RCSI The ABC of Viral Hepatitis PDF

Leading the world to better health The ABC of viral hepatitis Prof. Karina O’ Connell Consultant Clinical Microbiologist, Beaumont Hospital  Source:https://phil.cdc.gov/phil/details.asp The ABC of viral hepatitis Class Year 2, Semester 1 Course Undergraduate Medic...

Leading the world to better health The ABC of viral hepatitis Prof. Karina O’ Connell Consultant Clinical Microbiologist, Beaumont Hospital  Source:https://phil.cdc.gov/phil/details.asp The ABC of viral hepatitis Class Year 2, Semester 1 Course Undergraduate Medicine Lecturer Prof Karina O’ Connell Date 9th October 2023  LEARNING OUTCOMES Discuss the epidemiology of hepatitis viruses and the infections they cause Describe the pathogenesis of hepatitis viruses Recognise and describe the clinical features and complications of hepatitis virus infections Outline the laboratory diagnosis of infections caused by hepatitis viruses Choose the appropriate antimicrobial agents to treat infections caused by hepatitis viruses Use the appropriate measures to prevent the acquisition and spread of viral hepatitis LEARNING OUTCOMES: DISCUSS THE EPIDEMIOLOGY OF HEPATITIS VIRUSES AND THE INFECTIONS THEY DESCRIBE THE PATHOGENESIS OF HEPATITIS VIRUSES  Hepatitis - Causes Hepatitis “inflammation of the liver” Infectious Non-infectious Bacterial Others Drugs Alcohol Vascular Autoimmune Metabolic Viral Hepatitis A, B,C, D (with B), E Cytomegalovirus Epstein Barr virus Rubella Yellow fever (Africa, South America) Hepatitis A Hepatitis B RNA virus - DNA virus infects hepatocytes enteroviruses Express viral proteins (picornavirus) on surface and triggers the cellular Virus not immune response cytopathic in itself; thought that cellular immunity cause Hepatitis D liver damage Incomplete viral particle Defective RNA virus Uses hepatitis B surface antigen for propagation Hepatitis E RNA virus Hepatitis C 4 genotypes RNA virus (flavivirus) At least 6 distinct genotypes (1-6) No cross protection (ie can get reinfected with another genotype)  Hepatitis B 3 virus forms : Dane particle, Spherical form & filaments * Infectious “Dane” Particle Filaments & Spheres Consist of surplus virus envelope (contain HBsAg) but lack DNA From Murray et. al., Medical Microbiology 5th edition, 2005, Chapter 66, published by Mosby Philadelphia,,  Hepatitis A Humans only - virus shed in faeces Transmission – Primarily person-to-person via faecal-oral route – Also - contaminated food and water Incubation period (time from infection to symptoms): 30 days (range 15-50) Period of Infectiousness 2 weeks before - 1 week after onset of symptoms Worldwide – Highest levels: developing countries (almost all children have antibodies indicating prior infection) – Developed countries most commonly seen in Travellers to endemic countries Household or sexual contacts of known cases gbMSM Occasional foodborne outbreaks Epidemiology  Hepatitis E Infects both animals and humans Four genotypes = different geographic distribution + epidemiology 1 and 2: humans, transmitted via faecally-contaminated water in developing countries 3 (dominant in Europe) and 4: humans, pigs and other mammals. Transmission to humans 1. Via food: undercooked/raw pig and game meat, processed pork and shellfish (genotype 3) 2. Spread directly through handling animals, particularly pigs 3. Contaminated water (when poor sanitation, outbreaks post flooding – monsoons/storms) Incubation period: 30-40 days post exposure (ie similar to hepatitis A and shorter than hepatitis B or C) Clinical Liver Disease, Volume: 15, Issue: S1, Pages: S37-S44, First published: 02 March 2020, DOI: (10.1002/cld.858)  Hepatitis B + C Hepatitis B Hepatitis C Vaccine preventable No