Aspirin for the prevention of hepatocellular carcinoma: an updated meta-analysis with particular focus on patients with chronic liver disease.

BACKGROUND: Previous studies have suggested a chemoprotective effect of aspirin in hepatocellular carcinoma (HCC), but evidence is limited for patients with chronic liver disease (CLD). Thus, we performed a meta-analysis of all observational studies, and aimed to provide a comprehensive and quantitative understanding of this topic. METHODS: The PubMed/MEDLINE, Scopus, Cochrane, and Web of Science databases were systematically searched until September 2021. We pooled the hazard ratio (HR) of HCC for aspirin use versus non-use and investigated the possible dose-risk and duration-risk associations. RESULTS: Ten studies involving 202,567 CLD patients were enrolled in this study. The pooled results showed a significant reduction in HCC risk in aspirin users than in non-users (HR = 0.64; 95% CI = 0.54-0.77; pheterogeneity < 0.001; I2 = 84.9%). In subgroup analyses, an aspirin dose of 100 mg/day (0.56, 0.44-0.72) showed a significant protective effect against HCC than 160 mg/day. The linear model showed a significant inverse association between the duration of aspirin use and HCC risk (exb(b) = 0.92; 95% CI = 0.90-0.94); also, a non-linear model revealed a comparable association (coef1 = 0.80, p1 < 0.001; coef2 = 1.13, p2 = 0.001). No significantly higher risk of gastrointestinal bleeding of the aspirin-treated group was detected. CONCLUSIONS: The present meta-analysis suggested a significant and duration-related association between reduced HCC risk and aspirin use in a broad at-risk population. Nevertheless, aspirin therapy applied to CLD patients should be carefully monitored, although there was no significantly higher risk of gastrointestinal bleeding. REGISTRATION: PROSPERO, CRD42021229892.

The clinical characteristics and prognostic factors of combined Hepatocellular Carcinoma and Cholangiocarcinoma, Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma after Surgical Resection: A propensity score matching analysis.

Background: Clinical characteristics and prognosis among combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CC) with HCC and intrahepatic cholangiocarcinoma (ICC) were inconsistent in previous studies. The aim of this study was to compare postoperative prognosis among cHCC-CC, HCC and ICC, and investigated the prognostic risk factor of cHCC-CC after surgical resection. Methods: A total of 1041 eligible patients with pathological diagnosis of cHCC-CC (n=135), HCC (n=698) and ICC (n=208) were enrolled in this study. Univariate and multivariate Cox analysis were applied for assessing important risk factors. cHCC-CC were further 1:1 matched with HCC and ICC on important clinical risk factors. Survival curves of matched and unmatched cohorts were depicted by Kaplan-Meier method with log-rank test. Results: Patients with cHCC-CC had similar rate of sex, age and cirrhosis with HCC (p<0.05) and comparable incidence of hepatitis B or C with ICC (p=0.197). Patients of cHCC-CC had intermediate prognosis between HCC and ICC, with median overall survival (OS) time of cHCC-CC, HCC and ICC of 20.5 months, 35.7 months and 11.6 months (p<0.001). In matched cohorts, the OS of cHCC-CC were worse than HCC (p<0.001) but comparable with ICC (p=0.06), while the disease-free survival (DFS) of cHCC-CC was worse than HCC but better than ICC (p<0.05). And lymph node infiltration and postoperative transarterial chemoembolization (TACE) were independent risk factors of cHCC-CC associated with prognosis. Conclusion: The long term survival of cHCC-CC was worse than HCC but comparable with ICC when matched on albumin level, tumor size, lymph node infiltration, tumor stage and margin. Presence of lymph node infiltration and no postoperative TACE were associated with poor prognosis of cHCC-CC.

Development and validation of a comprehensive radiomics nomogram for prognostic prediction of primary hepatic sarcomatoid carcinoma after surgical resection.

