Search Results (148)

Liver cancer has high incidence and mortality rates worldwide, with hepatocellular carcinoma (HCC) being the main histological subtype, accounting for 90% of primary liver cancers. The high mutation rate of viruses combined with endoplasmic reticulum stress may lead to the occurrence of cancer. Hepatitis B virus (HBV) infection is one of the most important pathogenic factors of HCC. The carcinogenic mechanisms of HBV have been widely studied. Among these mechanisms, immune escape and vaccine escape caused by mutations in the HBV S gene have been reported in numerous studies of patients with chronic hepatitis B. In addition, pre-S1/S2 mutations and surface protein truncation mutations may activate multiple signaling pathways. This activation leads to the abnormal proliferation and differentiation of hepatocytes, thereby contributing to the development of HCC. This review aims to integrate the existing literature, summarize the common mutations in the HBV S gene region, and explore the related pathogenic mechanisms. Full article

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, but its molecular drivers remain underexplored in Latin American populations. This study investigated the prevalence, co-occurrence, and tissue distribution of somatic mutations in the TERT promoter (C228T/C250T) and CTNNB1 exon 3, as well as TERT gene expression, in liver tissues from Brazilian patients. A total of 85 samples (42 HCC, 21 cirrhosis, and 22 hepatitis) were analysed using Sanger sequencing and RT-qPCR. TERT promoter mutations were detected in 47.6% of HCC tissues, including C228T (45.2%) and C250T (2.4%), and were also present in 19% of cirrhotic tissues but absent in hepatitis samples, supporting their emergence in early hepatocarcinogenesis. CTNNB1 exon 3 mutations occurred in 17.2% of HCCs and significantly co-occurred with TERTp mutations (66.7%, p = 0.0485), although the number of CTNNB1-mutated cases was limited. TERT expression was significantly upregulated in HCC tissues regardless of mutation status (p < 0.001). This is the first study to characterise these mutations in Brazilian HCC patients, highlighting the C228T mutation as a promising biomarker for early detection and molecular surveillance in cirrhotic individuals. Despite the genetic admixture of the studied population, the mutational patterns were comparable to those reported in more homogeneous populations, reinforcing the global relevance of these molecular alterations. Full article

This study analyzes the intersection of energy, urban planning, decarbonization, and sustainability as a central axis for addressing urban development challenges in Latin America. A systematic search of the Scopus database selected 509 articles published between 2019 and 2024. The documents were thematically classified into urban planning (274), energy (79), and decarbonization (147), identifying only 10 studies that simultaneously integrate at least two of these dimensions in Latin American contexts. While this sample of 10 articles does not allow for generalizations about the region, the article selects representative cases to contextualize the type of research conducted, rather than offering extrapolable results. An exploratory multivariate analysis was applied to identify patterns, thematic gaps, and convergence trends, including Principal Component Analysis (PCA) to reduce the dimensionality of the set of key concepts and Hierarchical Clustering (HCC) to group terms according to their semantic proximity. These results are complemented by co-occurrence and thematic concentration maps generated from keywords extracted from the selected articles. The findings reveal a low level of integration among the topics analyzed, justifying the need to establish new lines of interdisciplinary research. The study proposes a replicable analytical tool that guides future regional research and contributes to the achievement of the Sustainable Development Goals, especially SDG 7 (Affordable and Clean Energy), SDG 11 (Sustainable Cities and Communities), and SDG 13 (Climate Action). Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are spreading worldwide as the most critical causes of cirrhosis and hepatocellular carcinoma (HCC). Thus, improving the screening and managing strategies for patients with MASLD or MASH is necessary. A traditional non-systemic review provided this narrative. Genetic variations associated with the development of MASLD and MASH, such as PNPLA3, TM6SF2, GCKR, MBOAT7, MERTK, and HSD17B13, were initially reviewed. PNPLA3 genetic variants appeared to be strongly associated with the increased pathogenesis of MASLD, MASH, cirrhosis, and HCC. We also reviewed the useful polygenic risk score (PRS) for the development of MASLD, MASH, their related cirrhosis, and the occurrence of HCC. PRSs appeared to be better predictors of MASLD, MASH, the development of cirrhosis, and the occurrence of HCC in patients with MASLD or MASH than any single-nucleotide polymorphisms. RNA interference and antisense nucleotides against the genetic variations of PNPLA3 and HSD17B13 are also being developed. Multidisciplinary collaboration and cooperation involving hepatologists, geneticists, pharmacologists, and pathologists should resolve complicated problems in MASLD and MASH. This narrative review highlights the importance of the genetic susceptibility and PRS as predictive markers and personalized medicine for patients with MASLD or MASH in the future. Full article

