Hepatitis A-B-C It s Not as easy a 1-2-3

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1 Hepatitis A-B-C It s Not as easy a IPAC-South Western Ontario Meeting November 25, 2016 Bryna Warshawsky, Public Health Physician, Public Health Ontario ; bryna.warshawsky@oahpp.ca 1 Outline Overview of the liver and hepatitis Hepatitis A Hepatitis B Hepatitis C 2 1

2 Overview of the liver and hepatitis The largest and most complex internal organ Performs a large number of functions Filters and fights off infection Filters and neutralizes toxins (e.g., alcohol, drugs) The Liver Produces bile and bile salts to help with fat digestion Manufactures proteins and hormones (e.g., cholesterol, estrogen, thyroglobulin) Helps control blood sugar Helps to clot the blood Ability to regenerate Courtesy Dr. Gary Garber, PHO 4 2

3 Diseases of the Liver Congenital diseases; glycogen storage, fat metabolism etc Acute disease: a) Infection-viral ( A, B, C, D, E) and other viruses b) Toxin-alcohol, drug c) Sepsis and septic shock, Reye syndrome d) Trauma e) Ascending cholangitis f) Congestive failure Chronic diseases: a) Viral (B,C) b) Toxin alcohol, drug c) Auto-immune d) Cancer- primary, secondary 5 Hepatitis symptoms Inflammation of the liver Symptoms include abrupt onset of: fever malaise anorexia nausea abdominal discomfort dark urine jaundice 6 3

4 Tests that indicate liver problems Liver enzymes ALT, AST Increased, released with damaged liver cells Bilirubin Increased, as not excreted INR, PT, PTT Prolonged, blood not clotting properly because clotting factors not being produced Albumin - low as proteins not being produced 7 Complications of liver disease Major complications of advanced hepatitis C include cirrhosis, hepatocellular cancer, and transplantation Severity of disease fibrosis F scores Score Description F4 F3 F2 F1 F0 Cirrhosis Severe fibrosis Moderate fibrosis Mild fibrosis No fibrosis HCC, hepatocellular carcinoma. Myers R, et al. Can J Gastroenterol Hepatol. 2014; 28(5):

5 Hepatitis is very burdensome Kwong JC, Crowcroft NS, Campitelli MA, Ratnasingham S, Daneman N, Deeks SL, Manuel DG. Ontario Burden of Infectious Disease Study Advisory Group; Ontario Burden of Infectious Disease Study (ONBOIDS): An OAHPP/ICES Report. Toronto: Ontario Agency for Health Protection and Promotion, Institute for Clinical Evaluative Sciences; Hepatitis in Ontario 2014 Cases Hospitalizations Deaths A B acute B chronic C Public Health Ontario, Reportable Disease Trends in Ontario,

6 Differences in hepatitis transmission 11 Hepatitis A 6

7 Hepatitis A key facts Fecal-oral spread o Food, water, travel, person-to-person, illicit drug use o Extremely hardy o Low infectious dose Long incubation period 2-6 weeks Infectious from half way through the incubation o Spreading before you know you have it Communicable for one week post onset of jaundice; longer in children 13 HAV IgM Hepatitis A serology indicates acute infection begins to rise 5-10 days before onset of symptoms lasts for up to 6 months, but can be longer HAV IgG indicates immunity begins to rise soon after symptom onset lasts forever provides long term protection; re-infection does not occur Total HAV - Not helpful Beware false positive 14 7

8 Hepatitis A Serologic Profile Courtesy Dr. Toni Mazzulli, PHO Hepatitis A genotyping Looks at the RNA Sequence variation within the VP1/P2A junction is used to define genotypes and subgenotype 1A most common 1B less common Used in outbreaks to detect linkage 16 8

9 Hepatitis A by age 70% of children (<6 years old) asymptomatic Case fatality increases with age and in immunocompromised or liver conditions o1.8% for those over 50 years of age 25% of adults require hospitalization o Higher percentages in Ontario Seroprevalence, Canada, Canadian Health Measures Survey 2011 o years 17% o years 65% 17 Travellers or likely to travel or new immigrants from HAV endemic countries Household or close contacts of children who are adopted from HAV endemic countries Men who have sex with men People who use illicit drugs People with chronic liver disease, including hepatitis B or C Canadian Immunization Guide Pre-exposure prophylaxis with hepatitis A vaccine Residents of communities with high rates of hepatitis A People with hemophilia A or B People who handle nonhuman primates People who work with hepatitis A virus in the lab People who wish to be vaccinated Bolded are publicly-funded 18 9

