HEPATITIS

1. HEPATITIS Diah Puspita Rini, dr., SpPK

2. Hepatitis is inflammation of the liver which can be caused by viruses, medications, or toxic agents. • Non viral : miliary TB, staphylococcal bacteriemia, salmonelloses, amebiasis, drugs, etc. • Viral hepatitis :, Hepatitis A,B,C,D,E CMV, Herpes, Epstein Barr virus, Rubella

3. 1 Hepatitis A 2 3 4 Viral Hepatitis 5 Hepatitis E Click to add Title 6 Hepatitis G Hepatitis B Click to add Title 7 Hepatitis TT Hepatitis C 8 Hepatitis Sen Hepatitis D

4. HCC VIRAL HEPATITIS A Major Public Health Problems • Cause Morbidity & Mortality • Chronic Hepatitis B & C Liver Cirrhosis

5. SYMPTOMS • a short, mild, flu-like illness • nausea, vomiting and diarrhoea • loss of appetite • weight loss • jaundice (yellow skin and white of eyes, darker yellow urine and pale faeces) • itchy skin • abdominal pain

6. Type of Hepatitis A B C D E Source of feces blood/ blood/ blood/ feces virus blood-derived blood-derived blood-derived body fluids body fluids body fluids Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral transmission permucosal permucosal permucosal Chronic no yes yes yes no infection Prevention pre/post- pre/post- blood donor pre/post- ensure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification

7. Hepatitis A (HAV) • Due to non enveloped, single stranded RNA picornavirus • Serum AST and ALT increased to hundreds for 1 to 3 weeks • Relative lymphocytosis is frequent

8. Serologic test for HAV • Ig M anti HAV : • appears at the same time as syptoms in > 99% of cases • peaks within first month, becomes nondetectable in 12 (usually 6) • Presence confirms diagnosis of recent acute infection • Anti HAV total: • Predominantly IgG • Almost always positive at onset of acute hepatitis and is usually detectable for life • Found in ± 50% of population, indicaes previous exposure to HAV

9. Hepatitis A Infection Typical Serological Course Total anti-HAV Symptoms Titre ALT Fecal HAV IgM anti-HAV 4 5 6 12 24 0 1 2 3 Months after exposure

10. Hepatitis B (HBV) • Due to enveloped, double stranded DNA hepadna virus • Divided into 3 stages: • Acute hepatitis: lasts 1-6 months, mild/ no symptoms • AST & ALT increased > tenfolds • Serum bilirubin is usually normal or slightly increased • HBsAg gradually arises to high titer and persist, HBeAg also appears

11. 2. Chronic hepatitis: transaminase increased > 50% for > 6 months, most cases resolve but some develop cirrhosis and liver failure • AST & ALT fall to 2-10x normal range • HBsAg usually remains high and HBeAg remains present 3. Chronic carrier: are usually but not always healthy and asymptomatic • AST and ALT fall to normal or < 2x normal • HBsAg positive > 6 months, HBc IgM negative, but anti HBc positive

12. 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.

13. Concentration of Hepatitis B Virus in Various Body Fluids Low/Not High Moderate Detectable blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears breastmilk

14. HBV: Structure

15. SEROLOGICAL TEST OF HBV 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.

17. 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 Years 0 4 8 16 20 24 28 36 12 32 52 Weeks after Exposure

18. Quiescent = inactive = quiet

19. Possible Outcomes of HBV Infection Acutehepatitis B infection 3-5% of adult-acquiredinfections 95% of infant-acquired infections Chronic HBV infection Chronic hepatitis 12-25% in 5 years Cirrhosis 20-23% in 5 years 6-15% in 5 years Hepatocellularcarcinoma Liver failure Liver transplant Death Death

20. Prevention • 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. • 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. • Other measures - screening of blood donors, blood and body fluid precautions.

21. HEPATITIS C (HCV)

23. Risk Factors Associated with Transmission of HCV • Transfusion or transplant from infected donor • Injecting drug use • Hemodialysis (yrs on treatment) • Accidental injuries with needles/sharps • Sexual/household exposure to anti-HCV-positive contact • Multiple sex partners • Birth to HCV-infected mother

24. 1 2 INCUBATION PERIOD ACUTE INFECTION 60 -80% ASYMPTOMATIC 20- 30% WITH JAUNDICE 80 -85% CHRONIC HEPATITIS 6 -7 WEEKS (Range 2 – 26 weeks) HCV INFECTION

25. Hepatitis C Virus Infection Typical Serologic Course anti-HCV Symptoms Titre ALT Normal 6 1 2 3 4 0 1 2 3 4 5 Months Years Time after Exposure

26. PROGRESSION • ACUTE HEPATITIS C • 15-40% will spontaneously resolve, generally within the first 6-18 months after acute onset. • 60-85% will progress to chronic infection • CHRONIC • 85-90% stable • 10-15% progress to cirrhosis

27. PROGRESSION • CIRRHOSIS • 75% slowly progressive • 25% progress to HCC • 2-4% liver failure • HCC • Risk increases for every year for a patient with chronic hepatitis C. • Patients without signs of cirrhosis can develop HCC Factors of poor prognosis: -Age >40 years -Alcohol > 50g/Hour -Male gender -Duration of infection -Co-infection HBV/HIV -Tobacco consumption

28. Diagnosis of HCV Infection • Direct tests : components of the HCV particle • 1.HCV RNA(PCR) • Qualitative • Quantitative • 2. HCV Core antigen • Usefull in detecting window peroid • Indirect tests: detect antibody against HCV • Anti HCV • RIBA (recombinant immunoblot assay)

29. Prevention of Hepatitis C • Screening of blood, organ, tissue donors • High-risk behavior modification • Blood and body fluid precautions

30. HEPATITIS D • Double stranded enveloped RNA virus • Depends upon HBV for expression and replication • Often severe with relatively high mortality in acute disease and frequent development of cirrhosis in chronic disease • Chronic HDV inf. Is more severe and higher mortality rate than other types of viral hepatitis • Serologic test : Anti HDV in px with HBsAg positive hepatitis

31. HEPATITIS E • Unveloped, single stranded enveloped RNA virus • Endemic area: Mexico, India, Africa, Burma, Russia • Serologic test: • Antibody to hepatitis E establish dx. • IgM antibodies indicate recent infection • Serologic markers for HVA, HBV, HCV and other cause of acute hepatiti are absent

32. Soal Kasus • Laki2 datang dengan keluhan demam 14 hari, sklera tampak ikterus, nyeri tekan abdomen kanan atas • Pemeriksaan Lab apa yg anda usulkan? • HBsAg (-) • HBsAb (+) • IgM anti HAV (+) • anti HBc (-) • Apa diagnosis pasien ini?

33. ??QUESTIONS??