(1) Background: Hepatitis C virus (HCV) infection poses a significant health burden, particularly in Mongolia, where the HCV prevalence is notably high. This study evaluates the long-term outcomes of HCV treatment with ledipasvir/sofosbuvir, focusing on mortality, viral relapse, and hepatocellular carcinoma (HCC) development. (2) Methods: This prospective, longitudinal cohort study initially enrolled patients with chronic HCV in Mongolia between 2016 and 2017, focusing on those who completed the five-year follow-up (n = 303). The study measured long-term mortality, HCC development, and viral relapse, employing non-invasive methods to assess liver fibrosis and liver function. (3) Results: At the outset, 98.2% of the patients achieved undetectable HCV RNA levels. Over five years, 6.27% experienced viral relapse and 3.30% developed hepatocellular carcinoma (HCC), with a mortality rate of 5.94%. In a multivariable analysis, the significant predictors for HCC occurrence included age (OR = 1.081, 95% CI = 1.021–1.145), liver cirrhosis (OR = 5.866, 95% CI = 1.672–22.577), and GGT level (OR = 1.011, 95% CI = 1.004–1.018). The independent predictors of mortality included age (OR = 1.083, 95% CI = 1.024–1.147), liver cirrhosis (OR = 6.529, 95% CI = 1.913–22.281), and GGT (OR = 1.011, 95% CI = 1.004–1.017). (4) Conclusions: This study demonstrates that ledipasvir/sofosbuvir effectively suppresses HCV initially and maintains low viral relapse rates over the long term. However, it emphasizes the need for continued management to reduce the long-term risk of HCC and mortality, especially in patients with severe liver fibrosis or cirrhosis. Full article

Novel direct antiviral-acting (DAA) molecules significantly improved efficacy and ameliorated outcomes of patients with chronic hepatitis C (CHC). The extensive use of DAA from 2015, due to large access to therapy, maximized rates of viral eradication with a safety profile in the majority of cases. Aims: We evaluated risk factors and the incidence of related clinical events and hepatocellular carcinoma (HCC) in cases with sustained virologic response (SVR) after DAA. We also aimed to apply a score assessment to identify the individual patient with unfavorable outcomes during an average follow-up (FU) of five years. Methods: In total, 470 cases consecutively recruited with CHC have been compared by non-invasive tests (NIT), as APRI, FORNS, FIB-4, LSPS, and transient elastography (TE) liver stiffness measurement (LSM), to identify cutoff related to major event onset. Results: Grouping of cases without or with related events development of both types hepatic (HE) (i.e., HCC or further cirrhosis decompensation or/with hospitalized septic state) or extrahepatic (EHE) (i.e., other tumors, bleeding, or thrombotic episodes and other organs pathologic conditions not liver related)allowed us to select the parameters to propose a novel risk stratification system (RISS) for the identification of the remnant individual patient’s risk for HCC occurrence, orthotopic liver transplant (OLT) need, or death during long-term follow-up (FU). Conclusions: Patients with cirrhosis and portal hypertension (PH) maintained a higher LSM mean value (>25 kPa), showed the lowest reduction of NIT scores, and developed events in 80/108 (74%) cases (67 and 13 of HE and EHE type), even after long-term successful DAA therapy. Furthermore, cases with RISS score ≥ 8 demonstrated a significant incidence of HCC (37/46, 80.4%) and a reduction in survival rate to 65.4% at 5-year FU. Full article

