From NAFLD to MASLD: When metabolic comorbidity matters.

INTRODUCTION AND OBJECTIVES: In a recent development, a cohort of hepatologists has proposed altering the nomenclature of non-alcoholic fatty liver disease (NAFLD) to metabolic-associated steatotic liver disease (MASLD), accompanied by modified diagnostic criteria. Our objective was to investigate the effect of the revised definition on identifying significant hepatic fibrosis. PATIENTS AND METHODS: From Jan 2009 to Dec 2022, a total of 428 patients with biopsy-proven hepatic steatosis were diagnosed with NAFLD. Patients were classified into subgroups according to MASLD and Cryptogenic-SLD diagnostic criteria. The clinical pathological features were compared between these two groups. Risk factors for significant fibrosis were analysed in the MASLD group. In total, 329 (76.9 %) patients were diagnosed with MASLD, and 99 (23.1 %) were diagnosed with Cryptogenic-SLD. RESULTS: Those with MASLD exhibited a higher degree of disease severity regarding histology features than Cryptogenic-SLD. The prevalence of significant fibrosis increased from 13 % to 26.6 % for one and two criteria present to 42.5 % for meeting three or more cardiometabolic risk factor (CMRF) criteria (p = 0.001). ALB (aOR:0.94,95 %CI:0.90-1.00; p = 0.030), lower levels of PLT (aOR:0.99, 95 %CI:0.99-1.00; p < 0.001), and more metabolic comorbidities (aOR:1.42,95 %CI:1.14-1.78; p = 0.012) were independent risk factors of significant fibrosis in MASLD. CONCLUSIONS: The new nomenclature of MASLD and SLD is more applicable to identifying significant fibrosis than NAFLD. Patients with three or more cardiometabolic risk factors are at higher risk of fibrosis.

[Efficacy Evaluation of Three Endoscopic Therapies of Isolated Gastric Varices with Modified Tissue Adhesive].

Objective: To evaluate the efficacy of three endoscopic therapies of isolated gastric varices (IGV) with modified tissue adhesive. Methods: A retrospective analysis was conducted with the clinical data of 73 IGV patients who were treated between January 2008 and December 2019 at Beijing Ditan Hospital. Patient clinical data on age, sex, etiology, biochemistry findings, Child-Pugh classification, the type of spontaneous shunt, preoperative bleeding history, and the presence or absence of liver cancer were collected. The three therapies evaluated were endoscopic intravenous injection of tissue glue combined with lauromacrogol, endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, and endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. Their respective clinical treatment outcomes, including ectopic embolism rate, survival rate, rebleeding rate, amount of lauromacrogol and tissue glue used, the number of endoscopic clips used, and the number of times of the procedure the patient underwent, were evaluated. Results: In the patient baseline data, Child-Pugh grade, preoperative thrombus formation, and the presence or absence of liver cancer, showed significant difference between the three therapies ( P<0.05). There was no significant difference in the rates of ectopic embolism among the three methods ( P>0.05), but no ectopic embolism occurred after endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, or after endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. There was no significant difference in the survival rate, the rebleeding rate, amount of lauromacrogol and tissue glue used for the three therapies, but there was significant difference in the number of endoscopic clips used and the number of times the procedure was conducted within one year ( P<0.05). Conclusion: The two endoscopic therapies of intravenous injection of modified tissue glue, one assisted by clip and the other assisted by clip and LOOP, can help reduce the number of procedures IGV patients undergo within one year.

A new algorithm for predicting long-term survival in chronic hepatitis B patients with variceal bleeding after endoscopic therapy.

BACKGROUND AND AIMS: A predictive algorithm for survival is urgently needed in clinical practice. This study aimed to establish an algorithm to predict long-term survival in chronic hepatitis B (CHB) patients with hepatic cirrhosis and variceal bleeding after endoscopic therapy. METHODS: This was a retrospective study in which 603 patients who followed-up for three years were randomly assigned into a training cohort and a validation cohort in a 2:1 ratio. A new score model was devised based on the result of Cox regression analysis in the training cohort, and was verified in the validation cohort. RESULTS: A prediction score model composed of age, neutrophil-lymphocyte ratio, gamma-glutamyl transpeptidase and MELD score was established. The score ranged from 0 to 11. Areas under the ROC curve of the score were 0.821 (p < 0.001, 95% CI: 0.769-0.873) and 0.827 (p < 0.001, 95% CI: 0.753-0.900) in the training cohort and validation cohort, respectively. Scores 0-4 and 5-11 identified patients as low-risk and high-risk categories, respectively. The cumulative 3-year survival rate was significantly higher in the low-risk group than in the high-risk group (p < 0.001). CONCLUSION: The new score model can be used to predict long-term survival in CHB patients with hepatic cirrhosis and variceal bleeding after endoscopic therapy.

A colorimetric/fluorescence dual-channel probe for highly discriminating detection of cysteine.

