World Hepatitis Day 2017:

Advanced management of
Hepatitis B & C

Dr. Shamshad Khan

MBBS,MRCP
Specialist, Internal Medicine
United Hospital, Dhaka
 World Hepatitis Day
• World Hepatitis Day is recognized annually on July 28th,
the birthday of Dr. Baruch Blumberg (1925-2011).
• Dr. Blumberg discovered the hepatitis B virus in 1967
and two years later developed the first hepatitis B
vaccine and for these achievements won the Nobel
Prize.
• The theme for this year’s global campaign is “Prevent
Hepatitis: It's up to you”.
• Viral hepatitis affects 400 million people globally and,
given the size of the epidemic, anyone and everyone can
be at risk.
• An estimated 95% of people with hepatitis are unaware
of their infection.
Ref: http://www.cdc.gov/hepatitis/worldhepdayresources.htm
 World Hepatitis Day

• Viral hepatitis is a major global health threat with around

240 million people living with chronic hepatitis B and up
to 150 million people living with chronic hepatitis C
• While many people worry more about contracting AIDS
than hepatitis, the reality is that every year 1.5 million
people worldwide die from either hepatitis B or C faster
than they would from HIV/AIDS.

Ref: http://www.cdc.gov/hepatitis/worldhepdayresources.htm
 Hepatitis- demand awareness & treatment

• Globally, lack of awareness, and poor access to hepatitis

treatment services mean that most people who need treatment do
not receive it.
• Over 90% of people with hepatitis C can be completely cured of
the virus within 3–6 months.
• Appropriate treatment of hepatitis B and C can prevent the
development of the major life-threatening complications of chronic
liver disease: cirrhosis and liver cancer.
• It is estimated that only 5% of people with chronic hepatitis know
of their infection, and less that 1% have access to treatment
• WHO advises that by scaling up treatment, 7 million lives can be
saved between 2015 and 2030.

Ref: http://www.who.int/campaigns/hepatitis-day/2016/event/en/
 Hepatitis

• The word “hepatitis” means inflammation of the liver.

• Viral hepatitis is caused by infection of one of five
viruses – hepatitis A, B, C, D or E.
• All hepatitis viruses can cause inflammation of the liver,
and chronic hepatitis B and C can lead to cirrhosis and
liver cancer.

Ref: http://www.who.int/campaigns/hepatitis-day/2016/event/en/
 Viral Hepatitis
5 types:

A: fecal-oral transmission
B: sexual fluids & blood to blood

C: blood to blood Vaccine

D: travels with B Preventable
E: fecal–oral transmission
Adapted from Corneil, 2003
Viral Hepatitis
 Hepatitis B virus (HBV)
• Epidemiology:
– At least 2 billion people, or 1/3 of the world’s
population, have been infected with HBV
– Approximately 240 million people, or about 6 % of the
world’s population, are chronically infected with HBV
with the highest rates of infection in Africa and Asia
– HBV-related liver disease is the cause of >200,000
deaths in the Asia-Pacific region

Ref: Hepatol Int (2016) 10:1–98

 Geographic Distribution of
Chronic HBV Infection

Country HBsAg+ (%)

China 5.3-122
South Korea 2.6-5.12
India 2.4-4.72
Taiwan 10-13.82
Vietnam 5.7-102
Japan 4.4-133
Africa 5-192 HBsAg Prevalence (%)1
Russia 1.4-82 >8: High
US/Europe 0.3-122 2–8: Intermediate
<2: Low
Bangladesh 5.54

1. WHO. Hepatitis B. 2002. 2. Custer B, et al. J Clin Gastroenterol. 2004;38(10 suppl):S158.

3. WHO/WPRO data. 4. Hepatobiliary Pancreat Dis Int. 2008 Dec;7(6):595-600.
 Who should be tested for HBV?
– Persons with liver disease
– Persons needing immunosuppressive or cancer
chemotherapy
– Injection drug users (IDU)
– Persons who have received unsafe injections (used
syringes or needles)
– Men who have sex with men (MSM)
– Persons with multiple sexual partners or history of
sexually transmitted infection
– Family members, household contacts and sex partner
of a person with hepatitis B
– Cont..
Ref: Hepatol Int (2016) 10:1–98
Who should be tested for HVB?
– Dialysis patients
– HCV- or HIV-infected individuals
– Pregnant female (preferably during the first trimester to
vaccinate unprotected mothers)
– Infants born to females with chronic HBV
– Blood or organ donors
– Health care workers

