Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. While 5-year overall survival (OS) is a common prognostic metric, it does not reflect the evolving prognosis of long-term survivors. The study aimed to evaluate dynamic changes in real-time survival among HCC patients over time using conditional survival (CS) analysis and to develop an individualized, time-updated prognostic model.

A total of 11,926 patients with primary HCC were included and randomly assigned to training (70%) and validation (30%) cohorts. CS was defined as the probability of surviving additional years given time already survived [CS(t1|t0) = OS(t1 + t0)/OS(t0), where OS(t0) represents the survival probability at t0-years from diagnosis, and OS(t0 + t1) represents survival at (t0 + t1)-years]. Univariable and multivariable Cox regressions were used to identify independent prognostic factors and construct a CS-nomogram. Model performance was assessed using area under the curve (AUC), calibration curves, and decision curve analysis.

CS analysis showed that real-time survival rate increased significantly with each additional year survived, with 5-year CS rising from 35.1% at diagnosis to 52.9%, 66.7%, 79.2%, and 90.2% after 1-4 years of survival. Eleven prognostic factors were included in the final model (all p < 0.05). The CS-nomogram demonstrated strong discrimination (5-year AUC > 0.84 in both cohorts) and good calibration. An interactive web-based tool was developed to facilitate clinical application.

CS analysis offers more accurate and dynamic prognostic information for HCC patients. The CS-nomogram provides personalized, time-adjusted survival estimates, supporting more informed decision-making and survivorship care.

Esophagogastric varices (EGV) and upper gastrointestinal bleeding are common and potentially fatal complications in patients with advanced hepatocellular carcinoma (aHCC). We aimed to evaluate the real-world prevalence of EGV among the aHCC population in the United States.

This retrospective cohort study utilized IQVIA's PharMetrics Plus Health Plans Claims database between January 1, 2016, and July 31, 2021 (study period). Adult patients with an aHCC diagnosis who initiated systemic therapies were included, while those with any secondary malignancies or prior liver transplant at baseline were excluded. The date of therapy initiation was the index date; baseline characteristics, prior procedures, and clinical events of interest were captured during the 12-month pre-index (baseline) period. Patients were followed for clinical outcomes (EGV- or bleeding-related emergency room [ER] visits or hospitalization) during the 6-month post-index period. Logistic regression was conducted to identify key predictors of post-index EGV- or bleeding-related ER visit or hospitalization.

904 patients with aHCC were included in the study (mean age: 61.3 years; 75.3% male). Sorafenib (423 patients, 46.8%) was the most prescribed aHCC treatment. During the entire study period, 458 patients (50.7%) underwent an esophagogastroduodenoscopy (EGD), of whom 209 (45.6%) had post-index EGV. Among 327 patients (36.2%) with a baseline EGD, 175 (53.5%) were diagnosed with EGV and 50 (15.3%) had variceal bleeding; 141 patients (15.6% of all patients) experienced ≥1 EGV- or bleeding-related ER visit or hospitalization post-index.

There is a high prevalence of EGV in patients with aHCC. The presence of EGV, gastrointestinal bleeding, and portal hypertension-related comorbidities was associated with an increased risk of subsequent EGV- or bleeding-related ER visits or hospitalizations in patients with aHCC. Assessment and stratification of varices should be considered in patients with aHCC before initiating systemic therapies to inform treatment decisions.

This study aimed to identify the predictors of liver decompensation and mortality in patients with HCC treated with trans arterial radioembolization (TARE).

A retrospective analysis of 140 HCC patients who underwent TARE was conducted. Kaplan-Meier and multivariate Cox regression analyses were performed to identify the key predictors of mortality and liver decompensation, defined as a total bilirubin level greater than 50 μmol/l or an upgrade in the Child-Pugh class within three months of the first TARE procedure.

The cohort comprised 69.3% males with a mean age of 71.3 ± 11.9 years. Most patients (73.6%) had Child-Pugh class A cirrhosis and 34.3% had BCLC stage B disease. Liver decompensation was recorded in 55 patients (39.2%) within three months of the first TARE procedure. A total of 80 patients (57.1%) died during the follow-up period. The median survival was significantly longer in those without liver decompensation (3.2 vs. 0.7 years, P < 0.001). Multivariate analysis revealed that male gender (adjusted odds ratio [aOR] 5.889, P = 0.009), cirrhosis (aOR 6.82, P = 0.047), and baseline international normalized ratio (INR) (aOR 316.664, P = 0.013) were independent predictors of liver decompensation. Cox regression analysis revealed several significant predictors of increased mortality including ascites (HR 2.012, 95% CI, 1.122-3.61; P = 0.019), portal vein invasion (HR 1.695, 95% CI, 1.057-2.718; P = 0.029), and diabetes mellitus (HR 1.823, 95% CI, 1.017-3.265; P = 0.044). Conversely, non-multifocal HCC (HR 0.593, 95% CI, 0.369-0.955; P = 0.031), treatment of the liver lobe other than the right lobe (HR, 0.482; 95% CI 0.236-0.986, P = 0.046), and age ≥60 years (HR 0.288, 95% CI, 0.139-0.597; P = 0.001) were associated with a reduced risk of mortality.

This study identified the key predictors of liver decompensation and mortality in patients with HCC undergoing TARE, potentially improving patient selection and management strategies.

Given the rising incidence of hepatocellular carcinoma (HCC) globally, especially in China, information about independent risk factors for survival and disease prognosis of the illness is scarce. In the field of HCC research, there is an urgent need for a scientific basis to enhance the accuracy of clinical diagnosis, optimize the course of therapy, and accurately predict the prognosis. Against this backdrop, the objective of this work was to develop a scientific, efficient, and methodical nomogram to forecast the survival prognosis of HCC.

A real-world study collected clinical data from January 1, 2011, to December 31, 2019, for individuals with HCC. Overall survival (OS) was determined using Kaplan-Meier analysis. Independent risk variables were identified using Cox proportional hazards regression. A nomogram predicting 1-, 3-, and 5-year OS was created. The reliability of the predictions of the model was assessed using receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA).

Data from 1,128 HCC cases showed 1-, 3-, and 5-year OS rates were 86.3%, 65.3%, and 43.1%, respectively. Univariate Cox regression identified 13 variables influencing HCC survival including age, HCC screening status, hepatitis C virus (HCV) status, nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) status, liver cirrhosis, elevated alpha-fetoprotein (AFP), Child-Pugh grade, tumor size, tumor number, treatment method, tumor thrombus, and extrahepatic metastasis (P<0.05). Multivariate analysis confirmed HCC screening status, tumor size, ALD, Child-Pugh classification, and therapy method as independent prognostic factors (P<0.05). The nomogram achieved an area under the ROC curve (AUC) of 0.868. Calibration curves of the 1-, 3-, and 5-year survival times and the DCA curve confirmed its predictive accuracy.

Patients without HCC screening, tumor size >5 cm, ALD, Child-Pugh grade C, and conservative treatment had a poor survival prognosis. A nomogram based on these risk variables provides a reliable tool for predicting the survival chances of patients with HCC.

External beam radiation therapy (RT) has shown promising effects for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) in recent studies. However, there is still a lack of consensus on the optimal RT scheme for PVTT treatment. We evaluated the efficacy and safety of image-guided 10-fraction hypofractionated RT in these patients.

Between January 2016 and March 2022, a total of 95 HCC patients with PVTT received 10-fraction hypofractionated image-guided radiation therapy (IGRT) at two institutes, and 69 patients were analyzed. Follow-up imaging was performed at three-month intervals after the completion of RT. The extent of PVTT was described according to the Liver Cancer Study Group of Japan classification: Vp1 = segmental portal vein branch, Vp2 = right/left anterior/posterior portal vein, Vp3 = right/left portal vein, and Vp4 = main portal vein. Response evaluation was performed using Response Evaluation Criteria in Solid Tumors, version 1.1. Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) were calculated from the start date of RT.

The median prescribed dose of 50 Gy (range: 40-50 Gy; biologically effective dose [BED]: 56-75Gy10) was delivered in 10 fractions. In this cohort, 4.3% of patients had Vp1, 20.3% had Vp2, 37.7% had Vp3, and 37.7% had Vp4. Median Planning target volume was 105.3 cc (interquartile range [IQR], 74.1-179.4 cc). Fifty-two (75.4%) patients received 50 Gy. With a median follow-up of 10.2 months (IQR, 6-21 months), the median OS was 20.3 months, and 1-year FFLP, PFS, and OS rates were 88.7%, 26.9%, and 62.2%, respectively. At 3 months follow-up, 13.0% had a complete response, 36.2% had a partial response, 46.4% had a stable disease and 4.4% had a progressive disease. In the multivariate analysis, alpha-fetoprotein level ≥ 600 IU/ml (hazard ratio [HR] 2.06, p = 0.03), Child-Pugh Class B or C (HR 2.30, p = 0.02), and stage IVA or IVB (4.05, p = 0.02) were significantly related to OS. During the follow-up period, there were 2 (2.9%) cases of grade ≥ 3 toxicity: grade 3 liver enzyme elevation (n = 1), and acute cholangitis (n = 1).

