HEPATITIS PEDIATRICS – 2

HAZEL ASPERA
 HEPATOTROPIC VIRUSES

Heterogenous group of infectious agents

Can cause similar acute clinical illnesses
In most pedia pts  acute phase causes
no to mild clinical dse
Morbidity r/t rare cases of acute liver
failure in susceptible pts or dev’t of
chronic liver disease (hepa B,C,D)
 PATHOGENESIS

Infection

Direct Immune-
Cytopathic Injury mediated Injury
 PRESENTING S X

 Icterus/Jaundice
 Hepatomegaly, tenderness
 Splenomegaly
 Lymphadenopathy
 Extrahepatic Sx (Usually w/ HBV & HCV)
 Rashes
 Arthritis
 Encephalopathy & Acute Liver Failure
 Bleeding
 Altered Sensorium
 Hyperreflexia
 COMMON BIOCHEMICAL PROFILES

•Inc Alanine •Inc Serum

Cholestasis

Altered Synthetic Fxns

Cytopathic Injury

• Abnormal CHON
Aminotransferase Conjugated Bilirubin synthesis
(ALT) •Inc Alkaline • Prolonged PT
•Inc Aspartate Phosphatase • Inc INR
Aminotransferase •Inc 5’-Nucleotidase
(AST) • Dec Albumin
•Inc γ-glutamyl
transpeptidase • Metabolic
Disturbances
• Hypoglycemia
• Lactic Acidosis
• Hyperammonemia
• Poor Clearance of
Meds Dependent on
the Liver
• Altered sensorium w/
Inc DTR
TO UNDERSTAND THIS, LET’S BACKTRACK!
 FUNCTIONS OF THE LIVER

 Metabolic
 Carbohydrate Metabolism
 Fat Metabolism
 Protein Metabolism
 Bilirubin conjugation & bile excretion
 Vitamin Storage
 Iron Storage
 Formation of Coagulation Factors
 Metabolism / Detoxification of Drugs, Hormones, etc.
 INFECTION + INFLAMMATION

 Metabolic
 Carbohydrate Metabolism  HYPOGLYCEMIA + LACTIC ACIDOSIS
 Fat Metabolism
 Protein Metabolism  AMMONIA NOT CONVERTED TO UREA 
HYPERAMMONEMIA  ENCEPHALOPATHY  CHANGED SENSORIUM +
HYPERREFLEXIA
 DEC ALBUMIN
 Bilirubin conjugation & bile excretion  INC CONJUGATED
BILIRUBIN  ICTERUS/JAUNDICE
 Vitamin Storage
 Iron Storage
 Formation of Coagulation Factors  INC PT  BLEEDING
 Metabolism / Detoxification of Drugs, Hormones, etc.  POOR
CLEARANCE OF MEDS DEPENDENT ON LIVER
 INFECTION + INFLAMMATION

Hepatocellular Damage
Inc AST, ALT, ALP, 5-Nucleotidase, GGT

Organs
Hepatomegaly w/
Splenomegaly Lymphadenopathy
tendernness

Extrahepatic
Rashes Arthritis
 DIFFERENTIAL DIAGNOSES

NEWBORN

• Infection
• Metabolic Dse
• Anatomic Causes
• Inherited Intrahepatic Cholestasis

LATER CHILDHOOD

• Extrahepatic obstxn
• Inflammatory conditions
• Immune dysregulation
• Toxins & Medications
COMPARISONS
 FEATURES OF HEPATOTROPIC VIRUSES

HAV HBV HCV HDV HEV

INCUBATION (days) 15-19 60-180 14-160 21-42 21-63
TRANSMISSION

 PARENTERAL R    
 FECAL-ORAL     
 SEXUAL   R  
 PERINATAL   U  
(5-15%)
CHRONIC INFECTION     
FULMINANT DSE R  R  
 DIAGNOSTIC BLOOD TESTS:
SE ROLOGY & V I R A L P C R

