聚乙二醇干扰素优于核苷（酸）类似物在慢性乙型肝炎的预

StephenW

Peginterferon is superior to nucleos(t)ide analogs for prevention of hepatocellular carcinoma in chronic hepatitis B                                 

• Kung-Hao Liang1,2,#,
• Chao-Wei Hsu1,#,
• Ming-Ling Chang1,
• Yi-Cheng Chen1,
• Ming-Wei Lai1 and
• Chau-Ting Yeh1,2,*
  

- Author Affiliations

                  

• 1Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
• 2Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
  

                  

• ↵*Corresponding author: Chau-Ting Yeh, M.D., Ph.D., Director, Liver Research Center, Chang Gung Memorial Hospital, 199, Tung                        Hwa North Road, Taipei, Taiwan, Tel: 886-3-3281200 ext 8125, Fax: 886-3-3282824, E-mail: [email protected]
  

                  

•                         

  ↵# These two authors contribute equally                        

  
  

               
                     Abstract

Background. Clinical factors associated with hepatocellular carcinoma (HCC) have been extensively studied in antiviral-treatment-naïve chronic hepatitis B virus (HBV) infected patients, but not in treatment-experienced patients. Due to the wide availability of antiviral agents which effectively suppressed HBV replication, we investigated HCC risk factors in treatment-experienced patients.

Methods. A cohort of 330 patients receiving pre-therapeutic liver biopsy was included to analyze HCC incidence in relationship with clinical parameters. Ultra-deep sequencing of the viral genome was performed on 11 entecavir- and peginterferon-treated patients.

Results. Initial univariate/multivariate explorations indicated that cirrhosis and antiviral-treatment methods were independently associated with HCC occurrence. The peginterferon-experienced patients had a lower HCC incidence than the nucleos(t)ide analog-treated patients (P=0.011). The peginterferon and entecavir monotherapy groups also differed in HCC incidence (P=0.018). Analysis of baseline-matched subgroups concurred with cohort analysis (peginterferon-experienced versus nucleotide-analog-treated, P=0.009; peginterferon versus entecavir, P=0.022). Viral loads of entecavir-treated patients were constantly suppressed lower than those of peginterferon-treated patients (P<0.001). Oncogenic surface antigen truncation mutations were detected in entecavir-treated patients with HCC but not in peginterferon-treated patients (P=0.015).

Conclusions. Treatment by peginterferon was associated with a lower HCC incidence compared with nucleos(t)ide-analog treatment in chronic HBV infection.

StephenW

聚乙二醇干扰素优于核苷（酸）类似物在慢性乙型肝炎的预防肝癌

    龚浩Liang1,2，＃，超威Hsu1，＃，明陵Chang1，易诚臣1，明伟Lai1和筹庭Yeh1,2，*

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作者机构

    1Liver研究中心，长庚医院，台湾桃园
    2Molecular医学研究中心，长庚大学，台湾桃园

    ↵*通讯作者：筹庭叶，医学博士，主任，肝病研究中心，长庚医院，199，通华北路，台北，台湾电话：886-3-3281200分机8125，传真：886-3-3282824，电邮：[email protected]

    ↵＃这两位作者也同样贡献

抽象

背景。肝细胞癌（HCC）的相关临床因素已被广泛研究在抗病毒治疗初治慢性乙型肝炎病毒（HBV）感染的病人，而不是在治疗经验的患者。由于有效地抑制乙肝病毒复制的抗病毒药物的广泛的可用性，我们研究肝癌危险因素的治疗经验的患者。

方法。对330名患者接受前期治疗肝活检的队列被列入分析肝癌发病率与临床参数的关系。 11 entecavir-和聚乙二醇干扰素治疗的患者中进行病毒基因组的超深度测序。

结果。最初的单变量/多变量的探索表明，肝硬化和抗病毒治疗方法进行了与肝癌的发生独立相关。聚乙二醇干扰素经验的患者有较低的肝癌发病率比核苷（酸）IDE模拟治疗的患者（P = 0.011）。聚乙二醇干扰素和恩替卡韦单药治疗组也有不同的肝癌发病率（P = 0.018）。的基线匹配亚组分析同意队列分析（聚乙二醇干扰素-经历与核苷酸类似物处理的，P = 0.009;聚乙二醇对恩替卡韦，P = 0.022）。恩替卡韦治疗的患者的病毒载量不断打压高于聚乙二醇干扰素治疗的患者（P <0.001）低。在恩替卡韦治疗的患者的HCC中检测致癌的表面抗原截短突变，但不是在聚乙二醇化干扰素治疗的患者（P = 0.015）。

结论。治疗聚乙二醇干扰素与较低的肝癌发病率与慢性HBV感染的核苷（酸）IDE模拟处理相比。