Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and a significant global health challenge due to its high mortality rate. The epidemiology of HCC is closely linked to the prevalence of chronic liver diseases, the predominant etiology being hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, alcohol consumption, and metabolic disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD). HCC incidence varies widely globally, with the highest rates observed in East Asia and sub-Saharan Africa. This geographic disparity is largely attributed to the endemicity of HBV and HCV in these regions. In Western countries, the incidence of HCC has been rising, driven by increasing rates of alcohol abuse and the presence of steatosis liver disease. MASLD-associated HCC has a higher body mass index, a higher rate of type 2 diabetes mellitus, hyperlipidemia, hypertension, and association with cardiovascular diseases. Steatosis-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related liver disease and viral hepatitis. Prevention strategies vary by region, focusing on vaccination against HBV, antiviral treatments for HBV and HCV, alcohol moderation, and lifestyle interventions along with weight reduction to reduce obesity and incidence of MASLD-related HCC incidence.

Male breast cancer (MBC) is rare, and due to the absence of male-specific screening programs, many patients are diagnosed at advanced stages and older ages. This study aims to analyze the long-term trend of MBC incidence and develop a competing risk model to improve survival rates. MBC data from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2019) were analyzed using the Age-Period-Cohort (APC) model to examine trends in age, period, and birth cohort effects of MBC incidence. A competing risk model was used to build a nomogram predicting breast cancer-specific survival (BCSS) for MBC patients, with model accuracy assessed using the concordance index (C-index) and calibration curves. These results were compared with the nomogram established by Cox model. Comparisons were made with traditional AJCC staging system using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). APC analysis showed MBC incidence increases with age, while period and birth cohort effects were not significant. A total of 2,057 patients were included in the competing risk analysis, which identified factors like older age, estrogen receptor (ER) negative, progesterone receptor (PR) negative, and advanced AJCC stage as being associated with shorter survival. The competing risk model demonstrated excellent predictive ability, surpassing the AJCC staging system in both accuracy and clinical utility. In contrast, the Cox regression model overestimated the risk of endpoint events and failed to provide accurate effect estimates. The high incidence and poor prognosis of MBC in the elderly population emphasize the need for improved screening and early diagnosis in high-risk groups. Our competing risk model, compared to the Cox model, more accurately reflects real-world conditions. Additionally, we have developed a competing risk nomogram to assist in identifying high-risk individuals and guiding clinical decision-making.

Sorafenib (SOR) is the first-line chemotherapeutic therapy for hepatocellular carcinoma (HCC) treatment, but SOR resistance is a key factor affecting the therapeutic effect. Emerging studies have suggested that circular RNAs (circRNAs) play an important role in the development of drug resistance in HCC cells. This paper aimed to elucidate the potential role and molecular mechanism of circRNA Scm polycomb group protein homolog 1 (circSCMH1) in SOR-resistant HCC cells. CircSCMH1, microRNA-485-5p (miR-485-5p), and hematological and neurological expressed 1 (HN1) contents were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8) assay was adopted to detect the SOR sensitivity of cells. Cell proliferation, migration, invasion, and apoptosis were assessed using colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), transwell, and flow cytometry assays. Glucose metabolism was analyzed using commercial kits. HN1, B cell lymphoma-2 (Bcl-2), and Bcl-2-associated X (Bax) protein levels were assessed using western blot. Binding between miR-485-5p and circSCMH1 or HN1 was verified using a dual-luciferase reporter. Xenograft tumor model was used to explore the function of circSCMH1 in vivo. CircSCMH1 expression and HN1 abundances were increased, but the miR-485-5p level was reduced in SOR-resistant HCC tissues and cells. Deficiency of circSCMH1 enhanced SOR sensitivity by suppressing cell proliferation, migration, invasion, and glucose metabolism and inducing cell apoptosis in SOR-resistant HCC cell lines (Huh7/SOR and Hep3B/SOR). Mechanistically, circSCMH1 sponged miR-485-5p to positively regulate HN1 expression. Importantly, circSCMH1 depletion inhibited tumor growth and increased SOR sensitivity in vivo. CircSCMH1 promoted SOR resistance in HCC cells at least partly through upregulating HN1 expression by sponging miR-485-5p. These findings elucidated a new regulatory pathway of chemo-resistance in SOR-resistant HCC cells and provided a possible circRNA-targeted therapy for HCC.

