Epidemiology and Prevention of Viral Hepatitis A to E: Hepatitis Branch Centers for Disease Control and Prevention An Overview

Viral Hepatitis - Historical Perspective A “Infectious” “Serum” Viral hepatitis Entericallytransmitted Parenterallytransmitted F, G, ? other E NANB BD C

Viral Hepatitis - Overview A A B B C C D D E E Source of virus fecesblood/ blood-derived body fluids blood/ blood-derived body fluids blood/ blood-derived body fluids feces Route of transmission fecal-oralpercutaneous permucosal percutaneous permucosal percutaneous permucosal fecal-oral Chronic infection noyes no Preventionpre/post- exposure immunization pre/post- exposure immunization blood donor screening; risk behavior modification pre/post- exposure immunization; risk behavior modification ensure safe drinking water Type of Hepatitis

47% 34% 16% 3% Hepatitis A Hepatitis B Hepatitis C Hepatitis Non-ABC Source: CDC Sentinel Counties Study on Viral Hepatitis Acute Viral Hepatitis by Type, United States,

Estimates of Acute and Chronic Disease Burden for Viral Hepatitis, United States HAV HBV HCV HDV Acute infections (x 1000)/year* Fulminant deaths/year100150?35 Chronic infections million 3.5 million70,000 Chronic liver disease deaths/year05, ,0001,000 * Range based on estimated annual incidence,

Hepatitis A Virus

Hepatitis A - Clinical Features Incubation period:Average 30 days Range days Jaundice by 14 yrs, 70%-80% Complications:Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis Chronic sequelae:None

Age-specific Mortality Due to Hepatitis A Age group (years) Case-Fatality (per 1000) < > Total 4.1 Source: Viral Hepatitis Surveillance Program,

Fecal HAV Symptoms ALT IgM anti-HAV Total anti-HAV Months after Exposure Titer Typical Serologic Course Hepatitis A Virus Infection

Concentration of Hepatitis A Virus in Various Body Fluids Source:Viral Hepatitis and Liver Disease 1984;9-22 J Infect Dis 1989;160: Feces Serum Saliva Urine Body Fluid Infectious Doses per ml

Hepatitis A Virus Transmission Close personal contact (e.g., household contact, sex contact, child day care centers) Contaminated food, water (e.g., infected food handlers, raw shellfish) Blood exposure (rare) (e.g., injecting drug use, transfusion)

Sources of Hepatitis A Virus Infection by Mutually Exclusive Groups, United States, Percentage of Cases Source: CDC, Viral Hepatitis Surveillance Program Year Personal contact Day care center Foreign travel Outbreak Drug use

Geographic Distribution of HAV Infection Anti-HAV Prevalence High Intermediate Low Very Low

Hepatitis B Virus

Hepatitis B - Clinical Features Incubation period:Average days Range days Clinical illness (jaundice):<5 yrs, <10% ³ 5 yrs, 30%-50% Acute case-fatality rate:0.5%-1% Chronic infection:<5 yrs, 30%-90% ³ 5 yrs, 2%-10% Premature mortality from chronic liver disease:15%-25%

Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Weeks after Exposure Titer Symptoms HBeAg anti-HBe Total anti-HBc IgM anti-HBc anti-HBs HBsAg

Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Weeks after Exposure Titer IgM anti-HBc Total anti-HBc HBsAg Acute (6 months) HBeAg Chronic (Years) anti-HBe Years

Rate of Reported Hepatitis B by Age Group United States, 1990 Rate of Reported Hepatitis B by Age Group United States, 1990 Age Group (Years) Rate (per 100,000) Source: CDC Viral Hepatitis Surveillance Program

Outcome of Hepatitis B Virus Infection by Age at Infection Outcome of Hepatitis B Virus Infection by Age at Infection Symptomatic Infection Chronic Infection Age at Infection Chronic Infection (%) Symptomatic Infection (%) Birth 1-6 months7-12 months 1-4 years Older Children and Adults

High (  8%): 45% of global population –lifetime risk of infection >60% –early childhood infections common Intermediate (2%-7%): 43% of global population –lifetime risk of infection 20%-60% –infections occur in all age groups Low (<2%): 12% of global population –lifetime risk of infection <20% –most infections occur in adult risk groups Global Patterns of Chronic HBV Infection

Geographic Distribution of Chronic HBV Infection HBsAg Prevalence ³ 8% - High 2-7% - Intermediate <2% - Low

Concentration of Hepatitis B Virus in Various Body Fluids Concentration of Hepatitis B Virus in Various Body Fluids HighModerate Low/Not Detectable bloodsemenurine serumvaginal fluidfeces wound exudatessalivasweat tears breastmilk