Hypofractionated RT demonstrated promising local PVTT control and OS rates with acceptable toxicity. These data suggest that 10-fraction image-guided hypofractionated RT (BED: 56-75 Gy10) is a feasible treatment option for PVTT in HCC patients.

In the phase III HIMALAYA study (NCT03298451), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib in unresectable HCC (uHCC) and demonstrated long-term survival benefits. We report an updated exploratory analysis of OS with 5 years of follow-up, including survival by multiple tumour response measures.

Participants were randomised to STRIDE (tremelimumab plus durvalumab), durvalumab or sorafenib. OS, depth of response and serious adverse events (AEs) were assessed. Extended long-term survivors (eLTS; ≥48 months beyond randomisation) were described. Updated data cut-off: 01 March 2024.

Median (95% CI) follow-up durations were 62.49 (59.47-64.79) months (STRIDE) and 59.86 (58.32-61.54) months (sorafenib). The OS HR (95% CI) for STRIDE versus sorafenib was 0.76 (0.65-0.89). OS rates at 60 months for STRIDE versus sorafenib were 19.6% versus 9.4% overall, 28.7% versus 12.7% in participants achieving disease control per RECIST v1.1 and 50.7% versus 26.3% in participants achieving >25% tumour shrinkage. No late-onset treatment-related serious AEs were reported for STRIDE. There were more eLTS with STRIDE (83/393, 21.1%) than sorafenib (45/389, 11.6%), and extended long-term survival occurred across all clinically relevant subgroups.

At 5 years, STRIDE sustained an OS benefit versus sorafenib and maintained a manageable safety profile. OS benefit with STRIDE was improved in participants with disease control. Data suggest that any degree of tumour shrinkage with STRIDE can be associated with improved OS, indicating that conventional response measures may not fully capture STRIDE benefits. Nevertheless, participants experiencing deep responses appear to have the greatest benefit. STRIDE continues to set new benchmarks in uHCC with 1 in 5 patients alive at 5 years.

The phase III HIMALAYA study showed that STRIDE (Single Tremelimumab Regular Interval Durvalumab) improved overall survival (OS) versus sorafenib in participants with unresectable HCC (uHCC), including after 4 years of follow-up. Understanding the efficacy and safety of STRIDE over the longer term is important for healthcare providers; here, we demonstrate that STRIDE sustained an OS benefit versus sorafenib and maintained a manageable safety profile after 5 years of follow-up. OS benefit with STRIDE was improved in participants with disease control and any degree of tumour shrinkage, indicating that conventional response measures may not fully capture the benefits of STRIDE. These findings are important as they set new benchmarks in uHCC and may help guide clinical decisions in the future.

Among the most common malignant tumors, hepatocellular carcinoma (HCC) is a primary liver cancer type that has a high mortality rate. HCC often presents insidiously, is prone to recurrence, and has limited treatment efficacy. Ferroptosis regulates tumorigenesis, progression, and metastasis, which is a novel form of iron-dependent cell death. Numerous studies suggest that HCC is sensitive to ferroptosis, indicating that targeted therapies aimed at inducing ferroptosis may represent a promising new approach to cancer treatment. This study aims to find genes associated with HCC and ferroptosis, as well as to screen for potential agents that may cause ferroptosis in HCC. Transcriptome and clinical sample data were obtained from the TCGA database to identify differentially expressed genes related to ferroptosis. Using various regression and survival analysis techniques, we developed a prognostic model based on four core genes and evaluated its predictive potential. Subsequently, we screened for potential therapeutic agents in the Connective Map (CMap) database, designated as compound Atorvastatin, based on differential genes from two risk groups and related to ferroptosis. Through experiments conducted in vivo and in vitro, we demonstrated that Atorvastatin can induce ferroptosis in HCC cells while inhibiting their growth and migration. In conclusion, this research targets ferroptosis therapy and provides new insights for improving the prediction and prevention of HCC.

Compared to overall survival, conditional survival is a more relevant measure of prognosis in surviving patients over time. This study developed and validated a nomogram-based dynamic prognostic model to predict the conditional survival estimates of patients with hepatocellular carcinoma (HCC) through an analysis of a nationwide cancer registry. This retrospective cohort study included 2492 patients with HCC registered in the Korea Liver Cancer Registry. Patients underwent hepatic resection (HR) from 2008 to 2017, were followed up until December 2019, and were divided into development and validation cohorts. Univariate and multivariate Cox regression analyses were conducted to determine the risk factors for conditional survival of patients who underwent HR. The patients were scored based on the Cox regression coefficients; the nomogram was predicted by calculating the survival probability with Cox model. Our dynamic prognostic model nomogram for predicting conditional overall survival demonstrated Harrell's C-index of 0.622 and 0.674 in the development and validation sets; for conditional disease-specific survival, it was 0.623 and 0.686 in the development and validation sets. The prediction power of the model is applicable in clinical practice. Factors incorporated in our nomogram included age, albumin, the ADV score, lymph node metastasis, and T stage in American Joint Commission on Cancer staging system. We developed and validated a nomogram to predict conditional survival estimates for overall survival and disease-specific survival. The proposed nomogram incorporating the ADV score presents a more accurate and useful prognostic prediction for patients with HCC who received HR.

This study assessed the validity of the hospital standardized mortality ratio (HSMR) risk-adjusted model by comparing models that include clinical information and the current model based on administrative information in South Korea.

The data of 53976 inpatients were analyzed. The current HSMR risk-adjusted model (Model 1) adjusts for sex, age, health coverage, emergency hospitalization status, main diagnosis, surgery status, and Charlson Comorbidity Index (CCI) using administrative data. As candidate variables, among clinical information, the American Society of Anesthesiologists score, Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) 3, present on admission CCI, and cancer stage were collected. Surgery status, intensive care in the intensive care unit, and CCI were selected as proxy variables among administrative data. In-hospital death was defined as the dependent variable, and a logistic regression analysis was performed. The statistical performance of each model was compared using C-index values.

There was a strong correlation between variables in the administrative data and those in the medical records. The C-index of the existing model (Model 1) was 0.785; Model 2, which included all clinical data, had a higher C-index of 0.857. In Model 4, in which APACHE II and SAPS 3 were replaced with variables recorded in the administrative data from Model 2, the C-index further increased to 0.863.

The HSMR assessment model improved when clinical data were adjusted. Simultaneously, the validity of the evaluation method could be secured even if some of the clinical information was replaced with the information in the administrative data.

Background The US Liver Imaging Reporting and Data System (LI-RADS) includes an assessment category (US-1, negative; US-2, subthreshold; and US-3, positive) and a visualization score reflecting image quality (VIS-A, no or minimal limitations; VIS-B, moderate limitations; and VIS-C, severe limitations). The US-3 and VIS-C impact patient treatment. Purpose To establish the distributions of categories and visualization scores, estimate the proportions of hepatocellular carcinoma (HCC) and overall malignancy in the US-3 category, and identify variables associated with the VIS-C score by conducting a meta-analysis. Materials and Methods A systematic search of articles published between January 1, 2017, and September 17, 2023, identified studies reporting distributions of US LI-RADS version 2017 categories or visualization scores. Characteristics of the study design, patient cohorts, and outcomes of interest (distributions of US categories and visualization scores, percentages of probable or definite HCC and malignancy in US-3 category, and variables associated with VIS-C) were extracted. For the meta-analysis, estimates were established with random-effects models. Results Fifteen studies comprising 39 166 US examinations were included. Of all examinations, 89.7% (95% CI: 86.8, 91.8) were categorized US-1; 4.4% (95% CI: 2.8, 6.2), US-2; and 5.9% (95% CI: 4.1, 8.0), US-3. Of the US-3 examinations, 25.9% (95% CI: 17.1, 34.7) had probable or definite HCC and 26.4% (95% CI: 18.4, 34.5) had overall malignancy. Among all examinations, 59.7% (95% CI: 46.9, 67.8) were assigned VIS-A; 32.5% (95% CI: 21.9, 41.6), VIS-B; and 7.8% (95% CI: 2.8, 14.3), VIS-C. Obesity (odds ratio [OR], 2.37; 95% CI: 1.57, 3.59), nonalcoholic fatty liver disease (NAFLD) (OR, 2.24; 95% CI: 1.64, 3.06), and Child-Pugh B or C (OR, 2.41; 95% CI: 1.43, 4.06) were associated with VIS-C score. Conclusion Overall, 90% of surveillance US results were negative (US-1), and 92% were of adequate quality (VIS-A or VIS-B); 26% of patients with US-3 results had HCC. VIS-C was associated with obesity, NAFLD, and cirrhosis. Systemic review registry no. CRD42022384925 © RSNA, 2025 Supplemental material is available for this article.

