THE JOUR;\IAL OF INFECTIOUS DISEASES. VOL. 139, ;\10, 5 • MAY 1979 © 1979 by The University of Chicago, 0022-1899/79/3905-0002$00.81
Non-B Hepatitis in Japanese Recipients of Blood Transfusions: Clinical and Serologic Studies after the Introduction of Laboratory Screening of Donor Blood for Hepatitis B Surface Antigen From the Surgical Clinic and Virus Laboratory, Sendai National Hospital, and the Department of Bacteriology, Tohoku University School of Medicine, Sendai, Japan
Akira T'ateda, Kaneo Kikuchi, Yoshio Numazaki, Ryoichi Shirachi, and Nakao Ishida
study were hospitalized and underwent surgery in the surgical clinic of the Sendai National Hospital during the period from December 1970 to February 1977. The patients received transfusions of 1 to 159 units of blood negative for HBsAg (1 unit = 200 ml) before and after surgery. Almost 80% of the 1,082 recipients in the study were older than 40 years. Malignant tumors were the underlying disease in 70% of the recipients, while the remaining 30% of cases did not involve tumors. Transfused blood. The blood used for transfusion was collected at the Japan Red Cross Blood Center in Miyagi Prefecture. It was screened for activity of serum aspartate aminotransferase (glutamic-oxalacetic transaminase [SGOTJ) «40 Karmen units acceptable), and counterimmunoelectrophoresis (CIE) was carried out to detect HBsAg. Diagnosis. The patients in the study had not received blood transfusions before admission to the hospital and did not show abnormal liver function at the time of admission. Diagnosis of post-transfusion hepatitis was based on elevation of the level of serum alanine aminotransferase (glutamic-pyruvic transaminase [SGPTJ) after transfusion. Infection with hepatitis was suspected in patients when the SGPT level was elevated by >50 Karmen units for longer than two weeks. A level of SGPT of >200 Karmen units was consid-
It is an undeniable fact that the incidence of post-transfusion hepatitis virus infection has decreased since the use of blood negative for hepatitis B surface antigen (HBsAg) was introduced [1-5]. However, it is also evident that post-transfusion hepatitis still occurs in approximately 10% of transfusion recipients despite the use of HBsAgnegative blood [6, 7]. These cases of post-transfusion hepatitis are referred to as non-A, non-B hepatitis [8-10]. Hepatitis virus type C has been suggested as a possible etiologic agent of the disease [11, 12], and transmission of non-A, non-B hepatitis from humans to chimpanzees has recently been demonstrated [13, 14J. This paper presents results of clinical and serological studies of post-transfusion hepatitis in Japanese recipients who underwent surgery in this hospital after the introduction of laboratory screening of donor blood for HBsAg in 1970. Materials and Methods
Patients.
The patients included in the present
Received for publication May 2, 1978, and in revised form November 27,1978. Please address requests for reprints to Dr. Akira Tateda, Surgical Clinic, Sendai National Hospital, Miyagino 2 Chome 8-8, Sendai 983, Japan.
511
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 7, 2015
Cases of hepatitis virus infection in Japanese recipients of blood transfusions were serologically and clinically analyzed after the introduction of laboratory screening of donor blood for hepatitis B surface antigen by counter immunoelectrophoresis. NonA, non-B hepatitis occurred in 116 (10.7%) and hepatitis type B in nine (0.9%) of the 1,082 recipients. The incubation period of the post-transfusion non-A, non-B hepatitis cases varied from two to 33 weeks, but most occurred within 15 weeks. In 97 (83.6%) of the 116 cases of non-A, non-B hepatitis studied, the duration of abnormal elevation of the level of serum alanine aminotransferase (glutamic-pyruvic transaminase [SGPT]) was 16 weeks. The cases of non-A, non-B hepatitis could be divided into three groups according to the pattern of elevation of SGPT levels. These findings may suggest either a multiple etiology for non-A, non-B hepatitis or a variety of clinical symptoms with a single etiology for the infection.
Tateda et al.
