Search Results (921)

Background/Objectives: Telomere dysfunction and the shelterin complex are implicated in cancer, yet the specific functions and interactions of telomerase and shelterin genes in hepatocellular carcinoma (HCC) tumorigenesis remain poorly understood. This study aims to investigate the clinico-biological functions and collaborative contributions of telomerase and shelterin components in hepatocarcinogenesis. Methods: We analyzed tumor and matched non-tumor tissues from 274 HCC patients who underwent hepatectomy. Telomere-related parameters, including TERT (telomerase reverse transcriptase) expression and telomere length measured by qRT-PCR, telomerase activity assessed by the Telomerase Repeated Amplification Protocol assay, and six shelterin components analyzed by RNA sequencing, were correlated with clinicopathological features. siRNA-mediated knockdown of TPP1 (POT1–TIN2 organizing protein) was performed to evaluate its regulatory effect on TERT expression. Findings were externally validated. Results: TERT and TPP1 were upregulated in tumors with increased telomerase activity and shortened telomere length. Among the shelterin components, TPP1 showed the strongest correlation with TERT, and its expression increased with tumor multiplicity and advancing stage. TPP1 expression also correlated with proliferation-associated genes, consistent with Gene Set Enrichment Analysis suggesting TPP1 involvement in proliferative activity. TPP1 knockdown suppressed TERT protein expression and inhibited HCC cell proliferation, with the strongest anti-proliferative effect observed after dual TERT–TPP1 knockdown. Clinically, high TPP1 expression was associated with significantly earlier HCC recurrence, and co-high expression of TPP1–TERT was linked to significantly worse survival after hepatectomy. Conclusions: The TERT–TPP1 axis enhances proliferative activity and is associated with aggressive features and poor outcomes in HCC. TPP1 represents a potential therapeutic target and prognostic biomarker for HCC. Full article

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, primarily driven by chronic inflammation from viral hepatitis, metabolic dysfunction, alcohol-induced liver disease, and cirrhosis. Conventional therapies often fail in advanced stages, highlighting the need for mechanism-based, precision-guided interventions. Plant-derived secondary metabolites represent a promising class of bioactive compounds with structural diversity, multitarget activity, anti-inflammatory effects, and favorable toxicity profiles. This review follows a semi-systematic narrative that synthesizes preclinical and experimental evidence on the anti-inflammatory and anticancer properties of key phytochemicals, including epigallocatechin-3-gallate, galangin, resveratrol, quercetin, curcumin, berberine, genistein, and thymoquinone. These compounds consistently modulate critical inflammation-driven signaling pathways, PI3K/AKT/mTOR, NF-κB, JAK/STAT, Wnt/β-catenin, and MAPK, resulting in apoptosis induction, cell cycle arrest, inhibition of angiogenesis, and reduced invasion and metastasis in multiple HCC models. Despite strong preclinical evidence, clinical translation remains limited by variable bioavailability, incomplete safety data, and insufficient human studies. A staged development strategy is recommended: standardized formulations, Good Laboratory Practice-compliant pharmacokinetic/toxicology studies, validation in patient-derived models, and early-phase, biomarker-guided clinical trials with combination therapy arms. Addressing regulatory, manufacturing, and quality control considerations will be essential for advancing these compounds as adjuvant or complementary agents in precision HCC therapy. Full article

Hepatocellular carcinoma (HCC) is the sixth most diagnosed cancer worldwide and represents the second cause of cancer-related death worldwide, according to the estimates by Global Cancer Observatory in 2020. Its prognosis is strictly associated with neoplastic stage and liver function. Several treatments are involved in the management of HCC, according to its stage and the patients’ performance status. The abscopal effect is a particular phenomenon taking place in locally advanced or in metastatic cancer, as a positive off-target result of ionizing radiation at a certain distance from the irradiated zone determining a systemic effect due to the increase in tumor immune response, and resulting in the shrinkage of neoplastic lesions with a subsequent increase in tumor prognosis. If future studies will allow one to master its etiological mechanisms and deliberately trigger them, it could represent a notable weapon in the treatment of hepatocellular carcinoma, particularly at advanced stages, in which sometimes it is able to positively modify the patients’ prognosis. The aim of this review is to evaluate the literature available on this intriguing topic and the characteristics of the mechanisms that originate the abscopal effect, the treatments that can elicit this phenomenon, and the possible relevant therapeutic implications. Full article

