Failure of Endoscopic Transmission of Hepatitis B RONALD L. KORETZ, MD, and R A L P H CAMACHO, MD
Emergency endoscopy was performed on two patients subsequently found to be hepatitis B surface antigen carriers. Before their carrier state was determined, nine other patients underwent endoscopy using the same instruments, which had been routinely cleaned between procedures. These patients were all notified within five days of the incident, given standard gamma globulin, and prospectively followed for the development of hepatitis. After one of the endoscopes was gas sterilized, the next three patients undergoing endoscopy were also followed. One of the hepatitis B surface antigen carriers was positive for antibody to e antigen; the other carrier had neither e antigen nor antibody. None of these individuals developed signs or symptoms of hepatitis, abnormal serum glutamic pyruvate transaminase elevations, or serologic evidence of hepatitis B exposure. From these data, and other recorded experiences, it appears that routine cleansing of endoscopy equipment is sufficient in preventing the transmission of hepatitis B.
Hepatitis B has been transmitted in a variety of nonparenteral fashions (1). Oral transmission has been demonstrated (1). Epidemics have been described in the families of hepatitis B surface antigen (HB~Ag) carriers (1). HB~Ag has been demonstrated in a variety of body fluids of carriers, including urine, saliva, bile, feces, sneeze droplets, semen, vaginal secretions, breast milk, and tears (1). Venereal transmission has been postulated (1). Transplacental transmission may o c c u r (1). I n f e c t e d clams have been implicated in outbreaks (1). Even mosquito and b e d b u g v e c t o r s have been proposed (1, 2). It is of concern, therefore, that hepatitis B might be t r a n s m i s s a b l e through infected e n d o s c o p i c equipment. Fiberoptic endoscopes cannot be autoclaved and are routinely only thoroughly washed in various soap solutions between uses with no attempt made to sterilize them (3). As the HBsAg carrier rate in the United States may be as high as 0.5% From the San Fernando Valley Medical Program, Olive ViewMidValley Medical Center, Van Nuys, California 91405. Address for reprint requests: Dr. Ronald Koretz, Suite 500, South Tower, Olive View-Midvalley Medical Center, 7533 Van Nuys Blvd., Van Nuys, California 91405.
of the population (4), it is inevitable that, sooner or later, some carrier will undergo an endoscopic procedure and potentially contaminate the instrument. It is not established whether or not patients who s u b s e q u e n t l y u n d e r g o e n d o s c o p y with that instrument are at risk of developing hepatitis. A patient underwent endoscopy at Olive View Medical Center for acute upper-gastrointestinal bleeding from esophageal varices. Subsequent evaluation found him to have HBsAg-positive postnecrotic cirrhosis. Prior to have having been discovered to be an HB~Ag carrier, however, four other patients also underwent endoscopy with the same instrument. About 2 months later, at Sepulveda Veterans Administration Hospital, five other patients were similarly exposed to an endoscope previously used on a patient (with upper-gastrointestinal bleeding) s u b s e q u e n t l y found to be an HB~Ag carrier. It is the purpose of this report to detail the follow-up events in these patients. MATERIALS AND METHODS
In both instances the knowledge of potential HBsAg contamination was discovered within a few days (3 and 5,
Digestive Diseases and Sciences, Vol. 24, No. 1 (January 1979)
0163-2116/79/0100-0021503.00/1 9 1979DigestiveDisease Systems, Inc.
21
KORETZ AND CAMACHO respectively). The 9 involved patients were notified, and each received 2 cc of a standard gamma globulin preparation known to contain some antibody against HB~Ag (anti-HB~). The situation was explained to each patient, and they agreed to be prospectively followed. Samples were obtained at monthly intervals (for 9 months) and tested for HBsAg, anti-HBs, and serum glutamic pyruvate transaminase (SGPT). The endoscopicqnstruments, previously having only undergone routine cleaning between procedures (3), underwent ethylene oxide sterilization and were then put back into routine use. The first three patients subsequently undergoing endoscopy at Olive View were followed as controls. They did not receive gamma globulin, although they were thoroughly informed as to the potential risk. No controls were followed from Sepulveda Veterans Administration Hospital. Blood specimens from both of the HB~Agcarriers were tested for e antigen and antibody by rheophoresis (5). Tests for both HB~Agand anti-HB~were performed using standard commercially available radioimmunoassay kits (Ausria and Ausab, Abbott Laboratories, North Chicago, Illinois).
