Prevalence and significance of hepatitis B surface antigen in a general hospital S. Victor Feinman, b sc (med), md, frcp[c]; Olaf Krassnitzky, md; Jonathan C. Sinclair, md, Damiana M. Wrobel, mrcs, lrcp; Barnet Berris, m sc, md, frcp[c], facp

Summary: Over a 6-month period 2025 patients admitted to New Mount Sinai Hospital, Toronto were screened for hepatitis B surface antigen (HBsAg) by counterimmunoelectrophoresis (CIEP) and radioimmunoassay (RIA). CIEP detected 12 HBsAg-positive patients and RIA 16. RIA is therefore the more sensitive test for HBsAg. Of the 16 patients 2 had liver disease previously diagnosed, 3 had malignant disease and 11 were asymptomatic

carriers. Of the 11 carriers all were born in countries where the carrier rate is known to be high. Routine screening of hospital patients on admission is of no value in detecting unsuspected liver disease but is of value in detecting asymptomatic carriers, which is of importance for the patient and his family. Routine screening tests for HBsAg in Canadian hospitals that treat many patients born in countries with a known high HBsAg prevalence is recommended. Routine screening is also recommended in all hospitals in Mediterranean and Asian countries. Resume: Prevalence et signification de I'antigene de surface de I'hSpatite B dans un hopital ge'ne'ral Au

cours

d'une

periode de 6

mois

nous avons

recherche

I'antigene de surface de I'hepatite B (AgsHB) chez 2025 malades admis au New Mount Sinai Hospital de Toronto par la methode d'immunoelectrophorese croisee (IEPC) et par essai radioimmunologique (ERI). La premiere de ces deux methodes, IEPC, a permis de deceler la positivite du serum a AgsHB chez 12 malades et la ERI

chez 16. Cette derniere methode est done la methode la plus sensible pour AgsHB. Sur ces 16 malades 2 souffraient d'une hepatopathie diagnostiquee auparavant, 3 avaient une maladie maligne et 11 etaient des porteurs asymptomatiques. Ces derniers etaient tous nes dans des pays ou le pourcentage de I'etat de porteur est eleve. Le depistage systematique des malades hospitalises au moment de leur entree n'a aucune valeur pour decouvrir des maladies hepatiques meconnues, mais, par contre, a une indeniable valeur pour decouvrir les porteurs asymptomatiques, ce qui est evidemment utile et pour le malade et pour sa famille. Nous conseillons done aux

frcp[c];

hopitaux canadiens qui traitent de nombreux malades nes dans des pays ou l'AgsHB predomine de proceder au depistage systematique de cet antigene. Ce depistage systematique est conseil le egalement a tous les hopitaux des pays mediterraneens et asiatiques. The importance of hepatitis B surface antigen (HBsAg, Aus¬ tralia antigen) as an indicator of hepatitis B virus in clinical liver disease is well recognized.1 The prevalence of HBsAg in the blood donor population of Ontario is 0.15%.* The significance of the asymptomatic HBsAg carrier state is being studied in detail at the liver clinic of New Mount Sinai Hospital3 as well as at other centres. Introduction of universal testing of blood donors for HBsAg has resulted in a distinct decrease in incidence of post-transfusion hepatitis.4 One survey, testing for HBsAg and anti-HBs (antibody to hepatitis B surface antigen), indicators of exposure to hepatitis B virus, showed that hepa¬ titis is more common in health personnel than in controls,5 and there have been a number of reports of hepatitis B epidemics in hospital personnel working in high-risk areas such as dialysis units, operating rooms and laboratories.6"9 In the present study a large number of patients admitted to a general hospital were screened for HBsAg with the

following objectives: 1. To determine the prevalence of HBsAg in individuals admitted to a general hospital in Toronto, and to de¬ termine what proportion of HB8Ag-positive individuals were asymptomatic carriers and what proportion were suffering from disease. In the asymptomatic carriers a correlation with ethnic origin was established. 2. To correlate the presence of HBsAg with the type of dis¬ ease present, specifically to determine whether it would aid in diagnosing unsuspected liver disease. 3. To determine whether there is an increased prevalence of antigenemia in diseases other than those affecting the liver. 4. To compare radioimmunoassay (RIA) with counterimmunoelectrophoresis (CIEP) as to sensitivity and speci¬ ficity in detecting HBsAg. 5. To reach a decision as to whether routine screening for HBsAg of all patients admitted to a hospital should be recommended.