Ref: Hepatol Int (2016) 10:1–98

Diagnosis criteria for phases of Chronic
HBV infection

Ref: Hepatol Int (2016) 10:1–98

 Management

• Goal & endpoint of the therapy in chronic HBV infection:

– The overall goal is global eradication of HBV infection
by various strategies including:
• Vaccination,
• Treatment and
• Prevention of transmission.

Ref: Hepatol Int (2016) 10:1–98

 Management
• The indications for treatment are generally based mainly
on the combination of three criteria:
– Serum HBV DNA levels,
– Serum ALT levels and
– Severity of liver disease (assessed by clinical evaluation,
liver biopsy or noninvasive methods).
• Patients with decompensated cirrhosis and detectable
HBV DNA require urgent antiviral treatment with NA(s).
• However, antiviral therapy may not be sufficient to
rescue all decompensated patients and they should be
considered for liver transplantation at the same time
Ref: Hepatol Int (2016) 10:1–98
Treatment indications
 Treatment Recommendations
(current available therapies, follow up & stopping rules during NA therapy)

• Treatment-naive patients can be treated with

– Tenofovir 300 mg daily
– Entecavir 0.5 mg daily
– Adefovir 10 mg daily
– Telbivudine 600 mg daily or
– Lamivudine 100 mg daily
• Tenofovir or Entecavir are the preferred NAs and should
be used as first-line therapy
• During NA therapy, HBeAg, anti-HBe (in patients with
HBeAg-positive) and ALT should be monitored every 3
months
Ref: Hepatol Int (2016) 10:1–98
 Treatment Recommendations
(current available therapies, follow up & stopping rules during NA therapy)
• The HBV DNA level should be measured at month 3 and 6 of
therapy and then every 3–6 months if agents with a low
genetic barrier are used (lamivudine, adefovir, telbivudine),
and every 6 months in patients treated with a high genetic
barrier to resistance, such as entecavir or tenofovir
• Renal function and bone profile should be monitored at least
every 3 months if Tenofovir or Adefovir is used
• For HBeAg-positive patients without liver cirrhosis, the
optimal duration of NA therapy is unknown, and the therapy
can be stopped after at least 1 year
• After stopping of NAs, patients should be monitored monthly
for the initial 3 months and then every 3–6 months thereafter
for relapse

Ref: Hepatol Int (2016) 10:1–98

 Combination therapy of IFN & NAs
• With current antiviral agents, most CHB patients fail to
obtain HBsAg seroclearance, which is the ultimate goal
of HBV therapy. Furthermore, relapse is common during
post NA therapy follow-up. Therefore, combination
therapy could be considered the ideal treatment for CHB.
• There are three approaches for administering
combination therapy:
– NA followed by addition of Peg-IFN and continuation
of
– NA; starting with Peg-IFN followed by addition of NA;
or
– Simultaneous administration of NA and Peg-IFN.
Ref: Hepatol Int (2016) 10:1–98
 Comparison of two treatment
strategies for CHB
Pegylated interferon Nucleos(t)ide analogues
Strategy Sustained off-therapy response Maintained on-treatment
(immune control) response (viral control)
Goal Low HBV DNA level (\2000 Undetectable HBV DNA
IU/ml) and normal ALT level and normal ALT level
level
Duration Finite Prolonged or indefinite
Effectiveness Sustained response in *30 % of Successful suppression of
patients after viral replication with
48 weeks of therapy continued
treatment, but high relapse
rate after stopping the
treatment
Contraindication Hepatic decompensation, Nil
immunosuppression,
pregnancy, psychiatric or
medical contraindications
 Treatment of chronic HBV infection in
special patient groups