months later. This was interpreted as being the result of passive immunization. No other anti-HB~ development was seen in the four patients. Follow-up in the VA group of patients was complete (9 months) in only one. Three were followed monthly for 5 months, and one for only 3 months. None of the patients developed signs or symptoms of hepatitis, abnormal SGPT, HBsAg, or anti-HBs. Two of the three controls were followed for the entire 9 months, and the third for 5 months, when she died suddenly at home. None developed evidence of hepatitis (clinical or biochemical) or circulating HB~Ag. Two of the three had preexisting antiHBs, and this persisted throughout the period of follow-up without change in titer. The HBsAg-positive patient at Olive View had neither e antigen nor antibody. The HBsAg carrier at the Sepulveda VA Hospital was found to be positive for anti-e.
RESULTS
DISCUSSION
The four patients at Olive View Hospital consisted of one woman (esophageal stricture) and three men (bleeding varices secondary to alcoholic cirrhosis, duodenal ulcer, and peptic esophagitis). One of the men (variceal bleeder) received several units of blood shortly after endoscopy. None of the other three patients received blood or were otherwise overtly exposed to hepatitis. The five VA patients were all men, two with alcoholic gastritis, two with esophagitis, and a fifth who underwent endoscopy for an abnormal upper-gastrointestinal x-ray with no diagnosis established. One of the patients with gastritis was subsequently transfused, and one of the patients with esophagitis received blood 2 months after endoscopy during a surgical repair for his esophageal reflux. The three control patients were all women, one with duodenal ulcer disease and two with functional bowel disease. The patient with the duodenal ulcer also received blood approximately 3 months after endoscopy during a surgical procedure for her ulcer disease. Two of the four Olive View Hospital patients completed 9 months of follow-up. The third was lost to follow-up after 5 months. The fourth expired after 6 months of follow-up. None of the four demonstrated any abnormalities in SGPT or developed any symptoms compatible with hepatitis. None developed circulating HBsAg. All were anti-HB~ negative prior to receiving globulin. One of the four demonstrated anti-HB~, in progressively decreasing titers, from 5 days after globulin receipt until 2
There is very little information available concerning endoscopic transmission of hepatitis. Axon et al (6) reported a retrospective survey of 176 patients who underwent endoscopy and were subsequently queried concerning episodes of jaundice. None of the 116 responders reported such an occurrence. Morris et al (7) reported on 65 patients who were endoscoped subsequent to an HBsAg-positive patient. Only 32 patients received any follow-up, and it is unclear how often or for how long this was obtained, except that they describe the follow-up visits as "infrequent." However, none of their patients developed abnormal liver function tests. One of their patients became HBsAg-positive between days 65 and 290 postendoscopy. McDonald and Silverstein (8) report an experience similar to ours, in which 4 patients were subsequently exposed to a "contaminated" gastroscope. Their follow-up was at 2- to 4-week intervals for 6 months, and again no evidence of hepatitis or hepatitis B exposure was seen. (One of their patients had preexisting and persistent levels of anti-HBs without change in titer.) A recent CDC Hepatitis Surveillance (9) reports three groups of patients who were followed for 6 months. Each group represented the first 5 patients undergoing endoscopy after the endoscope was used on a HB~Ag-positive individual. The exact details are not reported, but two of the three HBsAg-positive individuals were also positive for e antigen. None of the 15 patients developed serologic evidence of hepatitis B exposure. In Edinburgh, 38 patients
22
Digestive Diseases and Sciences, VoL 24, No. t (January 1979)