10 Post-exposure prophylaxis (PEP) recommendations Household and close contacts, including sexual contacts Handled diapers or assisted with the toileting or other personal care of cases Shared illicit drugs with a case Day care contacts if case attends day care Contacts of food handlers Co-workers Patrons - based on risk assessment Infectious Diseases Protocol 19 Hepatitis A vaccine Post-exposure prophylaxis (PEP) products Give ASAP and up to 14 days after last exposure ~80% effective if given with 8 days of onset Sagliocca L et al. Lancet, ; Immune globulin (IG) Pre-formed protection from concentrated antibodies Potency in Canada is unknown Give ASAP and up to 14 days after last exposure Efficacy ranges from 47 to 96% 20 10

11 Post-exposure prophylaxis (PEP) recommendations Criteria Ontario NACI Infants < 6 months Ig??? Infants 6 to 12 months Ig Vaccine Healthy 1-49 Vaccine Vaccine Healthy Vaccine Healthy adults 60 Vaccine & Ig / sometime vaccine alone Vaccine & may use Ig / vaccine for outbreaks Immunocompromised Vaccine & Ig Vaccine & Ig Chronic liver disease Vaccine & Ig Vaccine & Ig 21 Trends over time Figure 1. Confirmed Hepatitis A cases; Ontario, 2000 to 2015 * Local or provincial outbreaks reported in iphis 11

12 Risky situations and outbreaks Risky situations Day cares Food handlers Distributed food products (e.g., frozen berries) 24 12

13 25 PEP in child care centres 26 13

14 PEP in child care centres Criteria Case with recent onset & known introduction Case greater than 14 days from onset; OR May already be spreading Contact with recent known external exposure Contact greater than 14 days from onset in case PEP recommendation Vaccinate children and staff Vaccinate children, staff and household members Vaccinate contact only, handwashing, surveillance Consider vaccinating children and staff 27 Food handlers Handled food while infectious Food not subsequently cooked Practices not hygienic or had diarrhea Patrons can be reached and still within 14 days of last exposure 28 14

15 Food handler incidents Toronto - August 2002 supermarket worker Middlesex-London - September supermarket worker Sudbury - January 2015 restaurant worker Wellington-Dufferin- Guelph January 2015 restaurant worker Toronto April juice bar worker Thunder Bay April 2015 restaurant worker 29 Frozen berries Contain some combination of strawberries, blackberries, blueberries, raspberries, cherries, pomegranate seeds Each input can come from several countries such as Mexico, Serbia, Bulgaria, Turkey, Egypt, Poland, Chile, Argentina, Morocco etc

16 Berry-related outbreak Ontario, Quebec, Newfoundland 2016 April 15, 2016 recall of Brand B berry blend 25 cases - 21 confirmed cases; 4 probable cases 19 from Ontario, 5 Quebec, 1 Newfoundland Onset February 26 to May 16, 2016 Genotyping: 1A 5; 1B 16; Undetermined 4 Median age 48 years (range 10 to 70 years) 56% males 42% hospitalized; 0 deaths 23 consumed or probably consumed Brand B 31 Berry-related outbreak Ontario, Quebec, Newfoundland 2016 Two frozen berry blend samples and one sample of Bulgarian blackberries tested positive no genotyping information available Post-exposure prophylaxis mainly with vaccine offered by retailer and health units 9,405 people vaccinated Ontario - 6,915 doses 5,802 retailer 1,113 public health units and private providers 32 16

17 Acknowledgements Tina Badiani Jackson Chung Lisa Fortuna Leigh Hobbs Christina Lee Yvonne Whitfield Public Health Ontario Laboratories Ministry of Health and Long- Term Care Public health units Federal and provincial partners Natasha Crowcroft Shelley Deeks Liane MacDonald Doug Sider Sarah Wilson PIDAC-I 33 Hepatitis B Some slides courtesy of Dr. Liane Macdonald, PHO 17

