Huaier granules combined with conventional therapy may improve survival in hepatocellular carcinomaDoes adding Huaier granules help liver cancer patients live longer when combined with standard treatment?

IntroductionHuaier granules (HEG), a traditional Chinese medicinal product primarily composed of Trametes robiniophila Murr., have been incorporated into comprehensive treatment strategies for various cancers. When combined with conventional antitumor therapies, it has demonstrated notable adjuvant and synergistic effects, improving quality of life and prolonging survival in patients. This study aimed to systematically review the clinical efficacy, safety, and potential mechanisms of HEG as adjuvant therapy in oncology, and to critically appraise the quality of available evidence to guide clinical practice and future research.MethodsA comprehensive systematic search of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP databases was conducted from inception to May 2024. Clinical studies, including randomized controlled trials (RCTs) and prospective and retrospective cohort studies, evaluating HEG combined with conventional cancer therapy were included. Preclinical studies investigating mechanisms were synthesized separately. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool for RCTs and the Newcastle-Ottawa Scale for observational studies. Evidence certainty was graded using a modified GRADE approach: A (high), B (moderate), C (low), and D (very low). A total of 56 studies involving 4,832 patients were included: 12 RCTs (n = 2,156), eight prospective cohorts (n = 1,089), 24 retrospective studies (n = 1,432), and 12 case series (n = 155). In hepatocellular carcinoma, HEG combined with transarterial chemoembolization (TACE) improved overall survival with a hazard ratio (HR) of 0.68 (95% confidence interval [CI], 0.52–0.89; two RCTs, moderate certainty) and progression-free survival with an HR of 0.71 (95% CI, 0.58–0.87). Similar benefits were observed when combined with chemotherapy for lung and gastric cancers (low to moderate certainty). However, most RCTs were single-center, open-label studies with heterogeneous outcome definitions. Preclinical studies suggest that immunomodulatory, antiangiogenic, and proapoptotic effects are primarily mediated by polysaccharide components (TPG-1, PS-T); however, direct clinical translation remains uncertain due to the lack of pharmacokinetic bridging data. Modern pharmacological research indicates that HEG possesses antiviral, anti-inflammatory, and immunomodulatory properties, as well as significant potential in antitumor therapy. This review comprehensively summarizes recent advances in the clinical application of HEG in antitumor therapy and explores its underlying mechanisms of action. Further in-depth research is needed to fully elucidate its mechanisms of action and ensure its safe and effective clinical use. Future clinical trials should focus on optimizing HEG application methods for various tumor types and treatment regimens to maximize its antitumor potential.