ENDOSCOPIC TRANSMISSION OF HEPATITIS B were exposed to an endoscope used previously on an e antigen-positive patient. Thirty were seen once more, 165-225 days later, and no serologic evidence of hepatitis B exposure was observed (10). Our experience with these nine patients is also consistent with the thesis that routine cleaning of fiberoptic endoscopes is adequate in removing the threat of hepatitis transmission. Two confounding factors exist in this study. The first is that all of the exposed patients received, within 7 days of exposure, gamma globulin containing a low titer of anti-HB~. Only one of the nine manifested serologic evidence of the passive transmission of anti-HB~, but we do not know if this dose of globulin provided some degree of protection to the patients. Certainly the administration of high doses of anti-HB~ appears to be protective against "small inoculum" HBsAg exposure (11-13) and some questions have been raised that even standard immune globulin is effective in prophylaxis (14). The second problem has to do with the e status of the HBgAg carrier. It has been proposed that carriers who are e antigen positive are more likely to devleop severe liver diseases themselves and be more communicable, whereas those who carry antibody to e have a better prognosis and may in fact be less infectious (15-17). The e status in the HB~Agpositive patients of three of the previous reports is unknown. The VA patient in this study was anti-e positive, and the Olive View carrier was not positive for either e antigen or anti-e. Hence, both these patients may have been less likely to transmit hepatitis B. (In the CDC study, however, two of the three were e antigen positive.) In conclusion, there is no evidence to date indicating that the contamination of a fiberoptic endoscope with blood or other secretions of an HB~Agpositive individual is likely to result in the transmission of hepatitis B if the endoscope is routinely cleaned. In fact, the only data currently available (1 retrospective and 5 prospective studies) would indicate that there is no risk. Unfortunately, the data base is not extensive. However, gas sterilization of such contaminated instruments appears unnecessary, as does the use of special instruments for HBsAg-positive individuals. Gamma globulin prophylaxis was not provided in the other studies, with no apparent adverse effects. Strict adherence to the routine cleaning technique between endoscopic procedures is probably the most important measure to be taken to avoid p a t i e n t - t o - p a t i e n t contamination with hepatitis B. Digestive Diseases and Sciences, Vol. 24, No. 1 (January 1979)
ACKNOWLEDGMENTS The authors wish to acknowledge the generous support of Gary L. Gitnick, MD, and his laboratory staff, Olive Stone, Kris Hauss, Maria Brezina, Dennis Bell, and A1 Bodt, in obtaining specimens and performing the laboratory procedures.
REFERENCES 1. Gitnick GL, Goldberg LS, Koretz R, Walsh JH: The liver and the antigens of Hepatitis B. Ann Intern Med 85:488-496, 1976 2. Wills W, Larouze B, London WT, MiUman I, Werner BG, Ogston W, Pourtoghva M, Diallo S, Blumberg BS: Hepatitis-B virus in bedbugs (Cimex hemipterus) from Senegal. Lancet 2:217-219, 1977 3. Instruction for Olympus Gastrointestinal Fiberscope. New Hyde Park, New York, Olympus Corporation of America, p 15 4. Chalmers TC, Alter HJ: Management of the asymptomatic carrier of the hepatitis-associated (Australia) antigen. N Engl J Med 285:613-616, 1971 5. Van Oss CF, Bronson PM: Immunorheophoresis. Immunochemistry 6:775-778, 1969 6. Axon ATR, Cotton PB, Phillips I, Avery SA: Disinfection of gastrointestinal fibre endoscopes. Lancet 1:656-658, 1974 7. Morris IM, Cattle DS, Smits BJ: Endoscopy and transmission of hepatitis B. Lancet 2:1152, 1975 8. McDonald GB, Silverstein FE: Can gastrointestinal endoscopy transmit hepatitis B to patients? Gastrointest Endosc 22:168-170, 1976 9. Center for Disease Control Hepatitis Surveillance Report No. 41. U.S. Department of Health, Education, and Welfare. Public Health Service, September 1977, pp 22-23 