• Chronic HBV infection in patients with

CKD, on dialysis and in renal transplant
patients:
– NAs (entecavir or telbivudine) represent the first-
line treatment options for chronic HBV-infected
patients with any level of renal dysfunction and
renal replacement therapy. NAs should be dose
adjusted based on creatinine clearance rates
– Peg-IFN should be avoided in renal transplant
patients because of the risk of rejection
 Treatment of chronic HBV infection in
special patient groups
• Chronic HBV infection and pregnant
females:
– Tenofovir is the drug of choice for mothers indicated for
antiviral treatment during the first through third trimester
of pregnancy. It is a pregnancy category B drug with
adequate safety data in HIV positive females and least
chance of viral resistance.
– For reduction of risk of mother-to-infant transmission
that occurs during perinatal period, short-term maternal
NAs starting from 28 to 32 weeks of gestation is
recommended using either tenofovir or telbuvidine for
those mothers with HBV DNA above 6–7 log IU/ml 10

– Breast-feeding is discouraged during maternal NAs

treatment.
 What Can You Do?
• Get educated about HBV

• Get tested for HBV

• Get protected with HBV vaccine

 Hepatitis C: Epidemiology
Global prevalence
 Total number of HCV infected patients globally is
around 180 million
 HCV genotype 1 is the most prevalent worldwide,
comprising 83.4 million cases (46.2% of all HCV
cases)
 Genotype 3 is the next most prevalent globally
(54.3 million, 30.1%)
 Genotypes 2, 4, and 6 are responsible for a total
22.8% of all cases
 Genotype 5 comprises the remaining <1%.
 Hepatitis C: Epidemiology in
Bangladesh
• 0.50% Mobin Khan Indian J Gastroenterol 2010
• 0.20% Ashraf H et al BMC Inf Dis 2010
• 0.88% Mahtab et al J of Cl & Exp Hepatology2011
• 0.60% Safiullah et al BMRC 2013
• 0.50% Masud et al DDW2015
 Hepatitis C: HCV Genotypes in
Bangladesh
3 50.19%
3 41%
 3+4 28.77%
 3+4 31%
1 14.14%
1 21%
2 2.8%  2, 4, 5 1.6%
4 1.9%  5+6 1.6%
5 0.23% HMJ 2008 Volume 2,
Number 4 n 577–581.
Mymensingh Med J.
2015 Jan;24(1):143-51
 Hepatitis C: How Transmitted
The most common method of transmitting hepatitis
C virus is through injectable drug use (IDU) and
sharing needles. Others are-
 Blood transfusion
 Intra-institutional
 IV drug use and Tattoo
 Hemodialysis
 Sexual (infrequent)
 Mother to newborn (infrequent)
Ref: http://www.epidemic.org/thefacts/hepatitisc/transmission/
 Hepatitis C: How Not
Transmitted
HCV is not transmitted through:
 Casual contact
 Respiratory droplets
 Sharing food
 Kissing
 Mosquito bites

Ref: http://www.medicalnewstoday.com/Updated 08 January 2016

 Hepatitis C: Symptoms
It is often referred to as a silent epidemic due to lack
of definite symptoms. During acute infection period
usually experience:
 Abdominal discomfort
 Nausea
 Fever
 Joint pain
 Fatigue
 Infrequently jaundice (Jaundice)
 Clay colored stools
 Hepatitis C: Protecting others
Hepatitis C can be spread through blood. So follow
these common precautions:
 Don't share razors, toothbrushes, nail clippers, or
anything else that could have your blood on it. Cover
any open wounds or sores with bandages.
 Carefully dispose of tampons, sanitary napkins,
tissues, used bandages, and anything else that might
have your blood on it.
 If you're using injected street drugs, get into a
treatment program. At the very least, don't share
needles or equipment with anyone else.
 Practice safer sex
Ref: http://www.webmd.com/hepatitis/hepc-guide/hepatitis-c-protecting-others
 Hepatitis C: Consequence of
HCV infection