We sought to develop Artificial Intelligence (AI) based models to predict non-transplantable recurrence (NTR) of hepatocellular carcinoma (HCC) following hepatic resection (HR).

HCC patients who underwent HR between 2000-2020 were identified from a multi-institutional database. NTR was defined as recurrence beyond Milan Criteria. Different machine learning (ML) and deep learning (DL) techniques were used to develop and validate two prediction models for NTR, one using only preoperative factors and a second using both preoperative and postoperative factors.

Overall, 1763 HCC patients were included. Among 877 patients with recurrence, 364 (41.5%) patients developed NTR. An ensemble AI model demonstrated the highest area under ROC curves (AUC) of 0.751 (95% CI: 0.719-0.782) and 0.717 (95% CI:0.653-0.782) in the training and testing cohorts, respectively which improved to 0.858 (95% CI: 0.835-0.884) and 0.764 (95% CI: 0.704-0.826), respectively after incorporation of postoperative pathologic factors. Radiologic tumor burden score and pathological microvascular invasion were the most important preoperative and postoperative factors, respectively to predict NTR. Patients predicted to develop NTR had overall 1- and 5-year survival of 75.6% and 28.2%, versus 93.4% and 55.9%, respectively, among patients predicted to not develop NTR (p < 0.0001).

The AI preoperative model may help inform decision of HR versus LT for HCC, while the combined AI model can frame individualized postoperative care (https://altaf-pawlik-hcc-ntr-calculator.streamlit.app/).

Postoperative delirium (POD) is a common complication in older patients with hepatocellular carcinoma (HCC) that adversely impacts clinical outcomes. We aimed to evaluate the risk factors for POD and to construct a predictive nomogram. Data for a total of 1481 older patients (training set: n=1109; validation set: n=372) who received liver resection for HCC were retrospectively retrieved from two prospective databases. The receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were used to evaluate the performance. The rate of POD was 13.3% (148/1109) in the training set and 16.4% (61/372) in the validation set. Multivariate analysis of the training set revealed that factors including age, history of cerebrovascular disease, American Society of Anesthesiologists (ASA) classification, albumin level, and surgical approach had significant effects on POD. The area under the ROC curves (AUC) for the nomogram, incorporating the aforementioned predictors, was 0.798 (95% CI 0.752-0.843) and 0.808 (95% CI 0.754-0.861) for the training and validation sets, respectively. The calibration curves of both sets showed a degree of agreement between the nomogram and the actual probability. DCA demonstrated that the newly established nomogram was highly effective for clinical decision-making. We developed and validated a nomogram with high sensitivity to assist clinicians in estimating the individual risk of POD in older patients with HCC.

Liver cancer is one of the most common malignant gastrointestinal tumors worldwide. This study intends to provide insight into the epidemiological characteristics and development trends of liver cancer incidence and mortality from 2010 to 2020 in Guangzhou, China.

Data were collected from the Cancer Registry and Reporting Office of Guangzhou Center for Disease Control and Prevention. Cross-sectional study, Joinpoint regression (JPR) model, and Age-Period-Cohort (APC) model were conducted to analyze the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) trend of liver cancer among the entire study period.

The age-standardized incidence and mortality of liver cancer in Guangzhou showed an overall decreasing trend. The disparity in risk of morbidity and mortality between the two sexes for liver cancer is increasing. The cohort effect was the most significant among those born in 1965~1969, and the risk of liver cancer incidence and mortality in the total population increased and then decreased with the birth cohort. Compared with the birth cohort born in 1950~1954 (the reference cohort), the risk of liver cancer incidence and mortality in the males born in 1995~1999 decreased by 32% and 41%, respectively, while the risk in the females decreased by 31% and 32%, respectively.

