Australia
antigen updated
A decade has passed since Blumberg, known reasons, excess surface material Alter and Visnich1 reported the discov- is released into the circulation as the small spherical and tubular forms of a decade of ery of Australia antigen expanding knowledge about viral hepa¬ HBsAg. Based on these discoveries, techniques titis. Australia antigen has survived fashionable name changes including he- have recently been developed for the patitis-associated antigen and hepatitis B clinical detection of circulating antiantigen, and is now known as hepatitis HBcAg and hepatitis B-specific DNA B surface antigen or HBsAg.2 With the polymerase. Important clinical observa¬ publication in this issue of the Journal of tions have already been made in cofour more papers on HBsAg it seems operative studies by Krugman and appropriate to pause and summarize Hoofnagle and their associates.10'11 In some recent advances that have been patients with hepatitis B infection, cir¬ made since the topic was reviewed in culating DNA polymerase appears soon before or at the time of elevated SGOT the Journal about 3 years ago.3 Perhaps the most important develop¬ values, after HBsAg first becomes dement has been the recognition of two tectable. Though usually transient, poly¬ separate antigen-antibody systems asso¬ merase persists in patients in whom ciated with hepatitis B infection. HBS- antigenemia fails to resolve.10 Its de¬ Ag-positive serum contains three mor- tection in serum may therefore reflect phologically distinct particles: small peak replication of hepatitis B virus, an spheres, long tubular forms and the interpretation consistent with the pre¬ larger Dane particles, which consist of sence of circulating Dane particles in most patients with chronic antigenemia an outer coat and an inner core.4 Anti¬ body against HBsAg agglutinates all and persisting hepatitis.12 Anti-HBcAg three particles, indicating that they also appears at about the time of clin¬ share a common antigen on their sur¬ ical and SGOT abnormalities, before face. In addition, Almeida, Rubenstein antibody to the surface antigen can be and Stott5 have shown that convalescent detected; titres then slowly decrease hepatitis serum contains a separate anti¬ after recovery from hepatitis. 10 In body directed specifically against the chronic HBsAg carriers, however, core inner core of the Dane particle. These antibody is virtually always detectable.11 immunologically distinct surface and Thus, its presence appears to be a sensi¬ tive indicator of recent replication of core antigens are now designated HBsAg and HBcAg, respectively;2 the corres- the virus. Of potentially great imporponding antibodies are termed anti-HBs- tance is the presence of anti-HBcAg in Ag and anti-HBcAg. The presence of occasional blood donors who have no DNA polymerase in purified core prep- other serologic evidence of hepatitis B arations has been documented,6'7 and exposure. Preliminary evidence favours the complex chemical composition of the infectivity of blood from at least both surface and core particles has been some of these donors.11 Thus, screening for core antibody may detect contamin¬ partially clarified.8'9 These findings have helped resolve ated blood that would remain undeearlier confusion about the relation¬ tected by currently available tests for ship of HBsAg to hepatitis B virus, and HBsAg. Further studies are needed to the pieces of the jigsaw puzzle are now settle this point, but the issue is impor¬ falling into place. It appears that the tant because even the most sensitive Dane particle may be the complete he¬ tests for surface antigen have had only patitis B virus. Its nucleocapsid core a limited effect in preventing postprobably replicates in nuclei of infected transfusion hepatitis.13 Another advance has been the recog¬ liver cells, and then is enveloped with surface coat material in the cytoplasm nition of HBsAg subtypes. HBsAg con¬ to produce the complete virion. For un¬ tains a common antigenic specificity .
