Hepatitis Vaccination: Questions and Answers

This area is currently very topical, with the recent development of an effective vaccine against hepatitis A, and the implementation plans of almost all provinces and territories for universal hepatitis B vaccination. In this article, the most frequently posed questions concerning immunoprophylaxis against viral hepatitis will be addressed.

Question: Is the new hepatitis A vaccine effective and who needs it?

Answer: Yes, the new hepatitis A vaccine (Havrix) is very effective. It induces protective titres of anti-bodies in greater than 95%, and 99% of people after the first and second doses, respectively. If time does not permit two doses six months apart, then a single Havrix-1440 (double strength) dose may be given. The first dose of the vaccine probably requires at least three weeks to induce significant antibodies, so those travellers who did not have the foresight to have the first dose administered at least three weeks before departure to a high-endemic area should also have standard gammaglobulin to assure protection. Protective antibody titres to the vaccine last at least three years. At this time the need for booster doses is unclear, but it’s likely that, similar to hepatitis B, they will be unnecessary. The vaccine should be administered as an IM injection into the deltoid. Children can be given half-strength (0.5 mL) doses.

Although the manufacturer has suggested a very broad range of people to be targeted for vaccination, the National Advisory Committee on Immunization (NACI) only recommends vaccinating:1) long-term or frequent travellers to endemic regions (which means basically everywhere except Canada, USA, Western Europe, Japan, Australia, and New Zealand).
2) residents of communities with high endemic rates of recurrent outbreaks of hepatitis A, and
3) residents and staff of institutions for the mentally handicapped.

Who Should Receive Hepatitis A Vaccination?

Long-term or frequent travellers to endemic regions
Residents of communities with high endemic rates of hepatitis A
Residents and staff of institutions for the mentally handicapped

Question: Is there any role for standard gammaglobulin in viral hepatitis prophylaxis?

Answer: Basically no. (See the answer above for one last small indication.) Development of highly effective hepatitis A vaccines has obviated the need for gammaglobulin. Note that standard gammaglobulin is useless for immunoprophylaxis against hepatitis B and C.

Question: What is universal hepatitis B vaccination?

Answer: This refers to vaccination of the entire population, usually at the neonatal or childhood level. The rationale for this is that targeted vaccination of high-risk groups has failed to achieve its aims, because most people in these risk groups are unaware or unwilling to be vaccinated. Moreover, 30% to 40% of hepatitis B virus (HBV) infections occur in people who deny any known risk factor.

Question: How is universal HBV vaccination being implemented in Canada?

Answer: As of this writing, eleven provinces and territories have opted for elementary schoolchild (grades 4 to 6) vaccination, and only four of the eleven have also targeted neonates. This is despite the recommendations of the Canadian Paediatric Society, NACI, and the American Public Health Service, that the first priority in universal vaccination should be neonates. Recently a consensus statement prepared by the Canadian Association for the Study of Liver (CASL) also endorsed a similar strategy of neonatal universal vaccination, with catch-up programs for school-aged children if funding permits.

Why then have provincial health authorities, against the recommendations of their own experts, implemented childhood vaccination schedules? It may be that most provincial health ministries followed the misguided example set by British Columbia, which started by targeting children in grade six. British Columbia was experiencing relatively high rates of acute hepatitis B in teenagers and young adults, especially around the greater Vancouver region, and in this age group, almost all acute HBV is transmitted through sexual contact or intravenous drug use. Accordingly, with schoolchild vaccination, one could observe tangible reduction in acute HBV infections within only a few years, rather than within 15 to 20 years with the neonatal program. However, most health ministries have apparently not distinguished between preventing disease versus preventing mortality. Although acute hepatitis B in teenagers and adults causes some morbidity, it is rarely fatal (approx. 0.3% fatality rate), and the risk of developing chronic carriage of HBV, which is widely quoted as 5% to 10% based on older literature, now seems to have been over-estimated. Recent studies, including an important study that followed up American soldiers acutely infected with HBV during a 1942 epidemic, 1 have found a carrier rate following acute HBV of only 0.3% to 0.9% 1-3.

