viral hepatitis a - e

8/17/2019 Viral Hepatitis A - E

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Viral Hepatitis A - E

Class IC2Course Tropical Medicine

Code TM

Title Professor

Lecturer Sam McConkey

Date 2015

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn


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Source of

virus

Faeces blood/

blood-derived body fluids

blood/


blood/


Faeces

Route of

transmission

Faecal-oral percutaneous

permucosal

percutaneous

permucosal

percutaneous

permucosal

Faecal-oral

Chronic

infection

no yes yes yes no

Prevention pre/post-

exposure

immunization

pre/post-

exposure

immunization

blood donor

screening;

risk behavior

modification

pre/post-

exposure

immunization;

risk behavior

modification

ensure safe

drinking

water

Type of Hepatitis

A B C D E


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HEPATITIS A VIRUS


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ACUTE VIRAL HEPATITIS

• HAV: small unencapsulated single stranded RNA virus

related to enterovirus

• Transmission primarily faeco-oral

•

Epidemiology varies in developed and developingcountries• Developed – human to human spread

• Developing - water and food borne transmission


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1 Jacobsen KH, Wiersma ST. Hepatitis A virus seroprevalence by age and world region, 1990 and 2005. Vaccine. 2010 Sep

24;28(41):6653 – 7.2 Estimates of prevalence of antibody to hepatitis A virus (anti-HAV IgG), a marker of previous HAV infection, are based on systematic

literature review conducted for the period of 1990 – 2005.


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PATHOLOGY OF HAV

• Degenerative and regenerative hepatic parynchymal

changes including lobular disarray and cellular

ballooning

• Liver injury is immune mediated

• Mononuclear inflammatory cellular infiltrate

• Similar to other acute viral hepatitis


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CLINICAL CHARACTERISTICS OF

HEPATITIS A IN PATIENTS BY AGE

1-14 years 15-39 years 40+years

Jaundice 61.7% 66.8% 70.3%

Hospitalised 17.1% 23.2% 41.6%

Death 0.1% 0.3% 2.1%


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ACUTE VIRAL HEPATITIS – CLINICAL

FEATURES

• Pre-icteric

– Malaise, fatigue, lethargy and weakness

– Anorexia and nausea with distaste for cigarettes

– Right upper quadrant pain

– Diarrhoea or constipation

– Diffuse aches and pains

– Fever and supra orbital headache.

• Jaundice

• Recovery


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PREVENTION OF HAV

• Avoidance of contaminated food

• Adequate hygiene and sanitation

• Passive immunisation

•

Active immunisation = VACCINE• Occupational risk

• Travellers

• Those who already have chronic hepatitis with C or B


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HEPATITIS E VIRUS


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CLINICAL FEATURES OF HEV

• Pathology

– classic morphology of acute infectioushepatitis, cholestasis more prevalent

• Incubation period 6 weeks (2-9 weeks)

• Asymptomatic cases common


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HEPATITIS E

• Mortality 0.1-0.2%, (pregnancy 10-20% mortality)

• No carrier state

• No life-long immunity exists

• No progression to active hepatitis or cirrhosis


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Symptoms

ALT IgG anti-HEV

IgM anti-HEV

Virus in stool

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Hepatitis E Virus Typical SerologicCourse

Titer

Weeks after Exposure


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DIAGNOSIS OF HEV

• Compatible epidemiological and clinical features

• Exclude Hepatitis A,B and CCMV and EBV infections

• Demonstrate 24-34nM particles in acute phase in

faeces.

• Serological testing now available


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HEPATITIS E - EPIDEMIOLOGIC FEATURES

Most outbreaks associated with faecally contaminateddrinking water.

Several other large epidemics have occurred since in the

Indian subcontinent and the USSR, China, Africa and Mexico.

Most developed countries:

a low prevalence of anti-HEV (


17/412010


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PREVENTION AND CONTROL MEASURES FOR

TRAVELERS TO HEV-ENDEMIC REGIONS

Avoid drinking water (and beverages with ice) ofunknown purity,

uncooked shellfish

uncooked fruit/vegetables


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PREVENTION OF HEV

• Sanitation

• Water supply

• Sewage disposal

[IG prepared from donors in Western countries does notprevent infection

Unknown efficacy of IG prepared from donors inendemic areas]


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BLOOD-BORNEHEPATITIS


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HBsAg Prevalence

High (≥ 8%)

Intermediate (2% to 8%)

Low (< 2%)

Mast EE, et al. MMWR Recomm Rep. 2006;55:1-33.

