Chronic viral hepatitis for medical students

Chronic Viral Hepatitis
Dagmawi Tewolde (Internist,
Ge fellow)

Introduction
• Chronic hepatitis represents a series of liver
disorders of varying causes and severity in which
hepatic inflammation and necrosis continue for at
least 6 months.
 Milder forms are nonprogressive or only slowly
progressive,
 while more severe forms may be associated with
scarring and architectural reorganization, which,
when advanced, lead ultimately to cirrhosis.

•Several categories of chronic hepatitis have been
recognized.
•These include
1. chronic viral hepatitis,
2. drug induced chronic hepatitis, and
3. autoimmune chronic hepatitis.

 Enveloped partially dsDNA virus
 Member of the Hepadnaviridae family
 Found in blood and all body fluids
 100 times more infectious than HIV
 Able to survive in dried blood for > than 1
week
Hepatitis B Virus

 Enveloped partially dsDNA virus
(42nm)
 Compact genomic structure (± 3.2 kb)
 4 overlapping open reading frames
 Reverse transcriptase/ DNA
polymerase domain overlaps with
surface gene
 Encodes 4 sets of viral proteins –
HBsAg, HB core Ag, viral polymerase
and HBx protein
3213 157
2856
2
4
5
8
preS1 preS2 S
8
3
4
Y
M
D
D
1376
X
1837
1816
1622
1903
2
3
0
9
DR1 DR2RNA
prim
er
EcoRI
3221, 1
c
o
r
e
precore
(+)
(-)
polymerase
Hepadnavirus
HBV Genome

1. HBV virions bind to the
hepatocyte receptor –
sodium taurocholate co-
transporting polypeptide
– and are internalized
2. In nucleus genome
repaired to form cccDNA
3. Translation of viral
mRNA to proteins in
cytoplasm
NEJM March 2004, 350;11
HBV Replication Cycle

4. Incorporation into ER
and reverse
transcription of RNA
5. Budding and secretion
of of viral cores to ER,
and packaging in Golgi
apparatus or
6. Recycling of genome
to nucleus with
repletion of
intranuclear cccDNA
NEJM March 2004, 350;11
HBV Replication Cycle (continued)

Genotype C
 Common in Asia
 More frequently associated with severe liver
disease and HCC than genotype B
Genotype B
 Associated with seroconversion from HBeAg
to anti-HBe at younger age than genotype C
Genotypes A and B
 Higher rates of antiviral response and HBeAg loss
following pegIFN alfa than genotypes D and C
Impact of HBV Genotype on
Disease Progression

sSA: HBV Genotypes and Subgenotypes
Clinical Outcomes
 Genotypes A, D and E: Predominant hepatitis B
genotypes in Africa
 Genotype A accounts for 90% of HBV infections in
Southern, Eastern, and Central Africa
 Mean age of those infected with genotype A was
6.5 years younger than those with non-A
 Predisposes to chronicity with an elevated risk of
HCC
 Increased response rates to IFN

 Genotype D –
 Genotype E – West Africa
 Genotypes D, A, F and (in Asia) B – higher rates of
HBeAg seroconversion
sSA: HBV Genotypes and
Subgenotypes
Clinical Outcomes (continued)
[
 Reduced response rates to IFN;
 Acute infection is associated with increased risk
of ALF

HBV Serologic Markers
HBsAg
 General infection marker
 First serologic marker to appear
 Infection considered chronic if persistent for > 6 months
 Indicative of number of infected hepatocytes

HBV Serologic Markers (continued)
HBeAg
Nucleocapsid antigen
Indicates active replication of virus – high infectivity
E.g. HBsAg carrier mother who are HBeAg positive
almost invariably(>90%) transmit HBV to their offspring
than HBsAg carrier mothers who are HBeAg
negative(10-15 %)
 Thus, HBeAg positivity signifies that there is ongoing
 Absent in precore or basal core promoter mutations
viral replication,
infectivity and
liver injury.

