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HEPATITIS Diah Puspita Rini, dr., SpPK • 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 Viral Hepatitis 3 1 Hepatitis A Title Click to add 5 Hepatitis E 2 Hepatitis B Title Click to add 6 Hepatitis G 7 Hepatitis TT 8 Hepatitis Sen 3 Hepatitis C 4 Hepatitis D VIRAL HEPATITIS A Major Public Health Problems • Cause Morbidity & Mortality • Chronic Hepatitis B & C Liver Cirrhosis 4 HCC 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 Type of Hepatitis A Source of virus Route of transmission Chronic infection Prevention B C D E feces blood/ blood/ blood/ blood-derived blood-derived blood-derived body fluids body fluids body fluids feces fecal-oral percutaneous percutaneous percutaneous permucosal permucosal permucosal fecal-oral no yes pre/postexposure immunization pre/postexposure immunization yes yes blood donor pre/postscreening; exposure risk behavior immunization; modification risk behavior modification no ensure safe drinking water 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 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 Hepatitis A Infection Typical Serological Course Total antiHAV Symptoms Titre ALT Fecal HAV IgM anti-HAV 0 1 2 3 4 5 6 Months after exposure 12 24 Hepatitis B (HBV) • Due to enveloped, double stranded DNA hepadna virus • Divided into 3 stages: 1. 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 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 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. Concentration of Hepatitis B Virus in Various Body Fluids High Moderate blood semen serum vaginal fluid wound exudates saliva Low/Not Detectable urine feces sweat tears breastmilk HBV : Structure 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. 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 0 4 8 12 16 20 24 28 32 36 52 Weeks after Exposure Years Serologic diagnosis of viral hepatitis Significance HBsAg HBeAg Anti-HBc Anti-HBc Anti-HBs IgG IgM IgG Acute HBV + + - + - Chronic HBV, + + + - - + - + - - Resolved HBV - - + + - Postvaccine - - - - + Active replication Chronic HBV, quiescent Immune HBV Quiescent = inactive = quiet 18 Possible Outcomes of HBV Infection Acute hepatitis B infection 3-5% of adultacquired infections 95% of infantacquired infections Chronic HBV infection Chronic hepatitis 12-25% in 5 years 6-15% in 5 years Cirrhosis Hepatocellular carcinoma Death 20-23% in 5 years Liver failure Liver transplant Death 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. HEPATITIS C (HCV) 22 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-HCVpositive contact Multiple sex partners Birth to HCV-infected mother HCV INFECTION INCUBATION 1 PERIOD 6 -7 WEEKS ACUTE 2 INFECTION 60 -80% ASYMPTOMATIC 20- 30% WITH JAUNDICE (Range 2 – 26 weeks) 80 -85% CHRONIC HEPATITIS 24 Hepatitis C Virus Infection Typical Serologic Course anti-HCV Symptoms Titre ALT Normal 0 1 2 3 4 Months 5 Time after Exposure 6 1 2 3 Years 4 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 PROGRESSION • CIRRHOSIS – 75% slowly progressive – 25% progress to HCC – 2-4% liver failure • HCC Factors of poor prognosis: -Age >40 years -Alcohol > 50g/Hour -Male gender -Duration of infection -Co-infection HBV/HIV -Tobacco consumption – Risk increases for every year for a patient with chronic hepatitis C. – Patients without signs of cirrhosis can develop HCC Diagnosis of HCV Infection Indirect tests: detect antibody against HCV 1. Anti HCV 2. RIBA (recombinant immunoblot assay) Direct tests : components of the HCV particle 1.HCV RNA(PCR) • Qualitative • Quantitative 2. HCV Core antigen Usefull in detecting window peroid 28 Prevention of Hepatitis C Screening of blood, organ, tissue donors High-risk behavior modification Blood and body fluid precautions 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 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 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? ??QUESTIONS??