Sexual Parenteral Perinatal Hepatitis B Virus Modes of Transmission Hepatitis B Virus Modes of Transmission

Prevent perinatal HBV transmission Routine vaccination of all infants Vaccination of children in high-risk groups Vaccination of adolescents – all unvaccinated children at years of age –“ high-risk ” adolescents at all ages Vaccination of adults in high-risk groups Elimination of Hepatitis B Virus Transmission United States Strategy

Hepatitis D (Delta) Virus HBsAg RNA  antigen

Coinfection – severe acute disease – low risk of chronic infection Superinfection – usually develop chronic HDV infection – high risk of severe chronic liver disease Hepatitis D - Clinical Features

Percutanous exposures – injecting drug use Permucosal exposures – sex contact Hepatitis D Virus Modes of Transmission Hepatitis D Virus Modes of Transmission

HBV - HDV Coinfection Typical Serologic Course Time after Exposure Titer anti-HBs Symptoms ALT Elevated Total anti-HDV IgM anti-HDV HDV RNA HBsAg

HBV - HDV Superinfection Typical Serologic Course Time after Exposure Titer Jaundice Symptoms ALT Total anti-HDV IgM anti-HDV HDV RNA HBsAg

Geographic Distribution of HDV Infection HDV Prevalence High Intermediate Low Very Low No Data Taiwan Pacific Islands

HBV-HDV Coinfection Pre or postexposure prophylaxis to prevent HBV infection HBV-HDV Superinfection Education to reduce risk behaviors among persons with chronic HBV infection Hepatitis D - Prevention

Hepatitis C: Leading-Edge Scientific and Clinical Advances

Features of Hepatitis C Virus Infection Incubation periodAverage 6-7 weeks Range 2-26 weeks Acute illness (jaundice)Mild (<20%) Case fatality rateLow Chronic infection75%-85% Chronic hepatitis70% (most asx) Cirrhosis10%-20% Mortality from CLD1%-5%

Chronic Hepatitis C Factors Promoting Progression or Severity Increased alcohol intake Age > 40 years at time of infection HIV co-infection ?Other –Male gender –Other co-infections (e.g., HBV)

Serologic Pattern of Acute HCV Infection with Recovery Symptoms +/- Time after Exposure Titer anti-HCV ALT Normal Years Months HCV RNA

Serologic Pattern of Acute HCV Infection with Progression to Chronic Infection Symptoms +/- Time after Exposure Titer anti-HCV ALT Normal Years Months HCV RNA

Estimated Incidence of Acute HCV Infection United States, Decline in transfusion recipients Decline in injection drug users Source: Hepatology 2000;31:777-82; Hepatology 1997;26:62S-65S

Transmission of HCV Percutaneous –Injecting drug use –Clotting factors before viral inactivation –Transfusion, transplant from infected donor –Therapeutic (contaminated equipment, unsafe injection practices) –Occupational (needlestick) Permucosal –Perinatal –Sexual

Sources of Infection for Persons with Hepatitis C Sexual 15% Other* 5% Unknown 10% Injecting drug use 60% Transfusion 10% (before screening) *Nosocomial; Health-care work; Perinatal Source: Centers for Disease Control and Prevention

Posttransfusion Hepatitis C All volunteer donors HBsAg Donor Screening for HIV Risk Factors Anti-HIV ALT/Anti-HBc Anti-HCV Improved HCV Tests Adapted from HJ Alter and Tobler and Busch, Clin Chem 1997

HCV Prevalence by Selected Groups United States Hemophilia Injecting drug users Surgeons, PSWs Hemodialysis Average Percent Anti-HCV Positive Gen population adults Military personnel STD clients Pregnant women

HCV Testing Routinely Recommended Ever injected illegal drugs Received clotting factors made before 1987 Received blood/organs before July 1992 Ever on chronic hemodialysis Evidence of liver disease Healthcare, emergency, public safety workers after needle stick/mucosal exposures to HCV-positive blood Children born to HCV-positive women Based on increased risk for infection Based on need for exposure management

Routine HCV Testing Not Recommended (Unless Risk Factor Identified) Health-care, emergency medical, and public safety workers Pregnant women Household (non-sexual) contacts of HCV-positive persons General population

HCV Infection Testing Algorithm for Diagnosis of Asymptomatic Persons EIA for Anti-HCV Negative (non-reactive) STOP Positive (repeat reactive) OR RIBA for Anti-HCV RT-PCR for HCV RNA Negative STOP Additional Laboratory Evaluation (e.g. PCR, ALT) Negative Positive Indeterminate Medical Evaluation Positive Negative PCR, Normal ALT Positive PCR, Abnormal ALT Source: MMWR 1998;47 (No. RR 19)

