The Efficacy Of Chinese Patent Medicine Combined With Entecavir For The Treatment Of Chronic HBV-related Liver Fibrosis Or Cirrhosis:a Systematic Review And Network Meta-analysis Of Randomized Controlled Trials (RCTs) Or Prospective Cohort Studies

ObjectiveTo determine whether entecavir,combined with Chinese patent medicine,such as“fuzhenghuayu capsule”,“anluohuaxian pills”,“fufangbiejiaruangan tablets”,shows superior efficiency compared with entecavir alone for the treatment of chronic HBV-related liver fibrosis and the management of cirrhosis.MethodsRegistration of protocol:The protocol was published in the PROSPERO database(identification number:CRD42018112547).We searched PubMed,Embase,China Network Knowledge Infrastructure(CNKI)and Wanfang for randomized controlled trials(RCTs)or "prospective cohort studies" of "fuzhenghuayu capsule","anluohuaxian pills","fufangbiejiaruangan tablets" respectively combine entecavir in the treatment of chronic HBV-related liver fibrosis or cirrhosis from their inception to September 30,2018.R 3.3.3 and Gemtc 0.14.3 software are used for data analysis after two investigators independently screened the literature according to pre-established inclusion and exclusion criteria,extracted the data,and assessed the risk of bias in the included studies.ResultsA total of 43 RCTs and 1 prospective cohort study were included,with a total of-3,929 patients.The results of network meta-analysis showed that in the various treatments included in the study:(1)Negative convertsion rate of HBV DNA:anluohuaxian pills+entecavir,fuzhenghuayu capsules+entecavir are higher than entecavir alone.The rest of the treatment differences are not statistically significant.Negative conversion rate of HBeAg:there is no statistical difference between treatments;Order to improve the effect of negative conversion rate of HBV DNA and HBeAg:anluohuaxian pills+entecavir>fuzhenghuayu capsules+entecavir>fufangbiejiaruangan tablets+entecavir>entecavir.(2)four indicators of liver fibrosis(HA,LN,PC-?,IV-C):The effect of three Chinese patent medicines combined with entecavir is better than that of entecavir alone.In reducing HA,anluohuaxian pills are better than fuzhenghuayu capsules.The rest of the treatment differences are not statistically significant.Order to reduce HA,LN and PC-?:anluohuaxian pills+entecavir)fuzhenghuayu capsules+entecavir>fufangbiejiaruangan tablets+entecavir>entecavir.Because of the inconsistency between the direct comparison evidence and the indirect comparative evidence for IV?C,the ranking probability cannot be obtained.(3)liver stiffness measurement:The effect of three Chinese patent medicines combined with entecavir is better than that of entecavir alone.The rest of the treatment differences are not statistically significant.Order to reduce liver stiffness measurement:fuzhenghuayu capsules?entecavir>anluohuaxian pills+entecavir>fufangbiejiaruangan tablets+entecavir>entecavir.(4)B-ultrasound indicators:Portal vein diameter,splenic vein diameter,splenic thickness:the effect of three Chinese patent medicines combined with entecavir is better compared to entecavir alone.The rest of the treatment differences are not statistically significant.Order to reduce portal vein diameter and splenic vein diameter:anluohuaxian pills+entecavir)fuzhenghuayu capsules+entecavir>fufangbiejiaruangan tablets+entecavir>entecavir.Order to reduce splenic thickness:fuzhenghuayu capsules+entecavir>fufangbiejiaruangan tablets+entecavir>anluohuaxian pills+entecavir)entecavir.(5)The overall adverse effects in included studies are mild and the incidence is low.Most of them are non-severe gastrointestinal reactions.ConclusionAll three Chinese patent medici.nes have obvious curative effect on reducing four indicators of liver fibrosis(HA,LN,PC-?,IV-C),portal vein diameter,splenic vein diameter,splenic thickness and liver stiffness measurement in patients with chronic hepatitis B-related liver fibrosis or cirrhosis.For the first three indicators,the efficacy of anluohuaxian pills may be the best.The latter two indicators,fuzhenghuayu capsules may have the best efficacy;for the negative conversion rate of HBV DNA,fuzhenghuayu capsules and anluohuaxian pills also have certain curative effect.The three kinds of Chinese patent medicines have have fewer adverse reactions and are safe.