The early detection, prevention, clinical diagnosis, and treatment of liver cancer in Guangzhou have made remarkable achievements in recent years. However, the risk of liver cancer in the elderly and the middle-aged males is still at a high level. Therefore, the publicity of knowledge related to the prevention and treatment of liver cancer among the relevant population groups should be actively carried out to enhance the rate of early diagnosis and treatment of liver cancer and to advocate a healthier lifestyle.

Increasing data indicated that long noncoding RNAs (lncRNAs) were directly or indirectly involved in the occurrence and development of tumors, including hepatocellular carcinoma (HCC). Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues, but its role in HCC progression is unclear. Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.

To study the role of ultrasound microbubbles (UTMBs) mediated HAND2-AS1 in the progression of HCC, in order to provide a new reference for the treatment of HCC.

In vitro, we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs, and detected cell proliferation, apoptosis, invasion and epithelial-mesenchymal transition (EMT) by cell counting kit-8 assay, flow cytometry, Transwell invasion assay and Western blotting, respectively. In addition, we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior. Next, the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2 (TIMP2) overexpression vector, and we detected cell proliferation, apoptosis, invasion and EMT. In vivo, we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.

We found that UTMBs carrying HAND2-AS1 restricted cell proliferation, invasion, and EMT, encouraged apoptosis, and HAND2-AS1 silencing eliminated the effect of UTMBs. Additionally, miR-873-5p targets the gene HAND2-AS1, which also targets the 3'UTR of TIMP2. And miR-873-5p mimic counteracted the impact of HAND2-AS1. Further, miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs. We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase (MMP) 2/MMP9. In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.

LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

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.

American Joint Committee on Cancer (AJCC)-TNM system doesn't accurately predict prognosis. Our study was designed to identify prognostic factors in patients with multiple hepatocellular carcinoma (MHCC), establish and validate a nomogram model to predict the risk and overall survival (OS) of MHCC patients.

We selected eligible HCC patients from the Surveillance, Epidemiology, and End Results (SEER) database, used univariate and multivariate COX regression to determine prognostic factors in MHCC patients, and used these factors to build a nomogram. The accuracy of the prediction was evaluated using the C-index, receiver operating characteristic (ROC) and calibration curve. Decision curve analysis (DCA), net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to compare the nomogram with AJCC-TNM staging system. Finally, the prognosis of different risks was analyzed using Kaplan-Meier (K-M) method.

4950 eligible patients with MHCC were enrolled in our study and randomly assigned to the training cohort and test cohort in a 7:3 ratio. After COX regression analysis, age, sex, histological grade, AJCC-TNM stage, tumor size, alpha-fetoprotein (AFP), surgery, radiotherapy and chemotherapy in total 9 factors could be used to independently determine OS of patients. the above factors were used to construct a nomogram, and the consistency C-index was 0.775. C-index, DCA, NRI and IDI showed that our nomogram was superior to the AJCC-TNM staging system. K-M plots for OS were performed using the log-rank test, the P-value of which was <0.001.

The practical nomogram can provide more accurate prognostic prediction for multiple hepatocellular carcinoma patients.

Hepatocellular carcinoma (HCC) is a growing health concern projected to cross over a million cases worldwide by 2025. HCC presents a significant burden of disease in Middle East and North African (MENA) countries due to a high prevalence of risk factors such as hepatitis C and B infections and rising incidence of non-alcoholic steatohepatitis and non-alcoholic fatty liver disease. In August 2022, an advisory meeting consisting of experts from 5 MENA countries was convened in an attempt to provide consensus recommendations on HCC screening, early diagnosis, current treatment modalities and unmet medical needs in the region. Data were collected from a pre-meeting survey questionnaire and responses analysed and presented during the advisory meeting. This review summarizes the evidence discussed at the meeting and provides expert recommendations on the management of HCC. The 2022 update of Barcelona clinic liver cancer (BCLC) staging and treatment strategy and its implementation in the MENA region was extensively discussed. A key consensus of the expert panel was that multidisciplinary care is crucial to effective patient management that results in better clinical outcomes and overall survival of the patient. The panel recommended the use of predictive and early response biomarkers to guide clinicians in arriving at more effective therapeutic decisions. The experts also emphasized the role of robust screening/surveillance systems, population-based registries, effective referral pathways and standardization of guidelines to ensure the successful management of HCC in the region.