HCV Counseling Prevent transmission to others –Direct exposure to blood –Perinatal exposure –Sexual exposure Refer to support group

Preventing HCV Transmission to Others Do not donate blood, body organs, other tissue or semen Do not share items that might have blood on them –personal care (e.g., razor, toothbrush) –home therapy (e.g., needles) Cover cuts and sores on the skin Avoid Direct Exposure to Blood HCV Counseling

Mother-to-Infant Transmission of HCV Postexposure prophylaxis not available No need to avoid pregnancy or breastfeeding –Consider bottle feeding if nipples cracked/bleeding No need to determine mode of delivery based on HCV infection status Test infants born to HCV-positive women –Consider testing any children born since woman became infected –Evaluate infected children for CLD HCV Counseling

Persons with One Long-Term Steady Sex Partner HCV Counseling Sexual Transmission of HCV Do not need to change their sexual practices Should discuss with their partner –Risk (low but not absent) of sexual transmission –Routine testing not recommended but counseling and testing of partner should be individualized May provide couple with reassurance Some couples might decide to use barrier precautions to lower limited risk further

Persons with High-Risk Sexual Behaviors HCV Counseling Sexual Transmission of HCV At risk for sexually transmitted diseases, e.g., HIV, HBV, gonorrhea, chlamydia, etc. Reduce risk –Limit number of partners –Use latex condoms –Get vaccinated against hepatitis B –MSMs also get vaccinated against hepatitis A

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 HCV Counseling

<1 % 1–2.4 % 2.5–4.9 % 5–10 % > 10 % No data available HCV Has Broad Global Prevalence

Hepatitis E Virus

Hepatitis E - Clinical Features Incubation period:Average 40 days Range days Case-fatality rate:Overall, 1%-3% Pregnant women, 15%-25% Illness severity:Increased with age Chronic sequelae:None identified

Hepatitis E Virus Infection Typical Serologic Course Weeks after Exposure Titer Symptoms ALT IgG anti-HEV IgM anti-HEV Virus in stool

Most outbreaks associated with fecally contaminated drinking water Minimal person-to-person transmission U.S. cases usually have history of travel to HEV-endemic areas Hepatitis E - Epidemiologic Features Hepatitis E - Epidemiologic Features

Geographic Distribution of Hepatitis E Outbreaks or Confirmed Infection in >25% of Sporadic Non-ABC Hepatitis

Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruit/vegetables not peeled or prepared by traveler IG prepared from donors in Western countries does not prevent infection Unknown efficacy of IG prepared from donors in endemic areas Vaccine? Prevention and Control Measures for Travelers to HEV-Endemic Regions

نحوه برخورد با بيماران هپاتيتي

شك به هپاتيت 1. فاز مقدماتي زودرس (Prodromal): تب، آرترالژي، آرتريت، راش 2. فاز قبل از ايكتر : بي ‌ حالي، خستگي، بي ‌ اشتهايي، درد عضلاني، تهوع، استفراغ، تغييرات بويايي و چشايي، علايم شبيه سرماخوردگي در معاينه فيزيكي : هپاتومگالي، لنفادنوپاتي زنجيره خلفي گردن 10 ـ 5% 3. فاز ايكتريك : اسكلرا و پوست زرد، مدفوع كم رنگ، ادرار تيره رنگ، كاهش درجه حرارت بعد از شروع زردي 4. فاز نقاهت : كاهش زردي بعد از چند هفته و بهبود علايم عمومي

آزمايشات درخواستي اوليه ALT – AST – LDH – ALP – Bil (D-T) PT مورفولوژي خون محيطي U/A

اثبات هپاتيت با بررسي آنزيمهاي كبدي ALT 10 ـ 8 برابر AST

انديكاسيونهاي بستري 1.PT طولاني : بيشتر از 3 ثانيه 2.Bil افزايش يابنده بيشتر از mg شواهد نارسايي كبد 4. بي اشتهايي, استفراغ هاي مكرر 5. خانم حامله با سوءتغذيه شديد

اثبات اتيولوژي عفوني دارويي توكسيك آنوكسي حاد كبد عوامل كمك كننده به تشخيص شرح حال اپيدميولوژي اپيدميولوژي تست هاي آزمايشگاهي ماركرهاي سرولوژيك

اثبات اتيولوژي عفوني دارويي توكسيك آنوكسي حاد كبد عوامل كمك كننده به تشخيص شرح حال اپيدميولوژي اپيدميولوژي تست هاي آزمايشگاهي ماركرهاي سرولوژيك