Objective: This study aimed to establish and validate a radiomics nomogram comprised of clinical factors and radiomics signatures to predict prognosis of primary hepatic sarcomatoid carcinoma (PHSC) patients after surgical resection. Methods: In this retrospective study, 79 patients with pathological confirmation of PHSC and underwent surgical resection were recruited. A radiomics nomogram was developed by radiomics signatures and independent clinical risk factors selecting from multivariate Cox regression. All patients were stratified as high risk and low risk by nomogram. Model performance and clinical usefulness were assessed by C-index, calibration curve, decision curve analysis (DCA) and survival curve. Results: A total of 79 PHSC were included with 1-year and 3-year overall survival rates of 63.3% and 35.4%, respectively. The least absolute shrinkage and selection operator (LASSO) method selected 3 features. Multivariate Cox analysis found six independent prognostic factors. The radiomics nomogram showed a significant prediction value with overall survival (HR: 7.111, 95%CI: 3.933-12.858, P<0.001). C-index of nomogram was 0.855 and 0.829 in training and validation set, respectively. Decision curve analysis validated the clinical utility of this nomogram. There was a significant difference in the 1-year and 3-year survival rates of stratified high-risk and low-risk patients in the whole cohort (30.6% vs. 90.1% and 5.6% vs. 62.4%, respectively, P < 0.001). Conclusion: This radiomics nomogram serve as a potential tool for predicting prognosis of PHSC after surgical resection, and help to identify high risk patients who may obtain feeble survival benefit from surgical resection.

The preoperative prognostic value of the radiomics nomogram based on CT combined with machine learning in patients with intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma is an aggressive liver carcinoma with increasing incidence and mortality. A good auxiliary prognostic prediction tool is desperately needed for the development of treatment strategies. The purpose of this study was to explore the prognostic value of the radiomics nomogram based on enhanced CT in intrahepatic cholangiocarcinoma. METHODS: In this retrospective study, 101 patients with pathological confirmation of intrahepatic cholangiocarcinoma were recruited. A radiomics nomogram was developed by radiomics score and independent clinical risk factors selecting from multivariate Cox regression. All patients were stratified as high risk and low risk by a nomogram. Model performance and clinical usefulness were assessed by calibration curve, ROC curve, and survival curve. RESULTS: A total of 101patients (mean age, 58.2 years old; range 36-79 years old) were included in the study. The 1-year, 3-year, and 5-year overall survival rates were 49.5%, 26.6%, and 14.4%, respectively, with a median survival time of 12.2 months in the whole set. The least absolute shrinkage and selection operator (LASSO) method selected 3 features. Multivariate Cox analysis found three independent prognostic factors. The radiomics nomogram showed a significant prognosis value with overall survival. There was a significant difference in the 1-year and 3-year survival rates of stratified high-risk and low-risk patients in the whole set (30.4% vs. 56.4% and 13.0% vs. 30.6%, respectively, p = 0.018). CONCLUSIONS: This radiomics nomogram has potential application value in the preoperative prognostic prediction of intrahepatic cholangiocarcinoma and may facilitate in clinical decision-making.

The effect and safety of preoperative biliary drainage in patients with hilar cholangiocarcinoma: an updated meta-analysis.

BACKGROUND: The effect and safety of preoperative biliary drainage (PBD) in patients with perihilar cholangiocarcinoma are still controversial; the aim of our study is to evaluate all aspects of PBD. METHODS: All included studies featured PBD versus non-PBD (NPBD) groups were from 1996 to 2019 and were extracted from Cochrane Library, Embase, PubMed, and Science Citation Index Expanded. RESULTS: Sixteen studies met the inclusion criteria and were included in this analysis. PBD may lead to a significantly higher incidence of overall morbidities (OR 0.67, 95% CI 0.53, 0.85; P = 0.0009) and intraoperative transfusions (OR 0.72, 95% CI 0.55, 0.94; P = 0.02); moreover, bile leakage (OR 0.58, 95% CI 0.24, 1.41; P = 0.04), infection (OR 0.31, 95% CI 0.20, 0.47; P < 0.00001), and cholangitis (OR 0.18, 95% CI 0.007, 0.48; P = 0.0007) are also related to PBD. However, NPBD was associated with more frequent hepatic insufficiency (OR 3.09, 95% CI 1.15, 8.31; P = 0.03). In the subgroup meta-analysis, the differences in the outcomes of bile leakage and overall morbidity lost significance between the PBD and NPBD groups when the mean total serum bilirubin (TSB) concentration was above 15 mg/dl. CONCLUSION: Meta-analysis demonstrated that compared to NPBD, PBD is associated with a greater risk of several kinds of infection and morbidities, but its ability to reduce postoperative hepatic insufficiency cannot be ignored. In patients with a high TSB concentration, PBD tends to be a better choice. However, these results need to be confirmed in a future prospective randomized trial with large samples to clarify the effects and find a specific TSB concentration for PBD.

