Hepatitis C in Pakistan Rashid A. Chotani Assistant Professor & Director, The Global Infectious...
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Transcript of Hepatitis C in Pakistan Rashid A. Chotani Assistant Professor & Director, The Global Infectious...
Hepatitis C in Hepatitis C in PakistanPakistan
Rashid A. ChotaniRashid A. ChotaniAssistant Professor & Director,Assistant Professor & Director,The Global Infectious Disease Surveillance & Alert SystemThe Global Infectious Disease Surveillance & Alert SystemThe Johns Hopkins Bloomberg School of Public HealthThe Johns Hopkins Bloomberg School of Public Health
AA““Infectious”Infectious”
““Serum”Serum”
Viral Viral hepatitishepatitis
EntericallyEntericallytransmittedtransmitted
ParenterallyParenterallytransmittedtransmitted
otherother
EE
““NANB”NANB”
BB DD
CC
A Historical A Historical PerspectivePerspective
The Hepatitis C VirusThe Hepatitis C Virus
Spherical, enveloped, single-stranded RNA vSpherical, enveloped, single-stranded RNA virusirus
Family FlaviviridaeFamily Flaviviridae HCV may produce ~ 1 trillion new viral particlHCV may produce ~ 1 trillion new viral particl
es each dayes each day RNA polymerase lacks proofreading capabiliRNA polymerase lacks proofreading capabili
tiesties Encodes a single polyprotein of 3011 amino Encodes a single polyprotein of 3011 amino
acids that is processed into 10 structural and acids that is processed into 10 structural and regulatory proteinsregulatory proteins
A single A single HCV HCV
floating amonfloating among hepato-g hepato-
cytescytes
The Hepatitis C VirusThe Hepatitis C Virus
Hepatitis C: Basic FactsHepatitis C: Basic Facts Hepatitis C is a global health problem affecting over 170 Hepatitis C is a global health problem affecting over 170
million people worldwide. million people worldwide. There is wide geographic variation in both prevalence and There is wide geographic variation in both prevalence and
genotype distribution of hepatitis C virus on a global level. genotype distribution of hepatitis C virus on a global level. Transmitted: Transmitted:
Body fluidsBody fluids Parenterally Parenterally
Hepatitis C is a leading cause of end-stage liver disease Hepatitis C is a leading cause of end-stage liver disease and hepatocellular carcinoma. and hepatocellular carcinoma.
Despite a declining incidence of new infections, the burden Despite a declining incidence of new infections, the burden of disease, both in terms of mortality and in terms of cost, of disease, both in terms of mortality and in terms of cost, is expected to increase over the next decade.is expected to increase over the next decade.
The prevalence is increasing worldwideThe prevalence is increasing worldwide WHO estimates ~ 200 million infected, 3.3% of the world’s poWHO estimates ~ 200 million infected, 3.3% of the world’s po
pulationpulation Infection due to HCV accounts for (worldwide):Infection due to HCV accounts for (worldwide):
20% of cases of acute hepatitis20% of cases of acute hepatitis 70% of cases of chronic hepatitis 70% of cases of chronic hepatitis 40% of cases of end-stage cirrhosis40% of cases of end-stage cirrhosis 60% of cases of hepatocellular carcinoma60% of cases of hepatocellular carcinoma 30% of liver transplants.30% of liver transplants.
170 million hepatitis C virus (HCV) carriers present worldwide170 million hepatitis C virus (HCV) carriers present worldwide 3 to 4 million new cases per year3 to 4 million new cases per year
Prevalence of HCV Prevalence of HCV WorldwideWorldwide
Prevalence of Hepatitis C Prevalence of Hepatitis C 20032003
>10% 2.5-9.9%
1-2.4%0-0.9%
Features of Hepatitis C Features of Hepatitis C Virus InfectionVirus Infection
Incubation periodIncubation period Average 6-7 Average 6-7 weeksweeks
Range 2-26 Range 2-26 weeksweeks
Acute illness (jaundice)Acute illness (jaundice) Mild (Mild (≤≤20%)20%)
Case fatality rateCase fatality rate LowLow
Chronic infectionChronic infection 60%-85%60%-85%
Chronic hepatitisChronic hepatitis 10%-70% 10%-70% (most (most asx)asx)
CirrhosisCirrhosis <5%-20%<5%-20%
Mortality from CLDMortality from CLD 1%-5%1%-5%
Age-related
Chronic Hepatitis C Factors Chronic Hepatitis C Factors Promoting Progression or Promoting Progression or SeveritySeverity
Increased alcohol intakeIncreased alcohol intake Age 30-49 years at time of infectionAge 30-49 years at time of infection
