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The Alphabet Soup of Viral Hepatitis Stephen J. Gluckman, M.D. Hepatitis “itis” in the “hepar” Hepatitis: causes Drugs Toxins Vasculitis Vascular CHF Shock Metabolic Infectious Bacterial Parasitic Fungal Rickettsial Viral EBV CMV A,B,C,D,E,(f),G Estimates of Acute and Chronic Disease Burden for Viral Hepatitis, United States Acute infections (x 1000)/year* Fulminant deaths/year Chronic infections Chronic liver disease deaths/year HAV HBV HCV HDV 125-200 140-320 35-180 6-13 100 150 ? 35 0 1-1.25 million 3.5 million 70,000 5,000 8-10,000 1,000 0 * Range based on estimated annual incidence, 1984-1994. Viral Hepatitis Transmission Clinical disease Diagnosis Treatment Prevention Health care risk HEPATITIS A VIRUS GEOGRAPHIC DISTRIBUTION OF HEPATITIS A VIRUS INFECTION Anti-HAV Prevalence High High/Intermediate Intermediate Low Very Low Hepatitis A: transmission Fecal-Oral Contaminated food and water Person to Person Minimal or no risk factor Blood Maternal-Fetal Needle stick HEPATITIS A, UNITED STATES Most disease occurs in the context of community-wide outbreaks Infection is also transmitted from person to person in households and extended family settings facilitated by asymptomatic infection among children No risk factor identified for 40%-50% of cases Hepatitis A: clinical disease Often sub-clinical Incubation period: 2 - 6 weeks Average 30 days Acute, self-limited illness Rarely fulminant No chronic sequellae EVENTS IN HEPATITIS A VIRUS INFECTION Clinical illness Infection ALT Response IgM IgG Viremia HAV in stool 0 1 2 3 4 5 6 Week 7 8 9 10 11 12 13 Hepatitis A: diagnosis, treatment and prevention Diagnosis: IgM for acute infection IgG for past infection Treatment: supportive There is no specific anti-viral for hepatitis A Prevention Safe water Hand washing Pre-exposure: vaccine Post-exposure: vaccine has replaced immune globulin Health Care Workers and HAV Minimal risk Fecal-oral: therefore The most important thing for the patient to do is to use the bathroom and wash hands The most important thing for the HCW to do is wash hands Prevention recommendation for HCW Know your HAV antibody status IF (+): protected IF (-): get vaccinated Hepatitis B Virus Hepatitis B: transmission Incubation period: 6 weeks to 6 months Perinatal The most common mode of transmission in the developing world Sexual The most common mode of transmission in developed countries Parenteral Blood products IVDA Hepatitis B: natural history Acute HBV Infection in Adults 90% 10% Chronic Resolves 30% 70% Benign Cirrhosis HCC Death Geographic Distribution of Chronic HBV Infection HBsAg Prevalence 8% - High 2-7% - Intermediate < 2% - Low Hepatitis B: testing What do they all mean? HBsAG: surface antigen Anti-HBsAG HBcAG: core antigen Anti-HBcAG IgM IgG HBeAG: e antigen Anti-HBeAG HBV DNA (viral load) Hepatitis B Serology HBsAG NEG NEG NEG POS POS NEG NEG POS POS NEG NEG NEG IgG AntiHBc NEG POS NEG POS POS POS IgM AntiHBc NEG NEG NEG NEG POS NEG Anti-HBs SUSCEP Immune: PAST INFECT Immune: CHRONIC RECENT SEVERAL VACCINA- CARRIER INFECT POSSIBIL TED -ITIES Hepatitis B: diagnosis Clinical Disease ANTI-HBSAG Titer HBSAG “Window” IGM ANTI-HBCAG Exposure Time (month) Hepatitis B: treatment There are many effective options Lamivudine (Emtricitabine) Tenofovir Adefovir Entecavir Telbivudine Interferon Hepatitis B: prevention Pre-exposure (A MUST FOR ALL!) Vaccine made by recombinant technology Only HBsAG – no risk of transmission Post-exposure HBIG Vaccinate Eliminating HBV in the United States: Strategy Prevent peri-natal HBV transmission Routine vaccination of all infants Vaccination of adolescents Vaccination of adults in risk groups Hepatitis B and Pregnancy No need to avoid pregnancy Neonate should get HBIG and Vaccine No need to alter mode of delivery Hepatitis B and Sexual Partners If monogamous Partner should be tested If (-) vaccinate If non-monogamous Condoms Health Care Workers and HBV Potentially high risk from needle stick type injury THERE IS NO REASON FOR ANY RISK! Recommendation: Get tested (antiHBsAG) and get immunized (or just get immunized if test not available) Hepatitis B HCW Needle Stick Management Check titer If (+) nothing else is necessary If (-) History of vaccination Give a single booster No history of vaccination HBIG and Vaccine Hepatitis C Virus Hepatitis C Transmission IVDA Major cause in the