Growth factors play a significant role in the immunopathogenesis of liver diseases, especially liver cirrhosis and hepatocellular carcinoma (HCC). The somatostatin analog octreotide has been used as treatment in advanced HCC, based on its anti-neoplastic effects in vitro. Therefore, the effect of somatostatin and octreotide was studied on several growth factors in patients with HCC. Nineteen patients with advanced HCC were treated with octreotide and compared with thirty-seven patients with viral cirrhosis (19 decompensated) treated with intravenous somatostatin for severe bleeding from portal gastropathy. Five growth factors, namely Gastrin, Insulin-like growth factor 1 (IGF 1), Hepatocyte growth factor (HGF), Stem cell factor (SCF) and Vascular endothelial growth factor (VEGF) were measured in serum before and after treatment with specific commercially available ELISAs. Seventeen healthy individuals and nineteen patients with chronic viral hepatitis C (CAH) were used as pre-treatment controls. Eighteen patients with advanced Primary Biliary Cholangitis (stage III and IV) before and after Ursodeoxycholic acid (UDCA) treatment were also studied. Pre-treatment levels of Gastrin were significantly increased in HCC, cirrhosis and PBC but not in CAH. Levels were significantly reduced by octreotide or somatostatin but also by UDCA in PBC. By contrast, IGF1 showed a mirror image being significantly reduced in HCC, cirrhosis and PBC, but not in CAH. Post-treatment levels were reduced in all groups, but not in PBC. Levels of HGF were significantly increased in HCC and cirrhosis but not in CAH and PBC. They were further increased in HCC after treatment. SCF increased only in HCC and was reduced after octreotide but not after somatostatin treatment. VEGF was reduced in cirrhosis and CAH but not in PBC. It was not significantly increased in HCC, but it was reduced by octreotide and was increased after UDCA. In this retrospective observational study, somatostatin and its analog octreotide have a significant effect on several growth factors involved in HCC pathogenesis. Full article

Background and Objectives: The increase in rates of cirrhosis and hepatocellular carcinoma (HCC) due to HCV infection supported the implementation of screening programs for control of this infection in Italy. The HepCoVe network has collected cases with chronic hepatitis C (CHC) in the Veneto region of North-East Italy since the 2000s. This platform allowed us to (a) compare the characteristics of the HCV cohort exposed to parenteral risk before or after 1995 (introduction of mandatory HCV testing), and (b) track the changes induced by IFN-based therapy and the novel direct-acting antivirals (DAA). Methods: From January 2000 to December 2005, 2703 prospectively recruited cases with CHC were analyzed and followed up for 16.2 ± 8.4 years, by a per protocol analysis. Results: Two epidemic waves occurred; the first, related to blood transfusions and infection with the HCV-1b and 2a/2c genotypes, affecting an elderly population, and the second, spread through drug addiction, among young people and with a prevalence of HCV-1a, 3a/3b and 4c/4d. Patients treated with DAA had more advanced liver disease; despite this, they achieved the highest SVR rate, compared to those who received an IFN-based regimen (95.1% vs. 61.5%; p < 0.01). The 10-year HCC incidence rate by KM was 0.81, 3.75, and 1.26 per 100 person-years (p-y) in cases with or without SVR and in the untreated group, respectively (p < 0.001). Conclusions: The period of exposure to HCV in Italy (born from 1939 to 1989) was supported by two epidemic waves. Unknowing cases of HCV infection are disappearing, particularly those included in the first cohort, among the “boomers”. Despite the eradication of HCV in all treated cases, antiviral therapy does not completely eliminate the risk of HCC onset. Full article

