Viral Hepatitis Viral Hepatitis in Reproductive Healthin Reproductive Health

JosJoséé BengoaBengoa

Training in Reproductive Health Training in Reproductive Health Research Research –– Geneva 2006Geneva 2006

15 march 200615 march 2006

Epidemiology of Hepatitis BEpidemiology of Hepatitis B Dr JosDr Joséé BengoaBengoaConsultant Geneva University HospitalConsultant Geneva University HospitalFranco Vietnamese Hospital, Ho Chi Franco Vietnamese Hospital, Ho Chi MinhMinh CityCity

Epidemiology of Hepatitis CEpidemiology of Hepatitis C Dr Pierre Jean Dr Pierre Jean MalMalèèConsultant Geneva University HospitalConsultant Geneva University HospitalFranco Vietnamese Hospital, Ho Chi Franco Vietnamese Hospital, Ho Chi MinhMinh CityCity

HB Vaccination ProgramsHB Vaccination Programs Dr Steven Dr Steven WiersmaWiersmaWHO, FCH Medical Officer/Hepatitis Focal PointWHO, FCH Medical Officer/Hepatitis Focal Point

New Interventions in Health Services New Interventions in Health Services Dr Rafael BengoaDr Rafael BengoaWHO, Director of Health Systems PoliciesWHO, Director of Health Systems Policies

Treatment of VHB and VHC Treatment of VHB and VHC Dr Pierre Jean Dr Pierre Jean MalMalèè

Honduras Hepatitis B project Honduras Hepatitis B project Dr Francesco AureliDr Francesco AureliDirector of Imagine Foundation, RomeDirector of Imagine Foundation, Rome

Vietnam Hepatitis B/C projectVietnam Hepatitis B/C project Dr JosDr Joséé BengoaBengoa

Epidemiology and Prevention Epidemiology and Prevention of Viral Hepatitisof Viral Hepatitis

Hepatitis BHepatitis B

Hepatitis CHepatitis C

Viral hepatitis Viral hepatitis

worldwideworldwide

VHBVHB 350350’’000000’’000000

VHCVHC 200200’’000000’’000000

Acute Viral Hepatitis A, B and C/NANB Acute Viral Hepatitis A, B and C/NANB by Year, United States, 1952by Year, United States, 1952--20002000

05

1015202530354045

1952 54 56 58

1960 62 64 66 68

1970 72 74 76 78

1980 82 84 86 88

1990 92 94 96 98

2000

Year

Repo

rted

case

s per

100

,000

pop

ulat

ion

Hepatitis A

Hepatitis C/ NANB

Hepatitis B

Total

CDC

Viral Hepatitis – Historical Perspective

AA““InfectiousInfectious””

““SerumSerum””

Viral Viral hepatitishepatitis

EntericallyEntericallytransmittedtransmitted

ParenterallyParenterallytransmittedtransmitted

otherother

EE

““NANBNANB””

BB DD

CC

CDC

Viral Hepatitis Overview

Source ofvirus

Route oftransmission

Chronicinfection

Prevention

modification

feces blood/blood-derived

body fluids

blood/blood-derived

body fluids

blood/blood-derived

body fluids

feces

fecal-oral percutaneouspermucosal

percutaneouspermucosal

percutaneouspermucosal

fecal-oral

no yes yes yes no

pre-exposure

immunization

pre/post-exposure

immunization

blood donorscreening;

risk behaviormodification

pre/post-exposure

immunization;risk behavior

ensure safedrinkingwater

Types of Viral Hepatitis

A B C D E

CDC

A, B, Cs of Viral Hepatitis• A

– fecal-oral spread: hygiene, drug use, men having sex with men, travelers, day care, food

– vaccine-preventable• B

– sexually transmitted – 100x more infectious than HIV– blood-borne (sex, injection drug use, mother-child,

and health care)– vaccine-preventable

• C– blood borne (injection drug use primarily)– 4-5 times more common than HIV– NOT vaccine-preventable!

CDC

Hepatitis B Virus

CDC

Geographic Distribution of Chronic HBV Infection

HBsAg Prevalence

≥8% - High 2-7% - Intermediate<2% - Low

CDC

Global Patterns of Chronic HBV Infection

High (>8%): 45% of global populationHigh (>8%): 45% of global population–– lifetime risk of infection >60%lifetime risk of infection >60%–– early childhood infections commonearly childhood infections common

Intermediate (2%Intermediate (2%--7%): 43% of global population7%): 43% of global population–– lifetime risk of infection 20%lifetime risk of infection 20%--60%60%–– infections occur in all age groupsinfections occur in all age groups

Low (<2%): 12% of global populationLow (<2%): 12% of global population–– lifetime risk of infection <20%lifetime risk of infection <20%–– most infections occur in adult risk groupsmost infections occur in adult risk groups

CDC

0

2

4

6

8

10

12

14

1967 1970 1973 1976 1979 1982 1985 1988 1991 1994 1997 2000

Year

Cas

es p

er 1

00,0

00 P

opul

atio

n

Source: NNDSS

Vaccine licensed

HBsAg screening of

pregnant women

recommended

OSHA Rule enactedAdolescent

Immunization recommended

Decline among MSM & HCWs

Decline amonginjecting

drug users

Infant Immunizationrecommended

CDC

Hepatitis B by Year (USA 1966-2000)

