1. Hepatitis A, B, C: Overview, Serologies, and Vaccination Connie Tien June 6, 2016

2. Objectives Develop a basic understanding of the modes of transmission, clinical manifestations, and laboratory findings of hepatitis A, B, C Know what serologies to order for acute versus chronic viral hepatitis A, B, C Know the screening and vaccination guidelines for hepatitis A, B, C

3. Basic Overview Hepatitis AHepatitis BHepatitis C Transmissio n Fecal-oral (e.g. contaminated food water) Blood (e.g. perinatal, blood transfusion, contaminated needles) Sexual transmission Blood (e.g. perinatal, blood transfusion, contaminated needles) Sexual transmission Incubation Period Average 28 days Range 15 to 50 days Average 120 days Range 45 to 160 days Average 45 days Range 14 to 180 days Symptoms of Acute Infection Fever Fatigue Loss of appetite Nausea Vomiting Abdominal pain Acholic stools Arthralgia Jaundice CDC. (2015). Viral Hepatitis-Resource Center: Health Professional Tools. Retrieved from CDC: Centers for Disease Control and Prevention: http://www.cdc.gov/hepatitis/resources/professionals/pdfs/abctable.pdf

4. Basic Overview AcuteChronic Hepatitis A, B, CHepatitis BHepatitis C Abnormal Labs Elevated AST/ALT (usually >1000) Elevated total bilirubin Normal or mild to moderate elevations in AST/ALT CourseUsually resolve within 3 months Rarely fulminant hepatic failure Many asymptomatic Chronic infection develops in: >90% of infants 25%–50% of children 1– 5 6%–10% of older children and adults Chronic infection develops in 75%-85% TreatmentSupportive careAntiviral therapy CDC. (2015). Viral Hepatitis-Resource Center: Health Professional Tools. Retrieved from CDC: Centers for Disease Control and Prevention: http://www.cdc.gov/hepatitis/resources/professionals/pdfs/abctable.pdf Chopra, S. (2015, August 6). Clinical manifestations and natural history of chronic hepatitis C virus infection. Retrieved from UpToDate: https://www.uptodate.com/ Lai, M., & Chopra, S. (2016, April 29). Overview of hepatitis A virus infection in adults. Retrieved from UpToDate: https://www.uptodate.com/ Lok, A. S. (2015, May 4). Clinical manifestations and natural history of hepatitis B virus infection. Retrieved from UpToDate: https://www.uptodate.com/

5. Hepatitis B Virus Hepatitis B virus contains hepatitis B surface + core antigens Hepatitis B vaccine contains hepatitis B surface antigen only Image from Wikipedia at https://en.wikipedia.org/wiki/File:Hepatitis_B_virus.png.

6. Basic Serologies SerologiesNameUseful to Determine Hepatitis A IgM anti-HAV IgG anti-HAV IgM hepatitis A antibody IgG hepatitis A antibody Acute infection Immunity through natural infection or immunization Hepatitis B HBsAg anti-HBs IgM anti-HBc IgG anti-HBc Hepatitis B surface antigen Hepatitis B surface antibody IgM hepatitis B core antibody IgG hepatitis B core antibody Acute/chronic infection Immunity through natural infection or immunization Acute exposure to the hepatitis B virus Prior exposure to the hepatitis B virus Hepatitis C anti-HCV HCV RNA PCR Hepatitis C antibody Hepatitis C RNA Acute/chronic infection Hepatitis C viral load Note: If IgG anti-HBc is not available can order total anti-HBc (measures IgM and IgG anti-HBc) instead.

7. What Serologies Do I Order? Acute InfectionChronic InfectionImmunity Hepatitis AIgM anti-HAV---IgG anti-HAV Hepatitis B HBsAg IgM anti-HBc HBsAg IgG anti-HBc HBsAg anti-HBs Hepatitis Canti-HCV --- Note: 1.Order an HCV RNA if anti-HCV is positive 2.If IgG anti-HBc is not available can order total anti-HBc (measures IgM and IgG anti-HBc) instead.

8. CDC Screening Recommendations for Chronic Hepatitis B All pregnant women Infants born to HBsAg-positive mothers Persons born in regions with intermediate or high rates of hepatitis B (HBsAg prevalence of ≥2%) U.S.–born persons not vaccinated as infants whose parents were born in regions with high rates of hepatitis B (HBsAg prevalence of ≥8%) Household, needle-sharing, or sex contacts of HBsAg-positive persons Injection drug users Men who have sex with men Patients with elevated liver enzymes (ALT/AST) of unknown etiology HIV-infected persons Hemodialysis patients Persons needing immunosuppressive or cytotoxic therapy Donors of blood, plasma, organs, tissues, or semen CDC. (2015). Viral Hepatitis-Resource Center: Health Professional Tools. Retrieved from CDC: Centers for Disease Control and Prevention: http://www.cdc.gov/hepatitis/resources/professionals/pdfs/abctable.pdf

9. CDC. (2008). Viral Hepatitis - Hepatitis B Information: Professional Resources. Retrieved from CDC: http://www.cdc.gov/hepatitis/hbv/pdfs/chronichepbtestingflwup.pdf