Those infected at a younger age have Those infected at a younger age have much better prognosismuch better prognosis
HIV co-infectionHIV co-infection OtherOther
Male genderMale gender Chronic HBV co-infectionChronic HBV co-infection
Serologic Pattern of Acute Serologic Pattern of Acute HCV Infection with RecoveryHCV Infection with Recovery
Symptoms +/-
Time after Exposure
Tit
er
anti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4YearsMonth
s
HCV RNA
Serologic Pattern of Acute Serologic Pattern of Acute HCV Infection with HCV Infection with Progression to Chronic Progression to Chronic InfectionInfection
Symptoms Symptoms +/-+/-
Time after ExposureTime after Exposure
Tit
er
Tit
er
anti-anti-HCVHCV
ALTALT
NormaNormall
00 11 22 33 44 55 66 11 22 33 44YearsYearsMonthMonth
ss
HCV RNA HCV RNA
Sources of Infection forSources of Infection forPersons with Hepatitis CPersons with Hepatitis C
Sexual 15%Sexual 15%
Other* 5%Other* 5%
Unknown 10%Unknown 10%
Injecting Injecting drug use drug use
60%60% Transfusion 10%Transfusion 10%(before screening)(before screening)
* Hemodialysis; health-care work; perinatal* Hemodialysis; health-care work; perinatal
Source: Centers for Disease Control and PreventionSource: Centers for Disease Control and Prevention
PakistanPakistan Total population: 149,911,000 Total population: 149,911,000 GDP per capita (Intl $, 2001): 2,146GDP per capita (Intl $, 2001): 2,146 Life expectancy at birth M/F (years): 61.1/6Life expectancy at birth M/F (years): 61.1/61.61.6 Healthy life expectancy at birth M/F (years):Healthy life expectancy at birth M/F (years): 54.2/52.3 54.2/52.3 Child mortality M/F (per 1,000): 105/115Child mortality M/F (per 1,000): 105/115 Adult mortality M/F (per 1,000): 227/201Adult mortality M/F (per 1,000): 227/201 Total health expenditure per capita (Intl $, Total health expenditure per capita (Intl $, 2001): 852001): 85 Total health expenditure as % of GDP (200Total health expenditure as % of GDP (2001): 3.91): 3.9
Burden of diseases in Burden of diseases in PakistanPakistanStudies in Pakistan have found Studies in Pakistan have found HCV:HCV:
60% among liver cancer patients 60% among liver cancer patients (Ahmed et al., 1995)(Ahmed et al., 1995)
51% among beta thalassemia major 51% among beta thalassemia major patients patients (Ahmed et al., 1995)(Ahmed et al., 1995)
46% among chronic liver disease pa46% among chronic liver disease patients tients (Mujeeb et al., 1998)(Mujeeb et al., 1998)
18% among cirrhotic patients 18% among cirrhotic patients (Mujeeb et (Mujeeb et
al., 1998)al., 1998)
20% among commercial blood dono20% among commercial blood donors rs (Mujeeb et al., 1998)(Mujeeb et al., 1998)
Risk FactorsRisk Factors
YesYesIntermediateIntermediatePeople with undiagnosed People with undiagnosed liver problemsliver problems
YesYesIntermediateIntermediateRecipients of blood and/or Recipients of blood and/or solid organs before 1992solid organs before 1992
YesYesIntermediateIntermediateHemodialysis patientsHemodialysis patients
YesYesHighHighRecipients of clotting Recipients of clotting factors made before 1987factors made before 1987
YesYesHighHighInjecting drug usersInjecting drug users
Testing Testing Recommended?Recommended?
Risk of Risk of InfectionInfection
PersonsPersons
Risk FactorsRisk Factors
NoNoLowLowPeople having sex with a People having sex with a steady partnersteady partner
NoNoLowLowPeople having sex with People having sex with mutiple partnersmutiple partners
Only after Only after known exposureknown exposure
LowLowHealthcare/public safety Healthcare/public safety workersworkers
After 12-18 After 12-18 months oldmonths old
IntermediateIntermediateInfants born to infected Infants born to infected mothersmothers
Testing Testing Recommended?Recommended?
Risk of Risk of InfectionInfection
PersonsPersons
1.1-5% - Intermediate
Anti-HCV Prevalence
>5% - High
0.2-1% - Low0.1% - Very Low
Unknown
Prevalence of anti-HCV amongst blood donors*
Risk Factor: Risk Factor: Unsafe injectionsUnsafe injections
1993: Luby et al.1993: Luby et al. 6.5% antibodies positive for HCV in Hafizaba6.5% antibodies positive for HCV in Hafizaba
d, Pakistand, Pakistan Shows an increased prevalence in Pakistan cShows an increased prevalence in Pakistan c
ompared to worldompared to world 1994: Luby et al.1994: Luby et al.
