Clinical Applications: Introduction to Viral Hepatitis A & B Online Training

Welcome to an Introduction to Hepatitis A & B. This course will review the role of viral Hepatitis A and B in liver disease and the serology assays useful in a diagnosis of viral hepatitis and patient management. This course was developed by Dr. Katherine Soreng, Ph.D. Removes toxins from blood   Metabolizes many medications   Produces proteins involved in blood clotting   Storage (examples: glycogen, Vitamins A, D, B12)   Protein and lipid metabolism   Bile production Liver Gallbladder Bile duct “The beginning of health is to know the disease” Chinese proverb Normal Liver injury/ inflammation   Liver fibrosis Liver failure/ liver cancer Cirrhosis Jaundice   Hepatomegaly   Bleeding/Bruising   Dark Urine   Pale Colored Stools Ascites   Jaundice with ascites (end stage HCC) Transplant is the only option but many will die waiting Viruses Bacteria Drugs Alcohol Metabolic disease Mouth & Upper GI Tract Lower Digestive Tract Arm & Leg Joints & Muscles Fever Jaundice Is there liver injury?   ALT AST Alkaline phosphatase LDH Total bilirubin What is causing the damage?   Viruses Metabolic disease Alcohol Upon successful completion of this course, you will be able to: Describe HAV and HBV transmission routes and risks Explain how HAV and HBV serological profiles relate to diagnostic assays Interpret HAV and HBV testing panel results Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Type of Hepatitis   A B C D E Genome RNA DNA RNA RNA RNA Source of virus feces blood/blood-derived body fluids blood/blood-derived body fluids blood/blood-derived body fluids feces Route of transmission fecal-oral percutaneous permucosal percutaneous permucosal percutaneous permucosal fecal-oral Chronic infection no yes yes yes no Prevention pre/post exposure immunization pre/post-exposure immunization blood donor screening; risk behavior modification pre/post exposure immunization; risk behavior modification ensure safe drinking water Death Recovery Time 6 months Liver damage Acute Acute Fulminant Acute HAV HEV HBV HCV HBV HCV Chronic Stable disease Progression HDV Prevalence of Infection High Intermediate Low No chronicity Contaminated food and water Prevalence varies Age Risk Vaccine available 1987 - 1997 NYC DC 0 - 4 5 - 9 10 - 19 > 20 Per 100,000 population http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm 2004 NYC DC 1987 - 1997 NYC DC 2004 NYC DC US HAV Incidence Decrease since 1995 Vaccine Introduction Contaminated food Contaminated water Poor sanitation Overcrowding USDA recommendation: “Hand washing is the number one defense against food-borne illness.” Usually mild, most recover   May be sick for several months   Frequently symptomless, especially in children   Can cause acute liver failure and death   Patient populations with the greatest risk for fulminant hepatitis, liver failure and death are: Persons 50 years of age or older   Persons with other liver diseases, such as hepatitis B or C Serology is commonly used to confirm acute cases of Hepatitis A   Manual and automated methods are available to identify antibody to the Hepatitis A virus But first a little basic immunology review might be helpful. Viruses Fungi Bacteria     Cellular Immunity Humoral Immunity Liver Virus CD4+ Helper T-Cell Cytokines CD8+ Killer T-Cell CD8+ Killer T-Cell B cell Cytokines IgM IgM IgG Class Switch   CD4+ T-cells “help” activate both arms of  adaptive immunity B-cells make antibody First comes IgM Then comes IgG IgM eventually disappears Memory B cells make only IgG Titer Months after exposure HAV Infection Symptoms Fecal HAV shedding HAV Infection ALT anti-HAV IgM Total anti-HAV Resolution and Immunity 0 24 1 5 6 12 3 4 2     Anti-HAV IgM Indicates acute infection   Can be detected in blood about 3-4 weeks after infection   IgM antibodies not generally detectable within 3-12 months Anti-HAV-Total Detects both IgM and IgG   Positive in acute and recovered hepatitis   Present in infected and vaccinated populations HAV IgM HAV Total Interpretation HAV IgM HAV Total Interpretation Neg Neg   HAV IgM HAV Total Interpretation Neg Neg Neg? HAV IgM HAV Total Interpretation Neg Neg Neg? Pos Pos   HAV IgM HAV Total Interpretation Neg Neg Neg? Pos Pos Acute HAV HAV IgM HAV Total Interpretation Neg Neg Neg? Pos Pos Acute HAV Neg Pos   HAV IgM HAV Total Interpretation Neg Neg Neg? Pos Pos Acute HAV Neg Pos Recovered or Vaccinated Hepatitis B surface antigen (HBsAg) prevalence High ≥ 8% Intermediate 2% - 7% Low < 2% Chronic Large Global Impact 1 Million deaths annually Prevalent in Asia Pacific populations Vaccine available 8 major HBV genotypes .Adapted from: Chu CJ, Lok AS. Hepathology. 