Hepatitis C in Pakistan

Hepatitis C in Pakistan
Rashid A. Chotani
Assistant Professor & Director,
The Global Infectious Disease Surveillance & Alert System
The Johns Hopkins Bloomberg School of Public Health
A Historical Perspective
Enterically
“Infectious” A E
transmitted
Viral “NANB”
hepatitis C
Parenterally
“Serum” B D
transmitted
other
The Hepatitis C Virus
 Spherical, enveloped, single-stranded RNA
virus
 Family Flaviviridae
 HCV may produce ~ 1 trillion new viral
particles each day
 RNA polymerase lacks proofreading
capabilities
 Encodes a single polyprotein of 3011 amino
acids that is processed into 10 structural and
regulatory proteins
The Hepatitis C Virus
A single
HCV
floating
among
hepato-
cytes
Hepatitis C: Basic Facts
 Hepatitis C is a global health problem affecting over 170
million people worldwide.
 There is wide geographic variation in both prevalence and
genotype distribution of hepatitis C virus on a global level.
 Transmitted:
 Body fluids
 Parenterally
 Hepatitis C is a leading cause of end-stage liver disease and
hepatocellular carcinoma.
 Despite a declining incidence of new infections, the burden
of disease, both in terms of mortality and in terms of cost, is
expected to increase over the next decade.
Prevalence of HCV Worldwide
 The prevalence is increasing worldwide
 WHO estimates ~ 200 million infected, 3.3% of the world’s
population
 Infection due to HCV accounts for (worldwide):
 20% of cases of acute hepatitis
 70% of cases of chronic hepatitis
 40% of cases of end-stage cirrhosis
 60% of cases of hepatocellular carcinoma
 30% of liver transplants.
 170 million hepatitis C virus (HCV) carriers present worldwide
 3 to 4 million new cases per year
Prevalence of Hepatitis C 2003
>10%
2.5-9.9%
1-2.4%
0-0.9%
Features of Hepatitis C
Virus Infection
Incubation period Average 6-7 weeks
Range 2-26 weeks
Acute illness (jaundice) Mild (≤20%)
Case fatality rate Low
Chronic infection 60%-85%
Age-
Chronic hepatitis related 10%-70% (most asx)
Cirrhosis <5%-20%
Mortality from CLD 1%-5%
Chronic Hepatitis C Factors
Promoting Progression or Severity
 Increased alcohol intake
 Age 30-49 years at time of infection
 Those infected at a younger age have
much better prognosis
 HIV co-infection
 Other
 Male gender
 Chronic HBV co-infection
Serologic Pattern of Acute HCV
Infection with Recovery
anti-
Symptoms HCV
+/-
HCV RNA
Titer
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Months Years
Time after Exposure
Serologic Pattern of Acute HCV
Infection with Progression to
Chronic Infection
anti-
HCV
Symptoms
+/-
HCV RNA
Titer
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Months Years
Time after Exposure
Sources of Infection for
Persons with Hepatitis C
Sexual 15%
Injecting
drug use
60% Transfusion 10%
(before screening)
Other* 5%
Unknown 10%
* Hemodialysis; health-care work; perinatal
Source: Centers for Disease Control and Prevention

Pakistan
 Total population: 149,911,000
 GDP per capita (Intl $, 2001): 2,146
 Life expectancy at birth M/F (years):
61.1/61.6
 Healthy life expectancy at birth M/F
(years): 54.2/52.3
 Child mortality M/F (per 1,000): 105/115
 Adult mortality M/F (per 1,000): 227/201
 Total health expenditure per capita (Intl $,
2001): 85
 Total health expenditure as % of GDP
(2001): 3.9
Burden of diseases in Pakistan
Studies in Pakistan have found HCV:
 60% among liver cancer patients
(Ahmed et al., 1995)
 51% among beta thalassemia major

patients (Ahmed et al., 1995)
 46% among chronic liver disease
patients (Mujeeb et al., 1998)
 18% among cirrhotic patients (Mujeeb et al.,
1998)
 20% among commercial blood
donors (Mujeeb et al., 1998)
Risk Factors
Persons Risk of Testing
Infection Recommended?
Injecting drug users High Yes
Recipients of clotting High Yes
factors made before 1987
Hemodialysis patients Intermediate Yes
Recipients of blood and/or Intermediate Yes
solid organs before 1992
People with undiagnosed Intermediate
liver problems Yes
Risk Factors
Persons Risk of Testing

Infection Recommended?
Infants born to infected After 12-18

Intermediate
mothers months old
Healthcare/public safety Low Only after
workers known exposure
People having sex with Low No
mutiple partners
People having sex with a Low No
steady partner
Prevalence of anti-HCV
amongst blood donors*
Anti-HCV
Prevalence
>5% - High
1.1-5% - Intermediate
0.2-1% - Low
0.1% - Very Low
Unknown
Risk Factor:
Unsafe injections
 1993: Luby et al.

 6.5% antibodies positive for HCV in Hafizabad,
Pakistan
 Shows an increased prevalence in Pakistan
compared to world
 1994: Luby et al.
 Follow up case control study to identify risk
factors
 Positive individuals were 8.2 times more likely
to receive > 5 injection per year
Risk Factor:
Unsafe injections
 1995: Aamir Javed Khan et al.