From the liver clinic, department of medicine, New Mount Sinai Hospital, University of Toronto and the Toronto Red Cross Centre Reprint requests to: Dr. S. V. Feinman, Suite 435, 600 University Ave., Toronto, Ont. M5G 1X5

Materials and methods

The

subjects of

study

2025 unselected conCMA JOURNAL/JANUARY 11, 1975/VOL. 112 43 this

were

secutive patients admitted to New Mount Sinai Hospital between August 1, 1973 and January 30, 1974. There were 1560 females and 465 males; 1156 were admitted to surgical services (653 to general surgery and 503 to gynecology), 593 were obstetric patients and 276 were admitted to the medical service. Ethnic origin, sex, age, clinical diagnosis and other pertinent findings were tabulated. The ethnic composition of the group is shown in Table I. On admission the patient's blood was examined for serum glutamic-pyruvic transaminase (SGPT) by the kinetic ultraviolet method.10 HBsAg was sought by two methods counter immunoelectrophoresis (CIEP)11 and radioimmuno¬ assay (RIA), using the Ausria-125 system (Abbott).12 A po¬ sitive test was one with a radioactivity count at least 2.1 times the negative control mean. In addition, each positive test was confirmed by a specific blocking test using rabbit antiserum to HBsAg, as well as by the confirmation system proposed by Prince et al.13 .

Results Of 2025 blood specimens tested 25 were positive by RIA for HBsAg on the first run. Seven of those proved negative on repeat testing by RIA and were therefore considered negative. Two samples were positive by RIA on repeat testing but this could not be confirmed by the blocking test and they therefore were considered negative. Sixteen patients had a result positive for HBsAg by RIA on repeat testing and that was confirmed by the blocking test; they were considered HBsAg-positive. Twelve of the 16 were also positive by CIEP. No specimen positive by CIEP was negative by RIA. RIA therefore detected 4 more HB«Agpositive subjects among the 2025 tested than did CIEP. The prevalence of HBsAg in the patient population as determined by RIA was 0.8% and by CIEP was 0.6%. The clinical diagnosis of the patients found to be positive for HBsAg, or the service to which they were admitted, is listed in Table II. Of the 16 patients who were HBsAgpositive 2 had known liver disease and 3 had malignant disease (1 gastric carcinoma, 1 bronchogenic carcinoma, 1 Hodgkin's disease); the other 11 were asymptomatic carriers and 8 were admitted to the obstetric service. The patients with malignant disease had had no blood transfusions before testing for HBsAg. HBsAg testing was of no value in detecting unsuspected liver disease in the two patients with known liver disease. Twelve of the 16 HB8Ag-positive persons were female. This finding is explained by the female : male ratio of approximately 3:1 in the patient population examined. There was no correlation between SGPT levels and the presence or absence of HBsAg. Of the 593 obstetric patients admitted during the study period 1.3% were HBsAg-positive and all were asymptoma¬ tic carriers. This carrier rate is approximately 10 times the carrier rate of the blood donor population in Toronto (0.15% ).2 The ethnic distribution of the eight HBsAg-posi¬ tive obstetric patients was: five Greek, one Italian, one Portuguese and one Chinese. Of the 593 obstetric patients 71 were Greek; therefore, 7% of the Greek obstetric pa¬ tients were HBsAg-positive. Among the general Greek ad¬ mission population 4.6% were HBsAg carriers. The increase in prevalence of HBsAg among the obstetric patients was therefore due to the high proportion of Mediterranean pa¬ tients admitted to the obstetric service in our hospital.