Prevention, recognition, and staging of hepatocellular carcinoma (HCC) rely primarily on abdominal imaging. Treatment of HCC varies widely based on tumor stage, lymph node involvement, and metastatic disease along with the patient's functional status. We present an unusual case of isolated extrahepatic HCC metastasis involving a solitary lesion in the pelvis, with no other evidence of viable intrahepatic or extrahepatic disease. The detection of this metastasis was aided by regular surveillance magnetic resonance imaging, alpha-fetoprotein monitoring, and pathological diagnosis. Our case highlights the importance of thoroughly evaluating interval changes on surveillance imaging in HCC.

Sorafenib is a first-line treatment option for patients with hepatocellular carcinoma (HCC). However, the impact of sorafenib resistance type on patient survival prediction and choice of second-line treatment regimen is unknown.

This study aims to explore the factors predicting resistance in patients with HCC receiving sorafenib, the impact of resistance on survival, and the optimal second-line treatment regimen.

This was a retrospective cohort study.

We recruited all patients with advanced HCC who received first-line sorafenib from January 2019 to January 2023 in two medical centers in China. They were divided into primary and secondary resistance groups according to tumor progression within 3 months. Resistance was the primary outcome of this study. The secondary outcomes were progression-free survival (PFS) and overall survival (OS).

A total of 424 patients met the inclusion criteria, including 165 patients (38.9%) in the primary group and 259 patients (61.1%) in the secondary group. The independent risk factors for primary resistance were alpha-fetoprotein (AFP) > 400 ng/mL and alanine aminotransferase (ALT) > 40 U/L. Patients in the primary group had significantly shorter median OS than those in the secondary group (9.0 months vs 23.0 months, p < 0.001). Compared with tyrosine kinase inhibitor (TKI) monotherapy, the use of TKI plus PD-1 inhibitor combination therapy as second-line treatment conferred a longer median PFS (6.0 vs 10.0 months, p < 0.001) and OS (13.0 vs 22.0 months, p < 0.001).

Sorafenib has a high incidence of primary resistance and short survival in patients who develop primary resistance. AFP and ALT are influential factors in primary resistance, and it is valuable to use these two metrics to guide the use of sorafenib. As second-line therapy, a TKI plus PD-1 inhibitor regimen should be preferentially recommended.

One of the foremost causes of global healthcare burden is cancer of the gastrointestinal tract. The medical records, lab results, radiographs, endoscopic images, tissue samples, and medical histories of patients with gastrointestinal malignancies provide an enormous amount of medical data. There are encouraging signs that the advent of artificial intelligence could enhance the treatment of gastrointestinal issues with this data. Deep learning algorithms can swiftly and effectively analyze unstructured, high-dimensional data, including texts, images, and waveforms, while advanced machine learning approaches could reveal new insights into disease risk factors and phenotypes. In summary, artificial intelligence has the potential to revolutionize various features of gastrointestinal cancer care, such as early detection, diagnosis, therapy, and prognosis. This paper highlights some of the many potential applications of artificial intelligence in this domain. Additionally, we discuss the present state of the discipline and its potential future developments.

Hepatocellular carcinoma (HCC) is usually diagnosed in patients at the age of > 45 years. We aimed to determine the prognosis of patients with HCC at the age of 30-44 years compared with that of patients at a more senior age.

Based on the Sun Yat-sen University Cancer Center database, a total of 1745 patients with HCC were retrospectively enrolled and were assigned to three age groups (30-44, 45-59, and 60-70 years). The primary endpoint was overall survival. Among baseline characteristics, five variables including sex, serum albumin level, total bilirubin level, the maximum tumor diameter, and the number of tumor nodules were adjusted using propensity score matching.

Patients aged 30-44 years presented a worse overall survival, a greater number of HCC nodules, a greater maximum tumor diameter, and higher serum alpha-fetoprotein (AFP) concentration than those aged 45-59 years in a crude analysis (p < 0.05). Using propensity score matching, the difference in overall survival between the two cohorts was canceled (p > 0.05).

The prognosis of patients with HCC at age 30-44 years was equal to that of patients aged 45-59 years.

Hepatocellular Carcinoma (HCC) is a serious primary solid tumor that is prevalent worldwide. Due to its high mortality rate, it is crucial to explore both early diagnosis and advanced treatment for HCC. In recent years, multi-omics approaches have emerged as promising tools to identify biomarkers and investigate molecular mechanisms of biological processes and diseases. In this study, we performed proteomics, phosphoproteomics, metabolomics, and lipidomics to reveal the molecular features of early- and advanced-stage HCC. The data obtained from these omics were analyzed separately and then integrated to provide a comprehensive understanding of the disease. The multi-omics results unveiled intricate biological pathways and interaction networks underlying the initiation and progression of HCC. Moreover, we proposed specific potential biomarker panels for both early- and advanced-stage HCC by overlapping our data with CPTAC database for HCC diagnosis, and deduced novel insights and mechanisms related to HCC origination and development, such as glucose depletion during tumor progression, ROCK1 deactivation and GSK3A activation.

Liver cancer is a highly prevalent and lethal form of cancer worldwide. In the absence of early diagnosis, treatment options for this disease are severely restricted. Recent advancements in genomics and bioinformatics have facilitated the discovery of a multitude of novel biomarkers that accurately depict an individual's disease diagnosis, progression, and treatment response. Leveraging these breakthroughs, personalized medicine employs an individual's biomarker profile to enable early detection of liver cancer and inform decisions regarding treatment selection, dosage determination, and prognosis assessment. The current lack of readily applicable, timely, and economically viable tools for biomarker analysis has hindered the incorporation of personalized medicine into regular clinical procedures. Over the past decade, significant advancements have been achieved in the field of molecular point-of-care testing (POCT) and amplification techniques, leading to substantial improvements in the diagnosis of liver cancer and the implementation of precision medicine. Instrument-free PCR technology or plasma PCR technology can shorten the complex procedure of in vitro detection of nucleic acid-based biomarkers. Also, compared to traditional ELISA, various nanomaterials modified with monoclonal antibodies to target proteins for recognition, capture, and detection have improved the efficiency of protein-based biomarker detection. These advances have reduced the time and cost of clinical detection of early-stage hepatocellular carcinoma and improved the efficiency of timely diagnosis and survival of suspected patients while reducing unnecessary testing costs and procedures. This review aims to provide a comprehensive overview of the current and emerging biomarkers employed in the early detection of liver cancer, as well as the advancements in point-of-care molecular testing technology and platforms. The primary objective is to assess their potential in facilitating the implementation of personalized medicine. This review ultimately revealed that the diagnosis of early-stage hepatocellular carcinoma not only requires sensitive biomarkers, but its various modifications and changes during the progression of cirrhosis to early-stage hepatocellular carcinoma will be a greater focus of our attention in the future. The rapid development of POCT has facilitated the opportunity to readily detect liver cancer in the general population in the future, and the integration of multi-pathway multiplexing and intelligent algorithms has improved the sensitivity and accuracy of early liver cancer biomarker detection. It is expected that the integration of point-of-care technology will be instrumental in the widespread adoption of personalized medicine in the foreseeable future.

In hepatocellular carcinoma (HCC), CD147 expression contributes to tumor malignancy; however, its relationship with the tumor-immune microenvironment (TIME) remains unclear. This study aimed to elucidate the clinicopathological characteristics associated with CD147 expression in HCC and investigate its association with the TIME, specifically its association with tumor-infiltrating lymphocytes (TILs) and oncostatin M (OSM). Using 397 HCC specimens from patients undergoing curative-intent resection, we assessed CD147 expression in tumor cells and quantified OSM-positive cells and various TILs (CD8+, CD4+, FOXP3+, and CD20+ cells) in the TIME. Using tissue microarrays, these assessments were performed through immunohistochemical analysis. We investigated the associations between CD147 expression status, the density of OSM-positive cells, and the densities of various TILs. High CD147 expression, found in 332 specimens (83.6%), was associated with advanced clinical stage (P = 0.029), fibrosis (P = 0.036), and higher densities of FOXP3+ cells (P = 0.0039), CD4+ cells (P = 0.0012), and OSM-positive cells (P = 0.0017). In CD147-high tumors, OSM-positive cell density was associated with all assessed TIL subsets (CD8+, CD4+, FOXP3+, and CD20+ cells; all Ps < 0.001), whereas in CD147-low tumors, OSM-positive cell density was associated only with FOXP3+ cells (P = 0.0004). In HCC, CD147 expression is associated with an immunosuppressive TIME, characterized by increased FOXP3+ regulatory T cells and a correlation with OSM-positive cells. These results elucidate the potential mechanisms through which CD147 facilitates tumor-immune evasion, suggesting the CD147 - OSM axis as a promising target for therapeutic intervention in HCC.