On the other hand, if infection occurs in neonates, it is well known that the chronic carriage rate is greater than 90%, and in early childhood (1 to 6 years), the chronicity rates following acute exposure to HBV are 10% to 80% in an inverse age-dependent manner. Therefore, to prevent chronic HBV carriage, with its attendant sequelae of cirrhosis and hepatocellular carcinoma, one must aim to prevent neonates and infants from being infected by HBV. Although this is partially addressed by universal screening of all pregnancies with hepatitis B immune globulin (HBIG) and vaccination for infants born to HBV-positive mothers, this approach is not completely effective because of high intrafamilial transmission rates. In households where the mother is negative for HBsAg, but at least one child is already infected, there is a 26% transmission rate between siblings. 4

In a static low-endemic population, childhood vaccination will eventually reduce the population pool of chronic HBV carriers, but in Canada the continuing influx of immigrants, the vast majority from high-endemic countries, defeats this strategy. The bottom line is that in immunocompetent individuals, the risk of chronic hepatitis is high before age five, and very low after age ten. Hence it makes sense to give the vaccine at a time when the chance of preventing chronic infection is highest. So, what is the answer to the question regarding the rationale for the current approach to childhood vaccination? Beats me!

Age-Dependent Outcome of  Acute Hepatitis B Infection

Age                                Risk of Becoming a Chronic Carrier
Neonate                                          > 90%
1 - yr.                                               > 80%
5 - yrs                                            10 - 30%
12 - yrs                                           < 10%
Teenager & adult                          0.3 - 0.9%

Question: What is the schedule for neonatal protection if the mother is a hepatitis B carrier?

Answer: For this patient, hepatitis B vaccine 0.5 mL i.m. is administered within the first 12h after birth, along with HBIG, 1 mL, at the same time (but different injection site). The second dose of vaccine should be given at one week, and the third at one to six months. Without intervention, the replicative HBV carrier (HBeAg-positive) mother has a greater than 80% chance of transmitting the infection to the newborn, while the HBeAg negative mother still has 15% to 20% rates. Because protection is not totally effective even with this immunoprophylaxis, there is still a 5% to 10% transmission rate of HBV.

Question: What are the immunoprophylaxis recommendations for household contacts if an individual is found to be positive for HBsAg or develops acute hepatitis B?

Answer: All household contacts should be screened for HBsAg and anti-HBs. If the spouse or sexual partner is negative for both, then he or she should be given 5 mL of HBIG and a course of vaccine, if the index case has acute hepatitis B, whereas vaccine alone should suffice for partners of chronic HBsAg carriers. Other household contacts, if serologically negative, require only a course of vaccination. In Canada, almost all public health units will carry out the above or slightly variant programs when notified of a positive HBsAg result.

Question: I have a general practice with very little ER work; why should I be vaccinated for HBV?

Answer: If your practice involves no work in emergency rooms, hospital wards, institutions for the handicapped and no administration of needles or minor surgery, and you never have hangnails, minor cuts and abrasions on your hands, then it is likely that you would not be susceptible to occupationally-acquired hepatitis B. There are very few practices that fit this description, and all other physicians would benefit from this safe and effective vaccine. Or, put another way, there has been several cases of unvaccinated physicians who died from occupationally-acquired acute hepatitis B; isn’t your life worth the $150.00 cost of a course of vaccine?

Question: I had a standard course of three deltoid injections of full-dose hepatitis B vaccination, but failed to make protective antibody titres.

What does this mean and what should I do now?
Answer: Lesser response rates to HBV vaccination are associated with age, increased body mass and smoking. For example, only 60% to 80% of those aged over 60 years make protective antibody titres. No one can reverse aging, but it you are overweight and smoke, losing weight and quitting smoking, followed by revaccination, might be effective. Even in healthy immunocompetent adults, about 5% will not develop protective antibodies after a course of vaccination. Recent work has discovered that the immune response to hepatitis B surface epitopes is genetically determined. For your interest, you probably have HLA haplotypes B8, DR3, SCO1; or B44, DR7, FC31. If a second complete course of vaccinations fails to induce protective titres, you will have to sadly accept that you are not protected against hepatitis B. You can blame your parents for giving you these bad genes.

Question: Is a booster dose needed after five or ten years for recipients of hepatitis B vaccination?

Answer: No. If you originally demonstrated an adequate antibody response, even though anti-HBs titres may gradually fall below the critical 10 IU/L level, the immune system will mount a sufficiently protective anamnestic response if rechallenged with hepatitis B. 5-6

Question: Is there anything on the horizon for a vaccine against hepatitis C?

Answer: No. Effects to develop an effective HCV vaccine have been frustrated by:
1) initial difficulties in actually identifying the virus responsible for hepatitis C (although we knew its molecular structure in 1989, it was not until 1996 that a putative HCV was identified),
2) difficulties in establishing stable cultures of the virus in a cell line, and
3) high mutability of the HCV, which like HIV, mutates at a high rate.