Hepatocellular carcinoma (HCC), a common consequence of chronic liver disease, ranks among the most prevalent cancers globally and contributes significantly to cancer-related mortality. Liver fibrosis is intimately associated with hepatic function and the likelihood of future HCC occurrence. Despite the fact that liver biopsy continues to be the gold standard for diagnosing fibrosis, its utility is hindered by cost and invasiveness, along with patient unease, procedural rejection, and potential adverse effects. Liver elastography has become a leading noninvasive means of assessing tissue stiffness with considerable diagnostic precision. Malignant tumors generally exhibit higher cellularity in comparison to benign ones, resulting in increased stiffness. Elastography techniques capitalize on alterations in tissue elasticity stemming from specific pathological or physiological processes. Technological innovations, such as advanced ultrasound imaging and artificial intelligence (AI)-integrated systems, are paving the way for enhanced diagnostic accuracy and risk prediction. Recent research underscores the potential of elastography in managing HCC patients, presenting novel clinical applications, including prediction of HCC development, differentiation between malignant and benign liver lesions, evaluating treatment response, and forecasting recurrence post-treatment, though certain findings remain contentious. Therefore, this review aims to sum up the latest advancements in liver elastography for HCC patients, outlining its applications while addressing existing limitations and avenues for future progress. Full article

Background/Objectives: Extrahepatic recurrence (EHR) is a significant negative prognostic factor in hepatocellular carcinoma (HCC). Although EHR is commonly observed in high-risk patients following HCC hepatectomy, its occurrence without concurrent intrahepatic HCC remains poorly understood. Therefore, this study aims to examine the clinical characteristics and risk factors associated with EHR in patients without intrahepatic HCC at diagnosis. Methods: This study included 1066 treatment-naïve patients who underwent curative hepatectomy for HCC at four tertiary academic centers between January 2004 and December 2019. After excluding those with intrahepatic recurrence (IHR), concurrent EHR, or incomplete clinical records, 569 patients were included in the final analysis. Risk factors for EHR were assessed using multivariate Cox regression over a median follow-up period of 3.91 years. Results: Among the cohort, 38 patients developed EHR post-surgery without residual intrahepatic HCC, with a median follow-up of 1.04 years. These patients experienced earlier initial HCC recurrence than those without EHR (1.73 vs. 4.43 years). Multivariate analysis revealed significant associations between EHR and microvascular invasion (hazard ratio [HR]: 2.418, p = 0.020), tumor necrosis (HR: 2.592, p = 0.009), and initial tumor staging beyond the Milan criteria (HR: 3.008, p = 0.001). Moreover, Cox regression analysis revealed that EHR strongly correlated with decreased post-hepatectomy survival (HR: 14.044, p < 0.001). Cumulative EHR and survival rates were closely linked to the number of risk factors present. Conclusions: EHR without detectable IHR is significant and warrants close monitoring in high-risk patients. Full article

