1173
antibody indicates either inactive chronic liver disease or asymptomatic carriage of HBsAg. The patients with a histological diagnosis of chronic persistent hepatitis showed a high incidence of both e antigen and e antibody. At the time of study there was cess
while
e
obvious difference in these two groups, but the association of e antibody with asymptomatic carriage or recovery from acute hepatitis B viral infection suggests that these patients may have a better prognosis than those with e antigenaemia who may progress to chronic active no
hepatitis. We thank the Medical Research Council and the Burton Charitable Trust for financial support and Dr G. Le Bouvier and Dr J. Hoofnagle for gifts of antisera.
Requests for reprints should be addressed to S. S. REFERENCES
J. O., Le Bouvier, G. L., Copenhagen Hepatitis Acuta Program New Engl.J. Med. 1973, 288, 1257. 2. Iwarson, S., Magnius, L., Lindholm, A., Lundin, P. Br. med. J. 1973, i, 84. 3. Hadziyannis, S., Le Bouvier, G. L. Iatriki, 1972, 22, 453. 4. Magnius, L., Berg, R., Bjorvatn, B., Svedmyr, A. Scand.J. infect. Dis. 1973, 5, 71. 5. Mosley, J. W., Edwards, V. M., Meilhaus, J. E., Redeker, A. G. Am.J. Epidemiol. 1972, 95, 529. 6. Magnius, L. O., Espmark, A. Acta path. microbiol. scand. B, 1972, 80, 335. 7. Magnius, L. O., Espmark, A.J. Immun. 1972, 109, 1017. 8. Magnius, L. O. Clin. exp. Immun. 1975, 20, 209. 9. Magnius, L., Lindholm, A., Lundin, P., Iwarson, S. J. Am. med. Ass. 1975, 231, 356. 10. Nielsen, J. O., Dietrichson, O., Juhl, E., Copenhagen Hepatitis Acuta Pro1. Nielsen,
gram Lancet, 1974, ii, 913.
e
ANTIGEN AND ANTI-e IN
HBsAg CARRIERS
S. V. FEINMAN
B. BERRIS
J.
C. SINCLAIR
Liver Clinic, Mount Sinai Hospital, and
Department of
Medicine, University of Toronto, Ontario, Canada D. M. WROBEL Toronto
Depot,
Canadian Red Cross
J. E. MAYNARD
B. L. MURPHY
previously described subtypes of HBsAg (a, d, y, w, and r) which are present on the HBsAg particles, the e specificity is not a surface component of the HBsAg particle. The physicochemical characteristics of the e antigen and the differences between this antigen and HBsAg have been described.2 Magnius and Espmark’ found a high frequency ofe antigen in HBsAg positive patients on hæmodialysis. They postulated that the e antigen is correlated with contagiousness. Nielsen et al. found the e antigen to be more common in patients with chronic hepatitis and cirrhosis who were HBsAg positive than in patients with acute hepatitis B, and suggested that the presence of e antigen might have prognostic significance. Because of the possible prognostic significance of e and anti-e in patients who are HBsAg positive, we studied the correlation between e/anti-e and the clinical, laboratory, and pathological status of 70 HBsAg-positive carriers. Patients and Methods The liver clinic at the Mount Sinai Hospital in Toronto, is involved in a long-term prospective study with a large group of HBsAg carriers. 70 were examined for e and anti-e, and liver biopsy was done in 31 of them. All 70 carriers have been followed up prospectively for at least three years. HBsAg was detected by radioimmunoassay/ The results were all confirmed by a blocking test, and the sera were also positive by cross-over immunoelectrophoresis. S.G.P.T. was measured by a modified kinetic spectrophotometric method.6 Histological criteria were based on the recommendations of an International Committee,7 with a subdivision of the chronic persisting hepatitis group into two subgroups-patients with predominantly lobular infiltrates and patients with predominantly portal and lobular infiltrates.8 e antigen and anti-e tests were done using modified rheophoresis plates with incubation at 27C in humidified petri dishes. The standard e antigen and e antibody reagents used were obtained from HBsAg-positive blood-donors verified and typed by Dr George Le Bouvier, Yale University School of Medicine. The e antigen reagent contains both e-1 and e-2 specificities. The e antibody reagent contained both anti-e 1 and anti-e 2.9 Normal controls consisted of 15 sera of healthy individuals who were negative for HBsAg.
Phoenix Laboratories Division, Bureau of Epidemiology, Center for Disease Control, Phoenix, Arizona, U.S.A.