This review aims to provide a broad, multidisciplinary perspective on how dynamic genomics and systems biology are transforming modern healthcare, with a focus on cancer especially liver cancer (HCC). It explains how integrating multi-omics technologies such as genomics, transcriptomics, proteomics, interactomics, metabolomics, and spatial transcriptomics deepens our understanding of the complex tumor environment. These innovations enable precise patient stratification based on molecular, spatial, and functional tumor characteristics, allowing for personalized treatment plans. Emphasizing the role of regulatory networks and cell-specific pathways, the review shows how mapping these networks using multi-omics data can predict resistance, identify therapeutic targets, and aid in the development of targeted therapies. The approach shifts from standard, uniform treatments to flexible, real-time strategies guided by technologies such as liquid biopsies and wearable biosensors. A case study showcases the benefits of personalized therapy, which integrates epigenetic modifications, checkpoint inhibitors, and ongoing multi-omics monitoring in a patient with HCC. Future innovations, such as cloud-based genomic ecosystems, federated learning for privacy, and AI-driven data analysis, are also discussed to enhance decision-making and outcomes. The review underscores a move toward predictive and preventive healthcare by integrating layered data into clinical workflows. It reviews ongoing clinical trials using advanced molecular and immunological techniques for HCC. Overall, it promotes a systemic, technological, and spatial approach to cancer treatment, emphasizing the importance of experimental, biochemical–functional, and biophysical data-driven insights in personalizing medicine. Full article

Background/Objectives: Atezolizumab plus bevacizumab (Atz+Bev) is widely used for advanced hepatocellular carcinoma (HCC), yet predictors of post-progression survival (PPS), a clinically meaningful endpoint reflecting the feasibility of treatment sequencing, remain unclear. We aimed to identify determinants of PPS and factors associated with successful transition to subsequent therapy after progressive disease (PD) on Atz+Bev. Methods: We retrospectively analyzed 132 patients with HCC who initiated Atz+Bev with Child–Pugh A and Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1. PPS was defined as survival from radiological PD to death; tumor response was assessed by RECIST v1.1. Results: Among 132 patients treated with Atz+Bev, median progression-free and overall survival were 9.2 and 21.2 months. PD occurred in 97 patients, with a median PPS of 9.2 months. At PD, 76 patients (78.4%) maintained both Child–Pugh A and ECOG PS 0/1; 93.4% of these patients transitioned to subsequent therapy, compared with 38.0% of patients who did not maintain Child–Pugh A and ECOG PS 0/1. The median PPS values were 14.7 and 2.0 months, respectively (p < 0.0001). In this PD cohort, disease control achieved with subsequent therapy after radiological PD was associated with longer PPS (16.1 vs. 5.0 mosnths; p = 0.0002). ECOG PS 0, Child–Pugh A, absence of portal vein invasion, and AFP < 400 ng/mL at PD independently predicted prolonged PPS. A baseline Child–Pugh score of 5 independently predicted preservation of Child–Pugh A and ECOG PS 0/1 at PD. Conclusions: Initiating Atz+Bev under optimal liver function (Child–Pugh 5) and preserving hepatic reserve and performance status through progression are critical for enabling subsequent therapy and achieving longer PPS. Full article