2002 Mai; 35(5):1274-6. Review. Chu CJ, et al. Gastroenterology. 2003 Aug; 125(2):444-51 A A A F F F G G D D D H E E B B C C Decreasing US Incidence of Hepatitis B Incidence ( per 100,000 population) Year 14 12 10 8 6 4 2 0 Source: CDC 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 Birth (spread from an infected mother to her baby during birth)   Sex with an infected partner   Sharing needles, syringes, or other drug-injection equipment   Sharing items such as razors or toothbrushes with an infected person   Direct contact with the blood or open sores of an infected person   Exposure to blood from needle sticks or other sharp instruments HBV infected maternal blood Acute HBV Death Fulminant hepatitis   Liver cancer Liver cirrhosis Liver injury Chronic hepatitis HBsAg carrier ~5%   Subclinical infection   Clinical infection   Recovery immunity ~95% Asymptomatic HBsAg carrier   Vertical transmission   Urine Feces Sweat Tears Breast milk Semen Vaginal fluid Saliva Blood Serum Wound exudates Low Viral Titer Moderate Viral Titer High Viral Titer Acute HBV Fulminant hepatitis   Death Clinical infection   Subclinical infection   Liver injury Liver cancer Liver cirrhosis Chronic hepatitis Asymptomatic HBsAg carrier HBsAg carrier ~90% Recovery/Immunity ~10% HBsAg carrier ~90% Recovery/Immunity ~10% Age at Infection Chronicity (%) < 6 months 90 - 95 > 6 months 80 1 - 4 years 30 - 50 > 4 years 5 - 10 Vaccine Dose and HBIG* Age Infant Born to Mother Known to be HBsAg Positive First Vaccine Dose Birth (within 12 hours) HBIG Birth (within 12 hours) Second Vaccine Dose 1 – 2 months Third Vaccine Dose 6 months Infant Born to Mother Not Screened for HBsAg First Vaccine Dose Birth (within 12 hours) HBIG Screen mother ASAP. If HBsAg positive, give ASAP but by no later than 1 week of age Second Vaccine Dose 1 – 2 months Third Vaccine Dose 6 months *Hepatitis B Immune Globulin Recommended Immunization Schedule for Persons Aged 0 Through 6 Years—United States 2009 http://www.cdc.gov/vaccines/recs/schedules/downloads/child/2009/09_0-6yrs_schedule_pr.pdf Envelope Viral DNA Surface antigens Nucleocapsid (core antigen) HBe Antigen Serology Manual and automated methods are available to identify antibody to the Hepatitis B virus   Molecular Tests Detect viral load for therapeutic decision making Anti-HBc IgM Anti-HBc total   HBsAg HBeAg Anti-HBe Anti-HBs Antibody detection   Antigen detection   Titer Anti-HBe Symptoms HBeAg HBsAg anti-HBc IgM anti-HBs Total anti-HBc Weeks after exposure 0 100 52 4 8 24 32 28 36 20 16 12 Titer Weeks after exposure 100 0 52 32 36 28 4 8 24 12 16 20 HBeAg Anti-HBe anti-HBc IgM HBsAg Total anti-HBc anti-HBs rarely seen Chronic replicative state Chronic non-replicative state 6 month = chronic Chronic Titer Weeks after exposure 100 52 0 4 28 32 36 24 8 12 16 18 Acute (6 months) Chronic (Years) HBeAg HBsAg anti-HBc IgM Total anti-HBc anti-HBs rarely seen Treatment options include: Interferon Alpha Pegylated Interferon Lamivudine Adefovir Entecavir Tenofovir Telbivudine Treatment is often lifelong - few are cured   Titer IgM anti-HBc anti-HBs rarely seen HBsAg Total anti-HBc Chronic replicative state Chronic non-replicative state HBeAg Anti-HBe Weeks after exposure 100 52 32 36 0 4 8 28 24 20 16 12   Test Result Probably Diagnosis HBsAg aHBcT aHBc IgM HBeAg aHBe aHBs Uninfected, unvaccinated — — — — — — Vaccinated (immune) — — — — — + Acute infection + + + + — — Active infection: recovering — + — — + — Recovered (immune) — + — — + + Chronic replicative infection + + — + — — Chronic nonreplicative infection + + — — + — HAV IgM HBsAg HBV Core IgM Interpretation HAV IgM HBsAg HBV Core IgM Interpretation Neg   Neg   Neg     HAV IgM HBsAg HBV Core IgM Interpretation Neg   Neg   Neg   Neg? HAV IgM HBsAg HBV Core IgM Interpretation Neg   Neg   Neg   Neg? Neg Pos Neg   HAV IgM HBsAg HBV Core IgM Interpretation Neg   Neg   Neg   Neg? Neg Pos Neg Chronic HBV? HAV IgM HBsAg HBV Core IgM Interpretation Neg   Neg   Neg   Neg? Neg Pos Neg Chronic HBV? Neg Pos Pos     HAV IgM HBsAg HBV Core IgM Interpretation Neg   Neg   Neg   Neg? Neg Pos Neg Chronic HBV? Neg Pos Pos   Acute HBV? Hepatitis A Infections often caused by contaminated food or water   No chronic infection   Vast majority of infections resolve   Serological testing Hepatitis B Infections transmitted via body fluids or vertically   Can cause chronic infection   Chronic infections usually benefit from treatment   Serological and molecular testing