1. Acute Hepatitis Dr. Kyaw Min MBBS, DTMH, MCTM, MPH, PhD, FACTM, FRSTMH

2. Contents Acute Viral Hepatitis; A,B,C,D,E,G Leptospirosis

3. Causes of acute hepatitis Infection*** viral/Bacteria Toxic and Drug-Induced Hepatitis: industrial toxins (e.g., carbon tetrachloride, trichloroethylene, and yellow phosphorus), Amanita and Galerina (hepatotoxic mushroom poisoning), Hepatotoxic drugs: Para, INH, Halothane, chlorpromazine, oral contraceptive agents

5. Properties of Hepatitis Viruses Six known Hepatitis type A virus (Picornaviridae) Hepatitis type B virus (Hepadnaviridae) Hepatitis type C virus (Flaviviridae) Hepatitis type D virus (viroid, unclassified) Hepatitis type E virus (Calicivirus) Hepatitis type G virus (Flaviviridae)

6. Overview of Hepatitis Virus VirusVirus groupNucleic acid Mode of infectionSeverity (chronicity) HAVEnterovirus 72(heptovirus) RNAFecal-oral+(acute) HBVhepadnavirusDNAPercutaneous; Per mucosal ++(chronic) HCVFlavivirusRNABlood transfusion- associated) + (chronic) HDVB-dependent small virus RNAblood+ (chronic) HEVCalicivirusRNAFecal-oral+(acute) HGV FlaviviridaeRNABlood?

7. Hep G virus Plus-strand RNA, 10 kb Flaviviridae Transmission through blood products No known disease

8. Other etiology Minor agents: EBV,CMV HSV,VZV Rubella, Measles Coxsackie B Adenovirus Yellow fever virus

9. Incubation Period HAV:15-45 days (30) HBV: 30-180 days (60-90) HCV: 15-160 days (50) HDV: 30-180 days (60-90) HEV: 14-60 days (40)

10. Preicteric Phase Systemic &nonspecific symptoms Flue like &Dyspepsia: Fever, sore throat, cough, headache Anorexia, malaise, nausea, Vomiting, abdominal pain Duration : 1-2 weeks

11. Icteric Phase Clinical jaundice Dark urine:1-5 days before jaundice Patient may feel better Resolution of fever pruritus

12. Icter

14. Icteric Phase Liver is enlarged, tender Cervical adenopathy(10-20%) Splenomegaly(10-20%) Fever is absent Encephalopathy :Irritability Lethargy, confusion

15. Convalescence Resolution of symptoms Liver is enlarged Pruritus Complete recovery: 1-2 months A,E 3-4 months B,C

16. Laboratory Findings CBC: leukopenia, lymphocytosis Atypical lymphocyte, Normal Hb; except hemorrhage Normal platelet; except DIC ESR is normal

17. Serologic Diagnosis Ig M anti-HAV HBs Ag and Ig M anti-HBc HCV Ab, HCV RNA PCR anti-HDV anti-HEV

18. Complications Hepatitis A: Relapsing hepatitis, Cholestatic hepatitis Hepatitis B: serum sickness Chronicity: HBV,HCV,HDV fulminancy: HAV,HBV,HDV, HEV

19. Diferential Diagnosis Viral hepatitis by minor agent Gram negative Sepsis Cholangitis, cholecystitis Flare up chronic hepatitis Drug-related hepatitis Ischemic hepatitis

20. Hepatitis A Virus Transmission Virus can be transmitted via fecal-oral route ingestion of contaminated food and water can cause infection HAV in shellfish from sewage- contaminated water Virus can be transmitted by food handlers, day-care workers, and children. (5 F)

21. Concentration of Hepatitis A Virus in Various Body Fluids Source:Viral Hepatitis and Liver Disease 1984;9-22 J Infect Dis 1989;160:887-890 Feces Serum Saliva Urine Body Fluid Infectious Doses per ml 10 0 10 2 10 4 10 6 10 8 10

22. Geographic Distribution of HAV Infection Anti-HAV Prevalence High Intermediate Low Very Low

23. Hepatitis A - Clinical Features Milder disease than Hepatitis B; asymptomatic infections are very common, especially in children. Adults, especially pregnant women, may develop more severe disease no chronic form of the disease. Complications: Fulminant hepatitis is rare: 0.1% of cases

24. Time course of HAV infection

25. Immunity Antibody protection against reinfection is lifelong

26. Laboratory Diagnosis Viral particles in the stool, by electron microscopy Specific IgM in serum PCR HAV-specific sequences in stool

27. HBV Structure & Antigens Dane particle Dane particle HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr, ayw and ayr) HBcAg = inner core protein ( a single serotype) HBeAg = secreted protein

28. Major eterminants of acute and chronic HBV infection

29. Symptoms of Acute Infection

30. Clinical outcomes of acute hepatitis B infection

31. Laboratory Diagnosis

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. Clinical syndromes HCV can cause acute infections but is more likely to establish chronic infections. Viremia Chronic persistent hepatitis Chronic active hepatitis Cirrhosis Liver failure

35. Serologic Pattern of Acute HCV Infection with Recovery Symptoms +/- Time after Exposure Titer anti- HCV ALT Normal 012345 61234 Years Months HCV RNA

37. Hepatitis D virus

38. HBV-HDV Coinfection Pre or postexposure prophylaxis to prevent HBV infection HBV-HDV Superinfection Education to reduce risk behaviors among persons with chronic HBV infection Hepatitis D - Prevention

39. Most outbreaks associated with fecally contaminated drinking water Minimal person-to-person transmission Hepatitis E - Epidemiologic Features Hepatitis E - Epidemiologic Features