BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is a common liver disease and may become the leading cause of severe liver disease in the future. The Global Burden of Disease (GBD) study assesses MAFLD's impact in countries and regions worldwide, providing insights into its prevalence. METHODS: Prevalence data for MAFLD from 1990 to 2021 by country and region in all sex and age groups were collected from the Global Health Data Exchange. The categorization of countries and geographic areas by development was performed using the Sociodemographic Index (SDI). RESULTS: Between 1990 and 2021, the global crude prevalence rate of MAFLD increased from 10.6% to 16.1% (beta-coefficient: 0.2%, 95% confidence interval [CI]: 0.2-0.2%, P  <0.001), and the age-standardized prevalence rate was increased from 12.1% to 15.0% (beta-coefficient: 0.1%, 95% CI: 0.1-0.1%, P  <0.001). In 2021, MAFLD was estimated to have affected 1.3 billion people worldwide. Significant uptrends were observed in all regions, super regions, and SDI categories. The fastest increase from 1990 to 2021 and the highest prevalence rate in 2021 were experienced by countries and territories with high-middle and middle SDI. An increase in the prevalence of MAFLD from 1990 to 2021 was demonstrated in all but six countries. CONCLUSIONS In 2021, the number of patients affected by MAFLD was doubled compared to 1990, and the prevalence rate increased by over 50%. The burden of MAFLD, as measured by prevalence, was more prominent in countries and territories with middle SDI and in those located in North African and Middle Eastern, possibly due to changes in lifestyle in these areas over the past 30 years.
Humans ; Global Burden of Disease ; Prevalence ; Male ; Female ; Middle Aged ; Adult ; Global Health ; Fatty Liver/epidemiology* ; Aged

CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

In recent years, the etiology of portal hypertension has undergone many changes. In addition to the focus on viral and alcoholic liver diseases, obesity, hyperlipidemia and diabetes patients, all kinds of drugs, especially after chemotherapy with platinum drugs, bone marrow proliferative diseases, autoimmune liver disease patients, need to be included in the high-risk screening population. The change in etiology brings about complex pathological and physiological states. We need to conduct a comprehensive evaluation, understand past medical history, improve portal vein computed tomography (CT), liver elastography, gastroscopy and other examinations, clarify the etiology, and choose personalized treatment plans for patients. Through technological innovation, we aim to improve the efficacy of endoscopic therapy, combined with new concepts such as artificial intelligence, big data, and multi omics, so as to obtain more accurate prediction of portal vein pressure and clinical characteristics, refine risk stratification, and make more accurate personalized decisions for clinical diagnosis and treatment.

Objective:To explore the changes of iron metabolism in patients with hepatitis B cirrhosis and esophageal and gastric varices complicated with portal vein thrombosis.Methods:This study was a cross-sectional study. 253 patients with hepatitis B cirrhosis with esophageal and gastric varices who were hospitalized in the Zhongshan Hospital, Fudan University from January 1, 2020 to December 31, 2021 were included in this study. They were divided into portal vein thrombosis group ( n=57) and non portal vein thrombosis group ( n=196) according to the presence or absence of portal vein thrombosis. The iron metabolism characteristics of the two groups were compared, and subgroups were analyzed according to the presence or absence of ascites, platelet count level, D-dimer level, and Child grade. The factors related to portal vein thrombosis were screened through multivariate logistic regression analysis. Results:The ratio of Child pugh B/C, ascites, D-dimer and platelet count in patients with hepatitis B cirrhosis and esophageal and gastric varices complicated with portal vein thrombosis was higher (all P<0.05). Patients with portal vein thrombosis had higher levels of soluble transferrin receptor [2.4(1.8, 3.6)mg/L vs 1.8(1.3, 2.7)mg/L, P=0.006], and lower levels of ferritin [33.1(18.9, 63.3)ng/ml vs 57.7(19.4, 142.5)ng/ml, P=0.038]. Layered analysis showed that ascites, platelet count levels, D-dimer levels, and Child-pugh grade did not affect the negative correlation trend between ferritin and portal vein thrombosis, and the positive correlation trend between soluble transferrin receptors and portal vein thrombosis. Moreover, soluble transferrin receptors showed a statistically significant positive correlation with portal vein thrombosis in the absence of ascites, low D-dimer levels, and Child-pugh grade A. Multivariate analysis suggested that after weighing Child-pugh grading, platelet count, and D-dimer levels, ferritin ( OR=0.943, 95% CI: 0.904-0.983, P=0.006) and soluble transferrin receptor ( OR=1.034, 95% CI: 0.001-1.067, P=0.044) were independently associated with portal vein thrombosis. Conclusions:In patients with hepatitis B cirrhosis with esophageal and gastric varices, the characteristics of iron metabolism in patients with portal vein thrombosis are different from those in patients without thrombosis, with higher levels of soluble transferrin receptor and lower levels of ferritin.

