PMID- 35368769 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220405 IS - 1741-427X (Print) IS - 1741-4288 (Electronic) IS - 1741-427X (Linking) VI - 2022 DP - 2022 TI - Bushen Jianpi Formula Combined with Entecavir for the Treatment of HBeAg-Negative Chronic Hepatitis B: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. PG - 6097221 LID - 10.1155/2022/6097221 [doi] LID - 6097221 AB - BACKGROUND: Bushen Jianpi formula (BSJPF, also known as Lingmao formula) is a traditional Chinese medicine for chronic hepatitis B (CHB). The previous study has suggested that the treatment combination of BSJPF and entecavir (ETV) can achieve a significant loss of hepatitis B e antigen (HBeAg) and a significant decrease in serum level of hepatitis B virus (HBV) DNA in HBeAg-positive CHB patients with mildly elevated alanine aminotransferase. OBJECTIVE: This study aimed to evaluate the efficacy and safety of BSJPF combined with ETV for treating HBeAg-negative CHB patients. METHODS: A total of 640 patients were assigned randomly to the treatment group (receiving BSJPF combined with ETV for 96 weeks) or the control group (receiving a placebo combined with ETV for 96 weeks) in a 1 : 1 ratio. The primary endpoints are the rate of loss of hepatitis B surface antigen (HBsAg). The secondary outcomes included the rate of decrease in the HBsAg concentration to >/=1 lg.IU/mL, the HBV DNA suppression, the decline of the level of covalently closed circular DNA (cccDNA) in the liver, histological improvements, and the rate of ALT normalization. RESULTS: The rate of HBsAg loss in the treatment group was significantly higher than that of the control group (5.5% versus 1.8%, P=0.031). There were 11.1% of patients in the treatment group who recorded a reduction in HBsAg >/=1 lg.IU/mL, which is better than 5.9% of patients in the control group (P=0.043). There was no significant difference between the two groups with regard to the rate of HBV DNA clearance, the reduction in intrahepatic cccDNA, and the rate of ALT normalization (P > 0.05). The rate of liver fibrosis improvement in the treatment group was better than that of the control group (35.5% versus 11.8%, P=0.031), but there was no difference in necroinflammatory improvement (P > 0.05). The adverse events (AEs) were similar between the two groups, except for the abnormal kidney function, with 2.2% in the control group and 0.0% in the treatment group (P=0.028). CONCLUSION: The combination of BSJPF and ETV can increase the rate of HBsAg loss and the rate of histological fibrosis improvement without serious adverse events in CHB patients. Trial Registration. This trial is registered with ChiCTR-IOR-16009880 on November 16, 2016-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=16836. CI - Copyright (c) 2022 Jing-Hao Zhang et al. FAU - Zhang, Jing-Hao AU - Zhang JH AUID- ORCID: 0000-0002-7102-6369 AD - Department of Hepatopathy, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Zhang, Xin AU - Zhang X AD - Laboratory of Cellular Immunity, Shanghai Key Laboratory of Traditional Chinese Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Zhou, Zhen-Hua AU - Zhou ZH AD - Laboratory of Cellular Immunity, Shanghai Key Laboratory of Traditional Chinese Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Zhu, Xiao-Jun AU - Zhu XJ AD - Department of Hepatopathy, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Zheng, Chao AU - Zheng C AD - Department of Hepatopathy, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Li, Man AU - Li M AD - Laboratory of Cellular Immunity, Shanghai Key Laboratory of Traditional Chinese Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Jin, Shu-Gen AU - Jin SG AD - Laboratory of Cellular Immunity, Shanghai Key Laboratory of Traditional Chinese Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Mao, De-Wen AU - Mao DW AUID- ORCID: 0000-0001-9438-9325 AD - Department of Hepatology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China. FAU - Xue, Jing-Dong AU - Xue JD AD - Department of Hepatology, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an 710003, China. FAU - Shi, Wei-Bing AU - Shi WB AD - Department of Infectious Diseases, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China. FAU - Chi, Xiao-Ling AU - Chi XL AD - Department of Hepatology, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou 510006, China. FAU - Wang, Xian-Bo AU - Wang XB AD - Department of Integrated TCM and Western Medicine, Ditan Hospital Affiliated of Capital Medical University, Beijing 100015, China. FAU - Li, Xiao-Dong AU - Li XD AD - Department of Hepatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, China. FAU - Li, Yong AU - Li Y AD - Department of Hepatology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, China. FAU - Wang, Hui AU - Wang H AD - Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. FAU - Li, Qin AU - Li Q AD - Department of Hepatology, Department of Infectious Disease, Fuzhou Infectious Diseases Hospital, Fuzhou 350000, China. FAU - Zhou, Da-Qiao AU - Zhou DQ AD - Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China. FAU - Wang, Cheng-Bao AU - Wang CB AD - Department of Infectious Diseases, Linyi People's Hospital, Linyi 276003, China. FAU - Shi, Chang-He AU - Shi CH AD - Qingdao Liver Diseases Institute, Qingdao Hospital of Infectious Diseases, Qingdao 266033, China. FAU - Li, Cheng-Zhong AU - Li CZ AD - Department of Infectious Diseases, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China. FAU - Wu, Jian-Hua AU - Wu JH AD - Department of Hepatopathy, Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361001, China. FAU - Kong, Xiao-Ni AU - Kong XN AD - Central Laboratory, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Sun, Xue-Hua AU - Sun XH AUID- ORCID: 0000-0002-8515-3860 AD - Department of Hepatopathy, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Gao, Yue-Qiu AU - Gao YQ AUID- ORCID: 0000-0001-7276-9810 AD - Department of Hepatopathy, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. AD - Laboratory of Cellular Immunity, Shanghai Key Laboratory of Traditional Chinese Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. LA - eng PT - Journal Article DEP - 20220325 PL - United States TA - Evid Based Complement Alternat Med JT - Evidence-based complementary and alternative medicine : eCAM JID - 101215021 PMC - PMC8975667 COIS- The authors declare no conflicts of interest. EDAT- 2022/04/05 06:00 MHDA- 2022/04/05 06:01 PMCR- 2022/03/25 CRDT- 2022/04/04 05:12 PHST- 2021/09/01 00:00 [received] PHST- 2022/02/28 00:00 [revised] PHST- 2022/03/03 00:00 [accepted] PHST- 2022/04/04 05:12 [entrez] PHST- 2022/04/05 06:00 [pubmed] PHST- 2022/04/05 06:01 [medline] PHST- 2022/03/25 00:00 [pmc-release] AID - 10.1155/2022/6097221 [doi] PST - epublish SO - Evid Based Complement Alternat Med. 2022 Mar 25;2022:6097221. doi: 10.1155/2022/6097221. eCollection 2022.