CAJ | 학술논문

目的探讨聚乙二醇干扰素(Peg-IFN) α-2a个体化治疗慢性乙型肝炎(CHB)患者的临床疗效。方法对92例慢性乙型肝炎患者给予Peg-IFN α-2a 180μg每周1次皮下注射。将12周HBV DNA仍为阳性的患者分为延长疗程(72周)组、联合核苷（酸）类似物（恩替卡韦或阿德福韦酯）组及常规治疗(48周)组。在治疗前、个体化治疗后12、24、36周以及停药后随访24周分别检测HBV基因型(PCR微板核酸杂交酶联免疫法)、HBV DNA载量（实时荧光定量PCR法）、HBsAg定量(ElecsysⅡ检测系统)，观察并比较各组患者病毒学应答及HBsAg水平下降情况，并分析影响疗效的因素。各组数据间比较采用t检验或X2检验，影响因素采用logistic回归法分析。结果延长疗程组的持久病毒学应答(SVR)率(78.3％，18/23)明显高于常规治疗组(38.1％，8/21)，x 2=7.33,P＜0.05 ;随访24周时的HBsAg水平平均下降幅度[（0.7±0.6）log10 IU/ml]也高于常规治疗组[(0.4±0.3) log10 IU/ml,t=2.11,P＜0.05]。联合恩替卡韦及阿德福韦酯组随访至24周时HBV DNA水平平均下降幅度分别达到（3.9±1.1）log10拷贝/ml及(3.7±1.3) log10拷贝/ml，明显大于常规治疗组（t值分别为8.45和6.31，P值均＜0.05），且该两组SVR率分别达到83.3％(15/18)及85.7％(12/14)，也明显高于常规治疗组（X2值分别为8.20和7.78，P值均＜0.05）;HBsAg水平平均下降幅度分别为(0.8±0.5) log10IU/ml和(0.9±0.3) log10 IU/ml，均明显高于常规治疗组[(0.4±0.3) log10 IU/ml，t值分别为3.05和4.58，P值均＜0.05]。Logitic回归分析显示HBV DNA载量和C基因型是影响病毒学应答的主要因素。结论 Peg-IFNα-2a抗病毒治疗早期应答不佳的患者可通过延长疗程至72周或联合恩替卡韦、阿德福韦酯等核苷（酸）类似物进行个体化治疗，可明显提高SVR率并降低HBsAg水平。
목적 탐토취을이순간우소(Peg-IFN) α-2a개체화치료만성을형간염(CHB)환자적림상료효。방법 대92례만성을형간염환자급여Peg-IFN α-2a 180μg매주1차피하주사。장12주HBV DNA잉위양성적환자분위연장료정(72주)조、연합핵감（산）유사물（은체잡위혹아덕복위지）조급상규치료(48주)조。재치료전、개체화치료후12、24、36주이급정약후수방24주분별검측HBV기인형(PCR미판핵산잡교매련면역법)、HBV DNA재량（실시형광정량PCR법）、HBsAg정량(ElecsysⅡ검측계통)，관찰병비교각조환자병독학응답급HBsAg수평하강정황，병분석영향료효적인소。각조수거간비교채용t검험혹X2검험，영향인소채용logistic회귀법분석。결과 연장료정조적지구병독학응답(SVR)솔(78.3％，18/23)명현고우상규치료조(38.1％，8/21)，x 2=7.33,P＜0.05 ;수방24주시적HBsAg수평평균하강폭도[（0.7±0.6）log10 IU/ml]야고우상규치료조[(0.4±0.3) log10 IU/ml,t=2.11,P＜0.05]。연합은체잡위급아덕복위지조수방지24주시HBV DNA수평평균하강폭도분별체도（3.9±1.1）log10고패/ml급(3.7±1.3) log10고패/ml，명현대우상규치료조（t치분별위8.45화6.31，P치균＜0.05），차해량조SVR솔분별체도83.3％(15/18)급85.7％(12/14)，야명현고우상규치료조（X2치분별위8.20화7.78，P치균＜0.05）;HBsAg수평평균하강폭도분별위(0.8±0.5) log10IU/ml화(0.9±0.3) log10 IU/ml，균명현고우상규치료조[(0.4±0.3) log10 IU/ml，t치분별위3.05화4.58，P치균＜0.05]。Logitic회귀분석현시HBV DNA재량화C기인형시영향병독학응답적주요인소。결론 Peg-IFNα-2a항병독치료조기응답불가적환자가통과연장료정지72주혹연합은체잡위、아덕복위지등핵감（산）유사물진행개체화치료，가명현제고SVR솔병강저HBsAg수평。
Objective To evaluate antiviral effects of Peg-IFNα-2a in patients with chronic hepatitis B. Methods 92 chronic hepatitis B patients were enrolled to receive the treatment with Peg-IFNα-2a 180μg subcutaneous injection once weekly. The patients who did not get early response were divided into 3 groups: group Ⅰ, extend the treatment to 72 weeks; group 2, combined with nucleot(s)ide analogue (entecavir or adefovir) treatment; group 3, continue the treatment until 48 weeks. HBV DNA and quantitative HBsAg were assessed at baseline, week12, 24,36 and after 24 weeks follow-up. Results Patients in group 1 had significantly higher SVR rate (78.3％) than patients in group 3 (38.1％, x2=7.33, P ＜ 0.05). The mean reduction of HBsAg in group 1 at 24 weeks of post-treatment follow up was higher than that in group 3 ( t=2.11,P ＜ 0.05). In group 2 the mean reductions ofHBV DNA at 24 weeks of post-treatment follow up were (3.9±1.1) log10 copy/ml and (3.7±1.3) log10 copy/ml respectively with combination of entecavir or adefovir, both of which were significantly higher than that in group 3( t =8.45 and 6.31, P ＜ 0.05); the SVR rates in the entecavir group and the adefovir group (83.3％ and 85.7％, respectively) were significantly higher than that in group 3 ( x 2 =8.20 and 7.78,P ＜ 0.05); the mean reductions of HBsAg in the entecavir group and the adefovir group [(0.8±0.5) log10 IU/ml and (0.9±0.3) log10 IU/ml, respectively ] were significantly greater thau group 3[ (0.4±0.3) log10 IU/ml, t =3.05 and 4.58, P ＜ 0.05]. The level of HBV DNA and C genotype were the main predictors of response. Conclusion Individualizing therapy by prolonging the duration of Peg-IFNα-2a treatment to 72 weeks or adding nucleoside analogues such as entecavir and adefovir in patients without early response may substantially increase the SVR rate and lead to the decrease of HBsAg.