18 Hepatitis B transmission Blood, blood products, CSF, pleural, peritoneal, semen and vaginal secretions and any other fluid containing blood and saliva (but much lower risk) Horizontal: Sexual, percutaneous (e.g., via injecting drug use), household contact Vertical: Mother to neonate, in utero or peripartum Risk after needlestick injury 6 to 30% Hepatitis B virus can survive on environmental surfaces for at least 7 days. Heymann DL, editor. Control of communicable diseases manual. 19th ed. Washington, DC: American Public Health Association; World Health Organization (WHO). Hepatitis B: Fact sheet N 204. Geneva: WHO. Updated July 2015 [accessed 2015 Sept 22]. Available from: Public Health Agency of Canada. Canadian Immunization Guide [Internet]. Ottawa: Her Majesty the Queen in Right of Canada; Modified Feb 25 [accessed 2015 Sept 10]. Chapter 4: Hepatitis B. Available from: Hepatitis B transmission by endemicity In highly endemic areas (>8% hepatitis B surface antigen (HBsAg) positive): Vertical transmission at birth Horizontal transmission, e.g., in first 5 years of life In areas with low HB endemicity (<2% HBsAg positive) Mostly horizontal transmission. In Canada: Most acute cases are unimmunized, aged 25 years or over A high proportion of hepatitis B carriers are from hepatitis B endemic areas World Health Organization (WHO). Hepatitis B: Fact sheet N 204. Geneva: WHO. Updated July 2015 [accessed 2015 Sept 22]. Available from: Public Health Agency of Canada. Canadian Immunization Guide [Internet]. Ottawa: Her Majesty the Queen in Right of Canada; Modified 2015 Feb 25 [accessed 2015 Sept 10]. Chapter 4: Hepatitis B. Available from:

19 High risk groups recommended for screening Immigrants as part of their routine pre-immigration health care evaluation (especially from endemic countries/developing countries) Non-vaccinated individuals whose parents were from HBV-endemic countries Household contacts of HBV carriers Sexual contacts of HBV carriers Persons with multiple sexual partners Men who have sex with men Persons who have used recreational or intravenous drugs Inmates Patients with chronic renal failure needing dialysis Patients with abnormal ALT / AST All pregnant women Patients needing immune modulation therapy or those who will develop immunosuppression such as cancer chemotherapy Can J Gastroenterol Dec; 26(12): Incubation period and acute infection 45 to 160 days Average 120 days HBsAg present in serum 30 to 60 days after infection Acute infection Asymptomatic in up to 50% of adults and 90% of children 1 to 2% case fatality rate, which increases with age 38 19

20 Rate of becoming a carrier Some will resolve infection within 6 months Others will carry it for longer or for life Called a carrier if virus present > 6 months Becoming a carrier dependant on age at acquisition infants: 90-95% carriers children < 5 years old: 25-50% carriers adults: 3-10% carriers immunocompromised more likely to be carriers 39 Chronic Hepatitis B Frequently asymptomatic for years / decades Cirrhosis and/or chronic liver failure: ~ 20% to 25% Hepatocellular carcinoma: ~ 5% Up to 25% of carriers die from sequelae Antiviral treatment recommended for some; access limited Public Health Agency of Canada. Canadian Immunization Guide [Internet]. Ottawa: Her Majesty the Queen in Right of Canada; Modified 2015 Feb 25 [accessed 2015 Sept 10]. Chapter 4: Hepatitis B. Available from: World Health Organization. Global alert and response: Hepatitis B [cited 2013 Oct 2]. Available from: Coffin CS, Fung SK, Ma MM. Management of chronic hepatitis B: Canadian Association for the Study of the Liver consensus guidelines. Can J Gastroenterol 2012;26(12):

21 Canadian HBsAg positive seroprevalence estimates 1% Canadian born, non-aboriginal 6% immigrants 4% Aboriginal 600,000 carriers in Canada Can J Gastroenterol Dec; 26(12): HBsAg Hepatitis B Antigen Acute infection or carrier Infectious Serology Anti-HBs Antibody to Hepatitis B Surface Antigen Immune to infection from either past infection or vaccination 42 21