512
40 ,..... ~
'-'
passive hemagglutination (RPHA) [17] for HBsAg and by passive hemagglutination -(PHA) [18] for antibody to HBsAg (anti-HBs). Reversecell" for RPHA was supplied by Yamanouchi Pharmaceutical Co., Tokyo, and Hebsgencell" for PHA was supplied by Green Cross Co., Osaka. In both the RPHA and PHA tests, all of the positive sera were retested, and results were confirmed by neutralization with anti-HBs or HBsAg. The immune adherence hemagglutination (IAHA) test for antibody to hepatitis A virus was performed by Dr. Y. Moritsugu, National Institute of Health of Japan. The CF antigen to cytomegalovirus (Davis strain) was prepared in this laboratory according to a procedure described previously [19], and the CF tests were performed by microtechnique. Results
Incidence of post-transfusion hepatitis after introduction of screening of donor blood for HBsAg. The annual incidence of post-transfusion hepatitis and the number of deaths due to the disease in patients undergoing surgery in this clinic since 1967 are shown in figure I. It is evident that the incidence of post-transfusion hepatitis decreased
-
z0
30
Screening for HBs-Ag (CIE)
W
o
Z W 0 ...... U Z
--0
20
•
~
......
10
0 .....
1969
.....
'o~
1970
-~~o---
1971
3
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I
.-+
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2
0- - - - 0 ' - -
_0"
.-+
Vl
:::J'" Q)
Q)
.-+
.-+ .-+
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.-+
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....
1967 1968
-
_
I-
-
"'TJ
c
co'
o, 0
-+>
1972 1973
1974 1975
1976
1977
Figure 1. Annual incidence of post-transfusion hepatitis and number of fatal cases due to the disease in patients undergoing surgery at Sendai National Hospital. HBs-Ag = hepatitis B surface antigen; CIE = counterimmunoelectrophoresis. Levels of serum alanine aminotransferase: (-------) = ~50 Karmen units; (0 - - - - 0) = ~200 Karmen units.
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 7, 2015
ered indicative of authentic hepatitis, and manifestation of jaundice or an icteric index of >15 units in the serum was indicative of icteric hepatitis. The cases were defined as protracted hepatitis when elevation of the SGPT level persisted for more than six months. To differentiate between post-transfusion hepatitis and involvement of the liver in malignant tumors or drug treatment of cancer, the patients were observed for a long period after the restoration of normal levels of SGPT, and the final diagnosis of post-transfusion hepatitis was decided nine to 12 months after transfusion. For cases that could not be diagnosed clinically, biopsy of the liver was performed with Menghini's needle and a histologic diagnosis was determined according to the criteria of Scheuer [15]. The diagnosis of postoperative hepatitis in patients who did not receive transfusions was based on the same criteria as those for post-transfusion hepatitis described above. Serological sur-oey. Blood was obtained from patients before transfusion and everyone or two weeks thereafter for at least three months. All of the serum specimens were stored at -20 C until use. Sera were tested by CIE [16] and by reversed
Post- Transiusion Non-B Hepatitis in Japan
513
Table 1. Annual incidence (December 1970 to February 1977) of postoperative hepatitis in surgical patients who did or did not receive blood transfusions after the introduction of screening of donor blood for hepatitis B surface antigen (HBsAg) by counterimmunoelectrophoresis. Patients Received transfusions Hepatitis Positive for HBsAg Positive for anti-HBs Negative for HBsAg and anti-HBs No transfusions Hepatitis
1970
1971
1972
1973
1974
1975
5 1 (20.0) 0 0 1 23 0
199 15 (7.5) 2 3 10 569
221 23 (10.4) 2 9 12 515 2 (0.4)
166 23 (13.9) 0 7 16 647 1 (0.2)
171 22 (12.9) 2 7 13 656 3 (0.5)
151 21 (13.9) 2 2 17 652 12* (1.8)
0
=
148 43 (29.1) 0 3 40 628 5 (0.8)
1977
Total
27 8 (29.7) 1* 0 7 45 0
1,082 156 (14.4) 9* 31 116 3,735 23* (0.6)
antibody to HBsAg.