Follow up case control study to identify risk fFollow up case control study to identify risk factorsactors
Positive individuals were 8.2 times more likelPositive individuals were 8.2 times more likely to receive > 5 injection per yeary to receive > 5 injection per year
Risk Factor: Risk Factor: Unsafe injectionsUnsafe injections
1995: Aamir Javed Khan et al.1995: Aamir Javed Khan et al. Investigated relationship between hepatitInvestigated relationship between hepatit
is B and C and injections in peri-urban Kis B and C and injections in peri-urban Karachiarachi
44% hepatitis C positive44% hepatitis C positive Those who received more injections were Those who received more injections were
more likely to be hepatitis C infected more likely to be hepatitis C infected 94% of the needles/syringes were reused94% of the needles/syringes were reused
Risk Factor: Risk Factor: TattooingTattooing
CDC found that in Pakistan, 7% of CDC found that in Pakistan, 7% of those with tattoos were positive those with tattoos were positive for HCVfor HCV
Risk Factor: Risk Factor: Body PiercingBody Piercing
In Pakistan, 7% of those with body In Pakistan, 7% of those with body piercing tested positive for HCV piercing tested positive for HCV (Luby et. al)(Luby et. al)
Tests for HCV: Tests for HCV: VVirological markersirological markers Detection of HCV antibodiesDetection of HCV antibodies
Enzyme immunoassays (EIA)Enzyme immunoassays (EIA) Enzyme-linked immunosorbent assays (ELISA)Enzyme-linked immunosorbent assays (ELISA) Detect a mixture of antibodies directed against various Detect a mixture of antibodies directed against various
viral epitopes viral epitopes HCV genotype determinationHCV genotype determination
Phylogenetic analysis can distinguish HCV types, subtPhylogenetic analysis can distinguish HCV types, subtypes and isolates on the basis of average sequence divypes and isolates on the basis of average sequence divergence rates ergence rates
Sequence-based assaySequence-based assay testing for type-specific antibodies with a competitive testing for type-specific antibodies with a competitive
EIA (so-called “serotyping”)EIA (so-called “serotyping”)
Tests for HCV: Tests for HCV: Virological markersVirological markers Assessment of HCV replicationAssessment of HCV replication
The presence of HCV RNA in peripheral bloThe presence of HCV RNA in peripheral blood is a reliable marker of active HCV od is a reliable marker of active HCV replicationreplication
HCV RNA is detectable within one to HCV RNA is detectable within one to two weeks after infectiontwo weeks after infection
HCV RNA levels are stable over time HCV RNA levels are stable over time in patients with chronic infection in patients with chronic infection (Nguyen TT, (Nguyen TT, et al.) et al.)
The HCV RNA level may increase slightly afThe HCV RNA level may increase slightly after several years of chronic infection. ter several years of chronic infection.
HCV RNA can be detected and/or quantified HCV RNA can be detected and/or quantified in serum or plasma by means of various catin serum or plasma by means of various categories of amplification techniquesegories of amplification techniques
HCV Spot TestHCV Spot Test
Diagnosis of HCV Diagnosis of HCV InfectionsInfections
Acute hepatitis C Acute hepatitis C Should be tested for anti-HCV by means of EIA Should be tested for anti-HCV by means of EIA Detection of HCV RNA without anti-HCV is strongly Detection of HCV RNA without anti-HCV is strongly
indicative of acute hepatitis Cindicative of acute hepatitis C Acute hepatitis C is unlikely if both markers are Acute hepatitis C is unlikely if both markers are
absent. absent. Chronic hepatitis CChronic hepatitis C
Certain in a patient with chronic liver disease when Certain in a patient with chronic liver disease when both anti-HCV and HCV RNA are detected both anti-HCV and HCV RNA are detected
High optical density ratio in EIA: true-positive High optical density ratio in EIA: true-positive result,result,
Low optical density ratio in EIA: no conclusion can Low optical density ratio in EIA: no conclusion can be drawn because anti-HCV antibody titers may fall be drawn because anti-HCV antibody titers may fall gradually after spontaneous clearance of the virusgradually after spontaneous clearance of the virus
Diagnosis of HCV Diagnosis of HCV InfectionsInfections
Mother-to-infant transmission Mother-to-infant transmission Should be based on HCV RNA detection Should be based on HCV RNA detection
with a sensitive technique rather than on with a sensitive technique rather than on anti-HCV detectionanti-HCV detection
Antibodies are passively transferred Antibodies are passively transferred in in uteroutero and remain detectable for several and remain detectable for several months to more than a year after delivery, months to more than a year after delivery, regardless of whether viral transmission regardless of whether viral transmission occurs occurs
Assessment of disease severity and prognosisAssessment of disease severity and prognosis Virologic tests have no prognostic valueVirologic tests have no prognostic value
Treatment of Treatment of Acute Hepatitis CAcute Hepatitis C
The optimal treatment schedule remains to be The optimal treatment schedule remains to be established for acute hepatitis C, and no established for acute hepatitis C, and no recommendations can yet be made regarding the use of recommendations can yet be made regarding the use of virologic tests in the decision to treat (Hoofnagle JH)virologic tests in the decision to treat (Hoofnagle JH)
Virologic response assessed at the end of therapy by Virologic response assessed at the end of therapy by means of a sensitive HCV RNA technique means of a sensitive HCV RNA technique If HCV RNA is negative, the sustained or transient If HCV RNA is negative, the sustained or transient
nature of the response is assessed 24 weeks laternature of the response is assessed 24 weeks later Negative HCV RNA detection at this second test Negative HCV RNA detection at this second test
indicates that therapy has been successful.indicates that therapy has been successful.
