hepatitis a n.
Skip this Video
Loading SlideShow in 5 Seconds..
Hepatitis A PowerPoint Presentation
Download Presentation
Hepatitis A

Loading in 2 Seconds...

play fullscreen
1 / 67

Hepatitis A - PowerPoint PPT Presentation

  • Uploaded on

Hepatitis A. The virus that does not cause chronic liver disease. Hepatitis A. “Infectious Hepatitis” First characterized in 1973 Detected in human feces Hepatovirus genus A reportable infectious disease U.S. rate of infection 4/100,000 Highest among children. Risk Factors.

I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
Download Presentation

Hepatitis A

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.

- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
    Presentation Transcript
    1. Hepatitis A The virus that does not cause chronic liver disease

    2. Hepatitis A • “Infectious Hepatitis” • First characterized in 1973 • Detected in human feces • Hepatovirus genus • A reportable infectious disease • U.S. rate of infection 4/100,000 • Highest among children

    3. Risk Factors • Sexual or household contact • International travel • Men who have sex w/ men (MSM) • Intravenous drug abuse (IVDA) • Daycare

    4. Transmission • Unwitting contact w/ infected person • Most cases unknown • Primary route is fecal oral either by person to person contact or ingestion of contaminated food or water

    5. Pathogenesis • After ingestion, the HAV survives gastric acid, moves to the small intestine and reaches the liver via the portal vein • Replicates in hepatocyte cytoplasm • Not a cytopathic virus • Immune mediated cell damage more likely • Once mature the HAV travels through sinusoids and enters bile canaliculi, released into the small intestine and systemic circulation, excreted in feces

    6. Clinical Features • Incubation is usually 2 to 4 weeks, rarely 6 weeks • Complete recovery within 2 months for > 50% • Within 6 months for almost all others

    7. Clinical Features • Low mortality in healthy people • High mortality when older than age 60 • High in presence of chronic liver disease • High morbidity • Around 20% need hospitalization • Lost work days • Most become jaundiced

    8. Clinical Features • Asymptomatic < 2 year old • Symptomatic – 5 and older ill about 8 weeks • Cholestatic – jaundice lasts > 10 weeks • Relapsing w/ 2 or more bouts acute HAV over a 6 to 10 week period • Acute liver failure – rare in young. When it occurs, is rapid i.e., within 4 weeks

    9. Signs and Symptoms • Prodrome lasts 1-2 weeks: fatigue, asthenia, anorexia, nausea, vomiting, and abdominal pain • Less common: fever, cephalgia, arthralgia, myalgia, and diarrhea • Dark urine is followed by jaundice and hepatomegaly • Less common: splenomegaly, cervical lymphadenopathy

    10. Diagnosis • During acute infection, anti HAV IgM appears first • HAV IgG antibody appears early in the course of infection and remains detectable for life, providing lifelong immunity

    11. PreventionImmunization • All children 12 – 24 months • Travelers, occupational exposure risk • All patients w/ hepatitis B or C or those awaiting liver transplantation • HIV positive patients • MSM • IVD users

    12. Immunize • People w/ clotting factor deficiencies • Lab workers handling live hepatitis A vaccine • Need for post exposure prophylaxis uncommon. Administration of the vaccine is effective. If needed, administer immune serum globulin within 2 weeks 0.02 ml/Kg IM

    13. Hepatitis A Vaccine • The vaccine is inactivated HAV • Schedule for 2 – 18 years depends upon the manufacturer: • Havirx: 720 EL U/.5mL @ 0, 6-12 mo • Vaqta: 25 U.5mL @ 0, 6-18 mo

    14. Hepatitis A Vaccine • For those over age 18: • Havirx: 1440 EL U/1mL @ 0, 6-12 mo • Vaqta: 50 U/1mL @ 0, 6-18 mo • Adverse effects: rarely anaphylaxis, injection site induration, erythema, edema, fatigue, mild fever, malaise, anorexia, nausea • Twinrix: • 720 El U/1mL 0, 1, 6 mo plus • 20 mcg HBV

    15. Questions?

    16. Hepatitis B

    17. The Virus • The hepatitis B virus is among the smallest genomes of all known animal viruses • A DNA virus that infects only humans • Belongs to the family Hepadnaviridae • Knowledge of the viral proteins that are perceived by the immune system as “antigens” aids understanding of the various tests used to diagnose acute, chronic, and resolved infection and verify response to immunization

    18. HBV Antigens • Outer envelope contains a surface protein called hepatitis B surface antigen • HBsAg is a marker of viral replication • Inner core contains the genome, the DNA polymerase w/ reverse transcriptase activity, hepatitis B core antigen (HBcAg) particles. This antigen is not detectable in serum • A truncated form of the major core polypeptide known as hepatitis e antigen (HBeAg) is the third antigen generated by virus activity. Marker of high infectivity

