自然経過でHBs抗原の陰性化をみた無症候性B型肝炎ウイルスキャリア住民における長期臨床経過のgenotype別比較検討  [in Japanese] Comparative analysis of clinical features in hepatitis B virus carrier residents who lost hepatitis B surface antigen during long-term follow-up according to a difference of genotype.  [in Japanese]

岩手県予防医学協会による住民検診において,1979年8月〜2000年7月の観察期間に,自然経過でHBs抗原が消失した52例を任意に抽出し,RFLP法によりHBV genotypeを検出し,genotype別にその臨床像を比較検討した.その内訳は,男性24例,女性28例で,観察開始時平均年齢は48.5±8.2歳 (31〜67歳),平均観察期間は12.9±4.5年 (47〜249カ月) である.これらの対象例には,原則として年に1回の肝機能とRPHA法およびPHA法によるHBs抗原・HBs抗体の測定,EIA法によるe抗原・e抗体の測定を行った.各genotypeの検出頻度は,Aが2例 (4%),Bが24例 (46%),Cが26例 (50%) であった.慢性疾患例に高頻度とされるgenotypeCでもHBs抗原が陰転化し予後良好な症例が存在したことが注目された.観察開始時からHBs抗原消失までの期間はgenotypeBにおいてgenotypeCより有意に短期間 (8.3±3.9年,10.6±4.1年,p<0.05) であったが,HBs抗原消失年齢においては差は認められず(58.4±8.6歳,58.5±7.8歳),HBs抗原の消失には,genotypeよりはむしろHBVの持続感染の期間が関与していると推察された.HBs抗原消失前のALTの最大値の平均はgenotypeBに比しgenotypeCが高値の傾向であったが (46.5±65.0 IU/L, 63.9±116.7 IU/L) 有意差は認められなかった.GenotypeB ではHBs抗原消失前後を通じ,全例e抗体持続続陽性であったが,genotypeCではe抗体持続陽性は81%で,e抗体の出現が遅れる症例やe抗体価が低値の例が散見され,genotype間の臨床像の相違が示唆された.

Randomly selected 52 HBV carrier residents who had lost HBsAg during a annual health-screening program (HBsAg/anti-HBs : RPHA, HBeAg/anti-HBe: EIA, serum ALT level) between August 1979 and July 2000 were enrolled in the present study. The subjects comprised 24 males and 28 females with a mean age at the start of follow-up of 48.5±8.2 years. The mean follow-up period was 12.9±4.5 years. Genotyping by RFLP method revealed 2(4%) of genotype A, 24(46%) of genotype B and 26(50%) of genotype C. Although disappearance of HBsAg occurred significantly earlier in genotype B than in genotype C (8.3±3.9 vs. 10.6±4.1 years, p<0.05), no significant difference was noted in the mean age of HBsAg disappearance between both groups suggesting that the duration of HBV infection played more important role in loss of HBsAg rather than difference in genotype. The mean maximum ALT level before loss of HBsAg tended to be higher in genotype C than in genotype B (63.9±116.7 vs. 46.5±65.0 IU/L). In all genotype B individuals, anti-HBe remained positive during follow-up, while, it did in 81% in genotype C ones and in some of genotype C, delayed appearance of anti-HBe or low anti-HBe titer was observed. It is speculated that these phenomena were caused by genotypical difference, however, stronger attention should be paid to that there existed a number of genotype C carriers who had lived their healthy lives irrespective of their dominance in chronic liver diseases.