Approximately 95% of patients with chronic hepatitis C achieve viral eradication through direct-acting antiviral (DAA) treatment. Ensuing clinical benefits include halting liver fibrosis, thereby reducing the need for liver transplantation, and decreasing both liver-related and overall mortality. It is well established that, although ameliorated, the risk of developing hepatocellular carcinoma (HCC) persists, particularly among patients with pre-treatment advanced fibrosis/cirrhosis. Current guidelines recommend indefinite HCC surveillance in these patients. However, a recent Markov model evaluation shows that HCC surveillance is cost-effective only for patients with cirrhosis but not so for those with F3 fibrosis, a finding which points out the need to better define the risk of HCC in hepatitis C patients after cure and further characterize pre- and post-treatment factors that might affect the incidence of HCC in this setting. We reviewed the literature analyzing this aspect. Here we summarize the main findings: male gender and older age are independent predictors of increased risk of post-cure HCC development. Moreover, non-invasive tests for hepatic fibrosis, namely FIB4, APRI, and liver stiffness, measured before and after treatment and their post-therapy change, contribute to better stratifying the risk of HCC occurrence. Furthermore, low serum albumin, as well as an AFP above 7 ng/mL prior to and after DAA therapy, also constitute independent predictors of HCC development. Considering these findings, we propose to classify patients with HCV viral eradication and advanced fibrosis/cirrhosis into groups of low, medium, or high risk of HCC and to adopt adequate surveillance strategies for each group, including protocols for abbreviated magnetic resonance imaging (MRI) for those at the highest risk. Full article

Formononetin (FM), an isoflavone with a range of anti-cancer activities, has not been fully elucidated regarding its anti-hepatocellular carcinoma (HCC) mechanisms. Therefore, this study aims to explore the underlying mechanisms of FM using a comprehensive pharmacology model based on computational technologies and omics technology. A network pharmacology approach was applied to detect the components and targets. A mathematical formula was used to evaluate the network contribution index (CI). Bioinformatics analysis was used to analyze clinical data related to HCC targets corresponding to the core component, and molecular docking simulations were conducted to assess binding activity. The results showed that FM induces oxidative DNA damage through ROS generation and triggers G2/M phase cell cycle arrest via the Chk1/Cdc25C/CDK1/CCNB1 signaling pathway. Subsequently, UPLC-MS/MS was applied for the analysis of differential metabolites and the exploration of distinct metabolic pathways. FM limited the synthesis of glutathione, promoted lipid peroxidation, and facilitated the generation of divalent iron. Finally, a colony formation assay, Western blot, and molecular dynamics simulation methods were executed to further validate the metabolomic results. FM exhibited a strong binding affinity for glutathione peroxidase 4 (GPX4). In addition, FM induces ferroptosis by inhibiting the p53/xCT/GPX4 signaling pathway. In vivo, FM could inhibit tumor growth. Conclusions: FM could induce DNA damage leading to cell cycle arrest and may also induce ferroptosis by regulating glutathione metabolism, thereby intervening in the occurrence and development of HCC, making it a promising candidate for HCC treatment. Full article

Background and Objectives: Primary liver cancer is a major cause of mortality, ranking third among the most fatal cancers. In Egypt, liver cancer constitutes 11.75% of gastrointestinal malignancies, with HCC representing 70.5% of cases. The landscape of HCC management was revolutionized by locoregional modalities, which offer a comparable alternative to conventional techniques, with low complications and minimal invasiveness. RFA is a technique that is suitable for early-stage lesions in the liver, with a high overall survival and low complication rates. However, the associated complications cause potential mortality and morbidity. The proper selection of patients may avoid such complications. This study presents a five-year experience of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) in Egypt, analyzing the predictors of complications and the computed tomography (CT) features associated with complications post-ablation. Materials and Methods: The study included 1000 cases (84% males with a mean age of 60), with 90% having HCC. Exclusion criteria included prior chemoembolization and non-HCC primary hepatic tumors. Patients underwent RFA at Cairo University Hospital and two private centers from January 2014 to January 2019. The workup involved clinical assessments, lab tests, and CT scans. Complications were classified as major or minor. Statistical analysis was conducted via SPSS software Version 22.0, with associations evaluated using a chi-square test. A decision tree was employed to determine the predictive values for different variables associated with the complications. Results: Overall, the rate of complications was 4%, and mortality stood low at 0.1%. Subcapsular lesions were associated with complications, as well as the lesion size, site, Child–Pugh classification, and the number of RFA sessions. Decision tree analysis determined the size of a lesion to be the most predictive factor of major complications, whereas the site of the lesion predicted the occurrence of minor complications. Conclusions: RFA offers low complication rates; however, precise patient selection is critical. The approach and imaging modality choice influence the outcomes. Clinician experience enhances early complication detection, thereby allowing for effective treatments. Full article