Adenosine 5'-Monophosphate-to-Threonine Ratio Promotes Abdominal Aortic Aneurysms via Up-Regulation of HLA-DR on Natural Killer Cells: A Bidirectional Mendelian Randomized Analysis.

Objective: Immune-metabolic interactions may have causal and therapeutic impacts on abdominal aortic aneurysms (AAAs). However, due to the lack of research on the relationship between immune-metabolic interactions and AAAs, further exploration of the mechanism faces challenges. Methods: A two-sample, two-step mediation analysis with Mendelian randomization (MR) based on genome-wide association studies (GWASs) was performed to determine the causal associations among blood immune cell signatures, metabolites, and AAAs. The stability, heterogeneity, and pleiotropy of the results were verified using a multivariate sensitivity analysis. Results: After multiple two-sample MRs using the AAA data from two large-scale GWAS databases, we determined that the human leukocyte antigen-DR (HLA-DR) levels on HLA-DR + natural killer (NK) cells (HLA-DR/NK) were associated with the causal effect of an AAA, with consistent results in the two databases (FinnGen: odds ratio (OR) = 1.054, 95% confidence interval (CI): 1.003-1.067, p-value = 0.036; UK Biobank: OR = 1.149, 95% CI: 1.046-1.261, p-value = 0.004). The metabolites associated with the risk of developing an AAA were enriched to find a specific metabolic model. We also found that the ratio of adenosine 5'-monophosphate (AMP) to threonine could act as a potential mediator between the HLA/NK and an AAA, with a direct effect (beta effect = 0.0496) and an indirect effect (beta effect = 0.0029). The mediation proportion was 5.56%. Conclusions: Our study found that an up-regulation of HLA-DR on HLA-DR/NK cells can increase the risk of an AAA via improvements in the AMP-to-threonine ratio, thus providing a potential new biomarker for the prediction and treatment of AAAs.

Predictors and incidence of depression and anxiety in women undergoing infertility treatment: A cross-sectional study.

The global incidence of infertility is increasing year by year, and the association between infertility and mental illness has been widely concerned. The aim of this study was to investigate the incidence of anxiety and depression in infertile women in China and explore the risk factors which might lead to anxiety and depression. From January 2020 to December 2020, female infertile patients who received assisted reproduction technology (ART) treatment at West China Second Hospital were recruited and a total of 1712 eligible female patients were finally enrolled in this study. Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionaire-9 (PHQ-9) were used to evaluate the patients' psychological status. The reliability of all scales was evaluated by Cronbach's α and Spearman-Brown half coefficient, and Kaiser-Meyer-Olkin (KMO) value was calculated by factor analysis to evaluate validity. Univariate and multivariate logistic regression analysis were applied for assessing independent risk factors of anxiety and depression, respectively. The incidence of anxiety and depression in infertile women were 25.2% and 31.3%, respectively. Cronbach's α coefficients and Spearman-Brown half-fold coefficients of GAD-7 and PHQ-9 were 0.870, 0.825, 0.852 and 0.793, respectively. Univariate and multivariate logistic regression analysis showed that education level (junior college degree or above, OR:1. 6, 95% CI: 1.2-2.1, P = 0.003), somatic symptoms (severe somatic symptoms, OR:15.2, 95%CI: 5.6-41.3, P<0.001), sleep quality (poor sleep quality, OR:9.3, 95% CI:4.7-18.4, P<0.001) were independent risk factors for anxiety. And age>35 years old, moderate and severe somatic symptoms and poor sleep quality were independent risk factors for depression. Somatic symptoms and poor sleep quality are both the risk factors of anxiety and depression symptoms of infertile woman. And high educated (junior college degree or above) patients are more likely to be complicated with anxiety symptoms, while elderly patients (age>35) are prone to be complicated with depression symptoms.