vaccine available Incubation Period Incubation Period 1-6 months 8 weeks (average) Transmission to humans 1. Perinatally 2. Sexually 3. Parenterally (‘blood-borne virus’) ▪Sharing equipment used by injecting drug users ▪Haemodialysis, non-sterile glucometer equipment ▪Sharing personal care items (toothbrushes, razors) ▪Needle-stick injuries ▪Ear-piercing, tattooing, acupuncture  Low prevalence areas Hepatitis B Acute infection sporadic / adults Spread = sex / parenterally High prevalence areas Acute infection in infants & young children Spread = Intrapartum /Close household contact  Worldwide prevalence Hepatitis C infection https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/hepatitis-c Match the Hepatitis virus… LEARNING OUTCOME: RECOGNISE AND DESCRIBE THE CLINICAL FEATURES AND COMPLICATIONS OF HEPATITIS VIRUS INFECTIONS  Patients don’t present with a hepatitis virus They present with symptoms/signs of hepatitis or complications of that viral infection https://surewash.com/products/surewash-pocket/  Clinical Presentation of Viral Hepatitis Signs/Symptoms Clinical findings Asymptomatic Symptomatic – Often preceded by prodromal symptoms (fever, Source:https://phil.cdc.gov/phil/details.asp appetite loss, nausea, fatigue, RUQ abdominal pain) Abnormal Liver Function Tests (LFTs) – dark urine bilirubin  Aspartate Aminotransferase – pale greasy stools (AST) need bile to absorb fats Alanine Aminotransferase (ALT) Bilirubin  – jaundice build up of bilirubin  Hepatitis A Clinical Course Acute Infection Asymptomatic in children Risk of symptomatic infection increases with age and coinfection (e.g., hepatitis B) – prodromal symptoms X 1-2 weeks Fulminant disease (acute hepatitis failure) unusual 6 months = chronic infection Positive = current hepatitis B infection (acute or chronic)  Are you “very” infectious? Hepatitis B e antigen (HBeAg) Detectable when the virus is actively reproducing (i.e. the person is infectious) Present in acute and chronic infection Also - Hepatitis B DNA Indicates presence of replicating virus Used to monitor and guide treatment  Has your immune system recognised there is a problem? Hepatitis B core Y Y Y Y antibody HBcAb Y Y First detectable antibody to appear after infection HBcAb (IgM) = acute infection then… HBcAb (IgG) = usually positive for life  Has the infection resolved (or have you been vaccinated)? Anti Hepatitis B surface antibody (Anti-HBs) Usually the last hepatitis B antibody to appear Positive = usually indicator that initial infection resolved (if Anti-HBs is the only positive HBV marker then the person has been vaccinated)  What does patient A have? Serology results A B HBsAg (surface antigen): Positive Hep BeAg (e antigen): Positive Hep Be Ab (e antibody): Negative Anti Hep B core IgM: Positive Anti Hep B core total (IgG): Negative Anti HBs (surface antibody): Negative  What does patient B have? Serology results A B HBsAg (surface antigen): Positive Positive Hep BeAg (e antigen): Positive Negative Hep Be Ab (e antibody): Negative Positive Anti Hep B core IgM: Positive Negative Anti Hep B core total (IgG): Negative Positive Anti HBs (surface antibody): Negative Negative  What does patient C have? Serology results C D HBsAg (surface antigen): Negative Hep BeAg (e antigen): Negative Hep Be Ab (e antibody): Positive Anti Hep B core IgM: Negative Anti Hep B core total (IgG): Positive Anti HBs (surface antibody): Positive  What does patient D have? Serology results C D HBsAg (surface antigen): Negative Hep BeAg (e antigen): Negative Hep Be Ab (e antibody): Positive Negative Anti Hep B core IgM: Negative Anti Hep B core total (IgG): Positive Anti HBs (surface antibody): Positive Positive  Hepatitis C Laboratory Diagnosis