    19. Hepatitis B Antibodies • Hepatitis B surface antibody is the antibody to surface antigen. HBsAb is protective and indicates either resolved infection or immunization • HBcAb is the antibody to core antigen. This is not a protective antibody. Only those who have been exposed to the virus will have this antibody • HBcAb is measured in serum as: • Anti HBc IgM (usually indicates new infection) • Anti HBc IgG (appears later) • HBeAb is the antibody to e antigen. Loss of e antigen w/ gain of e antibody is called seroconversion. Not a protective antibody

    20. Epidemiology • Prevalence of HBV varies markedly around the world, w/ > 75% of cases in Asia and the Western Pacific • Vaccine available > 20 years, but perinatal and early life exposure continue to be a major source of infection in endemic areas • Most acute HBV cases in the U.S. are seen among young adults, males > females, who use injection drugs and in those who engage in high risk sexual behaviors • In the U.S., hundreds of people die each year of fulminant HBV • World wide, chronic HBV and its complications including hepatocellular carcinoma account for > 1 million deaths each year

    21. Risk Factors • Percutaneous and mucous membrane exposure. The virus is 100 x more infectious than HIV, 10 x more infectious than HCV and is present in all body fluids. Present on horizontal surfaces, eating utensils, personal hygiene items, etc. • Babies born to infected mother • Household contact • Hemodialysis • Receipt of blood products prior to the early 1970s • Receipt of previously infected donor liver

    22. Markers of Exposure • Surface antigen appears as early as 1-2 weeks following exposure, as late as 11-12 weeks • HBV DNA measurable soon after • HBeAg appears shortly after HBsAg • Hepatitis occurs 1 – 7 weeks after appearance of HBsAg

    23. Pathophysiology • Governed by interaction between the virus and host immune response • Following inoculation by the HBV, cytokine release, cell injury and viral clearance follow • HBsAg disappears by six months and is accompanied by sero conversion to protective HBsAb • Persistent virus replication after six months ->chronic hepatitis and is the result of a compromised (newborn/HIV) or relatively tolerant immune system status

    24. Four Stages of Infection • Age at time of infection predicts chronicity in most cases. Infants and young children usually become chronically infected. When acquired in adults, the virus is cleared by the healthy immune system in about 95% of cases, leading to natural immunity • Immune tolerant phase, there is active viral replication. ALT and AST are normal. Immune system does not recognize HBV as “foreign” • In the immune clearance phase, enzymes rise reflecting immune mediated lysis of infected hepatocytes. This phase can last for years. Seroconversion of HBeAg to HBeAb occurs

    25. Stages of Infection • Low or non-replicative phase. Also known as inactive carrier (or inappropriately “healthy carrier”). Characterized by resolution of necroinflammation, normalization of enzymes and low levels of HBV DNA. This stage may last for life • Reactivation. Spontaneous or immunosuppression mediated (cancer chemotherapy or high dose corticosteroid therapy)

    26. Signs and Symptoms • Incubation period: a few weeks to 6 months • About 30% develop jaundice • 10% to 20% of patients develop serum sickness, i.e., fever, arthralgias, rash • Fulminant hepatitis B occurs in < 1% of cases. 80% mortality without liver transplantation • Enzyme elevations of 1,000-2,000 typical

    27. Signs and Symptoms • Fatigue, RUQ discomfort may be the only symptoms • Those in the immune tolerant phase are usually asymptomatic. The phase lasts until late puberty into adulthood

    28. Signs of Decompensation • See section on Cirrhosis and Portal Hypertension • Refer to a liver transplantation center • Patient education for people with chronic liver disease should be reinforced • Refer to “Ten Tips for People w/ Chronic Liver Disease”

    29. Prevention • Two forms of vaccine now available. • Twinrix – contains both hepatitis A and B vaccines available in an accelerated schedule or standard series • Individual hepatitis B vaccine • Standard schedule is given: • Time 0 • 1 mo • 6 mo

    30. Prevention • Educate to avoid IVDU, high risk sexual activity • Prevent peri natal transmission. Serology of pregnant women for HBsAg is standard of practice in U.S. • If pregnant female has high viremia, refer to hepatologist for treatment during the 3rd trimester to reduce risk of transmission to neonate • Babies of HBsAg mothers receive hepatitis B immune globulin with 12 hours of birth and begin the vaccine series immediately

    31. Treatment • Six approved medications as of July 2008 • Interferon alpha • Pegylated interferon • Lamivudine • Adefovir Dipivoxil • Entecavir • Telbivudine • Tenofovir approved • Refer to hepatologist

