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Viral Hepatitis - Historical Perspective
A“Infectious”
“Serum”
Viral hepatitis
Entericallytransmitted
Parenterallytransmitted
F, G,? other
E
NANB
B D C
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Viral Hepatitis
A B C D ESource ofvirus
faeces blood/blood-derived
body fluids
blood/blood-derived
body fluids
blood/blood-derived
body fluids
feces
Route oftransmission
fecal-oral percutaneouspermucosal
percutaneouspermucosal
percutaneouspermucosal
fecal-oral
Chronicinfection
no yes yes yes no
Prevention pre/post-exposure
immunization
pre/post-exposure
immunization
blood donorscreening;
risk behaviormodification
pre/post-exposure
immunization;risk behaviormodification
ensure safedrinking
water
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HAV Transmission
Close personal contact household contact, sex contact, child day care
centers
Contaminated food, water infected food handlers, raw shellfish
Blood exposure (rare) injecting drug use, transfusion
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Hepatitis A - Clinical Features
Incubation period: Mean 30 daysRange 15-50 days
Jaundice by <6 yrs, <10% age group: 6-14 yrs 40%-50%
>14 yrs 70%-80% Complications: Fulminant hepatitis
Cholestatic hepatitisRelapsing hepatitis
Chronic sequelae: None
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HAV - Typical Serologic Course
FecalHAV
Symptoms
ALT
IgM anti-HAV
Total anti-HAV
Months after Exposure
Tite
r
0 1 2 3 4 5 6 12
24
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Serological Testing
• HAV total Ab appears 4-5 weeks after infection and remains positive for the patient’s lifetime
• HAV IgM is present at the onset of symptoms and usually disappears after 4-6 months.
• The presence of total Ig without IgM indicates past infection
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Hepatitis A Virus
• Highest virus concentrations occur in stool 1-2 weeks before the onset of illness. Transmission is most likely at this time.
• Minimal virus present in stool 1 week after the onset of jaundice.
• In neonates and young children, virus may be detected in stool for months.
Treatment• Treatment is supportive.• Patients who develop fulminant infection require aggressive
supportive therapy, and should be transferred to a center capable of performing liver transplantation
• Approximately 85 percent of HAV-infected individuals have full clinical and biochemical recovery within three months, and nearly all have complete recovery by six months.
• Passive immunization with intramuscular polyclonal serum immune globulin as preexposure or postexposure prophylaxis
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Clinical Features
• Incubation period: Mean: 60-90 days Range: 45-180
days
• Clinical illness (jaundice): <5 yrs, <10% 5 yrs, 30%-50%
• Acute case-fatality rate: 0.5%-1%• Chronic infection: <5 yrs, 30%-90%
5 yrs, 2%-10% • Premature mortality from
chronic liver disease: 15%-25%
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Acute HBV Infection with Recovery
Weeks after Exposure
Titer
Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBsHBsAg
0 4 8 12 16 20 24 28 32 36 52 100
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Progression to Chronic HBV Infection
Weeks after Exposure
Titer
IgM anti-HBc
Total anti-HBc
HBsAg
Acute(6 months)
HBeAg
Chronic(Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52 Years
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HBV Transmission
• Parenteral• Sexual• Perinatal
• Risk of transmission increases with the level of HBV DNA in serum and HBeAg positive
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HBV Concentrations in Various Body Fluids
High ModerateLow/Not
Detectable
blood semen urineserum vaginal fluid feces
wound exudates saliva sweattears
breast milk
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HBV DNA Testing
• Assess of viral replication in chronic HBsAg carriers.
• Assess the risk of progression toward cirrhosis and hepatocellular carcinoma.