Background: Chemokine CCL5 may drive inflammation and vascular risk in advanced liver disease, but its cardiovascular implications are unclear. Secreted by hepatic, endothelial, macrophage, and lymphocytic cells, CCL5 is involved in cytokine regulation. Its serum levels rise in acute liver injury and hepatocellular carcinoma (HCC), but decline with fibrosis progression in end-stage liver disease (ESLD). CCL5 has also been linked to atherosclerosis. This study aimed to evaluate serum CCL5 levels in ESLD patients listed for liver transplantation (LT) and to assess their potential role as markers of cardiovascular (CV) risk and portal hypertension. Methods: We conducted an observational cohort study. Between 2019 and 2022, patients with ESLD evaluated for LT were enrolled. Data on liver pathology, CV risk, and laboratory parameters were collected. Serum CCL5 concentrations were measured using Sigma Aldrich^® CCL5 ELISA kits (MilliporeSigma, St. Louis, MO, USA). The database was analyzed with IBM^® SPSS^® Statistics version 20 (Chicago, IL, USA). Results: Overall, 46 patients were included, 50% with viral hepatitis and 28.3% with alcohol-related liver disease. HCC was present in 37% of cases. The median CV risk scores (CAD_LT = 7, mCAD_LT = 7, CAR_OLT = 18) placed the population at moderate CV risk. Serum CCL5 levels did not vary significantly between viral vs. non-viral cirrhosis (5511.8 vs. 6272.5 pg/mL, p = 0.15) and were not influenced by the presence of HCC (6098.4 vs. 5771.3 pg/mL, p = 0.55). We did not detect a correlation with MELD score (p = 0.21) or CV risk scores (CAD_LT: p = 0.58; mCAD_LT: p = 0.70; CAR_OLT: p = 0.22). Patients with thrombocytopenia (<100,000/µL, 54.3%) or a history of esophageal variceal ligation had lower CCL5 levels (5170.9 vs. 6750.8 pg/mL, p = 0.002 and 4252.0 vs. 6237.5 pg/mL, p = 0.003, respectively). Similarly, patients with a history of previous variceal bleeding and spontaneous bacterial peritonitis (SBP) had lower levels of CCL5 (4373.8 vs. 6119.9 pg/mL, p = 0.02 and 3404.3 vs. 6606.7 pg/mL, p = 0.01, respectively). We found a negative correlation between CCL5 and QTc interval duration (τ = −0.216, p = 0.037), left ventricle size (LV: τ = −0.235, p = 0.027), and pulmonary artery pressure (RV/RA gradient: τ = −0.225, p = 0.03). CCL5 correlated positively with the inflammatory markers C-reactive protein (CRP) (τ = 0.246, p = 0.018) and fibrinogen (r = 0.216, p = 0.04). Conclusions: In liver transplant candidates, serum CCL5 is not associated with cardiovascular risk scores or coronary atherosclerotic burden, but is inversely associated with clinical markers of portal hypertension severity. These findings suggest that CCL5 may serve as a potential non-invasive surrogate marker of portal hypertension rather than a cardiovascular risk biomarker in ESLD. Full article

Background: The combination of hepatic arterial infusion chemotherapy (HAIC) with immune checkpoint inhibitors (ICIs) and anti-angiogenic agents represents a potential therapeutic strategy for advanced hepatocellular carcinoma (HCC). This study aimed to compare the efficacy and safety of triple therapies combining HAIC with ICIs and either bevacizumab or tyrosine kinase inhibitors (TKIs) in these patients. Methods: This retrospective single-center study enrolled 65 consecutive patients with advanced HCC who received HAIC combined with ICIs plus either bevacizumab (bevacizumab group, n = 31) or TKIs (TKIs group, n = 34) between June 2021 and June 2023. Primary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety profiles. Results: The bevacizumab group demonstrated significantly prolonged median PFS (10.9 vs. 7.4 months, p = 0.001) and higher ORR (83.9% vs. 61.8%, p = 0.047) compared with the TKIs group. DOR was longer in the bevacizumab group (7.9 vs. 5.3 months, p = 0.008). Median overall survival (OS) was not reached in the bevacizumab group versus 22.6 months in the TKIs group. Grade 3–4 adverse events occurred in 67.7% of the bevacizumab group and 73.5% of the TKIs group, with distinct toxicity profiles. Gastrointestinal hemorrhage (45.2%) and gastric ulcer (22.6%) predominated in the bevacizumab group, whereas the TKIs group exhibited more hepatic enzyme elevations (aspartate aminotransferase, 67.6%; alanine aminotransferase, 61.8%), proteinuria (29.4%), diarrhea (26.5%), hand-foot syndrome (20.6%), and reactive cutaneous capillary endothelial proliferation (11.8%). Conclusions: Bevacizumab-containing triplet therapy was associated with improved tumor control and delayed progression compared to TKIs-based regimens in advanced HCC. The higher bleeding risk in the bevacizumab group highlights the necessity of standardized baseline evaluation and adequate preventive measures. Full article

