1.. viral hepatitis

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1.. viral hepatitis

  1. 1. Acute Viral Hepatitis FAKULTAS KEDOKTERAN UNIVERSITAS ISLAM SUMATERA UTARA 2013
  2. 2. WHAT IS VIRAL HEPATITIS ?  A serious disease caused by virus that attacks the liver . There are various strains of viral hepatitis which can cause lifelong infection, cirrhosis ( scarring) of the liver , liver cancer , liver failure, and death.
  3. 3. Etiology Major agents:  HAV  HBV  HGV  HCV  TTV  HDV  HFV  HEV ?
  4. 4. Minor agents:  EBV,CMV  HSV,VZV  Rubella,Measles  Coxsackie B  Adenovirus
  5. 5. Transmission HAV HBV HCV HDV HEV Fecal-oral + - - - + Percutan. + + + + - Perinatal - + + + - Sexual + + + + -
  6. 6. Epidemiology HAV:fecal-oral HEV:fecal-oral Rarely bloodborne  HBV:percutaneous contact Mucous membrane contact Sexual contact Perinatal:third trimester and 2 months postpartum HDV : like HBV 
  7. 7. Epidemiology  HCV: Percutaneous transmission Transfusion(0.1 %),needle stick(1.8 %) Mucousal transmission (rare) Sexual transmission is rare(monogamy) Perinatal transmission is uncommon (HIV coinfection,less than 5 % )
  8. 8. Sexual transmission of HCV  Multiple sexual partner  HIV and STD  Anal sex  Open sore  Sex during menstruation
  9. 9. Pathology  Infiltration of mononuclear cells  Hepatic cells necrosis  Kupfer cells hyperplasia  Variable degrees of cholestasis  In more severe cases; Bridging necrosis
  10. 10. Clinical Stages  Incubation period  Prodromal (preicteric) phase  Icteric phase  Convalescence
  11. 11. Variation in staging Asymptomatic Anicteric Fulminant Chronic
  12. 12. 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)
  13. 13. Preicteric Phase Systemic & nonspecific symptoms  Flu-like syndrome & dyspepsia  Fever, sore throat, cough, headache  Fever, anorexia, malaise, nausea, vomiting, abdominal pain  Duration : 1-2 weeks
  14. 14. Icteric Phase  Clinical jaundice  Dark urine : 1-5 days before jaundice  Patient may feel better  Resolution of fever  Pruritus
  15. 15. Icterus
  16. 16. Icterus
  17. 17. Jaundice
  18. 18. Icteric Phase  Liver is enlarged,tender  Cervical adenopathy(10-20%)  Splenomegaly(10-20%)  Fever is absent  Encephalopathy :Irritability, lethargy, confusion
  19. 19. Convalescence  Resolution of symptoms  Liver is enlarged  Pruritus  Complete recovery: 1-2 months A,E 3-4 months B,C (3/4)
  20. 20. Laboratory Findings  CBC :leukopenia, lymphocytosis  Normal Hb; except haemorrhage  Normal platelet; except DIC  ESR is normal
  21. 21.  Serum bilirubin : 5-20 mg/dl  Direct bil ≥ indirect bil  SGOT/SGPT = 400-4000 IU  ALP : mild elevation  PT is usually normal : Severe hepatitis  prolonged PT  Hypoglycemia
  22. 22. Serologic Diagnosis  Ig M anti-HAV  HBs Ag and Ig M anti-HBc  HCV Ab, HCV RNA PCR  anti-HDV  anti-HEV
  23. 23. Complications  Hepatitis A : Relapsing hepatitis  Cholestatic hepatitis  Chronicity : HBV,HCV,HDV  Fulminancy : HAV, HBV, HDV, HEV
  24. 24. Diferential Diagnosis  Viral hepatitis by minor agent  Gram negative Sepsis  Cholangitis, cholecystitis  Acute on chronic hepatitis  Drug-related hepatitis  Ischemic hepatitis
  25. 25. Management Indication of admission:  Bilirubin>20 mg/dl  Hypoglycemia  Abnormal PT  Hypoalbuminemia
  26. 26.  Poor oral intake  Mental change,letargy  Low compliance  Other chronic disease
  27. 27. Management  Restriction activity  Drug &Alcohol avoidance  Isolation is not necessary, unless special cases  Symptomatic
  28. 28. Monitoring  Regular physical examination  Liver size, mental state, icterus  Check of LFT, PT, Bilirubin  Serial check of HBsAg and HCVAb
  29. 29. Prevention  Hand washing, hygiene  Universal percaution  No sharing of personal items (razor, toothbrush, nail clipper)  Sexual barrier
  30. 30. Chronic Viral Hepatitis
  31. 31. Chronic hepatitis (CH)  Definition: chronic necroinflammatory injury characterized by liver cell necrosis and inflammation lasting more than 6 months that can lead insidiously to liver cirrhosis, end-stage liver disease and hepatocellular carcinoma.  Prevalence: ~ 2-3% of the population (Hungary)
  32. 32. Major causes of chronic hepatitis   Chronic hepatitis C (70-80%) Chronic hepatitis B (10-20%)  Chronic hepatitis D Chronic autoimmune hepatitis (<10%) Wilson’s disease Haemochromatosis  α1-Antitrypsin deficiency  Drug-induced chronic hepatitis Cryptogenic hepatitis (non-A-E hepatitis)    
  33. 33. Clinical appearance of CH  mostly asymptomatic ~20%: mild fatique; rarely: mild RUQ pain  discovered by screening lab tests: - mildly elevated ALT and AST (<10x ULN); - ALT>AST - AP and γ-GT: normal or minimally elevated  progression to cirrhosis is slow: years, decades
  34. 34. Late symptoms of CH  Marked symptoms only in the stage of cirrhosis: marked fatique, muscle weakness and wasting, poor appetite, nausea, weight loss; dark urine, jaundice, itching; abdominal swelling, ascites, edema, UGI bleeding, hepatic encephalopathy, etc.
