中国肝脏病杂志（电子版）
中國肝髒病雜誌（電子版）
중국간장병잡지（전자판）
CHINESE JOURNAL OF LIVER DISEASES(ELECTRONIC VERSION)
2015年
1期
95-101
,共7页
高歌%徐永红%张凤娟%韩冬梅%边城
高歌%徐永紅%張鳳娟%韓鼕梅%邊城
고가%서영홍%장봉연%한동매%변성
肝硬化%肝炎病毒,乙型%核苷(酸)类似物%突变%肝细胞癌
肝硬化%肝炎病毒,乙型%覈苷(痠)類似物%突變%肝細胞癌
간경화%간염병독,을형%핵감(산)유사물%돌변%간세포암
Cirrhosis%Hepatitis B virus%Nucleos(t)ide analogue%Mutation%Hepatocellular carcinoma
目的：研究HBV相关肝硬化患者核苷（酸）类似物（NUCs）治疗过程中，HCC发生与HBV P区耐药突变模式及患者治疗方案的关系，为评估HCC发生风险，指导HBV相关肝硬化抗病毒治疗提供帮助。方法回顾性分析2012年5月至2014年5月青岛市传染病医院收治的79例基线（治疗前）为HBV相关肝硬化患者，既往服用NUCs出现疗效不佳或病毒学突破，此次住院采用焦磷酸测序检测到HBV P区耐药突变患者的临床资料，根据有无进展为HCC将病例分为肝癌组和对照组，比较两组间在基线肝硬化水平（代偿期/失代偿期）、基线HBV DNA、基线ALT、基线AST、性别、年龄、HBsAg、HBeAg、AFP及耐药突变模式等方面的差异。根据既往初始用药，分析初始服用阿德福韦酯（ADV）患者与初始服用拉米夫定（LAM）患者在HCC发生和病毒突变模式上的差异。结果79例患者中，有10例进展为HCC。肝癌组患者平均年龄[（58.30±6.40）岁]大于对照组[（51.64±7.69）岁]（t=2.609，P=0.011）；肝癌组患者平均AFP水平[（566.24±563.79）ng/ml]大于对照组[（17.32±77.04）ng/ml]（t=－7.879，P=0.000）；肝癌组出现rtA181T突变的比例（70.0%）、年龄＞50岁患者的比例（100.0%）均显著高于对照组（分别为24.6%、52.2%）（χ2=6.488，P=0.011；χ2=6.365， P=0.012）。初始服用ADV出现疗效不佳或病毒学突破患者HCC发生率（23.7%）显著大于初始服用LAM出现疗效不佳或病毒学突破患者（2.8%）（χ2=5.240，P=0.022）。结论 HBV相关肝硬化患者NUCs治疗过程中，HBV rtA181T突变可能与HCC的发生有关；年龄＞50岁的HBV相关肝硬化患者，服用ADV出现疗效不佳或病毒学突破，需进行HBV P区耐药突变检测，并密切监测HCC发生；肝硬化患者初始服用ADV发生耐药突变较初始服用LAM发生耐药突变可能更容易进展为HCC。
目的：研究HBV相關肝硬化患者覈苷（痠）類似物（NUCs）治療過程中，HCC髮生與HBV P區耐藥突變模式及患者治療方案的關繫，為評估HCC髮生風險，指導HBV相關肝硬化抗病毒治療提供幫助。方法迴顧性分析2012年5月至2014年5月青島市傳染病醫院收治的79例基線（治療前）為HBV相關肝硬化患者，既往服用NUCs齣現療效不佳或病毒學突破，此次住院採用焦燐痠測序檢測到HBV P區耐藥突變患者的臨床資料，根據有無進展為HCC將病例分為肝癌組和對照組，比較兩組間在基線肝硬化水平（代償期/失代償期）、基線HBV DNA、基線ALT、基線AST、性彆、年齡、HBsAg、HBeAg、AFP及耐藥突變模式等方麵的差異。根據既往初始用藥，分析初始服用阿德福韋酯（ADV）患者與初始服用拉米伕定（LAM）患者在HCC髮生和病毒突變模式上的差異。結果79例患者中，有10例進展為HCC。肝癌組患者平均年齡[（58.30±6.40）歲]大于對照組[（51.64±7.69）歲]（t=2.609，P=0.011）；肝癌組患者平均AFP水平[（566.24±563.79）ng/ml]大于對照組[（17.32±77.04）ng/ml]（t=－7.879，P=0.000）；肝癌組齣現rtA181T突變的比例（70.0%）、年齡＞50歲患者的比例（100.0%）均顯著高于對照組（分彆為24.6%、52.2%）（χ2=6.488，P=0.011；χ2=6.365， P=0.012）。初始服用ADV齣現療效不佳或病毒學突破患者HCC髮生率（23.7%）顯著大于初始服用LAM齣現療效不佳或病毒學突破患者（2.8%）（χ2=5.240，P=0.022）。結論 HBV相關肝硬化患者NUCs治療過程中，HBV rtA181T突變可能與HCC的髮生有關；年齡＞50歲的HBV相關肝硬化患者，服用ADV齣現療效不佳或病毒學突破，需進行HBV P區耐藥突變檢測，併密切鑑測HCC髮生；肝硬化患者初始服用ADV髮生耐藥突變較初始服用LAM髮生耐藥突變可能更容易進展為HCC。
목적：연구HBV상관간경화환자핵감（산）유사물（NUCs）치료과정중，HCC발생여HBV P구내약돌변모식급환자치료방안적관계，위평고HCC발생풍험，지도HBV상관간경화항병독치료제공방조。방법회고성분석2012년5월지2014년5월청도시전염병의원수치적79례기선（치료전）위HBV상관간경화환자，기왕복용NUCs출현료효불가혹병독학돌파，차차주원채용초린산측서검측도HBV P구내약돌변환자적림상자료，근거유무진전위HCC장병례분위간암조화대조조，비교량조간재기선간경화수평（대상기/실대상기）、기선HBV DNA、기선ALT、기선AST、성별、년령、HBsAg、HBeAg、AFP급내약돌변모식등방면적차이。근거기왕초시용약，분석초시복용아덕복위지（ADV）환자여초시복용랍미부정（LAM）환자재HCC발생화병독돌변모식상적차이。결과79례환자중，유10례진전위HCC。간암조환자평균년령[（58.30±6.40）세]대우대조조[（51.64±7.69）세]（t=2.609，P=0.011）；간암조환자평균AFP수평[（566.24±563.79）ng/ml]대우대조조[（17.32±77.04）ng/ml]（t=－7.879，P=0.000）；간암조출현rtA181T돌변적비례（70.0%）、년령＞50세환자적비례（100.0%）균현저고우대조조（분별위24.6%、52.2%）（χ2=6.488，P=0.011；χ2=6.365， P=0.012）。초시복용ADV출현료효불가혹병독학돌파환자HCC발생솔（23.7%）현저대우초시복용LAM출현료효불가혹병독학돌파환자（2.8%）（χ2=5.240，P=0.022）。결론 HBV상관간경화환자NUCs치료과정중，HBV rtA181T돌변가능여HCC적발생유관；년령＞50세적HBV상관간경화환자，복용ADV출현료효불가혹병독학돌파，수진행HBV P구내약돌변검측，병밀절감측HCC발생；간경화환자초시복용ADV발생내약돌변교초시복용LAM발생내약돌변가능경용역진전위HCC。