HAV HBV HCV HDV HEV

Acute/Active Infection

Anti-HAV IGM (+) Anti-HBc IGM (+) Anti-HCV (+) Anti-HDV IgM (+) Anti-HEV IgM (+)

Blood PCR + HBsAG (+) HCV RNA (+) Blood PCR + Blood PCR +
Anti-HBs (-) HBsAG (+)
HBV DNA (+) Anti-HBS (-)
Past Infection (Recovered)

Anti-HAV IgG (+) Anti-HBs (+) Anti-HCV (+) Anti-HDV IgG (+) Anti-HEV IgG
Anti-HBc IgG (+) Blood PCR - Blood PCR - (+)
Blood PCR -
Chronic Infection

N/A Anti-HBc IgG (+) Anti-HCV (+) Anti-HDV IgG (+) N/A
HBsAg (+) Blood PCR + Blood PCR –
Anti-HBs (-) HBsAg (+)
PCR (+) or (-) Anti-HBS (-)
Vaccine Response

Anti-HAV IgG (+) Anti-HBs (+) N/A N/A N/A

Anti-HBc (-)
 TEXTBOOK COMPARISON
A B C D E
ETIOLOGY RNAV dsDNA ssRNA, Cannot produce RNAV
Picornavirus 6 major infection w/o
genotypes Hep B
EPIDEMIOLOGY Common Worldwide Common liver Coinfection – Fecal-oral
worldwide disease in adults similar transmission
Contact incubation to Incubation 15-
Fecal-oral transmission Perinatal HBV 60d (~40)
transmission transmission in
Perinatal kids Suprainfection –
High contagious transmission 2-8wks
Mean incubation Incubation 2-
– 3wks 24wks (~7-
9wks)

PATHOGENESIS Immune Primarily Cytopathic Cytopathic

Cytopathic
Predominantly + Immune No distinct
noncytopathoge features
nic No distinct
features Usually severe

Acute – least
severe
 TEXTBOOK COMPARISON
A B C D E
CLINICAL Anicteric , In many Mild, insiduous Similar to other Similar to Hep A
MANIFESTATION similar to AGE children: Hep viruses
S asymptomatic ALF – rare No chronic dse
Acute febrile i Chronic dse – Coinfection – except in
Llness Jaundice, most likely acute immuno-
fatigue, (clinically silent, compromised
Typical duration: anorexia, slow fibrosis) Superinfection –
7-14 days malaise chronic
DIAGNOSTICS Anti-HAV (IgM) Depends on Anti-HCV (not Coinfection – IgM Ab (after
whether acute or protective) IgM to HDV 2-4 1wk)
chronic (see wks
table later) Viral RNA – stool
Superinfection – & serum
IgM to HDV
10wks
TREATMENT No specific Acute: Acute: 1-2 No specific vax –
treatment supportive antivirals x 12- vax for HBV
24 wks
Supportive Chronic: In
treatment evolution Chronic:
Peginterferon
IFN-α2b, Lamivudine
Adefovir, Entecavir IFN-α2b
Tenofivir, Ribavarin
Peginterferon α2
(children >3yo)
 TEXTBOOK COMPARISON
A B C D E
PREVENTION IgA Screen moms & No vax No vax Recombinant
vax babies vax (adults)
HAV vax If (+), screen Vax for HBV
Antivirals in yearly w/ liver
moms with inc UTZ & α-
viral load fetoprotein

HBIG in specific Vax vs Hepa A &

post-exposure B
circumstances
(temporary
protection 3-6
mos)

Universal vax
PROGNOSIS & ALF infrequent Favorable but / G 1: Poor
COMPLICATIONS risk for ALF response to Tx
Prolonged
cholestatic Chronic – G 2 & 3: highly
syndrome cirrhosis, HCC responsive