Diagnosis: HBV/HDV Co-infection Anti-HDV positive Suspicion of HDV co-infection based on: Risk factors (e.g., IVDA) Risk factors (e.g., IVDA) Clinical signs of severe hepatities Clinical signs of severe hepatities Check anti-HDV Diagnosis: Chronic HBV infection HBsAg positive with or without Abnormal aminotransferase Check HBsAg and ALT/ AST in 6-9 months Re-check anti-HCV In 3-6 months Consider possibility of HEV Infection if recent foreign travel Diagnosis: Acute hepatitis A infection Diagnosis: Acute hepatitis B infection Diagnosis: Acute HCV infection or exacebation of infection or exacebation of chronic HCV infection Consider non-viral etiologies (e.g., Ischemia, toxins) or other infectious Etiologies (e.g., CMV, EBV) Anti-HAV IgM positive Anti-HBc IgM positive With or without HBsAg Anti-HCV positive Negative serologies Obtain viral serologies: Anti-HAV IgM Anti-HAV IgM HBsAg and Anti-HBc IgMHBsAg and Anti-HBc IgM Anti-HCV (EIA or RIBA)Anti-HCV (EIA or RIBA) Suspicion of acute viral hepatitis based upon: History, physical exam, epidemiologic situation History, physical exam, epidemiologic situation Elevated serum aminotransferase activity (ALT/AST)Elevated serum aminotransferase activity (ALT/AST) آزمايشات تكميلي براي تشخيص يا اثبات اتيولوژي هپاتيت اتيولوژي هپاتيت

درمان غيراختصاصي و پيگيري بيمار 1. رژيم غذايي 2. سرم قندي 3. استراحت نسبي در بستر 4. تست هاي آزمايشگاهي : 1.2 هفته اول هفته اي 2 بار 2. 2 هفته دوم هفته اي 1 بار بررسي HBS Ag هر دوماه تا منفي شدن HBS Ag T.A

Needle Stick HBV30% HBV30% HCV3% HCV3% HIV0.3% HIV0.3%

واكسيناسيون

Up to 9 out of 10 babies born to infected mothers will end up being hepatitis B carriers for the rest of their lives, if they do not get the shots. If you make sure your babies get all 3 shots, plus a shot called H-BIG, they have a 95% chance of being safe from hepatitis B for life. Can my baby die from hepatitis B? Most babies do not die from hepatitis B. carriers

6 months old Hepatitis B Vaccine Baby Shots for Hepatitis B if the mother has Hepatitis B months old Hepatitis B Vaccine + Birth H-BIG Hepatitis B Vaccine

If you have never had hepatitis B, you can get 3 shots and get long lasting protection. 321 Hepatitis B can be prevented!

Babies who end up as carriers have a 1 out of 4 chance of dying from liver problems. Up to 9 out of 10 babies born to infected mothers will end up being carriers for the rest of their lives, if they do not get the shots. 19 out of 20 babies who get the shots will be protected for life! What if my baby does not get these shots?

HBV-HDV Coinfection Pre or postexposure prophylaxis to prevent HBV infection HBV-HDV Superinfection Education to reduce risk behaviors among persons with chronic HBV infection Hepatitis D - Prevention

Preexposure –travelers to intermediate and high HAV-endemic regions Postexposure (within 14 days) Routine –household and other intimate contacts Selected situations –institutions (e.g., day care centers) –common source exposure (e.g., food prepared by infected food handler) Hepatitis A Prevention - Immune Globulin

Many cases occur in community-wide outbreaks –no risk factor identified for most cases –highest attack rates in 5-14 year olds –children serve as reservoir of infection Persons at increased risk of infection –travelers –homosexual men –injecting drug users Hepatitis A Vaccination Strategies Epidemiologic Considerations Hepatitis A Vaccination Strategies Epidemiologic Considerations

Persons at increased risk for infection –travelers to intermediate and high HAV-endemic countries –homosexual and bisexual men –drug users –persons with chronic liver disease Communities with high rates of hepatitis A (e.g., Alaska Natives, American Indians) Preexposure Vaccination ACIP Recommendations - Hepatitis A Vaccine

Estimated Incidence of Acute Hepatitis B United States, Estimated Incidence of Acute Hepatitis B United States, Vaccine licensed HBsAg screening of pregnant women recommended Infant immunization recommended OSHA Rule enacted Adolescent immunization recommended * Decline among homosexual men & HCWs Decline among injecting drug users Year Cases per 100,000 Population * Provisional date

Postexposure Management for HCV IG, antivirals not recommended for prophylaxis Follow-up after needlesticks, sharps, or mucosal exposures to HCV-positive blood –Test source for anti-HCV –Test worker if source anti-HCV positive Anti-HCV and ALT at baseline and 4-6 months later For earlier diagnosis, HCV RNA by PCR at 4-6 weeks –Confirm all anti-HCV results with RIBA Refer infected worker to specialist for medical evaluation and management