Treatment of Treatment of Chronic Hepatitis CChronic Hepatitis C
Based on a combination of:Based on a combination of: pegylated interferon (IFN) alfa, pegylated interferon (IFN) alfa, either pegylated IFN alfa-2a either pegylated IFN alfa-2a
or pegylated IFNalfa-2bor pegylated IFNalfa-2b and ribavirinand ribavirin
General Prevention StrategiesGeneral Prevention Strategies Communication of information about HCV to health Communication of information about HCV to health
care and public health professionals care and public health professionals Education of the public and persons at risk for infectionEducation of the public and persons at risk for infection Integration of prevention and control activities into Integration of prevention and control activities into
public health programs to:public health programs to: Identify, counsel, and test persons at risk for HCV infectionIdentify, counsel, and test persons at risk for HCV infection Provide referral for medical evaluation of those found to be Provide referral for medical evaluation of those found to be
infected infected Conduct outreach and community-based activities to address Conduct outreach and community-based activities to address
practices that put people at risk for HCV infectionpractices that put people at risk for HCV infection Surveillance to monitor acute and chronic disease Surveillance to monitor acute and chronic disease
trends and evaluate the effectiveness of strategiestrends and evaluate the effectiveness of strategies Epidemiologic and laboratory investigations to better Epidemiologic and laboratory investigations to better
guide prevention efforts. guide prevention efforts.
Prevention Strategies Prevention Strategies in Pakistanin Pakistan
Methadone treatment programsMethadone treatment programs Needle and syringe exchange programsNeedle and syringe exchange programs Comprehensive risk-modifying educational proComprehensive risk-modifying educational pro
gramsgrams Ensuring access to sterile syringes through phEnsuring access to sterile syringes through ph
ysician prescription and pharmacy sales of syrysician prescription and pharmacy sales of syringes to IDUs inges to IDUs
IDUs should be educated about:IDUs should be educated about: the importance of hand washing before and after givthe importance of hand washing before and after giv
ing injectionsing injections not using the others' injection equipmentnot using the others' injection equipment avoiding any contact with blood from other personsavoiding any contact with blood from other persons
Future ResearchFuture Research Development of reliable, reproducible, and efficient Development of reliable, reproducible, and efficient
culture systems for propagating HCVculture systems for propagating HCV Role of genetic factors in the pathogenesis of HCVRole of genetic factors in the pathogenesis of HCV Development of less-toxic therapies and molecular-Development of less-toxic therapies and molecular-
based agents that specifically inhibit viral replication based agents that specifically inhibit viral replication and/or translation of viral RNA. and/or translation of viral RNA.
Directed investigation examining the development and Directed investigation examining the development and progression of hepatic fibrosis progression of hepatic fibrosis
Establishment of Hepatitis Clinical Research Network Establishment of Hepatitis Clinical Research Network to conduct of research related to the natural history, to conduct of research related to the natural history, prevention, and treatment of hepatitis C. prevention, and treatment of hepatitis C.
Examine the pattern of HCV disease progression in Examine the pattern of HCV disease progression in persons infected for at least two decades, including persons infected for at least two decades, including those infected as infants and as childrenthose infected as infants and as children
Future ResearchFuture Research Analysis of effectiveness of infection-control strategiesAnalysis of effectiveness of infection-control strategies Better understanding of factors that might predict Better understanding of factors that might predict
transmission transmission Understanding side effect management and increasing Understanding side effect management and increasing
patient adherence to therapy. patient adherence to therapy. Analysis of effect of health insuranceAnalysis of effect of health insurance Clearly establish the role of liver biopsy in the Clearly establish the role of liver biopsy in the
therapeutic management of patients with chronic therapeutic management of patients with chronic hepatitis C. hepatitis C.
International standardization of viral RNA titers International standardization of viral RNA titers Role of fatty liver, obesity, diabetes, and hepatic iron Role of fatty liver, obesity, diabetes, and hepatic iron
stores in the natural history of hepatitis C and stores in the natural history of hepatitis C and responses to therapy. responses to therapy.
Better understand HIV co-infected patientsBetter understand HIV co-infected patients