- 學位論文
B型肝炎病毒隱性感染在肝細胞癌家族之盛行率及臨床特徵
Prevalence and Clinical Features of Occult Hepatitis B Virus Infection in Families with Hepatocellular Carcinoma
摘要
研究背景：肝細胞癌（hepatocellular carcinoma；HCC）病例家族是B型肝炎病毒感染的高危險性族群，本研究目的在於調查HCC家族B型肝炎隱性感染的家族聚集程度，及探討B型肝炎隱性感染的臨床表徵。材料與方法：研究個案來自兩個來源：HBsAg陽性之HCC指標病例一等親共601名HBsAg陰性個案，他們來自251個家族；另一個是來自公務人員世代所選取的602名HBsAg陰性個案做為對照組，對照組和HCC指標病例親屬在年齡上配對。我們採用Nested PCR偵測 HBV X 和Core基因區，X基因區可測得HBV DNA者，才進一步分析Core 基因區。B型肝炎病毒隱性感染的定義為X基因區可測得HBV DNA者。對於隱性感染者，進一步使用Real time PCR測量病毒量。結果：HCC家族B型肝炎隱性感染盛行率(26.0%)顯著高於對照組(18.4%)(P=0.0017)，且具有顯著家族聚集(corrected familial recurrence risk ratio:2.59)。和家族內隱性感染正相關的因子包括anti-HCV陽性(P=0.0332)、HCC指標病例為女性(P=0.0433)、及家中HBsAg人數( P trend=0.0414)。對Core和X基因區皆可測得者的HBV DNA濃度顯著高於只有X基因區可測得者（P<0.0001）。ALT/AST異常及肝臟實質病變（由超音波測量)的危險性隨無隱性感染、只有X基因區可測得者、X和Core基因區皆可測得者漸增，對於X和Core基因區皆可測得者和無隱性感染者比較，OR (95% CI) 對於ALT異常、AST異常和肝臟實質病變，分別為5.31 (95%CI=2.66-10.60)、4.15 (95%CI=2.10-8.24)、和2.19 (95%CI=1.40-6.06)。結論：HCC病例家族中有B型肝炎隱性感染的家族聚集。B型肝炎隱性感染可能導致肝臟疾病。
並列摘要
Background & Aims: Taiwan is an endemic area of hepatitis B virus (HBV) infection. This study aimed to assess the extent to which occult HBV infection aggregates in families with HCC, and to determine the association between occult HBV infection and hepatic abnormalities. Material and Methods: Study subjects consisted of 601 HBsAg-negative first-degree relatives from 251 families with HCC and 602 HBsAg-negative, age-matched unrelated individuals as controls. Occult HBV infection was defined by the detection of HBV DNA in serum by PCR amplification assay on the X region of HBV. PCR assay on core region was performed in subjects who showed positivity in X region. Results: Occult HBV infection was detected in 26.0% of relatives from families with HCC and in 18.4% of controls (P=0.0017). The familial recurrence risk ratio for occult HBV infection was 2.59. Anti-HCV positivity, female gender of HCC proband, and number of HBsAg-positive relatives in a family were positively associated with an increased likelihood of occult HBV infection. Circulating HBV DNA was higher in relatives who showed positivity in both X and core regions than in those who showed positivity in the X region only (P<0.0001). The presence of occult HBV was associated with elevated ALT (odds ratios were 2.01 [95% CI: 1.06-3.80] and 5.31 [2.66-10.60], respectively, for positivity for X region and both X and core regions), irrespective of age, sex, alcohol drinking, and anti-HCV status. Conclusions: There is familial aggregation of occult HBV infection in families with HCC. Occult HBV infection may increase risk of hepatic abnormalities.