PegIFN-α治疗ALT正常或轻度升高METAVIR评分≥G2S2HBeAg阴性慢性乙型肝炎的疗效评价

发布时间：2018-03-16 14:17

  本文选题：HBeAg阴性慢性乙型肝炎　切入点：丙氨酸氨基转移酶　出处：《兰州大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景:乙型肝炎病毒(Hepatitis B Virus,HBV)是导致肝硬化(Liver Cirrhosis,LC)和肝癌(Hepatocellular Carcinoma,HCC)的最主要因素,慢性乙型肝炎(Chronic Hepatitis B,CHB)仍然带来了重大的健康和经济负担,特别是在亚太地区国家。越来越多的临床与基础研究表明,HBe Ag(Hepatitis B e Antigen)阴性CHB在HBV感染的慢性病毒性肝炎患者中所占的比例逐年升高。目前临床上主要依据丙氨酸氨基转移酶(Alanine Aminotransferase,ALT)高于2倍正常值上限(Upper Limit of Normal Value,ULN)启动抗病毒治疗,而越来越多的资料表明,ALT正常或轻度升高的HBe Ag阴性患者肝组织存在中重度炎症或纤维化病变者不在少数。聚乙二醇干扰素α是一类兼有免疫调节与抗病毒效应的抗病毒药物,现有的研究资料均提示聚乙二醇干扰素α对HBe Ag阳性或HBe Ag阴性CHB患者均有较强的抗病毒效应,但很少有研究针对ALT正常或轻度异常且病理证实存在中重度病变的HBe Ag阴性CHB患者进行聚乙二醇干扰素α的治疗及随访观察,评估其对这部分患者的疗效及疗效预测问题。目的:分析聚乙二醇干扰素α对ALT正常或轻度升高且METAVIR评分≥G2S2的HBe Ag阴性CHB患者的疗效及疗效预测因素。方法:对ALT正常或轻度升高且METAVIR评分≥G2S2的HBe Ag阴性CHB患者进行连续48周的聚乙二醇干扰素α治疗,收集治疗前、治疗12周、24周、36周、48周相关的生化学、病毒学、血清学、肝脏硬度值(Liver Stiffness Measurement,LSM)等资料进行回顾性分析。结果:(1)根据纳入排除标准,共有42例ALT正常或轻度升高HBe Ag阴性CHB患者进入本次研究,平均年龄为37.62±10.12岁,男性24例,女性18例,14例患者治疗前血清HBV DNA低于检测下限肝组织HBV DNA存在复制,28例患者治疗前血清中HBV DNA存在复制。(2)治疗过程中,ALT水平呈波动性升高,至48周时上升至最高水平,与基线ALT水平相比,差异具有统计学意义(P0.05);血清HBV DNA水平逐渐下降,基线血清HBV DNA水平与各随访点血清HBV DNA水平相比,差异具有统计学意义(P0.05);HBs Ag(Hepatitis B s Antigen)滴度逐渐下降,基线HBs Ag滴度与各随访点HBs Ag滴度及各随访点之间差异均具有统计学意义(P0.05);LSM波动性下降,基线LSM与12周、36周LSM差异具有统计学意义。(3)14例治疗前血清HBV NDA低于检测下限的患者,治疗48周结束时,HBs Ag水平由基线时的(2.74±1.03)log10IU/m L下降至(1.79±1.69)log10IU/m L,有4例患者HBs Ag滴度达到100IU/ml,占28.57%(4/14),其中1例患者发生了HBs Ag的清除,完全应答(Complete Response,CR)率为7.14%(1/14)。(4)14例治疗前血清HBV DNA低于检测下限的患者,治疗过程中,血清ALT水平至12周、24周稍有下降,后逐渐升高,下降及升高水平无统计学意义(P0.05);血清HBs Ag滴度逐渐下降,24周后下降水平具有统计学意义(P0.05);LSM波动性升高,升高水平无统计学意义(P0.05)。(5)28例治疗前血清中HBV DNA复制的患者,治疗48周结束时,22例患者血清HBV DNA低于检测下限,病毒学应答(Virological Response,VR)率为78.60%(22/28),原发无应答与部分应答率为17.90%(5/28);6例患者HBs Ag滴度达到100IU/ml,占21.43%(6/28),其中1例患者发生了HBs Ag的清除,完全应答率为3.57%(1/28)。(6)28例治疗前血清HBV DNA复制的患者,治疗过程中,病毒学应答组ALT水平在12周升高,后逐渐下降,升高及下降水平无统计学意义(P0.05);血清HBV DNA水平逐渐下降,基线与12周、24周、36周、48周之间差异具有统计学意义(P0.05);HBs Ag滴度逐渐下降,基线与36周、基线与48周、12周与48周、24周与36周、24周与48周、36周与48周之间差异具有统计学意义(P0.05);LSM波动性下降,基线与12周、24周、36周之间差异具有统计学意义(P0.05)。病毒学应答组与无应答组在年龄、性别分布、家族史有无、白细胞计数、血小板计数、基线ALT水平、基线HBV DNA水平、基线HBs Ag滴度、基线LSM及治疗各随访点ALT水平、HBV DNA水平、HBs Ag滴度、LSM均无统计学差异(P0.05)。(7)多因素二分类logistics回归分析显示没有能预测治疗48周时病毒学应答的因素(P0.05)。结论:(1)聚乙二醇干扰素α对ALT正常或轻度升高METAVIR评分≥G2S2的HBe Ag阴性CHB患者治疗48周结束时具有较高的抗病毒效应,病毒学应答率为78.60%,与ALT≥2ULN的HBe Ag阴性CHB患者疗效相似;(2)聚乙二醇干扰素α对ALT正常或轻度升高METAVIR评分≥G2S2且基线HBV DNA阴性的HBe Ag阴性CHB患者可以显著降低HBs Ag滴度,尤其是在治疗24周以后。
[Abstract]:Background: hepatitis B virus (Hepatitis B Virus HBV (Liver Cirrhosis) is leading to cirrhosis, and hepatocellular carcinoma (LC) Hepatocellular Carcinoma, HCC) the most important factor in chronic hepatitis B (Chronic, Hepatitis, B, CHB) still pose a major health and economic burden, especially in countries in the Asia Pacific Region. The basic and clinical more and more studies show that HBe Ag (Hepatitis B e Antigen) CHB negative for HBV infection in patients with chronic viral hepatitis in the proportion increased year by year. At present the main clinical basis of alanine aminotransferase (Alanine, Aminotransferase, ALT) 2 times higher than the upper limit of normal (Upper Limit of Normal Value, ULN) to start antiviral therapy, and more and more data show