한국에서의 B형 간염 바이러스의 수직감염에 관한 연구

Abstract

[영문]

[한글]

B형 간염의 수직감염은 HBsAg양성인 산모에서 출생한 아이에게 B형 간염이 감염되는 것

을 말하며, 그 감염경로는 경태반 감염 또는 분만시나 출생후 감염의 세가지 가능성이 있

다. 이중 어느 것이 가장 중요하게 작용하는지에 대해서는 아직도 정설이 없다.

저자는 B형 간염의 수직감염 상태를 파악하고 예방대책을 강구하고자 산모, 제대혈 및

영아의 B형 간염 표지자를 검사하여 분석 검토하였다. 연구대상은 1982년부터 1983년까지

서울 제일병원과 부천 제일병원에서 분만한 간질환이 없는 산모와 신생아 각각 537예를

대상으로 하였다. 혈청중의 각종 B형간염 표지자의 검출은 가장 예민도가 높은 방사면역

측정법에 의하였으며 산모의 혈청중 HBsAg, anti-HBc, anti-HBs를 검사하고, HBsAg양성인

산모에서는 다시 HBeAg, anti-HBe를 검사하였다. 산모가 HBsAg양성인 경우는 제대혈의 H

BsAg, anti-HBc, anti-HBs, HBeAg, anti-HBe를, 산모가 anti-HBs양성인 경우는 제대혈의

anti-HBs를 검사하였다. 또한 HBsAg양성인 산모아에서 출생한 신생아에 대해서는 이들 다

섯가지 B형간염 표지자의 변동을 2∼6개월간 추적 관찰하였다.

결과를 요약하면 다음과 같다.

1. 산모 537예중 HBsAg은 40예에서 검출되어 7.4%의 양성률을 나타내었고, HBsAg양성인

산모 40예중 HBeAg양성이 18예 (45.0%), anti-HBe양성이 20예 (50.0%)였으며, 2예 (5.0%

)에서는 HBeAg 및 anti-HBe가 모두 음성이었다.

2. HBsAg양성인 산모 40예중 분만시 채혈한 제대혈에서 HBsAg양성이 24예로 60.0%이었

고, 산모의 HBeAg 및 anti-HBe양성여부와 제대혈의 HBsAg출현과의 관계를 보면, HBeAg양

성인 산모 18예중에서 13예(72.2%), anti-HBe양성인 산모 20예중 10예 (50.0%), HBeAg과

anti-HBe 모두 음성인 산모 2예중 1예 (50.0%)에서 제대혈의 HBsAg이 양성이었다.

3. 산모의 HBsAg치와 제대혈의 HBsAg출현과의 관계를 보면 산모의 HBsAg이 10,000cpm미

만이었던 21예중 14예 (66.7%)에서 제대혈의 HBsAg이 양성이었고, 산모의 HBsAg이 10,000

cpm이상이었던 19예중 10예 (52.6%)에서 제대혈의 HBsAg이 양성으로, 산모의 HBsAg치와

제대혈의 HBsAg출현여부간에는 상관관계가 없었다.

4. Anti-HBs양성인 산모 256예중 제대혈의 anti-HBs양성이 207예 (80.9%)이었고, 산모

의 anti-HBs치가 높을수록 제대혈에서의 anti-HBs치가 높아 상관관계가 있었다.

5. HBsAg양성인 산모 40예로부터 출생한 영아중 22예에 대해서, 생후 2개월부터 6개월

까지 추적 관찰한 결과, 2개월에 1예, 3개월에 3예, 4개월에 2예, 총 6예 (27.3%)에서 HB

sAg이 양성이었다.

6. HBIG와 HB vaccine으로 치료한 14예중 1예 (7.1%)에서, 대조군 8예중 5예 (62.5%)에

서 영아의 HBsAg이 양성이어서 대조군에 비해 치료군에서 통계학적으로 의의있게 수직감

염률이 낮았다.

7. 치료를 하지 않은 대조군에서 어머니가 HBeAg양성인 경우 3예중 2예 (66.7%) anti-H

Be양성인 경우 5예중 3예 (60.7%)에서 영아의 HBsAg이 양성이어서 HBeAg 및 anti-HBe양성

유무에 따라 서로 치아가 없었다. 또한 제대혈의 HBsAg이 양성인 경우(80.0%)가 음성이었

던 경우(33.3%)보다 영아의 HBsAg양성률이 높았다.

이상의 결과를 종합하면 B형간염의 수직감염은 경태반감염보다 분만시 및 출생후 감염

이 중요하며 수직감염률은 62.5%였다. 일반적으로 알려진 바와는 달리 anti-HBe양성인 산

모로부터 출생한 아이에서도 B형간염의 감염률이 높았는데 이것은 새로운 사실로써 계속

추구 관찰해 보아야 할 것이다.