10. McClelland DBL, Burrell CJ, Tonkin RW, Reading RC: Hepatitis B: absence of transmission by gastrointestinal endoscopy. Br Med J 1:23-24, 1978 11. Prince AM, Szmuness W, Mann MK, Vyas GN, Grady GF, Shapiro FL, Suki WN, Friedman EA, Stengel KH: Hepatitis B "immune" globulin: Effectiveness in prevention of dialysis-associated hepatitis. N Engl J Med 293:1063-1067, 1975 12. Grady GF, Lee VA: Hepatitis B immune globulin-prevention of hepatitis from accidental exposure among medical personnel. N Engl J Med 293:1067-1070, 1975 13. Redeker AG, Mosley JW, Gocke DJ, McKee AP, Pollack W: Hepatitis B immune globulin as a prophylactic measure for spouses exposed to acute type B hepatitis. N Engl J Med 293:1055-1059, 1975 14. Iwarson S, Ahlmen J, Ericksson E, Hermodsson S, Kjellman H, Ljanggren C, Selander D: Hepatitis B immune serum globulin and standard gamma globulin in prevention of hepatitis B infection among hospital staff: A preliminary report. Am J Med Sci 270:385-389, 1975 15. Alter HJ, Seeff LB, Kaplan PM, McAuliffe VJ, Wright EC, Gerin JL, Purcell RH, Holland PV, Zimmerman HJ: Type B hepatitis: The infectivity of blood positive for e antigen and
23
KORETZ AND CAMACHO DNA polymerase after accidental needlestick exposure. N Engl J Med 295:909-913, 1976 16. Okada K, Kamiyana I, lnomata M, Mitsunobu I, Miyakawa Y, Mayuni M: e-Antigen and anti-e in the serum of asymptomatic mothers as indicators of positive and negative trans-
24
mission of hepatitis B virus to their infants. N Engl J Med 294:746-749, 1976 17. Magnius LO, Lindholm A, Landin P, Iwarson S: A new antigen-antibody system. Clinical significance in long-term carriers of hepatitis B surface antigen. JAMA 231:356-359, 1975
Digestive Diseases and Sciences, Vol. 24, No. 1 (January 1979)
Emergency endoscopy was performed on two patients subsequently found to be hepatitis B surface antigen carriers. Before their carrier state was determined, nine other patients underwent endoscopy using the same instruments, which had been routinely cleaned between procedures. These patients were all notified within five days of the incident, given standard gamma globulin, and prospectively followed for the development of hepatitis. After one of the endoscopes was gas sterilized, the next three patients undergoing endoscopy were also followed. One of the hepatitis B surface antigen carriers was positive for antibody to e antigen; the other carrier had neither e antigen nor antibody. None of these individuals developed signs or symptoms of hepatitis, abnormal serum glutamic pyruvate transaminase elevations, or serologic evidence of hepatitis B exposure. From these data, and other recorded experiences, it appears that routine cleansing of endoscopy equipment is sufficient in preventing the transmission of hepatitis B.
Hepatitis B has been transmitted in a variety of nonparenteral fashions (1). Oral transmission has been demonstrated (1). Epidemics have been described in the families of hepatitis B surface antigen (HB~Ag) carriers (1). HB~Ag has been demonstrated in a variety of body fluids of carriers, including urine, saliva, bile, feces, sneeze droplets, semen, vaginal secretions, breast milk, and tears (1). Venereal transmission has been postulated (1). Transplacental transmission may o c c u r (1). I n f e c t e d clams have been implicated in outbreaks (1). Even mosquito and b e d b u g v e c t o r s have been proposed (1, 2). It is of concern, therefore, that hepatitis B might be t r a n s m i s s a b l e through infected e n d o s c o p i c equipment. Fiberoptic endoscopes cannot be autoclaved and are routinely only thoroughly washed in various soap solutions between uses with no attempt made to sterilize them (3). As the HBsAg carrier rate in the United States may be as high as 0.5% From the San Fernando Valley Medical Program, Olive ViewMidValley Medical Center, Van Nuys, California 91405. Address for reprint requests: Dr. Ronald Koretz, Suite 500, South Tower, Olive View-Midvalley Medical Center, 7533 Van Nuys Blvd., Van Nuys, California 91405.
