721
spectacles, neither will they,
as
they will consider it
civilised to do so. If we do, we shall benefit but the whole world by our example. 93 Uxbridge Road, Rickmansworth, Herts WD3 2DQ
not
to
be
un-
only ourselves B. M. WRIGHT
SAFETY OF HEPATITIS-B VACCINES: NO EVIDENCE OF AUTOIMMUNITY Zuckerman rightly draws attention (March dangers of immunising human beings with purified 20 nm particles of HBsAg derived from chronic carriers. One of his arguments is that the negative results for autoantibodies reported in chimpanzees by Dr Trepo and his colleagues (March 3, p. 488) may not apply to man. We looked
SIR,-Professor
10, p. 547)
to
the
for evidence of autoimmune reactions after HB vaccination in volunteers during the Loire Valley haemodiaiysis unit’s programme of HB protection’ which has now been fully described2 For this pilot study, five renal patients and fifteen staff members were selected to represent a cross-section for sex, age, and responses to the vaccine. 3-6 stored serum samples were available from each person, taken before and 1-16 months after the first injection of the vaccine, making a total of 92 coded specimens. There were ten females (two patients and eight staff, aged 18-46, mean age 29) and ten males (three patients and seven staff, aged 22-56, mean 29). All sera were tested by indirect immunofluorescence, undiluted on human stomach and pancreas, and at 1:10 dilutions on human thyroid, rat liver, and rat kidney. This was supplemented by the latex Fll agglutination test for rheumatoid factors and by hxmagglutination with ’Thymune T & M’ (Wellcome Reagents) or with Fujizoki "microsome" kits for the detection of thyroglobulin and thyroid microsomal antibodies respectively. None of the twenty subjects showed any organ-specific reactions-i.e., thyroid, gastric (parietal cell), or pancreatic isletcell antibodies, either before or up to 16 months after vaccination. Of the non-organ-specific reactions looked for, mitochondrial, liver and kidney microsomal, ribosomal, cardiolipin fluorescent, and reticulin antibodies were negative in all 92 sera. Nuclear antibodies (A.N.A.) were found in only 1 specimen taken 8 months after vaccination from a hxmodialysis case (weak diffuse pattern A.N.A. to titre of 1:10), the other 4 samples (0, 3, 12, and 16 months) being negative. Smooth-muscle antibodies (S.M.A.) were detected at a titre not exceeding 1:10 in all samples from three of the staff members and did not fluctuate in intensity during follow-up. On opening the code it was interesting to find that two of these volunteers had had low-titre anti-HBs even before vaccination-i.e., they had encountered the virus and reacted anamnestically to the vaccine. The third staff member with S.M.A. had apparently no previous contact with hepatitis B virus (H.B.v.) but had transient HBsAg after the injections. S.M.A. is commonly found during viral infections. In this series the, frequency of S.M.A. thus 13% (normal One staff member
10-12). was positive specimens). Heterophile reactions was
for rheumatoid factor (5 have been described in human sera tested on rat tissues. One such antibody "brush border"4 was found in the same three subjects who had S.M.A., and rat "bile-duct" fluorescence was seen in all specimens of four individuals unrelated to any other feature. One haemodialysis case showed a fluorescence of connective tissue in rat sections. The significance of various heterophile reactions is not fully worked out. 1 2
3 4
Maupas, P., Goudeau, A., Coursaget, P., Drucker, J. Lancet, 1976, i, 1367. Maupas, P., Goudeau, A., Coursaget, P., Drucker, J., Barm, F., Andre, M. in Viral Hepatitis (edited by G. N. Vyas, S N Cohen, and R. Schmid), p 539 Philadelphia, 1978. Holborow, E. J Proc.R. Soc. Med. 1972, 65, 481. Ireton, H. J C., Miller, H. K., McGiven, A. R. Clin. exp Immun. 1971, 8, 783
We conclude that vaccination with purified HBs antigen not lead to significant autoimmunisation in men and women who are likely to benefit from this procedure. Seventeen French hxmodialysis centres have now taken up this preventive measure for their staff and patients (total vaccinated individuals 1240), thereby greatly reducing the incidence of clinical hepatitis B, and 1000 women and children in Senegal have been vaccinated for prevention of primary hepatic cancer which is mainly associated with H.B.v. infection and carrier state in that part of Africa.