22 Serology Anti-HBc Antibody to Hepatitis B Core Exposure to virus past or current IgM anti-hbc recent infection within past 6 months Total anti-hbc IgM and IgG IgG will persist for life 43 Serology HBeAg Hepatitis B e antigen Highly infectious HBeAg negative and anti-hbe positive Less infectious although still infectious if HBsAg positive HB DNA Measure of viral replication and load; used to assess need for treatment 44 22

23 Serology Question 1 HBsAg Positive Anti-HBs Negative IgM HBc Negative Total HBc Positive Chronic carrier 45 Serology Question 2 HBsAg Positive Anti-HBs Negative IgM HBc Positive HBeAg Positive Anti-HBe - Negative Acute case Highly infectious 46 23

24 Serology Question 3 HBsAg Negative Anti-HBs Positive IgM HBc Negative Total HBc Negative Vaccinated Responded 10 IU/L 47 Serology Question 4 HBsAg Negative Anti-HBs Positive IgM HBc Negative Total HBc Positive Resolved case 48 24

25 Hepatitis B Vaccine Safe and effective vaccine for pre-exposure prophylaxis Given in Grade 7 Given to babies born to carrier mothers (along with hepatitis B immune globulin) Given to high risk groups Should it be given to newborns / infants? 49 Vaccination recommendations Immigrated to Canada from a high prevalence area of HB Children born in Canada whose families have immigrated from areas where there is a high prevalence of HB and who may be exposed to HB carriers through their extended families or when visiting their family's country of origin. Children and workers in child care settings in which there is a child or worker who has acute HB or is an HB carrier. Vaccination should also be considered for all child care workers. Household and sexual contacts of acute HB cases and HB carriers 50 25

26 Vaccination recommendations Persons with lifestyle risks for infection, including: persons who have unprotected sex with new partners persons who have had more than one sexual partner in the previous 6 months persons with a history of sexually transmitted infections persons seeking evaluation or treatment for a sexually transmitted infection persons who engage in high risk sexual practices persons who use injection drugs men who have sex with men (MSM) 51 Vaccination recommendations Persons with chronic liver disease from any cause, including persons infected with hepatitis C. Hemophiliacs and other people receiving repeated infusions of blood or blood products. Persons with chronic renal disease or who are undergoing chronic dialysis (hemodialysis or peritoneal dialysis) Persons with congenital immuno-deficiencies Persons who have undergone hematopoietic stem cell transplantation (HSCT) or are awaiting solid organ transplant HIV-infected persons 52 26

27 Vaccination recommendations Household or close contacts of children adopted from HBendemic countries if the adopted child is HBsAg positive Populations or communities in which HB is highly endemic Residents and staff of institutions for the developmentally challenged Staff and inmates of correctional facilities 53 Vaccination recommendations Travellers to HB endemic areas Health care workers, emergency service workers, and others with potential occupational exposure to blood, blood products and bodily fluids that may contain HB virus Any person who wishes to decrease his or her risk of HB Sources: Canadian Immunization Guide. Hepatitis B Chapter canadian-immunization-guide-canadien-immunisation/indexeng.php?page=

28 Post-vaccination serology 1 to 6 months after completing course of therapy: Immunocompromised periodic monitoring considered Chronic renal disease / dialysis monitor yearly High risk pregnant women immunized before or during pregnancy Infants born to carrier mothers At risk for percutaneous or mucosal exposure, such as men who have sex with men Sexual partner and household contact of a case or carrier Health care workers Sources: Canadian Immunization Guide. Hepatitis B Chapter 55 Hepatitis B Immune Globulin Post-exposure management with HBIG indicated if: Baby born to carrier mothers Non-immune sexual contact under certain circumstances Non-immune needle stick injury under certain circumstances 56 28

29 Hepatitis D virus infection Hepatitis D virus infection only occurs in the presence of hepatitis B infection Hepatitis D virus needs hepatitis B virus to replicate Co-infection or super-infection with hepatitis B Transmission: bloodborne via percutaneous or mucosal contact Infection can be acute or chronic, asymptomatic or symptomatic Chronic hepatitis B carriers most at risk; rare in Canada Hepatitis C 29