Discussion This survey had both epidemiologic and clinical aims. The study showed that the prevalence of HBsAg in patients of a general hospital in downtown Toronto (0.8%) is approximately four times higher than in the nonhospitalized 44 CMA JOURNAL/JANUARY 11, 1975/VOL. 112

blood donor population. Similar prevalence figures were reported in Austria,14 where HBsAg was detected by CIEP in blood samples of 1.8% of hospital patients and 0.46% of blood donors. A hospital survey in Denmark15 detected HBsAg in 0.34% of patients (approximately three times the prevalence in blood donors). These findings are in contrast to data from Scotland,16 where the incidence of HBsAg in hospital patients tested by CIEP (0.116%) was similar to that in blood donors (0.119%). These data can be interpreted only when one considers several modifying factors, of which the most important may be the ethnic composition of the hospital patients. This was not analysed in the above three reports. As Table I shows, there were no HB«Ag-positive individuals among the 978 patients born in Canada, but 13% of the Chinese and 4.6% of the Greek patients were HBsAg-positive. (It is of interest that of 379 pregnant Greek women hospitalized in Athens 3.4% were positive for HBsAg when tested by CIEP.17 When one considers that RIA detects 25 to 50% more carriers than CIEP our results seem quite consistent.) It is therefore not surprising that in Scotland, where the hospital population would contain few if any patients of Mediterranean origin, there is no difference in the HBsAg prevalence rate between hospital patients and blood donors. Another modifying factor is the clinical composition of the patients treated in any hospital. Hospitals treating large numbers of drug addicts, those with special units for in¬ fectious diseases, those with hemodialysis units, and those treating malignant diseases and therefore having large num¬ bers of patients on immunosuppressive therapy may be expected to have a high proportion of HBsAg-positive individuals. Routine screening of hospital admissions, in our study at least, did not help in detecting subclinical liver disease. Of the 16 HBsAg-positive patients only 2 had liver disease and in both the diagnosis had been made on clinical grounds without serologic testing; 1 had acute hepatitis B and the other had liver cirrhosis, most probably posthepatitic. Of the remaining 14 patients 3 had malignant disease. The significance of finding HBsAg in patients with malignant disease in the absence of a history of liver disease or pre¬ vious treatment with immunosuppressive agents or blood Table I.Ethnic

origin of patients screened

Table II.Clinical diagnosis of, HBsAg-positive patients

or

service

admitting

transfusions deserves further study. The other 11 patients were asymptomatic carriers. This study confirmed the increased sensitivity of R'1A18 over CIEP in detecting HBSAg. Whereas CIEP detected HB8Ag in 0.6% of tested patients, RIA detected HB5Ag in 0.8%. The difference in sensitivity resulted in four more HB8Ag-positive patients being detected by RIA than by CIEP. The yield might be higher still if an improved RIA system (Ausria II) were to be used (F. R. Bishai, personal communication). As with any other laboratory test, increased sensitivity is associated with decreased specificity. Therefore, sera that were positive for HB8Ag by RIA. were tested for specificity by a 'blocking test. In 2 of the 18 cases (approximately 11%) the positive RIA results could not be confirmed by this specificity test and therefore these samples were not considered positive for HBAg. Of the 16 positive samples 4 were negative by CIEP; it is possible that the titre of HB.Ag was too low in these 4 to be detected by CIEP. It is of interest that these four patients were over 50 years old (three were more than 70 years old). One patient had liver cirrhosis and three had malignant disease. This underlines the necessity for confirmation tests when using RIA. It is apparent that screening of hospital patients in our study was not of value in detecting unsuspected liver disease but it was of importance in identifying carriers. This is of epidemiologic significance both for the patient and his family, and for any health personnel with whom the patient might come in contact. We therefore recommend that in Canadian hospitals serving many patients from countries where the carrier rate is high, routine screening for HB5Ag be done. In Mediterranean and Asian countries routine screening of all hospital patients on admission is recommended. If patients known to have infectious disease could be positively identified, then not only their blood but also their excreta and secretions could be handled with special care, since HB3Ag has been found in urine, stools, semen and saliva, as well as in blood.19

