Viral Hepatitis MIU BCPS 2015

Taher Hegab, PharmD, PhD, BCPS
Review the treatment and prevention of both

acute and chronic viral hepatitis.
Viral Hepatitis Taher Hegab 2015
IDSA practice guidelines update: Chronic

hepatitis B updates, 2009
Anna S.F. Lok and Brian J McMahon: AASLD Practice
Guidelines. Hepatology. Sept 2009 p1-36.
Recommendations for Testing, Managing, and

Treating Hepatitis C 2014,
Guidelines by AASLD and IDSA
Hepatitis A
Fecal-oral spread: hygiene, drug use, sexual, travelers, day care,
food
Vaccine-preventable
Self resolving, very low mortality
Hepatitis B
sexually transmitted 100x more infectious than HIV

blood-borne (sex, injection drug use, mother-child, and health
care)
vaccine-preventable
Chronicity: 2-10%
Hepatitis C
blood borne (e.g. injection drug use) 10x more infectious than
HIV
5 times more prevalent than HIV in the US
Major problem in Egypt
NOT vaccine-preventable!
Chronicity: 85%
Hepatitis D
Only in patients co-infected with hepatitis B
Highest mortality rate of all hepatitis viruses (20%)
Transmission:
Incubation:
Fecal-oral spread: hygiene, drug use, sexual, travelers, day care, food (Water,
milk, shellfish, vegetables)
14-50 days
Symptoms:
Jaundice, fever, malaise, anorexia, nausea, vomiting, diarrhea, myalgia, fever,
abdominal pain
Self resolving within 2 month
Very low mortality (less than 1%), associated with fulminant

hepatitis
No chronocity
Diagnosis
Clinical signs and symptoms
Recent possible exposures
Laboratory data
Elevation of aminotransferases
IgM antibody to HAV (anti-HAV): before and during
infection. Presence indicate active or recent infection
IgG antibodies indicate previous infection and
provide lifelong protective immunity against
subsequent infection.
Interpretation of HAV serology data:

Lab test
Result
Interpretation
IgM anti HAV

IgG anti HAV
Negative
Negative
Susceptible to
infection
IgM anti HAV
Positive
Active infection
IgG anti HAV
Positive
Immune due to
natural infection or
vaccination
Management:
Supportive: bed rest and fluids

Avoid hapatotoxic medications
Pre-exposure prophylaxis:
Active with vaccinations
Havrix (GlaxoSmithKline)
Vaqta (Merck)
Twinrix: combination HAV and HBV product
(GlaxoSmithKline)
Pasive with immunoglobulins:

IGIM
Populations requiring pre-exposure

prophylaxis with HAV vaccine (CDC
recommendations):
All children at age 1 year

Travelers to countries where Hepatitis A is common
Family and caregivers of recent adoptees from
countries where Hepatitis A is common
Men who have sexual encounters with other men
Users of recreational drugs, whether injected or not
People with chronic or long-term liver disease,
including Hepatitis B or Hepatitis C
People with clotting-factor disorders
http://www.cdc.gov/hepatitis/A/PDFs/HepAGeneralFactSheet.pdf
10
Populations requiring HAV pre-exposure

prophylaxis with immune globulin:
Travelers to endemic countries
Children younger than 1 year (vaccine not approved
for this age group)
Doses: 0.02 mL/kg intramuscularly (3 months
coverage or more); 0.06 mL/kg intramuscularly (35
months coverage); repeat every 5 months if travel
or exposure is prolonged
Use IGIM not IGIV

11
Post-exposure prophylaxis:
IGIM: 0.02 mL/kg intramuscularly within 2 weeks of

exposure
HAV vaccination (for individual 12 months to 40
years of age)
Offer to those not previously vaccinated in

the following situations
Close personal contact with a documented infected

person
Staff and attendee of day care centers if on the
employee or the staff was diagnosed with HAV
12
A 50-year-old woman is seeking advice

regarding a recent possible exposure to
hepatitis A virus (HAV).
She saw on the local news report that a chef
at a local restaurant where she had eaten
about 3 weeks ago had active HAV. Having
heard that HAV could be transmitted through
food,
She would like to know her options. She has
not previously received the HAV vaccine.
13
A.
B.
C.
D.
Which is the best recommendation for this