If perinatal – inc 25%  HCC,

risk for cirrhosis
chronicity
 APPROACH TO ACUTE OR CHRONIC
HEPATITIS
 ACUTE HEPATITIS (for primary pediatrician)
 Identify deterioration, development of ALF
 If + refer to transplant center
 CHRONIC HEPATITIS
 Close follow-up & referral to pediatric hepatologist
 Avoid further insult to the liver
 Do HAV vaccine
 Avoid alcohol, obesity
 Care with taking new meds
 Offer appropriate support for pt and educate social circle
HEPATITIS A
 ETIOLOGY

 HAV
 RNAV
 Picornavirus fam
 Heat stable
 Limited host range (humans, primates)
 EPIDEMIOLOGY

 Occurs throughout the world, prevalent in developing

countries
 Highly contagious
 Person to person: fecal to oral
 Perinatal Transmission: Rare
 Mean incubation period: 3 wks
 Fecal excretion @ late incubation  Peaks before onset of SSx
 resolves 2wks after onset of jaundice
 Duration of excretion prolonged in infants
 CLINICAL MANIFESTATIONS

ACUTE HEPATITIS only

Anicteric Illness – Indistinguishable from
viral gastroenteritis
Symptomatic in:
Adolescents
Adults
Pts w/ underlying liver d/o
Immunocompromised
 CLINICAL MANIFESTATIONS

Acute Febrile Illness w/ abrupt onset of:

Anorexia
Nausea
Malaise
Vomiting
Jaundice
 CLINICAL MANIFESTATIONS

Typical Duration: 7-14 days

Other Organ Systems Affected:
Regional lymphadenopathy
Splenomegaly
Mod. bone marrow hypoplasia  Aplastic
anemia
Small intestine  change in villous structure
Ulceration of GIT
 CLINICAL MANIFESTATIONS

Rare
Pancreatitis
Myocarditis
Nephritis
Arthritis
Leukocytoclastic vasculitis
Cryoglobulinemia
 DIAGNOSIS

 Anti-HAV IgM Ab
 Neutralizing Anti-HAV IgG Ab
 Other tests (universal and do not help w/ DDx):
 ALT
 AST
 Bilirubin
 Alkaline Phosphatase
 5’-Nucleotidase
 GGT
 COMPLICATIONS

Most achieve full recovery

Distinct complications
ALF (Infrequent)
Prolonged Cholestatic Syndrome
 Waxes & wanes over several months
 Pruritic & fat malabsorption
 Occurs in absence of liver synthetic dysfxn
 Resolves without sequelae
 TREATMENT

No specific Tx
Supportive Tx
IV Hydration
Antipruritic Agents
Fat-soluble vitamins
Serial monitoring for ALF  Prompt
referral to Transplant Center!
 PREVENTION

Patients contagious 2wks before &

approx 7 days after onset of jaundice
CAREFUL HANDWASHING
CONTACT & STANDARD PRECAUTIONS
 PREVENTION

 PROPHYLAXIS
 PREEXPOSURE
 Ig
 Up to 2 mos protection for: BOTH <2 wks to travel:
 Children <12 mos • Older pts
 Allergic to vaccine • Immunocompromised
 Elects not to receive vaccine • Chronic liver dse
 HAV vaccine • Other medical cond’ns
 Preferred
 POSTEXPOSURE
 Ig
 Not effective >2wks after exposure
 Not routinely recommended for sporadic nonhousehold exposure
 Given to:
 Children <12mo
 Immunocompromised
 Chronic liver dse
 Vaccine contraindicated
 HAV vaccine
 Healthy pts 12 mos – 40 yrs
 Long-term protection, availability, ease of administration, less or similar cost
 PREVENTION

INDICATIONS & UPDATED DOSAGE FOR Ig Prophylaxis

PREEXPOSURE
> Up to 1 mo travel 0.1 mL/kg
> Up to 2 mo travel 0.2mL/kg
> More than 2 mo 0.2mL/kg (repeat q2mo)
POSTEXPOSURE 0.1mL/kg
 PREVENTION