of the population (4), it is inevitable that, sooner or later, some carrier will undergo an endoscopic procedure and potentially contaminate the instrument. It is not established whether or not patients who s u b s e q u e n t l y u n d e r g o e n d o s c o p y with that instrument are at risk of developing hepatitis. A patient underwent endoscopy at Olive View Medical Center for acute upper-gastrointestinal bleeding from esophageal varices. Subsequent evaluation found him to have HBsAg-positive postnecrotic cirrhosis. Prior to have having been discovered to be an HB~Ag carrier, however, four other patients also underwent endoscopy with the same instrument. About 2 months later, at Sepulveda Veterans Administration Hospital, five other patients were similarly exposed to an endoscope previously used on a patient (with upper-gastrointestinal bleeding) s u b s e q u e n t l y found to be an HB~Ag carrier. It is the purpose of this report to detail the follow-up events in these patients. MATERIALS AND METHODS
In both instances the knowledge of potential HBsAg contamination was discovered within a few days (3 and 5,
Digestive Diseases and Sciences, Vol. 24, No. 1 (January 1979)
0163-2116/79/0100-0021503.00/1 9 1979DigestiveDisease Systems, Inc.
21
KORETZ AND CAMACHO respectively). The 9 involved patients were notified, and each received 2 cc of a standard gamma globulin preparation known to contain some antibody against HB~Ag (anti-HB~). The situation was explained to each patient, and they agreed to be prospectively followed. Samples were obtained at monthly intervals (for 9 months) and tested for HBsAg, anti-HBs, and serum glutamic pyruvate transaminase (SGPT). The endoscopicqnstruments, previously having only undergone routine cleaning between procedures (3), underwent ethylene oxide sterilization and were then put back into routine use. The first three patients subsequently undergoing endoscopy at Olive View were followed as controls. They did not receive gamma globulin, although they were thoroughly informed as to the potential risk. No controls were followed from Sepulveda Veterans Administration Hospital. Blood specimens from both of the HB~Agcarriers were tested for e antigen and antibody by rheophoresis (5). Tests for both HB~Agand anti-HB~were performed using standard commercially available radioimmunoassay kits (Ausria and Ausab, Abbott Laboratories, North Chicago, Illinois).
months later. This was interpreted as being the result of passive immunization. No other anti-HB~ development was seen in the four patients. Follow-up in the VA group of patients was complete (9 months) in only one. Three were followed monthly for 5 months, and one for only 3 months. None of the patients developed signs or symptoms of hepatitis, abnormal SGPT, HBsAg, or anti-HBs. Two of the three controls were followed for the entire 9 months, and the third for 5 months, when she died suddenly at home. None developed evidence of hepatitis (clinical or biochemical) or circulating HB~Ag. Two of the three had preexisting antiHBs, and this persisted throughout the period of follow-up without change in titer. The HBsAg-positive patient at Olive View had neither e antigen nor antibody. The HBsAg carrier at the Sepulveda VA Hospital was found to be positive for anti-e.
