1. HEPATITIS
Khalid Bzeizi

2. What Is Hepatitis?
The word "hepatitis" means inflammation of the liver. Toxins, certain drugs, some diseases, heavy alcohol use, bacterial and viral infections can all cause hepatitis.

3. Hepatitis
Acute Hepatitis
Subacute Hepatitis
Chronic Hepatitis

4. Drug Induced Hepatitis
Penicillin
Halothane
Paracetamol
Isoniazid
Statins
Rifampicin
Herbal Medicines

5. Autoimmune Hepatitis
Classical
Anti LKM
Anti SLA

6. Viral Hepatitis Common viruses cause hepatitis include A,B,C,D,E
Viral Hepatitis: Hepatitis A through E (more than 95% of viral cause).
Herpes simplex, Cytomegalovirus, Epstein-Barr, yellow fever virus, adenoviruses.

7. Hepatitis A
An acute liver disease caused by the hepatitis A virus (HAV),
Duration: few weeks to several months.
It does not lead to chronic infection.

9. Hepatitis A Virus 6

10. Transmission of HAV
Ingestion of food or water contaminated with faecal matter

11. Clinical Manifestations
Incubation period 2 – 6 weeks
May be asymptomatic
Overt illness in 5%
Present as two stages,
1 Preicteric
2 Icteric

12. Clinical features Malaise Anorexia Nausea, vomitting liver tenderness
Onset of Jaundice
Recovery in 4-6 weeks
Mortality 0.1 – 1 %

13. Hepatitis A - Clinical Complications
Complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis
Chronic sequelae: None 7

14. Laboratory Diagnosis
Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA.
Past Infection i.e. immunity is determined by the detection of HAV-IgG by EIA.
Cell culture – difficult and take up to 4 weeks, not routinely performed
Direct Detection – EM, RT-PCR of faeces. Can detect illness earlier than serology but rarely performed.

15. Hepatitis A Infection Typical Serological Course Total anti-HAV Titer
Symptoms
Titer
ALT
Fecal
HAV
IgM anti-HAV 1 2 3 4 5 6 12 24
Months after exposure 9

16. Treatment No specific antiviral drug is available
Treatment is symptomatic
Specific passive prophylaxis by pooled normal human immunoglobulin given before exposure or in early incubation period can prevent or attenuate clinical illness.

17. Vaccination for HAV
Hepatitis A vaccination is recommended for all children starting at age 1 year, travellers to certain countries, and others at risk.
A full course containing two intramuscular injections of the vaccine
Protection starts after 4 weeks after injection and lasts for 10 – 20 years

18. Hepatitis B Infection

19. Hepatitis B Causative agent: Double stranded DNA virus.
Ranges in severity from a mild illness, lasting a few weeks (acute), to a serious long-term (chronic) illness that leads to cirrhosis and/or liver cancer.

20. Most Important Infectious Disease
There are more than 350 million carriers
25% of them will develop chronic active hepatitis.
World wide 1 million deaths a year are attributed to HBV related liver disease and Hepatocellular Carcinoma

22. Transmission of HBV Horizontal Transmission Vertical Transmission
Child-to-Child
Contaminated Needles
Sexual
Health Care Worker
Transfusion
Hemodialysis
Perinatal
Common in regions with HBsAg prevalence of > 2%
CDC Fact Sheet.
Lee. N Engl J Med. 1997;337(24):
Lavanchy. J Viral Hepat. 2004;11(2):

23. Hepatitis B - Clinical Features
Incubation period: Average days
Clinical illness (jaundice): <5 yrs, <10% yrs, 30%-50%
Acute case-fatality rate: 0.5%-1%
Chronic infection: <5 yrs, 30%-90% yrs, 2%-10% 29

24. Diagnosis
A battery of serological tests are used for the diagnosis of acute and chronic hepatitis B infection.
HBsAg - used as a general marker of infection.
HBsAb - used to document recovery and/or immunity to HBV infection.
anti-HBc IgM - marker of acute infection.
anti-HBcIgG - past or chronic infection.
HBeAg - indicates active replication of virus and therefore infectiveness.
Anti-Hbe - virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV.
HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.

