소아의 만성 B형 간염의 자연 경과 = Natural History of Chronic Hepatitis B in Children

다국어 초록 (Multilingual Abstract)

Purpose:We investigated the spontaneous seroconversion rate of hepatitis B viral markers and predictive factors affecting seroconversion in children with chronic hepatitis B.
Methods:The study population included 214 children diagnosed as chronic hepatitis B, with positive HBsAg, HBeAg and HBVDNA over six months, and all patients had a family history of chronic Hepatitis B. They were followed between May 1982 and Febrary 2003 in the Department of Pediatrics, Yonsei University College of Medicine. Serum HBsAg, HBeAg, anti-HBs, HBVDNA, and AST/ALT were measured every six months.
Results:The mean age of patients was 7.4±4.5 years. The loss of HBeAg, HBVDNA and HBsAg were observed in 44(19.2%), 34(15.9%) and 3(1.4%) children respectively. The patients with serum ALT levels over three times normal and with HBVDNA less than 1,000 pg/dL showed significantly higher seroconversion rates of HBeAg and HBVDNA(P<0.001). By analyzing with the life table method, the cumulative seroconversion rate of HBeAg was 11% at 10 and 35% at 19 years of age, while HBVDNA was 9% at 10 and 32% at 19 years of age. In cases of HBsAg, the cumulative seroconversion rate was only 1.5% at 19 years of age. The age of patients, serum ALT and HBVDNA levels were proven as signifincant factors influencing the seroconversion of HBeAg and HBVDNA(P<0.001).
Conclusion:In children with chronic hepatitis B, the seroconversion rate of HBeAg and HBVDNA are expected to be 35% and 32%, respectively, by the age of 19 years. The age of patients, serum ALT and HBVDNA levels seem to have significant influence on HBeAg and HBVDNA seroconversion.

국문 초록 (Abstract)

목 적 : HBeAg과 HBVDNA의 음전 여부는 만성 B형 간염의 치유 효과 판정에 중요한 지표이다. 소아의 만성 B형 간염에서 HBeAg과 HBVDNA의 자연 음전율은 인종과 지역별로 다양하게 보고되고 있으나, 우리나라에서의 연구는 부족한 실정이다. 이에 저자들은 만성 B형 간염 환아를 장기간 추적 관찰하여 이들의 임상 경과와 HBsAg, HBeAg 및 HBVDNA의 자연 음전율에 대하여 알아보고자 하였다. 방 법 : 1982년 5월부터 2003년 2월까지 약 21년간 연세대학교 의과대학 세브란스병원 소아과에 내원하여 HBsAg, HBeAg, HBVDNA가 6개월 이상 양성이었던 260례의 환아 중 B형 간염의 가족력이 있는 214례를 수직감염된 환아로 생각하고 이들을 대상으로 조사 분석하였다. 환아들의 HBsAg, HBeAg, HBVDNA, AST/ALT 등을 6개월 간격으로 검사하였고, 이들의 임상 양상과 HBsAg, HBeAg 및 HBVDNA의 자연 음전율 및 이에 영향을 주는 인자들을 생명분석표, Cox proportional hazard model 등의 통계법을 이용하여 조사 분석하였다.결 과 : 진단 당시 환자들의 평균 연령은 7.4±4.5세였으며, HBVDNA의 평균값은 1,755±1,415 pg/dL였고, ALT의 최고 값의 평균은 97±163 IU/L였다. 모든 환아에서 B형 간염의 가족력이 있었다. 41례(19.2%)의 환아에서 추적 관찰하는 동안 HBeAg이 음전 되었고, 34례(15.9%)에서 HBVDNA가 음전 되었으며, 3례(1.4%)에서 HBsAg이 음전 되었다. 환아들의 B형 간염 표지자들의 음전율은 혈청 ALT치가 정상의 3배 이상 증가한 군에서 HBeAg과 HBVDNA의 음전율이 통계학적으로 의미 있게 높았으며(P<0.001), HBVDNA치가 1,000 pg/dL 미만으로 낮은 군에서 HBeAg과 HBVDNA의 음전율이 의미 있게 높았다(P<0.001). 생명분석표로 분석한 결과 HBeAg은 10세까지 11%, 19세까지 35%가 음전 되며, HBVDNA는 10세까지 9 %, 19세까지 32%에서 음전 되고, HBsAg은 5세에 최고조를 이루어 그 이후 19세까지 1.5%만이 음전 되는 것으로 분석되었다. Cox 모델로 분석한 결과 시간 경과에 따른 HBeAg과 HBVDNA의 음전율은 연령, 혈청 ALT치 및 혈청 HBVDNA 치가 통계학적으로 유의하게 영향을 주는 것으로 조사되었다(P<0.001).