Hepatitis B virus (HBV) infection is a major global health problem which progresses to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Early prediction of disease changes and intervention are essential to slow disease progression and protect liver function. This study aimed to analyze the clinical characteristics of patients with HBV-related LC and HCC at different serum alanine aminotransferase (ALT) levels and explore the risk factors of HBV infection progressing to LC/HCC.

A total of 379 patients with HBV infection treated in The Third People's Hospital of Shenzhen between January 2014 and December 2016 without any antiviral drug therapy were enrolled. Patients were divided into the LC/HCC and non-LC/HCC groups based on clinical diagnosis, which was determined through imaging and expressions of pathological and laboratory test markers, and patients with LC/HCC were further divided into three groups according to the serum ALT levels. Differences in general information, clinical symptoms, and expression levels of serological indices of the above groups were compared and analyzed, logistic regression was used to analyze the risk factors for LC/HCC development, and the clinical diagnostic efficacy of indicators was judged by the receiver operator characteristic (ROC).

LC/HCC mainly occurred in the ALT normal and mildly elevated groups, with 70.83% of patients with HCC having an LC background. In the comparison of different ALT level groups, the moderately-severely elevated group had the highest proportion of patients with skin jaundice, abdominal varices, rebound tenderness, higher white blood cell and neutrophil (NEUT) counts; and higher levels of aspartate aminotransferase, glutamyl transpeptidase, total bilirubin, and direct bilirubin. The LC/HCC group was older and had significantly higher proportions of male patients, alcohol consumption, and combined hypertension than the non-LC/HCC group (all P < 0.05). Logistic regression analysis showed that age, combined hypertension, abdominal varicose veins, subcostal palpation, and NEUT count were risk factors for LC/HCC development; and the area under the curve for this model on the ROC analysis was 0.935 (95% confidence interval 0.899-0.972) with specificity and sensitivity of 97.4% and 70.7%, respectively.

Advanced age, combined hypertension, abdominal varicose veins, subcostal palpation, and high NEUT count are risk factors for LC/HCC development in patients with untreated HBV infection.

Hepatocellular carcinoma (HCC) is a common type of cancer. We hypothesize that circular RNA-0006091 (circ-0006091) affects the progression of HCC. The study aims to investigate the effect of circ-0006091 in HCC cells.

The levels of circ-0006091, microRNA-622 (miR-622), and cyclin B1 (CCNB1) were assayed using qRT-PCR and western blotting. The metastasis of the HCC cells was measured with wound healing and transwell assays. The protein expression levels of MMP-2 and MMP-9 were assayed with western blotting. Dual-luciferase reporter and RNA-pulldown assays were used to determine the link between miR-622 and circ-0006091 or CCNB1. Mice-based tests were used to determine the effect of circ-0006091 on the proliferation of HCC cells.

The levels of circ-0006091 and CCNB1 were increased in the HCC cells, but miR-622 was down-regulated. Deficiency of circ-0006091 reduced the metastasis of the HCC cells, and silencing of circ-0006091 decreased the activities of MMP-2 and MMP-9 in the same cells. Circ-0006091 modulated the CCNB1 level in the HCC cells via miR-622. Silencing of circ-0006091 suppressed the proliferation of the HCC cells in vivo.

Circ-0006091 regulated HCC cell metastasis via the miR-622/CCNB1 axis, a possible therapeutic target in managing HCC.

This study analyzes nationwide trends in HCC hospitalizations focusing on interventional liver-directed treatments and the influence of age and gender. Using data from the German Federal Statistical Office all hospitalizations for HCC between 2010 and 2020 were included. Uni- and multivariable logistic regression analyses were performed to identify variables independently associated with the use of liver-directed therapies. Due to the COVID-19 pandemic, data from 2020 were analyzed separately. A total of 134,713 hospitalizations (2010-2019) were included, increasing by 3.4% annually (12,707 to 13,143). The mean in-hospital stay (-15.0% [7.2 to 6.1 days]) and mortality (-23.2% [6.8 to 5.2%]) decreased while transarterial, surgical, and percutaneous ablative interventions increased by 38.6, 31.5, and 19.3%, respectively. In-hospital mortality was 7.7% in admissions with surgical treatment, while it was 0.6 and 0.5% for transarterial and percutaneous interventions. Mortality was higher in females (6.2 vs. 5.7%). Females (OR 0.89 [0.86,0.91], p < 0.001) and patients ≥80 years (OR 0.81 [0.79,0.84], p < 0.001) were less likely to receive liver-directed treatments. Liver-directed therapies were increasingly performed while in-hospital mortality and in-hospital stay decreased. Minimally invasive approaches showed lower mortality, shorter in-hospital stay, and lower costs compared to surgery. Proportionately, more women and older patients were hospitalized, receiving fewer liver-directed treatments while their mortality was higher.

