Ningning ZHAO, Bing WEI, Shiying TANG

Department of Traditional Chinese Medicine, Chengde Medical University/Hebei Provincial Key Laboratory of Research and Development of Traditional Chinese Medicine, Chengde Medical University, Chengde 067000, China

Abstract [Objectives] The purpose was to study the clinical efficacy and safety of Banxia Xiexin decoction in treating bile reflux gastritis (BRG). [Methods] Randomized controlled trial was adopted to conduct scientific and standardized assessment on the risk of bias in the included articles. With overall effect and epigastric pain relief as indices, meta-analysis was performed, and sensitivity and safety analysis was conducted on the included literature. [Results] A total of 13 articles were included, involving a total of 1 478 patients. The results of meta-analysis show that the efficacy of Banxia Xiexin decoction alone and Banxia Xiexin decoction-Western medicine combination is better than that of Western medicine alone. [Conclusions] Banxia Xiexin decoction is safe and effective in treating bile reflux gastritis. However, as the 13 articles included are all low in quality and there is a certain degree of publication bias, the objectivity of the results is affected to some extent.

Key words Banxia Xiexin decoction, Bile reflux gastritis, Meta-analysis, Systematic review

1 Introduction

Bile reflux gastritis (BRG) is a comprehensive symptom, with gastric mucosal damage as the main manifestation, and is a common digestive system disease, accounting for about 12.8% of gastritis incidence[1]. In traditional Chinese medicine, the disease can be attributed to epigastric pain, gastric flatulence,etc[2].. The clinical symptoms mainly include epigastric pain, nausea, vomiting, hiccups,etc., and vomiting is accompanied by yellow-green bitter water[3]. In the prescription, Rhizoma Coptidis and Radix Scutellariae can clear away heat and dry dampness, dried ginger can dispel cold, and ginseng, jujube and Radix et Rhizoma Glycyrrhizae can warm middle-jiao and tonify deficiency. The combination of the Chinese herbs above can harmonize the spleen and stomach[4]. This article retrieves all relevant research literature at home and abroad, and comprehensively and systematically evaluates the efficacy of Banxia Xiexin decoction in the treatment of bile reflux gastritis, with a view to better clinical application and promotion.

2 Research method

2.1 Literature inclusion and exclusion criteria

2.1.1Research object. Patients with a clear diagnosis of bile reflux gastritis were selected, and gender, age, race, occupation, source,etc. were not limited.

2.1.2Intervention measure. The patients in the treatment group were given with Banxia Xiexin decoction combined with conventional Western medicine, and those in the control group were given with Western medicine. The administration dosage and method of the two groups were not limited, but the usage of Western medicine in the two groups was the same.

2.1.3Research type. Research type was limited to randomized controlled trial, language was limited to Chinese or English, and source of literature was unlimited.

2.1.4Outcome indicators. The outcome indicators included overall effect and stomach pain relief.

2.1.5Exclusion criteria. Research types such as case report, animal experiment, personal experience summary and systematic review were excluded. Literature with experiment involving other TCM preparation or other TCM intervention program or literature without access to full data were excluded.

2.2 Retrieval strategyA total of 7 databases were selected for literature search, including Pubmed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, China BioMedical Literature Database and Vip Database. The retrieval time was from the establishment of the databases to February 29, 2020. Chinese search terms were 膽汁反流性胃炎, 繼發(fā)性膽汁反流性胃炎, 原發(fā)性膽汁反流性胃炎 and 半夏瀉心湯; and English search terms were bile reflux gastritis, BRG, alkaline reflux gastritis, Banxia Xiexin and Banxia Xiexin decoction. The databases were searched by combining subject words and free words.

2.3 Data collection and analysis

2.3.1Literature screening and data extraction. Literature screening and data extraction was independently completed by two researchers. In case of disagreement, it was solved by discuss or discussion with third party. The data extracted included (i) general information about papers (author, time,etc.); (ii) experimental design (such as random and blinding methods); (iii) basic information about objects included (number of people, gender,etc.); (iv) intervention measures; (v) outcome indicators.

2.3.2Literature quality evaluation. The methodological quality of the included studies was assessed using the method recommended by the Cochrane manual. The assessment contents included (i) which specific random allocation method was used; (ii) whether it was allocation concealment; (iii) whether blinding method (participant blinding, implementer blinding, blinding of measurement outcome indicators) was adopted; (iv) whether the outcome indicator data was complete; (v) whether the research results were selectively reported; (vi) whether there was other bias. The assessment grades included "low risk", "unknown risk" and "high risk". The results are expressed as bias risk assessment chart or bias risk overview chart.

2.4 Statistical analysisRevMan 5.3 software was used for meta-analysis. For counting data, relative risk (RR) or odds ratio (OR) was used as its effect index, and for measurement data, mean (MD) was used as its effect index. The confidence interval (CI) was set as 95%, andP<0.05 means the difference was statistically significant. Heterogeneity analysis was performed for the results of each included study usingχ2test. IfI2≤20% andP≥0.1 orP<0.1, it meant that there was little heterogeneity and good homogeneity between studies, and fixed-effect model was adopted; and ifI2≥50% andP<0.1, it meant that there was heterogeneity between studies, and random effects model could be used.

