中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2013年
9期
679-683
,共5页
谭友文%张园海%江伟俊%邢茂迎%满晓波%毛建忠%葛国洪%吴翠松%祝美琴
譚友文%張園海%江偉俊%邢茂迎%滿曉波%毛建忠%葛國洪%吳翠鬆%祝美琴
담우문%장완해%강위준%형무영%만효파%모건충%갈국홍%오취송%축미금
癌,肝细胞%复发%肿瘤转移%肝炎病毒,乙型%变异
癌,肝細胞%複髮%腫瘤轉移%肝炎病毒,乙型%變異
암,간세포%복발%종류전이%간염병독,을형%변이
Carcinoma,hepatocellular%Recurrence%Neoplasm metastasis%Hepatitis B virus%Variation
目的 探讨肝细胞癌(HCC)复发或转移与HBV DNA水平及其基本核心启动子(BCP)区1762/1764双突变的关系. 方法 选择163例HCC患者进行120周的随访,收集患者一般资料、生物化学指标、瘤体资料、HBV病毒学指标等,用实时定量PCR检测HBV DNA水平,基因测序法检测BCP区1762/1764双突变情况,并用logistic回归分析HCC复发或转移的发生率与这些资料的关系.两均数比较采用两独立样本t检验；多个样本均数比较采用方差分析；计数资料采用x2检验；筛选影响因素采用二分类logistic回归分析. 结果 共有157例患者进入最终的有效追踪.110例在手术后或肝动脉栓塞化疗术(TACE)后2年内出现肿瘤的复发或转移,其发生率随着时间的推移而逐渐上升,在12、24、48、72、96周和120周分别为2.55％(4例)、8.92％ (14例)、17.83％ (28例)、40.76％ (64例)、58.60％ (92例)和70.06％(110例).对基线资料的单因素分析显示血清高水平Y-谷氨酰转移酶、无包膜瘤体、门静脉栓塞、较大肝癌、BCP变异、HBV DNA水平与HCC的高复发或转移率有关.多因素分析显示HBV DNA水平和BCP区1762/1764双突变与HBV相关性HCC复发和转移高度相关.复发或转移率随着HBV DNA水平的上升而增加,在基线HBV DNA水平＜3log10拷贝/ml的HCC患者中,肿瘤的复发或转移率为42.1％ (8/19)；在基线HBV DNA水平≥5log10拷贝/ml的HCC患者中,肿瘤的复发或转移率升为87.0％ (67/77,x 2=22.308,P＜0.01).在157例HCC患者中,BCP区1762/1764双突变阴性43例,有22例(51.2％)发生肿瘤的复发或转移；BCP区1762/1764双突变阳性114例中有88例(77.2％)发生肿瘤的复发或转移(x2=6.022,P＜0.05).通过logistic回归分析,显示BCP区1762/1764双突变阳性患者较双突变阴性患者有更高的HCC复发或转移率(OR=5.264,95％可信区间为1.436～ 12.574).结论 HBV BCP区1762/1764双突变和基线HBV DNA水平与HBV相关性HCC复发和转移相关.
目的 探討肝細胞癌(HCC)複髮或轉移與HBV DNA水平及其基本覈心啟動子(BCP)區1762/1764雙突變的關繫. 方法 選擇163例HCC患者進行120週的隨訪,收集患者一般資料、生物化學指標、瘤體資料、HBV病毒學指標等,用實時定量PCR檢測HBV DNA水平,基因測序法檢測BCP區1762/1764雙突變情況,併用logistic迴歸分析HCC複髮或轉移的髮生率與這些資料的關繫.兩均數比較採用兩獨立樣本t檢驗；多箇樣本均數比較採用方差分析；計數資料採用x2檢驗；篩選影響因素採用二分類logistic迴歸分析. 結果 共有157例患者進入最終的有效追蹤.110例在手術後或肝動脈栓塞化療術(TACE)後2年內齣現腫瘤的複髮或轉移,其髮生率隨著時間的推移而逐漸上升,在12、24、48、72、96週和120週分彆為2.55％(4例)、8.92％ (14例)、17.83％ (28例)、40.76％ (64例)、58.60％ (92例)和70.06％(110例).對基線資料的單因素分析顯示血清高水平Y-穀氨酰轉移酶、無包膜瘤體、門靜脈栓塞、較大肝癌、BCP變異、HBV DNA水平與HCC的高複髮或轉移率有關.多因素分析顯示HBV DNA水平和BCP區1762/1764雙突變與HBV相關性HCC複髮和轉移高度相關.複髮或轉移率隨著HBV DNA水平的上升而增加,在基線HBV DNA水平＜3log10拷貝/ml的HCC患者中,腫瘤的複髮或轉移率為42.1％ (8/19)；在基線HBV DNA水平≥5log10拷貝/ml的HCC患者中,腫瘤的複髮或轉移率升為87.0％ (67/77,x 2=22.308,P＜0.01).在157例HCC患者中,BCP區1762/1764雙突變陰性43例,有22例(51.2％)髮生腫瘤的複髮或轉移；BCP區1762/1764雙突變暘性114例中有88例(77.2％)髮生腫瘤的複髮或轉移(x2=6.022,P＜0.05).通過logistic迴歸分析,顯示BCP區1762/1764雙突變暘性患者較雙突變陰性患者有更高的HCC複髮或轉移率(OR=5.264,95％可信區間為1.436～ 12.574).結論 HBV BCP區1762/1764雙突變和基線HBV DNA水平與HBV相關性HCC複髮和轉移相關.