Asymptomatic chronic carriage Acute hepatitis

Chronic hepatitis Cirrhosis Hepatocellular
carcinoma Extrahepatic manifestations Death
Ref: Rev Med Virol. 2003 Jan-Feb;13(1):57-68
 Hepatitis C: Whom to be tested
AASLD RECOMMENDATION
one-time testing should be performed for all persons with
behaviors, exposures, and conditions associated with an
increased risk of HCV infection:
1. Risk behaviors
Injection-drug use (current or ever, including those who
injected once)
Intranasal illicit drug use
2. Risk exposures
Long-term hemodialysis (ever)
Getting a tattoo in an unregulated setting
Healthcare, emergency medical, and public safety
workers after needlesticks, sharps, or mucosal
exposures to HCV-infected blood
Children born to HCV-infected women
 Hepatitis C: Whom
AASLD
to be tested
RECOMMENDATION
 Prior recipients of transfusions or organ transplants,
including persons who:
•Were notified that they received blood from a donor who later
tested positive for HCV infection
• Received a transfusion of blood or blood components, or
underwent an organ transplant before July 1992
• Received clotting factor concentrates produced before 1987
• Persons who were ever incarcerated
3. Other
 HIV infection
 Unexplained chronic liver disease and chronic hepatitis
including elevated alanine aminotransferase levels
 Solid organ donors (deceased and living)
 Hepatitis C: How to be tested
RECOMMENDATION

 Anti-HCV antibodies are the first-line diagnostic test

for HCV infection
 In the case of suspected acute hepatitis C or in
immunocompromised patients, HCV RNA testing
should be part of the initial evaluation
 If anti-HCV antibodies are detected, HCV RNA should
be determined by a sensitive molecular method Anti-
HCV-positive, HCV RNA negative individuals should be
retested for HCV RNA three months later to confirm true
convalescence
 Hepatitis C: How to be tested

RECOMMENDATIO
N

Ref: AASLD Recommendations for Testing, Managing, and Treating Hepatitis C 2015
 Hepatitis C: Treatment
timelines
>90%

>70%

SVR 55%
%
42%
34%

16%
6%

TIME
 Hepatitis C: Paradigm shift of
treatment
US FDA Announcements to DAAs

 6 Dec 2013 : Approved sofosbuvir

 10 Oct 2014 : Approved ledipasvir + sofosbuvir
 24 Jul 2015 : Approved daclatasvir
 28 Jan 2016: Approved elbasvir + grazoprevir
 28 June 2016: Approved sofosbuvir + velpatasvir

Ref:
www.fda.gov/NewsEvents/Newsroom/PressAnnouncements
 Hepatitis C: Treatment
recommendation
RECOMMENDATION

Notwithstanding the respective costs of these options,

IFN-free regimens are the best options when
available in HCV-monoinfected and in HIV-coinfected
patients without cirrhosis or with compensated (Child-
Pugh A) or decompensated (Child-Pugh B or C)
cirrhosis, because of their virological efficacy, ease of
use and tolerability .

Ref: Journal of Hepatology 2015 vol. 63 j 199–236

 Hepatitis C: latest & commonly
used drugs

& …Recommended
Product Presentation Posology
180, 135 or 90 μg of
PegIFN-α2a Once weekly subcutaneous injection
Solution for injection
Two capsules in the morning and 3 in the
evening if body weight <75 kg
Ribavirin 200 mg Capsule
Three capsules in the morning and 3 in the
evening if body weight ≥75 kg
Sofosbuvir 400 mg Tablet One tablet once daily (morning)
Daclatasvir 60 mg Tablet One tablet once daily (morning)
400 mg of sofosbuvir
Sofosbuvir/
and 90 mg of One tablet once daily (morning)
Ledipasvir
ledipasvir Tablet
 Hepatitis C: less commonly
used drugs
& …Recommended
Product Presentation Posology
Capsules
Simeprevir containing 150 mg One capsule once daily (morning)
of simeprevir
Tablets containing
75 mg of
Paritaprevir
paritaprevir, 12.5
/ombitasvir/ Two tablets once daily (morning)
mg of
ritonavir
ombitasvir and 50
mg of ritonavir
Tablets containing
One tablet twice daily (morning and
Dasabuvir 250 mg of
evening)
dasabuvir
 Hepatitis C: Treatment recommendation