Anti-HBs (HBsAb)
 Recovery and/or immunity to HBV
 Detectable after immunity conferred by HBV
vaccination
Anti-HBe (HBeAb)
 Generally indicates virus is no longer replicating
 Present in HBeAg negative disease

Anti-HBc total (HBcAb total)
IgG core Ab
 Past exposure to HBV
IgM Core Ab
 Acute infection or reactivation
HbcAg
 HbcAg is coated by HBsAg and can’t be picked
from serum

Chronic Hepatitis B
• The likelihood of chronicity after acute hepatitis B
varies as a function of age
 Infection at birth is associated with clinically
silent acute infection but a 90% chance of
chronic infection,
 while infection in young adulthood in
immunocompetent persons is typically
associated with clinically apparent acute
hepatitis but a risk of chronicity of only
approximately 1%.

Clinical features of CHB
The spectrum of clinical features of chronic hepatitis B
is broad, ranging
 from asymptomatic infection
 to debilitating disease or even end-stage,
fatal hepatic failure.
 Fatigue is a common symptom, and
 persistent or intermittent jaundice is a common
feature in severe or advanced cases.

1. Intermittent deepening of jaundice and
2. recurrence of malaise and anorexia,
3. as well as worsening fatigue, are reminiscent of
acute hepatitis; such exacerbations;
 may occur spontaneously, often coinciding with
evidence of virologic reactivation;
 lead to progressive liver injury; and,
 when superimposed on well-established
cirrhosis, may cause hepatic decompensation.

Complications of cirrhosis occur in end-stage chronic
hepatitis and include
1. Ascites,
2. Edema,
3. Bleeding Gastroesophageal Varices,
4. Hepatic Encephalopathy,
5. Coagulopathy, Or
6. Hypersplenism.

Laboratory Findings
 Aminotransferase elevations tend to be modest for
chronic hepatitis B but may fluctuate in the range of
100–1000 units.
 ALT tends to be more elevated than AST; however,
once cirrhosis is established, AST tends to exceed
ALT.
 Levels of ALP activity tend to be normal or only
marginally elevated.

•In severe cases, moderate elevations in serum
bilirubin 3–10 mg/dL occur.
•Hypoalbuminemia and prolongation of the
prothrombin time occur in severe or end-stage cases.
Hyperglobulinemia and
detectable circulating autoantibodies are distinctly
absent in chronic hepatitis B (in contrast to
autoimmune hepatitis).
Laboratory Findings

Assessment of Liver Disease
Stage
& HBV Treatment Consideration
22

Spectrum of Disease
15 - 40%
90–95% neonatal
infection
Acute
HBV
infecti
on
Chronic
HBV
infection
Fatal
progres
sive
liver
failure
Cirrhosis
HCC
Deat
h
Decompensa
ted cirrhosis
Fulminant
hepatic
failure
0.5-1%
20-50% childhood
infection
<5% adult infection
20%/yr
<1 –5%/yr

Phase
Immune
Tolerant
Immune
Active
Immune
Control
Immune Escape
Liver
Minimal
inflammation
and fibrosis
Chronic active
inflammation
Mild hepatitis
and minimal
fibrosis
Active
inflammation
and progressive
fibrosis
Anti-HBeAg
HBV DNA
ALT activity
 Natural history is dynamic and complex.
 Phases have variable duration and are not necessarily sequential.
 All phases potentially require treatment.
HBeAg
Phases of Chronic HBV
Infection

Marker
Immune
Tolerant
Chronic HBV Disease
Immune
control
Occult
HBV
Immune
Clearance
HBeAg
Positive
Immune Escape
HBeAg Negative
HBsAg    
HBeAg  
Anti-HBe  
Anti-HBc IgG     
HBV DNA
IU/ml
>200 000 >20 000 > 2 000 < 2 000 < 200
ALT Normal ↑ ↑ Normal Normal
Immunologic Markers:
Chronic HBV Infection

HBV DNA
levels Age at infection
Host
immune
status
HBV
mutations
and
genotype
Diabetes
Mellitus
Alcohol
use
Coinfection
with HCV or
HIV
Disease
Progression
Iron
overload
HBeAg
status
Factors Influencing Natural
History

Liver Biopsy
 Liver biopsy has been considered the gold
standard to grade and stage liver disease and
assess the role of co-factors
 Standardised biopsy scoring systems - METAVIR
and Knodell and Ishak score
Stage