대조군에 비해 치료군에서 의의있게 수직감염를이 낮아 예방효과가 뚜렷하였으므로 HBs

Ag양성인 산모로부터 출생한 신생아에서는 HBeAg양성유무에 상관없이 HBIG 및 HB vaccine

으로 예방하는 것이 바람직할 것으로 생각된다.

Study on Vortical Transmission of Hepatitis B Virus in Korea

Seung Jin Paik

Department of Medical Science The Graduate School, Yonsei University

(Directed by Professor Heung Jai Choi, M.D.)

Since Stokes et al (1951) first reported the possibility of maternal-fetal

transmission of hepatitis B virus (HBV), many authors have suggested the route of

vertical transmission in the pre-, peri- or postnatal period. However, the exact

mode of transmission of HBV from antigen-positive mothers to their infants has not

been clarified. The frequency of vertical transmission was different according to

investigators, methods of test for HB markers and countries.

The several factors have reported to increase the risk of vertical transmission:

a high titer of maternal MBsAg, presence of HBsAg in the baby's umbilical cord

blood, antigenemia in sibling and presence of HBeAg in mother's blood. Among these

factors the presence of HBeAg in mother's blood is believed to be the most

important indicator of transmission.

And recently treatment with HBIG (hepatitis B immune globulin) and HB vaccine has

been recommended in preventing neonatal infection.

This study is purposed to detect the frequency of vertical transmission in Korea

and to evaluate the effectiveness of treatment with HBIG and HB vaccine in

prevention.

A total of 537 pregnant women without liver disease and their babies has been

studied from 1982 to 1983. HB markers, including HBsAg, anti-HBs anti-HBc, HBeAg

and anti-HBe, in sera of mother's, their babies and umbilical cord blood were

tested by radioimmunoassy(RIA).

Babies born to HBsAg carrier mothers were divided into treated group with HBIG

and HB vaccine and untreated control group. Their sera were tested for HB markers

periodically during 6 months after birth.

The results were summarized as follows :

1. Of total 537 mothers without liver disease, serum HBsAg was positive in

40(7.4%), anti-HBs was positive in 256(47.7%), and anti-HBc was positive in

372(69.3%). Among 40 HBsAg positive mothers, serum HBeAg was positive in 18(45.0%),

and anti-HBe was positive in 20(50.0%), and both HBeAg and anti-HBe were negative

in 2(5.0%).

2. Among 40 HBsAg carrier mothers, umbilical cord blood of their babies was HBsAg

positive in 24(60.0%). HBsAg in cord blood samples of babies was positive in

13(72.2%) of 18 HBeAg positive mothers and in 10(50.0%) of 20 anti-HBe positive

mothers and 1(50.0%) of 2 mothers negative both HBeAg and anti-HBe.

3. There was no correlation between HBsAg values of mother's serum and the

presence of HBsAg in the baby's cord blood.

4. Of 256 anti-HBs positive mothers, cord blood of their babies was anti-HBs

positive in 207(80.9%) and there was close relationship between anti-HBs values of

mothers and cord blood.

5. Among 40 babies born to HBsAg carrier mothers, their blood samples were tasted

for HB markers periodically during their 6 months of age in 22 babies and 6(27.3%)

of these had become HBsAg positive.

6. Among 40 babies horn to HBsAg carrier mothers, the frequency of vortical

transmission in babies treated with HBIG and HB vaccine (7.1%: 1 of 14) was

significantly lower than in babies not treated (62.5%: 5 of 8).

7. Among 8 babies not treated, HBsAg had become positive in 4(80.0%) of 5 babies

with HBsAg positive cord blood whereas in 1(33.3%) of 3 babies with HBsAg negative

cord blood; in 2(66.7%) of 3 babies born to HBeAg positive mothers and in 3(60.0%)

of 5 babies born to anti-HBe positive mothers.

In conclusion, the most likely route of vertical transmission seems to be

contamination of baby with maternal blood at the time of delivery or close contact

between mother and baby during postpartum period rather than transplacental

transmission. The incidence of HBs antic-enemia in babies of anti-HBe positive

mothers was as high as in babies of HBeAg positive mothers, in contrast to previous

reports of other investigators suggesting HBeAg may be an indicator of transmission

and anti-HBe may be that of absence of transmission of HB virus from carrier

mothers to infants. This study also suggested that treatment with HBIG and HB

vaccine appears to be effective, as compared to no treatment, in preventing

neonatal hepatitis B virus infection in all newborn infants born to HBsAg positive

mothers regardless of the presence of HBeAg or anti-HBe.