The transcription factor carbohydrate response element binding protein (ChREBP) has emerged as a crucial regulator of hepatic glucose and lipid metabolism. The increased ChREBP activity involves the pro-oncogenic PI3K/AKT/mTOR signaling pathway that induces aberrant lipogenesis, thereby promoting hepatocellular carcinomas (HCC). However, the molecular pathogenesis of ChREBP-related hepatocarcinogenesis remains unexplored in the high-fat diet (HFD)-induced mouse model. Male C57BL/6J (WT) and liver-specific (L)-ChREBP-KO mice were maintained on either a HFD or a control diet for 12, 24, and 48 weeks, starting at the age of 4 weeks. At the end of the feeding period, mice were perfused, and liver tissues were formalin-fixed, paraffin-embedded, sectioned, and stained for histological and immunohistochemical analysis. Biochemical and gene expression analysis were conducted using serum and frozen liver tissue. Mice fed with HFD showed a significant increase (p < 0.05) in body weight from 8 weeks onwards compared to the control. WT and L-ChREBP-KO mice also demonstrated a significant increase (p < 0.05) in liver-to-body weight ratio in the 48-week HFD group. HFD mice exhibited a gradual rise in hepatic lipid accumulation over time, with 24-week mice showing a 20–30% increase in fat content, which further advanced to 80–100% fat accumulation at 48 weeks. Both dietary source and the increased expression of lipogenic pathways at transcriptional and protein levels induced steatosis and steatohepatitis in the HFD group. Moreover, WT mice on a HFD exhibited markedly higher inflammation compared to the L-ChREBP-KO mice. The enhanced lipogenesis, glycolysis, persistent inflammation, and activation of the AKT/mTOR pathway collectively resulted in significant metabolic disturbances, thereby promoting HCC development and progression in WT mice. In contrast, hepatic loss of ChREBP resulted in reduced hepatocyte proliferation in the HFD group, which significantly contributed to the impaired hepatocarcinogenesis and a reduced HCC occurrence in the L-ChREBP-KO mice. Our present study implicates that prolonged HFD feeding contributes to NAFLD/NASH, which in turn progresses to HCC development in WT mice. Collectively, hepatic ChREBP deletion ameliorates hepatic inflammation and metabolic alterations, thereby impairing NASH-driven hepatocarcinogenesis. Full article

Introduction: Curative treatment of HCC can be achieved by liver transplantation. In the framework of transplantation, add-on transarterial chemoembolization (TACE) can be performed as bridging therapy for local tumor control. The association between TACE and an increased incidence of hepatic arterial complications after transplantation has been investigated in multiple research items; however, the exact association remains unclear. The aim of this report was to explore the role of pre-transplantation TACE and pre-existing vascular celiac pathologies on the occurrence of postoperative hepatic arterial complications. Methods: This retrospective single-center study included all patients who underwent liver transplantation between 2008 and 2020. Arterial complication was defined as any postoperative occlusion, stenosis >50%, dissection or aneurysm on cross-sectional imaging. Results: This study encompasses 109 patients after transplantation, of which 80 underwent TACE prior to transplantation. The overall incidence of postoperative arterial complications did not differ between the groups (TACE 8/80 vs. control 6/29, p = 0.19). Further analysis showed no significant differences in the occurrence of specific complications (Occlusion: TACE 9/80 vs. control 3/29, p = 0.56; Stenosis: TACE 4/80 vs. control 5/29, p = 0.05; Dissection: TACE 1/80 vs. control 1/29; p = 0.46). Furthermore, linear regression analysis for preoperative TACE therapy, anatomic variants and pre-existing pathologies of the hepatic vasculature showed no association with postoperative arterial complications. Conclusions: Preoperative TACE therapy showed no influence on the incidence of post-transplant arterial complications in patients after liver transplantation. Furthermore, preoperative TACE therapy as well as anatomic variants and pre-existing arterial pathologies of the celiac axis could not be identified as risk factors for complications at the arterial anastomotic site after transplantation. Full article