Stage continued..
 Not widely available in resource-limited settings
 Costly; invasive – risks of bleeding and pneumothorax
 Sampling error
 Expert histological interpretation
Liver Biopsy

Blood/Serum-based tests
 APRI
 Fib-4
 FibroTest (patented commercial test)
Transient Elastography
 Fibroscan
Assessment of Liver Disease Stage
(continued)
Non-invasive methods

Use of accurate and validated NITs in
resource-limited settings
 Will help with optimal selection of persons with
CHB for antiviral Rx
 Few validated studies in sSA
(continued)

APRI and Fib-4
 Indirect markers of fibrosis
(ALT, AST, platelets)
 Readily available in
low-/middle-income
countries
 Less costly
 No expertise required for
interpretation
 Outpatient setting
Fibrotest
 Patented commercial
test
 Expensive
 Accredited laboratory
NITs not validated to
assess all stages of
fibrosis/cirrhosis
(continued)

APRI = (AST/ULN) x 100) / platelet count (109
/L)
Validated for the diagnosis of both significant fibrosis ≥
F2 and cirrhosis (F4)
WHO Guidelines recommend the use of a single high
cut-off >2 for identifying adults with cirrhosis (F4) and in
need of antiviral therapy
FIB-4 = (age (yr) x AST (IU/L)) / (platelet count (109
/L
x [ALT (IU/L)])
Validated for the diagnosis of significant fibrosis ≥F3, but
not cirrhosis
(continued)

Transient Elastography –
Fibroscan (range is
between 0 and 75 kPa)
 Less than 10 minutes to
perform
 Outpatient / community
setting
 Costly and requires
operator training
 Regular maintenance
and recalibration
 Lack of extensively
validated cut-off values
for specific stages of
fibrosis
Uses single cut-off value:
Significant fibrosis
(≥ F2 ) >7- 8.5 kPa
Cirrhosis (F4) >11-14 kPa
Mean cut-off 12.5 kPa to
diagnose cirrhosis
(continued)

2015 WHO Guidelines for the Prevention, Care and Treatment of Persons with Hepatitis B
(continued)

 Results of NITs may be impacted by intercurrent
diseases that may falsely increase or decrease the
scores:
 Heavy alcohol intake (due to AST elevation from
alcoholic hepatitis)
 Use of drugs and traditional herbal medicines may
increase ALT/AST
 Malaria or HIV (may decrease platelet count)
 Hepatitis flares or acute hepatitis, congestive heart
failure or a recent meal may also increase high liver
stiffness (fibroscan)
(continued)

Fibroscan and APRI
 Most useful tests for
assessing cirrhosis in
LMICs (conditional
recommendation)
 PPV for detection of
cirrhosis was low for all
NITs, in particular for
APRI (detecting only 1/3
of persons with cirrhosis)
 Very limited evaluation in
sSA
FIB-4
 Not considered or
recommended
 Developed and validated
for detection of fibrosis
stages ≥F3 and not
cirrhosis
2015 WHO Guidelines for the Prevention, Care and Treatment of Persons with Hepatitis B Virus Infection
2015 WHO Guidance on
Assessing Liver Disease Stage

& HBV Treatment Considerations
Current Treatment of Chronic Hepatitis B
Chronic HBV infection: defined as persistence of
hepatitis B surface antigen (HBsAg) for six months or
more after an acute infection with HBV
Major advancements in therapeutic options – 2
major strategies
 Interferon (IFN)-based therapy
 Nucleos(t)ide analogue therapy

& HBV Treatment Considerations
(continued)
Understanding the natural history and the phase of
chronic infection
 Important in guiding treatment decisions
CURE is difficult as this is dependent on the
eradication of hepatic intranuclear HBV cccDNA

First-Line Treatment of Chronic HBV

Goals of HBV Treatment
Prevention of long-term complications of chronic
hepatitis B
 Cirrhosis
 Liver failure
 Hepatocellular carcinoma

(continued)
Difficult to measure these clinical outcomes –
surrogate measures
 Biochemical: normalization of serum ALT
 Virological
 Durable suppression to undetectable HBV DNA
 Durable HBeAg loss or seroconversion to anti-Hbe
 Durable HBsAg loss seroconversion to anti-HBs
status
 Histological
 Decrease in necro-inflammatory score
 Possibly regression of fibrosis on liver biopsy