transfusions, and one of these patients died of fulminant hepatitis. Incidence of hepatitis type B after transfusion of screened blood. The RPHA method was used for detection of HBsAg in sera from the 1,082 recipients before and after transfusion. As shown in table 1, HBsAg was detected in nine (0.9%) of the 1,082 patients who received screened blood. All blood transfused into five of these nine patients was tested again for HBsAg by RPHA. HBsAg was detected in three samples (representing blood transfused into three patients) but not in the two remaining samples. Thus the two patients who received blood negative for HBsAg as determined by RPHA developed type B hepatitis. No anti-HBs was demonstrated before transfusion in blood from any of the above nine patients with type B hepatitis. The relationship between clinical response and
and mortality due to the disease was almost eliminated after the introduction of screening of donor blood for HBsAg by CIE in December 1970. However, it is also evident that post-transfusion hepatitis was not completely eliminated by this procedure since approximately lO%of those who received blood that had been screened developed the disease. Moreover, post-transfusion hepatitis occurred in 43 (29.1%) of 148 recipients in 1976 (figure 1, table 1). During the period when all donor blood was screened by CIE (December 1970 through February 1977), post-transfusion hepatitis occurred in 156 (14.4%) ofthe 1,082 recipients (table 1). However, during the same period acute hepatitis developed in 23 (0.6%) of 3,667 patients who underwent surgery without blood transfusions (table 1). In 1975, postoperative hepatitis occurred in 12 (1.8%) of 652 patients who did not receive blood
Table 2. Clinical and serologic responses for hepatitis type B in surgical patients. Blood used for transfusions was screened for hepatitis B surface antigen (HBsAg) by counterimmunoelectrophoresis. No. of patients with indicated serologic response(s) Clinical response Post-transfusion hepatitis Suspected hepatitis Authentic hepatitis Icteric Anicteric Non-hepatitis, post-transfusion Postoperative hepatitis without transfusion NOTE.
No. of patients
HBsAg only
HBsAg and anti-HBs
156 66
5 0
4 0
26 64 926 23
4 1 0 0
2 2 0 0
See Materials and Methods for criteria used for diagnosis of hepatitis. Anti-HBs
Primary anti-HBs only 1
o o 1 45
o antibody to HBsAg.
Secondary anti-HBs only 30 11 5 14 127 1
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 7, 2015
NOTE. Data are numbers of patients; numbers in parentheses are percentages. Anti-HBs 'One patient died of fulminant hepatitis.
1976
Tateda et al.
514
10
G D
CIE positivs
CIE negative
~
VI
W
VI
« o
u,
o o
z
~
---------
-----f---
r---
r--,...-0
0
0
3
4
5
0
0
0
6
7
~8
RPHA TITERS (log 2
)
Figure 2. Comparison of the sensitivity of two methods of screening, counterimmunoelectrophoresis (CIE) and reversed passive hemagglutination (RPHA), in detection of hepatitis B surface antigen.
determined by CIE at the Japan Red Cross Blood Center in Miyagi Prefecture, were tested by RPHA in this laboratory between October 1976 and July 1977. HBsAg was detected in 23 (0.8%) of the 2,840 samples tested. These RPHA-positive samples were then tested by CIE in this laboratory.
20
o : suspected •
hepatitis
: authentic hepatitis
15 lJ)
Figure 3. Distribution of the incubation periods of 116 cases of posttransfusion non-A, non-B hepatitis. (All 116 patients were negative for both hepatitis B surface antigen [HBsAg] and antibody to HBsAg.)