designated
a
and
one
of two
mutually
exclusive specificities, d and y; other markers known as w and r also occur.14 These determinants are all virus-specific rather than host-related, and their stu¬ dy therefore provides useful informa¬ tion in epidemiologic surveys. For ex¬ ample, subtypes generally "breed true''
within hemodialysis units and in family clusterings of the antigen; in this issue of the Journal (page 46) Perry and asso¬ ciates report the same finding in an in¬ stitution for the mentally retarded. Al¬ though some authors have attributed pathogenic significance to the different subtypes, in fact geographic and epi¬ demiologic factors probably account for the variable subtype patterns reported in clinical surveys of HBsAg.14,K A major discovery from earlier stu¬ dies of HBsAg was the recognition that nonparenteral spread of hepatitis B can occur.3 Recent observations have pro¬ vided further information on this point. For example, there is increasing evi¬ dence for spread of HBsAg to sexual contacts,16 for clustering of the antigen within families 17,18 and for maternal-toinfant transmission either transplacentally or at the time of delivery.19 In this issue of the Journal (page 43) Feinman and colleagues report a disproportionate incidence of antigenemia among hospitalized patients of Chinese or Mediterranean origin living in Toronto. Also in this issue (page 49) Richer and asso¬ ciates suggest that antigenemia in Mont¬ real blood donors reflects in part an inordinate frequency of childhood institutionalization in the donor group. These disparate findings from Canada's two largest urban areas indicate the value of epidemiologic analysis in HBsAg sur¬ veys. The individual response to HBsAg exposure clearly depends on host-related factors, yet their nature remains poorly understood. Recent attention has focused on immunologic responses and functions, but so far the lymphocyte20,21 are more definite than hypotheses the somewhat nebulous data. One area that needs further study is the clinical
CMA JOURNAL/JANUARY 11, 1975/VOL. 112 11
sera 26 underline the need for scrupulous technique when working with potentially infectious materials. Equally worrisome is recent evidence 27, 28 that antigen-positive dentists can transmit hepatitis to large numbers of their patients. Such data raise complex epidemiologic and social issues, but on the basis of present evidence, compulsory HB.Ag screening of specific occupational groups is probably not justified. 29 The flood of advances in hepatitis research will no doubt continue - for example, the protective value of hightitre anti-HB8Ag immune globulin is being assessed, 30 a vaccine against hepatitis B may be imminent, 30 and there is renewed optimism that hepatitis A virus can be identified. .' In the meantime, the survey of hepatitis B antigenemia among Canadian blood donors reported in this issue of the Journal (page 53) by Moore and Perrault will serve to give Canadian physicians an idea of the magnitude of the problem across the country. Their data and their recommendations are of great interest. Their emphasis is on the safety of blood transfusion, and in this respect all physicians can contribute to the greater safety of blood transfusion by recognizing the magnitude of the problem of hepatitis B antigenemia. The four papers on hepatitis B surface antigen indicate that
significance of HB.Ag-antibody complexes. Although these do not appear responsible for the liver damage in hepatitis B infection, they may account for prodromal joint manifestations and have even been implicated in the pathogenesis of glomerulonephritis. 22 Of related interest is the increasing evidence that seemingly healthy antigen carriers often have subclinical liver disease. A recent Canadian study, 23 for example, demonstrated a wide spectrum of histologic abnormalities including chronic aggressive hepatitis in asymptomatic HB.Ag carriers. Thus, the conclusion of Feinman and colleagues in this issue of the Journal that HB5Ag screening in their hospital did not detect subclinical liver disease may be unwarranted because the authors did not exclude the presence of subclinical disease in their antigen-positive patients. Of particular concern has been the high incidence of hepatitis B infection among health workers. Earlier devastating outbreaks in renal dialysis units have gradually been brought under control with the adoption of careful precautions, but recent outbreaks have occurred in oncology units . and even among surgical staff members who have operated on HB.Ag-positive patients. 25 These findings and the frequent presence of HB8Ag in laboratory quality control
Basic Prenatal Supplement
'g
Each Prenavite film-coated tablet suppi ies: 150 mg ferrous fumarate, 4,000 lU. Vit. A acetate, 400 lUVit. D2,l00mgascorbic acid (as ascorbate), 2.5 mg folic acid, 125 mg calcium carbonate. Prenavite Forte has 50% more iron. Film-coated- easy to swallow. 1 tablet daily.
. Prenavite Forte Full information available on request.
x
Allen & Hanburys
(Formerly BDH Pharmaceuticals) *. Toronto, Montreal
.. .