(continued)
 Aim to reduce number
of infected hepatocytes
& reduce HBV viral
replication level
 HBsAg serum levels
reflect the
transcriptionally
active cccDNA
 HBsAg serum levels
lowest in immune
control phase
Gut 2002 50(1):100
 HBsAg clearance is
associated with:
 reduced incidence of
cirrhosis
 reduced incidence of
HCC
 improved survival
HBsAg clearance is the ideal endpoint of
therapy

(continued)
CURE IS DEPENDENT ON
ERADICATION OF cccDNA
HBsAg clearance is the closest
to cure in chronic HBV

Who to treat
• As a priority, all adults & adolescents with CHB and
 ALT levels
 HBeAg status or
 HBV DNA levels.
 Strong recommendation,
 moderate quality of evidence
clinical evidence of compensated or
decompensated cirrhosis
or cirrhosis based on APRI score >2 in adults
should be treated, regardless of

Treatment is recommended for adults with CHB
who do not have clinical evidence of cirrhosis (or
based on APRI score ≤2 in adults), but
Who to treat
are aged more than 30 years (in particular), and
have persistently abnormal ALT levels and
evidence of high-level HBV replication (HBV DNA >20 000
IU/mL), regardless of HBeAg status.
Strong recommendation
moderate quality of evidence)

Where HBV DNA testing is not available:
Treatment may be considered based on
persistently abnormal ALT levels alone,
regardless of HBeAg status.
Who to treat
 Conditional recommendation
 low quality of evidence

Who not to treat but continue to monitor
Antiviral therapy is not recommended and can be deferred in
persons
without clinical evidence of cirrhosis (or APRI score
≤2 in adults), and
with persistently normal ALT levels and
low levels of HBV DNA replication (HBV DNA <2000
IU/mL), regardless of HBeAg status or age.
 (Strong recommendation,
 low quality of evidence)

Who not to treat but continue to monitor
Where HBV DNA testing is not available: Treatment
can be deferred in HBeAg-positive persons
 aged 30 years or less and
 persistently normal ALT levels.
 Conditional recommendation
 low quality of evidence)

Treatment Strategies for
Chronic HBV
Nucleos(t)ide analogue
therapy
 Antiviral activity
 Long-term (potentially
indefinite) treatment
 Aim for on-treatment viral
suppression (HBV DNA -)
 Maintained through
continuous antiviral therapy
 Suppression of replication
to undetectable levels to
avoid resistance
Interferon (IFN)-based
therapy
 Dual Antiviral and
immunomodulatory activity
 Finite course of treatment
 Aim for sustained off-
treatment immune control
( HBsAg +, HBeAg, and
HBV DNA <2,000 IU/ml)
through dual mode of action
 Successful in 30-50%
patients

Approved Therapeutic Options for
HBV
• Sub-Saharan Africa
 Lamivudine and tenofovir
widely available as part of
HIV antiretroviral therapy
 Not always accessible
for Rx of HBV
monoinfection
 Entecavir not widely
available, no generics
 Standard interferon
 Pegylated interferon
 Lamivudine
 Telbivudine
 Entecavir
 Tenofovir 
emtricitabine

Factors Favoring IFN as Initial
Therapy
 Patient preference
 No coinfection with HIV
 Concomitant HCV or
HDV infection
 Specific patient
demographics
 Younger individuals
 Young woman wanting
future pregnancy
 Favorable predictors of
response
 Genotype A or B > C or D
 Low HBV DNA
 baseline <2x106
- 2x108
IU/mL
 12 weeks <20 000 IU/mL
 High ALT (baseline) >2-5x
ULN
 High activity scores on
biopsy (A2)

Factors Associated with Choosing
Nucleos(t)ides as Initial Therapy
 Favourable predictors of
response
 High ALT
 Low HBV DNA
(baseline < 1x107
IU/mL
and on treatment)
 Specific patient
demographics
 Older people
 Patient preference
 Concomitant HIV
infection
 No HCV coinfection
 Cirrhosis

