Viral Hepatitis Series Hepatitis A and B slides.pptx

Viral Hepatitis Series: Hepatitis A and B Ana (Simonyan) Muscarella, PharmD, BCACP Clinical Pharmacist, Infectious Disease Vanderbilt Specialty Pharmacy [email protected] Objectives • Review populations at risk for acquiring hepatitis A virus (HAV) and hepatitis B virus (HBV) • Identify a...

Viral Hepatitis Series: Hepatitis A and B Ana (Simonyan) Muscarella, PharmD, BCACP Clinical Pharmacist, Infectious Disease Vanderbilt Specialty Pharmacy [email protected] Objectives • Review populations at risk for acquiring hepatitis A virus (HAV) and hepatitis B virus (HBV) • Identify acute versus chronic HAV and HBV using lab serologies • Recommend prevention and treatment strategies for HAV and HBV Hepatitis A Virus Hepatitis A Virus (HAV) General Information • Single-stranded RNA virus • Replicates in liver, excreted in bile, shed in stool • Transmitted via fecal-oral route (person-person contact or contaminated food or water) • Acute only, does not progress to chronic infection or chronic liver disease (relapse possible) • Vaccine preventable Prevention of Hepatitis A Virus Infection in the United States, Recommendations of the Advisory Committee on Immunization Practices, 2020. CDC MMWR Report. 2020. Sexually Transmitted Infections Treatment Guidelines, 2021. CDC website. 2021. HAV Clinical Features • Incubation period: 28 days (15-50 days) • Likelihood of symptoms depends on age • Age <6 years, 70% of infections asymptomatic • Adults more likely to be symptomatic and have jaundice • Typical presentation includes: • Abrupt onset • Mild and self-limiting (usually resolve in 2-3 months) • Symptoms of fever, malaise, anorexia, nausea, vomiting, jaundice, dark urine, pale stools Prevention of Hepatitis A Virus Infection in the United States, Recommendations of the Advisory Committee on Immunization Practices, 2020. CDC MMWR Report. 2020. Sexually Transmitted Infections Treatment Guidelines, 2021. CDC website. 2021. HAV Serologic Markers • IgM anti-HAV: indicates acute infection • IgG anti-HAV: indicates immunity (either through past infection or vaccination) Treatment and Prevention of HAV • Treatment: supportive care • Prevention • Pre-exposure prophylaxis • Offer vaccination if appropriate • Inactive hepatitis A vaccine alone (Havrix™, Vaqta™) as 2 dose-series or in combination with hepatitis B if also a risk factor (Twinrix™) as a 3-dose series • Consider administration of immune globulin (IG) as GamaSTAN™ administered IM if appropriate • Post-exposure prophylaxis (PEP) • May consider administration of hep A vaccine and/or IG as GamaSTAN™ administered IM Prevention of Hepatitis A Virus Infection in the United States, Recommendations of the Advisory Committee on Immunization Practices, 2020. CDC MMWR Report. 2020. Sexually Transmitted Infections Treatment Guidelines, 2021. CDC website. 2021. Relevant HAV Risk Factors Persons at increased risk for acquisition of HAV infection • • • • • • • • International travelers Men who have sex with men Persons who use injection or noninjection drugs Persons experiencing homelessness Persons who are incarcerated Persons who have close personal contacts of persons with HAV infection Persons with occupational risk for exposure Group settings for persons with developmental disabilities Persons at risk for severe disease from HAV infection • Persons >40 years of age • Chronic liver disease (i.e. hepatitis B virus infection, hepatitis C virus infection, cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, AST/ALT level twice the upper limit of normal) • Persons with HIV infection • Immunocompromised persons (i.e. including chronic renal failure undergoing dialysis; solid organ, bone marrow, or stem cell transplant recipients; persons requiring treatment with immunosuppressive drugs/biologics or long-term systemic corticosteroids) Prevention of Hepatitis A Virus Infection in the United States, Recommendations of the Advisory Committee on Immunization Practices, 2020. CDC MMWR Report. 