Livers, Volume 5, Issue 4 (December 2025) – 2 articles

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is associated with poor clinical prognosis and high mortality, despite the advances related to therapeutic options for HCC. Therefore, exploring alternative therapeutic options and their associated mechanisms is relevant and urgently needed. Natural products may be an important source of novel anti-cancer compounds. Coffee consumption is associated with protective effects against liver diseases, but the molecular mechanisms underlying these benefits remain poorly understood. Objectives: In this study, we evaluated the in vitro effects of green (GC) and roasted coffee (RC) extracts, alongside chlorogenic acid (CGA), on the proliferation of HepG2 hepatocellular carcinoma cells. Results: Both coffee extracts and CGAs significantly reduced HepG2 cell viability and cell proliferation in a dose-dependent manner. GC at 500 µg/mL and CGA at 400 and 800 µM significantly induced caspase-3 activity. In addition, HepG2 cells treated with coffee extracts (500 and 1000 µg/mL) resulted in dose-dependent membrane permeabilization, leading to an increased number of necrotic cells. Despite these anti-proliferative effects, TOP/FOP luciferase assays revealed minimal activation of the Wnt/β-catenin signaling pathway. Among canonical Wnt target genes, only c-Myc expression was notably downregulated after treatment. Moreover, β-catenin protein levels and subcellular localization remained largely unchanged. Conclusions: These findings suggest that coffee extracts and chlorogenic acids inhibit HepG2 cell proliferation, highlighting their hepatoprotective properties, even in cells containing mutations that constitutively activate Wnt signaling. Full article

Background: Liver cancer, either primary or metastatic, is a leading cause of cancer-related deaths and in many cases is presented in stages requiring major hepatectomy. Adequate future liver remnant (FLR) volume is essential before any major hepatectomy. Portal vein embolization (PVE) has long been the standard technique for preoperative liver hypertrophy, but liver venous deprivation (LVD) has emerged as a novel method, potentially offering faster and superior results. The aim of this study is to compare FLR hypertrophy outcomes between LVD and PVE in patients undergoing major hepatectomy for liver malignancy. Methods: A systematic literature search was conducted across PubMed, Cochrane library, and clinicaltrials.gov for studies assessing FLR volume changes after LVD or PVE in patients with primary or secondary liver tumors undergoing liver resection. Data extraction was performed independently by two reviewers. The study protocol was registered in PROSPERO and was prepared according to the PRISMA guidelines. Results: Twelve retrospective cohort studies were included in this systematic review. Liver venous deprivation consistently demonstrated superior FLR hypertrophy, with a faster and higher percentage increase compared to PVE. Time to resection was also shorter in the LVD groups in most studies. Safety outcomes were comparable, with no consistent difference in post-procedural complications or mortality. Conclusions: Liver venous deprivation may potentially be a safe and effective alternative to PVE, offering more robust and rapid FLR hypertrophy with similar morbidity and mortality rates. While current evidence supports its superiority in selected patients, future validation with larger prospective clinical trials is essential before it can be adopted as standard management of patients with insufficient FLR volume. Full article