Background: There is an observed variation in the burden of hepatocellular carcinoma (HCC) across different US populations. Our study aims to comprehensively assess variations in HCC incidence and mortality rates across different regions of the US. Understanding these geographical differences is crucial, given prior evidence indicating variations in the incidence of viral hepatitis and metabolic dysfunction-associated steatotic liver disease and varying access to curative HCC treatment among states. Methods: HCC age-adjusted incidence rates between 2001 and 2021 were obtained from the United States Cancer Statistics (USCS) database (which covers approximately 98% of the US population). HCC age-adjusted mortality rates between 2000 and 2022 were obtained from the National Center of Health Statistics (NCHS) database (covering approximately 100% of the US population). The rates were categorized by US geographical region into West, Midwest, Northeast, and South. Incidence rates were also categorized by race/ethnicity. Time trends [annual percentage change (APC) and average APC (AAPC)] were estimated by using Joinpoint Regression via the weighted Bayesian Information Criteria (p < 0.05). Results: Between 2001 and 2021, there were 491,039 patients diagnosed with HCC in the US (74.2% males). The highest incidence rate per 100,000 population was noted in the West (7.38), followed by the South (6.85). Overall incidence rates increased between 2001 and 2015 and then significantly decreased until 2021 (APC = -2.29). Most cases were in the South (38.8%), which also had the greatest increase in incidence (AAPC = 2.74). All four geographical regions exhibited an overall similar trend with an increase in incidence over the first 10-15 years followed by stable or decreasing rates. While stratification of the trends by race/ethnicity showed slight variations among the regions and groups, the findings are largely similar to all race/ethnic groups combined. Between 2000 and 2022, there were 370,450 patients whose death was attributed to HCC in the US (71.6% males). The highest mortality rate per 100,000 population was noted in the South (5.02), followed by the West (4.99). Overall mortality rates significantly increased between 2000 and 2013 (APC = 1.90), then stabilized between 2013 and 2016, and then significantly decreased till 2022 (APC = -1.59). Most deaths occurred in the South (35.8%), which also had the greatest increase in mortality (AAPC = 1.33). All four geographical regions followed an overall similar trend, with an increase in mortality over the first 10-15 years, followed by stable or decreasing rates. Conclusions: Our analysis, capturing about 98% of the US population, demonstrates an increase in HCC incidence and mortality rates in all geographical regions from 2000 to around 2014-2016, followed by stabilizing and decreasing incidence and mortality rates. We observed regional variations, with the highest incidence and mortality rates noted in the West and South regions and the fastest increase in both incidence and mortality noted in the South. Our findings are likely attributable to the introduction of antiviral therapy. Furthermore, demographic, socioeconomic, and comorbid variability across geographical regions in the US might also play a role in the observed trends. We provide important epidemiologic data for HCC in the US, prompting further studies to investigate the underlying factors responsible for the observed regional variations in HCC incidence and mortality.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Transforming growth factor beta (TGF-β) is highly expressed in the liver tumor microenvironment and is known to inhibit immune cell activity. Here, we used human induced pluripotent stem cells (iPSCs) to produce natural killer (NK) cells engineered to mediate improved anti-HCC activity. Specifically, we produced iPSC-NK cells with either knockout TGF-β receptor 2 (TGFBR2-KO) or expression of a dominant negative (DN) form of the TGF-β receptor 2 (TGFBR2-DN) combined with chimeric antigen receptors (CARs) that target either GPC3 or AFP. The TGFBR2-KO and TGFBR2-DN iPSC-NK cells are resistant to TGF-β inhibition and improved anti-HCC activity. However, expression of anti-HCC CARs on iPSC-NK cells did not lead to effective anti-HCC activity unless there was also inhibition of TGF-β activity. Our findings demonstrate that TGF-β signaling blockade is required for effective NK cell function against HCC and potentially other malignancies that express high levels of TGF-β.

Hepatocellular carcinoma (HCC) is the leading oncologic cause of death among patients with cirrhosis, but large studies examining mortality trends are lacking.

To evaluate survival among patients with HCC in one of the largest integrated health care systems in the US.

This retrospective cohort study included 3441 adult patients who received a diagnosis of HCC between January 1, 2006, and December 31, 2019, with end of follow-up on December 31, 2020. The study period was further categorized as era 1, defined as 2006 to 2012, and era 2, defined as 2013 to 2019. Statistical analysis was conducted from January 2021 to June 2024.

Patient demographic characteristics and disease factors.

All-cause and HCC-specific mortality were used as primary end points, and survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression analyses were adjusted for age at diagnosis, sex, race and ethnicity, cause of disease, Barcelona Clinic Liver Cancer (BCLC) stage, alpha-fetoprotein level, and treatment type.

Of 3441 patients with HCC, 2581 (75.0%) were men, and the median age was 65 years (IQR, 58-73 years). A total of 1195 patients (34.7%) received curative treatment, 1374 (39.9%) received noncurative treatment, and 872 (25.3%) received no treatment. During the study period, 2500 patients (72.7%) experienced all-cause mortality, and 1809 (52.6%) had HCC-specific mortality. In multivariable analysis, being 70 years of age or older (adjusted hazard ratio [AHR], 1.39; 95% CI, 1.22-1.59), male sex (AHR, 1.20; 95% CI, 1.07-1.35), BCLC stage C or D (AHR, 2.40; 95% CI, 2.15-2.67), increasing alpha-fetoprotein level (vs <20 ng/mL; 20-99 ng/mL: AHR, 1.20; 95% CI, 1.04-1.38; ≥1000 ng/mL: AHR, 2.84; 95% CI, 2.45-3.25), noncurative treatment (AHR, 2.51; 95% CI, 2.16-2.90), and no treatment (AHR, 3.15; 95% CI, 2.64-3.76) were associated with higher all-cause mortality, while Asian or Other Pacific Islander race and ethnicity (vs non-Hispanic White; AHR, 0.76; 95% CI, 0.65-0.88) was associated with lower all-cause mortality. Survival improved in diagnosis era 2 (2013-2019; n = 2007) compared with diagnosis era 1 (2006-2012; n = 1434).

This large, racially and ethnically diverse cohort study of patients with HCC found improving survival over time, especially among individuals with early-stage HCC receiving potentially curative treatments. This study highlights the importance of surveillance for detection of HCC at early stages, particularly among groups at risk for poorer outcomes.

Liver cancer is one of the most lethal gastrointestinal malignancies. Emerging evidence has underscored the pivotal role of long non-coding RNAs (lncRNAs) in tumorigenesis, with ST8SIA6-AS1 identified as a novel oncogenic lncRNA contributing to liver cancer progression. ST8SIA6-AS1 is consistently upregulated in hepatic cancer tissues and is strongly associated with unfavorable prognosis. Moreover, it demonstrates high diagnostic efficacy in detecting HCC. ST8SIA6-AS1 is involved in various cellular processes including proliferation, migration, and invasion, primarily through its function as a competing endogenous RNA (ceRNA), thereby facilitating hepatocarcinogenesis and disease advancement. This review provides a detailed examination of the molecular functions and regulatory mechanisms of ST8SIA6-AS1 in hepatocellular carcinoma (HCC) and highlights its potential as a promising biomarker for liver cancer, aiming to propel the development of innovative therapeutic strategies for HCC management.

Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Tamoxifen has been evaluated in randomised clinical trials in people with hepatocellular cancer. The reported results have been inconsistent.

To evaluate the benefits and harms of tamoxifen or tamoxifen plus any other anticancer drugs compared with no intervention, placebo, any type of standard care, or alternative treatment in adults with hepatocellular carcinoma, irrespective of sex, administered dose, type of formulation, and duration of treatment.

We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and major trials registries, and handsearched reference lists up to 26 March 2024.

Parallel-group randomised clinical trials including adults (aged 18 years and above) diagnosed with advanced or unresectable hepatocellular carcinoma. Had we found cross-over trials, we would have included only the first trial phase. We did not consider data from quasi-randomised trials for analysis.

Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our important outcomes were disease progression, and adverse events considered non-serious.

We assessed risk of bias using the RoB 2 tool.

We used standard Cochrane methods and Review Manager. We meta-analysed the outcome data at the longest follow-up. We presented the results of dichotomous outcomes as risk ratios (RR) and continuous data as mean difference (MD), with 95% confidence intervals (CI) using the random-effects model. We summarised the certainty of evidence using GRADE.