2020. Endemic Areas for HAV Highest endemic areas  Africa, Asia, and Central and South America Prevention of Hepatitis A Virus Infection in the United States, Recommendations of the Advisory Committee on Immunization Practices, 2020. CDC MMWR Repo 2020. HAV Vaccination Recommendations Persons at increased risk for acquisition of HAV infection Persons at risk for severe disease from HAV infection Other persons recommended for vaccination • International travelers • Men who have sex with men • Persons who use injection or noninjection drugs • Persons with occupational risk for exposure • Persons who anticipate close personal contact with an international adoptee (i.e. household contact, caretaker, regular babysitter) • Persons Prevention of Hepatitis A Virus Infection in the United States, Recommendations of the Advisory Committee onexperiencing Immunization • Persons with chronic liver disease • Persons with HIV • Pregnant women at risk for HAV infection or severe outcome from HAV infection • Any person requesting vaccination Children • All children aged 1223 months • Unvaccinated children and adolescents 2-18 years (catch-up vaccination) Vaccines for Preventing HAV Vaccine Trade name (manufacturer) Age group (years) Dose Rout Schedule e Booster Hep A inactivated (2 doses) Havrix™ (GlaxoSmithKline) 1 – 18 0.5 mL IM None >19 1 mL 0, 6 – 12 months Hep A inactivated (2doses) Vaqta™ (Merck) 1 – 18 0.5 mL IM None >19 1 mL 0, 6 – 18 months Combined Hep A and Hep B (3 doses) Twinrix™ (GlaxoSmithKline) >18 (primary) 1 mL IM 0, 1 month, 6 months None 0, 7, 21 – 30 days 12 months >18 (accelerated) Prevention of Hepatitis A Virus Infection in the United States, Recommendations of the Advisory Committee on Immunization Pre-exposure Prophylaxis Recommendations for International Travel Age Health status Hep A vaccine recommended? IG recommended? Dose of IG recommended Less than 6 months Healthy No Yes 0.1 – 0.2 mL/kg (depending on duration of travel)* 6 – 11 months Healthy Yes, 1 dose No N/A 12 months – 40 years Healthy Yes No N/A >40 years Healthy Yes Only if traveling in less than 2 weeks >6 months Immunocompromise d or chronic liver disease Yes Only if traveling in less than 2 weeks >6 months Persons who elect No Yes (Administer single dose as soon as travel is considered and complete dose on schedule) (Administer single dose as soon as travel is considered and complete dose on schedule) (Administer single dose as soon as travel is considered and complete dose on schedule) *0.1 mL/kg for travel up to 1 month;not 0.2 to mL/kg for travel up to 2 months, 0.2mL/kg every 2 months for travel of receive ≥2 months duration. vaccine or vaccine is contraindicated Prevention of Hepatitis A Virus Infection in the United States, Recommendations of the Advisory Committee on Immunization 0.1 – 0.2 mL/kg (depending on duration of travel)* 0.1 – 0.2 mL/kg (depending on duration of travel)* 0.1 – 0.2 mL/kg (depending on duration of travel)* If hep A vaccine and IG administered simultaneously, must be Post-exposure Prophylaxis Recommendations To be administered within 2 weeks of exposure Age Health status Hep A vaccine recommended? IG recommended? Dose of IG recommended <12 months Healthy No Yes 0.1 mL/kg 12 months – 40 years Healthy Yes, 1 dose No N/A >40 years Healthy Yes, 1 dose Based on provider risk assessment 0.1 mL/kg Yes, 1 dose Yes 0.1 mL/kg No Yes 0.1 mL/kg (consider second dose within 6 months for longterm immunity) (consider second dose within 6 months for longterm immunity) >12 months Immunocompromise d or chronic liver disease >12 months Persons who elect not to receive vaccine or vaccine is contraindicated Prevention of Hepatitis A Virus Infection in the United States, Recommendations of the Advisory Committee on Immunization (consider second dose within 6 months for longterm immunity) If hep A vaccine and IG administered simultaneously, must be Other important considerations • If hep A vaccine and IG administered simultaneously, must be done in different anatomic sites! • Live vaccines should be administered at least 2 weeks before or at least 6 months after administration of IG • Vaccine series can be completed using vaccines from different manufacturers (can be completed with Twinrix™ as