HCV-monoinfected or HCV/HIV coinfected patients with chronic hepatitis C

without cirrhosis, including treatment-naïve patients and patients who failed on a
treatment based on PegIFN-a and ribavirin (RBV)

PegIFN-α,
Patients Ribavirin and Sofosbuvir Sofosbuvir and Sofosbuvir
sofosbuvir and Ribavirin daclatasvir and ledipasvir
Genotype 1a
8-12 wk,
12 wk No 12 wk without RBV
Genotype 1b without RBV

12 wk without
Genotype 2 12 wk 12 wk No
RBV

12 wk without
Genotype 3 12 wk 24 wk No
RBV
12 wk without 12 wk without
Genotype 4 12 wk No
RBV RBV
Genotype 5 12 wk without 12 wk without
12 wk No
or 6 RBV RBV
Ref: Journal of Hepatology 2015 vol. 63 j 199–236
 Hepatitis C: Treatment recommendation
HCV-monoinfected or HCV/HIV coinfected patients with chronic hepatitis C
without cirrhosis, including treatment-naïve patients and patients who failed on a
treatment based on PegIFN-a and ribavirin (RBV)
PegIFN-α,
Patients Ribavirin and Sofosbuvir Sofosbuvir and Sofosbuvir
sofosbuvir and Ribavirin daclatasvir and ledipasvir
12 wk with RBV, or 24
Genotype 1a 12 wk with
wk without RBV, or 24
12 wk No RBV, or 24 wk
wk with RBV if negative
Genotype 1b without RBV
predictors of response
12 wk without
Genotype 2 12 wk 16-20 wk No
RBV
24 wk with
Genotype 3 12 wk No No
RBV
12 wk with
Genotype 4 12 wk No RBV, or 24 wk 12 wk with RBV, or 24
without RBV wk without RBV, or 24
12 wk with wk with RBV if negative
Genotype 5 predictors of response
12 wk No RBV, or 24 wk
or 6
without RBV

Ref: Journal of Hepatology 2015 vol. 63 j 199–236

 Hepatitis C: Treatment recommendation
Patients with decompensated cirrhosis (Child-Pugh B and Child-Pugh C, up to
12 points) without an indication for liver transplantation

Patients Sofosbuvir Sofosbuvir and Sofosbuvir

and Ribavirin daclatasvir and ledipasvir
Genotype 1a 12 wk with RBV
Or
No 24 wk without RBV
Genotype 1b 12 wk with RBV (If RBV contraindicated
Or or poor tolerated)
Genotype 2 16-20 wk 24 wk without RBV No
(If RBV
Genotype 3 No contraindicated or No
poor tolerated) 12 wk with RBV
Genotype 4 No
Or
24 wk without RBV
Genotype 5 (If RBV contraindicated
No
or 6 or poor tolerated)
Ref: Journal of Hepatology 2015 vol. 63 j 199–236
 Hepatitis C: Treatment of special groups
HCV-monoinfected or HCV/HIV coinfected patients with chronic hepatitis C
without cirrhosis, including treatment-naïve patients and patients who failed on a
treatment based on PegIFN-a and ribavirin (RBV)

Pediatric Patients
• The diagnosis of perinatally acquired HCV requires a
positive anti-HCV test after 18 months of age or older
• Antiviral treatment for hepatitis C can be administered to
children between 2 and 17 years of age
• Combined pegylated interferon-α and ribavirin remains
the standard therapy for pediatric hepatitis C virus (HCV)
infections in 2016
• Clinical trials of interferon-free DAA regimens have been
initiated for children ages 3-17 years2
Ref: 1. APASL consensus statements and management algorithms for
hepatitis C virus infection, 2012; 2. Curr Opin Pediatr. 2016 Feb;28(1):93-100
 Hepatitis C: Treatment of special groups
Pediatric Patients

