brief about viral hepatitis

1. VIRAL HEPATITIS
SUMAN RAJ BARAL

2. 2
Viral Hepatitis - Historical Perspective
A“Infectious”
“Serum”
Viral
hepatitis
Enterically
transmitted
Parenterally
transmitted
F, G,
? other
E
NANB
B D C

3. 3
Viral Hepatitis
A B C D E
Source of
virus
faeces blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
feces
Route of
transmission
fecal-oral percutaneous
permucosal
percutaneous
permucosal
percutaneous
permucosal
fecal-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

4. Hepatitis A

5. 5
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

6. 6
Hepatitis A - Clinical Features
Incubation period: Mean 30 days
Range 15-50 days
Jaundice by <6 yrs, <10%
age group: 6-14 yrs 40%-50%
>14 yrs 70%-80%
Complications: Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
Chronic sequelae: None

7. 7
HAV - Typical Serologic Course
Fecal
HAV
Sympto
ms
ALT
IgM anti-HAV
Total anti-HAV
Months after Exposure
Titer
0 1 2 3 4 5 6 1
2
2
4

8. 8
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

9. 9
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.

10. 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

11. 11
Hepatitis
B

12. 12
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%

13. 13
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

14. 14
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

15. 15
HBV Transmission
• Parenteral
• Sexual
• Perinatal
• Risk of transmission increases
with the level of HBV DNA in
serum and HBeAg positive

16. 16
HBV Concentrations in Various
Body Fluids
High Moderate
Low/Not
Detectable
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breast milk

17. 17
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

18. 18
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)

19. 19
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

20. 20
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

21. 21
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-20S
NIH Consensus Development Conference Panel Statement Management of Hepatitis C, 2002

22. 22
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%

23. 23
Acute Hepatitis C
Chronic Hepatitis
75%-85 %
Cirrhosis 20 %
10-20 years
Hoofnagle JH Hepatology. 1997;26 (suppl 1): 15S-20S
Di Bisceglie, Hepatology, 2000
Natural History of Hepatitis C

24. 24
Acute HCV Infection with Recovery
Symptoms
+/-
Time after Exposure
Titer
HCV Ab
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
YearsMonths
HCV RNA

25. 25
Acute HCV Infection with Progression to
Chronic Infection
Symptoms
+/-
Time after Exposure
Titer
HCV Ab
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
YearsMonths
HCV
RNA

26. 26
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

27. 27
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.

28. 28
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

29. 29
Diagnostic Tests for HCV
• Anti-HCV
• Qualitative PCR
• Quantitative PCR
• Genotyping assays

30. 30
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

31. 31
Hepatitis D Virus

32. 32
HDV Transmission
 Percutanous exposures
injecting drug use
 Permucosal exposures
sex contact

33. 33
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

34. HBV - HDV Coinfection
Time after Exposure
Titer
anti-
HBs
Symptoms
ALT
Elevated
Total anti-
HDV
IgM anti-HDV
HDV RNA
HBsAg

35. HBV - HDV Superinfection
Time after Exposure
Titer
Jaundice
Symptoms
ALT
Total anti-HDV
IgM anti-HDV
HDV RNA
HBsAg

36. Treatment
• The only drug approved at present for
treatment of chronic hepatitis D is Interferon
Alfa (IFNa)
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37. 37
Hepatitis E Virus
 Most outbreaks associated with
fecally contaminated drinking water
 Minimal person-to-person transmission
 Most cases usually have history of travel
to HEV-endemic areas

38. 38
Hepatitis E Virus
 Incubation period: Average 40 days
Range 15-60
days
 Case-fatality rate: 1%-3% overall
15%-25% in
pregnancy
 Illness severity: Increased with age
 Chronic sequelae: None identified

39. 39
Typical Serological Course - HEV
Weeks after Exposure
Titer
Symptoms
ALT
IgM anti-HEV
Virus in stool
0 1 2 3 4 5 6 7 8 9 1
0
1
1
1
2
1
3
anti-HEV

40. 40
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

41. 41
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

42. TREATMENT Of HEV
 SUPPORTIVE
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43. 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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44. THANK YOU
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