USA % (+) after 1 year of using HCV 65, HBV 50, HIV 14 Blood transfusion Very low risk today Sex Very low risk: 0.1%/yr for spouse of known positive Higher risk with more partners Unknown: up to 40% HCW Needle stick: 1.8% Perinatal: 5% Higher with HIV co-infection Breast Milk: no identified risk Hepatitis C: natural history Acute Infection 80 % 20 % Chronic Infection Rate of Progression Resolution Slow Intermediate Rapid 30% of all with chronic infection Cirrhosis 2-5 % HCC DEATH Hepatitis C: clinical course Incubation period: 4 - 8 weeks Acute disease generally sub-clinical or mild Poor correlation between liver transaminases and histology Prognosis best based on histology Chronic Hepatitis C Factors Promoting Progression or Severity Alcohol intake Even a little alcohol intake Miniscule amounts of alcohol intake Age > 40 years at time of infection HIV co-infection Other Male gender Chronic HBV co-infection Laboratory Pattern of Acute HCV Infection with Progression to Chronic Infection anti-HCV Exposure Symptoms +/- Titer HCV RNA ALT Normal 0 1 2 3 4 Months 5 6 1 Time after Exposure 2 3 Years 4 Hepatitis C Diagnosis IgG screen Can take months to become positive If IgG is (+) then must get viral load Management Vaccinate for Hepatitis A and B Counsel about alcohol avoidance Consider treatment with pegylated interferon and ribavirin Response rates about 50% Prevention No vaccine Clean needles Hepatitis C and Pregnancy No need to avoid pregnancy or breast feeding Post exposure prophylaxis is not available No need to alter mode of delivery Test infant and 15-18 months Hepatitis C and Sexual Partners If one long-term steady partner No need to change sexual practices May choose to use condoms If multiple partners Remind them that they are at risk for other STD’s Use condoms Occupational Transmission of HCV Inefficient transmission by occupational exposure Prevalence 1-2% among health care workers Not higher than adults in the general population Average incidence 1.8% following needle stick from HCV-positive source Associated with hollow-bore needles Case reports of transmission from blood splash to eye; one from exposure to non-intact skin Hepatitis C HCW Needle Stick Management No post-exposure prophylaxis available Check HCW HCV Antibody If HCV antibody (-) Recheck antibody at 3 and 6 months OR Check HCV PCR at 1 month If either (+) consider treatment with pegylated interferon and ribavirin Other Transmission Issues HCV not spread by kissing, hugging, sneezing, coughing, food or water, sharing eating utensils or drinking glasses, or casual contact Do not exclude from work, school, play, child-care or other settings based on HCV infection status Hepatitis D (delta) Virus d antigen HBsAg RNA Hepatitis D (HDV) Defective pathogen that REQUIRES co-infection with hepatitis B Simultaneous acute infection Severe acute disease Low risk of chronic disease Superimposed on chronic HBV infection Usually develop chronic hepatitis D also Severe chronic liver disease Geographic Distribution of HDV Infection Taiwan Pacific Islands HDV Prevalence High Intermediate Low Very Low No Data Hepatitis D Transmission: Sex, blood Clinical: acute and chronic, but only in the presence of co-infection with hepatitis B Diagnosis: serology Treatment: treat B Prevention: prevent B Health care risk: unclear Hepatitis E Virus Geographic Distribution of Hepatitis E Hepatitis E – Clinical Features Transmission: fecal-oral Drinking water USA cases have history of travel to endemic areas Incubation period 15-60 days Fatality 1% *Pregnant women 15%-25% Chronic Sequellae: none in most people Case reports of chronic hepatitis in organ transplant recipients Hepatitis E Diagnosis: serology Treatment: supportive Prevention: avoid unsafe water No evidence that IgG works No vaccine Health care worker risk: minimal Hepatitis G Global distribution Spread similar to HCV 30% homology with HCV Not pathogenic in humans Protective if co-infection with HIV Decreased mortality In vitro decreased HIV production Viral Hepatitis - Summary 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 yes yes no pre/postpre/postblood donor pre/postensure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification Summary Patient Consider Hepatitis A and B immunization for all patients HCW Risks From a Needle Stick HAV: minimal HBV: 30% HCV: 1.8% HDV: ? HEV: minimal HGV: none known (HIV: 0.3%) Questions?