Efficacy and safety of combining Chinese medicine with Western medicine for gallstone treatment

Abstract

Background: Background gallstones are a common and multiple disease, with a high global prevalence, complications such as cholecystitis, pancreatitis, and even increased risk of cancer. Oral Chinese medicine, as the main treatment method of traditional Chinese medicine, is widely used in the treatment of gallstones. This study aimed to evaluate the efficacy and safety of Chinese medicine combined with Western medicine for the treatment of gallstones.

Methods: We searched PubMed, Web of Science, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, WanFang, Chinese Scientific Journal Database (VIP), and Chinese BioMedical Literature Database. The search time was set to be up to July 2, 2024. Data analysis using Revman 5.3 software. The protocol is registered in the PROSPERO database (CRD42024567327).

Results: Ultimately, 912 patients from 8 randomized controlled trials were included. The meta-analysis results of traditional Chinese medicine combined with Western medicine versus Western medicine were as follows: imaging examination (standardized mean difference, SMD = -1.51, 95% confidence interval [CI] (-2.36, -0.65), P < .001), total cholesterol level (SMD = -2.14, 95% CI (-3.61, -0.67), P = .004), total bile acid level (SMD = -0.97, 95% CI (-3.36, -1.42), P = .043), traditional Chinese medicine symptom scores (SMD = -1.88, 95% CI (-3.16, -0.60), P = .004), occurrence of adverse reaction (odds ratio = 0.51, 95% CI (0.21, 1.24), P = .14).

Conclusion: The curative effect of Chinese medicine combined with Western medicine in the treatment of gallstones is better than that of Western medicine and is safety. Due to the limited quantity and quality of the included literature, more literature on double-blind randomized controlled trials with large samples is needed in the later stage to verify this conclusion.

Keywords: Western medicine; gallstones; meta-analysis; systematic review; traditional Chinese medicine.

Figure 1.

Literature screening process and results. A preliminary search of 3247 potentially relevant articles on traditional Chinese medicine treatment of gallstones was conducted from the database, and 780 duplicate records were deleted. Then 2443 articles were excluded by reviewing titles and abstracts. After reading the full text and checking against the inclusion and exclusion criteria, 16 articles were excluded. As a result, a total of 8^[–21] published articles were included in the meta-analysis. RCT= randomized controlled trial. The graphic framework is from Page et al,^[22] licensed under CC BY 4.0.

Figure 2.

Risk of bias graph. The quality of the 8 randomized controlled trials (RCTs) included was systematically assessed according to the quality assessment tools recommended by the Cochrane Manual. Seven studies that explicitly described the correct method for generating random sequences (random number table method) were rated as low risk. One study mentioned grouping by order of admission, which was rated as high risk. Because none of the RCTs mentioned allocation procedures and constraint methods, they were rated as ambiguous risks. Because of the absence of data flaws and the selection of favorable outcome reports, the integrity of all investigators’ results data and selective reporting were judged to be low-risk bias. However, no details of other biases were found in all the studies, which were rated as unclear risks.

Figure 3.

Risk of bias summary. The quality of the 8 randomized controlled trials (RCTs) included was systematically assessed according to the quality assessment tools recommended by the Cochrane Manual. Seven studies that explicitly described the correct method for generating random sequences (random number table method) were rated as low risk. One study mentioned grouping by order of admission, which was rated as high risk. Because none of the RCTs mentioned allocation procedures and constraint methods, they were rated as ambiguous risks. Because of the absence of data flaws and the selection of favorable outcome reports, the integrity of all investigators’ results data and selective reporting were judged to be low-risk bias. However, no details of other biases were found in all the studies, which were rated as unclear risks.

Figure 4.