This study was supported by the research department of New Mount Sinai Hospital, Toronto. We wish to thank Jonathan P. Miller, PhD of Abbott Laboratories for supplying Ausria-125 kits, the department of laboratories of New Mount Sinai Hospital, Toronto for the collection of specimens and Mrs. Carol Taylor for technical assistance. References 1. BLUMBERO BS, ALTER JH, VISNICH 5: A "new" antigen in leukemia sera. JAMA 191: 541, 1965 2. WROBEL DM, FEINMAN SV, Basuus B, et al: Frequency of hepatitis B antigen in blood donors. Can Med Assoc 1 108: 570, 1972 3. FEINMAN SV, SINCLAIR JC, Basuus B, et al: The clinical and epidemiological significance of the HB3Ag (Australia antigen - carrier state). Gastroenterology, in press 4. ALTER HJ, HOLLAND PV PURCELL RH: Posttransfusion hepatitis after exclusion of commerciaf and hepatitis B antigen positive donors. Ann Intern Med 77: 691, 1972 5. LEWIS TL, ALTER HI, CHALMERS TC, et al: A comparison of the frequency of hepatitis B antigen and antibody in hospital and nonhospital personnel. N Engi I Med 289: 647, 1973 6. POLAKOFF 5, COSSART YE, Tnarn-r HE: Hepatitis in dialysis units in the United Kingdom. Br Med I III: 94, 1972 7. JONES P0, GOLDSMITH HI, WRIGHT FK, et al: Viral hepatitis: A staff hazard in dialysis units. Lancet I: 835, 1967 8. RosENsEsiG JL, JONES DP, Kn'rrz LR, et al: Viral hepatitis: an occupational hazard to surgeons. JAMA 223: 395, 1973 9. TRaMsuu. ML, GRENIER DI: Homologous serum jaundice: an occupational hazard to medical personnel. JAMA 145: 965, 1951 10. WRO5LEWSKI 5, LA Dua IS: Serum glutamic pyruvic transaminase in cardiac and hepatic disease. Proc Soc Exp Blol Med 91: 569, 1956 11. Mooas BPL, MEADE D: Counter-inimunoelectrophoresis for detection of hepatitis B antigen and antibody: a technique for large scale use. Can I Public Health 63: 453, 1972 12. LING CM, OvEsaY LR: Prevalence of hepatitis B virus antigen as revealed by direct radioimmune assay with 125 I-antibody. I immunol 109: 834, 1972 13. PRINCE AM, BROTMAN B, JAss D, et al: Specificity of the direct solidphase radloimmunoassay for detection of hepatitis-B antigen. Lancet I: 1346, 1973 14. WEWALKA F, GNAN F, KRASSNITZKY 0, et al: Au-SH-antigen in liver disease. Vox Sang 19: 311, 1970 15. Lous P. SKINHOJ P, 0ssas.r H: HAA-antigen determination in 12,000 patients in a general Copenhagen hospital. Ibid, p 3 16. PAYNE RW, BARR A, WALLACE J: Hepatitis B antigen (HBAg) and its antibody (HBAb) in hospital patients. I Clin Pathol 27: 125, 1974 17. PAPAEVANGELOU G, TRIcHoPouLos D, KREMASTINOU T, et al: Prevalence of hepatitis B antigen and antibody in prostitutes. Br Med I II: 256, 1974 18. ALTER H.T, HOLLAND PV, PURCELL RH, et al: The Ausria test: critical evaluation of sensitivity and specificity. Blood 42: 947, 1973 19. HEATHCOTE I, CAMERON CH, DANE DS: Hepatitis B antigen in saliva and semen. Lancet I: 71, 1974

CMA JOURNAL/JANUARY 11, 1975/VOL. 112 45

Prevalence and significance of hepatitis B surface antigen in a general hospital.

Over a 6-month period 2025 patients admitted to New Mount Sinai Hospital, Toronto were screened for hepatitis B surface antigen (HBsAg) by counter-imm...
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