patient?
Initiate HAV vaccine.
Administer HAV immune globulin.
Continue to observe the patient for
symptoms.
Initiate HAV vaccine and immune globulin.
14
A.
B.
C.
D.
Which is the best recommendation for this

patient?
Initiate HAV vaccine.
Administer HAV immune globulin.
Continue to observe the patient for
symptoms.
Initiate HAV vaccine and immune globulin.
The period for administration should
be within 14 days of exposure
15
DNA virus; there are more than 350 million infected

patients worldwide.
Transmission routes
Can be acute or chronic disease
Parenteral: Intravenous drug abuse, needle stick, transfusion,

ear or body piercing
Bodily fluids: saliva, semen, vaginal fluids
Sexual contact: Heterosexual and homosexual; prostitution
Perinatal: Mother to child at birth
Risk of developing chronic infection after an acute infection is

90% in neonates, 25%30% in children younger than 5 years,
and 10% in adults.
Chronic infection with HBV increases the risk of developing
hepatocellular carcinoma
16
Diagnosis:
Clinical signs and symptoms:
Nausea, vomiting, diarrhea, myalgia, fever,
abdominal pain, jaundice (30% may have no
symptoms)
Liver function tests

Serology
17
18
Test
Results
Interpretation
HBsAg
anti-HBc
anti-HBs
Negative
Negative
Negative
Susceptible
(Never infected or vaccinated)
HBsAg
anti-HBc
anti-HBs
Negative
Negative
Positive
Immune
(Due to vaccine)
HBsAg
anti-HBc
anti-HBs
Negative
Positive
Positive
Immune
(Resolved Infection)
HBsAg
anti-HBc
IgM anti-HBc
anti-HBs
Positive
Positive
Positive
Negative
Acutely Infected
HBsAg
anti-HBc
anti-HBs
IgM anti-HBc
Positive
Positive
Negative
Negative
Chronically Infected
HBsAg
anti-HBc
anti-HBs
Negative
Positive
Negative
Four Possible Interpretations

19
HBsAg
anti-HBc
anti-HBs
Negative
Positive
Negative

1.
2.
3.
4.
Resolved infection (most common)

False-positive anti-HBc, thus susceptible
Low level chronic infection
Resolving acute infection
20
Screening:
Use HBV surface antigen (HBsAg)
Screening recommended in the following

population:
Pregnant women, Infants born to HBsAgpositive mothers
Past or current intravenous drug users
People with elevated ALT/AST of unknown etiology
HIV infected patients
Donors of blood, plasma, organs, tissues, or semen
Household contacts and sex partners of HBV
People born in geographic regions with HBsAg prevalence
greater than 2%
Men who have sex with men
21
Chronic infection versus carrier
22
Treatment is supportive.
Antiviral therapy generally not necessary for

symptomatic acute hepatitis B
Fluids and antiemetics
consider treatment for patients with:
fulminant hepatitis B
protracted, severe acute hepatitis B (increase in INR, severe
jaundice > 4 weeks)
Treatment options:
lamivudine or telbivudine if anticipated duration of

treatment is short otherwise entecavir preferred for all other
situations
interferon alfa is contraindicated in acute illness
23
24
Goals of treatment:
sustained suppression of HBV replication
remission of liver disease
prevention of cirrhosis, hepatic failure, and
hepatocellular carcinoma
Need to distinguish if HBV is:

HBeAg positive or negative
Harbour YMDD mutation of DNA polymerase
Indicate resistance to lamivudine and telbivudine
25
HBeAg positive chronic hepatitis B

consider treatment if
ALT > 2 times normal and HBV DNA > 20,000

units/mL
liver biopsy shows moderate-to-severe inflammation
or significant fibrosis
in patients with compensated liver disease, consider

3-6 month delay of treatment to determine if
spontaneous HBeAg seroconversion occurs
patients with icteric ALT flares should be treated
promptly
26
27
HBeAg-negative chronic hepatitis B
consider treatment if ALT > 2 times normal and HBV