30 Modes of Transmission Injection and inhalation drug use Blood and blood products like clotting factors (prior to early 1990s) Sexual (particularly men who have sex with men, HIV positive) Mother to child, approximately 6% risk Medical and dental procedures (e.g. dialysis, endoscopy) Sharing of personal hygiene items Tattooing and body piercing Occupational / needle stick injuries - 1.8% risk 59 Incarcerated Foreign born Indigenous people Other groups with higher rates of infection Born between 1945 and

31 Hepatitis C Virus (HCV) 70% of people who are infected are asymptomatic If develop symptoms, incubation period is 6 to 7 weeks (range 2 weeks to 6 months) Two markers of exposure: Antibody to hepatitis C current infection or past infection that has resolved antibodies not protective Hepatitis C RNA current infection 61 Hepatitis C Virus (HCV) After infection, 15 to 25% of people clear infection within six month (RNA negative) 75 to 85% remain infected (RNA positive) Often asymptomatic for many years Can spread their infection At risk for long term complications 62 31

32 Long Term Complications Of every 100 people with hepatitis C clear their infection develop chronic infection develop chronic liver disease 5 20 will go on to develop cirrhosis over a period of years 1 5 will die from the consequences of chronic infection (liver cancer or liver failure) Centers for Disease Control and Prevention. Accessed May 17, Risk of Hepatitis C progression Male Older at time of infection ( >40) Ethanol intake Co-infection with Hepatitis B or HIV Obesity Progression of disease usually takes >15 year Courtesy of Dr. Gary Garber, PHO 64 32

33 Genotypes 6 genotypes, 50 to 100 subtypes Type 1 most common in Canada Important to know genotype to tailor treatment, although less so now 65 Estimated prevalence of hepatitis C in Canada < 1% of Canadians chronically infected with hepatitis C ~ 0.64% to 0.71% have chronic hepatitis C ~ 44% undiagnosed Rates much higher in those who use injection drugs (66%) Trubnikov et al CCDR Minuk et al. Can J Gastroenterology and Hepatology

34 Confirmed hepatitis C cases Rate per 100,000 population 02/12/2016 Reported cases and rates of hepatitis C: Ontario, Testing of accumulated chronic cases RDIS to iphis transition Year Confirmed Cases Rate Source: Ontario Ministry of Health and Long-Term Care, integrated Public Health Information System (iphis) database, extracted by Public Health Ontario [2016/05/20] Population data: Ontario - Population Estimates , Ontario Ministry of Health and Long-Term Care, IntelliHEALTH ONTARIO, Date Extracted: [2014/07/02] Canadian population - Source: Statistics Canada. Table Estimates of population, by age group and sex for July 1, Canada, provinces and territories, annual (persons unless otherwise noted) PublicHealthOntario.ca Courtesy Christina Renda, PHO 67 Reported cases and rates of hepatitis C: Ontario and Canada, Ontario Cases: MOHLTC, integrated Public Health Information System (iphis) database, extracted [2015/05/13]. Ontario Population: Population Estimates [ ], Statistics Canada, distributed by MOHLTC, received [2014/07/03]. Canadian Rates: Public Health Agency of Canada, Canadian Notifiable Disease Section, received by PHO [2015/07/10]; national data available up to PublicHealthOntario.ca 68 34

35 Current provincial hepatitis C case definition Ontario Confirmed Case Laboratory confirmation of infection with/without symptoms: Detection of Hepatitis C virus (HCV) antibodies, (if > 18 months of age) OR Detection of Hepatitis C virus ribonucleic acid (RNA) PublicHealthOntario.ca 69 Possible new case definition Time between the RNA positive RNA negative RNA unknown current laboratory testing and previous HCV negative laboratory tests < 24 months Newly acquired Newly acquired Newly acquired Infectious Resolved Unknown 24 months / unknown Previously acquired / Unspecified Previously acquired / Unspecified Previously acquired/ Unspecified Infectious Resolved Unknown PublicHealthOntario.ca Courtesy Michael Whelan, PHO 70 35

36 New Treatments Direct acting antiviral drugs Highly effective 95% cure rate Oral medications 8 to 12 weeks of therapy Very well tolerate Work well for all genotypes Very expensive PublicHealthOntario.ca 71 HCV Cascade-USA PublicHealthOntario.ca 36

37 Treatment as Prevention If you treat enough people, could prevent transmission Would require significant investment Must prevent re-infection through harm reduction PublicHealthOntario.ca 73 37