Recommended treatment regimen for CHC in children

Genotyp Duration Regimen
e (weeks)
1&4 48 Ribavirin PEG-IFN-α-2a
15 180 μg/1.73
2
mg/kg/da m /week OR
2&3 24 y PEG-IFN-α-2b
2
60 μg/m /week
AND
Antiviral response rates in children to peginterferon alfa and
ribavirin are similar to those in adults.

Ref: J Clin Transl Hepatol. 2015 Mar; 3(1): 36–41.

 Hepatitis C: Treatment of special groups
HBV Coinfection
• Patients should be treated with the same regimens,
following the same rules as HCV monoinfected patients
• If HBV replicates at significant levels before, during or
after HCV clearance, concurrent HBV
nucleoside/nucleotide analogue therapy is indicated

Ref: Journal of Hepatology 2015 vol. 63 j 199–236

 Hepatitis C: Treatment of special groups

HBV Coinfection
• Patients should be treated with the same regimens,
following the same rules as HCV monoinfected patients
• If HBV replicates at significant levels before, during or
after HCV clearance, concurrent HBV
nucleoside/nucleotide analogue therapy is indicated

Ref: Journal of Hepatology 2015 vol. 63 j 199–236

 Hepatitis C: Treatment of
special groups
Patients with Haemodialysis
• Haemodialysis patients, particularly those who are
suitable candidates for renal transplantation, should be
considered for antiviral therapy

• Haemodialysis patients should receive an IFN-free, if

possible ribavirin-free regimen, for 12 weeks in patients
without cirrhosis, for 24 weeks in patients with cirrhosis

• Simeprevir, daclatasvir, and the combination of ritonavir

boosted paritaprevir, ombitasvir and dasabuvir are cleared
by hepatic metabolism and can be used in patients with
severe renal disease
 Hepatitis C: Treatment of
special groups
Patients with Haemodialysis
In a multicenter, prospective, non-randomized and
observational study conducted between June 2014 and
June 2015 in accordance with Good Clinical Practice
guidelines and
ethical principles that have their origin in the Declaration
of Helsinki. HCV-infected patients received SOF, 400 mg
QD (n=7) or TIW (n=5), after hemodialysis along with
daclatasvir, ledipasvir, simeprevir or ribavirin for 12 or 24
weeks, at the discretion of the local multidisciplinary
expert advices. Patients were eligible for the study if they
were 18 years old; required hemodialysis (estimated
glomerular filtration rate < 15 mL/min/1.73 m2)
Ref: Journal of Hepatology 2016 : 6037 (online publication)
 Hepatitis C: Treatment of
special groups
Patients with Haemodialysis
Result:
Plasma concentrations of sofosbuvir or its inactive metabolite
sofosbuvir-007 did not accumulate with either regimen between
hemodialysis sessions or throughout the treatment
course. Hemodialysis did not remove any other associated anti-
HCV agents. Clinical and biological tolerance was good for
all patients. Two relapses occurred with the 3 times a week
regimen and none with the once daily.

Lay summery:
In this pharmacokinetic study, sofosbuvir full dose (400 mg once-
daily) administered every day with another Direct Antiviral Agent
did not accumulate in hemodialysis patients and was safe and
effective.

Ref: Journal of Hepatology 2016 : 6037 (online publication)

 Hepatitis C: Treatment of
special groups
Patients with Haemodialysis
•The need for dose adjustments for the approved HCV
DAAs in patients on dialysis is unknown. No safety dosing
and efficacy data is available in this population. These
drugs should thus be used with extreme caution in
patients with severe renal disease, and only in extreme
life-threatening situations for patients on dialysis

Ref: Journal of Hepatology 2015 vol. 63 j 199–236

Q&A
Thank you
for patience
hearing