VACCINES
 2 activated, highly immunogenic, safe vaccines
 Both approved for kids >12mos
 IM x 2 doses (2 nd dose after 6-12mos)
 Protective titer >10yrs
 If immunocompromised, older or w/ chronic illness  BOTH
Ig & vax
 Available combo HAV & HBV vax for >18yo
 Vax effective @ outbreaks  rapid seroconversion +
long incubation period
 PROGNOSIS

Excellent without long-term sequelae

Only feared complication  ALF
Remains major cause of morbidity  inc
socioeconomic impact during epidemics & in
endemic areas
HEPATITIS B
 ETIOLOGY

 HBV
 DNAV
 Circular, partially dS
 4 constitutive genes
 S – surface  HBsAg
 C – core  HBcAg  (proteolytic clearance)  HBeAg (correlates w/ DNA levels)
 X
 P – polymer
 Hepadnaviridae fam
 Replicates predominantly in liver
 Also: Lymphocytes, spleen, kidney, pancreas
 EPIDEMIOLOGY

 Worldwide, est 400mil pts chronically af fected

 ¼ of chronic carriers  serious sequelae
 Many infections in children asymptomatic
 HBV concentrations
 High in:
 Blood
 Serum
 Serous exudates
 Mod in:
 Silva
 Vaginal fluid
 Semen
 EPIDEMIOLOGY

 Ef ficient transmission – blood & sex

 Incubation period: 45 -160 days (mean 120 days)
 Risk factors:
 IV drugs or blood products
 Needles (acupuncture, tattoos)
 Sexual contact
 Institutionalized care
 Intimate contact w/ carriers
 EPIDEMIOLOGY

 Perinatal exposure to HBsAg from mom

 Highest risk if mom HBeAg +
 90% become chronically affected without Tx
 Risks:
 Inc maternal viral load
 Delivery of prior infant who is + despite prophylaxis
 Serologic Markers & Antigenemia  1-3 mos after birth
 Possible source: virus in amniotic fluid, maternal feces or blood
 Give HBIg or HBV vax w/in 2h of delivery
 Mothers w/ infants who develop chronic HBV  Subsequent
pregnancies: Antiviral therapy in 3 rd trimester
 HBsAg – inconsistently recovered in breasmilk
 EPIDEMIOLOGY

 Risk of developing chronic HBV – being HBsAg (+) >6mos

 Inversely r/t age of acquisition
 Risk for chronic infection:
 90% <1yr
 30% 1-5yr
 2% adults
 Chronic infection – assoc w/ dev’t of chronic liver disease & HCC
 CA risk independent of cirrhosis  most prevalent CA-related death
in young adults in Asia
 EPIDEMIOLOGY

10 GENOTYPES
A Pandemic
B
Asia
C
D South Europe
E Africa
F USA
G USA + France
H Central America
I Southeast Asia
J Japan
 PATHOGENESIS

 Acute response similar to other viruses

 Persistent of histologic changes  chronic liver
disease
 UNLIKE OTHER HEPA VIRUSES
 PREDOMINANTLY NONCYTOPATHOGENIC
 Injury mostly by immune-mediated processes
 Most complete immune response associated with highest
clearance BUT WITH highest injury
 Infection of hepatocytes  Expression of viral
antigens on surface (HBcAg, HBeAg)  Antigens (w/
class I MHC CHONs)  Cell target for cytotoxic T-cell
lysis
 PATHOGENESIS

 Chronic hepatitis
 Less well-understood
 Core CHON or MHC Class I CHONs may not be recognized 
some cytotoxic lymphocytes might not be activated or some
other unknown mechanism interferes w/ destruction of
hepatocytes
 Tolerance phenomenon predom. in prenatal cases  Inc.
incidence in children w/ no or little liver inflamm, normal liver
enzyems, & markedly inc HBV viral load
 End-stage liver disease rarely develops  (uncontrolled viral
replication cycles?)  HCC risk is high
 PATHOGENESIS

