[1]周宇辰,胡承光,袁国盛,等.抗病毒联合抗肝纤维化治疗慢性乙型肝炎肝纤维化降低肝细胞癌发生:144周的前瞻性队列研究[J].南方医科大学学报,2019,(06):633.[doi:10.12122/j.issn.1673-4254.2019.06.02]
点击复制

抗病毒联合抗肝纤维化治疗慢性乙型肝炎肝纤维化降低肝细胞癌发生:144周的前瞻性队列研究()
分享到:

《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2019年06期
页码:
633
栏目:
出版日期:
2019-06-16

文章信息/Info

Title:
Antiviral and antifibrotic therapies reduce occurrence of hepatocellular carcinoma in patients with chronic hepatitis B and liver fibrosis: a 144-week prospective cohort study
作者:
周宇辰胡承光袁国盛刘俊维任彦瑜唐淬蓉杨淑玲戴琳李园杨定华
关键词:
慢性乙型肝炎肝纤维化肝细胞癌抗病毒抗纤维化
Keywords:
hepatitis B chronic liver fibrosis hepatocellular carcinoma anti-viral anti-fibrosis
DOI:
10.12122/j.issn.1673-4254.2019.06.02
摘要:
目的比较不同抗病毒和抗肝纤维化联合方案治疗慢性乙型肝炎(CHB)-肝纤维化的疗效、安全性及肝细胞癌(HCC)的发 生率。方法2010年6月~2018年6月在南方医科大学南方医院接受抗病毒治疗的CHB肝纤维化患者840例构成随访队列。性 别、年龄(相差≤5岁)、HBeAg状态、肝脏硬度值测定(LSM)基本匹配后按1∶1分别进入3个队列的单用抗病毒药组(恩替卡韦、 替诺福韦酯及阿德福韦酯3个抗病毒药,为对照组)和联合用药组(3个抗病毒药分别与复方鳖甲软肝片组联合,为观察组)。比 较3 个队列6 组患者各随访时间点HBV DNA累积转阴率、丙氨酸转氨酶复常率、肝纤维化逆转程度及HCC的发生率等。结 果随访满144周纳入分析的病例共749例。随着治疗时间的延长,与基线时比较,6组患者的HBV DNA累积转阴率均逐渐增 加(均P<0.001);丙氨酸转氨酶复常率也随着治疗时间的延长而逐渐升高(均P<0.001)。联合用药组均比单用药组显示出更好 的逆转肝纤维化效果(χ2 ETV队列=11.345,χ2 TDF队列=10.160,χ2 ADV队列=6.358,均P<0.05)。观察到144周访视点,单用恩替卡韦组、恩替卡 韦联合复方鳖甲软肝片组、单用阿德福韦酯组以及阿德福韦酯联合复方鳖甲软肝片组的HCC发生率分别为2.2%、1.7%、1.7%、 3.3%,替诺福韦酯队列的2组均无HCC病例发生,各组间的差别无统计学意义(χ2=6.813,P=0.138);与文献报道的未抗病毒治疗 的CHB随访3年7.2%的HCC发生率比较,本研究3年积累HCC发生率(1.3%,P<0.05)明显较低。结论抗病毒联合抗纤维化 治疗能有效逆转CHB-肝纤维化,降低HCC发生率;替诺福韦酯可能在降低HCC发生方面更有优势。
Abstract:
Objective To compare the efficacy and safety of different antiviral and antifibrotic regimens in patients with chronic hepatitis B (CHB) and hepatic fibrosis and the incidence of hepatocellular carcinoma (HCC) associated with these therapies. Methods A total of 840 patients with CHB and concurrent hepatic fibrosis, who received antiviral therapy in Nanfang Hospital between June, 2010 and June, 2018, were enrolled in this follow-up cohort study. The patients were assigned to 3 cohorts matched for gender, age (difference≤5 years), HBeAg status and liver stiffness measurement (LSM) for treatment with one of the 3 antiviral drugs, namely entecavir, tenofovir dipivoxil and adefovir dipivoxil; each cohort was divided into 2 groups, with one of the groups having a combined treatment with Fufang Biejiaruangan tablet. The cumulative negative conversion rate of HBV DNA, normalization rate of ALT, hepatic fibrosis regression and the incidence of HCC were compared among the 3 cohorts and across the 6 groups at 144 weeks. Results A total of 749 patients were available to follow-up at 144 weeks. Compared with the baseline data, the cumulative negative conversion rate of HBV DNA increased gradually and the abnormal rate of ALT decreased significantly over time during the treatment in all the 6 groups (all P<0.001). Compared with the any of the antiviral drugs used alone, the combined treatments all resulted in significantly better antifibrotic effects (χ2 ETV cohort=11.345, χ2 TDF cohort=10.160, χ2 ADV cohort= 6.358; all P<0.05). At 144 weeks, the incidence of HCC were 2.2% , 1.7% , 1.7% and 3.3% in enecavir group, enecavir with Biejiaruangan tablet group, adefovir group, and adefovir with Biejiaruangan tablet group, respectively, showing no significant difference between the two cohorts (4 groups; χ2=6.813, P=0.138). None of the patients in the 2 groups with tenofovir treatment had HCC by the end of the observation. Conclusion Antiviral therapy combined with antifibrotic therapy can effectively reverse hepatic fibrosis and reduce the incidence of HCC in patients with CHB; among the 3 antiviral drugs, tenofovir dipivoxil can be a better option for reducing the incidence of HCC in these patients.