 Investigated relationship between
hepatitis B and C and injections in peri-
urban Karachi
 44% hepatitis C positive
 Those who received more injections were
more likely to be hepatitis C infected
 94% of the needles/syringes were reused
Risk Factor:
Tattooing
 CDC found that in Pakistan, 7% of

those with tattoos were positive
for HCV
Risk Factor:
Body Piercing
 In Pakistan, 7% of those with body

piercing tested positive for HCV
(Luby et. al)
Tests for HCV: Virological markers
 Detection of HCV antibodies
 Enzyme immunoassays (EIA)
 Enzyme-linked immunosorbent assays (ELISA)
 Detect a mixture of antibodies directed against various
viral epitopes
 HCV genotype determination
 Phylogenetic analysis can distinguish HCV types,
subtypes and isolates on the basis of average sequence
divergence rates
 Sequence-based assay
 testing for type-specific antibodies with a competitive
EIA (so-called “serotyping”)
Tests for HCV: Virological markers
 Assessment of HCV replication
 The presence of HCV RNA in peripheral
blood is a reliable marker of active

HCV replication
 HCV RNA is detectable within one to
two weeks after infection
 HCV RNA levels are stable over time
in patients with chronic infection (Nguyen TT,
et al.)
 The HCV RNA level may increase slightly
after several years of chronic infection.
 HCV RNA can be detected and/or quantified
in serum or plasma by means of various
categories of amplification techniques
HCV Spot Test

Diagnosis of HCV Infections
 Acute hepatitis C
 Should be tested for anti-HCV by means of EIA
 Detection of HCV RNA without anti-HCV is strongly
indicative of acute hepatitis C
 Acute hepatitis C is unlikely if both markers are
absent.
 Chronic hepatitis C
 Certain in a patient with chronic liver disease when
both anti-HCV and HCV RNA are detected
 High optical density ratio in EIA: true-positive result,
 Low optical density ratio in EIA: no conclusion can
be drawn because anti-HCV antibody titers may fall
gradually after spontaneous clearance of the virus
Diagnosis of HCV Infections
 Mother-to-infant transmission
 Should be based on HCV RNA detection
with a sensitive technique rather than on

anti-HCV detection
 Antibodies are passively transferred in
utero and remain detectable for several

months to more than a year after delivery,
regardless of whether viral transmission
occurs
 Assessment of disease severity and prognosis
 Virologic tests have no prognostic value
Treatment of
Acute Hepatitis C
 The optimal treatment schedule remains to be
established for acute hepatitis C, and no
recommendations can yet be made regarding the use of
virologic tests in the decision to treat (Hoofnagle JH)
 Virologic response assessed at the end of therapy by
means of a sensitive HCV RNA technique
 If HCV RNA is negative, the sustained or transient
nature of the response is assessed 24 weeks later

 Negative HCV RNA detection at this second test
indicates that therapy has been successful.

Treatment of
Chronic Hepatitis C
 Based on a combination of:
 pegylated interferon (IFN) alfa,
 either pegylated IFN alfa-2a
or pegylated IFNalfa-2b
 and ribavirin
General Prevention Strategies
 Communication of information about HCV to health care
and public health professionals
 Education of the public and persons at risk for infection
 Integration of prevention and control activities into
public health programs to:
 Identify, counsel, and test persons at risk for HCV infection
 Provide referral for medical evaluation of those found to be
infected
 Conduct outreach and community-based activities to address
practices that put people at risk for HCV infection
 Surveillance to monitor acute and chronic disease
trends and evaluate the effectiveness of strategies
 Epidemiologic and laboratory investigations to better
guide prevention efforts.
Prevention Strategies
in Pakistan
 Methadone treatment programs
 Needle and syringe exchange programs
 Comprehensive risk-modifying educational
programs
 Ensuring access to sterile syringes through
physician prescription and pharmacy sales of
syringes to IDUs
 IDUs should be educated about:
 the importance of hand washing before and after
giving injections
 not using the others' injection equipment
 avoiding any contact with blood from other persons
Future Research
 Development of reliable, reproducible, and efficient
culture systems for propagating HCV
 Role of genetic factors in the pathogenesis of HCV
 Development of less-toxic therapies and molecular-
based agents that specifically inhibit viral replication
and/or translation of viral RNA.
 Directed investigation examining the development and
progression of hepatic fibrosis
 Establishment of Hepatitis Clinical Research Network to
conduct of research related to the natural history,
prevention, and treatment of hepatitis C.
 Examine the pattern of HCV disease progression in
persons infected for at least two decades, including
those infected as infants and as children
Future Research
 Analysis of effectiveness of infection-control strategies
 Better understanding of factors that might predict
transmission
 Understanding side effect management and increasing
patient adherence to therapy.
 Analysis of effect of health insurance
 Clearly establish the role of liver biopsy in the
therapeutic management of patients with chronic
hepatitis C.
 International standardization of viral RNA titers
 Role of fatty liver, obesity, diabetes, and hepatic iron
stores in the natural history of hepatitis C and
responses to therapy.
 Better understand HIV co-infected patients

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Hepatitis C in Pakistan

* Hemodialysis; health-care work; perinatal

Source: Centers for Disease Control and Prevention

 51% among beta thalassemia major

Persons Risk of Testing

Infants born to infected After 12-18

 1993: Luby et al.

 1995: Aamir Javed Khan et al.

 CDC found that in Pakistan, 7% of

 In Pakistan, 7% of those with body

blood is a reliable marker of active

HCV Spot Test

with a sensitive technique rather than on

utero and remain detectable for several

nature of the response is assessed 24 weeks later

indicates that therapy has been successful.

 either pegylated IFN alfa-2a

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