Evaluation of the Efficacy, Safety, and Clinical Outcomes of Ginsenosides as Adjuvant Therapy in Hepatocellular Carcinoma: A Meta-Analysis and Systematic Review

Background: Ginsenosides (GS), including total GS, Rh2, Rg3 and compound K (CK), have been utilized as adjuvants in transarterial chemoembolization (TACE), surgery, and chemotherapy for hepatocellular carcinoma (HCC) therapy. However, the safety and efficacy of such combination treatments have been contradictory across different studies. This study aims to systematically evaluate the efficacy and safety of GS as adjuvant therapy for HCC. Methods: A literature search of PubMed, CNKI, Wanfang Data, Cochrane Library, Embase, and Web of Science was conducted up to May 2024 for clinical randomized controlled trials (RCTs) on GS-based adjuvant treatments for HCC. Two researchers independently screened the literature, extracted relevant data, and assessed study quality. Meta-analysis was conducted using RevMan 5.4. Results: Nineteen articles involving 1448 patients were included. Meta-analysis showed that GS as an adjuvant therapy for HCC improved disease control rate (risk ratio (RR) = 1.42, 95% CI [1.26, 1.60]), objective response rate (RR = 1.20, 95% CI [1.09, 1.32]), life quality (RR = 1.49, 95% CI [1.23, 1.79]), 1-year overall survival rate (RR = 1.27, 95% CI [1.06, 1.52]), 2-year overall survival rate (RR = 1.43, 95% CI [1.06, 1.95]), ehanced Child-Pugh in A level (RR = 1.59, 95% CI [1.08, 2.34]), Child-Pugh in B level (RR = 1.28, 95% CI [1.08, 1.52]); increased CD3+ (MD = 8.81, 95% CI [3.91, 13.71]), NKC (MD = 8.00, 95% CI [6.76, 9.24]) and CD4+ (MD = 9.38, 95% CI [8.04, 10.72]), and reduced incidence of adverse reactions including nausea and vomiting (RR = 0.66, 95% CI [0.57, 0.77]), anorexia (RR = 0.33, 95% CI [0.21, 0.50]), leukopenia (RR = 0.55, 95% CI [0.46, 0.67]) and myelosuppression (RR = 0.54, 95% CI [0.40, 0.74]); decreased Child-Pugh in C level (RR = 0.43, 95% CI [0.27, 0.68]) and CD4+/CD8+ ratio (MD = 0.50, 95% CI [0.47, 0.57]). Conclusions: In summary, GS combined with Western medical approaches (TACE, surgery, chemotherapy) for the treatment of HCC can improve clinical efficacy, increase overall survival rates, enhance patient life quality, and reduce the occurrence of adverse reactions. However, due to the generally low quality of the included studies, more large-sample, multi-center, high-quality, RCTs are warranted to further consolidate these findings.