that the presence of moderate to severe inflammation or fibrosis ALT normal or mildly elevated HBe Ag negative patients with liver tissue were few. Interferon alpha is a Both types of immune regulation of antiviral drugs and antiviral effect, the available data suggest that pegylated interferon alpha on HBe Ag or HBe CHB positive Ag negative patients had strong antiviral effects, but few studies have focused on the treatment and follow-up of ALT normal or mildly abnormal and pathological lesions confirmed the presence of severe HBe Ag negative CHB patients pegylated interferon alpha, the assessment for these patients to predict efficacy and problems. Objective: to analyze the pegylated interferon alpha on ALT normal or slightly elevated and predict the effect of METAVIR score was G2S2 HBe Ag negative CHB patients and effect factors. Methods: ALT normal or slightly elevated and METAVIR score was G2S2 HBe Ag negative CHB patients were 48 consecutive weeks of therapy with pegylated interferon alpha, collected before treatment, treatment for 12 weeks, 24 weeks, 36 weeks, 48 weeks of related biochemistry, virology, Serum, liver stiffness values (Liver Stiffness Measurement, LSM), were retrospectively analyzed. Results: (1) according to the inclusion and exclusion criteria, a total of 42 cases of ALT normal or slightly elevated HBe Ag negative CHB patients in this study, the average age was 37.62 + 10.12 years old, male 24 cases, female 18 cases, 14 patients before treatment serum HBV DNA in liver tissue below the detection limit HBV DNA replication, 28 patients were treated with HBV DNA in serum before replication. (2) in the course of treatment, the level of ALT increased volatility, to 48 weeks rose to the highest level, compared with the baseline level of ALT, the difference was statistically significant (P0.05); the serum HBV DNA level decreased compared to baseline serum HBV DNA level and the follow-up serum HBV DNA level, the difference was statistically significant (P0.05); HBs Ag (Hepatitis B s Antigen) was gradually decreased, baseline HBs titer of Ag and HBs Ag were all follow-up points And the differences between each follow-up point were statistically significant (P0.05); LSM volatility decreased baseline LSM and 12 weeks, 36 weeks were statistically significant difference in LSM. (3) of 14 patients before treatment serum HBV NDA below the detection limit of the end of 48 weeks of treatment, the level of Ag by HBs at baseline (2.74 + 1.03) log10IU/m L down to (1.79 + 1.69) log10IU/m L, 4 cases of patients with HBs Ag titer reached 100IU/ml, accounting for 28.57% (4/14), of which 1 cases occurred in patients with clear HBs Ag, complete response (Complete Response CR) rate was 7.14% (1/14). (4) of 14 patients with refractory before treatment the serum HBV DNA was below the detection limit, the course of treatment, the serum level of ALT to 12 weeks, 24 weeks after a slight decline, gradually increased, decreased and increased the level of no statistical significance (P0.05); serum HBs Ag titer decreased gradually after 24 weeks decreased with statistical significance (P0.05); LSM volatility elevated, elevated levels of no statistical significance 涔，

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