With the rapid rise in hepatocellular carcinoma (HCC) incidence associated with metabolic dysfunction-associated steatotic liver disease (MASLD), malnutrition has emerged as a critical comorbidity that affects treatment tolerance and survival outcomes. This review systematically examines the challenges of assessing malnutrition in metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma (MASLD-HCC), its multidimensional pathological mechanisms, and emerging intervention strategies. In current clinical practice, the absence of specialized assessment tools limits the effectiveness of existing evaluation systems in addressing distinct phenotypes, such as obesity and ascites. The underlying mechanisms are complex; disruptions of the “gut-liver-muscle axis”, centered on intestinal dysbiosis, form a key network driving metabolic reprogramming, chronic inflammation, and muscle wasting. Regarding interventions, microbiome-targeted therapies - including fecal microbiota transplantation and probiotics/synbiotics - have shown promise in preclinical studies for modulating immunometabolism and improving nutritional status. However, their translation into routine clinical practice remains constrained by major bottlenecks, including insufficient large-scale randomized controlled trial evidence, uncertainty regarding long-term safety, and inadequate standardization. Future efforts should urgently focus on establishing precise assessment systems and conducting high-quality clinical validation.
Imaging is central to nearly every stage of hepatocellular carcinoma (HCC) management, from surveillance and noninvasive diagnosis to staging, locoregional therapy planning, treatment response assessment, and recurrence monitoring. Recent progress begins with imaging hardware but depends just as much on acquisition design, reconstruction, quantification, harmonization, and workflow integration. This narrative review examines how ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear or hybrid imaging have changed HCC care, while separating clinically established tools from technologies that remain largely translational. Ultrasound has advanced beyond screening through contrast-enhanced ultrasound (CEUS), Kupffer-phase agents, elastography, and fusion navigation. CT has progressed through spectral imaging, deep learning reconstruction, and cone-beam guidance, whereas photon-counting CT remains promising but early. MRI has consolidated its role through 3T platforms, multichannel coils, accelerated acquisitions, hepatobiliary contrast agents, diffusion-based imaging, magnetic resonance elastography (MRE), and abbreviated protocols. Positron emission tomography remains constrained by tracer biology in early HCC, although novel tracers and positron emission tomography (PET)/MRI broaden selected applications. Across modalities, imaging advances are most useful when acquisition and biomarker extraction are reproducible enough to support the Liver Imaging Reporting and Data System (LI-RADS), treatment response assessment, and downstream clinical decisions. Evidence is strongest for CEUS, gadoxetic acid-enhanced MRI, MRE for selected risk questions, and image-guided interventional platforms, whereas spectral CT has growing selected-use evidence but still requires broader standardization of quantitative thresholds. By contrast, radiomics, deep learning, advanced diffusion models, photon-counting CT, and theranostic-oriented molecular imaging still face important barriers related to external validity, harmonization, and clinical qualification.
Metabolic dysfunction-associated steatotic liver disease/ metabolic dysfunction-associated steatohepatitis (MASLD/MASH) has become a leading cause of advanced chronic liver disease and hepatocellular carcinoma (HCC). Among all histological features, liver fibrosis is the strongest predictor of liver-related outcomes and is increasingly recognized not only as a marker of disease severity but also as an active driver of hepatocarcinogenesis. Fibrosis promotes malignant transformation through persistent inflammation, extracellular matrix (ECM) remodeling, tissue stiffening, immune dysregulation, angiogenesis, genomic instability, and epigenetic reprogramming. Although lifestyle modification and metabolism-directed therapies can improve steatosis and steatohepatitis, established fibrosis often persists, underscoring the need for targeted antifibrotic strategies. This review summarizes the cellular and molecular mechanisms underlying MASLD-associated fibrogenesis, with particular emphasis on hepatic stellate cell activation, matrix turnover, inflammatory signaling, and fibrotic memory. We discuss current and emerging therapeutic approaches, including lifestyle-based interventions, incretin-based therapies, thyroid hormone receptor-β agonists, peroxisome proliferator-activated receptor (PPAR) agonists, fibroblast growth factor 21 (FGF21) analogs, immunomodulatory agents, and direct antifibrotic strategies targeting transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), ECM remodeling, mechanotransduction, and myofibroblast persistence. Recent clinical trials demonstrate encouraging histological improvements, particularly with metabolism-directed and pleiotropic agents; however, no randomized trial has yet shown that fibrosis regression reduces HCC incidence. Reliable non-invasive biomarkers, molecular risk signatures, liquid biopsy approaches, and multi-omics-based precision medicine will therefore be essential to monitor fibrosis regression, identify residual cancer risk, and guide individualized surveillance. We propose that antifibrotic therapy in MASLD/MASH warrants consideration not only as a strategy for fibrosis reversal but also as a potential disease-modifying approach to interrupt fibrosis-driven hepatocarcinogenesis and reduce the long-term burden of HCC.
Hepatocellular carcinoma (HCC) remains a significant global health issue, linked to chronic liver diseases such as viral hepatitis, cirrhosis, and metabolic dysfunction-related steatohepatitis. Early, accurate diagnosis is vital for treatment, but many cases are diagnosed at advanced stage. Contrast-enhanced ultrasound (CEUS) is a valuable, radiation-free tool for real-time liver lesion assessment with high accuracy. This review examines the growing role of ultrasound and CEUS in diagnosing, monitoring, and post-treatment care of HCC. CEUS has sensitivity and specificity similar to computed tomography and magnetic resonance imaging, especially for nodules ≥ 1 cm, and helps clarify uncertain Liver Imaging Reporting and Data System findings. Dynamic CEUS improves diagnosis by allowing microvascular perfusion measurement. Artificial intelligence (AI) and machine learning integration promises automated lesion classification and better consistency. CEUS is especially useful in outpatient and resource-limited settings, enabling quick decision-making and reducing delays. Meta-analyses and studies support CEUS for initial detection and post-treatment follow-up. As advanced ultrasound becomes more accessible, CEUS can be more widely used in hepatology. Future steps include standard protocols, clinician training, and AI integration. Overall, CEUS complements other imaging methods and aids precision medicine in liver cancer management.