Custer B, et al. J Clin Gastroenterol. 2004;38(10 suppl):S158-S168.

HBsAg

Positive, %

Taiwan 10.0-13.8

Vietnam 5.7-10.0

China 5.3-12.0

Africa 5.0-19.0

Philippines 5.0-16.0

Thailand 4.6-8.0

Japan 4.4-13.0

Indonesia 4.0

SouthKorea

2.6-5.1

India 2.4-4.7

Russia 1.4-8.0

US 0.2-0.5

PREVALENCE OF HBV: GLOBAL

ESTIMATES


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CLINICAL FEATURES OF ACUTE

HEPATITIS B

• Jaundice, malaise

– Similar to HAV but incubation period is 10 weeks(6weeks to 6

months)

• More insidious onset and prolonged course

• Extrahepatic manifestations are more common – Urticarial/maculopapular rash

– Polyarthritis

–

Polyarteritis nodosa and acute glomerulonephritis are rarecomplications


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OUTCOME OF HBV INFECTION

• Chronic infection

– 5-10% adults

– 90% children


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Fattovich G et al. Gastroenterology. 2004;127:S35-S50. ; Yang HI, et al. N Engl J Med. 2002;347:168-174. ; Tang B, et al. JMed Virol. 2004;72:35-40.

RISK FACTORS FOR PROGRESSION OF LIVER

DISEASE (CIRRHOSIS, LIVER FAILURE, HCC)

• HBV genotype

• HBeAg positivity

• Presence of hepatic inflammation/

fibrosis/cirrhosis

–

Severity at presentation• Sustained activity of liver disease

– Elevated ALT

– Elevated HBV DNA

• HBV/HCV and HBV/HDV

coinfection

• Liver iron

• Liver fat

• High geographic endemicity

• Older age

• Male sex

• Immune status: HIV or organ

transplant• Alcohol abuse

• Smoking

• Positive family history for liver

cancer*

• Aflatoxin exposure*

*HCC only


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Lok AS, et al. Hepatology. 2007;45:507-539.

HBeAg Positive HBeAg NegativeALT < 1 x ULN ALT > 2 x ULN

Monitor patient HBV DNA> 20,000 IU/mL

HBV DNA< 2000 IU/mL

HBV DNA≥ 20,000 IU/mL

Treat if persistent Monitor patient Treat if persistent

ALT 1-2 x ULNALT 1-2 x ULN

HBV DNA > 20,000 IU/mL

Consider biopsy if persistent

or > 40 yrs; treat if needed

HBV DNA

2000-20,000 IU/mL

Consider biopsy; treat if needed

ALT < 1 x ULN ALT > 2 x ULN

AASLD GUIDELINES FOR CHRONIC

HEPATITIS B TREATMENT INITIATION


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HEPATITIS B AND PREGNANCY

Mother

Worsening of hepatitis

before or during

pregnancy? Worsening of hepatitis

after delivery?

Hepatitis B and other

disorders duringpregnancy

Infant

Transmission of HBV?

Teratogenicity of

drugs? Risk of fulminant

hepatic failure?

Breast-feeding?


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HBV TRANSMISSION: WHEN DOES IT

HAPPEN?

• In utero transmission

– Very rare (< 10%); associated with high HBV DNA levels[1]

• During amniocentesis

– Very rare; no transmission reported in 2 case series[2,3]

• At birth!

– HBeAg-positive mothers: 85%

– HBeAg-negative mothers: 31%[4]

1. Wang Z, et al. J Med Virol. 2003;71:360-366. 2. Alexander JM, et al. Infect Dis Obstet Gynecol.1999;7:283-286. 3. Towers CV, et al. Am J Obstet Gynecol. 2001;184:1514-1518. 4. Beasley RP, et al.

Am J Epidemiol. 1977;105:94-98.