 ALF seen in infants of chronic carrier moms w/

AntiHBe or affected w/ precore mutant strain
 Postulate: HBeAg exposure in utero of infants of
chronic carriers  induces tolerance to virus
 Immune mechanisms involved in extrahepatic
conditions
 Circulating immune complexes w/ HBsAg
 Polyarteritis nodosa
 Membranous/Membranoproliferative Glomerulonephritis
 Polymyalgia Rheumatica
 Leukocytoclastic vasculitis
 Guillan-Barre Syndrome
 CLINICAL MANIFESTATIONS

 Many acute cases in kids  Asymptomatic

 Usual acute symptomatic episode similar to HAV & HCV BUT
may be more severe
 More likely to involve skin & joints
 First biochemical evidence : elevation of serum ALT (rise
before devt of fatigue, anorexia, & malaise @ approx 6-7 wks
p exposure)
 In a few children, illness preceded by serum-sickness-like
prodrome: arthralgia or skin lesions, inc urticarial, purpuric,
macular or maculopapular rashes.
 Extrahepatic: Polyarteritis nodosa, glomerulonephritis,
aplastic anemia
 Jaundice in 25% - begins 8wk p exposure, lasts approx 4 wks
 CLINICAL MANIFESTATIONS

 Usual course in children: 6 -8wks

 Greater rate of symptomatic illness and ILF in B than in A .
 Most patients recover.
 Chronic carrier state 10% cases acquired in adulthood
 Chronic infection occurs in up to 90% perinatally -infected
cases
 Cirrhosis and HCC only seen with chronic infection
 3 phases of chrobic HBV:
 Immune tolerant (most children, no Tx developed)
 Immune active (most Tx target this phase)
 Inactive
DIAGNOSIS
 DIAGNOSIS
HBsAg Total Anti- IGM Anti Anti-HBs HBV DNA
HBc HBc
Never infected - - - - -
Early acute
Transient p vaccination + - - - +/-
(up to 18 days)
Acute infection + + + - +
Acute resolving infection - + + +/- +/-
Recovered from past
infection & immune - + - + -
Chronic infection + + - - +
False +, past infection,
Low-level chronic,
passive immunity from - + - - +/-
HBsAG + mom
Immune if anti-HBS
≥10mIU/mL, passive - - - + -
immunity from Ig
 COMPLICATIONS

 ALF with coagulopathy, encephalopathy, cerebral edema

 Risk of ALF increased with co/super -infection with HDV or in
immunocompromised host
 Mortality from ALF >30% (liver transplant only ef fective
intervention)
 Chronic hepatitis  cirrhosis, end-stage liver dse, HCC
 Membranous glomerulonephritis w/ deposition of complement
& HBeAg in glomerular capillaries – rare complication
COMPLICATIONS
 TREATMENT

 Acute HBV : Supportive

 Close monitoring for liver failure & extrahepatic morbidities
 Chronic HBV: In evolution
 No 1 drug achieves consistent, complete eradication of virus
 Tx should be individualized, under care of pediatric hepatologist
 Goal of Tx: reduce viral replication (undetectable HBV DNA in serum,
dev’t of anti-HBe)
 Treatment indicated for pts in immune active form (evidenced by
elevated ALT and/or AST, + fibrosis on liver biopsy)
 TREATMENT

 Strategies:
 IFN-α2b – immunomodulatory and antiviral
 Lamivudine – oral synthetic nucleoside analog (inhibits viral reverse
transcriptase)
 Adefovir – purine analog that inhibits viral replication
 Entecavir – nucleoside analog that inhibits replication
 Tenofovir – nucleotide analog that inhibits viral replication
 Peginterferon-α 2 – same mechanism as IFN but given once weekly
 Immune tolerant pts (normal ALT and AST, HBeAG + with
elevated viral load) – not considered for Tx
 PREVENTION