25. Typical Serologic Course
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Total anti-HBc
Titre
anti-HBs
HBsAg
IgM anti-HBc 4 8 12 16 20 24 28 32 36 52
100
Weeks after Exposure 30

26. Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Acute
(6 months)
Chronic
(Years)
HBeAg
anti-HBe
HBsAg
Total anti-HBc
Titre
IgM anti-HBc 4 8 12 16 20 24 28 32 36 52
Years
Weeks after Exposure 31

27. Hepatitis B Virus Modes of Transmission
Sexual - sex workers and homosexuals are particular at risk.
Parenteral - IVDA, Health Workers are at increased risk.
Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations. 2 2 2

28. Disease Progression Occurs in 15% to 40% of Chronic HBV Patients

29. Treatment
Interferon
Lamivudine .
Adefovir
Entecavir
Tenofovir

30. Vaccination Genetically Engineered
Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries.

31. Hepatitis B Immunoglobulin
Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive

32. Hepatitis C Infection

33. What is Hepatitis C Virus
Hepatitis C virus was also known as Non A or Non B virus found while doing experiments on Chimpanzees.
HCV infections are seen only in humans
The epidemiology is like HBV infection.

34. Hepatitis C Virus capsid envelope protein protease/helicase
RNA-dependent
RNA polymerase
c22
33c
c-100 5’ 3’
core E1 E2
NS2
NS3
NS4
NS5
hypervariable
region 7 7 7

35. 14 14 14

36. Hepatitis C - Clinical Features
Incubation period: Average 6-7 wks
Range 2-26 wks
Clinical illness (jaundice): % (20-30%)
Chronic hepatitis: 70%
Persistent infection: %
Immunity: No protective antibody
response identified 8 8 8

37. Hepatitis C virus Six genotypes are identified.
In Saudi Arabia, genotype 4 accounts for around 65% of cases and genotype 1 around 25%.
Genotypes 1 and 4 are relatively more difficult to treat compared to genotypes 2 & 3.

38. How HCV transmitted Blood transfusions Transplantation of organs
Injectable drug abusers
Immunocompromised
Sexual transmission ?
Less important
Vertical transmission is possible

39. Clinical features Overt Jaundice is seen in 5% of patients
About 50 – 80% patients progress to
chronic hepatitis
May progress to Cirrhosis, or Hepatocellular carcinoma

40. Laboratory Diagnosis
HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.
ELISA test results to be confirmed with Immunoblotting assay
HCV-RNA

41. HCV Treatment
Pegylated Interferon
Ribavirin
DAAs
No vaccine

42. Hepatitis D Virus
The delta agent is a defective virus which shows similarities with the viroids in plants.
The agent consists of a particle 35 nm in diameter consisting of the delta antigen surrounded by an outer coat of HBsAg.
The genome of the virus is very small and consists of a single-stranded RNA

43. 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.
may present as an acute hepatitis. 20 20 20

44. Hepatitis E Virus Calicivirus-like viruses
unenveloped RNA virus, nm in diameter
+ve stranded RNA genome, 7.6 kb in size.
very labile and sensitive
Can only be cultured recently

45. Hepatitis E - Clinical Features
Incubation period: Average 40 days
Range days
Case-fatality rate: Overall, 1%-3% Pregnant women, %-25%
Illness severity: Increased with age
Chronic sequelae: None identified 27 27 27

46. Epidemiologic Features
Hepatitis E -
Epidemiologic Features
Most outbreaks associated with faecally contaminated drinking water.
Several other large epidemics have occurred since in the Indian subcontinent and the USSR, China, Africa and Mexico.
Minimal person-to-person transmission. 29 29 29