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441 Therapeutics
Presented By: Jamilah Al-Saidan, Msc.
HEPATITS PATIENTS
SPECIAL POPULATIONS
 Outline:
 Identify the special populations
 What makes them special
 Mode of management
HEPATITS PATIENTS
SPECIAL POPULATIONS
 Those patients needing special considerations:
 Patients with Lamivudine resistance
 HBV/HIV coinfection
 Normal ALT levels
 Immunosuppression/Chemotherapy
 Patients to undergo Liver Transplantation
 Pregnant females
 Pediatric patients
I)Lamivudine Resistance
 Lamivudine resistance sometimes occurs with the
long term use of lamivudine; unfortunately leads to
emergence of a resistant hepatitis B virus (YMDD)
mutant.
 Lamivudine resistance increases the cross-resistance
to other nucleoside and anti-nucleotide analouges,
and limits sensitivity to entecavir.
1)Lamivudine Resistance
 Compensated Disease:
 Decompensated Disease:
 Add adefovir to
 Add adefovir to lami-
lamivudine and continue
lamivudine to decrease
risk of adefovir
resistance OR
 Switch to entecavir
monotherapy
vudine since the
consequences of of wild
type HBV returning are
potentially more
hazardous in these
patients.
2)HBV/HIV coinfection:
 HBV/HIV coinfection:
 HBV/HIV coinfected patients can be HBs Ag
negative and only anti-HBc positive.
 Lamivudine, tenofovir and emtricitabine are antiHIV medications that also possess activity against
HBV.
 Adefovir and entecavir have no activity against
HIV.
2)HBV/HIV coinfection:
 Main messages 1)Do not compromise treatment of one virus over the
other
 2)Do not rapidly discontinue HAART ( severe hepatic
flare)
 Treatment recommendations depend on whether
treatment for HIV is indicated.
2)HBV/HIV coinfection:
No Immediate
HIV Treatment
needed
• Evaluate and monitor HBV DNA, HBeAg,
and ALT
• Consider liver biopsy to determine if
treatment necessary
Immediate
HIV treatment
needed
• Evaluate and monitor HBV DNA, HBeAg,
and ALT
• Aim for HBV DNA less than 2000IU/mL
• Monitor LFT’s, esp during 1st 4-6months
as HBV levels drop and CD4 count
increases
2)HBV/HIV coinfection:
 No immediate HIV treatment required:
 If disease is active treat with entecavir, adefovir, or
PEG-IFN alfa-2a
 Avoid the antivirals with anti HIV activity (Lamivudine,
tenofovir and emtricitabine ) as resistance will arise
Immediate
treatment of HIV
required
•Two active anti-
HBV drugs and at
least 3 anti HIV
agents
•Consider interferon
for young patients
with low HBV DNA
and high ALT, CD4
> 350,CELLS/mm,
and who have not
yet received
antiretroviral
therapy
Lamivudine
resistance
present
• Use HAART that
includes tenofovir
• Use HAART that
Lamivudine
includes tenofovir
resistance
plus lamivudine or
not present
emtricitabine
3)Normal ALT Levels
If HBV DNA level is greater
than 2000 IU/L and
patient demonstrates
-Precore or core promoter
Young pt minimal
liver disease
mutant HBV
-HBeAg negativity
-Detectable anti-HBe
This is an indication that
significant HBV replication
may be present.
Patient more
than 35-40 yrs
• Immunotolerant phaseno treatment
• If ALT increasestreatment
•
•
•
•
Liver Biopsy
Treat if:
disease present
Active HBV replication
4)Immunosuppression/Chemotherapy
 Immunosuppression can reactivate chronic HBV
 Screen high risk pts for HBsAg prior to chemotherapy
 Lamivudine prophylaxis can reduce rate of HBV
reactivation, reduce severity of flares and improve
survival.
 The following are candidates for lamivudine
prophylaxis:
 HBsAg positive organ transplant recipients
 Cancer patients undergoing chemotherapy
4)Immunosuppression/Chemotherapy
Prophylaxis
• Lamivudine 100mg day orally within
one week before beginning
chemotherapy
Postchemotherapy
• Lamuvidine for greater than 12 weeks
after end of chemotherapy
• Continue for longer if prechemotherapy
HBV DNA greater than 2000 IU/L.
5)Liver Transplantation
 Transplantation has become routine for patients with




chronic hepatitisB and ESLD
Success has been enhanced by advances in antiviral
therapy
HBIG use is limited because of its high cost
Treatment recommendations depend on:
PRESENCE or ABSENCE of active viral replication
pre/post transplantation
Liver transplantation Treatment
recommendations depend on:
• Pretransplant: None Needed
• Post-transplant: HBIG 400-800IU/day q. four weeks for 2-3yrs
No Active HBV • If HBV DNA undetectable d/c HBIG or continue HBIG low dose
Replication
Active HBV
Replication
• Pretransplant: Lamivudine 100mg p.o more than 4 weeks before
transplant, aim for HBV DNA to decrease to undetectable levels
• Post-transplant: HBIG 400-800 IU/day IM for 7days, then every
4weeks for 2-3yrs
• If HBV DNA undetectable d/c HBIG or continue HBIG low dose
6)Pregnancy
 Little data on safety of antiviral drugs in pregnancy
 Avoid antiviral therapy in pregnant females unless




indicated for example there is hepatic decompensation
Vertical transmission: This implies transmission of the
hepatitis B virus from mother to infant.
Ten percent of infants born to women with acute HBV
infection during the first trimester of pregnancy are HBsAg
positive at birth.
80 to 90% of neonates become HBsAg postive without
prophylactic therapy if acute maternal infection develops
during the third trimester of pregnancy.[
To reduce risk of vertical transmission: give lamivudine in
late pregnancy to mothers with high viral load
 This variable rate of vertical transmission from
mothers with acute disease is explained by the fact
that the placenta is a reasonably effective barrier to the
spread of HBV infection.
6)Pregnancy
Reduce risk of vertical
transmission
Woman who becomes
pregnant while on
anti-HBV therapy
• Lamivudine in late pregnancy may help reduce
it, but may not prevent it if precore mutation is
present
• Continue Lamivudine treatment (100mg/day)
• Weigh stage of liver disease in mother and
potential benefit of treatment against the small
risk to the fetus
7)Pediatric Patients
 Perinatal infection is followed by a prolonged
immunotolerant phase, that is characterized by
HBeAg positivity, high HBV DNA, normal ALT
 Usually asymptomatic and histologically mild
 Monitor children regularly (liver ultrasound)
 Consider treating if ALT becomes elevated above twice
the ULN or if biopsy shows more than mild hepatitis
Children > 2 yrs, ALT> 2 x ULN
IFN alpha
(preffered)
• 6 MU/m2 SC 3 X /week for
6 months
Lamivudine
• 3mg/kg per day orally, up
to 100mg/day for 12 months
THANK YOU
FOR YOUR ATTENTION