    32. The Cholestatic Liver Diseases Adults

    33. Cholestatic Liver DiseaseEtiologies • Immune Mediated: PBC, PSC, autoimmune cholangitis, liver allograft rejection, graft-versus-host disease • Infectious: acute viral hepatitis • Genetic and Developmental: cystic fibrosis, Alagille’s syndrome (syndrome w/ paucity of intrahepatic bile ducts), fibro polycystic liver disease

    34. Cholestatic Liver DiseaseEtiologies • Neoplastic: Cholangiocarcinoma • Drug-Induced Ductopenia: amoxicillin, amitriptyline, cyproheptadine, erythromycin, tetracycline, thiabendazole • Ischemic • Idiopathic

    35. Pathogenesis of Cholestatic Disorders • Immune response (inflammation, auto-antibody) or hepatotoxic injury to bile ducts • Bile duct injury by bile acids - > • Retention of bile acids in hepatocytes - > • Liver cell damage, apoptosis, necrosis, fibrosis, cirrhosis - > liver failure

    36. Complications of Chronic Cholestasis • Pruritis believed to be 2/2 increased opioid receptor tone, or centrally mediated • Fatigue • Bone disease: osteopenia, osteoporosis • Fat soluble vitamin deficiency • Malabsorption (Sprue, bile salt deficiency, pancreatic insufficiency)

    37. Pruritis in Cholestasis • Therapy: • Urso in AICP, PBC (15-30mg/Kg/day) • Opiate antagonist naltrexone (50mg/day) • 5-HT3 antagonist odansetron • SSRI sertaline • Bile acid sequesterant cholestyramine 4gm t.i.d. to q.i.d. • Antihistamines rarely effective • Rifampin 150mg to 300mg b.i.d.

    38. Fatigue in Cholestasis • High prevalence in Primary Biliary Cirrhosis unrelated to disease severity or duration • Pathogenesis • ?decreased hypothalamic cortico-tropin-releasing hormone • ?CNS accumulation of manganese • Prognosis worse • No effective treatment

    39. Bone Disease in Cholestasis • Clinical manifestations: low bone density, fractures of axial and/or appendicular skeleton • Pathogenesis: hyperbilirubinemia impairs osteoblast proliferative activity • Therapy: bisphosphonates, calcium, vitamin D, weight bearing exercise, estrogens appear to be safe

    40. 1. Primary Biliary CirrhosisA chronic and progressive disease of unknown etiology affecting primarily middle-aged women

    41. Primary Biliary Cirrhosis • Affects all races • 9:1 ratio female > male, age 20 – 65 • Characterized by small intrahepatic bile duct destruction and cholestasis • In the presence of cirrhosis, male > likely than female to develop hepatocellular carcinoma

    42. PBCLaboratory Findings • Alk Phos 2x to 20x ULN in > 90% of patients • AST-ALT 1x to 5x ULN > 90% • Bilirubin – variable. When elevated, may indicate advanced cirrhosis or 2nd condition • Hypercholesterolemia in 80% of patients

    43. Hypercholesterolemia Unique in PBC • Hypercholesterolemia • No obvious increase in heart disease • Some lipid lowering agents cause rise • Cholestyramine or Urso may mobilize cholesterol deposits

    44. PBCLaboratory Findings • IgM 1x to 5x ULN > 90% • Anti mitochondrial antibody > 1:20 titer >90% • Anti nuclear and/or smooth muscle antibody > 1:80 may be seen in “overlap syndrome” • Liver biopsy helpful to grade and stage disease, determine if cirrhosis present

    45. PBC Treatment • Slowly progressive, even if asymptomatic • Ursodeoxycholic acid only effective therapy. May improve natural history • Transplant curative • Manage disease specific complications

    46. Effects of Ursodeoxycholate • Urso is a hydrophilic bile acid having multiple anti-inflammatory and immunomodulatory actions • Urso administration in the setting of pro-apoptotic stimuli (bile salts, ethanol, TGF-beta, FAS ligand) inhibits in vitro apoptosis (programmed cell death) • Reduces mitochondrial membrane permeability

    47. Monitor for and Treat PBC Associated Disorders • Keratoconjunctivitis Sicca • Scleroderma, CREST syndrome • Gallstones • Arthropathies: • Rheumatoid, psoriatic arthritis, Raynaud’s phenomenon, Hypertrophic osteodystrophy, Avascular necrosis, Chondrocalcinosis • Thyroid disease, renal tubular acidosis

    48. PBC Associated Disorders • Malabsorption • Celiac Sprue • 6% of PBC patients have Celiac Sprue • 3% of Sprue patients have PBC • Bile salt deficiency • Pancreatic insufficiency