恩替卡韦附加栓塞干扰素疗法在未治疗的慢性乙型肝炎患者

StephenW

Entecavir Add-On Peg-interferon Therapy Plays a Positive Role in Reversing Hepatic Fibrosis in treatment-naïve Chronic Hepatitis B Patients: A Prospective and Randomized Controlled Trial
Jing-Mao Yang  1 , Li-Ping Chen  2 , Ya-Jie Wang  3 , Bei Lyu  4 , Hong Zhao  5 , Zhi-Yin Shang  1 , Jun Li  1 , Zhen-Yu Fan  1 , Sheng-Di Wu  4 , Xiao Ming  1 , Xian Li  1 , Shao-Ping Huang  1 , Ji-Lin Cheng  1
Affiliations
Affiliations

    1
    Department of Gastroenterology and Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201500, China.
    2
    Shanghai Medical College of Fudan University, Shanghai 200032, China.
    3
    Department of Gastroenterology and Hepatology, Jinshan Hospital, Fudan University, Shanghai 201500, China.
    4
    Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
    5
    Department of Gastroenterology and Hepatology, Dongyang People's Hospital, Dongyang, Zhejiang 322100, China.

    PMID: 32568867 DOI: 10.1097/CM9.0000000000000857

Abstract

Background: The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.

Methods: All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (n = 70) or peg-interferon add-on therapy from weeks 26 to 52 (n = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria.

Results: At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P < 0.001; combination therapy: 5.7 [3.0, 18.8] vs. 3.2 [2.0, 4.3] ng/mL, P < 0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs. 7.8 [5.4, 11.1] kPa, P = 0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs. 4.1% [3/73], P = 0.809) and HBeAg conversion rate (12.5% [7/56] vs. 11.0% [8/73], P = 0.787), as well as HBV-DNA, sustained virologic response (93.2% vs. 98.5%, P = 0.150) between the two groups.

Conclusions: Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.

Trial registration: ClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132.
Associated data

    ClinicalTrials.gov/NCT02849132

StephenW

恩替卡韦附加栓塞干扰素疗法在未治疗的慢性乙型肝炎患者中在逆转肝纤维化中发挥积极作用：一项前瞻性随机对照试验
杨敬茂1，陈丽萍2，王亚杰3，北柳4，洪昭5，尚志银1，李俊1，范振宇1，吴声迪4，小明1，仙丽1，黄少平1，程吉林1
隶属关系
隶属关系

    1个
    复旦大学上海公共卫生临床中心消化内科，上海201500
    2
    复旦大学上海医学院，上海200032
    3
    复旦大学附属金山医院消化内科，上海201500。
    4
    复旦大学附属中山医院消化内科，上海200032
    5
    东阳市人民医院消化内科，浙江东阳322100

    PMID：32568867 DOI：10.1097 / CM9.0000000000000857

抽象

背景：恩替卡韦（ETV）附加钉-干扰素治疗与未经治疗的乙型肝炎病毒（HBV）患者的ETV单药治疗相比仍存在争议。我们调查了在正在进行的ETV治疗中添加聚乙二醇干扰素是否会产生更好的疗效。

方法：所有患者均于2013年8月至2015年1月之间从上海公共卫生临床中心和中山医院招募。符合条件的HBV患者（n = 144）被随机分为（1：1）以接受ETV单药治疗（n = 70）或聚乙二醇干扰素加用治疗从第26周到52周（n = 74）。对患者进行了至少2年的随访。每3个月评估一次指标，包括乙型肝炎表面抗原（HBsAg）和乙型肝炎e抗原（HBeAg）血清转化率，持续的病毒学应答，瞬时弹性成像值和组织学评分，直至研究结束。 HBsAg丢失的患者比率被定义为主要终点标准。

结果：在第26周，两组均无患者发生HBsAg血清转化。在第52周时，单一疗法组的一名患者为HBsAg阴性，但联合疗法组无一例。单药治疗组的肝功能恢复效果明显好于联合治疗组。在第78周，联合组的一名患者发生了HBsAg血清转换。在第104周时，联合疗法组中只有3例患者的HBsAg阴性，而单一疗法中只有1例。与基线相比，平均丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平和瞬时弹性成像值明显降低。两组均显示甲胎蛋白下降良好（单一疗法：4.5 [2.8，7.1] vs. 2.2 [1.8，3.1] ng / mL，P <0.001；联合疗法：5.7 [3.0，18.8] vs. 3.2 [2.0， 4.3] ng / mL，P <0.001）和肝活检分数的改善结果。与单一疗法组相比，联合疗法组在组织学上有更好的改善（瞬时弹性成像值分别为6.6 [4.9，9.8]与7.8 [5.4，11.1] kPa，P = 0.028）。但是HBsAg转化率（1.8％[1/56] vs. 4.1％[3/73]，P = 0.809）和HBeAg转化率（12.5％[7/56] vs. 11.0％）没有显着差异[8/73]，P = 0.787）以及HBV-DNA在两组之间持续的病毒学应答（93.2％对98.5％，P = 0.150）。

结论：两种疗法均支持肝功能恢复和组织学改善。与单一疗法相比，联合疗法在HBsAg或HBeAg血清转化中未显示出更好的抗病毒疗效。然而，与单一疗法相比，联合疗法在逆转肝纤维化中发挥了更积极的作用。

试用注册：ClinicalTrials.gov：NCT02849132； https://clinicaltrials.gov/ct2/show/NCT02849132。
关联数据

    ClinicalTrials.gov/NCT02849132

StephenW

https://journals.lww.com/cmj/Abs ... _plays_a.99200.aspx