well) • Revaccination/booster dosing not recommended • Pre and post vaccination serologic testing not recommended for routine vaccination Concept check #1 • A 45-year-old patient presents to your pharmacy asking if he should obtain the hepatitis A vaccine. Upon reviewing his medications and past medical history, you discover he was recently diagnosed with cirrhosis and has HIV. He is currently enrolled in a rehabilitation program for use of injection drugs. He is immune to hepatitis B. What risk factors does the patient have? Concept check #1 • Would you recommend vaccination to our patient at this time? Why or why not? Hepatitis B Virus HBV General Information • Enveloped, partially double stranded DNA virus • Transmitted through infected blood and body fluids • Can be present as either acute or chronic infection • Can persist indefinitely within a hepatocyte serving as a reservoir of viral replication (once chronic  no cure, only suppression) • Risk of developing chronic infection depends on age (higher risk with younger age) • Vaccine preventable CDC Hepatitis B Information. Accessed at: How Likely to Progress from Acute  Chronic? • Varies based on age at infection • ~90% of infants and 25%–50% of children aged 1–5 years will remain chronically infected with HBV • ~95% of adults recover completely from HBV infection and do not become chronically infected • Untreated chronic infection leads to cirrhosis in up to 40% of patients • Chronic HBV infection accounts for at least 50% of hepatocellular carcinoma (HCC) cases Hep B screening (and vaccination, if eligible) is CDC Hepatitis B Information. Accessed at: critical! Epidemiology of HBV 1. World Health Organization. Hepatitis B: Key Facts. Geneva: World Health Organization. 2020. 2. CDC Viral Hepatitis Surveillance Report, 2019. • In 2015, estimated ~257 million people (3.5% of world population) have chronic hepatitis B infection, with ~68% living in Western Pacific or Africa1 • The incidence of HBV in the U.S. is estimated to be ~20,000 cases per year (in 2019)2 • The prevalence of HBV in the U.S is estimated to be 0.3 to 0.7% of the population3 HBV Clinical Features • Incubation period: 90 days (60-150 days) • Likelihood of symptoms depends on age • 30-50% of people >5 years of age have symptoms (most severe in those age >60) • Many asymptomatic • Typical presentation may include: • Symptoms lasting several weeks to months • • • • • • • • • • Fever Fatigue Loss of appetite Nausea/vomiting Abdominal pain Dark urine Jaundice Joint pain Clay-colored stool Elevated liver enzymes (AST/ALT) CDC Hepatitis B Information. Accessed at: Indications for HBV Screening Terrault et al. Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. HBV Serologic Markers Hepatitis B surface antigen (HBsAg) Hepatitis B surface antibody (anti-HBs) Total antibody to hepatitis B core antigen (Total anti-HBc) IgM antibody to hepatitis B core antigen (IgM anti-HBc) Hepatitis B e antigen (HBeAg) Antibody to hepatitis B antigen (anti-HBe) HBV DNA • Main outer surface protein of HBV • Indicates active infection and becomes detectable in blood at ~4 weeks after infection (may be transiently positive for 2-3 weeks after vaccination) • Becomes present following declining HBsAg levels • Indicates recovery from natural infection or immune response to HBV vaccination • Forms in response to hepatitis B core antigen peptides • Indicates past exposure to virus • Indicates infection in prior 6 months • Most reliable test from distinguishing acute from chronic HBV infection • Associated with elevated HBV DNA levels and high infectivity • Variably present based on production inside of hepatocyte • Appears after declining HBeAg levels • Indicates a favorable immune response to HBV infection • Indicates presence of active infection (acute or chronic), used to monitor response to antiviral therapy HBV Serologic Markers – Acute Infection Graphic provided from: HBV Serologic Markers – Chronic Infection Graphic provided from: Interpreting HBV Serologic Markers Screening test results Interpretation Management Vaccination Recommended? HBsA g Anti-HBc AntiHBs + + - Chronic hepatitis B HBV treatment may be indicated No - + + Past HBV infection/exposur e No further management unless immunocompromised or undergoing immunosuppressive therapy No - + - False positive, past infection, or low-level chronic infection Consider additional testing Yes - - + Immune No further testing needed No Terrault et al. Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. Concept check #2: Example HBV panel How would you classify this patient’s hepatitis B status? Prevention of HBV • Pre-exposure prophylaxis • Eligible patients may be vaccinated using any hep B monovalent vaccine (Engerix-B™, Recombivax HB™, or Heplisav-B™) or combined vaccine if also at risk for hepatitis A (Twinrix™) • Post-exposure prophylaxis • Vaccination or hepatitis B immune globulin (HBIG) Terrault et al. Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. Other Preventative Measures • Vaccinate household contacts • Use barrier protection during sexual intercourse if partner is unvaccinated • Do not share toothbrushes or razors • Do not share needles or injection equipment • Cover open cuts and scratches • Clean blood spills with bleach based cleaner • Do not donate blood, organs, or sperm Terrault et al. Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. HBV Vaccination Recommendations Children • All infants • All unvaccinated children <19 years Persons at risk for infection through sexual exposure • • • • Sex partners of hepatitis B surface antigen positive persons Sexually active persons not in a long-term, mutually monogamous relationship Persons seeking evaluation or treatment for an STI Men who have sex with men Persons at risk for infection by percutaneous or mucosal exposure to blood • • • • • Household contacts of HBsAg-positive persons Residents and staff of facilities for developmentally disabled persons Health care and public safety personnel with risk to exposure to blood or contaminated body fluids Hemodialysis patients Persons with diabetes Other • • • • • • Persons with a history of current or recent injection drug use International travelers to countries with high-intermediate levels of endemic HBV infection Persons with hepatitis C virus infection and/or chronic liver disease Persons with HIV Incarcerated persons Pregnancy CDC MMWR Report. 2018. Hepatitis B Vaccination Recommendations. HBV Vaccine Schedules ACIP Adult and Child Immunization Schedules. Accessed at: Available HBV Vaccines Vaccine Formulation Mont h0 Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Monovalent vaccines Heplisav-B™ X X Engerix-B™ X X RecombivaxHB™ X X X (dialysis patients >20 years only) X X Combination vaccines Twinrix™ X X Pediarix™ X X X X Note: vaccines are available as 0.5 mL or 1 mL IM injections at various doses. Other important considerations • Post-vaccination serologic testing is only recommended for immunocompromised persons, persons with HIV, persons on hemodialysis, sexual partners of HBsAg positive persons, and healthcare workers at risk for exposure • Vaccination series does not need to be re-started if interrupted • Boosters not recommended for immunocompetent individuals • All pregnant women should be tested for HBV • Vaccine protection lasts ~30 years, although anti-HBs HBV Post-exposure Prophylaxis • Treatment depends on exposed person’s vaccine status and immunity to HBV • If immune  no further action needed • If not immune  vaccinate patient, consider addition of hepatitis B IG at dose of 0.06 mL/kg • 1 dose recommended for unvaccinated or individuals with incomplete vaccinations • 2 doses recommended for individuals non-responsive to the vaccine 2018 AASLD Guidance: Who to Treat for Chronic HBV • Decision to treat is based on: • • • • Cirrhosis status Treatment history Liver enzyme elevation HBV DNA level • HBeAg negative patients: >2000 IU copies/mL • HBeAg positive patients: >20,000 IU copies/mL • Other factors such as age, symptoms, family history, and comorbidities • Adults with immune-active chronic HBV • This includes patients with other chronic viral infections such as HIV and HCV regardless of disease activity AASLD = American Association for the Study of