
Recombivax HB / Engerix-B
requires 3 DOSES over 6 Months
REDUCED EFFICACY in some patient populations
Diabetes:
<40 y/o = >90% effective
>70 y/o <40% effective , worse when OLDER
OBESE** / **ELDERLY** / **SMOKERS** / **Immunocompromised
- *HEPLISAV-B**
- *new HBV Vaccine**
Advantages / Disadvantages
ONLY 2 DOSES = 0 / 1 month
Contains a ADJUVANT
BETTER EFFICACY
especially for diabetics / 40-70 / obesity / smokers
BUT it showed an:
INCREASED RISK IN ACUTE MI
Recommendations for HBV POST-exposure
what do we need to know?
we have to know THE SOURCE of the HBV
- *HBsAg POS**
- *HBIG & Vaccine Series**
HBsAg neg / Unknown
just the HBV Vaccine series
HBV Vaccine Dosing Schedule for INFANTS
based on what?
Based on Two factors:
MOTHER’s HBsAg STATUS
BIRTH WEIGHT
HBV Vaccine Dosing for infants
Mother’s HBsAg is POSITIVE
REGARDLESS of WEIGHT
HBV Vaccine + HBIG
within 12 hours of birth
Test for anti-HBs @ 9-12 months
HBV Vaccine Dosing for infants
Mother’s HBsAg is negative
>2kg = vaccine within 24 hours of birth
< 2kg = vaccine @day 30 or @hospital discharge
No need to Test for anti-HBs if immunocompetent
WHO to test PRIOR to HBV Vaccination?
Household, sexual, or needle contacts of HBsAg + Persons
HIV Positive
Elevated LFT
M-M Sex / Inject Drugs
Immunosupressive therapy
DONORS
blood / plasma / organs / tissue /semen
WHO & WHEN
to test AFTER HBV vaccination
anti-HBs @ 1-2 Months AFTER the last dose of the vaccine series
INFANTS
born to HBsAg POSitive / Unknown mother status
Health care professionals
HIV infected persons
Immunocompromised persons
Sex partners of HBsAg Positive
TWINRIX
for what & Indication?
BOTH A & B
Hepatitis Vaccines
> 18 years old
PRE-exposure Prophylaxis
Difference between
ACUTE & CHRONIC
viral hepatitis
CHRONIC =
> 6 MONTHS
same for all
Recommendations for HAV
PRE-exposure
GIVE THESE PEOPLE HAV VACCINE!
Children @ 1 y/o
Occupational risk / M-M Sex / Inj Drug User
- *CHRONIC LIVER DISEASE**
- *HBV / HCV / CIRRHOTIC**
Persons w/ clotting factor disorders
Work / living / traveling to high HAV rates
WHY do we treat HBV?
to REDUCE CHANCE of Developing CIRRHOSIS
& HCC
Only HEP that does NOT need to develop into cirrhotic state
to develop CANCER
WHEN to treat HBV?
What Serological tests / Other levels
HBeAg = “ENVELOPE” Antigen Positive
indicates ACTIVE replication of HBV virus
Treat patients based on HIGH LEVELS of:
ALT / HBV DNA
+ Moderate to severe inflammation / fibrosis
If HBV DNA is HIGH >20k
& ALT is HIGH > 2 ULN (35 for men / 25 for women)
–> body is trying to fight it off = TREAT IT
if levels are norma = not trying to fight it = we do not treat
WHEN to treat HBV?
If patient does NOT meet HBsAg Pos/Neg definition of treatment
HBsAg +POS / HBeAg -Neg
age >40 y/o
Family History of HCC
CO-Inefected w/ HIV** or **HCV
Moderate to severe fibrosis ~1mil VL
Cirrhosis w/ low VL
Therapies for CHRONIC HBV
TDF** / **TAF / Entecavir
NRTI’s
TAF has less liver disease issues
pegINTERFERON
PegINF
Positives & Negatives
Pegylated Interferon = HBV Treatment
positive is NO CHANCE OF RESISTANCE
Negatives = SIDE EFFECTS
PSYCHIATRIC complaints / Depression CI
+ many more & also many contraindications
How LONG do we take HBV Treatment?
LIFELONG
WHEN do we MONITOR anti-HBV Agents?