Objective:To investigate whether discontinuation of previous targeted immunotherapy increases the risk of rebleeding in patients with advanced liver cancer complicated with esophageal and gastric variceal bleeding after endoscopic treatment.Methods:A retrospective cohort study was conducted to include advanced liver cancer patients who were diagnosed with esophageal and gastric variceal bleeding through endoscopic examination and treated under endoscopy at Zhongshan Hospital, Fudan University from March 1, 2020 to March 1, 2022, due to upper gastrointestinal bleeding. We collected clinical data from patients and divided them into targeted immunotherapy group and non targeted immunotherapy group based on whether they received targeted immunotherapy before bleeding; Follow up observation was conducted for 6 months to evaluate the patient′s re bleeding and survival status.Results:A total of 55 patients were included, of which 24 had previously received targeted immunotherapy and 31 had not received targeted immunotherapy. There was no significant difference between the two groups in gender distribution, etiology, hypertension and diabetes (all P>0.05). The age of the target immunotherapy group was younger than that of the non target immunotherapy group, and the level of fibrinogen was higher than that of the non target immunotherapy group, with statistical significance ( P=0.002, 0.017). There was no statistically significant difference in the 6-month re bleeding rate (20.83% vs 22.58%, P=0.269) and 6-month mortality rate (45.83% vs 29.03%, P=0.199) between the targeted and non targeted groups of patients. Further Cox regression multivariate analysis revealed that Child-pugh grading was an independent risk factor for 6-month survival in patients with advanced liver cancer with esophageal and gastric varices ( HR=2.64, P=0.009). Conclusions:Targeted immunotherapy does not increase the rate of rebleeding in patients with advanced unresectable liver cancer after endoscopic treatment of esophageal and gastric varices. Child-pugh grading is a factor that affects the 6-month survival of advanced liver cancer patients after bleeding, and the poorer the liver function, the shorter the survival period.

Endoscopic ligation,sclerotherapy and injection of tissue glue combined with medicine treatment have replaced surgical shunt and devascularization as the first-line treatment recommended by guidelines for esophagogastric variceal bleeding in patients with cirrhosis and portal hypertension.However,some of the variceal bleeding induced by non-cirrhotic portal hypertension.Comorbidities such as diabetes,portal vein thrombosis,liver tumors,and hepatic artery-portal vein fistulas have reduced the efficacy of endoscopic treatment,and have increased the rate of complication such as ectopic embolism.Traditional endoscopic techniques are facing substantial challenges.The urgent needs for precise injection techniques,complete variceal obliteration,and the prevention of ectopic embolism have become apparent.The era of precision medicine in variceal endoscopic treatment has been ushered in by advancements such as preoperative assessments using computed tomography(CT)and ultrasound endoscopy,ultrasound-guided tissue glue injection with spring coil assistance,and immediate postoperative ultrasound endoscopic evaluation.This progress is anticipated to overcome the diagnostic and therapeutic limitations associated with non-cirrhotic portal hypertension.Integrating CT imaging virtual simulation and other technological innovations,to surpass conventional interventional techniques,is helpful of achieving a comprehensive endoscopic approach to the diagnosis and treatment of portal hypertension.

Objective To evaluate the effect of para-esophageal and para-gastric vessels(PEPGV)on endoscopic secondary prophylaxis for varices.Methods The clinical data of patients with cirrhosis-related esophagogastric varices(EGV)who underwent endoscopic variceal ligation and/or obliteration,and had hepatic venous pressure gradient(HVPG)result between January 2020 and December 2020 in Zhongshan Hospital,Fudan University were retrospectively analyzed.Patients were divided into a group without PEPGV and a group with PEPGV based on CT imaging of the portal vein.The main outcome was 2-year re-bleeding.Results A total of 69 patients were included,and 27 of them had PEPGV.There was no statistical difference in baseline characteristics,blood indexes(included hemoglobin level,prothrombin time and albumin level),HVPG,and the secondary prophylactic endoscopic treatment ways between the two groups.A total of 25 patients experienced re-bleeding within 2 years after endoscopic treatment,including 15 in the group with PEPGV and 10 in the group without PEPGV.Kaplan-Meier analysis showed that the cumulative 2-year re-bleeding rate was significantly higher in the group with PEPGV than in the group without PEPGV(60.07％vs 32.79％,P=0.022).Further multivariate Cox analysis showed that PEPGV was an independent predictor of re-bleeding after endoscopic treatment in EGV patients(HR=2.33,95％CI 1.01-5.39,P=0.047).Conclusions The PEPGV is an independent predictor of re-bleeding after endoscopic treatment in EGV patients.It is suggested that when patients with EGV receive endoscopic treatment to prevent re-bleeding,portal vascular CT is suggested to evaluate PEPGV.For patients with giant extraluminal vascular masses,fully evaluating other treatment options such as transjugular intrahepatic portosystemic shunt,or adjusting endoscopic treatment ways is recommended.