참고문헌 (Reference)

1 "Treatment of chronic hepatitis B" 1 : 232-241, 2001

2 "The significance of spontaneous hepatitis B antigen seroconversion in childhood:with special emphasis on the clearance of hepatitis B e antigen before three years of age" 22 : 1387-1392, 1995

3 "The Therapeutic Effect of interferon- alpha treatment in children with chronic hepatitis B" 40 : 955-964, 1997

4 "Spontaneous seroconversion in hepatitis B e antigen-positive chronic hepatitis B:implications for interferon therapy" 176 : 845-850, 1997

5 "Spontaneous loss of HBsAg in children with chronic hepatitis B virus infection" 15 : 382-386, 1992

6 "Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in chinese patients with chronic hepatitis B virus infection" 92 : 1839-1843, 1987

7 "Spontaneous HBeAg clearance rate and its affecting factors in patients with chronic hepatitis B in Korea" 24 : 1313-1319, 1992

8 "Seroepidermiology of HBV infection in South Korea 1995 through 1999" 16 : 153-159, 2001

9 "Precore stop codon mutant in chronic hepatitis B virus infection in children:its relation to hepatitis B e seroconversion and maternal hepatitis B surface antigen" 28 : 915-922, 1998

10 "Outcome of chronic hepatitis B in Caucasian children during a 20-year observation period" 29 : 184-190, 1998

11 "Natural history of hepatitis B infection in children" 15 : E11-E19, 2000

12 "Natural history and prognosis of hepatitis B" 23 : 47-58, 2003

13 "Mutations in hepatitis B virus precore and core promotor in children with chronic hepatitis B infection - comparison between vertical and non-vertical transmission" 43 : 779-791, 2000

14 "Management of chronic hepatitis B-treatment of chronic hepatitis B virus infection : when, who, what for and how" 15 : E31-E33, 2000

15 "Long-term outcome of chronic type B hepatitis in patients who acquired hepatitis B virus infection in childhood" 99 : 805-810, 1990

16 "Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B" 35 : 1522-1527, 2002

17 "Long-term follow up of chronic hepatitis B virus infection in children of different ethinic origins" 186 : 295-301, 2002

18 "Immune responses in hepatitis B virus infection" 23 : 21-37, 2003

19 "Hepatitis B virus infection" 337 : 1733-1745, 1997

20 "Hepatitis B viral markers of Korean adults in the late 1990s : Survey data of 70,347 health screenees" 33 : 642-652, 1999

21 "Hepatitis B antigenemia at birth:A long-term follow-up study" 133 : 374-377, 1998

22 "HBsAg＋ and HBsAg－ chronic active hepatitis, liver cirrhrosis and hepatocellular carcinoma in Korea : prevalence and difference in age distribution" 33 : 127-131, 1992

23 "Global control of hepatitis B virus infection" 2 : 395-403, 2002

24 "Factors affection clearance of hepatitis B e antigen in hepatitis B surface antigen carrier children" 115 : 385-390, 1989

25 "Epidermiology and prevention of hepatitis B" 23 : 39-46, 2003

26 "Clinical study on distribution of hepatitis B virus markers in Korean population" 15 : 163-171, 1983

27 "Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children" 12 : 657-662, 1990

28 "Cellular immune response to hepatitis B core antigen in maternal-infant transmission of hepatitis B virus" 15 : 770-776, 1992

29 "An important public health issue" 47 : 51-55, 2001

30 "Acute hepatitis B virus infection:relation of age to the clinical expression of disease and subsequent developement of the carrier state" 151 : 599-603, 1985

31 "A survey of HBs antigenemia among healthy primary and Middle School Children pregnant women in Kyung Pook Province" 26 : 1118-1125, 1983

32 "A study of ten-year follow-up for immune responses of plasma derived HB vaccine(Hepavax-B)" 52 : 48-57, 1997

33 "A longitudinal follow-up of asymptomatic hepatitis B surface antigen-positive Chinese children" 8 : 1130-1133, 1988

34 "A case of primary hepatocellular carcinoma following vertical transmission of hepatitis B virus in a child" 34 : 1573-1580, 1991