We included 10 trials that randomised 1715 participants with advanced, unresectable, or terminal stage hepatocellular carcinoma. Six were single-centre trials conducted in Hong Kong, Italy, and Spain, while three were conducted as multicentre trials in single countries (France, Italy, and Spain), and one trial was conducted in nine countries in the Asia-Pacific region (Australia, Hong Kong, Indonesia, Malaysia, Myanmar, New Zealand, Singapore, South Korea, and Thailand). The experimental intervention was tamoxifen in all trials. The control interventions were no intervention (three trials), placebo (six trials), and symptomatic treatment (one trial). Co-interventions were best supportive care (three trials) and standard care (one trial). The remaining six trials did not provide this information. The number of participants in the trials ranged from 22 to 496 (median 99), mean age was 63.7 (standard deviation 4.18) years, and mean proportion of men was 74.7% (standard deviation 42%). Follow-up was three months to five years.

Ten trials evaluated oral tamoxifen at five different dosages (ranging from 20 mg per day to 120 mg per day). All trials investigated one or more of our outcomes. We performed meta-analyses when at least two trials assessed similar types of tamoxifen versus similar control interventions. Eight trials evaluated all-cause mortality at varied follow-up points. Tamoxifen versus the control interventions (i.e. no treatment, placebo, and symptomatic treatment) results in little to no difference in mortality between one and five years (RR 0.99, 95% CI 0.92 to 1.06; 8 trials, 1364 participants; low-certainty evidence). In total, 488/682 (71.5%) participants died in the tamoxifen groups versus 487/682 (71.4%) in the control groups. The separate analysis results for one, between two and three, and five years were comparable to the analysis result for all follow-up periods taken together. The evidence is very uncertain about the effect of tamoxifen versus no treatment on serious adverse events at one-year follow-up (RR 0.44, 95% CI 0.19 to 1.06; 1 trial, 36 participants; very low-certainty evidence). A total of 5/20 (25.0%) participants in the tamoxifen group versus 9/16 (56.3%) participants in the control group experienced serious adverse events. One trial measured health-related quality of life at baseline and at nine months' follow-up, using the Spitzer Quality of Life Index. The evidence is very uncertain about the effect of tamoxifen versus no treatment on health-related quality of life (MD 0.03, 95% CI -0.45 to 0.51; 1 trial, 420 participants; very low-certainty evidence). A second trial found no appreciable difference in global health-related quality of life scores. No further data were provided. Tamoxifen versus control interventions (i.e. no treatment, placebo, or symptomatic treatment) results in little to no difference in disease progression between one and five years' follow-up (RR 1.02, 95% CI 0.91 to 1.14; 4 trials, 720 participants; low-certainty evidence). A total of 191/358 (53.3%) participants in the tamoxifen group versus 198/362 (54.7%) participants in the control group had progression of hepatocellular carcinoma. Tamoxifen versus control interventions (i.e. no treatment or placebo) may have little to no effect on adverse events considered non-serious during treatment, but the evidence is very uncertain (RR 1.17, 95% CI 0.45 to 3.06; 4 trials, 462 participants; very low-certainty evidence). A total of 10/265 (3.8%) participants in the tamoxifen group versus 6/197 (3.0%) participants in the control group had adverse events considered non-serious. We identified no trials with participants diagnosed with early stages of hepatocellular carcinoma. We identified no ongoing trials.

Based on the low- and very low-certainty evidence, the effects of tamoxifen on all-cause mortality, disease progression, serious adverse events, health-related quality of life, and adverse events considered non-serious in adults with advanced, unresectable, or terminal stage hepatocellular carcinoma when compared with no intervention, placebo, or symptomatic treatment could not be established. Our findings are mostly based on trials at high risk of bias with insufficient power (fewer than 100 participants), and a lack of trial data on clinically important outcomes. Therefore, firm conclusions cannot be drawn. Trials comparing tamoxifen administered with any other anticancer drug versus standard care, usual care, or alternative treatment as control interventions were lacking. Evidence on the benefits and harms of tamoxifen in participants at the early stages of hepatocellular carcinoma was also lacking.

This Cochrane review had no dedicated funding.

Protocol available via DOI: 10.1002/14651858.CD014869.

Long non-coding RNAs (lncRNAs) play an important role in tumor progression, including in hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV). Therefore, the aim of this study was to investigate the role of LINC02532 in HCC, mainly for diagnostic prognostic value and cellular function, as well as mechanistic aspects.

Initially, GEO and VirBase databases were used to screen for aberrant lncRNAs in HBV-HCC.Then, HBV-HCC persons followed up in our center were retrospectively studied to investigate the diagnostic, prognostic value of LINC02532 in HBV-HCC. Subsequently, the role of LINC02532 in HBV-HCC was measured using cellular function assay methods and possible mechanisms were analyzed in conjunction with bioinformatic predictive science.

LINC02532 was a lncRNA abnormally expressed in HBV-HCC. LINC02532 was significantly up-regulated in the expression level in HBV-HCC tissues compared with normal tissues from patients. Moreover, LINC02532 could distinguish HBV-HCC and predict the prognosis of HBV-HCC. In vitro experiments showed that LINC02532 could regulate miR-455-3p and promote the malignant characterization of HBV-HCC cells. CHEK2 was a target gene of miR-455-3p.

The prognosis and diagnosis of HBV-HCC can rely on the expression of LINC02532. LINC02532 was important for further progression of HBV-HCC, by moderating miR-455-3p/CHEK2.

Due to the increasing interest in the use of artificial intelligence (AI) algorithms in hepatocellular carcinoma detection, we performed a systematic review and meta-analysis to pool the data on diagnostic performance metrics of AI and to compare them with clinicians' performance. A search in PubMed and Scopus was performed in January 2024 to find studies that evaluated and/or validated an AI algorithm for the detection of HCC. We performed a meta-analysis to pool the data on the metrics of diagnostic performance. Subgroup analysis based on the modality of imaging and meta-regression based on multiple parameters were performed to find potential sources of heterogeneity. The risk of bias was assessed using Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Study Risk of Bias Assessment Tool (PROBAST) reporting guidelines. Out of 3177 studies screened, 44 eligible studies were included. The pooled sensitivity and specificity for internally validated AI algorithms were 84% (95% CI: 81,87) and 92% (95% CI: 90,94), respectively. Externally validated AI algorithms had a pooled sensitivity of 85% (95% CI: 78,89) and specificity of 84% (95% CI: 72,91). When clinicians were internally validated, their pooled sensitivity was 70% (95% CI: 60,78), while their pooled specificity was 85% (95% CI: 77,90). This study implies that AI can perform as a diagnostic supplement for clinicians and radiologists by screening images and highlighting regions of interest, thus improving workflow.

The relationship between lymph node (LN) status and survival outcome in hepatocellular carcinoma (HCC) is a highly controversial topic. The aim of this study was to investigate the prognostic factors in patients without LN metastasis (LNM) and to construct a nomogram to predict cancer-specific survival (CSS) in this group of patients.

We screened 6840 eligible HCC patients in the Surveillance, Epidemiology and End Results（SEER）database between 2010 and 2019 and randomized them into a training cohort and an internal validation cohort, and recruited 160 patients from Zhongnan Hospital of Wuhan University as an external validation cohort. Independent prognostic factors obtained from univariate and multivariate analysis were used to construct a nomogram prediction model. The concordance index (C-index), area under curve (AUC), calibration plots and decision curve analysis (DCA) were used to assess the predictive power and clinical application of the model.

Univariate and multivariate analysis revealed age, gender, bone metastasis, lung metastasis, AFP, T stage, surgery and chemotherapy as independent prognostic factors. The C-index of the constructed nomogram for the training cohort, internal validation cohort and external validation cohort are 0.746, 0.740, and 0.777, respectively. In the training cohort, the AUC at 1-, 3-, and 5-year were 0.81, 0.800, and 0.800, respectively. Calibration curves showed great agreement between the actual observations and predictions for the three cohorts. The DCA results suggest that the nomogram model has more clinical application potential.

We constructed a nomogram to predict CSS in HCC patients without LNM. The model has been internally and externally validated to have excellent predictive performance and can help clinicians determine prognosis and make treatment decisions.

Primary liver tumors constitute one of the most common tumors. These are aggressive tumors with poor survival. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), most commonly used functional imaging, shows limited tracer retention and poor tumor to background ratios (TBR). Novel 68Ga-fibroblast-activation-protein inhibitor (FAPI) PET/CT has shown better tracer uptake and detection efficacy in liver tumors. However, most of the available literature is limited to single center studies with limited number of patients. So, we tried to review and analyze the head-to-head comparison of 18F-FDG PET/CT and 68Ga-FAPI PET/CT in evaluation of liver tumors.

Literature available on head to head comparison of diagnostic accuracy of 18F-FDG PET/CT and 68Ga-FAPI PET/CT was searched in databases like PubMed, SCOPUS, EMBASE and Google Scholar for published original studies till April 2023. The relevant studies were selected and assessed using the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. A random-effect model was used for calculating pooled sensitivity and specificity. They were represented with 95% confidence intervals (95% CI) and demonstrated in Forest plots. I-square statistic was used to assess heterogeneity in the studies.

