1,721,143 research outputs found
The urgent need for multidisciplinary approaches in managing alcohol-associated liver disease: Editorial on “The prognostic impact of psychiatric intervention on alcohol-associated liver disease: The UK Biobank cohort study”
Full text linkMachine-learning model to predict the cause of death using a stacking ensemble method for observational data
Full text linkOBJECTIVE: Cause of death is used as an important outcome of clinical research; however, access to cause-of-death data is limited. This study aimed to develop and validate a machine-learning model that predicts the cause of death from the patient's last medical checkup. MATERIALS AND METHODS: To classify the mortality status and each individual cause of death, we used a stacking ensemble method. The prediction outcomes were all-cause mortality, 8 leading causes of death in South Korea, and other causes. The clinical data of study populations were extracted from the national claims (n = 174 747) and electronic health records (n = 729 065) and were used for model development and external validation. Moreover, we imputed the cause of death from the data of 3 US claims databases (n = 994 518, 995 372, and 407 604, respectively). All databases were formatted to the Observational Medical Outcomes Partnership Common Data Model. RESULTS: The generalized area under the receiver operating characteristic curve (AUROC) of the model predicting the cause of death within 60 days was 0.9511. Moreover, the AUROC of the external validation was 0.8887. Among the causes of death imputed in the Medicare Supplemental database, 11.32% of deaths were due to malignant neoplastic disease. DISCUSSION: This study showed the potential of machine-learning models as a new alternative to address the lack of access to cause-of-death data. All processes were disclosed to maintain transparency, and the model was easily applicable to other institutions. CONCLUSION: A machine-learning model with competent performance was developed to predict cause of death
A New Understanding of Long Non-Coding RNA in Hepatocellular Carcinoma—From m6A Modification to Blood Biomarkers
Full text linkWith recent advancements in biological research, long non-coding RNAs (lncRNAs) with lengths exceeding 200 nucleotides have emerged as pivotal regulators of gene expression and cellular phenotypic modulation. Despite initial skepticism due to their low sequence conservation and expression levels, their significance in various biological processes has become increasingly apparent. We provided an overview of lncRNAs and discussed their defining features and modes of operation. We then explored their crucial function in the hepatocarcinogenesis process, elucidating their complex involvement in hepatocellular carcinoma (HCC). The influential role of lncRNAs within the HCC tumor microenvironment is emphasized, illustrating their potential as key modulators of disease dynamics. We also investigated the significant influence of N6-methyladenosine (m6A) modification on lncRNA function in HCC, enhancing our understanding of both their roles and their upstream regulators. Additionally, the potential of lncRNAs as promising biomarkers was discussed in liver cancer diagnosis, suggesting a novel avenue for future research and clinical application. Finally, our work underscored the dual potential of lncRNAs as both contributors to HCC pathogenesis and innovative tools for its diagnosis. Existing challenges and prospective trajectories in lncRNA research are also discussed, emphasizing their potential in advancing liver cancer research
Role of Immune Cells in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma
Full text linkHepatocellular carcinoma (HCC) develops almost entirely in the presence of chronic inflammation. Chronic hepatitis B virus (HBV) infection with recurrent immune-mediated liver damage ultimately leads to cirrhosis and HCC. It is widely accepted that HBV infection induces the dysfunction of the innate and adaptive immune responses that engage various immune cells. Natural killer (NK) cells are associated with early antiviral and antitumor properties. On the other hand, inflammatory cells release various cytokines and chemokines that may promote HCC tumorigenesis. Moreover, immunosuppressive cells such as regulatory T cells (Treg) and myeloid-derived suppressive cells play a critical role in hepatocarcinogenesis. HBV-specific CD8+ T cells have been identified as pivotal players in antiviral responses, whilst extremely activated CD8+ T cells induce enormous inflammatory responses, and chronic inflammation can facilitate hepatocarcinogenesis. Controlling and maintaining the balance in the immune system is an important aspect in the management of HBV-related HCC. We conducted a review of the current knowledge on the immunopathogenesis of HBV-induced inflammation and the role of such immune activation in the tumorigenesis of HCC based on the recent studies on innate and adaptive immune cell dysfunction in HBV-related HCC