HBV Treatment Strategies
What is the best HBV treatment in our setting?
 Interferon (IFN)-based therapy has best chance of
HBsAg eradication
with finite Rx
BUT interferon (IFN) has limitations in sub-
Saharan Africa:
 Long immune tolerant phase
 High HBV DNA levels and often minimal necro-
inflammation
 Liver biopsy assessment is advisable
 Expensive and close monitoring required

Majority of HBV Rx candidates in sub-Saharan Africa not suitable
for IFN-based Rx
2015 WHO HBV Guidelines recommend entecavir and tenofovir as
first-line Rx
HBV Treatment Strategies

Efficacy: Tenofovir and
Entecavir
Network meta-analysis
 21 pair-wise comparison RCTs comprising 5073
HBeAg positive nucleoside-naïve persons
 16 trials comprising 2604 HBeAgnegative
nucleoside-naïve persons
Tenofovir monotherapy had highest probability of
achieving undetectable HBV DNA at end of 1 year
of Rx
 HBeAg-positive 94.1% (95% CI: 74.7–98.9%)
 HBeAg-negative 97.6% (95% CI: 56.7–99.9%)

Entecavir monotherapy: Undetectable HBV DNA at end
of 1 year of Rx
 HBeAg-positive 64.5% (95% CI: 49.1–80.5%)
 HBeAg-negative 91.9% (95% CI: 87.3–95.1%)
All other antiviral therapies had very low probability of
achieving this outcome
Efficacy: Tenofovir and
Entecavir (continued)

Long-Term Effectiveness of
Entecavir and Tenofovir after 3
and 5 Years
 Mortality
 Entecavir : 3% and
3.8%
 Tenofovir : 0.7% and
1.4%
 HCC
 Entecavir: 3.9% and
6.6%
 Tenofovir: 1.4% and
2.4%
 Genotypic resistance
 Entecavir at 5 years of Rx
(0.8-1.2%)
 Tenofovir: no resistance
at 8 years
Low cumulative rates of:

Recommended NAs and Dosages
for Adults

Assessment Prior to Treatment
Initiation
 Assess severity of chronic liver disease
 Assessment of the level of viral replication
 HBV DNA, HBeAg and HBeAb status (if
available)
 Assessment for the presence of co-morbidities
 Lifestyle counseling
 Preventive measures
 HBsAg screening with HBV vaccination of non-
immune family members and sexual contacts

Preparation for HBV Treatment
Patient counseling
 Indications for
treatment
 Benefits and side-
effects of treatment
 Need for and
willingness to commit
to long-term treatment
 Need for follow-up
monitoring both on and
off therapy
 Importance of full
adherence for treatment
 efficacy of treatment
 Risks of non-adherence
 risk of drug resistance
 progression of disease
 risk of acute liver failure
with abrupt cessation of
treatment
 Cost implications of
treatment and follow up

Toxicity of NAs
Nephrotoxicity: Assess renal function before NA
initiation
 Serum creatinine level
 Estimated glomerular filtration rate
 Urine dipsticks for proteinuria and glycosuria

Toxicity of NAs (continued)
 Risk factors for renal dysfunction
 decompensated cirrhosis
 CrCl <50 mL/min
 poorly controlled hypertension and diabetes
 proteinuria, active glomerulonephritis
 solid organ transplantation
 older age, BMI <18.5 kg/m2 or body weight <50 kg
 boosted protease inhibitor for HIV
 concomitant nephrotoxic drugs
Monitoring should be more frequent in those at higher
risk of renal dysfunction

Toxicity of NAs (continued)
Nephrotoxicity: Assess renal function before NA
initiation
 solid organ transplantation
 older age, BMI <18.5 kg/m2 or body weight <50 kg
 boosted protease inhibitor for HIV
 concomitant nephrotoxic drugs
Monitoring should be more frequent in those at higher
risk of renal dysfunction

Monitoring Long-Term NA Therapy
 HBV DNA every 6 -12
months
 HBsAg and HBeAg
every 6-12 months
 ALT and AST (for
APRI) annually
 Renal function
(annually)
 more frequently if risk
factors for renal
dysfunction
 Adherence to therapy
 Monitor for HCC
 alpha-fetoprotein and
Ultrasound liver every
6-12 months
Long-term NA therapy

