中华传染病杂志
中華傳染病雜誌
중화전염병잡지
CHINESE JOURNAL OF INFECTIOUS DISEASES
2012年
8期
478-483
,共6页
谢榕%江建宁%苏明华%刘志红%钟少华%何丽霞%梁延秀%黄小红%郭稳稳%符武岛%胡家光%祝美琴
謝榕%江建寧%囌明華%劉誌紅%鐘少華%何麗霞%樑延秀%黃小紅%郭穩穩%符武島%鬍傢光%祝美琴
사용%강건저%소명화%류지홍%종소화%하려하%량연수%황소홍%곽은은%부무도%호가광%축미금
肝炎,乙型,慢性%核苷类%抗病毒药%抗药性,病毒%再治疗%变异(遗传学)
肝炎,乙型,慢性%覈苷類%抗病毒藥%抗藥性,病毒%再治療%變異(遺傳學)
간염,을형,만성%핵감류%항병독약%항약성,병독%재치료%변이(유전학)
Hepatitis B,chronic%Nucleosides%Antiviral agents%Drug resistance,viral%Retreatment%Variation (genetics)
目的 探讨慢性乙型肝炎(CHB)经治患者核苷类药物(NA)再治疗的效果及其耐药情况.方法 104例研究对象为初次无间断NA单药治疗至少3个月、停药后再次NA治疗至少1年的CHB患者.分为3组:A组39例,停药时已达慢性乙型肝炎防治指南中的停药标准；B组33例,停药时未达到停药标准但HBV DNA＜1.0×103拷贝/mL；C组32例,停药时未达到停药标准且HBV DNA＞1.0×103拷贝/mL.比较基线ALT、HBV DNA、HBeAg水平对再治疗的影响,以及3组患者不同再治疗方案的累计耐药率.套式PCR检测HBV P基因区耐药变异位点.统计学处理采用Wilcoxon秩和检验与x2检验.结果 基线ALT＜1.3×正常值上限(ULN)的患者ALT复常时间为2个月,ALT≥1.3×ULN的患者ALT复常时间为4个月,差异有统计学意义(Z=2.281,P=0.023);基线HBV DNA＜5 lg拷贝/mL的患者病毒学应答时间为1个月,HBV DNA≥5 lg拷贝/mL的患者为2个月,差异有统计学意义(Z=2.054,P=0.040);基线HBeAg阴性者病毒学应答及ALT复常时间分别为1个月和3个月,均早于HBeAg阳性者的2个月和4.5个月(Z=2.580、2.304,均P＜0.05).A组患者再治疗时病毒学应答时间及HBeAg血清学转换时间均比初次治疗快,分别为(1.61±1.76)、(3.38±3.34)个月和(3.48±4.06)、(9.92±11.22)个月(Z=-2.854、-1.094,均P＜0.05).A组病毒学应答时间早于B、C组,分别为(1.61±1.76)、(3.13±3.06)和(3.41±3.26)个月(Z=-2.025,P＜0.01；Z=2.474,P＜0.05).A组累计HBeAg血清学转换率高于B、C组,分别为80.0％、36.8％和37.5％(x2=4.368、5.100,均P＜0.05).共有13例发生耐药,4例检测到基因型耐药；继续原方案治疗C组累计耐药率明显高于A、B组,分别为44％、9％和0(x2=5.019、6.588,均P＜0.05)；采用无交叉耐药位点NA联合治疗方案的14例患者未发现耐药.结论 对于符合抗病毒治疗的CHB经治患者,停药后再治疗时间越早越好；没有交叉耐药位点的NA联合治疗方案可以降低经治患者的耐药风险.
目的 探討慢性乙型肝炎(CHB)經治患者覈苷類藥物(NA)再治療的效果及其耐藥情況.方法 104例研究對象為初次無間斷NA單藥治療至少3箇月、停藥後再次NA治療至少1年的CHB患者.分為3組:A組39例,停藥時已達慢性乙型肝炎防治指南中的停藥標準；B組33例,停藥時未達到停藥標準但HBV DNA＜1.0×103拷貝/mL；C組32例,停藥時未達到停藥標準且HBV DNA＞1.0×103拷貝/mL.比較基線ALT、HBV DNA、HBeAg水平對再治療的影響,以及3組患者不同再治療方案的纍計耐藥率.套式PCR檢測HBV P基因區耐藥變異位點.統計學處理採用Wilcoxon秩和檢驗與x2檢驗.結果 基線ALT＜1.3×正常值上限(ULN)的患者ALT複常時間為2箇月,ALT≥1.3×ULN的患者ALT複常時間為4箇月,差異有統計學意義(Z=2.281,P=0.023);基線HBV DNA＜5 lg拷貝/mL的患者病毒學應答時間為1箇月,HBV DNA≥5 lg拷貝/mL的患者為2箇月,差異有統計學意義(Z=2.054,P=0.040);基線HBeAg陰性者病毒學應答及ALT複常時間分彆為1箇月和3箇月,均早于HBeAg暘性者的2箇月和4.5箇月(Z=2.580、2.304,均P＜0.05).A組患者再治療時病毒學應答時間及HBeAg血清學轉換時間均比初次治療快,分彆為(1.61±1.76)、(3.38±3.34)箇月和(3.48±4.06)、(9.92±11.22)箇月(Z=-2.854、-1.094,均P＜0.05).A組病毒學應答時間早于B、C組,分彆為(1.61±1.76)、(3.13±3.06)和(3.41±3.26)箇月(Z=-2.025,P＜0.01；Z=2.474,P＜0.05).A組纍計HBeAg血清學轉換率高于B、C組,分彆為80.0％、36.8％和37.5％(x2=4.368、5.100,均P＜0.05).共有13例髮生耐藥,4例檢測到基因型耐藥；繼續原方案治療C組纍計耐藥率明顯高于A、B組,分彆為44％、9％和0(x2=5.019、6.588,均P＜0.05)；採用無交扠耐藥位點NA聯閤治療方案的14例患者未髮現耐藥.結論 對于符閤抗病毒治療的CHB經治患者,停藥後再治療時間越早越好；沒有交扠耐藥位點的NA聯閤治療方案可以降低經治患者的耐藥風險.