does
W.H.O Autoimmune Serology Reference Middlesex Hospital Medical School, London W1P9PG
Laboratory,
D. DONIACH G. F. BOTTAZZO PH. MAUPAS P. COURSAGET A. GOUDEAU
Institute of
Virology, Faculty of Medicine and Pharmacology,
Tours 3700, France
HEPATOCELLULAR CARCINOMA AND HEPATITIS B VIRUS MARKERS IN EUROPE
SIR,-We have followed with interest the recent report’ and (Feb. 24, p. 433) on hepatitis B virus (H.B.v.) and
comments
hepatocellular carcinoma (H.C.C.). We agree with Dr Johnson a relationship could be established if enough patients with
that
an otherwise normal liver were studied. Another would be to study patients with cirrhosis of the liver with and without H.c.c. to see if H.B.v. markers are found more often in the tumour group. We have studied a group of H.c.c. and cirrhotic patients who were tested for HBsAg by inverse passive hasmagglutination and for anti-HBc by radio-
H.C.C.
in
approach
SERUM HEPATITIS B VIRUS MARKERS IN H.C.C. AND CIRRHOSIS
immunoassay (’Corab’ Abbot).
with hepatoma on 7 of the 12 by or Of examination. the laparotomy necropsy patients with cirrhosis and hepatoma, 8 were histologically proved and the rest had a high level of fetoprotein. All patients positive for HBsAg were also positive for antiHBc (table). Hepatitis B virus markers were found more often in patients with H.c.c. with or without cirrhosis than in healthy controls (/=36-9, p
spectacles, neither will they,
as
they will consider it
civilised to do so. If we do, we shall benefit but the whole world by our example. 93 Uxbridge Road, Rickmansworth, Herts WD3 2DQ
not
to
be
un-
only ourselves B. M. WRIGHT
SAFETY OF HEPATITIS-B VACCINES: NO EVIDENCE OF AUTOIMMUNITY Zuckerman rightly draws attention (March dangers of immunising human beings with purified 20 nm particles of HBsAg derived from chronic carriers. One of his arguments is that the negative results for autoantibodies reported in chimpanzees by Dr Trepo and his colleagues (March 3, p. 488) may not apply to man. We looked
SIR,-Professor
10, p. 547)
to
the
for evidence of autoimmune reactions after HB vaccination in volunteers during the Loire Valley haemodiaiysis unit’s programme of HB protection’ which has now been fully described2 For this pilot study, five renal patients and fifteen staff members were selected to represent a cross-section for sex, age, and responses to the vaccine. 3-6 stored serum samples were available from each person, taken before and 1-16 months after the first injection of the vaccine, making a total of 92 coded specimens. There were ten females (two patients and eight staff, aged 18-46, mean age 29) and ten males (three patients and seven staff, aged 22-56, mean 29). All sera were tested by indirect immunofluorescence, undiluted on human stomach and pancreas, and at 1:10 dilutions on human thyroid, rat liver, and rat kidney. This was supplemented by the latex Fll agglutination test for rheumatoid factors and by hxmagglutination with ’Thymune T & M’ (Wellcome Reagents) or with Fujizoki "microsome" kits for the detection of thyroglobulin and thyroid microsomal antibodies respectively. None of the twenty subjects showed any organ-specific reactions-i.e., thyroid, gastric (parietal cell), or pancreatic isletcell antibodies, either before or up to 16 months after vaccination. Of the non-organ-specific reactions looked for, mitochondrial, liver and kidney microsomal, ribosomal, cardiolipin fluorescent, and reticulin antibodies were negative in all 92 sera. Nuclear antibodies (A.N.A.) were found in only 1 specimen taken 8 months after vaccination from a hxmodialysis