Forest plot of the meta-analysis comparing the imaging improvement. A total of 5 randomized controlled trial studies^[–18,21] reported imaging improvements, 3 of which^[15,17,18] described changes in gallstone diameter, 1^[16] described gallbladder emptying rate, and 1^[21] described gallbladder wall thickness and gallbladder shrinkage. Among the 3 studies finally included,^[15,17,18] 2 of them^[17,18] used TCM + basic therapy + UDCA as the treatment group intervention, and 1 study^[15] used TCM + UDCA. There were 2 studies^[15,17] where the treatment group was treated for 2 months and 1 study^[18] for 8 weeks. As the duration of treatment and composition of Chinese medicines included in the studies were inconsistent, standardized mean difference (SMD) were used. Due to the significant heterogeneity (P < .00001, I² = 93%), a random effects model was adopted. The results showed that the gallstone diameter of the Chinese medicine combined with the western medicine treatment group was significantly reduced (SMD = -1.51, 95% Cl (-2.36, -0.65), P < .001). A sensitivity analysis is required, which is done by excluding each study individually. Results show that heterogeneity has no obvious change, but it is worth noting that after eliminating the study^[17] of Liu, heterogeneity changed significantly (P = .29, I² = 18%). This shows that the imaging improvement of meta-analysis results lacks robustness, vulnerable to the research of the change of the number of significant changes (Table S2, Supplemental Digital Content, https://links.lww.com/MD/P284). TCM = traditional Chinese medicine.

Figure 5.

Forest plot of the meta-analysis comparing the TC. In the last 3 studies included,^[14,20,21] a heterogeneity test was conducted for the level of TC. The results indicated significant heterogeneity among the studies (P < .00001, I² = 95%), leading to the adoption of a stricter random effects model. Meta-analysis indicated a statistically significant difference in TC levels (SMD = -2.14, 95% Cl (-3.61, -0.67), P = .004). After excluding the study by Chen,^[21] there was a notable change in heterogeneity (P = .2, I² = 40%) according to sensitivity analysis presented in Table S3, Supplemental Digital Content, https://links.lww.com/MD/P285. This suggests that the meta-analysis results regarding TC levels lack robustness and are susceptible to significant changes due to alterations in the number of studies. TC = total cholesterol.

Figure 6.

Forest plot of the meta-analysis comparing the TBA. The treatment group was divided into 3 studies.^[14,20,21] Heterogeneity inspection revealed significant heterogeneity in TBA levels among the studies (P < .00001, I² = 99%). Sensitivity analysis demonstrated that the association remained stable (see Table S4, Supplemental Digital Content, https://links.lww.com/MD/P286). Meta-analysis indicated a statistically significant difference in TBA levels (SMD = -0.97, 95% CI (−3.36, −1.42), P = .043). TBA = total bile acids.

Figure 7.

Forest plot of the meta-analysis comparing the TCM symptom scores. A total of 5 studies^[,–21] involving a total of 476 participants reported changes in TCM symptom scores, of which 2^[18,21] were not analyzed because they had only a single symptom score and no overall TCM symptom score. In the last 3 studies included,^[,–21] the heterogeneity test suggested that there was great heterogeneity among the studies (P < .00001, I² = 95%), so a random effects model was used. Results show that there is statistical significance (SMD = −1.88, 95% CI (−3.16, −0.60), P = .004). Sensitivity analysis showed that heterogeneity changed significantly (P = .1, I² = 63%) after exclusion of Zhao’s study.^[15] This suggests that the TCM symptom score of meta-analysis results lacks robustness (Table S5, Supplemental Digital Content, https://links.lww.com/MD/P287). TCM = traditional Chinese medicine.

Figure 8.

Forest plot of the meta-analysis comparing the occurrence of adverse reaction. A total of 463 participants in 4 studies reported^{[15,16,18,20]} the occurrence of adverse drug reactions, including dizziness, loose stools, rubella, diarrhea, nausea, and vomiting. The adverse drug reactions in the treatment group and the control group were mild and resolved without specific management measures. Three other studies^[14,19,21] reported no adverse effects and were not included in the analysis. The heterogeneity test showed that there was no significant heterogeneity among the studies (P = .97, I² = 0%), and the fixed effect model was used. The results showed that the difference was not statistically significant (OR = 0.51, 95% CI (0.21, 1.24), P = .14), indicating that the combination of TCM and Western medicine did not increase the incidence of adverse reactions. TCM = traditional Chinese medicine.