DNA > 20,000 units/mL (AASLD Grade I)
if HBV DNA > 2,000 units/mL and ALT 2 times upper
limit of normal
consider liver biopsy (AASLD Grade II-2)
treatment may be started if liver biopsy shows either of
(AASLD Grade I)
moderate-to-severe inflammation
significant fibrosis
treatment may be considered in patients with HBV DNA

2,000-20,000 units/mL, especially in older patients and
patients with cirrhosis
28
29
treatment options
Interferons
Peginterferon alfa-2a (long-acting) -180 mcg
subcutaneously once weekly for 48 weeks (AASLD
Grade I)
interferon alfa 2b (short-acting)
adult dose 5 million units/day or 10 million units 3
times/week subcutaneously (AASLD Grade I)
pediatric dose 6 million units/m2 (maximum 10 million
units) 3 times/week subcutaneously (AASLD Grade I)
interferon therapy contraindicated with advanced

cirrhosis
30
Reverse transcriptase inhibitors
Preferred agents:
Entecavir
0.5 mg orally once daily in treatment-naive patients

1 mg orally once daily in patients with lamiduvine-refractory infection
Tenofovir 300 mg orally once daily
Second line:
Lamivudine 100 mg orally once daily (not recommended in patients

coinfected with HIV)
Telbivudine 600 mg orally once daily

Adefovir 10 mg orally once daily (not recommended in patients with
HIV/hepatitis B co-infection who are not receiving concurrent HIV
treatment due to risk for emergence of HIV resistance)
31
Interferons adverse effects:
Bone marrow suppression

Psychiatric side effects
Flu like symptoms
Anorexia, alopecia, thyroid dysfunction, neuropathy
Reverse transcriptase inhibitors:
Rebound hepatitis upon discontinuation

N/V/abdominal pain
Lactic acidosis (black box warning)
Reduction in BMD
Nephrotoxicity (Adefovir)
CK elevation, peripheral neuropathy (Telbivudine)
32
treatment duration
interferon treatment regimen duration may range
from 12-48 weeks
nucleoside analogue treatment regimen duration
may range from 48-52 weeks
if HBeAg positive, goal of treatment is
seroconversion from HBeAg to anti-HBe antibody
33
34
Biochemical:
Liver function tests
Virologic:
Decrease of HBV DNA to undetectable level
Loss of HBeAg if HBeAg positive
Non-responders:
decrease in HBV DNA of less than 2 log/mL after
at least 24 weeks of therapy
Should receive alternate therapy
35
45 YO women with history of IVDA,

diagnosed 8 month with HBV. Treatment
nave no ascites, no encephalopathy.
AST 650 IU/mL, ALT 850 IU/mL
SCr 0.9 mg/dL, INR 1.3, and albumin 3.9
g/dL
HBsAg (+), HBeAg (+), YMDD mutation
HBV DNA 100,700 IU/mL
Biopsy: severe necroinflammation/bridging
fibrosis
36
Which is the best course of action?

A. Withhold drug therapy and recheck HBV DNA in 6
months.
B. Initiate PEG-IFN-2a plus ribavirin.
C. Initiate lamivudine 100 mg/day.
D. Initiate tenofovir 300 mg/day.
37
Which is the best course of action?

A. Withhold drug therapy and recheck HBV DNA in 6
months.
B. Initiate PEG-IFN-2a plus ribavirin.
C. Initiate lamivudine 100 mg/day.
D. Initiate tenofovir 300 mg/day.
38
39
HBV IG IM within 7 days of exposure PLUS

vaccination series
Children born to HBsAg-positive mothers
should receive vaccine plus HBV immune
globulin within 12 hours of birth.
40
Genotype 1-6
Genotype 1 most common in US
Genotype 4 most common in Egypt
Major cause of chronic liver disease

Main cause of liver transplant
60-85% of patient will develop chronic
disease
41
Blood born (transfusion, IV drug use)
Low risk of transmission:
Snorting cocaine or other drugs

Occupational exposure
Tattooing
From pregnant mother to child
Sexual transmission
Nonsexual household contacts (rare)
Sharing razors and tooth brush
42
43
Serum Anti HCV antibodies