Pooled sensitivity and specificity of FAPI PET/CT and 18F-FDG PET/CT for detection of primary liver tumors was 94.3% (95% CI: 90.6-96.8%); 89.3% (95% CI: 71.8-97.7%) and 56.1% (95% CI: 49.7-62.5%); 96.4% (95% CI: 81.7-99.9%) respectively. Pooled sensitivity for detection of extrahepatic metastatic disease was 92.2% (range: 88.1-100%; 95% CI: 87.8-95.4%) and 72.4% (range: 69.8-76.5; 95% CI: 65.9-78.2%) respectively. Also, the maximum standardized uptake value (SUVmax) and TBR were higher for FAPI PET/CT than 18F-FDG PET/CT in the included studies.

Overall, FAPI PET/CT showed higher sensitivity for detection of liver tumors with better SUVmax and TBR than 18F-FDG PET/CT.

Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Gene therapy, which uses genes to treat or prevent diseases, holds potential for treatment, especially for tumours. Trials on the effects of gene therapy in people with hepatocellular carcinoma have been published or are ongoing.

To evaluate the benefits and harms of gene therapy in people with hepatocellular carcinoma, irrespective of sex, administered dose, and type of formulation.

We identified randomised clinical trials through electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We searched five online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The date of last search was 20 January 2023.

We aimed to include randomised clinical trials assessing any type of gene therapy in people diagnosed with hepatocellular carcinoma, irrespective of year, language of publication, format, or outcomes reported.

We followed Cochrane methodology and used Review Manager to prepare the review. The primary outcomes were all-cause mortality/overall survival (whatever data were provided), serious adverse events during treatment, and health-related quality of life. The secondary outcomes were proportion of people with disease progression, adverse events considered non-serious, and proportion of people without improvement in liver function tests. We assessed risk of bias of the included trials using RoB 2 and the certainty of evidence using GRADE. We presented the results of time-to-event outcomes as hazard ratios (HR), dichotomous outcomes as risk ratios (RR), and continuous outcomes as mean difference (MD) with their 95% confidence intervals (CI). Our primary analyses were based on intention-to-treat and outcome data at the longest follow-up.

We included six randomised clinical trials with 364 participants. The participants had unresectable (i.e. advanced inoperable) hepatocellular carcinoma. We found no trials assessing the effects of gene therapy in people with operable hepatocellular carcinoma. Four trials were conducted in China, one in several countries (from North America, Asia, and Europe), and one in Egypt. The number of participants in the six trials ranged from 10 to 129 (median 47), median age was 55.2 years, and the mean proportion of males was 72.7%. The follow-up duration ranged from six months to five years. As the trials compared different types of gene therapy and had different controls, we could not perform meta-analyses. Five of the six trials administered co-interventions equally to the experimental and control groups. All trials assessed one or more outcomes of interest in this review. The certainty of evidence was very low in five of the six comparisons and low in the double-dose gene therapy comparison. Below, we reported the results of the primary outcomes only. Pexastimogene devacirepvec (Pexa-Vec) plus best supportive care versus best supportive care alone There is uncertainty about whether there may be little to no difference between the effect of Pexa-Vec plus best supportive care compared with best supportive care alone on overall survival (HR 1.19, 95% CI 0.78 to 1.82; 1 trial (censored observation at 20-month follow-up), 129 participants; very low-certainty evidence) and on serious adverse events (RR 1.42, 95% CI 0.60 to 3.33; 1 trial at 20 months after treatment, 129 participants; very low-certainty evidence). The trial reported quality of life narratively as "assessment of quality of life and time to symptomatic progression was confounded by the high patient dropout rate." Adenovirus-thymidine kinase with ganciclovir (ADV-TK/GCV) plus liver transplantation versus liver transplantation alone There is uncertainty about whether ADV-TK/GCV plus liver transplantation may benefit all-cause mortality at the two-year follow-up (RR 0.39, 95% CI 0.20 to 0.76; 1 trial, 45 participants; very low-certainty evidence). The trial did not report serious adverse events other than mortality or quality of life. Double-dose ADV-TK/GCV plus liver transplantation versus liver transplantation alone There is uncertainty about whether double-dose ADV-TK/GCV plus liver transplantation versus liver transplantation may benefit all-cause mortality at five-year follow-up (RR 0.40, 95% CI 0.22 to 0.73; 1 trial, 86 participants; low-certainty evidence). The trial did not report serious adverse events other than mortality or quality of life. Recombinant human adenovirus-p53 with hydroxycamptothecin (rAd-p53/HCT) versus hydroxycamptothecin alone There is uncertainty about whether there may be little to no difference between the effect of rAd-p53/HCT versus hydroxycamptothecin alone on the overall survival at 12-month follow-up (RR 3.06, 95% CI 0.16 to 60.47; 1 trial, 48 participants; very low-certainty evidence). The trial did not report serious adverse events or quality of life. rAd-p53/5-Fu (5-fluorouracil) plus transarterial chemoembolisation versus transarterial chemoembolisation alone The trial included 46 participants. We had insufficient data to assess overall survival. The trial did not report serious adverse events or quality of life. E1B-deleted (dl1520) adenovirus versus percutaneous ethanol injection The trial included 10 participants. It did not report data on overall survival, serious adverse events, or health-related quality of life. One trial did not provide any information on sponsorship; one trial received a national research grant, one trial by the Pedersen foundation, and three were industry-funded trials. We found five ongoing randomised clinical trials.

The evidence is very uncertain about the effects of gene therapy on the studied outcomes because of high risk of bias and imprecision of outcome results. The trials were underpowered and lacked trial data on clinically important outcomes. There was only one trial per comparison, and we could not perform meta-analyses. Therefore, we do not know if gene therapy may reduce, increase, or have little to no effect on all-cause mortality or overall survival, or serious adverse events in adults with unresectable hepatocellular carcinoma. The impact of gene therapy on adverse events needs to be investigated further. Evidence on the effect of gene therapy on health-related quality of life is lacking.

Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal role in the development and progression of liver cancer. This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer. We discuss the genetic underpinnings of liver cancer, emphasizing the critical role of risk-associated genetic variants, somatic mutations, and epigenetic alterations. We also explore the intricate interplay between environmental factors and genetics, highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy, and advancements in high-throughput sequencing technologies. By synthesizing the latest research findings, we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer, shedding light on their potential to revolutionize early detection, risk assessment, and targeted therapies in the fight against this devastating disease.

This study aimed to explore the impact of sex on clinical features and survival among hepatocellular carcinoma (HCC) patients.

HCC case data from the Surveillance, Epidemiology, and End Results (SEER) database for the period 2010 to 2015 were selected for analysis. Kaplan-Meier curves displayed overall survival. Univariate cox regression examined the prognostic characteristics of individual features, and multivariate Cox regression assessed hazard ratios.

This study comprised 3486 HCC patients, with 2682 males and 804 females. Across all age groups, there was a higher prevalence of males compared to females. Survival curves among female patients showed no significant differences across various age groups. However, among male patients, those under 60 demonstrated notably higher survival rates compared to those aged 60 and above. Regarding various ethnicities, TNM staging systems, tumor sizes, the presence of lung/bone/brain metastases, location in Purchased/Referred Care Delivery Areas, SEER historic stages, tumor grades, and individuals receiving chemotherapy, the proportion of male patients consistently exceeded that of female patients. Within the female patient group, individuals receiving chemotherapy exhibited significantly higher survival rates compared to those who did not. However, the administration of chemotherapy showed no significant impact on the survival rate of male patients. Multivariate Cox regression analysis revealed age, gender, and the administration of chemotherapy key factors influencing the overall survival prognosis.

Age, gender, and the administration of chemotherapy are influential factors in the prognosis of both male and female HCC patients.

Early diagnosis of hepatocellular carcinoma (HCC) as well as evaluation of prognosis and prediction of treatment efficacy remains challenging due to the missing specific non-invasive biomarkers. The aim of this study was to identify disease-specific microRNA (miRNA) patterns for diagnosis, prediction of prognosis, and treatment response in patients with HCC.

The study population included 42 HCC patients from SORAMIC clinical trial: 22 patients received sorafenib monotherapy, 20 patients underwent 90Y radioembolization in combination with sorafenib. 20 individuals were included in the control group. HCC patients underwent collection of plasma samples before and 7-9 weeks after the beginning of the treatment. Isolation of circulating miRNAs, preparation of small RNA sequencing libraries and next-generation sequencing were performed. Association analysis for novel diagnostic, prognostic, and treatment-related candidate biomarkers was performed.