Hepatocellular carcinoma (HCC) is a heterogeneous tumor associated with several risk factors, with non-alcoholic fatty liver disease (NAFLD) emerging as an important cause of liver tumorigenesis. Due to the obesity epidemics, the occurrence of NAFLD has significantly increased with nearly 30% prevalence worldwide. HCC often arises in the background of chronic liver disease (CLD), such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Gut microbiome (GM) alterations have been linked to NAFLD progression and HCC development, with several investigations reporting a crucial role for the gut–liver axis and microbial metabolites in promoting CLD. Moreover, the GM affects liver homeostasis, energy status, and the immune microenvironment, influencing the response to immunotherapy with interesting therapeutic implications. In this review, we summarize the main changes in the GM and derived metabolites (e.g., short-chain fatty acids and bile acids) occurring in HCC patients and influencing NAFLD progression, emphasizing their potential as early diagnostic biomarkers and prognostic tools. We discuss the weight loss effects of diet-based interventions and healthy lifestyles for the treatment of NAFLD patients, highlighting their impact on the restoration of the intestinal barrier and GM structure. We also describe encouraging preclinical findings on the modulation of GM to improve liver functions in CLD, boost the antitumor immune response (e.g., probiotic supplementations or anti-hypercholesterolemic drug treatment), and ultimately delay NAFLD progression to HCC. The development of safe and effective strategies that target the gut–liver axis holds promise for liver cancer prevention and treatment, especially if personalized options will be considered. Full article

Objective: Postoperative nausea and vomiting (PONV) was one of the common complications in patients with HCC who had undergone TACE. This study was a prospective analysis of patient data to investigate risk factors for PONV in patients after TACE. Material and Methods: Data were collected from 212 patients undergoing TACE in the interventional department between August 2022 and August 2023. Including: gender, age, education, BMI, operation time, concomitant underlying diseases and drugs, preoperative limosis, history of nausea and vomiting, history of kinetosis, history of smoking or drinking, and occurrence of PONV. A visual analog scale was used to measured pain. Neuropsychological status was also assessed, using the 7-item Generalized Anxiety Disorder Questionnaire (GAD-7) and the Patient Health Questionnaire-9(PHQ-9). To identify risk factors for PONV, multiple logistic regression analysis was used. The receiver operating characteristic (ROC) curve was plotted to assess the regression model. The clinical trial number did not apply in the study. Results: In this study, 212 out of a total of 904 patients with HCC undergoing TACE during their hospital stay were included for analysis. Among the included patients, the incidence of PONV was as high as 42% (89/212). Multiple logistic regression analysis showed that chronic gastritis (odds ratio [OR] = 10.350; p = 0.020), VAS (OR = 3.835; p = 0.003), epirubicin (OR = 26.685; p < 0.001), and the dosage of lipiodol (≥5 mL) (OR = 1.385; p < 0.001) were independent risk factors of PONV after TACE. The ROC curve demonstrated that the AUC was 0.902, the sensitivity was 84.3%, and the specificity was 87%. Conclusions: PONV is highly prevalent among patients with HCC after TACE. Chronic gastritis, pain, epirubicin, and the dosage of lipiodol were independent risk factors for PONV. The risk prediction model that was constructed according to the aforementioned factors demonstrated good discriminatory capacity for predicting the risk of post-TACE PONV, which can improve the recognition of medical providers, and has a good ability to prevent and treat nausea and vomiting. Full article