Hepatitis C antibody (Anti-HCV) – positive 2-6 months⃰ after exposure to hepatitis C, will remain positive even if patient has cleared the infection Hepatitis C antigen (HCV ag) – positive in acute and chronic infection Hepatitis C virus (HCV) RNA – positive in acute and chronic infection Anti-HCV HCV ag HCV RNA Acute (infectious) NEGATIVE/POSITIVE* POSITIVE POSITIVE Chronic (infectious) POSITIVE POSITIVE POSITIVE Infection cleared POSITIVE NEGATIVE NEGATIVE (non-infectious) LEARNING OUTCOMES: CHOOSE THE APPROPRIATE ANTIMICROBIAL AGENTS TO TREAT INFECTIONS CAUSED BY HEPATITIS VIRUSES USE THE APPROPRIATE MEASURES TO PREVENT THE ACQUISITION AND SPREAD OF VIRAL HEPATITIS  Hepatitis A Treatment = supportive care Prevention = Hygiene Advice to Sanitation travellers Vaccination 1. Vaccination 2. Passive Immunisation Inactivated (not live) vaccine (Immunoglobulin) = Post-exposure prophylaxis Post-exposure: Management of contacts of cases and for In addition to or instead of the outbreak control vaccine Needs to be given within 2 weeks Pre-exposure: of exposure to be effective 1. Travellers to endemic Persons aged over 60 years countries > 12 months and at risk of 2. At risk individuals: severe complications – Chronic liver disease (those with chronic liver – Injecting drug users disease, including chronic hepatitis B or C infection) – gbMSM – Workers exposed to raw untreated sewage http://www.immunisation.ie/en/Downloads/NIACGuidelines/PDFFile_17407_en.pdf  Hepatitis E Acute infection usually self limiting = symptomatic treatment Chronic infection in transplant patients – Reduce immunosuppression – antivirals  Hepatitis B Acute infection = supportive therapy Chronic infection 1. Patient education 2. Vaccination 3. Antiviral therapy - Aim = prevent progression to cirrhosis / liver failure/cancer but can’t eradicate the virus - Goal = reduce Hepatitis B DNA below detectable levels + seroconversion of e antigen to e antibody 4. Monitor for Liver Cancer (Ultrasound, Alpha Feta Protein) 5. Transplant (Fulminant hepatitis, End Stage Chronic Hepatitis)  Prevention Strategy varies with high & low prevalence areas 1. Standard precautions & avoidance of risk factors – safe sex – screen blood products – clean needles / disposable – good practice (standard precautions) hand hygiene gloves , goggles, aprons etc safe disposal of sharps 2. Passive Immunisation (Immunoglobulin) = Post-exposure prophylaxis Immunoglobulin (asap) ▪neonates ▪needle stick if no vaccine or inadequate antibodies ▪after high risk sexual exposure Vaccine - Given along with above 3. Pre-exposure prophylaxis = vaccination Cloned surface antigen(HBsAg) – Therefore you develop antibodies to HBsAg only i.e. Anti-HBs – There is no Hep B core antigen so WILL NOT have detectable Anti Hep B core Course of 3 Titres >10 IU/ml – ideally >100 IU/ml of Anti-HBs Who gets vaccinated? High risk groups ( e.g. healthcare staff) Part of national immunisation program  Hepatitis C Management Acute infection No post-exposure prophylaxis ? postpone treatment to see if spontaneous clearance….arguments for and against Chronic infection Goal = sustained virological response (no detectable RNA at end of therapy and beyond 12 weeks after therapy is stopped Treatment regimens: – Depends on genotype, other co-infections (e.g., HIV), past history of antiviral treatment and degree of fibrosis – Directly-acting antivirals +/- interferon – Also give hepatitis A + B vaccine  Prevention Standard Precautions Avoidance of risk factors – safe sex – screen blood products – clean needles / disposable – good practice (standard precautions) hand hygiene gloves , goggles, aprons etc safe disposal of sharps No vaccine / immunoglobulin available Thank you