相似文献/References:

[1]李新瑜,熊伟,韩路军,等.核磁共振动态增强成像评价肝纤维化的临床应用[J].南方医科大学学报,2011,(07):1259.
[2]阎丽,王战会,杨洁,等.恩替卡韦联合阿德福韦酯对既往核苷类似物治疗失败的慢性乙肝患者疗效分析[J].南方医科大学学报,2011,(06):1009.
[3]黄亮,漆林艳,陈志良,等.复方抗肝纤维化处方的优化[J].南方医科大学学报,2012,(01):106.
[4]黄珊,张文雍,潘春球,等.胆管结扎诱导的肝纤维化大鼠肝脏上皮间质表型的变化[J].南方医科大学学报,2012,(02):173.
[5]樊和斌,郭亚兵,杨洁,等.慢性乙型肝炎患者HBV基因型及其临床意义[J].南方医科大学学报,2005,(02):229.
 FAN He-bin,GUO Ya-bing,YANG Jie,et al.Genotyping of hepatitis B virus and its clinical significance in patients with chronic hepatitis B[J].Journal of Southern Medical University,2005,(06):229.
[6]于宏,曹治宸,耿建英,等.干扰素α治疗慢性乙型肝炎患者肝纤维化的实验研究[J].南方医科大学学报,2005,(11):1409.
 YU Hong,CAO Zhi-chen,GENG Jian-ying,et al.Effect of interferon alpha on liver fibrosis in patients with chronic hepatitis B[J].Journal of Southern Medical University,2005,(06):1409.
[7]李旭,宁佐伟,罗薇,等.腹腔持续注射血管紧张素-(1-7)对胆管结扎大鼠肝纤维化的抑制作用[J].南方医科大学学报,2012,(07):944.
[8]陈建蓉,王霁,秦天强,等.复方甘草酸苷治疗慢性乙型肝炎的效果及安全性的meta分析[J].南方医科大学学报,2014,(08):1224.
[9]李旭,蔡双明,宁佐伟,等.螺内酯对肝纤维化大鼠肝窦血管生成的抑制作用[J].南方医科大学学报,2012,(08):1135.
[10]苏荣,罗娜,杨延斌,等.HBeAg阴性慢性乙型肝炎患者乙肝病毒基因变异和分型研究[J].南方医科大学学报,2012,(12):1804.
[11]梁建新,屈杏芬,曾文铤,等. 氧化苦参碱在治疗慢性乙型肝炎中抗肝纤维化的作用机制[J].南方医科大学学报,2010,(08):1871.
 LIANG Jian-xin,QU Xing-fen,ZENG Wen-ting,et al.Mechanism of oxymatrine in preventing hepatic fibrosis formation in patients with chronic hepatitis B[J].Journal of Southern Medical University,2010,(06):1871.

更新日期/Last Update: 1900-01-01