RESULTS
DISCUSSION
The four patients at Olive View Hospital consisted of one woman (esophageal stricture) and three men (bleeding varices secondary to alcoholic cirrhosis, duodenal ulcer, and peptic esophagitis). One of the men (variceal bleeder) received several units of blood shortly after endoscopy. None of the other three patients received blood or were otherwise overtly exposed to hepatitis. The five VA patients were all men, two with alcoholic gastritis, two with esophagitis, and a fifth who underwent endoscopy for an abnormal upper-gastrointestinal x-ray with no diagnosis established. One of the patients with gastritis was subsequently transfused, and one of the patients with esophagitis received blood 2 months after endoscopy during a surgical repair for his esophageal reflux. The three control patients were all women, one with duodenal ulcer disease and two with functional bowel disease. The patient with the duodenal ulcer also received blood approximately 3 months after endoscopy during a surgical procedure for her ulcer disease. Two of the four Olive View Hospital patients completed 9 months of follow-up. The third was lost to follow-up after 5 months. The fourth expired after 6 months of follow-up. None of the four demonstrated any abnormalities in SGPT or developed any symptoms compatible with hepatitis. None developed circulating HBsAg. All were anti-HB~ negative prior to receiving globulin. One of the four demonstrated anti-HB~, in progressively decreasing titers, from 5 days after globulin receipt until 2
There is very little information available concerning endoscopic transmission of hepatitis. Axon et al (6) reported a retrospective survey of 176 patients who underwent endoscopy and were subsequently queried concerning episodes of jaundice. None of the 116 responders reported such an occurrence. Morris et al (7) reported on 65 patients who were endoscoped subsequent to an HBsAg-positive patient. Only 32 patients received any follow-up, and it is unclear how often or for how long this was obtained, except that they describe the follow-up visits as "infrequent." However, none of their patients developed abnormal liver function tests. One of their patients became HBsAg-positive between days 65 and 290 postendoscopy. McDonald and Silverstein (8) report an experience similar to ours, in which 4 patients were subsequently exposed to a "contaminated" gastroscope. Their follow-up was at 2- to 4-week intervals for 6 months, and again no evidence of hepatitis or hepatitis B exposure was seen. (One of their patients had preexisting and persistent levels of anti-HBs without change in titer.) A recent CDC Hepatitis Surveillance (9) reports three groups of patients who were followed for 6 months. Each group represented the first 5 patients undergoing endoscopy after the endoscope was used on a HB~Ag-positive individual. The exact details are not reported, but two of the three HBsAg-positive individuals were also positive for e antigen. None of the 15 patients developed serologic evidence of hepatitis B exposure. In Edinburgh, 38 patients
22
Digestive Diseases and Sciences, VoL 24, No. t (January 1979)
ENDOSCOPIC TRANSMISSION OF HEPATITIS B were exposed to an endoscope used previously on an e antigen-positive patient. Thirty were seen once more, 165-225 days later, and no serologic evidence of hepatitis B exposure was observed (10). Our experience with these nine patients is also consistent with the thesis that routine cleaning of fiberoptic endoscopes is adequate in removing the threat of hepatitis transmission. Two confounding factors exist in this study. The first is that all of the exposed patients received, within 7 days of exposure, gamma globulin containing a low titer of anti-HB~. Only one of the nine manifested serologic evidence of the passive transmission of anti-HB~, but we do not know if this dose of globulin provided some degree of protection to the patients. Certainly the administration of high doses of anti-HB~ appears to be protective against "small inoculum" HBsAg exposure (11-13) and some questions have been raised that even standard immune globulin is effective in prophylaxis (14). The second problem has to do with the e status of the HBgAg carrier. It has been proposed that carriers who are e antigen positive are more likely to devleop severe liver diseases themselves and be more communicable, whereas those who carry antibody to e have a better prognosis and may in fact be less infectious (15-17). The e status in the HB~Agpositive patients of three of the previous reports is unknown. The VA patient in this study was anti-e positive, and the Olive View carrier was not positive for either e antigen or anti-e. Hence, both these patients may have been less likely to transmit hepatitis B. (In the CDC study, however, two of the three were e antigen positive.) In conclusion, there is no evidence to date indicating that the contamination of a fiberoptic endoscope with blood or other secretions of an HB~Agpositive individual is likely to result in the transmission of hepatitis B if the endoscope is routinely cleaned. In fact, the only data currently available (1 retrospective and 5 prospective studies) would indicate that there is no risk. Unfortunately, the data base is not extensive. However, gas sterilization of such contaminated instruments appears unnecessary, as does the use of special instruments for HBsAg-positive individuals. Gamma globulin prophylaxis was not provided in the other studies, with no apparent adverse effects. Strict adherence to the routine cleaning technique between endoscopic procedures is probably the most important measure to be taken to avoid p a t i e n t - t o - p a t i e n t contamination with hepatitis B. Digestive Diseases and Sciences, Vol. 24, No. 1 (January 1979)
ACKNOWLEDGMENTS The authors wish to acknowledge the generous support of Gary L. Gitnick, MD, and his laboratory staff, Olive Stone, Kris Hauss, Maria Brezina, Dennis Bell, and A1 Bodt, in obtaining specimens and performing the laboratory procedures.