• Incubation period: Average 60-90 daysRange 45-180 days

• Clinical illness <5 yrs, <10%(jaundice): >5 yrs, 30%-50%

• Acute case-fatality rate: 0.5%-1%

• Chronic infection: <5 yrs, 30%-90%>5 yrs, 2%-10%

• Premature mortality fromchronic liver disease: 15%-25%

CDC

Hepatitis B – Clinical Features

Outcome of HBV InfectionOutcome of HBV Infection

Infection

Asymptomatic Symptomatic acute hepatitis B

ResolvedImmune Chronic infection

Asymptomatic CirrhosisLiver cancer

ResolvedImmune

Chronic infection

Asymptomatic CirrhosisLiver cancer

CDC

Outcome of Hepatitis B Virus Infectionby Age at Infection

Chr

onic

Infe

ctio

n (%

)

100100

Symptomatic Infection

Chronic Infection

Birth

1 -6

mos

7-12

mos

1 -4

yrs

Old

er C

hild

r en

and

Adul

ts

0

20

40

60

8080

60

40

20

0

Symptom

ati c In fec ti on (%)

CDC

Weeks after Exposure

Symptoms

HBeAg anti-HBe

Total anti-HBc

IgM anti-HBc

anti-HBsHBsAg

0 4 8 12 16 20 24 28 32 36 52 100

Tite

rTypical Serologic Course

CDC

Acute Hepatitis B Virus Infection with Recovery

Progression to Chronic Hepatitis B Virus InfectionTypical Serologic Course

IgM anti-HBc

Total anti-HBcHBsAg

Acute(6 months)

HBeAg

Chronic(Years)

anti-HBe

0 4 8 12 16 20 24 28 32 36 52

Weeks after Exposure

Tite

r

CDC

• Sexual

• Parenteral

• Perinatal

HBV Modes of Transmission

CDC

Low/NotHigh Moderate Detectable

semenserum vaginal fluidblood

wound exudates saliva

urinefecessweattears

breast milk

Concentration of HBV in Various Body Fluids

CDC

Blood transfusion 0%

Other* 15%

Unknown 32%

Hemodialysis 0%Multiple sex partners 17%

Injection drug use 14%

Men who have sex with men 6%

Sexual contact with hepatitis B patient 13%

Medical Employee 1%

Household contact of hepatitis B patient 2%

Risk Factors Associated with Reported Hepatitis B, 1990-2000, USA

*Other: Surgery, dental surgery, acupuncture, tattoo, other percutaneous injury

CDCSource: NNDSS/VHSP

Prevalence of VHBPrevalence of VHB

HBV serologic markers in USAHBV serologic markers in USA

Chinese/SEAChinese/SEA 13%13%drug usersdrug users 6%6%homosexual males 6%homosexual males 6%HIV infectedHIV infected 8%8%pregnant females 0.4 pregnant females 0.4 –– 1.5 %1.5 %

Phases of hepatitis B infectionPhases of hepatitis B infection

immunotoleranceimmunotolerance-- virus is non pathogenic for liver cellsvirus is non pathogenic for liver cells-- may last several yearsmay last several yearsimmunoeliminationimmunoelimination-- active hepatitis, high ALT, fibrosis, cirrhosisactive hepatitis, high ALT, fibrosis, cirrhosis-- HBeAgHBeAg positive chronic hepatitispositive chronic hepatitisinactive carrier of inactive carrier of HBsAgHBsAg-- low low viremiaviremia, , HBeAgHBeAg negativenegativereactivationreactivation-- viral mutation, viral mutation, HBeAgHBeAg negativenegative

Complications of viral hepatitisComplications of viral hepatitis

CirrhosisCirrhosisin in HBeAgHBeAg + 3% per year+ 3% per year

HCCHCC ((hepatocellularhepatocellular carcinoma)carcinoma)risk of 2 % per year risk of 2 % per year increased risk in VHB high increased risk in VHB high viremiaviremia

N N EnglEngl J Med September 15, 2005J Med September 15, 2005Major Causes of Death among Men Major Causes of Death among Men

and Women in Chinaand Women in ChinaJiangJiang He, M.D., Ph.D., He, M.D., Ph.D., DongfengDongfeng GuGu, M.D., , M.D., XiguiXigui Wu,etWu,et alal

Take home messagesTake home messages

hepatitis B is a world wide public health issuehepatitis B is a world wide public health issuemajor country differences in prevalence existmajor country differences in prevalence existtransmission: sexual, transmission: sexual, perinatalperinatal and and parenteralparenteralit is a vaccine preventable diseaseit is a vaccine preventable diseasecirrhosis and liver cancer will represent a cirrhosis and liver cancer will represent a major challenge in terms of health care costsmajor challenge in terms of health care costsbreakthroughs in therapy but very high costbreakthroughs in therapy but very high cost