Objective To explore the effects of anticoagulation treatment to postoperative bleeding events in liver cirrhosis patients with gastric varices and portal vein thrombosis.Methods Patients diagnosed with portal vein thrombosis and treated with endoscopic cyanoacrylate injection at Zhongshan Hospital,Fudan University due to gastric variceal bleeding from January 2023 to December 2023 were included.Clinical data of patients were collected,and patients were divided into anticoagulant group and non-anticoagulant group based on whether anticoagulant treatment was performed within 48 h after treatment.Re-bleeding in patients was evaluated in 6 weeks of follow-up.Cox regression was used for univariate and multivariate analysis of re-bleeding within 6 weeks after treatment.Results A total of 160 patients were included,of whom 65 patients received anticoagulation treatment within 48 h after endoscopic cyanoacrylate injection.There were no statistically significant differences in gender,etiology of liver cirrhosis,dosage of cyanoacrylate and sclerosing agents,and Child-Pugh grading between the two groups.There was no statistically significant difference in re-bleeding rate within 6 weeks after treatment between the two groups(1.54％vs 1.05％,P=0.795).Multivariate Cox regression analysis showed that the large amount of cyanoacrylate was a risk factor for re-bleeding within 6 weeks after endoscopic treatment(HR=5.862,P=0.015).Conclusions For patients with liver cirrhosis,gastric varices,and portal vein thrombosis,who receive endoscopic cyanoacrylate injection,early anticoagulation does not increase the risk of re-bleeding after treatment,while a large amount of cyanoacrylate injection may be a risk factor for re-bleeding.However,sample should be increased to verify.

Objective To compare the efficacy and safety of endoscopic ligation treatment and endoscopic tissue glue injection for secondary prevention of gastric variceal bleeding.Methods Patients with cirrhosis and esophagogastric variceal bleeding treated with gastric variceal ligation in Zhongshan Hospital,Fudan University,from January 2017 to December 2019 were screened(ligation group).And during the same period,patients underwent endoscopic cyanoacrylate treatment were also screened(tissue glue group).59 patients were included in the two groups after propensity score matching.Univariate and multivariate Cox proportional hazard regression models were used to anslyze risk factors for re-bleeding.Kaplan-Meier curves were plotted to analyze re-bleeding rate and mortality of the two treatment groups.Results There was no statistically significant difference in the eradication rate of esophagogastric varices between the ligation group and the tissue glue group(83.05％vs 79.66％,P=0.778);the ligation group required fewer median endoscopic treatments for variceal eradication(2 vs 3,P=0.017)and a lower average dosage of cyanoacrylate(0.70 mL vs 2.67 mL,P＜0.001).Multivariate Cox regression analysis showed that portal shunt was a risk factor for esophagogastric varices re-bleeding(HR=3.14,95％CI 1.02-9.68,P=0.046),endoscopic variceal ligation was a protective factor against re-bleeding(HR=0.25,95％CI 0.08-0.71,P=0.010).Compared with endoscopic cyanoacrylate injection,endoscopic ligation treatment did not significantly increase the 2-year risk of esophagogastric variceal re-bleeding(18.69％vs 36.29％,P=0.067)or risk of death(1.69％vs 3.39％,P=1.000);patients with GOV1 type had a significantly lower risk of re-bleeding after endoscopic ligation treatment(0 vs 40.27％,P=0.012)and there was a trend towards a lower re-bleeding risk in patients with GOV2 type after endoscopic ligation treatment(13.27％vs 34.16％,P=0.056).Conclusions Endoscopic ligation treatment has higher eradication rate for esophagogastric varices,and does not increase the risk of re-bleeding,death,or other adverse events.Therefore,it can be considered an effective secondary prevention way for patients with gastric varices.

According to the pathophysiological characteristics, upper gastrointestinal bleeding can be divided into acid related disease bleeding and esophageal and gastric varices bleeding. Esophageal and gastric variceal bleeding is a common critical condition of Portal hypertension, with dangerous onset and high mortality. With the improvement of endoscopic treatment technology, endoscopy has become the first line treatment plan for esophageal and gastric variceal bleeding. The commonly used endoscopic management methods for varicose veins include variceal ligation, tissue glue combined with sclerosing agent embolization, ultrasound guided coil combined with tissue glue embolization, and other management measures. Early identification of gastrointestinal bleeding related to varicose veins, stratified diagnosis and treatment of high-risk patients, reasonable selection of endoscopic examination timing, and personalized decision-making of treatment choices are key to improving efficacy.