A Prospective Study of HBV Immunity and HBV Vaccination in Patients With NAFLD in Canada
Condition: Non-Alcoholic Fatty Liver Disease; Hepatitis B; Vaccine Reaction
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Observational

Summary: 
      (1) Due to missed childhood vaccination programs, the majority of adult patients with NAFLD
      in Canada do not have immunity to hepatitis B. (2) Adults with NAFLD who receive the HBV
      vaccine have reduced immunogenic responses in the setting of obesity (i.e., protective
      anti-HBs titres). Aims: (1) To determine the sero-prevalence of immunity against hepatitis B
      in a cohort of prospectively evaluated adult NAFLD patients. (2) To prospectively determine
      HBV vaccine responses (anti-HBs titres) in adult NAFLD patients.
    

Detailed description: 
      The hepatitis B virus (HBV) is truly a global human pathogen that affects at least 2 billion
      people worldwide including ~240 million chronic hepatitis B (CHB) carriers that are at risk
      for end-stage liver disease. The diagnosis of CHB is confirmed by the persistence of the HBV
      surface antigen (HBsAg) in serum for >6 months. However, a latent form of HBV infection known
      as occult hepatitis B infection (OBI) characterized by low-level viremia (i.e., HBV DNA < 200
      IU/ml) despite undetectable serum HBsAg has been described with unclear clinical
      consequences.

      A safe and effective HBV vaccine has been available for ~3 decades and consists of
      recombinant HBsAg which contains the major viral antigenic epitopes and induces a protective
      neutralizing antibody to HBsAg (anti-HBs) response in >85% of children vaccinated. Canada is
      a low HBV-endemic region and in Alberta, and Ontario, public health uses maternal screening
      for HBsAg to identify babies at-risk for CHB. Thus, all infants born to HBsAg (+) mothers are
      given passive-active immunoprophylaxis with hepatitis B immune globulin (HBIG) and the HBV
      vaccine within 12 hours of birth, as well as 2 doses at ~2 and ~6 months of age. Testing of
      the infants for anti-HBs is recommended at 9 months to ensure immunity. In the late 1990's, a
      universal HBV childhood vaccination program was initiated in all Canadian provinces and
      jurisdictions. In Alberta and in Ontario, school-age children are scheduled to receive the
      3-dose HBV vaccine series in grade 5. However there remain a significant proportion of adult
      Canadians (i.e., born before 1985) who missed childhood vaccination programs. Although
      current guidelines recommend that certain high-risk populations receive hepatitis B
      immunization, appropriate identification and compliance is generally much lower in adults
      compared to children.

      According to the most recent Canadian Association for the Study of Liver Disease guidelines,
      all adults with diabetes, as well as all patients with chronic liver disease should receive
      the hepatitis B vaccine. The basis for these recommendations are two-fold, (1) diabetics may
      be at risk of blood-borne virus (BBV) exposure through contact with contaminated blood
      glucose monitoring devices and (2) diabetic patients are at increased risk of the metabolic
      syndrome and the development of non-alcoholic fatty liver disease (NAFLD). The improvement in
      blood glucose monitoring devices, and increased knowledge has reduced the risk of HBV
      exposure in patients with diabetes. Further, the investigators' initial seroepidemiological
      survey of acute HBV outbreaks in Alberta revealed a decreasing prevalence in diabetic
      patients. Therefore the main incentive for HBV vaccination in diabetics is due to the
      concomitant risk of the metabolic syndrome and advanced liver disease due to NAFLD. There is
      limited data on HBV vaccination in NAFLD patients. Further studies are required in a North
      American adult (Canadian population).

      The investigators propose that adults with NAFLD should undergo comprehensive screening for
      hepatitis B immunogenicity, in addition to screening for infection, and catch up or booster
      vaccinations should be administered to non-immunized patients with confirmatory immunity
      testing thereafter.
    

Intervention name(s): Engerix-B
Intervention type(s): Biological
Intervention description(s): Hepatitis B Vaccine
Other intervention name(s): Twinrix
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        NAFLD patients will be recruited from large tertiary liver clinics in Canada
      
Biospecimen description: 
      PBMCs will be cryopreserved to assess HBV specific T and B cell responses.