LJJ
lJ)
« o u, o c
10
z
15 INCUBATION PERIOD (weeks)
35
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 7, 2015
detection of HBsAg is shown in table 2. All of the nine patients positive for HBsAg had authentic hepatitis; six of the nine had icteric hepatitis. Anti-HBs responses were demonstrated in both patients with hepatitis and those without the disease who were admitted to the clinic during the same period. Primary anti-HBs responses without detection of HBsAg were found in 46 (4.3%) of the 1,082 recipients; only one (2.2%) of the 46 developed hepatitis, while the remaining 45 (97.8%) showed no symptoms. Secondary anti-HBs responses were demonstrated in 30 (19.2%) of 156 patients with hepatitis and in 127 (13.7%) of 926 patients without hepatitis. However, an anti-HBs response was demonstrated in only one (4.3%) of the 23 patients with postoperative hepatitis who did not receive transfusions. Of the 156 patients with post-transfusion hepatitis, 116 (74.3%) were negative for both HBsAg and anti-HBs (table 2). When seven paired sera from these patients with non-B hepatitis were prepared and tested for antibody to hepatitis A virus, no increase in titer of antibody to the virus was demonstrated by IAHA. In addition, 54 of the above 116 patients with non-B hepatitis and 55 patients without hepatitis were tested serologically for antibodies to cytomegalovirus. No difference could be detected between seroconversion rates of patients with non-B hepatitis and those without hepatitis. Comparison of the sensitivity of two screening methods, CIE and RPHA, for detection of HBsAg. All 2,840 blood samples negative for HBsAg, as
515
Post- Transfusion Non-B Hepatitis in Japan
authentic hepatitis; 15 of the 61 were icteric. The remaining 55 cases (48.3%) were classified as suspected hepatitis according to the degree of elevation of the level of SGPT as described in Materials and Methods. Of the 23 cases of hepatitis that occurred in patients who did not receive transfusions, 10 were authentic and 13 were suspected. Incubation period. The incubation periods of the 116 cases of post-transfusion non-B hepatitis are shown in figure 3. The incubation periods varied from two to 33 weeks, but most of the cases were detected within 15 weeks. There was no significant difference in the incubation period between authentic and suspected cases of hepatitis. The distribution curve was monophasic, with a peak at three weeks. Duration of SGPT elevation. The duration of elevation of SGPT levels to >50 Karmen units is shown in figure 4. In 97 (83.6%) of the 116 cases of post-transfusion non-B hepatitis, the duration of abnormal elevation of the SGPT level was 16
25
D : suspected 20
hepatitis
•
: authentic hepatitis
~
: postoperative hepatitis without transfusion
(/)
W
(/) 15
«
U I.L
o
o 10 Z
5
56
68
DURATION (weeks) Figure 4. Distribution of duration of cases of post-transfusion non-A, non-B hepatitis and cases of postoperative nonB hepatitis in patients who did not receive transfusions.
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 7, 2015
The titers determined by RPHA and results of CIE are shown in figure 2. Of the 23 samples, six had a RPHA titer of >64 and were positive by CIE, but 17 had a RPHA titer of
Non-B Hepatitis in Japanese Recipients of Blood Transfusions: Clinical and Serologic Studies after the Introduction of Laboratory Screening of Donor Blood for Hepatitis B Surface Antigen From the Surgical Clinic and Virus Laboratory, Sendai National Hospital, and the Department of Bacteriology, Tohoku University School of Medicine, Sendai, Japan
Akira T'ateda, Kaneo Kikuchi, Yoshio Numazaki, Ryoichi Shirachi, and Nakao Ishida
study were hospitalized and underwent surgery in the surgical clinic of the Sendai National Hospital during the period from December 1970 to February 1977. The patients received transfusions of 1 to 159 units of blood negative for HBsAg (1 unit = 200 ml) before and after surgery. Almost 80% of the 1,082 recipients in the study were older than 40 years. Malignant tumors were the underlying disease in 70% of the recipients, while the remaining 30% of cases did not involve tumors. Transfused blood. The blood used for transfusion was collected at the Japan Red Cross Blood Center in Miyagi Prefecture. It was screened for activity of serum aspartate aminotransferase (glutamic-oxalacetic transaminase [SGOTJ) «40 Karmen units acceptable), and counterimmunoelectrophoresis (CIE) was carried out to detect HBsAg. Diagnosis. The patients in the study had not received blood transfusions before admission to the hospital and did not show abnormal liver function at the time of admission. Diagnosis of post-transfusion hepatitis was based on elevation of the level of serum alanine aminotransferase (glutamic-pyruvic transaminase [SGPTJ) after transfusion. Infection with hepatitis was suspected in patients when the SGPT level was elevated by >50 Karmen units for longer than two weeks. A level of SGPT of >200 Karmen units was consid-
It is an undeniable fact that the incidence of post-transfusion hepatitis virus infection has decreased since the use of blood negative for hepatitis B surface antigen (HBsAg) was introduced [1-5]. However, it is also evident that post-transfusion hepatitis still occurs in approximately 10% of transfusion recipients despite the use of HBsAgnegative blood [6, 7]. These cases of post-transfusion hepatitis are referred to as non-A, non-B hepatitis [8-10]. Hepatitis virus type C has been suggested as a possible etiologic agent of the disease [11, 12], and transmission of non-A, non-B hepatitis from humans to chimpanzees has recently been demonstrated [13, 14J. This paper presents results of clinical and serological studies of post-transfusion hepatitis in Japanese recipients who underwent surgery in this hospital after the introduction of laboratory screening of donor blood for HBsAg in 1970. Materials and Methods
Patients.