In this work, a novel fluorescence (FL) probe for selective and sensitive detection of Cys with colorimetric and FL dual signal changes was reported. The probe was synthesized by two step of sulfonamide reaction coupling between a sulfonyl benzoxadiazole (SBD) dye and dansyl chloride linked with rigid piperazine group. The probe showed a specific off-on response to Cys in aqueous solution with nanomolar LOD, and without interference by a range of amino acids and several competing analytes. Upon addition of Cys, the probe will undergo sequential substitution and intramolecular rearrangement reactions, yielding a 4-amino SBD derivative, which results in generation of strong yellow fluorescence emission at 575 nm accompanied by a two-step red shift in the absorption spectral. Moreover, it can be used for imaging of endogenous Cys in living cells.

[The relationship between gastroesophageal reflux disease and idiopathic pulmonary interstitial fibrosis].

OBJECTIVE: To determine the prevalence of gastroesophageal reflux disease (GERD) in patients with idiopathic pulmonary interstitial fibrosis (IPIF). METHODS: From December 2006 to January 2008, 24 consecutive patients with IPIF admitted to Beijing Chaoyang Hospital underwent 24-hour esophageal pH monitoring and esophageal manometry. Meanwhile, 23 patients with diffuse parenchymal lung disease (DPLD) (excluding IPIF) admitted to the hospital in the same period served as a control group. Comparison of the prevalence of pathologic esophageal acid exposure GERD symptoms, and ineffective esophageal motility (IEM) between the two groups was made. In this study, nocturnal acid exposure is defined as acid reflux episodes occurring from 10pm to 6am. RESULTS: (1) 16 out of the 24 (66.7%) patients with IPIF were demonstrated to have pathologic esophageal acid exposure; the prevalence of GERD in IPIF patients was significantly higher than that in other DPLD patients, whose prevalence was 26.1% (P < 0.05) ; (2) 87.5% patients with IPIF and GERD (GERD-IPIF) had nocturnal acid exposure episodes; (3) only 37.5% of the GERD-IPIF patients was found to have typical GERD symptoms such as heartburn and regurgitation; (4) The prevalence of IEM was similar in IPIF and other DPLD patients, being 42.9% and 39.1% respectively (P > 0.05). CONCLUSIONS: IPIF patients have higher prevalence of GERD and most of them usually do not show typical reflux symptoms. It is hereby suggested that IPIF patients should be screened with pH monitoring for GERD.

Crystal structure of a non-hemorrhagic fibrin(ogen)olytic metalloproteinase complexed with a novel natural tri-peptide inhibitor from venom of Agkistrodon acutus.

Thrombotic occlusive diseases pose a great threat to human health. Thrombolytic agents are in widespread use for the dissolution of arterial and venous pathologic thrombi in these kinds of diseases. Snake venom metalloproteinases (SVMPs) can act directly on fibrin/fibrinogen and are therefore potential candidates for therapeutic use against thrombotic occlusive diseases. In this study, we have determined the crystal structure of FII, a novel non-hemorrhagic SVMP isolated from Anhui Agkistrodon acutus snake venom by molecular replacement. The structure reveals that FII is a member of the P-I class SVMPs. The Zn2+ ion essential for hydrolytic activity is found in the active site and is tetrahedrally co-ordinated by three histidine residues and water molecule. Unambiguous electron density for a tri-peptide with sequence KNL is also found located near the active site. Biochemical evidences show that the tri-peptide KNL can inhibit the enzymatic activity of FII.

Enzymological characterization of FII(a), a fibrinolytic enzyme from Agkistrodon acutus venom.

AIM: To study the enzymological characterization of a fibrinolytic enzyme (FII(a)) from Agkistrodon acutus venom. METHODS: The fibrinogenolytic effect and the influences of several protease inhibitors, chelating agents, and metal ions on fibrinogenolytic activity were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The metal content of FII(a) was determined by atomic absorption spectroscopy. RESULTS: After incubation with FII(a) (0.25 g/L), Aalpha-, Bbeta- and gamma-chains of fibrinogen disappeared within 5 min, 30 min, and 8 h , respectively. The molecular weights of major degradation products were 45,000 and 41,000, which were different from those bands produced by plasmin. The fibrinogenolytic activity of FIIa was strongly inhibited by ethylenediamine tetraacetic acid (EDTA), ethyleneglycol tetraacetic acid (EGTA), dithiothreitol and cysteine, but not by phenylmethyl-sulfonyl fluoride and soybean trypsin inhibitor. Zinc (3171+/-25 mg/kg), potassium (489+/-17 mg/kg) and calcium (319+/-13 mg/kg) were found in FIIa. Zn2+, Ca2+ and Mg2+ could recover the fibrinogenolytic activity of FIIa, which was inhibited by EDTA. Only Ca2+ could recover the fibrinogenolytic activity inhibited by EGTA. CONCLUSION: FIIa can degrade the Aalpha-, Bbeta- and gamma-chains of fibrinogen. FII(a) is a metalloproteinase, and Zn2+, Ca2+, and disulfide bonds are necessary for its fibrinogenolytic activity.