Objective During hepatitis B virus-related cirrhosis patients with nucleos (t) ide analogues (NUCs) treatment, to investigate the relationship between hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) mutations and patient initial taking NUCs.Methods The clinical data of 79 patients with baseline for HBV related liver cirrhosis, who experienced poor efifcacy or virological breakthrough during NUCs treatment and genotyped by pyroscquencing for 9 mutation sites in the HBV P gene that have been previously correlated to NUC efifcacy, were analyzed, retrospectively. Analysis of patients with previous drug use, drug-resistant mutation patterns. According to HCC occurred, we divided 79 patients into two groups to compare the differences in cirrhosis at baseline levels (compensated/decompensated), baseline HBV DNA, baseline alanine aminotransferase (ALT), baseline aspartate aminotransferase (AST), sex, age, HBsAg, HBeAg and resistance mutation patterns and other aspects of comparison, respectively. According to previous initial application LAM or ADV, patients were divided into two groups to compare the differences in HCC patients and virus mutation patterns, respectively.Results HCC patients were found in 12.66% (10/79) of the 79 patients. The average age of HCC group was older than that of liver cirrhosis (LC) group [(58.30 ± 6.40) years old vs. (51.64 ± 7.69) years old;t = 2.609,P = 0.011]. The serum AFP level at HCC group was higher than that at LC group [(566.24 ± 563.79) ng/ml vs. (17.32 ± 77.04) ng/ml;t =-7.879,P = 0.000]. The presence of rtA181T mutation and age>50 years occurred more frequently in HCC group (70.0%, 100.0%) than those in LC group (24.6%, 52.2%) (χ2 = 6.488,P = 0.011;χ2 = 6.365,P = 0.012), respectively. The initial taking ADV or LAM patients were found in 48.10% (38/79) or 45.57% (36/79) of the 79 patients, respectively. HCC occurred more frequently in the initial taking ADV group (23.7%) than that in the initial taking LAM group (2.8%) (χ2 = 5.240,P = 0.022).Conclusions During HBV-related cirrhosis patients with NUCs treatment, emergence of the rtA181T mutant might be associated with occurrence of HCC. HBV-related cirrhosis patients who are older than 50 years old and initial taking ADV poor efifcacy or virologic breakthrough occurs, needed to detect HBV P gene mutation and close follow-up of HCC development in the subsequent courses of antiviral therapy. An initial dose of ADV-resistant mutation in patients with cirrhosis compared with an initial dose of LAM-resistant mutation may be more likely to progress to HCC.