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality. It usually arises in cirrhotic liver, where chronic inflammation and fibrosis create a tumor-permissive microenvironment. Dysregulation of microRNAs (miRNAs), particularly upregulation of the oncomiR miR-221 and loss of the tumor suppressor miR-199a-3p represent key drivers of liver carcinogenesis. The TG221 transgenic mouse, designed to overexpress miR-221 in hepatocytes, provides a relevant in vivo platform for mechanistic studies and for testing preventive and therapeutic approaches. The TG221 model recapitulates miR-221-driven tumorigenesis, including suppression of p27, p57 and Bmf. It is characterized by steatohepatitic injury and accelerated tumor formation after genotoxic challenge. In the cirrhotic CCl₄-induced background, TG221 mice develop fibrosis and cirrhosis followed by dysplastic and malignant lesions, mirroring the natural history of human HCC. Metformin administered during early fibrosis prevented macroscopic tumor formation and suppressed PI3K/AKT/mTOR signaling. Anti-miR-221 and miR-199a-3p mimics reduced tumor burden, restored tumor-suppressive pathways and improved liver integrity, thus indicating feasible chemopreventive strategies. From a therapeutic point of view, miR-199a-3p replacement synergized with palbociclib and overcame sorafenib resistance. A miR-199a-3p-responsive oncolytic adenovirus achieved tumor-selective replication with minimal toxicity. This review highlights the importance of the TG221 transgenic mouse as a powerful model for studying miRNA-driven hepatocarcinogenesis and enables preclinical evaluation of RNA-based chemopreventive and therapeutic approaches. Metformin, miRNA inhibition, miRNA replacement and miRNA-guided viral therapies emerge as promising approaches for advancing precision prevention and treatment strategies in HCC. Full article

Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes that drive liver tumor initiation and progression. By degrading and reorganizing extracellular matrix components, MMPs facilitate tumor expansion, tissue invasion, and metastatic dissemination. In addition, these enzymes regulate the availability of growth factors, cytokines, and chemokines, thereby influencing angiogenesis, inflammation, immune cell recruitment, and the development of an immunosuppressive tumor microenvironment. Aberrant expression or activity of multiple MMP family members is consistently associated with aggressive clinicopathologic features, including vascular invasion, increased metastatic potential, and reduced patient survival, highlighting their promise as prognostic markers and actionable therapeutic targets. Past attempts to modulate MMP activity were hindered by broad inhibition profiles and dose-limiting toxicities, underscoring the need for improved specificity and delivery strategies. Recent advances in molecular design, biologics engineering, and nanotechnology have revitalized interest in MMP targeting by enabling more selective, context-dependent modulation of proteolytic activity. Preclinical studies demonstrate that carefully tuned MMP inhibition can limit tumor invasion, enhance anti-angiogenic responses, and potentially improve the efficacy of existing systemic therapies, including immuno-oncology agents. This review synthesizes current knowledge on the multifaceted roles of MMPs in HCC pathobiology and evaluates emerging therapeutic strategies that may finally unlock the clinical potential of targeting these proteases. Full article

Liver cancer remains a significant global health challenge, with hepatocellular carcinoma (HCC) being the most prevalent form. Despite advancements in treatment, high recurrence rates and the limited efficacy of conventional therapies highlight the need for novel interventions. Cinobufagin (CB), a bufadienolide extracted from the parotid secretion of Bufo gargarizans and B. melanostictus, has emerged as a promising compound with multiple antitumor mechanisms. This comprehensive review assesses the current evidence regarding CB and its containing medicine, cinobufacini, in liver cancer models. Cinobufacini is a traditional Chinese medicine extract, whereas CB refers specifically to one of its active components. The pharmacodynamic actions of CB include induction of apoptosis, DNA damage, inhibition of proliferation and migration, and modulation of key oncogenic pathways such as PI3K/Akt/mTOR, Akt/ERK, and AURKA-mTOR-eIF4E. Additionally, CB disrupts tumor metabolism and induces oxidative stress. Preclinical studies, both in vitro and in vivo, demonstrate significant antitumor efficacy. However, concerns remain regarding CB’s toxicity profile at high doses. This review emphasizes the therapeutic potential of CB in HCC treatment and advocates for further translational research to optimize its clinical applicability, dosage, and safety. Full article