  35. 35. Diagnostic tests for chr. hepatitis Type of CH Screening test Confirm. test CHC Anti-HCV HCV RNA CHB HBsAg, anti-HBc HBV DNA, CHD Anti-HDV HDV RNA Autoimmune ANA, SMA, anti-LKM Excl. of others,, histology Wilson’s dis. Coeruloplasmin Urine and hep. copper Haemochromatosis Se iron, TFS histology, genetic testing α1-AT def. Histology α1-AT
  36. 36. Chronic hepatitis C (CHC)  Hepatitis C is a common infection with variable course  170 million infected pts worldwide  CHC can led to liver cirrhosis and hepatocellular carcinoma (HCC)  2nd or 3rd most common cause of liver cirrhosis and HCC  No effective vaccine at present  Prevention: avoidandance of high-risk behaviors
  37. 37. Risk Factors Associated with Transmission of HCV • Illegal injection drug use • Transfusion or transplant from infected donor • Occupational exposure to blood – Mostly needle sticks • Iatrogenic (unsafe injections) • Birth to HCV-infected mother • Sexual/household exposure to anti-HCV positive contact • Multiple sex partners
  38. 38. Natural history of HCV infection Acute hepatitis 85% 15% Recovery and clearance of HCV-RNA Persistent infection 60-70% Chronic hepatitis 20-30% Liver cirrhosis ~5% HCC
  39. 39. Factors promoting the progression of CHC  High viral dose, genotype 1, quasispecies  Older age, male sex  Immunodeficiency  Alcohol abuse  Co-infection with HBV, HIV  Iron overload  Environmental contaminants, geography
  40. 40. Epidemiology of HBV  HBV is a common cause of viral hepatitis  400 million carriers worldwide  Prevalence in the population of developed countries: carriers: 1%, anti-HBsAg +: 10 %; incidence: 35 per 100 000 in a year; in the 3rd world (Far/Middle East): carriers: 8%; anti-HBsAg +: 50 %
  41. 41. Transmission of HBV HBV is present in all body fluids and secretions!  Highly contagious! Blood cc. may be as high as 1013/ml  Vertical transmission: in the perinatal period; > 90%  Horizontal transmission: by blood, blood products, surgery injection-drug abuse, needle-stick injury sexual activity, occupational exposure household contact tattooing, shaving, etc.
  42. 42. Natural history of HBV infection 1% Acute hepatitis 10% Persistent infection Fulminant hepatitis 90% Recovery and clearance of HBV-DNA 2-3% Chronic active hepatitis 1% Liver cirrhosis Carrier state 100-fold risk HCC
  43. 43. Natural History of Chronic HBV Infection Resolution Acute Infection Stabilisation Chronic Hepatitis Chronic Carrier Compensated Cirrhosis Cirrhosis Liver Cancer Progression Decompensated Cirrhosis (Death) 30–50 Years Adapted from Feitelson, Lab Invest 1994 Death
  44. 44. Healthy Liver Cirrhosis Liver Fibrosis Liver Cancer
  45. 45. Diagnosis of CHC  Screening for liver disease elevated se ALT (<10x UNL)  Screening for HCV infection se anti-HCV (enzyme immunoassay)  Confirmation: detection of viremia se HCV RNA (rtPCR)
  46. 46. Diagnosis of CHB  Follow-up of patients with acute HBV infection  Screening for liver disease (elevated se ALT)  Screening for HBV infection se HBsAg (enzyme immunoassay)  Confirmation: detailed serology; detection of viremia se HBV-DNA (PCR)
  47. 47. Serological markers in hepatitis B
  48. 48. Evaluation of patients with CHB and C  Clinical: signs and symptoms of chronic hepatitis; evaluation of coexisting diseases  Laboratory: se ALT, bilirubin, albumin, prothrombin (se AP, GGT , Fe, transferrin saturation, ferritin, renal function tests, autoimmune markers)  Virological: HBV: serology, se HBV-DNA; anti-HDV HCV: se HCV-RNA, viral titer, genotype  Histological: liver biopsy histology
  49. 49. CHC: current therapies    Interferon-α: may eradicate HCV infection; antiviral, immunoregulator, anti-inflammatory; may inhibit fibro- and carcinogenesis; costly, unpleasant (injection!); 5-20% efficacy Interferon-α + ribavirin doubled efficacy in HCV clearance Iron reduction (venesections) biochemical but not virological improvement; improved responsiveness to IFNα
  50. 50. CHB: current therapies  Interferon-α: may eradicate HBV infection; antiviral, immunoregulator, anti-inflammatory; may inhibit fibro- and carcinogenesis; costly, unpleasant, 20-30% efficacy  Lamivudine, adefovir, entecavir (virostatic drugs): advantages: oral administration; well tolerable; less contraindications disadv.: relapse after discontinuation; escape; long-term (>12 mo) treatment
  51. 51. Side effects of therapy Interferon-alpha:   Early: flu-like illnes, fatique, cytopenias Late: depression with suicidal risk, psychosis, anorexia, weight loss, sepsis, thyroid dysfunction, deteoriation of liver disease, hair-loss Ribavirin: • Dose-dependent, mild, reversible hemolytic anemia
  52. 52. Therapy of end-stage CHB and C: liver transplantation     CHC is the leading indication for OLT Antiviral pretreatment is advised Recurrence of the infection is universal; a great problem in hepatitis B infection; survival rate is less affected by HCV Therapy with IFN, ribavirin or lamivudine is possible

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