Extrahepatic morbidities and mortality of NAFLD: an umbrella review of meta-analyses.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions currently and may contribute to multiple extrahepatic outcomes. AIM: To comprehensively summarise evidence of associations between NAFLD and risk of extrahepatic outcomes. METHODS: We conducted an umbrella review. We searched PubMed, Web of Science and Cochrane database from inception to 27 November 2021. RESULTS: We included 22 meta-analyses with 374 original studies in our analysis. Subjects with NAFLD had an increased risk of mortality, multiple cardiovascular complications, extrahepatic cancers, diabetes and chronic kidney disease (CKD) than those without NAFLD. Excess risks of several other extrahepatic outcomes including hypothyroidism, urolithiasis, gastro-oesophageal reflux disease, gallstones, depression and worse maternal and foetal outcomes were also observed in this population. However, associations were not significant for prostate cancer, female organ genital cancer, haematological cancer, diabetic retinopathy or osteoporotic fracture. The risks of CVD, diabetes and CKD were similar in obese and non-obese patients. Most associations were heterogeneous across regions; significantly, Europeans with NAFLD were more prone to all-cause mortality than North Americans. The certainty of evidence was graded from only very low to moderate as all included studies were observational. CONCLUSIONS: Patients with NAFLD are at heightened risk of extrahepatic outcomes. However, the certainty of evidence is only from very low to moderate. Further studies at low risk of bias are required to support the evidence and elucidate any causal associations.

Comprehensive radiomics nomogram for predicting survival of patients with combined hepatocellular carcinoma and cholangiocarcinoma.

BACKGROUND: Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CCA) is defined as a single nodule showing differentiation into HCC and intrahepatic cholangiocarcinoma and has a poor prognosis. AIM: To develop a radiomics nomogram for predicting post-resection survival of patients with cHCC-CCA. METHODS: Patients with pathologically diagnosed cHCC-CCA were randomly divided into training and validation sets. Radiomics features were extracted from portal venous phase computed tomography (CT) images using the least absolute shrinkage and selection operator Cox regression and random forest analysis. A nomogram integrating the radiomics score and clinical factors was developed using univariate analysis and multivariate Cox regression. Nomogram performance was assessed in terms of the C-index as well as calibration, decision, and survival curves. RESULTS: CT and clinical data of 118 patients were included in the study. The radiomics score, vascular invasion, anatomical resection, total bilirubin level, and satellite lesions were found to be independent predictors of overall survival (OS) and were therefore included in an integrative nomogram. The nomogram was more strongly associated with OS (hazard ratio: 8.155, 95% confidence interval: 4.498-14.785, P < 0.001) than a model based on the radiomics score or only clinical factors. The area under the curve values for 1-year and 3-year OS in the training set were 0.878 and 0.875, respectively. Patients stratified as being at high risk of poor prognosis showed a significantly shorter median OS than those stratified as being at low risk (6.1 vs 81.6 mo, P < 0.001). CONCLUSION: This nomogram may predict survival of cHCC-CCA patients after hepatectomy and therefore help identify those more likely to benefit from surgery.

Differentiation of Intrahepatic Cholangiocarcinoma and Hepatic Lymphoma Based on Radiomics and Machine Learning in Contrast-Enhanced Computer Tomography.

Purpose: This study aimed to explore the ability of texture parameters combining with machine learning methods in distinguishing intrahepatic cholangiocarcinoma (ICCA) and hepatic lymphoma (HL). Method: A total of 28 patients with HL and 101 patients with ICCA were included. A total of 45 texture features were extracted by the software LifeX from contrast-enhanced computer tomography (CECT) images and 38 of them were eligible. A total of 5 feature selection methods and 9 feature classification methods were used to build the best diagnostic models, combining with the 10-fold cross-validation to assess the accuracy of these models. The discriminative ability of each model was evaluated by receiver operating characteristic analysis. Result: A total of 45 predictive models were built by the cross combination of each selection and classification method to differentiate ICCA from HL. According to the results of test group, most of the models performed well with a large area under the curve (AUC) (>0.85) and high accuracy (>0.85). Random Forest (RF)_Linear Discriminant Analysis (LDA) (AUC = 0.997, accuracy = 0.969) was the best model among all the 45 models. Conclusion: Combining texture parameters from CECT with multiple machine learning models can differentiate ICCA and HL effectively, and RF_LDA performed the best in this process.

miR-590-5p promotes liver cancer growth and chemotherapy resistance through directly targeting FOXO1.

