Identifying the Well-suited Chinese Herbal Products for Hepatocellular Carcinoma (HCC) Patients in Terms of Hazard Ratio and Child-Pugh Score Improvement: A Frequentist Statistical Analysis Applying ‘Netmeta’

Hepatocellular carcinoma (HCC) causes high mortality and global burden. In addition to the conventional western treatments, HCC patients are actively seeking adjuvant therapies, such as traditional Chinese medicine (TCM), hoping to improve treatment outcomes and prolong survival. Until 2021, only two network meta-analyses (NMAs) compare different HCC treatments, which, however, did not compare all forms of TCM formulations, and there is no evidence informing which TCM works best for an outcome. This frequentist NMA, conducted with R (version 4.0.2) under the random-effect model, ranks all TCM integrative treatments by P-scores with its ‘netmeta’ package for two outcomes, survival (hazard ratio) and Child-Pugh score improvement (odds ratio). There are 289 RCTs retrieved from literature screening for NMA. For survival, the combination of Buxu Huadu decoction and Jinshuibao capsule ranks first overall (P-score 0.9745, HR 0.1962). Fugan injection is the best TCM injection (P-score 0.9809, HR 0.3051). Shugan Huazhuo decoction (P-score 0.9448, HR 0.3728) and Peiyuan Guben capsule (P-score 0.9677, HR 0.2946) are the best decoction and product for oral administration respectively. Aidi injection ranks first in Child-Pugh score improvement (P-score 0.7539, OR 4.3429). This NMA guides clinical decision making in all kinds of settings. Multi-centered RCTs are warranted for further verification. Keywords: traditional Chinese medicine (TCM), hepatocellular carcinoma (HCC), network meta-analysis (NMA), adjuvant treatments, frequentist statistical analysis