The patients included in the present
Received for publication May 2, 1978, and in revised form November 27,1978. Please address requests for reprints to Dr. Akira Tateda, Surgical Clinic, Sendai National Hospital, Miyagino 2 Chome 8-8, Sendai 983, Japan.
511
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 7, 2015
Cases of hepatitis virus infection in Japanese recipients of blood transfusions were serologically and clinically analyzed after the introduction of laboratory screening of donor blood for hepatitis B surface antigen by counter immunoelectrophoresis. NonA, non-B hepatitis occurred in 116 (10.7%) and hepatitis type B in nine (0.9%) of the 1,082 recipients. The incubation period of the post-transfusion non-A, non-B hepatitis cases varied from two to 33 weeks, but most occurred within 15 weeks. In 97 (83.6%) of the 116 cases of non-A, non-B hepatitis studied, the duration of abnormal elevation of the level of serum alanine aminotransferase (glutamic-pyruvic transaminase [SGPT]) was 16 weeks. The cases of non-A, non-B hepatitis could be divided into three groups according to the pattern of elevation of SGPT levels. These findings may suggest either a multiple etiology for non-A, non-B hepatitis or a variety of clinical symptoms with a single etiology for the infection.
Tateda et al.
512
40 ,..... ~
'-'
passive hemagglutination (RPHA) [17] for HBsAg and by passive hemagglutination -(PHA) [18] for antibody to HBsAg (anti-HBs). Reversecell" for RPHA was supplied by Yamanouchi Pharmaceutical Co., Tokyo, and Hebsgencell" for PHA was supplied by Green Cross Co., Osaka. In both the RPHA and PHA tests, all of the positive sera were retested, and results were confirmed by neutralization with anti-HBs or HBsAg. The immune adherence hemagglutination (IAHA) test for antibody to hepatitis A virus was performed by Dr. Y. Moritsugu, National Institute of Health of Japan. The CF antigen to cytomegalovirus (Davis strain) was prepared in this laboratory according to a procedure described previously [19], and the CF tests were performed by microtechnique. Results
Incidence of post-transfusion hepatitis after introduction of screening of donor blood for HBsAg. The annual incidence of post-transfusion hepatitis and the number of deaths due to the disease in patients undergoing surgery in this clinic since 1967 are shown in figure I. It is evident that the incidence of post-transfusion hepatitis decreased
-
z0
30
Screening for HBs-Ag (CIE)
W
o
Z W 0 ...... U Z
--0
20
•
~
......
10
0 .....
1969
.....
'o~
1970
-~~o---
1971
3
""U
I
.-+
CD
"0
2
0- - - - 0 ' - -
_0"
.-+
Vl
:::J'" Q)
Q)
.-+
.-+ .-+
o,
Vl
, , ".'"
~.
CD :::J
.-+
.C
Q)
:::J
Q)
_.0
0
-+>
:::J
/-----,,,,,,, '
.....------
....
1967 1968
-
_
I-
-
"'TJ
c
co'
o, 0
-+>
1972 1973
1974 1975
1976
1977
Figure 1. Annual incidence of post-transfusion hepatitis and number of fatal cases due to the disease in patients undergoing surgery at Sendai National Hospital. HBs-Ag = hepatitis B surface antigen; CIE = counterimmunoelectrophoresis. Levels of serum alanine aminotransferase: (-------) = ~50 Karmen units; (0 - - - - 0) = ~200 Karmen units.