Serum HCV RNA
Qualitative to confirm +ve antibody test
Quantitatively (viral load) to monitor response to
treatment
Genotype testing to guide treatment option
44
45
46
Acute HCV infection

Treat with interferon based therapy for 12-24
weeks
May add ribavirin
May delay for 8-12 weeks to assess for

spontaneous resolution
Treatment may prevent development of chronic
infection
47
Goal of therapy
Attain SVR
(persistent absence of HCV RNA in serum 6 months or
more after completing antiviral treatment)
Prevent progression to cirrhosis
Current guidelines at hcvguidelines.org
48
Treatment is widely recommended for patients

with elevated (ALT) levels who meet the following
criteria:
Age greater than 18 years
Positive HCV antibody and serum HCV RNA test results
Compensated liver disease (e.g. no hepatic
encephalopathy or ascites)
Acceptable hematologic and biochemical indices
(hemoglobin at least 13 g/dL for men and 12 g/dL for
women; neutrophil count >1500/mm3, serum creatinine
< 1.5 mg/dL)
Willingness to be treated and to adhere to treatment
requirements
No contraindications for treatment
49
Traditional therapy with pegylated interferon

plus ribavirin
Many new agents (direct-acting antiviral
(DAA) agent)
Continuous update of the guidelines at
hcvguidelines.org
50
Oral nucleoside analog
Ribavirin is associated with dose related

anemia
May require discontinuation of therapy or treatment

with erythropoietin
Category X drug
Require negative pregnancy test, two forms of

barrier contraception during and 6 month after
treatment
51
NS3/4A Protease inhibitors

Telaprevir, Boceprevir, Semiprevir, Paritaprevir
NS5A polymerase inhibitor

Ledipasvir, Ombitasvir
NS5B Nucleoside inhibitor

Sofosbuvir
NS5B non-Nucleoside inhibitor

Dasabuvir
52
Drugs
Duration
Ledipasvir (90 mg)/sofosbuvir (400 mg)

(Harvoni, Gilead)
12 weeks
Paritaprevir (150 mg)/ritonavir (100

mg)/ombitasvir (25 mg) (Viekirax, AbbVie)
Plus
twice-daily dosed dasabuvir (250 mg)
(Exviera, AbbVie)
12 weeks
Daily Sofosbuvir (400 mg) (Sovaldi, Gilead)

Plus
Simeprevir (150 mg) (Olysio, Janssen)
With or without
weight-based RBV (1000 mg [<75 kg] to
1200 mg [>75 kg])
12 weeks (no
cirrhosis)
24 weeks
(cirrhosis)
24 weeks
(cirrhosis)
53
Drugs
Duration
ledipasvir (90 mg)/sofosbuvir (400 mg)
12 weeks
Daily Paritaprevir (150 mg)/ritonavir (100

mg)/ombitasvir (25 mg)
Plus
12 weeks (no
cirrhosis)

Plus
Plus
weight-based RBV (1000 mg [<75 kg] to 1200 mg
[>75 kg])
12 weeks
(cirrhosis)
Daily sofosbuvir (400 mg) plus simeprevir (150 mg)
12 weeks
54
Daily sofosbuvir (400 mg) and weight-based

RBV (1000 mg [<75 kg] to 1200 mg [75 kg])
for 24 weeks.
PEG-IFN and RBV with or without sofosbuvir,
simeprevir, telaprevir, or boceprevir for 12
weeks to 48 weeks.
Monotherapy with PEG-IFN, RBV, or a directacting antiviral
55
Daily Sofosbuvir (400 mg)

Plus
weight-based RBV (1000 mg [<75 kg] to 1200 mg
[>75 kg])
For
12 weeks
Extending treatment to 16 weeks is

recommended in patients with cirrhosis
56
PEG-IFN and RBV for 24 weeks

Telaprevir-, boceprevir-, or ledipasvircontaining regimens
57

Plus
weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg])
For
24 weeks
Alternative regimen:
Plus
weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg])
Plus
plus weekly PEG-IFN
For
12 weeks
58
PEG-IFN and RBV for 24 weeks to 48 weeks

Telaprevir-, boceprevir-, or simeprevir-based
regimens should not be used for patients
with genotype 3 HCV infection.
59
Drugs
Duration
12 weeks