AJ
.
antigen updated
A decade has passed since Blumberg, known reasons, excess surface material Alter and Visnich1 reported the discov- is released into the circulation as the small spherical and tubular forms of a decade of ery of Australia antigen expanding knowledge about viral hepa¬ HBsAg. Based on these discoveries, techniques titis. Australia antigen has survived fashionable name changes including he- have recently been developed for the patitis-associated antigen and hepatitis B clinical detection of circulating antiantigen, and is now known as hepatitis HBcAg and hepatitis B-specific DNA B surface antigen or HBsAg.2 With the polymerase. Important clinical observa¬ publication in this issue of the Journal of tions have already been made in cofour more papers on HBsAg it seems operative studies by Krugman and appropriate to pause and summarize Hoofnagle and their associates.10'11 In some recent advances that have been patients with hepatitis B infection, cir¬ made since the topic was reviewed in culating DNA polymerase appears soon before or at the time of elevated SGOT the Journal about 3 years ago.3 Perhaps the most important develop¬ values, after HBsAg first becomes dement has been the recognition of two tectable. Though usually transient, poly¬ separate antigen-antibody systems asso¬ merase persists in patients in whom ciated with hepatitis B infection. HBS- antigenemia fails to resolve.10 Its de¬ Ag-positive serum contains three mor- tection in serum may therefore reflect phologically distinct particles: small peak replication of hepatitis B virus, an spheres, long tubular forms and the interpretation consistent with the pre¬ larger Dane particles, which consist of sence of circulating Dane particles in most patients with chronic antigenemia an outer coat and an inner core.4 Anti¬ body against HBsAg agglutinates all and persisting hepatitis.12 Anti-HBcAg three particles, indicating that they also appears at about the time of clin¬ share a common antigen on their sur¬ ical and SGOT abnormalities, before face. In addition, Almeida, Rubenstein antibody to the surface antigen can be and Stott5 have shown that convalescent detected; titres then slowly decrease hepatitis serum contains a separate anti¬ after recovery from hepatitis. 10 In body directed specifically against the chronic HBsAg carriers, however, core inner core of the Dane particle. These antibody is virtually always detectable.11 immunologically distinct surface and Thus, its presence appears to be a sensi¬ tive indicator of recent replication of core antigens are now designated HBsAg and HBcAg, respectively;2 the corres- the virus. Of potentially great imporponding antibodies are termed anti-HBs- tance is the presence of anti-HBcAg in Ag and anti-HBcAg. The presence of occasional blood donors who have no DNA polymerase in purified core prep- other serologic evidence of hepatitis B arations has been documented,6'7 and exposure. Preliminary evidence favours the complex chemical composition of the infectivity of blood from at least both surface and core particles has been some of these donors.11 Thus, screening for core antibody may detect contamin¬ partially clarified.8'9 These findings have helped resolve ated blood that would remain undeearlier confusion about the relation¬ tected by currently available tests for ship of HBsAg to hepatitis B virus, and HBsAg. Further studies are needed to the pieces of the jigsaw puzzle are now settle this point, but the issue is impor¬ falling into place. It appears that the tant because even the most sensitive Dane particle may be the complete he¬ tests for surface antigen have had only patitis B virus. Its nucleocapsid core a limited effect in preventing postprobably replicates in nuclei of infected transfusion hepatitis.13 Another advance has been the recog¬ liver cells, and then is enveloped with surface coat material in the cytoplasm nition of HBsAg subtypes. HBsAg con¬ to produce the complete virion. For un¬ tains a common antigenic specificity .