A total of 42 differentially expressed (16 up-regulated and 26 down-regulated) miRNAs were identified comparing baseline and control group plasma samples. hsa-miR-215-5p and hsa-miR-192-5p were down-regulated, while hsa-miR-483-5p and hsa-miR-23b-3p were up-regulated comparing baseline and 7-9 weeks post-sorafenib monotherapy samples. hsa-miR-215-5p was the sole down-regulated miRNA in the same combination therapy comparison. hsa-miR-183-5p, hsa-miR-28-3p, and hsa-miR-1246 were found to be significantly up-regulated comparing non-responders versus responders to sorafenib. High hsa-miR-215-5p expression was significantly associated with worse HCC patients' prognosis.

Systematic miRNA profiling of highly characterized samples from SORAMIC study revealed a subset of potential miRNA biomarkers for HCC diagnosis and prognosis of sorafenib-treated patients' survival.

Hepatobiliary cancer (HBC), including hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), is currently one of the malignant tumors that mainly cause human death. Many HBCs are diagnosed in the late stage, which increases the disease burden, indicating that effective prevention strategies and identification of risk factors are urgent. Many studies have reported the role of thyroid hormones on HBC. Our research aims to assess the causal effects and investigate the mediation effects between thyroid function and HBC.

Utilizing the Mendelian randomization (MR) approach, the study employs single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to explore causal links between thyroid function [free thyroxine (FT4), thyroid stimulating hormone (TSH), hyperthyroidism and hypothyroidism] and HBC. Data were sourced from the ThyroidOmic consortium and FinnGen consortium. The analysis included univariable and multivariable MR analysis, followed by mediation analysis.

The study found a significant causal association between high FT4 levels and the reduced risk of BTC, but not HCC. However, TSH, hyperthyroidism and hypothyroidism had no causal associations with the risk of HBC. Notably, we also demonstrated that only higher FT4 levels with the reference range (FT4-RR) could reduce the risk of BTC because this protective effect no longer existed under the conditions of hyperthyroidism or hypothyroidism. Finally, we found that the protective effect of FT4-RR on BTC was mediated partially by decreasing the risk of metabolic syndrome (MetS) and reducing the waist circumference (WC).

The findings suggest that higher FT4-RR may have a protective effect against BTC, which is partially mediated by decreased risk of MetS and a reduction in WC. This study highlights the potential role of FT4 in the pathogenesis of BTC and underscores that MetS and WC may play mediation effects as two mediators in this process.

Although the elderly constitute more than a third of hepatocellular carcinoma (HCC) patients, they have not been adequately represented in treatment and prognosis studies. Thus, there is not enough evidence to guide the treatment of such patients. The objective of this study is to identify the prognostic factors of older patients with HCC and to construct a new prognostic model for predicting their overall survival (OS).

2,721 HCC patients aged ≥ 65 were extracted from the public database-Surveillance, Epidemiology, and End Results (SEER) and randomly divided into a training set and an internal validation set with a ratio of 7:3. 101 patients diagnosed from 2008 to 2017 in the First Affiliated Hospital of Zhejiang University School of Medicine were identified as the external validation set. Univariate cox regression analyses and multivariate cox regression analyses were adopted to identify these independent prognostic factors. A predictive nomogram-based risk stratification model was proposed and evaluated using area under the receiver operating characteristic curve (AUC), calibration curves, and a decision curve analysis (DCA).

These attributes including age, sex, marital status, T stage, N stage, surgery, chemotherapy, tumor size, alpha-fetoprotein level, fibrosis score, bone metastasis, lung metastasis, and grade were the independent prognostic factors for older patients with HCC while predicting survival duration. We found that the nomogram provided a good assessment of OS at 1, 3, and 5 years in older patients with HCC (1-year OS: (training set: AUC = 0.823 (95%CI 0.803-0.845); internal validation set: AUC = 0.847 (95%CI 0.818-0.876); external validation set: AUC = 0.732 (95%CI 0.521-0.943)); 3-year OS: (training set: AUC = 0.813 (95%CI 0.790-0.837); internal validation set: AUC = 0.844 (95%CI 0.812-0.876); external validation set: AUC = 0.780 (95%CI 0.674-0.887)); 5-year OS: (training set: AUC = 0.839 (95%CI 0.806-0.872); internal validation set: AUC = 0.800 (95%CI 0.751-0.849); external validation set: AUC = 0.821 (95%CI 0.727-0.914)). The calibration curves showed that the nomogram was with strong calibration. The DCA indicated that the nomogram can be used as an effective tool in clinical practice. The risk stratification of all subgroups was statistically significant (p < 0.05). In the stratification analysis of surgery, larger resection (LR) achieved a better survival curve than local destruction (LD), but a worse one than segmental resection (SR) and liver transplantation (LT) (p < 0.0001). With the consideration of the friendship to clinicians, we further developed an online interface (OHCCPredictor) for such a predictive function ( https://juntaotan.shinyapps.io/dynnomapp_hcc/ ). With such an easily obtained online tool, clinicians will be provided helpful assistance in formulating personalized therapy to assess the prognosis of older patients with HCC.

Age, sex, marital status, T stage, N stage, surgery, chemotherapy, tumor size, AFP level, fibrosis score, bone metastasis, lung metastasis, and grade were independent prognostic factors for elderly patients with HCC. The constructed nomogram model based on the above factors could accurately predict the prognosis of such patients. Besides, the developed online web interface of the predictive model provide easily obtained access for clinicians.

Programmed cell death protein 1 (PD-1) or its ligand (PD-L1) monoclonal antibody combined with bevacizumab (a monoclonal antibody targeting vascular endothelial growth factor) has been established as first-line systemic treatment for advanced hepatocellular carcinoma (HCC). Radiotherapy is a crucial local treatment for HCC. Mutual efficacy enhancement has been reported between radiotherapy, anti-angiogenesis therapy and immunotherapy in preclinical researches, but not been validated in clinical practice. Whether radiotherapy can enhance efficacy of anti-PD-1 immunotherapy plus bevacizumab for HCC remains unclear. This retrospective observational study aimed to appraise efficacy and safety of the combination of radiotherapy with pembrolizumab (a PD-1 monoclonal antibody) and bevacizumab for advanced HCC for the first time.

Patients with advanced HCC treated by intrahepatic tumor-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab were consecutively included. Clinicopathological characteristics, therapeutic outcomes and treatment-related adverse events (TRAEs) were recorded and evaluated.

A total of 23 patients were eventually enrolled. Median cycles of pembrolizumab and bevacizumab were 4 (median, 1-8) and 4 (median, 1-9) cycles. The objective response rates and disease control rates of irradiated intrahepatic HCC and non-irradiated extrahepatic HCC were 34.8% [95% confidence interval (CI), 16.4-57.3%] vs. 10.0% (95% CI, 1.2-31.7%), and 91.3% (95% CI, 72.0-98.9%) vs. 70.0% (95% CI, 45.7-88.1%), respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.6 (95% CI, 4.7-8.5) and 18.3 (95% CI, 8.2-33.6) months, and 12-month PFS and OS rates were 17.5% (95% CI, 7.0-28.0%) and 60.9% (95% CI, 50.7-71.1%). Two patients (8.7%) with locally advanced, unresectable HCC eventually underwent curative resection of tumors after this trimodal treatment. Eighteen patients (78.3%) had ≥ grade 3 TRAEs, with myelosuppression and transaminase increase as the most common.

This study firstly reported that combining radiotherapy with pembrolizumab and bevacizumab was preliminarily a feasible and effective therapeutic choice for advanced HCC in despite of more TRAEs. This tri-modal regimen may be a potential conversion therapy for unresectable, locally advanced HCC. The limitations of this study are its retrospective nature and small sample size; therefore, big-sample prospective studies are warranted to further investigate this tri-modal regimen.

Hepatocellular carcinoma (HCC) is one of the most common types of cancers worldwide, ranking fifth among men and seventh among women, resulting in more than 7 million deaths annually. With the development of medical technology, the 5-year survival rate of HCC patients can be increased to 70%. However, HCC patients are often at increased risk of cardiovascular disease (CVD) death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients. Moreover, CVD and cancer have become major disease burdens worldwide. Thus, further research is needed to lessen the risk of CVD death in HCC patient survivors.

To determine the independent risk factors for CVD death in HCC patients and predict cardiovascular mortality (CVM) in HCC patients.

This study was conducted on the basis of the Surveillance, Epidemiology, and End Results database and included HCC patients with a diagnosis period from 2010 to 2015. The independent risk factors were identified using the Fine-Gray model. A nomograph was constructed to predict the CVM in HCC patients. The nomograph performance was measured using Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) value. Moreover, the net benefit was estimated via decision curve analysis (DCA).

