Efficacy and safety of He-He-Shu-Yang Particles plus Anluohuaxian Pills for early liver fibrosis in Chronic Hepatitis B patients: study protocol for a multicenter, randomized controlled trial

Background: In recent years, more and more studies revealed that liver fibrosis progression could happen at early stage in chronic hepatitis B (CHB) patients. However, there is no anti-fibrotic agent available at present in modern medicine.He-He-Shu-YangParticles (HHSYP) and Anluohuaxian Pills (AHP)are two commonly used Traditional Chinese Medicine (TCM) agents for liver fibrosis, but there is no data of them for early liver fibrosis(F1 or F2) in multicenter, randomized controlled trial. Therefore, the aim of this study is to evaluate efficacy and safety ofHHSYP plus AHP for early liver fibrosis in CHB patients. Methods/design: For the 72-week randomized controlled study, 480 CHB patients with early liver fibrosis are randomly assigned at a 2:1 ratio to two groups: the intervention group and the placebo group. The intervention group was treated with HHSYP plus AHP. The placebo group was treated with placebo of HHSYP and AHP. The primary end point is the histological change after 72-week treatment.Discussion: Although previous studies have confirmed the anti-fibrosis efficacy of HHSYP and AHP in CHB patients, the efficacy and safety of their combination treatment for early liver fibrosis is still not clear.Therefore, this will be the first multicenter randomized trial to prove the efficacy and safety of combination TCM treatment of HHSYP and AHP for early liver fibrosis, which will use histological changes as the primary end point. This will provide reliable data for the TCM combination treatment of early liver fibrosis and might give a new direction for further international studies on liver fibrosis.Ethics and dissemination: This study protocol was approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (BF2018-175-01) and all other participating centers (Project number2018ZX10725506-003).The study findings will be published in peer-reviewed journals and presented at the national and international conferences. Trial registration: Chinese Clinical Trial Registration: ChiCTR1900025897, Registered:13 September 2019, http://www.chictr.org.cn/edit.aspx?pid=40222&htm=4