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 7, 2015
ered indicative of authentic hepatitis, and manifestation of jaundice or an icteric index of >15 units in the serum was indicative of icteric hepatitis. The cases were defined as protracted hepatitis when elevation of the SGPT level persisted for more than six months. To differentiate between post-transfusion hepatitis and involvement of the liver in malignant tumors or drug treatment of cancer, the patients were observed for a long period after the restoration of normal levels of SGPT, and the final diagnosis of post-transfusion hepatitis was decided nine to 12 months after transfusion. For cases that could not be diagnosed clinically, biopsy of the liver was performed with Menghini's needle and a histologic diagnosis was determined according to the criteria of Scheuer [15]. The diagnosis of postoperative hepatitis in patients who did not receive transfusions was based on the same criteria as those for post-transfusion hepatitis described above. Serological sur-oey. Blood was obtained from patients before transfusion and everyone or two weeks thereafter for at least three months. All of the serum specimens were stored at -20 C until use. Sera were tested by CIE [16] and by reversed
Post- Transiusion Non-B Hepatitis in Japan
513
Table 1. Annual incidence (December 1970 to February 1977) of postoperative hepatitis in surgical patients who did or did not receive blood transfusions after the introduction of screening of donor blood for hepatitis B surface antigen (HBsAg) by counterimmunoelectrophoresis. Patients Received transfusions Hepatitis Positive for HBsAg Positive for anti-HBs Negative for HBsAg and anti-HBs No transfusions Hepatitis
1970
1971
1972
1973
1974
1975
5 1 (20.0) 0 0 1 23 0
199 15 (7.5) 2 3 10 569
221 23 (10.4) 2 9 12 515 2 (0.4)
166 23 (13.9) 0 7 16 647 1 (0.2)
171 22 (12.9) 2 7 13 656 3 (0.5)
151 21 (13.9) 2 2 17 652 12* (1.8)
0
=
148 43 (29.1) 0 3 40 628 5 (0.8)
1977
Total
27 8 (29.7) 1* 0 7 45 0
1,082 156 (14.4) 9* 31 116 3,735 23* (0.6)
antibody to HBsAg.
transfusions, and one of these patients died of fulminant hepatitis. Incidence of hepatitis type B after transfusion of screened blood. The RPHA method was used for detection of HBsAg in sera from the 1,082 recipients before and after transfusion. As shown in table 1, HBsAg was detected in nine (0.9%) of the 1,082 patients who received screened blood. All blood transfused into five of these nine patients was tested again for HBsAg by RPHA. HBsAg was detected in three samples (representing blood transfused into three patients) but not in the two remaining samples. Thus the two patients who received blood negative for HBsAg as determined by RPHA developed type B hepatitis. No anti-HBs was demonstrated before transfusion in blood from any of the above nine patients with type B hepatitis. The relationship between clinical response and
and mortality due to the disease was almost eliminated after the introduction of screening of donor blood for HBsAg by CIE in December 1970. However, it is also evident that post-transfusion hepatitis was not completely eliminated by this procedure since approximately lO%of those who received blood that had been screened developed the disease. Moreover, post-transfusion hepatitis occurred in 43 (29.1%) of 148 recipients in 1976 (figure 1, table 1). During the period when all donor blood was screened by CIE (December 1970 through February 1977), post-transfusion hepatitis occurred in 156 (14.4%) ofthe 1,082 recipients (table 1). However, during the same period acute hepatitis developed in 23 (0.6%) of 3,667 patients who underwent surgery without blood transfusions (table 1). In 1975, postoperative hepatitis occurred in 12 (1.8%) of 652 patients who did not receive blood
Table 2. Clinical and serologic responses for hepatitis type B in surgical patients. Blood used for transfusions was screened for hepatitis B surface antigen (HBsAg) by counterimmunoelectrophoresis. No. of patients with indicated serologic response(s) Clinical response Post-transfusion hepatitis Suspected hepatitis Authentic hepatitis Icteric Anicteric Non-hepatitis, post-transfusion Postoperative hepatitis without transfusion NOTE.
No. of patients
HBsAg only
HBsAg and anti-HBs
156 66
5 0
4 0
26 64 926 23
4 1 0 0
2 2 0 0
See Materials and Methods for criteria used for diagnosis of hepatitis. Anti-HBs
Primary anti-HBs only 1
o o 1 45
o antibody to HBsAg.
Secondary anti-HBs only 30 11 5 14 127 1
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 7, 2015
NOTE. Data are numbers of patients; numbers in parentheses are percentages. Anti-HBs 'One patient died of fulminant hepatitis.
1976
Tateda et al.
