VIRAL HEPATITISSUMAN RAJ BARAL

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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

Hepatitis A

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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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Hepatitis B

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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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Diagnostic Tests for HCV

• Anti-HCV• Qualitative PCR• Quantitative PCR• Genotyping assays

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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 Virus

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HDV Transmission Percutanous exposures

injecting drug use Permucosal exposures

sex contact

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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

TREATMENT Of HEV

SUPPORTIVE

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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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THANK YOU

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