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Gould Professor of Medicine
Director, Division of Digestive Diseases
University of Cincinnati College of Medicine
Kenneth E. Sherman, MD, PhD, has disclosed that he has received consulting fees from Gilead Sciences and Theratechnologies; has received funds for research from AbbVie, Gilead Sciences, and Intercept; and has served on data and safety monitoring boards for Horizon Pharma and Inovio.
Despite the availability of highly effective hepatitis B vaccines since the early 1980s, we still see more than 20,000 acute hepatitis B cases per year in the United States. Estimates show that only 25% to 30% of US adults are vaccinated and that approximately 2 million people are living with hepatitis B virus (HBV). Here’s why I think newer vaccines might make a difference.
New HBV Vaccine
Currently, there are 4 FDA-approved HBV vaccines available in the United States, plus one other combination formulation that provides immunization against both hepatitis A and hepatitis B. The 2 oldest HBV vaccines are single-antigen vaccines approved more than 30 years ago, each of which is given as a 3-dose series.
More recently, a single-antigen vaccine was approved by the FDA for use in adults in 2017. It contains an immune adjuvant to improve immunogenicity and requires 2 doses only.
And the newest vaccine was approved for use in adults in 2021. It differs from the other vaccines in 2 ways. First, it is a trivalent vaccine containing 3 hepatitis B surface antigens (HBsAg), whereas the other vaccines contain the single HBsAg only. Second, it is produced in Chinese hamster ovary cells, a mammalian cell line, so the HBsAg is folded into its native conformation with mammalian posttranslational glycosylation, resulting in improved immunologic responses.
Because the trivalent vaccine is the newest, it’s worth reviewing its pivotal phase III trials: PROTECT, conducted in adults up to 90 years of age, and CONSTANT, which enrolled adults aged 18-45 years. Both trials met their endpoints of noninferiority in seroprotection rates.
Secondary endpoints included assessment of the geometric mean titer at the end of the complete series vs the titer of one of the older single-antigen vaccines. The trivalent vaccine achieved a more than 4-fold higher geometric mean titer in all age groups, suggestive of a durable vaccine response. And among adults aged 45 years or older enrolled on the PROTECT trial, the trivalent vaccine was superior.
Like the older nonadjuvanted vaccines, the trivalent vaccine has a 3-dose schedule to be given at 0, 1, and 6 months, which may prove challenging for some individuals, given that we know from previous data that people may fail to present for later doses of an HBV vaccine schedule. In comparison, the adjuvanted 2-dose vaccine series is given at 0 and 1 month, meaning that the patient does not need to return for a third dose.
Although all approved HBV vaccines are effective, there are some patients who may not achieve seroprotection after vaccination. Populations at high risk for hepatitis B infection are often less likely to respond well to current vaccination strategies (eg, patients with HIV, those with chronic liver disease or chronic kidney disease, those on renal dialysis, elderly patients, or those with diabetes). We know that patients with chronic hepatitis C are less likely to respond to hepatitis B vaccination, particularly if they have hepatic fibrosis.
In addition, we are in the midst of an obesity epidemic in the United States, leading to nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. If these people develop fibrosis, their overall response rates are lower, with patients with cirrhosis having the lowest responses.
In these populations at risk for poor response, vaccine efficacy is important. One option is to treat all of those patients like dialysis patients by increasing the dose, though this may add additional cost.
Another question to consider is whether efficacy is improved with the newer vaccines in patients with suboptimal responses? To me, the answer is maybe.
The phase III studies of the trivalent vaccine and the adjuvanted vaccine showed that they were indeed effective in the subgroups of patients who may typically be at risk for poor response: those with diabetes, or who are obese.
And what about patients who have already had poor response? In nonresponders and low responders to conventional single-antigen vaccines, data on the trivalent vaccine’s efficacy are limited. But as I mentioned earlier, there is evidence that the trivalent vaccine did better than a single-antigen vaccine in patients older than 45 years of age.
For the adjuvanted vaccine, there are ongoing trials, and Awad and colleagues showed satisfactory results in dialysis patients with a 4-dose series, although this formulation is not approved in that group of patients by the FDA. Previously, Janssen and colleagues reported superior seroprotection with a 3-dose vaccine series compared to 4 double-doses in patients with chronic kidney disease.
Similarly, I am involved with a study through the National Institutes of Health and the AIDS Clinical Trials Group looking at HBV revaccination of nonresponder patients with HIV, specifically whether a 2- or 3-dose series of the adjuvanted vaccine would be more effective than another round of the older vaccines.
Our practice is to do whatever we need to do to get a high-risk patient vaccinated, because at the end of the day, vaccines are very inexpensive relative to the cost of an acute case of hepatitis B or the downstream complications and costs associated both for the individual and for society as a whole
In our clinic, we have discovered that having HBV vaccines available at the time we see patients is a much more effective strategy than giving patients a recommendation or even a prescription to later get the vaccine at a pharmacy or in their primary care physician’s office. We work hard to ensure that patients with chronic liver disease—which is whom I see in my practice—start their vaccination series before they leave the clinic. I think it is so important to make it as easy as possible for patients to be vaccinated against HBV. It is not just a matter of record keeping, but of making it available at the time you have access to the patient.
What is your experience of accessing or providing HBV vaccination to your adult patients? Take part in our poll or share your comments with other readers in the discussion section below.