• Decision to treat.• Assess treatment efficacy and failure
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Approved Therapies for HBV Infection
• Interferons– Interferon alpha 2b (5 million units qd or 10 million units
TIW for 12-24 weeks)– Pegylated interferon alpha 2a (180 ug once/week for 48
weeks)• Nucleoside analogues
– Lamivudine (100 mg qd)– Entecavir (0.5 mg qd; 1 mg if lamivudine resistance)
• Nucleotide analogues– Adefovir (10 mg qd)
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HCV - Sources of Infection
Sexual 15%
Other* 5%Unknown 10%
Injecting drug use 60%
Transfusion 10%(before screening)
*Nosocomial; Health-care work; Perinatal
Source: Centers for Disease Control and Prevention
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Other Transmission Issues
• HCV is not spread by kissing, hugging, sneezing, coughing, food or water, sharing eating utensils or drinking glasses, or casual contact
• HCV infection status should not be used to exclude patients from work, school, play, child-care or other settings
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Acute Hepatitis C Clinical Presentation and Natural History
• HCV RNA can be detected in blood within 1-3 weeks after exposure
• Average time from exposure to seroconversion is 8-9 weeks
• Average time from exposure to symptoms period 6-7 weeks
• Liver injury (elevations in ALT) with 4-12 weeks
• Symptoms develop in only of 20% of patients– Nonspecific 10%-20%– Jaundice in only 20%-30%
CDC. MMWR. 1998; 47(No. RR-19):1-39. Hoofnagle JH Hepatology. 1997;26 (suppl 1): 15S-20SNIH Consensus Development Conference Panel Statement Management of Hepatitis C, 2002
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Hepatitis C Infection
• Incubation period Average 6-7 weeks Range 2-26 weeks• Case fatality rate Low• Chronic infection 75%-85%• Chronic hepatitis 70% (most asx)• Cirrhosis 10%-20%• Mortality from CLD 1%-5%
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Acute Hepatitis C
Chronic Hepatitis 75%-85 %
Cirrhosis 20 %
10-20 years
Hoofnagle JH Hepatology. 1997;26 (suppl 1): 15S-20SDi Bisceglie, Hepatology, 2000
Natural History of Hepatitis C
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Acute HCV Infection with Recovery
Symptoms +/-
Time after Exposure
Tite
r
HCV Ab
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4YearsMonths
HCV RNA
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Acute HCV Infection with Progression to Chronic Infection
Symptoms +/-
Time after Exposure
Tite
r
HCV Ab
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4YearsMonths
HCV RNA
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Hepatitis C Complications
• Hepatitis encephalopathy – if untreated can lead to: Confusion Disorientation Hallucination Stupor/Coma
• Jaundice• Pruritus• Renal damage/failure• Hypo/Hyperthyroidism• Varices of Esophagus, Stomach, Rectum• Muscle Wasting
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Extrahepatic Manifestations of Hepatitis C
• Hematologic: Mixed cryoglobulinemia(10%–25% of HCV patients)*
• Renal: Glomerulonephritis
• Dermatologic:– Porphyria cutanea tarda
– Cutaneous necrotizing vasculitis
– Lichen planus
Management of Hepatitis C. NIH Consensus Statement, 2002.
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Chronic Hepatitis C Factors Promoting Progression or Severity
• Increased alcohol intake• Age > 40 years at time of
infection• HIV co-infection• Other
– Male gender– Chronic HBV co-infection
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Treatment for Hepatitis C
Interferon + Ribavirin x 6-12 months – about 40% - 50% sustain viral clearance > 3 years.
Predictive Factors for Treatment Response: Low initial viral load levels Young age Low Fibrosis Score (Liver Biopsy) Female
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Hepatitis D - Clinical Features
Coinfection severe acute disease low risk of chronic infection
Superinfection usually develop chronic HDV infection high risk of severe chronic liver
disease
HBV - HDV Coinfection
Time after Exposure
Tite
r anti-HBs
Symptoms
ALT Elevated
Total anti-HDV
IgM anti-HDV
HDV RNA
HBsAg
HBV - HDV Superinfection
Time after Exposure
Tite
r
Jaundice
Symptoms
ALTTotal anti-HDV
IgM anti-HDV
HDV RNAHBsAg
Treatment
• The only drug approved at present for treatment of chronic hepatitis D is Interferon Alfa (IFNa)
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Hepatitis E Virus
Most outbreaks associated withfecally contaminated drinking water
Minimal person-to-person transmission Most cases usually have history of travel
to HEV-endemic areas
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Hepatitis E Virus Incubation period: Average 40 days
Range 15-60 days
Case-fatality rate: 1%-3% overall15%-25% in
pregnancy Illness severity: Increased with age Chronic sequelae: None identified
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Typical Serological Course - HEV
Weeks after Exposure
Tite
r
Symptoms
ALT
IgM anti-HEV
Virus in stool
0 1 2 3 4 5 6 7 8 9 10
11
12
13
anti-HEV
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Serological Profile HEV IgM is usually present at the onset
of symptoms and persists for 3-4 months
HEV IgG is also present at the onset of symptoms and persists for the patient’s lifetime
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HEV Detection Culture is worthless PCR can detect HEV RNA in serum
and stool specimens from 2 weeks before, to 2 weeks after, the onset of symptoms
Nucleic acid sequencing is useful for tracking HEV outbreaks
UNIVERSAL PRECAUTIONS !!!
When there is a risk of splashing, particularly with power tools Use of a full face mask ideally, or protective spectacles; Use of fully waterproof, disposable gowns and drapes, particularly during
seroconversion; Boots to be worn, not clogs, to avoid injury from dropped sharps; Double gloving needed (a larger size on the inside is more comfortable); Allow only essential personnel in theatre; Avoid unnecessary movement in theatre; Respect is required for sharps, with passage in a kidney dish; A slow meticulous operative technique is needed with minimised bleeding.
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