10. CDC Screening Recommendations for Chronic Hepatitis C Persons born from 1945–1965 Recipients of clotting factor concentrates before 1987 Recipients of blood transfusions or donated organs before July 1992 Persons who currently inject drugs or who have injected drugs in the past, even if once or many years ago Children born to infected mothers (do not test before age 18 mos.) Persons with known exposures to HCV (e.g., healthcare workers after needlesticks, recipients of blood or organs from a donor who later tested positive for HCV) Patients with signs or symptoms of liver disease (e.g., abnormal liver enzyme tests) HIV-infected persons Long-term hemodialysis patients Donors of blood, plasma, organs, tissues, or semen CDC. (2015). Viral Hepatitis-Resource Center: Health Professional Tools. Retrieved from CDC: Centers for Disease Control and Prevention: http://www.cdc.gov/hepatitis/resources/professionals/pdfs/abctable.pdf

11. Case 1 A 30 year old man with no significant past medical history presents for a 1 week history of fatigue, jaundice, pruritus, nausea, vomiting, and right upper quadrant pain. He recently traveled to Mexico 1 month ago for a 2 week honeymoon. While he was there, he got a tattoo of his wife’s name on his arm. Vital signs are within normal limits. Physical exam is significant for jaundice and hepatomegaly. Lab abnormalities include an AST of 1500, ALT of 2000, and total bilirubin of 7.

12. Case 1 Question What serologies should be ordered to assess for acute viral hepatitis?

13. Case 1 Answer What serologies should be ordered to assess for acute viral hepatitis? IgM anti-HAV HBsAg IgM anti-HBc anti-HCV

14. Case 2 A 45 year old male with no significant past medical history presents for follow- up of his lab tests which were significant for an AST of 65 and ALT of 70. He is asymptomatic. His parents immigrated from Africa, but he was born in the US. He cannot recall if he has had the hepatitis B vaccine. There is no family history of liver cancer. He denies smoking or alcohol use. However, he does have a history of IV drug use in his 20s. He denies history of blood transfusions or tattoos. Vital signs are within normal limits. BMI is 22. Physical exam is unremarkable.

15. Case 2 Question What serologies should be ordered to assess for chronic viral hepatitis?

16. Case 2 Answer What viral hepatitis serologies would be most helpful in assessing for chronic viral hepatitis? HBsAg IgG anti-HBc anti-HCV

17. CDC Vaccination Recommendations for Hepatitis A All children at age 1 year Travelers to regions with intermediate or high rates of hepatitis A Men who have sex with men Users of illegal drugs (injection and non-injection) Persons with clotting-factor disorders Persons who work with HAV infected primates or with HAV in a research laboratory Persons with chronic liver disease, including HBV- and HCV-infected persons with chronic liver disease Family and care givers of recent adoptees from countries where hepatitis A is common Anyone else seeking long-term protection CDC. (2015). Viral Hepatitis-Resource Center: Health Professional Tools. Retrieved from CDC: Centers for Disease Control and Prevention: http://www.cdc.gov/hepatitis/resources/professionals/pdfs/abctable.pdf

18. CDC Vaccination Recommendations for Hepatitis B All infants at birth Older children who have not previously been vaccinated Susceptible sex partners of infected persons Persons with multiple sex partners Persons seeking evaluation or treatment for an STD Men who have sex with men Injection drug users Susceptible household contacts of infected persons Healthcare and public safety workers exposed to blood on the job Persons with chronic liver disease, including HCV-infected persons with chronic liver disease Persons with HIV infection Persons with end-stage renal disease, including predialysis, hemodialysis, peritoneal dialysis, and home dialysis patients Residents and staff of facilities for developmentally disabled persons Travelers to regions with intermediate or high rates of hepatitis B (HBsAg prevalence of ≥2%) Unvaccinated adults with diabetes mellitus 19–59 (for those aged ≥60 years, at the discretion of clinician) Anyone else seeking long-term protection CDC. (2015). Viral Hepatitis-Resource Center: Health Professional Tools. Retrieved from CDC: Centers for Disease Control and Prevention: http://www.cdc.gov/hepatitis/resources/professionals/pdfs/abctable.pdf

19. Case 3 The patient from case 2 was found to be positive for hepatitis C. What serologies are needed to see if he would benefit from the hepatitis A and/or B vaccines?

20. Case 3 Answer What serologies are needed to see if he would benefit from the hepatitis A and/or B vaccines? IgG anti-HAV HBsAg anti-HBs

21. Summary Certain viral hepatitis serologies are more helpful for determining acute infection vs chronic infection vs immunity Individuals at risk should be screened for chronic hepatitis B and/or C Individuals who are susceptible to hepatitis A and/or B or anyone who would like long-term protection should be vaccinated for hepatitis A and/or B

22. References CDC. (2015). Viral Hepatitis-Resource Center: Health Professional Tools. Retrieved from CDC: Centers for Disease Control and Prevention: http://www.cdc.gov/hepatitis/resources/professionals/pdfs/abctable.pdf CDC. (2008). Viral Hepatitis - Hepatitis B Information: Professional Resources. Retrieved from CDC: http://www.cdc.gov/hepatitis/hbv/pdfs/chronichepbtestingflwup.pdf Chopra, S. (2015, August 6). Clinical manifestations and natural history of chronic hepatitis C virus infection. Retrieved from UpToDate: https://www.uptodate.com/ Lai, M., & Chopra, S. (2016, April 29). Overview of hepatitis A virus infection in adults. Retrieved from UpToDate: https://www.uptodate.com/ Lok, A. S. (2015, May 4). Clinical manifestations and natural history of hepatitis B virus infection. Retrieved from UpToDate: https://www.uptodate.com/