Plus
weight-based RBV
12 weeks
Daily sofosbuvir (400 mg)

Plus
weight-based RBV
24 weeks
60
Alternate regimens
Drugs
Duration

Plus
weight-based RBV
Plus
weekly PEG-IFN
12 weeks

Plus
Simeprevir (150 mg)
with or without
weight-based RBV
12 weeks
61
PEG-IFN and RBV with or without simeprevir

for 24 weeks to 48 weeks
Telaprevir- or boceprevir-based regimens
62
Treatment-naive patients:
Alternative regimen for treatment-naive patients

Plus
weight-based RBV
Plus weekly
PEG-IFN
For
12 weeks
weight-based RBV
Plus weekly
PEG-IFN
For
24 weeks
63

For
12 weeks
Alternative regimen for treatment-naive patients

Plus
weight-based RBV
Plus weekly
PEG-IFN
For
12 weeks
64

Telaprevir- or boceprevir-based regimens
65
No vaccine or immune globulin available

Risk factor modification:
IVDA
Sexual contacts (barrier contraception)
Avoid blood exposure (sharing razors, tooth brush
etc.)
HAV and HBV vaccination
66
Pharmacotherapy: Principles and Practice. Third

edition
ACCP Updates in Therapeutics 2014:
Pharmacotherapy Preparatory Review and
Recertification Course
67

Viral Hepatitis MIU BCPS 2015

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Taher Hegab, PharmD, PhD, BCPS

Review the treatment and prevention of both

Viral Hepatitis Taher Hegab 2015

IDSA practice guidelines update: Chronic

Recommendations for Testing, Managing, and

Viral Hepatitis Taher Hegab 2015

sexually transmitted 100x more infectious than HIV

Viral Hepatitis Taher Hegab 2015

Viral Hepatitis Taher Hegab 2015

Jaundice, fever, malaise, anorexia, nausea, vomiting, diarrhea, myalgia, fever,

Self resolving within 2 month

Very low mortality (less than 1%), associated with fulminant

Viral Hepatitis Taher Hegab 2015

Viral Hepatitis Taher Hegab 2015

Interpretation of HAV serology data:

IgM anti HAV

IgM anti HAV

IgG anti HAV

Viral Hepatitis Taher Hegab 2015

Supportive: bed rest and fluids

Pasive with immunoglobulins:

Viral Hepatitis Taher Hegab 2015

Populations requiring pre-exposure

All children at age 1 year

Populations requiring HAV pre-exposure

Use IGIM not IGIV

IGIM: 0.02 mL/kg intramuscularly within 2 weeks of

Offer to those not previously vaccinated in

Close personal contact with a documented infected

Viral Hepatitis Taher Hegab 2015

A 50-year-old woman is seeking advice

Which is the best recommendation for this

Viral Hepatitis Taher Hegab 2015

Which is the best recommendation for this

DNA virus; there are more than 350 million infected

Can be acute or chronic disease

Parenteral: Intravenous drug abuse, needle stick, transfusion,

Risk of developing chronic infection after an acute infection is

Viral Hepatitis Taher Hegab 2015

Liver function tests

Viral Hepatitis Taher Hegab 2015

Viral Hepatitis Taher Hegab 2015

Four Possible Interpretations

Four Possible Interpretations

Four Possible Interpretations

Resolved infection (most common)

Viral Hepatitis Taher Hegab 2015

Screening recommended in the following

Viral Hepatitis Taher Hegab 2015

Chronic infection versus carrier

Viral Hepatitis Taher Hegab 2015

Antiviral therapy generally not necessary for

Fluids and antiemetics

consider treatment for patients with:

lamivudine or telbivudine if anticipated duration of

Viral Hepatitis Taher Hegab 2015

Viral Hepatitis Taher Hegab 2015

Need to distinguish if HBV is:

Viral Hepatitis Taher Hegab 2015

HBeAg positive chronic hepatitis B

ALT > 2 times normal and HBV DNA > 20,000

in patients with compensated liver disease, consider

HBeAg-negative chronic hepatitis B

consider treatment if ALT > 2 times normal and HBV