목적 탐토만성을형간염(CHB)경치환자핵감류약물(NA)재치료적효과급기내약정황.방법 104례연구대상위초차무간단NA단약치료지소3개월、정약후재차NA치료지소1년적CHB환자.분위3조:A조39례,정약시이체만성을형간염방치지남중적정약표준；B조33례,정약시미체도정약표준단HBV DNA＜1.0×103고패/mL；C조32례,정약시미체도정약표준차HBV DNA＞1.0×103고패/mL.비교기선ALT、HBV DNA、HBeAg수평대재치료적영향,이급3조환자불동재치료방안적루계내약솔.투식PCR검측HBV P기인구내약변이위점.통계학처리채용Wilcoxon질화검험여x2검험.결과 기선ALT＜1.3×정상치상한(ULN)적환자ALT복상시간위2개월,ALT≥1.3×ULN적환자ALT복상시간위4개월,차이유통계학의의(Z=2.281,P=0.023);기선HBV DNA＜5 lg고패/mL적환자병독학응답시간위1개월,HBV DNA≥5 lg고패/mL적환자위2개월,차이유통계학의의(Z=2.054,P=0.040);기선HBeAg음성자병독학응답급ALT복상시간분별위1개월화3개월,균조우HBeAg양성자적2개월화4.5개월(Z=2.580、2.304,균P＜0.05).A조환자재치료시병독학응답시간급HBeAg혈청학전환시간균비초차치료쾌,분별위(1.61±1.76)、(3.38±3.34)개월화(3.48±4.06)、(9.92±11.22)개월(Z=-2.854、-1.094,균P＜0.05).A조병독학응답시간조우B、C조,분별위(1.61±1.76)、(3.13±3.06)화(3.41±3.26)개월(Z=-2.025,P＜0.01；Z=2.474,P＜0.05).A조루계HBeAg혈청학전환솔고우B、C조,분별위80.0％、36.8％화37.5％(x2=4.368、5.100,균P＜0.05).공유13례발생내약,4례검측도기인형내약；계속원방안치료C조루계내약솔명현고우A、B조,분별위44％、9％화0(x2=5.019、6.588,균P＜0.05)；채용무교차내약위점NA연합치료방안적14례환자미발현내약.결론 대우부합항병독치료적CHB경치환자,정약후재치료시간월조월호；몰유교차내약위점적NA연합치료방안가이강저경치환자적내약풍험.
Objective To evaluate the efficacy and drug resistance profiles of nucleosides (NA) retreatment in NA experienced chronic hepatitis B (CHB) patients. Methods Totally 104 NA experienced CHB subjects were enrolled in this study.All these subjects had received at least 3 months NA monotherapy and stopped the treatment,and then received NA retreatment for at least one year.The subjects were divided into three groups according to the following criteria:reached the therapy endpoint of China guideline when they stopped NA-naive treatment (group A,n =39); did not reach the therapy endpoint when they stopped NA-naive treatment but hepatitis B virus (HBV) DNA＜1.0× 103 copy/mL (group B,n=33); and with HBV DNA＞1.0× 103 copy/mL (group C,n=32).The efficacy and drug resistance profiles of retreatment were compared among three groups. The effects of baseline alanine aminotransferase (ALT) levels,HBV DNA levels and HBeAg titers on the retreatment efficacies were analyzed. The mutations of HBV P gene were detected by nested polymerase chain reaction (PCR) and direct sequencing.The data were analyzd by Wilcoxon test and x2 test.Results The time to ALT normalization in patients with baseline ALT＜ 1.3 × upper limit normal (ULN) was shorter than that in patients with ALT≥1.3×ULN (2 months vs 4 months; Z=2.281,P=0.023).The time to virological response in patients with baseline HBV DNA＜5 lg copy/mL was shorter than that in patients with HBV DNA≥5 lg copy/mL (1 month vs 2 months; Z=2.054,P =0.040). The time to virological response and ALT normalization in baseline HBeAg negative were both shorter than those in patients with baseline HBeAg positive patents ( 1 month vs 3 months and 2 months vs 4.5 months,respectively; Z=2.580 and 2.304,respectively; both P＜0.05). The subjects in group A achieved virological response and HBeAg seroconversion after retreatment earlier compared to previous NA-naive therapy ([1.61 ± 1.76] months vs [3.48±4.066]months and [3.38 ± 3.34] months vs [9.92-11.22] months,respectively; Z=-2.854 and-1.094,respectively; both P＜0.05).The cumulative HBeAg seroconversion rate in group A was higher compared to those in group B and group C (80.0％ vs 36.8％ and 37.5％,respectively; x2 =4.368 and 5.100,respectively; both P＜0.05).Thirteen patients developed clinical resistance and four of them developed genotypic resistance proved by PCR direct sequencing.Among the patients retreated with the same regimen as previous in the C group,the cumulative resistance rate was highest compared to group A and B (44％ vs 9％ and 0,respectively; x2 =5.019 and 6.588,respectively;both P＜0.05).No resistance was detected in the 14 patients retreated with combined NA treatment without cross resistance.Conclusions For NA experienced CHB patients who fulfill the indication of antiviral therapy,the retreatment should be started as earlier as possible. Retreatment with NA combination without cross resistance can prevent (reduce) the risk of developing drug resistance.
