(Informed Parent 4/2000)

Taken from :Pulse 16/9/00

Vaccination against hepatitis B is associated with a 1.6 fold increase in the risk of developing lupus erythematosus, an analysis of the UK General Practice Research Database (GPRD) has revealed.

The study by French and Dutch researchers found that among people aged over 40, lupus risk was elevated 2.6-fold by the vaccine.

The analysis was prompted by 274 reports to the French pharmacovigilance system of autoimmune disorders associated with hepatitis B vaccination -including 32 reports of lupus.

The study identified 255 patients on the GPRD who had had at least two diagnoses of lupus or discoid lupus, at least one by a specialist, between 1989 and 1998. Each case was matched to up to 10 controls from the same practice.

The overall incidence of lupus was 10.7 per 100,000 patients per year. Incidence was highest in those aged 40 to 59, and was 6-fold higher in women than men.

Results were presented to the International Society for Pharmacoepidemiology in Barcelona last month.

Prof. Peter Hayes, a member of the Government’s advisory group on hepatitis and professor of hepatology at Edinburgh Royal Infirmary, said:

‘Epidemiological studies are very important but we mustn’t overreact. And 1.6 is not a greatly increased risk.’

He said hepatitis B vaccine had ‘remarkably few side-effects’ although there had been rare reports of associations with demyelinating disease and Guillain-Barré syndrome. No causal link had been established, he stressed.

Prof Hayes said further work was needed on the risk-benefit balance of the vaccine as people vaccinated in Britain were not representative of the general population. Although a few million were vaccinated annually, they were mainly high-risk groups including NHS staff, travellers, people with liver disease and drug addicts.

The risk-benefits balance might alter if a mass vaccination campaign were to be considered, he said.

Dr Robert Aston, a member of the Government’s Joint Committee on Vaccination and Immunisation and consultant in communicable disease control at Wigan and Bolton health authority, said it was ‘dangerous to jump to premature conclusions’ from a single study.

Editor: How long will it be before the hepatitis B vaccine is introduced into the UK immunisation programme? It’s used in the USA and we usually follow in their footsteps.

It’s interesting to look at what the hefty volume entitled ‘Vaccines’ by Plotkin and Mortimer has to say on the hepatitis B vaccine. Under the beading ‘Indications for vaccination’ (page 429) it states:

When hepatitis B vaccine became available (USA), the Advisory Committee on Immunisation Practices (ACIP) of the Centers for Disease Control recommended vaccination for individuals who are at high risk. After more than a decade, however, it became apparent that this approach had little impact on the incidence of hepatitis B in the United States (Fig 14-7)

It has been predicted that the strategy of targeting hepatitis B vaccine only to members of high-risk groups would continue to have very little impact in controlling HBV infection. Only universal immunisation of infants, and possibly older children, could have a measureable impact over the next 2 decades. The ACIP and the American Academy of Pediatrics, therefore, have now recommended that hepatitis B vaccine be included among routine childhood immunisations. Although priorities for use of the vaccine in various countries of the world depend on financial resources, most experts now agree that hepatitis B vaccine should be given routinely to all children. As a result, efforts are also under way to add hepatitis B vaccine to the World Health Organisation’s EPI (Expanded Program of Immunisation).

A few pages ahead under the heading ‘Universal Hepatitis B Immunisation’ the above statements are elaborated on. There is an admission that in the first 10 years of the Hepatitis B vaccine being available not only did it appear to have little impact, but ‘in fact, the number of reported cases actually continued increase up to 1985.’

It continues:

‘The only risk groups in which the number of cases has declined have been health care workers and homosexual men. The decreased incidence in the latter group may be due to the adoption of safer sexual practices to prevent HIV-1 infection rather than the use hepatitis B vaccine. The failure of a vaccination strategy aimed at higher-risk groups has been due, in part, to failure of most individuals at risk to be vaccinated (80% of vaccine recipient have been health care workers). In addition, in carefully investigated hepatitis B cases, 40% have no identified risk. Such individuals would never be reached in a targeted vaccination strategy.

As indicated previously, in an effort to control hepatitis B in the USA more effectively, (Editor: Strange choice of wording ‘more effectively.’ when the authors openly admit that the vaccine had little impact and the cases rose in the first few years of its introduction.) the ACIP and the Committee on Infectious Diseases of the American Academy of Pediatrics now recommend universal immunisation against HBV in childhood. The US Public Health Service has already added hepatitis B vaccine to the list of routine immunisations of children. However even if effective universal childhood immunisation against HBV would not have any measurable effect for 15 to 20 years, when the vaccinated cohort reaches the age in which most risks occur. The ACIP, therefore, continue recommend that high-risk individuals school-aged children for an interim period to minimise any lag in the impact of the immunisation program.

Italy and several Asian countries have also embarked on programs of universal hepatitis B vaccination of infants.’

Figures for the efficacy of the hepatitis vaccine are commented on under the heading ‘Immunogenicity’ on page 432. It states that a complete series of 3 or 4 inoculations of the vaccine has consistently induced an antibody response in approximately 95% of seronegative immunocompetent recipients. (immunocompetent -meaning: possessing the ability to mount a normal immune response, seronegative -meaning: lacking an antibody of a specific type in serum; used to mean absence of prior infection with a specific agent, immunocompetent recipients.)

For those of you who want the figures, the authors state that generally anti-HBs values that exceed 10 S/N units are indicative of immunity to hepatitis B.

Levels less than 2.1 S/N indicate susceptibility. Values between 2.1 and 10 S/N may or may not be protective. (S/N = ratio of sample counts per minute to the mean negative control)

They also mention that the seroconversion rate decreases with age, especially in the over 40s, but in infants, children and young adults the vaccine is highly immunogenic.

Long term follow-up of vaccine recipients has shown that most vaccinees retain detectable anti-HBs levels for long periods. Apparently similar data from the CDC suggest that protection may persist even when antibody levels are low or undetectable. (Our emphasis.) Thus, the need for routine booster doses of the vaccine after the initial series is not clear.

Editor: It is indeed ‘not clear’ especially when there is quite obviously a large question mark surrounding the role antibody levels play in protection.

Also if the immunogenicity has been shown to induce the ‘so-called’ required antibody response in 95% of the recipients then why did the vaccination have little impact on the rate of hepatitis B since its introduction in the USA?