 Most ef fective prevention: screening pregnant mothers, use

HBIG and HBV vax in infants (w/in 12h of birth)
 Mothers with HBV DNA viral load >200,000IU/mL receive an
antiviral s.a. telbuvudine, lamivudine, or tenofovir during 3 rd
trimester (especially if w/ previous child who developed
chronic HBV after receiving HBIG and HBV vax)
 Identify household, sexual, and needle -sharing contacts with
known cases.
 HBIG indivated only for specific postexposure circumstances,
provides temp protection (3 -6mos)
 PREVENTION

 Universal vaccination: 2 single -antigen vaccines (Recombivax

HB and Engerix-B) approved for children
 3 combination vaccines used for subsequent immunization
dosing, enable integration of HBV into regular immunization
schedule
 Seropositivity is >95% with all vaccines after the 2 nd dose
 3 rd dose – booster, long-term immunity
 4 th dose – for immunosuppressed and infants BW <2,000g
 Postvaccination testing for HBsAg and anti-HBs done at 9-18
months
 PREVENTION

 Postexposure prophylaxis:
 Depend on conditions under which person exposed to HBv
 Vaccination should never be postponed
 Special populations:
 Pts with cirrhosis may not respond well to HBV vaccine. Repeating
titers should be performed.
 Pts with IBD – freq have not been immunized or did not devlop
complete immunity. May be at risk for fulminant HBV (reactivation)
when immunosuppression started as part of treatment regimen,
specifically with biologic agents such as infliximab
 PROGNOSIS

 Acute HBV: generally favorable, despite risk of ALLF

 Risk of chronic infection  liver cirrhosis and HCC
 Perinatal transmission leading to chronicity  high incidence
of HCC in young adults in endemic areas
HEPATITIS C
 ETIOLOGY

 sRNAV
 Flaviviridae fam
 6 major genotypes
 Genetic variation  differences in clinical course and response to
treatment
 Most common in US: genotype 1b, least responsive to
pediatric medications
 EPIDEMIOLOGY

 In US, most common cause of chronic liver disease in adults.

 85% of infected adults remain chronically infected.
 In children: <11yo 0.2%
≥11yo 0.4% seroprevalence
 Risk factors
 Blood transfusion before 1992
 Illegal drug use with exposure to blood or blood products from infected
persons (most common)
 Sexual transmission (2 nd most common)
 Occupational exposure
 Perinatal transmission (most common in children)
 Up to 5% of infants born to viremic mothers
 HIV coinfection and high viremia titers  increase transmission rate to 20%
 Incubation period 2-24 wks (~7-9wks)
 PATHOGENESIS

 Cytopathic mechanisms, but immune-mediated injury can also

occur.
 Cytopathic component appears to be mild  least severe of hepa
virus infections.
 Indistinguishable from other hepa viruses
 Chronic cases: lymphoid aggregates or follicles in portal
tracts, Steatosis
 CLINICAL MANIFESTATIONS

 Acute: mild and insiduous, ALF rare

 Chronic: likely; 6-19% of children achieve spontaneous
sustained clearance of virus during 6yr follow up
 Clinically silent until complication develops
 Serum aminotransferase levels fluctuate
 Histologic inflammation is universal
 Progression to liver fibrosis is slow (unless with comorbid factors)
 25% progress to cirrhosis, liver failure, occ. Primary HCC within 20 -30
years
 (Progression is rare in pediatric age range)
 DIAGNOSIS

 Anti-HCV – great predictive value in high -risk populations

 False positive rate as high as 50-60% in low-risk populations
 False negatives b/c antibodies are negative for as long as 1 -3 mos
after onset of illness
 NOT a protective antibody and does not confer immunity
 HCV virologic assay (PCR)
 Qualitative  pts with recent infection
 Quantitative  monitor response to therapy
 DIAGNOSIS

 Determining HCV genotype is important!