Screening and prediction of nonalcoholic fatty liver disease using a peripheral insulin resistance index: Potential benefits and limitations
Full text linkSGLT2i impact on HCC incidence in patients with fatty liver disease and diabetes: a nation-wide cohort study in South Korea
Full text linkThis study evaluated the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cancer development, particularly in hepatocellular carcinoma (HCC), in individuals with concomitant fatty liver disease (FLD) and type 2 diabetes mellitus (T2DM). Using data from Korea's Health Insurance Review and Assessment Service, we performed Kaplan-Meier and Cox regression analyses in patients with non-alcoholic fatty liver disease (NAFLD) and T2DM (NAFLD-T2DM cohort) and those with chronic viral hepatitis (CVH) alongside FLD and T2DM (FLD-T2DM-CVH cohort). In the propensity score (PS) matched NAFLD-T2DM cohort (N = 107,972), SGLT2i use was not associated with the occurrence of overall cancer, including HCC. However, old age, male sex, liver cirrhosis, and hypothyroidism were identified as independent risk factors for HCC occurrence, whereas statin and fibrate usage were associated with reduced HCC risk in this cohort in multivariate Cox analysis. In the PS-matched FLD-T2DM-CVH cohort (N = 2798), a significant decrease in HCC occurrence was observed among SGLT2i users (P = 0.03). This finding remained consistent in the multivariate Cox regression analysis (Hazard ratio = 2.21, 95% confidence interval = 1.01-4.85, P = 0.048). In conclusion, SGLT2i may be a beneficial option for diabetes management in patients with concomitant T2DM, FLD, and CVH while affirming the overall safety of SGLT2i in other types of cancer
Impact of Antihypertensive and Lipid-Lowering Agents on Hepatocellular Carcinoma Risk in Patients with Fatty Liver Disease and Diabetes
No full textBACKGROUND/AIM: This study aimed to evaluate the effects of antihypertensives, lipid-lowering agents, and antiplatelet medications on hepatocellular carcinoma (HCC) risk in patients with fatty liver disease (FLD) and type 2 diabetes (T2D). METHOD: Using data from Korea Health Insurance Review and Assessment Service, 212,443 FLD-T2D patients were analyzed through Cox regression, propensity score matching (PSM), and Kaplan-Meier analysis. The analysis considered medication use and its relation to HCC development. Cohort admission day was set as the date of the first oral hypoglycemic prescription. RESULTS: The multivariate Cox regression analysis revealed that old age, male sex, chronic viral hepatitis, alcoholic liver disease, liver cirrhosis, using a combination of insulin and oral hypoglycemic agents for antidiabetic treatment, and calcium channel blocker (CCB) use were significantly correlated with higher HCC development risk, whereas dyslipidemia and statin, ezetimibe, and fibrate use was correlated with lower HCC risk, in the study cohort of 212,443 patients. Patients who used statins (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.42-0.80, P = 0.001) and fibrates (HR = 0.46, 95% CI = 0.22-0.93, P = 0.031) showed a significantly lower risk of HCC development even after PSM. In contrast, CCB use was linked to an elevated HCC risk (HR = 1.35, 95% CI = 1.05-1.72, P = 0.019), highlighting the differential impact of various medications on HCC incidence. CONCLUSION: The use of specific medications, such as statins and fibrates, may offer protective effects against HCC in patients with FLD-T2D, whereas that of CCB may increase the risk. This underscores the importance of tailored medication strategies for the management of chronic conditions
Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study