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1. Linnemann CC, et al. Lancet. 1974;2:155.2. Hill JB, et al. Obstet Gynecol. 2002;99:1049-1052.3. Cornberg M, et al. J Viral Hepat. 2008;15:1-21.

4. Johnson MA, et al. Clin Pharmacokinet. 1999;36:41-66.

BREAST-FEEDING AND RISK OF HBV

TRANSMISSION

• HBV can be detected in breast milk[1]

• Neonates that are correctly immunized may be breast-

fed[2,3]

• Caveat: nucleos(t)ide analogues can be detected in

breast milk[4]


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PREVENTION OF HBV TRANSMISSION BY

POSTNATAL VACCINATION

• Active plus passive immunization most effective[1]

•

Role of maternal HBV DNA on transmision[2]

– HBV DNA < 150 pg/mL (1.1 x 107 IU/mL) = 0% transmission

– HBV DNA > 150 pg/mL = 32% transmission

No Vaccine Passive

Immunization

Passive + Active

Immunization

Infants without HBV, % 5 72 95

1. Ranger-Rogez S, et al. Expert Rev Ant Infect Ther. 2004;2:133-145.

2. del Canho R, et al. Vaccine. 1997;15:1624-1630.


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MANAGEMENT OF CHRONIC HEPATITIS

B

Antiviral therapy is indicated in progressive liver

disease Cytokine therapies – interferon alpha 40% successful

Nucleoside analogues –

lamivudine

Combination therapies: prednisone and interferon

Viral suppression therapy – requires therapy for 1-10 years

Liver transplantation with lamivudine and HB hyper immune serum


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PREVENTION

• Vaccination

– At risk groups

– ?all neonates

• Hepatitis B Immunoglobulin

– Within 48 hours of the incident - PEP

– Neonates at risk

• Other measures - screening of blood donors, blood and body

fluid precautions.


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HBsAg

RNA

antigen

Hepatitis D (Delta) Virus


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HEPATITIS D (HDV)

Discovered 1977

Incomplete RNA virus – dependant on HBV

Single stranded RNA molecule, HDAg surrounded by

HBsAg

HDV particles contain delta antigen and an RNAgenome inside a coat of HBV surface antigen


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INTRODUCTION

• Hepatitis C virus

– 1980s: Non-A/Non-B virus: post transfusion hepatitis – Flavivirus (RNA) – Screening blood tests available by early 1990s

• Worldwide health problem – 130 million infections – Cirrhosis, hepatocellular carcinoma, liver transplant

• HIV co-infection – common risk factors

• Seroprevalence rate• 15% Central Africa and Egypt

• 5% China

• 1% in developed countries


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EPIDEMIOLOGY IN HEPATITIS C

• Developed countries

– Injecting drug users

– Health care workers

–

Individuals onhaemodialysis

– Those who engage in

high-risk sexual

practices

• Developing countries

– Transfusions of

unscreened blood

– Unsafe injections or other

parenteral exposure toblood

– Use of blood contaminated

instruments

– Traditional scarification

– Tattoos, ear-piercing

– acupuncture


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CLINICAL FEATURES OF HCV

INFECTION

• Ranges from asymptomatic to fulminant hepatitis (0.1%)

• 70-80% cases are asymptomatic

• Icteric cases are more likely to recover

• Incubation period is up to 6-12 weeks

• 80% will progress to chronic hepatitis

•

10-20% will develop cirrhosis• 1-5% will develop HCC

• May be complicated by aplastic anaemia


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CHRONIC HEPATITIS C

• Aminotransferases abnormal by factor of 2-4• 10-20% will develop cirrhosis

• Differing rates of progression• Greater age at infection

• Concomitant alcohol abuse• Concomitant HBV or HIV infection

• Complications• Autoimmune hepatitis

• Cryoblobulinaemia

• Porphyria cunea tarda

• Lymphocytic sialo-adenitis

• Glomerlunephritis

• lymphoma


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MODERN ERA TREATMENT FOR

HEPATITIS C

• 1998

– Interferon-alpha plus ribavirin

• 2001

– Pegylated interferon-alpha plus ribavirin

• 2005 – date

– Small molecule therapy

– 20+ in development. Many now on market.

viral hepatitis a - e

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