The study included 21545 HCC patients, of whom 619 died of CVD. Age (< 60) [1.981 (1.573-2.496), P < 0.001], marital status (married) [unmarried: 1.370 (1.076-1.745), P = 0.011], alpha fetoprotein (normal) [0.778 (0.640-0.946), P = 0.012], tumor size (≤ 2 cm) [(2, 5] cm: 1.420 (1.060-1.903), P = 0.019; > 5 cm: 2.090 (1.543-2.830), P < 0.001], surgery (no) [0.376 (0.297-0.476), P < 0.001], and chemotherapy(none/unknown) [0.578 (0.472-0.709), P < 0.001] were independent risk factors for CVD death in HCC patients. The discrimination and calibration of the nomograph were better. The C-index values for the training and validation sets were 0.736 and 0.665, respectively. The AUC values of the ROC curves at 2, 4, and 6 years were 0.702, 0.725, 0.740 in the training set and 0.697, 0.710, 0.744 in the validation set, respectively. The calibration curves showed that the predicted probabilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities. DCA demonstrated that the prediction model has a high net benefit.

Risk factors for CVD death in HCC patients were investigated for the first time. The nomograph served as an important reference tool for relevant clinical management decisions.

Liver cancer is a complex disease that presents many challenges in its diagnosis, treatment, and prevention. It's mortality rate in the United States is a significant and warrants attention.

To assess the trend of mortality rate due to HCC in the US from 1999 to 2020 by demographic groups for differences in trend of mortality.

We used the CDC wonder database to collect mortality rate data due to HCC as a multiple cause of death in the US from 1999 to 2020 by sex, race, age, and state of residence. The SEER Joinpoint program was used to calculate trends, defined as average annual percent change (AAPC) and to identify disparities between groups. All age-adjusted rates (AAMR) are reported per 100,000.

From 1999 to 2020, we found that women observed an uptrend (AAPC1.6%) and men observed a slightly higher uptrend in mortality (AAPC 1.8%). In addition, AI/AN population had a significant uptrend (AAPC 2.3%). The AAPI population observed a downtrend (AAPC -2.6%). The Black or African American population observed an uptrend (AAPC 1.8%) The white population also observed an uptrend (AAPC 2.2%). In the 2010 to 2020 time period, Mississippi had the lowest AAMR of any state with 15.2, while Hawaii had with the highest with 38.8.

This investigation assesses mortality rates and trends due to HCC cancer in the US and found significant differences in mortality rates and mortality rate trends due to HCC by demographic status in the US. Addressing the disparities in HCC incidence and mortality by race, ethnicity, state, and region, as well as improving access to screening, surveillance, and effective treatments, can reduce the burden of HCC and improve outcomes for patients.

Hepatocellular carcinoma (HCC) is a complex malignancy, and precise prognosis assessment is vital for personalized treatment decisions.

This study aimed to develop a multi-level prognostic risk model for HCC, offering individualized prognosis assessment and treatment guidance.

By utilizing data from The Cancer Genome Atlas (TCGA) and the Surveillance, Epidemiology, and End Results (SEER) database, we performed differential gene expression analysis to identify genes associated with survival in HCC patients. The HCC Differential Gene Prognostic Model (HCC-DGPM) was developed through multivariate Cox regression. Clinical indicators were incorporated into the HCC-DGPM using Cox regression, leading to the creation of the HCC Multilevel Prognostic Model (HCC-MLPM). Immune function was evaluated using single-sample Gene Set Enrichment Analysis (ssGSEA), and immune cell infiltration was assessed. Patient responsiveness to immunotherapy was evaluated using the Immunophenoscore (IPS). Clinical drug responsiveness was investigated using drug-related information from the TCGA database. Cox regression, Kaplan-Meier analysis, and trend association tests were conducted.

Seven differentially expressed genes from the TCGA database were used to construct the HCC-DGPM. Additionally, four clinical indicators associated with survival were identified from the SEER database for model adjustment. The adjusted HCC-MLPM showed significantly improved discriminative capacity (AUC=0.819 vs. 0.724). External validation involving 153 HCC patients from the International Cancer Genome Consortium (ICGC) database verified the performance of the HCC-MLPM (AUC=0.776). Significantly, the HCC-MLPM exhibited predictive capacity for patient response to immunotherapy and clinical drug efficacy (P < 0.05).

This study offers comprehensive insights into HCC prognosis and develops predictive models to enhance patient outcomes. The evaluation of immune function, immune cell infiltration, and clinical drug responsiveness enhances our comprehension and management of HCC.

Treatment choices in hepatocellular carcinoma (HCC) involve consideration of tradeoffs between the benefits, toxicities, inconvenience, and costs. Stated preference elicitation methods have been used in the medical field to help evaluate complex treatment decision-making. The aim of this study was to conduct a scoping review to assess the evidence base for the use of preference elicitation tools or willingness to pay/willingness to accept methods for HCC treatment decision-making from both the patient and provider perspective.

We performed a scoping review to identify abstracts or manuscripts focused on the role preference elicitation tools or willingness to pay/willingness to accept methods for HCC treatment options among patients, caregivers, and/or providers. Two researchers independently screened full-text references and resolved conflicts through discussion. We summarized key findings, including the type and setting of preference-elicitation tools used for HCC treatment decisions.

Ten published abstracts or manuscripts evaluated the role of preference elicitation tools for HCC treatments. The studies revealed several attributes that are considered by patients and providers making HCC treatment decisions. Many of the studies reviewed suggested that while patients place the most value on extending their overall survival, they are willing to forgo overall survival to avoid risks of treatments and maintain quality of life. Studies of physicians and surgeons found that provider preferences are dependent on patient characteristics, provider specialty, and surgeon or hospital-related factors.

This scoping review explored both patient and physician preferences towards treatment modalities in all stages of HCC. The studies revealed a large scope of potential attributes that may be important to patients and that many patients are willing to forgo survival to maintain quality of life. Further research should explore both preference elicitation of currently available and emerging therapies for HCC as well as the use of this data to develop patient-facing tools to assist in navigating treatment options.

The condition of sarcopenia, defined as a progressive loss of musculoskeletal mass and muscular strength, is very common in patients with hepatocellular carcinoma (HCC) and presents a remarkable association with its prognosis. Thus, the early identification of sarcopenic patients represents one of the potential new approaches in the global assessment of HCC, and there is increasing interest regarding the potential therapeutic implications of this condition. The gold standard for the quantification of muscle mass is magnetic resonance imaging (MRI) or computed tomography (CT), but these techniques are not always feasible because of the high-cost equipment needed. A new possibility in sarcopenia identification could be muscle ultrasound examination. The measurement of specific parameters such as the muscle thickness, muscular fascicles length or pennation angle has shown a good correlation with CT or MRI values and a good diagnostic accuracy in the detection of sarcopenia. Recently, these results were also confirmed specifically in patients with chronic liver disease. This review summarizes the role of imaging for the diagnosis of sarcopenia in patients with HCC, focusing on the advantages and disadvantages of the diagnostic techniques currently validated for this aim and the future perspectives for the identification of this condition.

The objective of this research was to determine the age cut-off for worse prognosis and investigate age-related differentially expressed genes (DEGs) in patients with advanced ovarian serous cystadenocarcinoma (AOSC).

In this research, we included a cohort of 20,846 patients diagnosed with AOSC, along with RNA-seq data from 374 patients in publicly available databases. Then we used the X-tile software to determine the age cut-off and stratified the patients into young and old groups. We utilized propensity score matching (PSM) to balance baseline between the young and old groups. Furthermore, we conducted an enrichment analysis of DEGs between the two age groups using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) to identify dysregulated pathways. To evaluate the potential prognostic value of the DEGs, we performed survival analysis, such as Kaplan-Meier analysis and Log rank test.

We stratified the patients into young group (n=16,336) and old group (n=4510) based on the cut-off age of 73 years by X-tile software. Age over 73 years was identified as an independent risk factor for overall survival (OS) and cancer-specific survival (CSS). Next, we identified 436 DEGs and found that the neurotrophin signaling pathway and translation factor activity were associated with prognosis outcomes. Among the top 10 hub genes (RELA, NFKBIA, TRAF6, IRAK2, TAB3, AKT1, TBP, EIF2S2, MAPK10, and SUPT3H), RELA, TAB3, AKT1, TBP, and SUPT3H were found to be significantly associated with poor prognosis in old patients with AOSC.

Our study determined 73 years as the cutoff value for age in patients with AOSC. RELA, TAB3, AKT1, TBP, and SUPT3H were identified as age-related DEGs that could contribute to the poor prognosis of older patients with AOSC.

Hepatocellular carcinoma (HCC) is a common worldwide cancer with a poor prognosis despite treatment advancements. Patients typically exhibit signs and symptoms pertaining to the liver. Extrahepatic metastasis of HCC is documented to be as low as 5% of cases. Bone metastasis ranks third following lungs and regional lymph nodes. The typical locations for bone metastasis include the vertebral column, pelvis, femora, and ribs, with skull metastasis, being reported in less than 1.6% of cases. Herein, we describe a case of HCC presenting with skull metastases and orbital invasion as the initial manifestation.