목적 탐토간세포암(HCC)복발혹전이여HBV DNA수평급기기본핵심계동자(BCP)구1762/1764쌍돌변적관계. 방법 선택163례HCC환자진행120주적수방,수집환자일반자료、생물화학지표、류체자료、HBV병독학지표등,용실시정량PCR검측HBV DNA수평,기인측서법검측BCP구1762/1764쌍돌변정황,병용logistic회귀분석HCC복발혹전이적발생솔여저사자료적관계.량균수비교채용량독립양본t검험；다개양본균수비교채용방차분석；계수자료채용x2검험；사선영향인소채용이분류logistic회귀분석. 결과 공유157례환자진입최종적유효추종.110례재수술후혹간동맥전새화료술(TACE)후2년내출현종류적복발혹전이,기발생솔수착시간적추이이축점상승,재12、24、48、72、96주화120주분별위2.55％(4례)、8.92％ (14례)、17.83％ (28례)、40.76％ (64례)、58.60％ (92례)화70.06％(110례).대기선자료적단인소분석현시혈청고수평Y-곡안선전이매、무포막류체、문정맥전새、교대간암、BCP변이、HBV DNA수평여HCC적고복발혹전이솔유관.다인소분석현시HBV DNA수평화BCP구1762/1764쌍돌변여HBV상관성HCC복발화전이고도상관.복발혹전이솔수착HBV DNA수평적상승이증가,재기선HBV DNA수평＜3log10고패/ml적HCC환자중,종류적복발혹전이솔위42.1％ (8/19)；재기선HBV DNA수평≥5log10고패/ml적HCC환자중,종류적복발혹전이솔승위87.0％ (67/77,x 2=22.308,P＜0.01).재157례HCC환자중,BCP구1762/1764쌍돌변음성43례,유22례(51.2％)발생종류적복발혹전이；BCP구1762/1764쌍돌변양성114례중유88례(77.2％)발생종류적복발혹전이(x2=6.022,P＜0.05).통과logistic회귀분석,현시BCP구1762/1764쌍돌변양성환자교쌍돌변음성환자유경고적HCC복발혹전이솔(OR=5.264,95％가신구간위1.436～ 12.574).결론 HBV BCP구1762/1764쌍돌변화기선HBV DNA수평여HBV상관성HCC복발화전이상관.
Objective To study the relationship between metastasis or recurrence of hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) DNA load or the presence of double mutation at 1762/1764 in the basic core promoter (BCP).Methods One-hundred-and-fifty-seven patients with HCC were included in the study.Events of tumor metastasis or recurrence were recorded during 120 weeks of clinical follow-up after treatment by surgery or transarterial chemoembolization (TACE).The 1-year follow-up included monthly alpha fetoprotein (AFP) measurement and abdominal ultrasonography (US),as well as helical computed tomographic (CT) scan performed every 3 months.Follow-up beyond 1-year (surveillance) included AFP measurement and abdominal US every 2 months and helical CT scan every 6 months.Suspected metastasis or recurrence was investigated by hepatic angiography and confirmed according to the combined imaging findings.Serum HBV DNA level was measured by real-time PCR.HBV genotypes were determined by PCR-restriction fragment length polymorphism analysis.Results Of the 157 HCC cases 110 experienced tumor metastasis or recurrence; the cumulative probability of post-treatment HCC metastasis or recurrence was 4 (2.55％) at week 12,14 (8.92％) at week 24,28 (17.83％) at week 48,64 (40.76％) at week 72,92 (58.60％) at week 96,and 110 (70.06％) at week 120.Multivariate analysis indicated that both the BCP 1762/1764 double mutations and HBV DNA levels were risk factors for HCC recurrence or metastasis.In particular,the incidence of HCC recurrence or metastasis increased with baseline serum HBV DNA levels in a dose-response manner,ranging from 8/19 (42.1％) for ＜ 3 log10 copies/ml HBV DNA to 35/61 (57.3％) for 3-5 log10 copies/ml and 67/77 (87.0％)for ＞ 5 log10 copies/ml.After adjusting for potential confounders,serum HBV DNA level remained independently associated with HCC metastasis or recurrence.HCC recurrence or metastasis occurred in 22/43 (51.2％) of patients without BCP 1762/1764 mutations and 88/114 (77.2％) of patients with BCP 1762/1764 mutations.The adjusted odds ratio for patients infected with BCP 1762/1764 double mutation HBV,compared with those infected with non-BCP 1762/1764 mutation HBV,was 5.264 (95％ CI:1.436-12.574,P ＜ 0.05).Conclusion Infection with HBV carrying the BCP 1762/1764 double mutation and presence of high HBV DNA load are independent risk factors for developing HCC metastasis or recurrence after surgery or TACE.
