Acute Hepatitis, Viruses, Hepatitis B

1. ACUTE HEPATITIS

2. Hepatitis
• Any disease process characterized by a diffuse inflammatory
infiltrate of liver tissue, with or without a degree of hepatocellular
necrosis and local fibrosis.
• Etiology
Infectious, Chemical, Toxic and Autoimmune

3. Clinical Forms
• Acute viral hepatitis
• Recent infection and inflammation of the liver
• Chronic viral hepatitis
• Persistent viral infection of liver tissue lasting
more than 6 months

4. • Causes of Acute Hepatitis
• Viruses (A,B,C,E,EBV,CMV)
• Alcohol
• Toxins (Carbon tetrachloride)
• Drugs (INH, PZA)

5. Acute Hepatitis
• Prodromal illness (Flu like)
• 􀀎 Vomiting
• 􀀎 Aversion to alcohol and cigarettes
• 􀀎 ABDOMINAL discomfort
• 􀀎 Pale faeces and dark urine
• 􀀎 Jaundice

6. Agents of Viral Hepatitis
• Enterically transmitted hepatitis
• Hepatitis A and E.
• Acute diseases with no chronic phase

7. • Blood-borne viral hepatitis
– Hepatitis B, C and D, all chronic infections
• Systemic agents not restricted to the liver
– HSV, VZV, EBV, CMV, HIV.

8. Hepatitis A
• Symptomatic Illness
• Symptomatic in 80% of adults but not children (<3%)
• Malaise, Vomiting and jaundice prominent
• Transmission patterns
• Person to person contact
• Common source outbreaks especially seafood

9. HAV Pathogenesis
• Ingested orally, Resistant to stomach acid
• Reaches the liver via the intestine
• Replicates in hepatocyte cytoplasm
• Secreted in the bile and excreted in faeces
• Cell mediated immune clearance and cyto-pathology
• Symptoms last 2-3 weeks

10. Laboratory Diagnosis of HAV
• Serological diagnosis
• Preferred method is EIA for anti-HAV IgM
• Acute antibody response with a rise in IgM
• Simultaneous gradual rise in IgG

12. HAV Prevention
•Inactivated whole-virus vaccine

13. Treatment
• Supportive re-hydration and nutrition
• Avoid alcohol
• Outcome
• �Recovery in > 99%, clinical relapse in 4-20%
• �Rarely need to hospitalize or transplant
• �Fulminant hepatitis <0.35%

14. Hepatitis E
• Epidemiology
• �A major cause of sporadic and epidemic
hepatitis
• �Water-borne
• �Only 5% of adult cases have jaundice

15. HEV Pathogenesis
• �Entry across intestinal mucosa (unknown)
• �Secreted in faeces
• 2 weeks before and 1 week after symptoms
• �Detected in serum for two weeks after onset
• �Affects liver Kupffer cells and hepatocytes
• �Cholestasis is a feature in 50% of cases
• �Injury appears immune mediated

16. Laboratory Diagnosis of HEV
• EIA based assays for IgM and IgG

17. HEV Prevention and Treatment
• Treatment
• Supportive therapy
• No specific treatment
• Prevention
• �No vaccines available
• �Recombinant protein in animal & human trials
• �Immune serum globulin is ineffective

18. • Alcoholic Hepatitis
• Can be acute or chronic
• Risk of cirrhosis variable…genetics, sex (women
• more susceptible,) presence of chronic hepatitis,
• possibly nutritional factor
• Presentation can range from an asymptomatic
• person to a critically ill one

19. • Drug induced Liver Disease
• 3 subtypes
• � Direct hepatotoxic group
• � Idiosyncratic reactions
• � Cholestatic reactions

20. • Direct hepatotoxic Group
• �Dose related severity
• �Latent period after exposure
• Examples…acetominophen, alcohol, carbon
• tetrachloride, niacin, vitamin A

21. • Idiosyncratic Reactions
• � Sporadic and rare
• � Not dose related
• � Occasionally fever and eosinophilia
• suggesting an allergic type reaction

22. • Cholestatic Reactions
• � Non-inflammatory (direct effect on bile
• secretion)…examples estrogens, anabolic steroids,
• azathioprine
• � Inflammatory (portal areas with cholangitis) often
• with allergic features…examples erythromycin,
• ampicillin-clavulanic and semi-synthetic penicillins,
• chlorpropamide

23. • Autoimmune Hepatitis
• 􀁺 Generally affects young females (less often postmenopausal)
• 􀁺 ANA and anti-smooth muscle antibodies each present
• in 70%
• 􀁺 Hypergammaglobulinemia
• 􀁺 Extrahepatic manifestations are clues…amenorrhea,
• thyroiditis, acne, Sjogrens, arthritis, Coomb-positive
• hemolytic anemia, nephritis
• 􀁺 Old name was Lupoid Hepatitis

24. Hepatitis B

25.  Parenteral - IV drug abusers, health workers are
at increased risk.
 Sexual - sex workers and homosexuals are
particular at risk.
 Perinatal(Vertical) - mother(HBeAg+) →infant.
HBV:HBV: Modes of TransmissionModes of Transmission

26. Pathogenesis & Immunity
• Virus enters hepatocytes via blood
• Immune response (cytotoxic T cell) to viral
antigens expressed on hepatocyte cell surface
responsible for clinical syndrome
• 5 % become chronic carriers (HBsAg> 6
months)

27. Clinical Features
Incubation period: Average 60-90 days
Insidious onset of symptoms : Tends to cause a more severe disease than
Hepatitis A.
Premature mortality from
chronic liver disease: 15%-25%

29. Possible Outcomes of HBV InfectionPossible Outcomes of HBV Infection
Acute hepatitis B infection
Chronic HBV infection
3-5% of adult-
acquired infections
95% of infant-
acquired infections
Cirrhosis
Chronic hepatitis
12-25% in 5 years
Liver failureHepatocellular
carcinoma
Liver transplant
6-15% in 5 years 20-23% in 5 years
DeathDeath

30. Prevention
• Vaccination
• - highly effective recombinant vaccines
• Hepatitis B Immunoglobulin (HBIG)
• -exposed within 48 hours of the incident/
neonates whose mothers are HBsAg and HBeAg
positive.
• Other measures
• -screening of blood donors, blood and body fluid
precautions.

33. Hepatitis B Vaccine
• Infants: several options that depend on status of the mother
– If mother HBsAg negative: birth, 1-2m,6-18m
– If mother HBsAg positive: vaccine and Hep B immune globulin within 12
hours of birth, 1-2m, 6m
• Adults
* 0,1, 6 months
• Vaccine recommended in
– All those aged 0-18
– Those at high risk

34. Hepatitis C

35. Pathology of HCV
• Acute Hepatitis C:
– Generally benign:
• No jaundice (80%)
• Usually asymptomatic
– Can be severe, but liver failure rare
Only real threat of acute Hepatitis C is its ability to
reach chronic stages undetected and untreated.

36. Pathology of HCV
• Chronic Hepatitis C:
– 70% of patients become chronic
– Possible results:
• Cirrhosis
• End-stage liver disease
• Hepatocellular carcinoma

37. Transmission
• Direct blood or fluid exposure
• Perinatal Transmission
• Transmission:
• Other things thought to be associated with HCV:
– Tatoos
– Acupuncture
– Ear Piercing

39. • Indications For Treatment
– Increased ALT activity
– Liver biopsy fibrosis
– Detectible serum HCV RNA

40. • Vaccine:
– Difficult:
• High mutation rate

44. THANKS