 Genotype 1 – poorly responsive to therapy
 Genotypes 2 & 3 – more favorable response
 Aminotransferase – fluctuate during infection, do not
correlate with degree of liver fibrosis
 Liver biopsy  now replaced with UTZ or magnetic resonance
elastography to assess fibrosis
 COMPLICATIONS

 Risk for ALF is low

 Risk for chronic hepa is highest of all hepatitis viruses

 In adults, risk factors for progressions

 Older age
 Obesity
 Male
 Moderate alcohol ingestion (2 1oz drinks/day)
 Progress to cirrhosis or HCC  major cause of morbidity, most
common indication for liver transplant
 TREATMENT

 1-2 oral meds with direct -acting antiviral properties, for 12 -24
wks (dependent on HCV genotype & other clinical factors)
 Goal of treatment: sustained viral response  (-) viremia
 Chronic hepatitis, for children >3 yo:
 Peginterferon
 IFNα2b
 Ribavirin
 Side ef fects of medications:
 Influenza-like symptoms
 Anemia
 Neutropenia
 Long-term effects: differences in weight, height, BMI, body
composition
 TREATMENT

 Genotypes 2 & 3: children have 80 -90% response rate to

therapy with peginterferon & ribavarin
 Children with mild or no cirrhosis:
 Genotypes 1,4,5,6: Sofosbuvir ±ledipasvir
 Genotypes 2, 3: Sofosbuvir + ribavarin
 PREVENTION

 No vaccine
 Once infected, screen patients yearly
 Liver ultrasound
 Serum fetoprotein
 Vaccinate vs Hepa A & B to prevent superinfection
 PROGNOSIS

 Check viral titers yearly to document spontaneous remission

 Most patients develop chronic hepatitis
 Refer to pediatric hepatologist
HEPATITIS D
 ETIOLOGY

 Smallest known animal virus

 Defective – cannot produce w/o concurrent HBV infection
 Incapable of making own coat of protein
 Outer coat: excess HBsAg from HBV
 Inner core: ssRNA (circ)
 EPIDEMIOLOGY

 Coinfection – same time as HBV

 Superinfection – a person already infected

 HDV uncommon in children, but must be considered if ALF

occurs
 Incubation period:
 Coinfection: similar to HBV
 Superinfection: approx 2-8wks
 PATHOGENESIS

 Cytopathic (unlike HBV)

 No distinguishing features, except that damage is usually
severe
 CLINICAL MANIFESTATIONS

 Similar to but more severe than of other hepatotropic viruses

 Coinfection:
 Acute hepatitis common
 Chronic hepatitis – low risk
 Superinfection:
 Acute illness rare
 Chronic hepatitis common
 High risk of ALF
 DIAGNOSIS

 IgM antibody to HDV

 Coinfection: 2-4 wks p infection
 Superinfection: 10 wks p
 TREATMENT

 Supportive measures
 No specific treatment
 Treat HBV infection
 Preferred regimen: IFN
 PREVENTION

 No vaccine
 Prevent HBV
 HBV vaccine
 HBIG
HEPATITIS E
 ETIOLOGY

 RNAV
 Nonenveloped sphere with spikes
 Similar structure to calciviruses
 EPIDEMIOLOGY

 Fecal-oral transmission (often waterborne)

 Assoc w/ shedding viral particles in stool
 Postulated to be the most common cause of acute hepatitis
and jaundice in the world
 Incubation period: 15 -60 days (~40)
 PATHOGENESIS

 Cytopathic
 CLINICAL MANIFESTATIONS

 Similar to HAV, but often more severe

 Chronic illness does not occur (except in immunosuppressed)
 Tends to af fect older pts (peak age 15-34 yrs)
 Major pathogen in pregnant women  ALF with high fatality
 DIAGNOSIS

 IgM antibody
 + after 1 wk of illness
 Viral RNA in stool and serum
 PREVENTION

 Recombinant hepatitis E vaccine highly ef fective in adults