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Simple Summary: Hepatocellular carcinoma (HCC), the most prevalent form of primary liver cancer, is a significant cause of cancer mortality. Patients with advanced HCC commonly receive systemic therapy, including tyrosine kinase inhibitors (TKIs) such as sorafenib and lenvatinib. However, TKI resistance remains a challenge. Statins, known for their lipid-lowering properties, also show potential anti-cancer effects, particularly in HCC, by inhibiting the mevalonate pathway. Evidence suggests statins may reduce HCC risk in patients with certain conditions and potentially enhance the efficacy of TKIs. Our study, utilizing data from Korea's Health Insurance Review and Assessment Service (HIRA), investigated the clinical benefits of statins in patients with advanced HCC treated with TKIs, verifying the timing, type, and dosage of statins and their impact on patient survival outcomes. We aimed to evaluate the survival benefits of coadministering statins and multityrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC). Data from the Health Insurance Review and Assessment Service in Korea (2010–2020) were utilized. Statin use (≥28 cumulative defined daily doses) was analyzed, with 1534 statin users matched to 6136 non-users (1:4 ratio) using propensity scores. Primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS). Statin use significantly improved OS (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.72–0.82, p < 0.001) and PFS (HR 0.78, 95% CI 0.74–0.84, p < 0.001). Continuous or post-TKI statin users had better OS, while discontinuation after TKI use led to poorer OS. Both lipophilic and hydrophilic statins improved OS and PFS, particularly with ≥730 cumulative defined daily doses. In conclusion, combining statins and TKIs in patients with advanced HCC yielded significant survival benefits, influenced by statin dosage and duration. Continuous statin administration post-TKI treatment is crucial for improving outcomes in patients with HCC. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluated the impact of alpha-fetoprotein (AFP) testing frequency on survival rates in hepatocellular carcinoma (HCC) patients. Analyzing data from 81,520 patients in Korea, it was found that increased AFP testing significantly improved survival, particularly in patients with hepatitis B undergoing antiviral treatment. Those tested three or more times before diagnosis had a higher likelihood of receiving curative treatments, such as liver transplantation. The study suggests that combining AFP tests with ultrasound screenings could better detect HCC early, offering enhanced treatment opportunities and improved survival chances, especially for hepatitis B patients. Guidelines vary on alpha-fetoprotein (AFP) testing for hepatocellular carcinoma (HCC) screening. This study aims to reassess AFP's role in HCC surveillance, utilizing a comprehensive, recent, nationwide cohort. Utilizing the National Health Claims Database from the Korean National Health Insurance Service, this research included data from 185,316 HCC patients registered between 2008 and 2018. Specifically, 81,520 patients diagnosed with HCC from 2008 to 2014 were analyzed. The study focused primarily on mortality and, secondarily, on the status of curative treatments. Multivariate analysis revealed that frequent AFP testing significantly impacts overall survival in HCC patients. Specifically, each additional AFP test correlated with a 6% relative improvement in survival (hazard ratio = 0.94, 95% CI: 0.940–0.947, p < 0.001). Patients who underwent AFP testing three or more times within two years prior to HCC diagnosis showed improved survival rates, with 55.6% receiving liver transplantation or hepatectomy. This trend was particularly pronounced in hepatitis B patients undergoing antiviral treatment. The findings highlight the potential of regular AFP testing to enhance survival in HCC patients, especially those with hepatitis B. Integrating frequent AFP testing with ultrasonography could increase the likelihood of early detection and access to curative treatments. [ABSTRACT FROM AUTHOR]

Summary: Background: As tenofovir disoproxil fumarate (TDF) requires long‐term use, a reduction in bone density should be considered a possibility when treating patients with chronic hepatitis B (CHB) with aging and systemic diseases. Patients treated with tenofovir alafenamide (TAF) have improved bone mineral density loss compared to patients treated with TDF. Although improvements in bone density caused by TAF have been reported, studies on the actual reduction of fractures are insufficient. Aim: To evaluate the impact of TAF on the risk of osteoporotic fractures in comparison with that of TDF. Methods: Using the national claims data of the Health Insurance Review and Assessment Service, we conducted a retrospective cohort study of 32,582 patients with CHB who had been initially treated with TDF or TAF between November 2017 and December 2020. The numbers of patients treated with TDF and TAF were 20,877 and 11,705, respectively. The annual fracture rate per 100 patients in each group was calculated, and the Cox proportional hazard ratio (HR) was analysed after applying inverse probability treatment weights (IPTW) for both groups. Results: Among 32,582 patients, the average age was 47.8 ± 11.2 years, 64.5% were men, and the follow‐up period was 24.4 ± 11.6 months. The incidence of osteoporotic fractures was 0.78 and 0.49 per 100 person‐years in the TDF and TAF groups, respectively. After application of IPTW, the HR was 