Hepatocellular carcinoma (HCC) is the main type of liver cancer and one of the malignancies with the highest mortality rates worldwide. HCC is associated with diverse etiological factors including alcohol use, viral infections, fatty liver disease, and liver cirrhosis (a major risk factor for HCC). Unfortunately, many patients are diagnosed at advanced stages of the disease and receive palliative treatment only. Therefore, early markers of HCC and novel therapeutic approaches are urgently needed. The endocannabinoid system is involved in various physiological processes such as motor coordination, emotional control, learning and memory, neuronal development, antinociception, and immunological processes. Interestingly, endocannabinoids modulate signaling pathways involved in cell survival, proliferation, apoptosis, autophagy, and immune response. Consistently, several cannabinoids have demonstrated potential antitumor properties in experimental models. The participation of metabotropic and ionotropic cannabinoid receptors in the biological effects of cannabinoids has been extensively described. In addition, cannabinoids interact with other targets, including several ion channels. Notably, several ion channels targeted by cannabinoids are involved in inflammation, proliferation, and apoptosis in liver diseases, including HCC. In this literature review, we describe and discuss both the endocannabinoid system and exogenous phytocannabinoids, such as cannabidiol and Δ⁹-tetrahydrocannabinol, along with their canonical receptors, as well as the cannabidiol-targeted ion channels and their role in liver cancer and its preceding liver diseases. The cannabidiol-ion channel association is an extraordinary opportunity in liver cancer prevention and therapy, with potential implications for several environments that are for the benefit of cancer patients, including sociocultural, public health, and economic systems. Full article

Hepatocellular carcinoma (HCC) remains one of the most common malignancies worldwide and a leading cause of cancer-related mortality. Current treatment options for advanced or unresectable HCC have limited efficacy and are often associated with systemic toxicity. In this study, a multifunctional, thermosensitive hydrogel-based delivery system was developed to enhance localized treatment of HCC. This system incorporates rhenium-188 sulfur colloid (¹⁸⁸Re-colloid), a β-emitting radiotherapeutic agent, and paclitaxel (PTX)-loaded micelles within a biodegradable PCL-PEG-PCL hydrogel matrix. The formulation enables in situ gelation at physiological temperatures, providing sustained release and prolonged retention of therapeutic agents at the tumor site. Physicochemical characterization confirmed the structural integrity and injectability of the formulations, while in vivo biodistribution studies in a murine hepatic tumor model demonstrated enhanced intratumoral accumulation and reduced systemic dispersion. The combined chemo-radiotherapeutic platform showed potential for improved therapeutic efficacy through synergistic action, offering a promising minimally invasive strategy for treating unresectable hepatocellular carcinoma. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer and cancer-related death worldwide. Beyond the well-known factors influencing the risk of HCC, experimental data from animal models and observational human studies support a significant role of the gut microbiota (GM) in HCC initiation and progression. Dysbiosis and increased intestinal permeability synergistically disrupt the ‘gut–liver axis,’ exposing the liver to bacterial metabolites and microbial-associated molecular patterns, thereby contributing to hepatocarcinogenesis. While these findings have expanded our understanding of HCC pathogenesis, a critical translational gap persists as most data derive from preclinical settings, with limited validation in large-scale clinical studies. Methods: This narrative review aimed to contextualise the current evidence on the GM-HCC axis and its clinical translatability. A literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science up to July 2025 using Medical Subject Headings and related keywords, including HCC, GM, dysbiosis, intestinal permeability, gut–liver axis, microbial metabolites, inflammation/immune modulation, and microbiota-targeted interventions (probiotics, antibiotics, and faecal microbiota transplantation). Reference lists of relevant articles were also screened to identify additional studies. Results: Preclinical models consistently indicate that dysbiosis and impaired gut barrier function can promote hepatic inflammation, immune dysregulation, and pro-tumorigenic signalling through microbe-derived products and metabolite perturbations, supporting a contributory role of the GM in hepatocarcinogenesis. In humans, HCC and advanced chronic liver disease are associated with altered microbial composition and function, increased markers of intestinal permeability, and changes in bile acid and other metabolite profiles; however, reported signatures are heterogeneous across cohorts and analytical platforms. Conclusions: The GM is a biologically plausible and experimentally supported contributor to HCC initiation and progression, with potential for biomarker development and therapeutic targeting. However, clinical translation is limited by predominantly preclinical/associative evidence, interindividual variability, and non-standardised microbiome methods. Large longitudinal studies and adequately powered randomised trials are needed to establish causality, validate biomarkers, and determine whether GM modulation improves HCC prevention, detection, stratification, or outcomes. Full article