Editor’s Note: On May 18, 2024, the “25th National Academic Conference on Traditional Chinese Medicine for Hepatobiliary Diseases” was successfully held in Chongqing. The conference invited masters of Chinese medicine, academicians, nationally renowned TCM doctors, and leading experts in hepatology from both traditional Chinese and Western medicine to present academic reports. The focus was on hot and challenging issues in TCM hepatology, showcasing the latest achievements in TCM treatment of liver diseases. At the conference, Associate Professor Jingjie Zhao from the TCM Department of Beijing Friendship Hospital, Capital Medical University, delivered a brilliant report titled “Quality Evaluation of Randomized Controlled Clinical Trials on TCM Intervention in Non-Alcoholic Fatty Liver Disease.” The following is a summary of her report for our readers.
Current Status of Clinical Evidence for TCM Intervention in MAFLD
In facing the modern epidemic of metabolic-associated fatty liver disease (MAFLD), primarily diagnosed through imaging, TCM’s ancient understanding seems somewhat inadequate. However, many TCM experts have developed new insights and relatively effective interventions through practical exploration of this new disease. Despite having theoretical and therapeutic efficacy, TCM treatment for MAFLD currently faces the dilemma of lacking high-level evidence.
Problems with Clinical Evidence
The team of Professor Hong You at the Beijing Friendship Hospital, Capital Medical University, which serves as the Beijing TCM Management Bureau’s collaborative project for tackling difficult and major diseases (fatty liver), conducted a quality evaluation and summary of endpoint indicators for existing randomized controlled trials (RCTs) on TCM interventions for MAFLD, including acupuncture and compound treatments. The main issues identified are as follows:
- According to the ROB2 risk of bias assessment standard, four main issues were identified:
- (1) Incomplete implementation of randomization and blinding methods: Most studies did not adequately describe the randomization process and allocation concealment, likely due to a lack of understanding of allocation concealment, and most did not blind the operators.
- (2) Inadequate description of treatment protocols: Most studies lacked detailed descriptions of treatment protocols, including specific dosages, durations, and administration methods, making it difficult to determine if the implementation was standardized.
- (3) Limited use of objective endpoint indicators: It was unclear whether outcome assessors were blinded, leading to a high risk of bias in subjective outcome evaluations.
- (4) Lack of pre-registration of studies: Without prior registration, it is difficult to assess selective reporting bias. Given the current state of evidence-based medicine, registering clinical studies is essential.
- According to the CONSORT 2017 reporting risk of bias assessment standard, six main issues were found:
- (1) Few studies clearly identified as randomized clinical trials in their titles and abstracts, hindering retrieval and dissemination of study results.
- (2) Most studies did not describe the type of randomization and allocation concealment mechanisms, reducing the accuracy and credibility of the results.
- (3) Nearly all studies did not mention methods for determining sample sizes.
- (4) Few studies described the setting and implementation of blinding.
- (5) Descriptions of recruitment and follow-up times were often unclear, and most studies did not report effect estimates and their precision.
- (6) Only a few studies discussed the generalizability, funding, and support for the trials. Most did not provide explanations of results, trial registration, or access to trial protocols, affecting the credibility and authenticity of the trials.
- Endpoint Indicator Analysis: The included studies were classified into six categories of 15 types based on the nature of the indicators. The use rates of biochemical indicators such as blood lipids (TC, TG, LDL-C, HDL-C) were 89.7%, and liver function indicators (ALT, AST, ALP, GGT, TBil, DBil) were 84.6%. Clinical evaluation indicators, such as clinical efficacy evaluation and TCM syndrome efficacy evaluation, were used in 66.7% and 68.0% of studies, respectively. Despite the high frequency of these indicators, there were issues such as unclear primary and secondary endpoints, lack of standardized fatty liver evaluation methods (liver biopsy or non-invasive techniques), and vague descriptions of efficacy indicators, especially TCM syndrome evaluations.
Overall, although the number of studies on TCM intervention in MAFLD has rapidly increased, the level of evidence has not seen a corresponding improvement. This suggests that researchers in TCM clinical studies should optimize the top-level design of RCTs, improve clinical research quality, enhance reporting standards, and solidify the evidence for the efficacy of TCM. This would expedite the integration of TCM into the international market and allow it to play a broader therapeutic role.
Improvements and Prospects
Professor Hong You’s team conducted a pilot RCT on electroacupuncture intervention in MAFLD, using non-acupoint shallow needling as the control group. After 12 weeks of electroacupuncture, the proton density fat fraction (MRI-PDFF) decreased by 33.6%, with 53.3% of patients showing a reduction of over 30%. In comparison, the FDA-approved Resmetirom showed a 36% decrease in MRI-PDFF after 12 weeks in its phase IIb study, with 24.2% to 25.9% of patients meeting histological improvement criteria after 24 weeks in phase III studies. The efficacy of Professor Hong You’s team’s study is comparable to these results. This study was published in Chinese Medicine in 2024.
Associate Professor Jingjie Zhao stated that following the pilot study, they are conducting a multicenter RCT on electroacupuncture intervention in MAFLD, aiming to provide high-quality evidence for this intervention.