miR-590-5p functions as an onco-miR or an anti-onco-miR in various types of cancers. However, the exact role of miR-590-5p in liver cancer remains to be elucidated. In the present study, we explored the predictive role of miR-590-5p expression in liver cancer patients. In addition, CCK-8 assay, colony formation assay, and analysis of xenograft tumors were performed to investigate the biological effects of miR-590-5p in liver cancer. A direct target of miR-590-5p was identified based on a luciferase assay and further molecular experiments. Our results demonstrated that miR-590-5p was upregulated in malignant tissues of liver cancer patients and in liver cancer cell lines. miR-590-5p expression was found to be inversely correlated with disease-free survival of liver cancer patients. Furthermore, both in vitro and in vivo experiments showed that miR-590-5p knockdown inhibited the growth of HepG2 and Bel-7404 tumor cells by promoting apoptosis and cell cycle arrest. We also demonstrated that increasing of miR-590-5p in 5-Fu resistant patients and liver cancer cells, and knockdown of miR-590-5p enhances chemosensitivity to 5-Fu in liver cancer. FOXO1 was identified as a direct and necessary target of miR-590-5p during regulating liver cancer growth. Taken together, our findings provide insights into the role of miR-590-5p in liver cancer. Moreover, it is suggested that miR-590-5p can serve as a novel therapeutic target and predictive biomarker for liver cancer.

Parenchymal-sparing versus extended hepatectomy for colorectal liver metastases: A systematic review and meta-analysis.

AIMS: To assess the safety and efficacy of parenchymal-sparing hepatectomy (PSH) as a treatment of colorectal liver metastases (CLM). METHODS: A comprehensive medical literature search was performed. Perioperative and long-term survival outcomes were pooled. Subgroup analysis and meta-regression analysis were performed to identify potential sources of heterogeneity. RESULTS: A total of 18 studies comprising 7081 CLM patients were eligible for this study. The PSH was performed on 3974 (56.1%) patients. We found that the OS (overall survival; hazard ratio [HR] = 1.01, 95% confidence interval [CI]: 0.94-1.08) and RFS (recurrence-free survival; HR = 1.00, 95% CI: 0.94-1.07) were comparable between non-PSH and PSH group. The perioperative outcomes were better in PSH than in non-PSH group. Non-PSH group was significantly associated with longer operative time (standard mean difference [SMD] = 1.17, 95% CI: 0.33-2.00), increased estimated blood loss (SMD = 1.36, 95% CI: 0.64-2.07), higher intraoperative transfusion rate (risk ratio [RR] = 2.27, 95% CI: 1.60-3.23), and more postoperative complications (RR = 1.39, 95% CI: 1.16-1.66). Meta-regression analyses revealed that no variable influenced the association between surgical types and the survival outcomes. CONCLUSIONS: This study shows that PSH is associated with better perioperative outcomes without compromising oncological outcomes. Given the increasing incidence of hepatic parenchyma, the PSH treatment offers a greater opportunity of repeat resection for intrahepatic recurrent tumors. It should be considered as an effective surgical approach for CLM.

The choose of different surgical therapies of hepatic alveolar echinococcosis: A single-center retrospective case-control study.

The aim of this study was to evaluate different surgical therapies for hepatic alveolar echinococcosis in different clinical stages.We analyze the clinical data of 115 patients who received surgical treatment in West China Hospital from January 2004 to June 2016. Among these patients, 77 cases underwent radical hepatic resection (group A, n = 77); 17 cases underwent palliative resection (group B, n = 17), and 21 cases underwent liver transplantation (group C, n = 21) with 12 cases of orthotopic liver transplantation and 9 cases of liver autotransplantation.The postoperative complication rate of radical hepatic resection group was 13.0% (10/77), which is statistically significant (P < .05) than the rate of palliative resection group 29.4% (5/17) or liver transplantation group 23.8% (5/21). The follow-up period ranged from 1 to 72 months. The overall median survival rate of radical resection was 72/77, higher than the rate of palliative group (12/17) or transplantation group (17/21), which was also statistically significant (P < .01).In our study, we believe in that all stages of hepatic alveolar echinococcosis should take active surgical interventions, and radical hepatic resection should be considered as the first-choice treatment for early stage of alveolar echinococcosis, while palliative surgery is still helpful to relieve symptoms and improve the life quality for advanced patients. Liver transplantation might also be an alternative option for the late-stage hepatic alveolar echinococcosis.