3 Results

3.1 Basic informationA total of 391 articles were searched, and after removing duplicate articles, 184 articles were remained. By reading the title and abstract of the literature, a total of 75 articles were included in the preliminary screening. After excluding the articles that did not meet the standards after reading the full text, a total of 13 articles[5-17]were included (Fig.1). All the articles reported overall effect, and 5 articles[5, 9, 11, 13, 17]clearly reported the treatment of epigastric pain (the data of two articles[5, 11]could not be accurately extracted, so they were excluded). The details of the included studies are shown in Table 1.

Fig.1 Screening procedure of literature

Table 1 Data extracted

NameYearNumberofpeopleinthetreatmentgroupNumberofpeopleinthecontrolgroupMale/FemaleInterventionmeasureControlgroupTreatmentcourseQingyiFAN2007554556/44BanxiaXiexindecoction(1dose/d,2times/d)+ControlgroupOmeprazoleenteric-coatedcapsule(20mg/time,2times/d),cisapridetablet(10mg,3times/d)4weeksXiuhuaPENG2009198198201/195BanxiaXiexindecoction(1dose/d,2times/d)+ControlgroupOmeprazoleenteric-coatedcapsule(20mg/time,2times/d),cisapridetablet(10mg/time,3times/d)4weeksTingLUO2006454056/29BanxiaXiexindecoction(1dose/d,2times/d)+ControlgroupRanitidinehydrochloridecapsule(0.15g/time,2times/d),metoclopramide(10mg,3times/d)4weeksXinhuaYU2013505065/35BanxiaXiexindecoction(powdertobetakenafterbeinginfusedinboil-ingwater,2times/d)+ControlgroupRanitidinecapsule(150mg/time,2times/d),motilintablet(10mg,3times/d)2weeksYimeiLIN2006403842/36BanxiaXiexindecoction(1dose/d,2times/d)+ControlgroupMotilintablet(10mg/time,3times/d),ranit-idinecapsule(150mg,2times/d)30dMingfangLI2011191920/18BanxiaXiexindecoction(1dose/d,2times/d)+ControlgroupMoxicillin(0.5g/time,3times/d),motilintablet(10mg/time,2times/d),sucralfate(4tablets/time,3times/d)4months

3.2 Literature qualityThe 13 articles adopted random methods, 2 of which used random number method, one of which used random grouping of odd and even numbers, and one of which used random grouping of visit order. All studies did not mention allocation concealment methods, blinding methods of participants and researchers, blinding methods of outcome assessors, or other biases. All studies reported complete results data (Fig.2).

3.3 Meta-analysis of overall effectThe 13 articles reported overall effect (Fig.3). The results show thatI2=0% andP=0.93, indicating that the heterogeneity between the studies was within an acceptable limit, so a fixed effect model was selected for data analysis. The combined effect size was calculated [RR=1.22, 95%CI(1.17, 1.27),P<0.000 01]. The results show that the overall effect of Banxia Xiexin decoction combined with Western medicine was better than that of conventional Western medicine alone in the treatment of bile reflux gastritis.

Fig.2 Risk of bias assessment

Fig.3 Forest plot of overall effect

3.4 Meta-analysis of epigastric painTwo studies evaluated the epigastric pain score of patients with BRG treated with Banxia Xiexin decoction. The results show thatP=0.007 andI2=80%, indicating that there was no homogeneity between the studies, so the random effect model was used. It is shown thatMD=-0.38,Z=5.94, 95%CI(-0.50, -0.28),P<0.000 01, and the difference is statistically significant (Fig.4). It indicates that the combination of Banxia Xiexin decoction and Western medicine is better than Western medicine alone in relieving patients with stomach pain.

Fig.4 Forest plot of epigastric pain score

3.5 Publication biasFig.5 shows that the funnel plot of overall effect is basically symmetrical, indicating that there was publication bias.

Fig.5 Funnel plot of publication bias

4 Discussion

Banxia Xiexin decoction was first recorded in Zhang Zhongjing’sSynopsisoftheGoldenChamberandTreatiseonFebrileDiseases[18]. Rhizoma Pinelliae is the monarch drug in the prescription, and it can strengthen spleen, dry dampness, remove distension and harmonize stomach; and dried ginger is the ministerial drug, and it can dispel cold and assist Rhizoma Pinelliae to invigorate spleen. Bile reflux gastritis is a common and frequently-occurring disease in the digestive system. The clinical efficacy of Western medicine is often not ideal, and the recurrence rate is high. The incidence of bile reflux gastritis is related to dysfunction of liver, gallbladder, spleen and stomach. Liver is for catharsis, spleen is for transportation and transformation, gallbladder is for soothing and stomach is for harmonizing. If they are dysfunctional, it will lead to dysfunction of the body, which becomes the key pathogenesis[19]. Banxia Xiexin decoction is well-matched and has been widely used because of its outstanding clinical efficacy.

A total of 13 articles were included in this study. Meta-analysis was used to analyze the overall effect and the relief of epigastric pain in the experimental group and the control group. The results show that Banxia Xiexin decoction is effective in treating bile reflux gastritis. However, this study has certain limitations: (i) The quality of the 13 articles included is generally low, and there is a certain publication bias. (ii) Clinical observation indicators are not uniform, and other key indicators should be added to standardize clinical testing.

In summary, compared with conventional Western medicine treatment alone, combination of Banxia Xiexin decoction and Western medicine is more effective.