Data from 4 studies presented at The American Association for the Study of Liver Diseases’ The Liver Meeting 2019, held November 8 to 12 in Boston, Massachusetts, report on safety, effectiveness, and best practice approaches in patients with chronic hepatitis B (HBV), including non- and low-responders and obese patients.
Commercially available HBV vaccines can successfully induce anti-hepatitis B surface antibody (anti-Hbs), which along with the loss of hepatitis B surface antigen (HbsAg), are considered a functional cure and the ideal treatment goal for patients with chronic HBV. However, functional cure is difficult to achieve in patients receiving nucelos(t)ide analogue (NA) or interferon therapy or those who are HBV asymptomatic carriers. Therefore, Yoshida and colleagues assessed the efficacy of nasal administrative therapeutic vaccine (NASVAC) on the kinetics of HbsAg in patients with chronic HBV receiving NA treatment (n=29), as well as asymptomatic HBV carriers (n=41).1
NASVAC was administered once every 2 weeks for a total of 10 times. Data was analyzed at 6 months after end of treatment. Results showed that NASVAC induced anti-HBs and reduced HbsAg in patients with chronic HBV receiving NA treatment and asymptomatic HBV carriers. Reduction in HBsAg occurred in 78.9% of patients receiving NA and 85.2% of asymptomatic patients.
In the NA group, the mean HbsAg reduction at 6 months after end of treatment was 19.9%, and 38.5% of patients showed anti-HBs in sera. In the asymptomatic group, 68.2% of patients had HBV-DNA reduction, and 3 patients showed a sustained HBV-DNA negativity. In total, 2 patients each from the NA group and the asymptomatic group achieved functional cure. Overall, the study authors concluded that, “NASVAC could be a novel immune therapy for achieving functional cure in HBV infected patients.”
Of patients vaccinated against HBV, 10% are nonresponders who are either unable to produce anti-HBs or demonstrate inadequately low titers of anti-HBs. Both of these groups remain susceptible to HBV infection postvaccination. Therefore, researchers used the NASVAC vaccine to assess the capacity of anti-HBs induction in HBV vaccine nonresponders (n=17) and responders with low-titers (n=22).2 NASVAC was administered nasally in 3 separate 80 µg doses of hepatitis B surface and core antigens each, every 2 weeks; titers were measured at 1, 3, and 6 months after the last NASVAC administration.
In the nonresponder group, anti-HBs antibody titers became positive after NASVAC in 82.4% of participants and anti-hepatitis B core antibody (anti-Hbc) titers became positive in 76.5% of participants. All participants in the low-responder group demonstrated an increase in anti-HBs titers to ³500 mIU/mL; the highest range of titers (>500 mIU/mL) occurred in 90.9% of participants. Moreover, anti-HBc titers became positive in 90.9% of the participants in the low-responder group. No participants experienced remarkable adverse events. Overall, the study authors concluded that, “NASVAC can effectively boost anti-HBs antibody production in all responders with low titers of the antibody following previous [HBV] vaccination.”
Despite the availability of vaccination, HBV remains a major cause of morbidity and mortality globally, possibly due to a varied immunologic response and developed immunity among some patients. Vaccinated obese patients, nonresponders, and patients with low titers of anti-HBs antibodies have low response rates and may be susceptible to HBV infection.
Previous studies have shown that patients with a body mass index (BMI) >30 kg/m² have response rates of 30%. However, there is a lack of evidence on how to manage HBV vaccine nonresponders. Yanny and colleagues3 conducted a systemic review to evaluate the efficacy of the HBV vaccine and best approaches to HBV vaccine nonresponse in patients with a BMI >30 kg/m². In the 18 studies (748 patients) analyzed from a PubMed literature search, compiled data showed HBV nonresponse in 43% of patients with a BMI >30 kg/m². Results found several avenues to increase vaccine efficacy: a repeat vaccination with the same dose showed increased immunologic seroconversion in 90% of these individuals, and an increase dose in the booster vaccine improved seroconversion to 78.7% in initial nonresponders. Further, a subcutaneous administration route improved seroconversion in 7% of initial nonresponders. Several small trials have noted that the immunomodulatory effects of delta insulin in patients who are obese can increase HBV vaccine response by 10% to 12%.3
In 2017, the Food and Drug Administration approved the 2-dose HBV vaccine, Heplisav-B. The fourth study compared Heplisav-B to the conventional 3-dose vaccine, Engerix-B, in patients with chronic liver diseases and identified factors that predicted seroconversion.4 In total, 115 adult patients who had completed either Heplisav-B or Engerix-B from 2015 to 2019 and had post vaccination HBsAb available at least 2 months after the completion of the vaccine were included. Of the included patients, 73 received the 3-dose and 42 received the 2-dose vaccine.
Results suggested that the 2-dose Heplisav-B resulted in better seroconversion than the 3-dose Engerix-B: seroprotective antibody levels were achieved in 48% of the Engerix-B group compared with 69% of the Heplisav-B group. Univariate analysis showed that renal failure (P =.01) and age (P =.0009) had significant effects on achieving immunogenicity, while cirrhosis did not (P =.07). Multivariate analysis showed that achieving immunity was less probable in patients who were older (odd ratio, 0.39) and patients who received the 3-dose vaccine (odds ratio, 0.93).
Overall, these studies suggested that the 2-dose vaccine is superior to the 3-dose vaccine. In addition, nasally administered NASVAC can effectively boost anti-HBs antibody production in non- and low-responders and obese patients, while also assisting in achieving a functional cure for chronic hepatitis B in asymptomatic patients or patients receiving NA treatment.
1. Yoshida O, Akbar SM, Kohara M, et al. Induction of anti-HBs and reduction of HbsAg by nasal administration of therapeutic vaccine containing HbsAg and HbcAg (NASVAC) in patients with chronic HBV infection. Presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. Abstract 0088.
2. Hiasa Y, Yoshida O, Guillen GE, et al. The HB vaccine containing HBS and HBC antigen (NASVAC) can effectively induce anti-HBs antibody in non-responders to the prophylactic vaccine. Presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. Abstract 0964.
3. Yanny B, Kabany ME, Saab S. Decreased hepatitis B vaccine efficacy in obese individuals and approaches to previously immunized non-responders. Presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. Abstract 0971.
4. Amjad W, Doycheva IB, Zhang T, Maheshwari A, Yoo HY, Thuluvath PJ. Comparison of immunogenicty of two dose hepatitis B vaccine (Heplisav-B) with three dose conventional vaccine (Energix-B) in liver disease cohort. Presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. Abstract 1018.