REFERENCES 1. Gitnick GL, Goldberg LS, Koretz R, Walsh JH: The liver and the antigens of Hepatitis B. Ann Intern Med 85:488-496, 1976 2. Wills W, Larouze B, London WT, MiUman I, Werner BG, Ogston W, Pourtoghva M, Diallo S, Blumberg BS: Hepatitis-B virus in bedbugs (Cimex hemipterus) from Senegal. Lancet 2:217-219, 1977 3. Instruction for Olympus Gastrointestinal Fiberscope. New Hyde Park, New York, Olympus Corporation of America, p 15 4. Chalmers TC, Alter HJ: Management of the asymptomatic carrier of the hepatitis-associated (Australia) antigen. N Engl J Med 285:613-616, 1971 5. Van Oss CF, Bronson PM: Immunorheophoresis. Immunochemistry 6:775-778, 1969 6. Axon ATR, Cotton PB, Phillips I, Avery SA: Disinfection of gastrointestinal fibre endoscopes. Lancet 1:656-658, 1974 7. Morris IM, Cattle DS, Smits BJ: Endoscopy and transmission of hepatitis B. Lancet 2:1152, 1975 8. McDonald GB, Silverstein FE: Can gastrointestinal endoscopy transmit hepatitis B to patients? Gastrointest Endosc 22:168-170, 1976 9. Center for Disease Control Hepatitis Surveillance Report No. 41. U.S. Department of Health, Education, and Welfare. Public Health Service, September 1977, pp 22-23 10. McClelland DBL, Burrell CJ, Tonkin RW, Reading RC: Hepatitis B: absence of transmission by gastrointestinal endoscopy. Br Med J 1:23-24, 1978 11. Prince AM, Szmuness W, Mann MK, Vyas GN, Grady GF, Shapiro FL, Suki WN, Friedman EA, Stengel KH: Hepatitis B "immune" globulin: Effectiveness in prevention of dialysis-associated hepatitis. N Engl J Med 293:1063-1067, 1975 12. Grady GF, Lee VA: Hepatitis B immune globulin-prevention of hepatitis from accidental exposure among medical personnel. N Engl J Med 293:1067-1070, 1975 13. Redeker AG, Mosley JW, Gocke DJ, McKee AP, Pollack W: Hepatitis B immune globulin as a prophylactic measure for spouses exposed to acute type B hepatitis. N Engl J Med 293:1055-1059, 1975 14. Iwarson S, Ahlmen J, Ericksson E, Hermodsson S, Kjellman H, Ljanggren C, Selander D: Hepatitis B immune serum globulin and standard gamma globulin in prevention of hepatitis B infection among hospital staff: A preliminary report. Am J Med Sci 270:385-389, 1975 15. Alter HJ, Seeff LB, Kaplan PM, McAuliffe VJ, Wright EC, Gerin JL, Purcell RH, Holland PV, Zimmerman HJ: Type B hepatitis: The infectivity of blood positive for e antigen and
23
KORETZ AND CAMACHO DNA polymerase after accidental needlestick exposure. N Engl J Med 295:909-913, 1976 16. Okada K, Kamiyana I, lnomata M, Mitsunobu I, Miyakawa Y, Mayuni M: e-Antigen and anti-e in the serum of asymptomatic mothers as indicators of positive and negative trans-
24
mission of hepatitis B virus to their infants. N Engl J Med 294:746-749, 1976 17. Magnius LO, Lindholm A, Landin P, Iwarson S: A new antigen-antibody system. Clinical significance in long-term carriers of hepatitis B surface antigen. JAMA 231:356-359, 1975
Digestive Diseases and Sciences, Vol. 24, No. 1 (January 1979)