Full text linkPlasma exosomal miRNAs are key regulators of cell-cell interactions associated with several biological functions in patients with cancer. This pilot study aimed to investigate the log2 fold change (log2FC) of the expression of exosomal miRNAs and related mRNAs in the blood of patients with cervical cancer to identify prognostic markers better than those currently available. We sequenced plasma exosomal RNA from 56 blood samples collected from 28 patients with cervical cancer, who had been treated with concurrent chemoradiotherapy (CCRT). Changes in the expression of miRNAs and mRNAs before and after CCRT were represented as log2FC. Their biological functions were studied by miRNA-mRNA network analysis, using ingenuity pathway analysis, after the selection of two groups of miRNAs, each associated with early progression (EP) and metastasis, also described as initial stage. Seven patients experienced EP, three of whom died within four months after progression. Reduced levels of miR-1228-5p, miR-33a-5p, miR-3200-3p, and miR-6815-5p and increased levels of miR-146a-3p in patients with EP revealed unresolved inflammation, with accompanying increased expression of PCK1 and decreased expression of FCGR1A. Increased levels of miR-605-5p, miR-6791-5p, miR-6780a-5p, and miR-6826-5p and decreased levels of miR-16-1-3p (or 15a-3p) were associated with the degree of metastasis and led to the systemic activation of myeloid, endothelial, and epithelial cells, as well as neurons, phagocytes, and platelets. Log2FCs in the expression of miRNAs and mRNAs from plasma exosomes after CCRT are associated with EP and metastasis, reflecting unresolved inflammation and systemic microenvironmental factors, respectively. However, this study, supported by preliminary data insufficient to reach clear conclusions, should be verified in larger prospective cohorts
Screening Plasma Exosomal RNAs as Diagnostic Markers for Cervical Cancer: An Analysis of Patients Who Underwent Primary Chemoradiotherapy
Full text linkThis preliminary study aimed to screen non-coding RNAs (ncRNAs) from plasma exosomes as a new method for cervical cancer diagnosis. Differentially expressed RNAs were initially selected from among a group of 12 healthy individuals (normal group) and a pretreatment group of 30 patients with cervical cancer (cancer group). Then, we analyzed the association between an ncRNA-mRNA network and cancer using ingenuity pathway analysis after secondary selection according to the number and correlation of mRNAs (or ncRNAs) relative to changes in the expression of primarily selected ncRNAs (or mRNAs) before and after chemoradiotherapy. The number of RNAs selected from the initial RNAs was one from 13 miRNAs, four from 42 piRNAs, four from 28 lncRNAs, nine from 18 snoRNAs, 10 from 76 snRNAs, nine from 474 tRNAs, nine from 64 yRNAs, and five from 67 mRNAs. The combination of miRNA (miR-142-3p), mRNAs (CXCL5, KIF2A, RGS18, APL6IP5, and DAPP1), and snoRNAs (SNORD17, SCARNA12, SNORA6, SNORA12, SCRNA1, SNORD97, SNORD62, and SNORD38A) clearly distinguished the normal samples from the cancer group samples. We present a method for efficiently screening eight classes of RNAs isolated from exosomes for cervical cancer diagnosis using mRNAs (or ncRNAs) altered by chemoradiotherapy
Infiltrative hepatocellular carcinoma with multiple lung metastasis completely cured using nivolumab: a case report
Full text linkThe current Food and Drug Administration-approved systemic treatments for advanced hepatocellular carcinoma (HCC) include multikinase inhibitors (tyrosine kinase inhibitor [TKI]) and immune checkpoint inhibitors (ICIs). Among ICIs, nivolumab is used as second-line therapy for advanced HCC after sorafenib failure or patient intolerance. In this case, a patient with infiltrative HCC and portal vein tumor thrombosis was treated with hepatic arterial infusion chemotherapy (HAIC) and radiation therapy. New lung metastasis developed after HAICs; thus, lenvatinib treatment was initiated. However, the disease progressed. Thereafter, sorafenib treatment was initiated but he developed intolerance, with grade 3 sorafenib-related diarrhea. Subsequently, nivolumab was administered as rescue therapy. He demonstrated a partial response to nivolumab after the third treatment and viable HCCs in the lungs and liver completely disappeared after the 24th treatment. These findings suggest that nivolumab could be used as an effective rescue therapy for advanced HCC progression after TKI treatment
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