514
10
G D
CIE positivs
CIE negative
~
VI
W
VI
« o
u,
o o
z
~
---------
-----f---
r---
r--,...-0
0
0
3
4
5
0
0
0
6
7
~8
RPHA TITERS (log 2
)
Figure 2. Comparison of the sensitivity of two methods of screening, counterimmunoelectrophoresis (CIE) and reversed passive hemagglutination (RPHA), in detection of hepatitis B surface antigen.
determined by CIE at the Japan Red Cross Blood Center in Miyagi Prefecture, were tested by RPHA in this laboratory between October 1976 and July 1977. HBsAg was detected in 23 (0.8%) of the 2,840 samples tested. These RPHA-positive samples were then tested by CIE in this laboratory.
20
o : suspected •
hepatitis
: authentic hepatitis
15 lJ)
Figure 3. Distribution of the incubation periods of 116 cases of posttransfusion non-A, non-B hepatitis. (All 116 patients were negative for both hepatitis B surface antigen [HBsAg] and antibody to HBsAg.)
LJJ
lJ)
« o u, o c
10
z
15 INCUBATION PERIOD (weeks)
35
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 7, 2015
detection of HBsAg is shown in table 2. All of the nine patients positive for HBsAg had authentic hepatitis; six of the nine had icteric hepatitis. Anti-HBs responses were demonstrated in both patients with hepatitis and those without the disease who were admitted to the clinic during the same period. Primary anti-HBs responses without detection of HBsAg were found in 46 (4.3%) of the 1,082 recipients; only one (2.2%) of the 46 developed hepatitis, while the remaining 45 (97.8%) showed no symptoms. Secondary anti-HBs responses were demonstrated in 30 (19.2%) of 156 patients with hepatitis and in 127 (13.7%) of 926 patients without hepatitis. However, an anti-HBs response was demonstrated in only one (4.3%) of the 23 patients with postoperative hepatitis who did not receive transfusions. Of the 156 patients with post-transfusion hepatitis, 116 (74.3%) were negative for both HBsAg and anti-HBs (table 2). When seven paired sera from these patients with non-B hepatitis were prepared and tested for antibody to hepatitis A virus, no increase in titer of antibody to the virus was demonstrated by IAHA. In addition, 54 of the above 116 patients with non-B hepatitis and 55 patients without hepatitis were tested serologically for antibodies to cytomegalovirus. No difference could be detected between seroconversion rates of patients with non-B hepatitis and those without hepatitis. Comparison of the sensitivity of two screening methods, CIE and RPHA, for detection of HBsAg. All 2,840 blood samples negative for HBsAg, as
515
Post- Transfusion Non-B Hepatitis in Japan
authentic hepatitis; 15 of the 61 were icteric. The remaining 55 cases (48.3%) were classified as suspected hepatitis according to the degree of elevation of the level of SGPT as described in Materials and Methods. Of the 23 cases of hepatitis that occurred in patients who did not receive transfusions, 10 were authentic and 13 were suspected. Incubation period. The incubation periods of the 116 cases of post-transfusion non-B hepatitis are shown in figure 3. The incubation periods varied from two to 33 weeks, but most of the cases were detected within 15 weeks. There was no significant difference in the incubation period between authentic and suspected cases of hepatitis. The distribution curve was monophasic, with a peak at three weeks. Duration of SGPT elevation. The duration of elevation of SGPT levels to >50 Karmen units is shown in figure 4. In 97 (83.6%) of the 116 cases of post-transfusion non-B hepatitis, the duration of abnormal elevation of the SGPT level was 16
25
D : suspected 20
hepatitis
•
: authentic hepatitis
~
: postoperative hepatitis without transfusion
(/)
W
(/) 15
«
U I.L
o
o 10 Z
5
56
68
DURATION (weeks) Figure 4. Distribution of duration of cases of post-transfusion non-A, non-B hepatitis and cases of postoperative nonB hepatitis in patients who did not receive transfusions.
Downloaded from http://jid.oxfordjournals.org/ at University of Arizona on September 7, 2015
The titers determined by RPHA and results of CIE are shown in figure 2. Of the 23 samples, six had a RPHA titer of >64 and were positive by CIE, but 17 had a RPHA titer of