0.68 (95% confidence interval 0.55–0.85, p = 0.001). Conclusion: TAF‐treated patients with CHB had a significantly lower risk of osteoporotic fracture than TDF‐treated patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to validate the integrin alpha-6 (ITGA6) gene as a potential blood marker for early detection of hepatocellular carcinoma (HCC). Our methodological approach involved analyzing genomic datasets, leading to the identification of ITGA6 among differentially expressed genes in HCC. Further validation and analyses revealed consistent upregulation of ITGA6 in HCC, its predominant expression in tumor endothelial cells (TECs), and associations with pro-tumorigenic immune cells. This research highlights the potential of ITGA6 as an early HCC detection marker and its role in the tumor microenvironment, paving the way for new strategies in HCC management. HCC remains a lethal cancer type, with early detection being critical for improved patient outcomes. This study introduces a comprehensive methodological approach to identify the ITGA6 gene as a potential blood marker for early HCC (eHCC) detection. We initially analyzed the GSE114564 dataset encompassing various stages of liver disease, identifying 972 differentially expressed genes in HCC. A refined analysis yielded 59 genes specifically differentially expressed in early HCC, including ITGA6. Subsequent validation in multiple datasets confirmed the consistent upregulation of ITGA6 in HCC. In addition, when analyzing progression-free survival (PFS) within the entire patient cohort and overall survival (OS) specifically among patients classified as tumor grade G1, the group of patients characterized by high expression levels of ITGA6 displayed an elevated risk ratio in relation to prognosis. Further analyses demonstrated the predominant expression of ITGA6 in TECs and its enrichment in angiogenesis-related pathways. Additionally, positive correlations were found between ITGA6 expression and pro-tumorigenic immune cells, but not with anti-tumorigenic immune cells. Our study elucidates the potential of ITGA6 as a blood-based marker for HCC early detection and diagnosis and its complex interplay with the tumor microenvironment. Further research may lead to novel strategies for HCC management and patient care. [ABSTRACT FROM AUTHOR]

A control group is defined as a group of people used for comparison. Depending on the type of study, it can be a group of healthy people or a group not exposed to risk factors. It is important to allow researchers to select the appropriate control participants. The Korea Biobank Project-sponsored biobanks are affiliated with the Korea Biobank Network (KBN), for which the National Biobank of Korea plays a central coordinating role among KBN biobanks. KBN organized several working groups to address new challenges and needs in biobanking. The "Normal Healthy Control Working Group" developed standardized criteria for three defined control groups, namely, normal, normal-plus, and disease-specific controls. Based on the consensus on the definition of a normal control, we applied the criteria for normal control participants to retrospective data. The main reason for exclusion from the "Normal-plus" group was blood test results beyond 5% of the reference range, including hypercholesterolemia. Subclassification of samples of normal controls by detailed criteria will help researchers select optimal normal controls for their studies. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) contribute to tumor progression, and microRNAs (miRs) play an important role in regulating the tumor-promoting properties of CAFs. The objectives of this study were to clarify the specific miR expression profile in CAFs of hepatocellular carcinoma (HCC) and identify its target gene signatures. Small-RNA-sequencing data were generated from nine pairs of CAFs and para-cancer fibroblasts isolated from human HCC and para-tumor tissues, respectively. Bioinformatic analyses were performed to identify the HCC-CAF-specific miR expression profile and the target gene signatures of the deregulated miRs in CAFs. Clinical and immunological implications of the target gene signatures were evaluated in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA_LIHC) database using Cox regression and TIMER analysis. The expressions of hsa-miR-101-3p and hsa-miR-490-3p were significantly downregulated in HCC-CAFs. Their expression in HCC tissue gradually decreased as HCC stage progressed in the clinical staging analysis. Bioinformatic network analysis using miRWalks, miRDB, and miRTarBase databases pointed to TGFBR1 as a common target gene of hsa-miR-101-3p and hsa-miR-490-3p. TGFBR1 expression was negatively correlated with miR-101-3p and miR-490-3p expression in HCC tissues and was also decreased by ectopic miR-101-3p and miR-490-3p expression. HCC patients with TGFBR1 overexpression and downregulated hsa-miR-101-3p and hsa-miR-490-3p demonstrated a significantly poorer prognosis in TCGA_LIHC. TGFBR1 expression was positively correlated with the infiltration of myeloid-derived suppressor cells, regulatory T cells, and M2 macrophages in a TIMER analysis. In conclusion, hsa-miR-101-3p and hsa-miR-490-3p were substantially downregulated miRs in CAFs of HCC, and their common target gene was TGFBR1. The downregulation of hsa-miR-101-3p and hsa-miR-490-3p, as well as high TGFBR1 expression, was associated with poor clinical outcome in HCC patients. In addition, TGFBR1 expression was correlated with the infiltration of immunosuppressive immune cells. [ABSTRACT FROM AUTHOR]