Liver Diseases FYI – Immune Phases of Chronic HBV Infection Goals of Chronic HBV Therapy • Achieve virologic suppression, undetectable HBV DNA levels in plasma • Improvement in serologic and histologic markers (loss of HBeAg and seroconversion to anti-HBe) • Prevent the clinical complications of this infection: cirrhosis, hepatocellular carcinoma, and liver-related mortality • Prevent HBV transmission • Control infection • Loss of hepatitis B surface antigen (spontaneously or with antiviral therapy) does not necessarily indicate complete HBV eradication • Reactivation can occur in certain settings (treatment with immunosuppressive, cytotoxic, or disease-modifying antirheumatic drugs) HBV Treatment Options • Preferred treatments • • • • Interferon-alpha-2b (Intron A™) Entecavir (Baraclude™) Tenofovir alafenamide fumarate (Vemlidy™) Tenofovir disproxil fumarate (Viread™) • Non-preferred treatments • • • • Adefovir (Hepsera™ Telbivudine (Tyzeka™) Lamivudine (Epivir™) Emtricitabine (Emtriva™) Approved HBV Anti-viral Therapy Figure 1 - Agents Approved by the U.S. FDA for the Treatment of Hepatitis B Virus (HBV) Infection https://cdn.hepatitisb.uw.edu/doc/457-3/agents-approved-us-fda-treatment-hepatitis-b-virus- Interferon-based regimens • Peginterferon alfa-2a preferred over interferon alpha-2b • More convenient dosing, improved efficacy, better tolerance • Peg-INF Dosing: 180mcg subcutaneously weekly x 48 weeks • Pregnancy category: C • Potential side effects: flu-like symptoms, depression, irritability, insomnia, neutropenia, anemia, thrombocytopenia, hypothyroidism, hyperthyroidism, rash, pruritus, thinning of hair, anorexia, nausea, weight loss • Monitoring: CBC, TSH, clinical monitoring for autoimmune, ischemic, neuropsychiatric and infectious complications • Contraindications: decompensated cirrhosis, autoimmune hepatitis, severe psychiatric comorbidity, poorly controlled seizure disorder, severe cardiopulmonary conditions Oral Antiviral Agents for HBV Entecavir (Baraclude™) Tenofovir disoproxil fumarate (Viread™) Tenofovir alafenamide fumarate (Vemlidy™) Dose 0.5 – 1 mg once daily 300 mg once daily 25 mg once daily Administration Take on empty stomach Take with or without food Take with food Adjustment needed for hepatic dysfunction? Recommended to use 1 mg if decompensated Not recommended if decompensated No Adjustment needed for renal dysfunction? Yes, adjust when CrCl Yes, adjust when CrCl Yes, adjust when CrCl <50 mL/min <15 mL/min <50 mL/min Recommended in HIV N coinfection? Y Y Recommended in pregnancy? Y N N FYI – HBV Reactivation Indications Chronic HBV Monitoring • Patients not on treatment should be monitored regularly to determine if indications for treatment have developed • Decision to discontinue therapy requires careful consideration • Based on HBeAg status, duration of DNA suppression, cirrhosis status • Monitor for virologic relapse, ALT flares, seroconversions and hepatic decompensation • HCC Screening • • • • • • All persons with cirrhosis Black men >40 years of age Asian men >40 years of age Asian females >50 years of age Persons with first-degree family member with history of HCC Persons with hepatitis D virus Concept check #3 A 45 year old Asian female seen in your clinic. The decision has been made to initiate treatment for her chronic hepatitis B infection. Labs and imaging are consistent with compensated cirrhosis and her CrCl >60mL/min. She denies ever being treated for hepatitis B in the past and is currently taking no other medications. Which treatment option would be an appropriate recommendation? a) b) c) d) Entecavir 0.5mg daily on an empty stomach Tenofovir alafenamide 300mg twice daily without regard to food Heplisav-B® x 2 doses 1 month apart Lamivudine 180mcg weekly Other helpful resources • https://www.cdc.gov/hepatitis/resources/professionals/tr aining/serology/training.htm • https://www.hepatitisb.uw.edu/ • https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.10 02/hep.27609 Viral Hepatitis Series: Hepatitis A and B Ana Simonyan, PharmD, BCACP Clinical Pharmacist, Infectious Disease Vanderbilt Specialty Pharmacy [email protected]