This study was to explore the trends of mortality rates for mental disorders by gender in urban and rural areas in China (2006-2020) and estimate the independent effects of age, period, and cohort on the mortality of mental disorders. This study employs data from the China Health Statistical Yearbook. The data were analysed using joinpoint regression analysis as well as age-period-cohort analysis. Results revealed the age-standardized mortality rates of mental disorders in China showed a downward trend, and women had a faster rate of decline than men over the years 2006-2020. Age, period, and birth cohort effects were statistically significant in the trend analysis of mental disorder mortality, and compared with period and cohort effects, age effects were the leading correlate of mental disorder mortality. The risk of death increased with advancing age. Our findings suggest that the mortality of mental disorders showed a downward trend, but some effective measures, especially regarding mental disorders, need to be taken to protect people with these disorders and prevent their occurrence in the setting of an ageing population.

Circular RNAs (circRNAs) serve as critical regulatory factors in cancer development. Nonetheless, the potential regulatory mechanism of circRNA sorting nexin 27 (circ_SNX27) in hepatocellular carcinoma (HCC) is still unknown.

The circ_SNX27, microRNA-637 (miR-637), and fibroblast growth factor receptor 1 (FGFR1) levels were quantified by quantitative real-time polymerase chain reaction and western blot analysis. Next, function experiments were conducted using in vitro assays and in vivo senograft study. The relationship between miR-637 with circ_SNX27 or FGFR1 was uncovered by dual-luciferase reporter and RNA pull-down assays.

The circ_SNX27 and FGFR1 levels were up-regulated, but miR-637 content was reduced in HCC. Circ_SNX27 down-regulation inhibited HCC cell proliferation, motility, and invasion and promoted apoptosis in vitro, as well as weakened tumor growth in vivo. Circ_SNX27 served as a sponge of miR-637 to promote FGFR1 expression. MiR-637 reduction abolished the restrained effect of circ_SNX27 absence on HCC cell development. Moreover, miR-637 curbed HCC cell malignant phenotype by regulating FGFR1.

Circ_SNX27 contributed to HCC development via miR-637/FGFR1 axis, offering a new idea for the treatment of HCC.

Liver cancer is the fifth most common cancer and the second leading cause of malignant death in Asia, and Asia reports 72.5% of the world's cases in 2020. As the most common histological type, hepatocellular carcinoma (HCC) accounts for the majority of incidence and mortality of liver cancer cases. This review presents the changing epidemiology of HCC in Asian countries in recent years. Globally, aged, male and Asian populations remain the group with the highest risk of HCC. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are still the leading risk factors of HCC with a slight decline in most Asian countries, which is mainly attributed to HBV vaccination of newborns, prevention of HCV horizontal transmission and treatment of chronic hepatitis. However, the prevalence of HCC caused by metabolic factors, including metabolic syndrome, obesity and non-alcoholic fatty liver diseases, is increasing rapidly in Asian countries, which may eventually become the major cause of HCC. Excessive alcohol consumption continues to be an important risk factor as the average consumption of alcohol is still growing. Hopefully, great effort has been made to better prevention and treatment of HCC in most Asian regions, which significantly prolongs the survival of HCC patients. Asian countries tend to use more aggressive intervention than European and American countries, but it remains unclear whether this preference is related to a better prognosis. In conclusion, HCC remains a major disease burden in Asia, and the management of HCC should be adjusted dynamically based on the changing epidemiology.