case (weak diffuse pattern A.N.A. to titre of 1:10), the other 4 samples (0, 3, 12, and 16 months) being negative. Smooth-muscle antibodies (S.M.A.) were detected at a titre not exceeding 1:10 in all samples from three of the staff members and did not fluctuate in intensity during follow-up. On opening the code it was interesting to find that two of these volunteers had had low-titre anti-HBs even before vaccination-i.e., they had encountered the virus and reacted anamnestically to the vaccine. The third staff member with S.M.A. had apparently no previous contact with hepatitis B virus (H.B.v.) but had transient HBsAg after the injections. S.M.A. is commonly found during viral infections. In this series the, frequency of S.M.A. thus 13% (normal One staff member
10-12). was positive specimens). Heterophile reactions was
for rheumatoid factor (5 have been described in human sera tested on rat tissues. One such antibody "brush border"4 was found in the same three subjects who had S.M.A., and rat "bile-duct" fluorescence was seen in all specimens of four individuals unrelated to any other feature. One haemodialysis case showed a fluorescence of connective tissue in rat sections. The significance of various heterophile reactions is not fully worked out. 1 2
3 4
Maupas, P., Goudeau, A., Coursaget, P., Drucker, J. Lancet, 1976, i, 1367. Maupas, P., Goudeau, A., Coursaget, P., Drucker, J., Barm, F., Andre, M. in Viral Hepatitis (edited by G. N. Vyas, S N Cohen, and R. Schmid), p 539 Philadelphia, 1978. Holborow, E. J Proc.R. Soc. Med. 1972, 65, 481. Ireton, H. J C., Miller, H. K., McGiven, A. R. Clin. exp Immun. 1971, 8, 783
We conclude that vaccination with purified HBs antigen not lead to significant autoimmunisation in men and women who are likely to benefit from this procedure. Seventeen French hxmodialysis centres have now taken up this preventive measure for their staff and patients (total vaccinated individuals 1240), thereby greatly reducing the incidence of clinical hepatitis B, and 1000 women and children in Senegal have been vaccinated for prevention of primary hepatic cancer which is mainly associated with H.B.v. infection and carrier state in that part of Africa.
does
W.H.O Autoimmune Serology Reference Middlesex Hospital Medical School, London W1P9PG
Laboratory,
D. DONIACH G. F. BOTTAZZO PH. MAUPAS P. COURSAGET A. GOUDEAU
Institute of
Virology, Faculty of Medicine and Pharmacology,
Tours 3700, France
HEPATOCELLULAR CARCINOMA AND HEPATITIS B VIRUS MARKERS IN EUROPE
SIR,-We have followed with interest the recent report’ and (Feb. 24, p. 433) on hepatitis B virus (H.B.v.) and
comments
hepatocellular carcinoma (H.C.C.). We agree with Dr Johnson a relationship could be established if enough patients with
that
an otherwise normal liver were studied. Another would be to study patients with cirrhosis of the liver with and without H.c.c. to see if H.B.v. markers are found more often in the tumour group. We have studied a group of H.c.c. and cirrhotic patients who were tested for HBsAg by inverse passive hasmagglutination and for anti-HBc by radio-
H.C.C.
in
approach
SERUM HEPATITIS B VIRUS MARKERS IN H.C.C. AND CIRRHOSIS
immunoassay (’Corab’ Abbot).
with hepatoma on 7 of the 12 by or Of examination. the laparotomy necropsy patients with cirrhosis and hepatoma, 8 were histologically proved and the rest had a high level of fetoprotein. All patients positive for HBsAg were also positive for antiHBc (table). Hepatitis B virus markers were found more often in patients with H.c.c. with or without cirrhosis than in healthy controls (/=36-9, p
