Hepatitis B infection Kenneth Kabagambe Executive Director The National Organization for People Living with Hepatitis B (NOPLHB Uganda
General introduction: Viral hepatitis in Uganda Viruses that affect the liver Commonly hepatitis A, B, C, D and E Rarely other viruses
Hepatitis A Transmitted through eating or drinking food contaminated by stool. Hepatitis A common in developing countries 2/3 of children infected by 5 years of age Mainly does not make them ill They become protected for life
Hepatitis A In developed countries, HAV occurs in outbreaks Contaminated salads, raw seafoods Travels to developing countries Causes sickness like sore throat, fever, fatigue Rarely may cause severe liver disease (liver failure) Prevention Good hygiene and sanitation practices vaccine
Hepatitis E Acquired through contaminated food & drinks In developing countries it occurs in outbreaks e.g Kitgum (2007), outbreak in Napak 2013-2014 Mainly causes mild disease More deaths among pregnant women Prevention Hygiene No readily available vaccine
Hepatitis C Transmitted through IV drug use, Sexual transmission Tattooing and body piercing blood transfusion before 1990 In Uganda at 3% across studies Causes liver scarring and its complications No vaccine
Hepatitis D Only infects in the presence of hepatitis B. The two viruses together cause more severe disease Vaccination against HBV protects against HDV
Hepatitis B virus DNA virus in the hepadnaviridae family Partially double stranded DNA Affects Humans
Hepatitis B infection: epidemiology Global health problem 2 billion persons with evidence of past or current infection 400 million have chronic HBV infection worldwide Major cause of morbidity and mortality World Health Organization, 2002. 2. Lok AS et al. Gastroenterology. 2001;120:1828-53. 3. Lee W. N Engl J Med. 1997;337:1733-45. 4. Poterucha JJ. Ann Intern Med. 1997;126:805-07. 5. Moyer LA, Mast EE. Am J Prev Med. 1994;10(suppl):45-55. 6. Stevens CE et al. J Med Virol. 1979;3:237-41.
Geographic Distribution of Chronic HBV Infection HBsAg Prevalence (%) 1 >8: High 2 8: Intermediate <2: Low 1. WHO. Hepatitis B. 2002. 2. Custer B, et al. J Clin Gastroenterol. 2004;38(10 suppl):s158. 3. WHO/WPRO data.
Uganda Bwogi et al. Afri Health Sci. 2005
Transmission of HBV Contact with infected blood Sexual contact with an infected person Sharing contaminated sharps including tattooing Mother to child Blood transfusion (contaminated)
Transmission of HBV HBV NOT TRANSMITTED THROUGH: Hugging Sharing clothes, cups, plates, basins, or toilets Sitting close to an infected person Therefore NO NEED FOR ISOLATION of infected persons
Who should be screened? Blood donors All persons with abnormal liver tests All HIV positive persons All most at risk persons- IVDU, MSM, sex workers Persons planning to take immunosuppressing therapy All persons from endemic areas Uganda 10%
Natural Progression of CHB 15% 40% of CHB patients may experience disease progression Liver Cancer (HCC) 5% 10% 10% 15% in 5 yr Chronic Infection 30% Cirrhosis Liver Transplantation Death 23% in 5 yr Acute flare Liver Failure Adapted from: Fattovich, et al. Gastroenterology. 2004;127:S35-S50. Torresi, et al. Gastroenterology. 2000;118:S83S103. Fattovich, et al. Hepatology. 1995;21:77-82. Perrillo, et al. Hepatology. 2001;33:424-432.
Clinical features Majority asymptomatic Usually vague constitutional symptoms Acute hepatitis- Jaundice, fever, abdominal pain, encephalopathy
NAs: Potency versus resistance Potency of HBV DNA suppression TDF ETV ADV LdT Likelihood of resistance development LAM Nucleoside analogue Nucleotide analogue
Primary Goal of Hepatitis B Therapy: Preventing Cirrhosis, HCC, and Death Durable Suppression of HBV Replication
Goals of HBV Therapy The clinical goal of HBV treatment Reduction in decompensation and HCC Reduction in mortality Normalization of liver enzymes If HBeAg positive - HBeAg loss and HBeAb seroconversion Suppression of HBV replication to undetectable levels (<10-15 IU/mL) Goal of cure (i.e negative HBsAg still very difficult with current therapy)
Monitoring Patients not on antiviral treatment Monitor Disease progression every 3-6 months Patients on treatment Adherence Treatment response- ALT, viral load, HBeAg loss, HBeAb seroconversion, ultimately HBsAg loss Drug toxicity Decompensation in patients with advanced fibrosis
Monitoring HCC screening In patients with cirrhosis or advanced fibrosis Family history of HCC Persons >30 years with high viral load Annual HIV screening if previously negative
Can Antiviral treatment be stopped? Lifelong treatment in patients with cirrhosis or APRI score >2 May be discontinued in patients who start treatment when HBeAg positive without cirrhosis And HBeAg loss/hbeab gain And persistently normal ALT And Who can be monitored closely When HBsAg becomes negative Treatment should be continued for at least one additional year after attaining these endpoints
Prevention HBV is vaccine preventable disease HBV vaccine prevents development of HCC
Hepatitis B Vaccines Available since 1981 Composed of HBsAg Elicits development of neutralizing antibodies to HBsAg Confers protection from infection Plasma-derived and recombinant formulations 24
Vaccination Prevention of mother to child transmission Exposed infants should get birth dose within 24 hours after birth HBV immunoglobulin + HBV recombinant vaccine at different sites Followed by regular vaccination Shown to reduce prevalence of HBV Antiviral therapy Not recommended for routine mother to child prevention
Childhood vaccination All children in areas of high endemicity In Uganda vaccine introduced in 2002 Pentavalent with DPT Schedule 6 weeks, 10 weeks, 14 weeks
Dose schedules Generally, 3 doses recommended First Injection - At any given time Time 0 Second Injection - At least one month after the first dose 4 weeks Third Injection - Six months after the first dose 6 months
Long-Term Protection with Hepatitis B Vaccine Vaccine provides long-term protection Immunity persists despite loss of anti-hbs Booster doses of hepatitis B vaccine NOT currently recommended 28
Prevention Vaccination of High risk groups Health care workers PWID Sex workers Close contacts of infected persons Standard infection prevention strategies for HBV Safe sex Safe injection practices, etc
Way forward Increase awareness Update epidemiological data Scale up screening Avail facilities for further testing Access to vaccine Access to treatment
Summary High prevalence of HBV in Uganda Chronicity of HBV depends on age of acquisition Liver damage in HBV is largely due to immune interaction than directly Early diagnosis through screening Treatment criteria should be used to select treatment candidates HBV is a vaccine preventable disease