Stopping NA Therapy
CIRRHOSIS
 Lifelong NA therapy
HBeAg positive chronic HBV
Consider stopping treatment if:
 HBeAg loss and seroconversion to anti-HBe after completion
of at least one additional year of treatment + persistently
normal ALT + persistently undetectable HBV DNA
 Need close monitoring after treatment cessation (20% may
relapse)
NO CIRRHOSIS

Stopping NA Therapy (continued)
HBeAg negative chronic HBV
 Lifelong NA therapy
Most patients with chronic HBV in sub-Saharan Africa
will need lifelong therapy
NO CIRRHOSIS

Conclusions: First-Line HBV
Treatment
 CURE is dependent on the eradication of intranuclear HBV
cccDNA
 HBsAg clearance is the closest to cure in chronic HBV
 Tenofovir, entecavir, and peginterferon are preferred first-line
drugs
 3rd generation NAs have high efficacy, very low rates of
resistance & excellent safety record, but therapy is
potentially lifelong
 PEG-IFN offers finite therapy & chance for cure through
dual antiviral and immunomodulatory action
 Majority of treatment candidates in sub-Saharan Africa are not
suitable for IFN-based treatment

Conclusions: First-Line HBV
Treatment (continued)
 2015 WHO HBV Guidelines recommend tenofovir
and entecavir
 Tenofovir has excellent resistance profile and 10%
HBsAg seroconversion at 8 years
 Sustainable access to affordable generic NAs
essential in sub-Saharan Africa, including for HBV
monoinfection

HBV and Pregnancy
Management
Considerations

HBV and Pregnancy
Natural History and Pregnancy
Outcomes
Conflicting data on natural history
 No worsening of liver disease in most women
 Case reports suggest HBV reactivation, hepatic exacerbations
and fulminant liver failure may occur
Adverse pregnancy outcomes – some reports of higher
rates of:
 Preterm births
 Gestational diabetes
 Antepartum hemorrhage
HBsAg positive mothers need close follow up during
pregnancy

Hepatitis B Screening in
Pregnancy
HBsAg screening of pregnant women essential:
AASLD and EASL
 First trimester of each pregnancy
 Pregnant women not immune to HBV and with risk
factors for infection should be vaccinated against HBV –
SAFE IN PREGNANCY
 Ongoing high-risk behavior during pregnancy and
HBsAg status unknown
 test for HBsAg at admission for delivery
 HBsAg positive women should be referred for additional
testing, counseling and medical management

HBV Management Strategies in
Pregnancy
Requiring HBV treatment and considering pregnancy
 Finite course IFN Rx (if favorable clinical profile) before
pregnancy
 If clinically stable, can defer treatment until after pregnancy
 Consider antiviral treatment in 3rd
trimester to prevent MTCT
Pregnant whilst on HBV treatment
 Consider need for treatment and risk of MTCT
 Review type of treatment
 Stop IFN and switch to antivirals
Pregnant and treatment not clinically indicated for HBV
infection
 Defer treatment until after pregnancy and then reassess need
 Consider antiviral treatment in 3rd
trimester to prevent MTCT

HBV Treatment in Pregnant Women
 Indications for Rx in HBV-
infected pregnant mother
same as usual indications:
 Drug of choice is
tenofovir
 similar rate of birth
defects to general
population
 Interferon is
contraindicated
 Risk of HBV flare -
close monitoring
required
 mother is untreated
 if antivirals stopped
during pregnancy or
soon after delivery

HBV Mother-to-Child
Transmission
 Over 60 million new HBV infections per annum
 The majority of infections are acquired in the
perinatal/neonatal period or in early childhood
 Perinatal infections are the reservoir of infections
in high endemic areas e.g. China, South-East Asia
 Horizontal transmission in early childhood from
infected family members (6 months to 5yrs)
accounts for most infections in sub-Saharan Africa

Perinatal HBV Transmission
Perinatal infection occurs:
 In utero (uncommon)
 During delivery
 After birth
 Breastfeeding (controversial)
J Med Virol 2002;67(1):20

