Abstract
The hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. It occurs primarily as manifestation of other pathological processes, such as viral hepatitis, cirrhosis, and toxin exposure that affect directly the cellular process. Studies were selected from PubMed and Scopus databases according to the PRISMA statement. The research filters were constructed using three parameters: flavonoids, hepatocellular carcinoma, and animal model. The bias analysis of the 34 selected works was done using the ARRIVE guidelines. The most widely used flavonoid in the studies was epigallocatechin gallate extracted from green tea. In general, the treatment with different flavonoids presented inhibition of tumor growth and antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory activities. The bias analysis evidenced the absence of methodological processes in all studies, such as the age or weight of the animals, the method of flavonoids' extraction, or the experimental designs, analytical methods, and outcome measures. It has been known that flavonoids have a protective effect against HCC. However, the absence or incomplete characterization of the animal models, treatment protocols, and phytochemical and toxicity analyses impaired the internal validity of the individual studies, making it difficult to determine the effectiveness of plant-derived products in the treatment of HCC.