Question: What should be done in case of a needlestick injury?

Answer: Management will slightly differ depending on whether the recipient (usually a health care worker) has previously been vaccinated for HBV. If vaccinated, then the recipient (as a baseline) and the source patient, should be tested for anti-HCV and anti HIV. If not vaccinated, then HBsAg should be added to the tests for the source patient, and both HBsAg and anti-HBs added to the recipient’s bloodwork. Since this article is focussed on hepatitis, we will only deal with the HBV and HCV-positive scenarios.

1) Source is HBsAg-positive, recipient unvaccinated (and negative for both HBsAg and HBs): give recipient HBIG, 5 mL, i.m., and first dose of hepatitis B vaccine. Complete the standard dosing protocol of vaccine at zero, one, and six months. Without intervention, there is about a 20% chance of the recipient contracting acute hepatitis B, and this figure is a composite of approximately a 50% to 80% chance if the source is HBeAg-positive (replicating, with high viral load), and a 10% to 15% chance if the source is HBeAg-negative.
2) Source is anti-HCV-positive, recipient anti-HCV-negative: test the recipient for ALT at baseline (as soon as possible after needlestick), and HCV-RNA by polymerase chain reaction and ALT at six to eight weeks after exposure. If HCV RNA is negative at this time, the chance of contracting acute hepatitis C is essentially zero. If the HCV-RNA test is not available locally, then the ALT should be repeated at three and six months, and the anti-HCV at six months. If they remain normal or negative at six months, the likelihood of developing HCV will be nil.
If HCV-RNA turns positive at six to eight weeks, this heralds the onset of acute hepatitis C, and these patients should be treated with a- interferon at a dose of three million units s.c. thrice weekly for 24 weeks. In centres where HCV-RNA is not available, the diagnosis of acute HCV can be made using a combination of the ALT and anti-HCV serology, realizing that the development of anti-HCV-positivity, even with third generation enzyme immunoassays, sometimes lags behind the acute hepatitis by a month or more. Therefore, before embarking on interferon therapy with its cost and side effects, I would recommend confirming the diagnosis by HCV-RNA which can be sent out to a lab in a larger centre.

Fortunately, acute HCV developing after needlestick injury is uncommon. Several series have indicated that the risk of this occurring is approximately 5% to 10%.

References and Further Reading

1. Seeff LB, et al. A serologic followup of the 1942 epidemic of post-vaccination hepatitis in the United States army. N Engl Med 1987;316:965-70.
2. Tassopoulos NC, et al. Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults. Gastroenterology 1987;92:1844-50.
3. Margolis HS, et al. Hepatitis B: evolving epidemiology and implications for control. Semin Liver Dis 1991;2:84 92.
4. Franks AL, et al. Hepatitis B virus infection among children born in the United States to Southeast Asian refugees. N Engl J Med 1989;321:1301-5.
5. Lai CL, et al. Five-year followup of a prospective randomized trial of hepatitis B recombinant DNA yeast vaccine vs placebo-derived vaccine in children: immunogenicity and anamnestic responses. Hepatology 1993;18:763-7.
6. Stevens CE, et al. Hepatitis B vaccine: an overview. In:Vyas GN, Dienstag J. Hoofnagle JH (eds). Viral Hepatitis and Liver Disease. Grune & Stratton, Orlando, FL. 1984.pp 275-91.
7. Bloom BS, et al. A reappraisal hepatitis B virus vaccination strategies using cost-effectiveness analysis. Ann Int Med 1993;118:298-306.
8. Canadian Pediatric Society. Hepatitis B in Canada: the case for universal vaccination. Can Med Assoc J 1992;146:25-8.
9. CASL Hepatitis Consensus Group. Management of viral hepatitis clinical and public health perspectives. A consensus statement. Can Med Assoc J (in press).
10. Katkov WN. Hepatitis vaccines. Med Clin N Amer 1996;80:1189-200.
11. Furesz J, et al. Safety and effectiveness of the new inactivated hepatitis A vaccine. Can Med Assoc J 1995;152:343-8.
12. Van Damme P, et al. Inactivated hepatitis A vaccine: reactogenicity, immunogenicity, and long-term antibody persistence. J Med Virol 1994;44:446-51.

Sharing is caring!

Leave a Comment