Risk Factors for Perinatal HBV
Transmission
 HBeAg positive mother
 >90% risk of infecting child with no treatment
 High maternal HBV DNA (>7.3 log10 IU/mL)
 Maternal acute HBV in 2nd
or 3rd
trimester or within
2 months of delivery
 Risk reduced to <10 % with active-passive
immunization
J Viral Hepat 2009;16(2):94; J Viral Hepat 2003;10(4):294

Prevention of Mother-to-Child
Transmission of HBV
• Significant relationship between maternal HBV DNA
level and rate of persistent infection in infant (> 8
log10 copies/mL or ~ 7.3 log10 IU/mL)
 HBeAg negative and positive mothers
 Treatment with lamivudine or tenofovir should be considered in
3rd
trimester in mothers with high viraemia to prevent MTCT;
tenofovir preferred antiviral
 If therapy is administered only for prevention of MTCT; may be
discontinued within the first 3 months after delivery
 Role of elective Cesarean section in preventing HBV MTCT
conflicting; not currently recommended
 Antiviral therapy for MTCT prevention must be combined
with neonatal HBV vaccination

Prevention of HBV with
Vaccination
 Current WHO guidelines recommend universal HBV vaccination
 WHO recommends birth dose of HBV vaccination in all endemic
countries
 HBV Vaccination ± HBIG prevents transmission in 80-95% cases
 monovalent HBV vaccine given within 24 hours, ideally within
12 hours
 followed by two or three doses to complete the primary series
 subsequent vaccines can be monovalent or combination
 doses 2 and three can be given at the same time as DTP
 Most sub-Saharan African countries administer HBV vaccine
at 6, 10, and 14 weeks

Passive Immunity with HBIG
 HBIG provides temporary immunity: 3-6 months
 HBIG prophylaxis plus HBV vaccination may be of
additional benefit for the following newborns if:
 Mothers HBsAg positive, HBeAg positive
 Mothers HBsAg positive, HBeAg negative, high HBV
DNA levels
 Full-term neonates born to mothers HBsAg
positive, HBeAg negative and low HBV DNA levels
 Protection against perinatally acquired infection achieved
by immediate vaccination against HBV (given within 24
hours) may not be significantly improved by the addition
of HBIG
2015 WHO Guidelines for the prevention, care and treatment of persons with

Risk of HBV Transmission
from Breastfeeding
 HBsAg detected in breast milk
 HBV vaccination plus HBIG gives protection
 No difference in rates of HBV infection in breastfed
versus bottle-fed babies
 Breast feeding not contraindicated
 stop if cracked or bleeding nipples
 concern if high maternal HBV DNA
 No data on effects on the infant of exposure to NAs
during breastfeeding

Conclusions: HBV and Pregnancy
 All pregnant women must be tested for HBsAg
 All neonates born to HBsAg positive mothers must receive
birth dose of HBV vaccine ± HBIG and complete vaccine
series
 High HBV DNA levels, typically observed in HBeAg positive
women
 ≥10% risk of transmission despite HBIG and vaccine
prophylaxis
 Consider tenofovir therapy in 3rd
trimester to prevent MTCT of
HBV
 Indications for HBV therapy in pregnancy are same as for
non-pregnant women
 Close follow-up for 6 months post-partum; risk of flares if not
on therapy or therapy stopped during pregnancy

• HBV/HCV
• HBV/HIV
• HBV/HDV
• HBV infection in Pregnancy
• Chemotherapeutic/Immunosuppressive therapy
Special Populations

• HBV/HCV – Treatment is for the dominant infection (the one
with higher viral load).
• HBV/HIV – Simultaneous treatment of both infections
required using TDF + LAM/emtricitabine + non nucleoside
reverse transcriptase inhibitor or protease inhibitor.
• HBV/HDV – Treatment is with PEG IFN for 48 weeks
Co-infection with HBV

• Reactivation of HBV may occur if an inactive CHB case is
inadvertently placed on chemotherapy.
• Any patient for immunosuppressive/chemotherapy should be
screened for HBV with HBsAg and if positive, should be
commenced on TDF or ETV at least one week before initiation
of chemotherapy and continued for 6 months after cessation.
Chemotherapy and immunosuppressive
therapy

Chronic viral hepatitis for medical students

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