designated
a
and
one
of two
mutually
exclusive specificities, d and y; other markers known as w and r also occur.14 These determinants are all virus-specific rather than host-related, and their stu¬ dy therefore provides useful informa¬ tion in epidemiologic surveys. For ex¬ ample, subtypes generally "breed true''
within hemodialysis units and in family clusterings of the antigen; in this issue of the Journal (page 46) Perry and asso¬ ciates report the same finding in an in¬ stitution for the mentally retarded. Al¬ though some authors have attributed pathogenic significance to the different subtypes, in fact geographic and epi¬ demiologic factors probably account for the variable subtype patterns reported in clinical surveys of HBsAg.14,K A major discovery from earlier stu¬ dies of HBsAg was the recognition that nonparenteral spread of hepatitis B can occur.3 Recent observations have pro¬ vided further information on this point. For example, there is increasing evi¬ dence for spread of HBsAg to sexual contacts,16 for clustering of the antigen within families 17,18 and for maternal-toinfant transmission either transplacentally or at the time of delivery.19 In this issue of the Journal (page 43) Feinman and colleagues report a disproportionate incidence of antigenemia among hospitalized patients of Chinese or Mediterranean origin living in Toronto. Also in this issue (page 49) Richer and asso¬ ciates suggest that antigenemia in Mont¬ real blood donors reflects in part an inordinate frequency of childhood institutionalization in the donor group. These disparate findings from Canada's two largest urban areas indicate the value of epidemiologic analysis in HBsAg sur¬ veys. The individual response to HBsAg exposure clearly depends on host-related factors, yet their nature remains poorly understood. Recent attention has focused on immunologic responses and functions, but so far the lymphocyte20,21 are more definite than hypotheses the somewhat nebulous data. One area that needs further study is the clinical
CMA JOURNAL/JANUARY 11, 1975/VOL. 112 11
sera 26 underline the need for scrupulous technique when working with potentially infectious materials. Equally worrisome is recent evidence 27, 28 that antigen-positive dentists can transmit hepatitis to large numbers of their patients. Such data raise complex epidemiologic and social issues, but on the basis of present evidence, compulsory HB.Ag screening of specific occupational groups is probably not justified. 29 The flood of advances in hepatitis research will no doubt continue - for example, the protective value of hightitre anti-HB8Ag immune globulin is being assessed, 30 a vaccine against hepatitis B may be imminent, 30 and there is renewed optimism that hepatitis A virus can be identified. .' In the meantime, the survey of hepatitis B antigenemia among Canadian blood donors reported in this issue of the Journal (page 53) by Moore and Perrault will serve to give Canadian physicians an idea of the magnitude of the problem across the country. Their data and their recommendations are of great interest. Their emphasis is on the safety of blood transfusion, and in this respect all physicians can contribute to the greater safety of blood transfusion by recognizing the magnitude of the problem of hepatitis B antigenemia. The four papers on hepatitis B surface antigen indicate that
significance of HB.Ag-antibody complexes. Although these do not appear responsible for the liver damage in hepatitis B infection, they may account for prodromal joint manifestations and have even been implicated in the pathogenesis of glomerulonephritis. 22 Of related interest is the increasing evidence that seemingly healthy antigen carriers often have subclinical liver disease. A recent Canadian study, 23 for example, demonstrated a wide spectrum of histologic abnormalities including chronic aggressive hepatitis in asymptomatic HB.Ag carriers. Thus, the conclusion of Feinman and colleagues in this issue of the Journal that HB5Ag screening in their hospital did not detect subclinical liver disease may be unwarranted because the authors did not exclude the presence of subclinical disease in their antigen-positive patients. Of particular concern has been the high incidence of hepatitis B infection among health workers. Earlier devastating outbreaks in renal dialysis units have gradually been brought under control with the adoption of careful precautions, but recent outbreaks have occurred in oncology units . and even among surgical staff members who have operated on HB.Ag-positive patients. 25 These findings and the frequent presence of HB8Ag in laboratory quality control
Basic Prenatal Supplement
'g
Each Prenavite film-coated tablet suppi ies: 150 mg ferrous fumarate, 4,000 lU. Vit. A acetate, 400 lUVit. D2,l00mgascorbic acid (as ascorbate), 2.5 mg folic acid, 125 mg calcium carbonate. Prenavite Forte has 50% more iron. Film-coated- easy to swallow. 1 tablet daily.
. Prenavite Forte Full information available on request.
x
Allen & Hanburys
(Formerly BDH Pharmaceuticals) *. Toronto, Montreal
.. .
AJ
.