PEG-IFN
Liver Chemistry + CBC + HBV DNA + TSH + HBesAG/Anti-HBe
during treatment= various
Posttreatment = 12 & 24 weeks
- *HBsAg**
- *every 5 months**
CONTRAIndications for IFN / PegIFN
Autoimmune disease
Uncontrolled Psychiatric disease
Cytopenias / Seizures
DE-COMPENSATED Cirrhosis
Resistance in HBV Treatments
LONGER you treat ==> HIGHER RESISTANCE
Even HIGHER if taken ANOTHER medication in the past
INTERFERON HAS NO RESISTANCE
Warnings for Anti-HBV Agents
FIRST RULE OUT HIV
before treating HBV
Ensure PATIENT COMPLIANCE
important due to –> hepatitis flare
Lactic Acidosis
- *Bone Density / Nephrotoxicity**
- LOWER RISK WITH TAF vs TDF*
Lamivudine has a risk for Pancreatitis
When do we monitor NRTI’s?
- *DURING TREATMENT**
- likely on the medication FOR LIFE*
Liver chemistry / serum creatinine
every 12 weeks
HBV DNA / HBeAg / Anti-HBe
every 24 weeks
HBsAg
q 6 - 12 months
AASLD Guideline for DURATION / Monitoring
of NRTI Treatment
HBeAg +POS+ with NO Cirrhosis
treatment should be continued until:
undetectable HBV DNA & persistantly normal ALT levels
at LEAST > 12 months of additional treatment
after the appearance of anti-HBe
- if we DC the therapy we need CLOSE monitoring for RELAPSE:*
- *every 3 MONTHS for >1 YEAR**
AASLD Guideline for DURATION / Monitoring
of NRTI Treatment
- *HBeAg +POS+ chronic HBV**
- *WITH CIRRHOSIS**
Patient has achieved undetectable HBV DNA level
+ Normal ALTs & Anti-HBe
STILL TREAT INDEFINITELY
AASLD Guideline for DURATION / Monitoring
of NRTI Treatment
ALL HBeAg -NEG- & Chronic HBV
NEGATIVE HBeAg but CHRONIC HEP B
TREATMENT IS STILL INDEFINITE
Recommendations for managing HBV RESISTANCE
PREVENTION
AVOID unnecessary treatment
Initiate POTENT antiviral tx w/ low rate resistance
Switch therapy w/ 1* non-response
ADHERENCE
Resistance to Adefovir
Recommendations for managing HBV RESISTANCE
Switch Strategy:
ENTECAVIR
Add Strategy:
typically add 2 drugs w/o cross resistance
Continue Adefovir + ADD Entacavir
MULTI-Drug Resistance
Recommendations for managing HBV RESISTANCE
Switch Strategy:
TENOFOVIR
Add Strategy:
Combo of
Tenofovir + Entecavir
Resistance to:
Lamivudine / Telbivudine / Entecavir
Recommendations for managing HBV RESISTANCE
Switch Strategy:
All switch to TENOFOVIR
Add Strategy:
Continue the Original drug + ADD TENOFOVIR
Renal Adjustment for TAF / TDF?
Dose adjustments for everything else!
still 300mg but every 24 - 48 - 72 -96 hours
CrCl <15 = Do NOT recommend TAF
NRTI’s & Pregnancy
- *TDF =** Pregnancy class B
- TAF = no human data yet*
Lamivudine / Entecavir = Pregnancy class C
Initiate TX if 3rd trimester w/ HBV DNA > 200k
DC DRUG @ BIRTH or <1mo post partum
WHEN to treat CHILDREN for HBV?
for 2-18 y/o
ALT > 1.3x ULN
+
HBV DNA > 104 IU/mL
do not treat if normal ALT
WHAT Agents to treat CHILDREN
with HBV?
High ALT + HBV DNA
Interferon
>1y/o for 24 weeks
Peg-IFN for >5y/o for HCV
- *Lamivudine + Entacavir**
- *>2 y/o** - same adult rec
TDF
for >12y/o for same adult rec
Pro / Con
of NUCLEOSIDE THERAPY for HBV
- *PRO**
- *Oral / High activity**
- low resistance w/ newer drugs*
- *Minimal ADR**
- *Negatives**
- *LONG TERM** / indefinite
- *renal toxicity rare**
- *slower action than IFN**
- may induce HIV*
PRO / CON
of INTERFERON-BASED THERAPY
for HBV
PRO
finite duration = 48-96 weeks
NO RESISTANCE
HIGH rate of viral loss / clearance
- *Negative**
- *SUBQ**
- *LOT OF ADR = PSYCHOLOGICAL**