Results The controls
Summary assess
A
new
antigen/antibody system, "e" and
anti-e, was described in 1972. In order to the clinical significance of e antigen and anti-e,
their presence was correlated with the clinical status, S.G.P.T. levels and liver biopsies of HBsAg carriers. 31 of the carriers had liver biopsies, 32 of 70 carriers had anti-e and 2 had e antigen. 28 of 55 carriers with normal S.G.P.T. and 4 of 15 patients with raised S.G.P.T. had anti-e. This difference is not statistically significant. 2 patients with e had raised S.G.P.T. All patients with normal histology, 45% of patients with mild, and 23% of patients with striking histological changes in the liver had anti-e. This association of anti-e with a normal or mildly abnormal liver was statistically significant. The 2 patients with e antigen had the most severe abnormalities in liver function and liver histology. Introduction
’
A NEw antigen/antibody system, "e" and anti-e, was described by Magnius and Espmark in 1972.1 Unlike the
were
negative for HBsAg, had e antigen nor anti-e.
normal
S.G.P.T.S, and had neither
36 (51%) of the carriers had neither anti-e nor e, 32 (46%) had anti-e, and 2 (1 4%) were positive fore antigen. An attempt was made to relate the presence of anti-e to S.G.P.T. Of 55 carriers with normal S.G.P.T., 28 had anti-e, and of 15 with persistently raised S.G.P.T., 4 had anti-e ("1.2 190. p>0.1). The 2 patients with e antigen both had
raised S.G.P.T.S. (>50 units). The criterion used in selection of patients for liver biopsy was repeated elevation of S.G.P.T. values with or without clinical symptoms. 3 of the 31 carriers had normal histology, and all 3 had anti-e in their serum. Liver biopsies of 15patients showed only lobular focal infiltrates with a very mild degree of infiltration in the portal tracts; 7 had anti-e but none had e antigen. 13 patients had heavy portal infiltrates with additional lobular focal infiltrations (portal infiltrations correlate well with persistently abnormal S.G.P.T. tests8), and none had a classical picture of chronic active hepatitis or cirrhosis; 3 had anti-e, 2 had e, and 8 had neither e nor anti-e. Anti-e
1174
frequently found in patients with normal or only moderately altered liver histology than in those with heavier portal infiltration (&khgr;2=6.18; p
antibody indicates either inactive chronic liver disease or asymptomatic carriage of HBsAg. The patients with a histological diagnosis of chronic persistent hepatitis showed a high incidence of both e antigen and e antibody. At the time of study there was cess
while
e
obvious difference in these two groups, but the association of e antibody with asymptomatic carriage or recovery from acute hepatitis B viral infection suggests that these patients may have a better prognosis than those with e antigenaemia who may progress to chronic active no
hepatitis. We thank the Medical Research Council and the Burton Charitable Trust for financial support and Dr G. Le Bouvier and Dr J. Hoofnagle for gifts of antisera.
Requests for reprints should be addressed to S. S. REFERENCES
J. O., Le Bouvier, G. L., Copenhagen Hepatitis Acuta Program New Engl.J. Med. 1973, 288, 1257. 2. Iwarson, S., Magnius, L., Lindholm, A., Lundin, P. Br. med. J. 1973, i, 84. 3. Hadziyannis, S., Le Bouvier, G. L. Iatriki, 1972, 22, 453. 4. Magnius, L., Berg, R., Bjorvatn, B., Svedmyr, A. Scand.J. infect. Dis. 1973, 5, 71. 5. Mosley, J. W., Edwards, V. M., Meilhaus, J. E., Redeker, A. G. Am.J. Epidemiol. 1972, 95, 529. 6. Magnius, L. O., Espmark, A. Acta path. microbiol. scand. B, 1972, 80, 335. 7. Magnius, L. O., Espmark, A.J. Immun. 1972, 109, 1017. 8. Magnius, L. O. Clin. exp. Immun. 1975, 20, 209. 9. Magnius, L., Lindholm, A., Lundin, P., Iwarson, S. J. Am. med. Ass. 1975, 231, 356. 10. Nielsen, J. O., Dietrichson, O., Juhl, E., Copenhagen Hepatitis Acuta Pro1. Nielsen,
gram Lancet, 1974, ii, 913.
e
ANTIGEN AND ANTI-e IN
HBsAg CARRIERS
S. V. FEINMAN
B. BERRIS
J.
C. SINCLAIR
Liver Clinic, Mount Sinai Hospital, and
Department of
Medicine, University of Toronto, Ontario, Canada D. M. WROBEL Toronto
Depot,
Canadian Red Cross
J. E. MAYNARD
B. L. MURPHY
previously described subtypes of HBsAg (a, d, y, w, and r) which are present on the HBsAg particles, the e specificity is not a surface component of the HBsAg particle. The physicochemical characteristics of the e antigen and the differences between this antigen and HBsAg have been described.2 Magnius and Espmark’ found a high frequency ofe antigen in HBsAg positive patients on hæmodialysis. They postulated that the e antigen is correlated with contagiousness. Nielsen et al. found the e antigen to be more common in patients with chronic hepatitis and cirrhosis who were HBsAg positive than in patients with acute hepatitis B, and suggested that the presence of e antigen might have prognostic significance. Because of the possible prognostic significance of e and anti-e in patients who are HBsAg positive, we studied the correlation between e/anti-e and the clinical, laboratory, and pathological status of 70 HBsAg-positive carriers. Patients and Methods The liver clinic at the Mount Sinai Hospital in Toronto, is involved in a long-term prospective study with a large group of HBsAg carriers. 70 were examined for e and anti-e, and liver biopsy was done in 31 of them. All 70 carriers have been followed up prospectively for at least three years. HBsAg was detected by radioimmunoassay/ The results were all confirmed by a blocking test, and the sera were also positive by cross-over immunoelectrophoresis. S.G.P.T. was measured by a modified kinetic spectrophotometric method.6 Histological criteria were based on the recommendations of an International Committee,7 with a subdivision of the chronic persisting hepatitis group into two subgroups-patients with predominantly lobular infiltrates and patients with predominantly portal and lobular infiltrates.8 e antigen and anti-e tests were done using modified rheophoresis plates with incubation at 27C in humidified petri dishes. The standard e antigen and e antibody reagents used were obtained from HBsAg-positive blood-donors verified and typed by Dr George Le Bouvier, Yale University School of Medicine. The e antigen reagent contains both e-1 and e-2 specificities. The e antibody reagent contained both anti-e 1 and anti-e 2.9 Normal controls consisted of 15 sera of healthy individuals who were negative for HBsAg.
Phoenix Laboratories Division, Bureau of Epidemiology, Center for Disease Control, Phoenix, Arizona, U.S.A.
Results The controls
Summary assess
A
new
antigen/antibody system, "e" and
anti-e, was described in 1972. In order to the clinical significance of e antigen and anti-e,
their presence was correlated with the clinical status, S.G.P.T. levels and liver biopsies of HBsAg carriers. 31 of the carriers had liver biopsies, 32 of 70 carriers had anti-e and 2 had e antigen. 28 of 55 carriers with normal S.G.P.T. and 4 of 15 patients with raised S.G.P.T. had anti-e. This difference is not statistically significant. 2 patients with e had raised S.G.P.T. All patients with normal histology, 45% of patients with mild, and 23% of patients with striking histological changes in the liver had anti-e. This association of anti-e with a normal or mildly abnormal liver was statistically significant. The 2 patients with e antigen had the most severe abnormalities in liver function and liver histology. Introduction
’
A NEw antigen/antibody system, "e" and anti-e, was described by Magnius and Espmark in 1972.1 Unlike the
were
negative for HBsAg, had e antigen nor anti-e.
normal
S.G.P.T.S, and had neither
36 (51%) of the carriers had neither anti-e nor e, 32 (46%) had anti-e, and 2 (1 4%) were positive fore antigen. An attempt was made to relate the presence of anti-e to S.G.P.T. Of 55 carriers with normal S.G.P.T., 28 had anti-e, and of 15 with persistently raised S.G.P.T., 4 had anti-e ("1.2 190. p>0.1). The 2 patients with e antigen both had
raised S.G.P.T.S. (>50 units). The criterion used in selection of patients for liver biopsy was repeated elevation of S.G.P.T. values with or without clinical symptoms. 3 of the 31 carriers had normal histology, and all 3 had anti-e in their serum. Liver biopsies of 15patients showed only lobular focal infiltrates with a very mild degree of infiltration in the portal tracts; 7 had anti-e but none had e antigen. 13 patients had heavy portal infiltrates with additional lobular focal infiltrations (portal infiltrations correlate well with persistently abnormal S.G.P.T. tests8), and none had a classical picture of chronic active hepatitis or cirrhosis; 3 had anti-e, 2 had e, and 8 had neither e nor anti-e. Anti-e
1174
frequently found in patients with normal or only moderately altered liver histology than in those with heavier portal infiltration (&khgr;2=6.18; p
