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Abstract: The wolf spider Lycosa singoriensis is a hunting spider with a widespread distribution in northwest China. The venom gland of spiders, which is a very specialized secretory tissue, can secrete abundant and complex toxin components. To extensively examine the transcripts expressed in the venom glands of L. singoriensis, we generated 833 expressed sequence tags (ESTs) from a directional cDNA library. Toxin-like sequences account for 69.1% of these ESTs, 17.3% are similar to cellular transcripts and 13.6% have no significant similarity to any known sequences. Here, we identified 223 novel toxin-like sequences, which can be classified into six different superfamilies; that means a novel potential source of ligands for varied ion channels was discovered. With the aid of Gene Ontology terms and homology to eukaryotic orthologous groups, the annotation of cellular transcripts revealed some cellular processes important for the toxin secretion of venom glands including protein synthesis, protein folding, tuned post-translational processing and trafficking, etc. [Copyright &y& Elsevier]

Background & Aims: aMAP score, as a hepatocellular carcinoma risk score, is proven to be associated with the degree of chronic hepatitis B‐related liver fibrosis. We aimed to evaluate the ability of aMAP score for metabolic dysfunction‐associated steatotic liver disease (MASLD; formerly NAFLD)‐related fibrosis diagnosis and establish a machine‐learning (ML) model to improve the diagnostic performance. Methods: A total of 946 biopsy‐proved MASLD patients from China and the United States were included in the analysis. The aMAP score, demographic/clinical indices and liver stiffness measurement (LSM) were included in seven ML algorithms to build fibrosis diagnostic models in the training set (N = 703). The performance of ML models was evaluated in the external validation set (N = 125). Results: The AUROCs of aMAP versus fibrosis‐4 index (FIB‐4) and aspartate aminotransferase‐platelet ratio (APRI) in cirrhosis and advanced fibrosis were (0.850 vs. 0.857 [P = 0.734], 0.735 [P = 0.001]) and (0.759 vs. 0.795 [P = 0.027], 0.709 [P = 0.049]). When using dual cut‐off values, aMAP had a smaller uncertainty area and higher accuracy (26.9%, 86.6%) than FIB‐4 (37.3%, 85.0%) and APRI (59.0%, 77.3%) in cirrhosis diagnosis. The seven ML models performed satisfactorily in most cases. In the validation set, the ML model comprising LSM and 5 indices (including age, sex, platelets, albumin and total bilirubin used in aMAP calculator), built by logistic regression algorithm (called LSM‐plus model), exhibited excellent performance. In cirrhosis and advanced fibrosis detection, the LSM‐plus model had higher accuracy (96.8%, 91.2%) than LSM alone (86.4%, 67.2%) and Agile score (76.0%, 83.2%), respectively. Additionally, the LSM‐plus model also displayed high specificity (cirrhosis: 98.3%; advanced fibrosis: 92.6%) with satisfactory AUROC (0.932, 0.875, respectively) and sensitivity (88.9%, 82.4%, respectively). Conclusions: The aMAP score is capable of diagnosing MASLD‐related fibrosis. The LSM‐plus model could accurately identify MASLD‐related cirrhosis and advanced fibrosis. [ABSTRACT FROM AUTHOR]

There are no data validating the performance of spleen stiffness measurement in ruling out high-risk varices in patients with HBV-related cirrhosis under maintained viral suppression. Thus, we aimed to prospectively validate the performance of spleen stiffness measurement (cut-off 46 kPa) combined with Baveno VI criteria in ruling out high-risk varices in these patients. Patients with cirrhosis were enrolled from April to December 2019 at the hepatology unit of the Nanfang Hospital, China. Liver and spleen transient elastography and esophagogastroduodenoscopy were performed at enrollment. Antiviral regimen(s) and virological responses, evaluated every 3-6 months, were recorded. Overall 341 patients with HBV-related cirrhosis under maintained viral suppression were enrolled, and the prevalence of high-risk varices was 20.5% (70/341). Baveno VI criteria spared 37.0% (126/341) esophagogastroduodenoscopies and no high-risk varices were missed (0/70). Eight cases of high-risk varices (8/70, 11.4%) were misclassified in patients (208/341, 61.0%) within the expanded Baveno VI criteria. The spleen stiffness measurement cut-off (≤46.0 kPa) was shown to safely rule out high-risk varices in these patients (the percentage of missed high-risk varices was 4.3%). Over half (61.6%, 210/341) of patients met the combined model (Baveno VI criteria and spleen stiffness measurement cut-off ≤46 kPa) and 4.3% (3/70) of high-risk varices cases were misclassified. This combined model exhibited a sensitivity of 95.71%, specificity of 76.38%, negative predictive value of 98.57%, and negative likelihood ratio of 0.06 for ruling out high-risk varices. We validated the excellent performance of Baveno VI criteria combined with spleen stiffness measurement (cut-off 46 kPa) for safely ruling out high-risk varices in patients with HBV-related cirrhosis under viral suppression; more than half of esophagogastroduodenoscopy procedures were spared using this combination. NCT04123509 Esophageal varices have important prognostic implications in patients with cirrhosis. Thus, their timely identification is important so that treatment can be initiated early. Herein, we validated the excellent performance of the combination of Baveno VI criteria with spleen stiffness measurement (cut-off 46 kPa) for ruling out high-risk esophageal varices in patients with HBV-related cirrhosis under maintained viral suppression (with antiviral treatment). This combined model was able to safely rule out high-risk varices (missed/total <5%) and over half (61.6%) of esophagogastroduodenoscopy procedures were spared. • Largest prospective study validating the performance of Baveno VI criteria in patients with cirrhosis under HBV suppression. • SSM (≤46 kPa) for ruling out high-risk varices was well validated in patients with cirrhosis under viral suppression. • More unnecessary endoscopies (>50%) can be safely avoided by combining Baveno VI criteria and SSM model. [ABSTRACT FROM AUTHOR]

Definitions and descriptions of acute-on-chronic liver failure (ACLF) vary between Western and Eastern types, and alcoholism and hepatitis B virus (HBV) are, respectively, the main etiologies. To determine whether there are unified diagnostic criteria and common treatment programs for different etiologies of ACLF, a multicenter prospective cohort with the same inclusion criteria and disease indicators as those used in the European Consortium Acute-on-Chronic Liver Failure in Cirrhosis Study is urgently needed in Asia, where the prevalence of HBV is high. A multicenter prospective cohort of 2,600 patients was designed, drawing from 14 nationwide liver centers from tertiary university hospitals in China, and 2,600 hospitalized patients with chronic liver disease (both cirrhotic and noncirrhotic) of various etiologies with acute decompensation or acute hepatic injury were continuously recruited from January 2015 to December 2016. Data were collected during hospitalization, and follow-ups were performed once a month, with plans to follow all patients until 36 months after hospital discharge. Of these patients, 1,859 (71.5%) had HBV-related disease, 1,833 had cirrhotic disease, and 767 had noncirrhotic disease. The numbers and proportions of enrolled patients from each participating center and the baseline characteristics of the patients with or without cirrhosis are presented. [ABSTRACT FROM AUTHOR]

Background: Accurate quantitative detection of hepatitis C virus (HCV) RNA is critical for diagnosis of acute or chronic HCV infection, and for follow-up of virologic response during HCV targeted therapy. In the present study, traceability and reproducibility of a novel China-certified domestic Sansure HCV RNA diagnostic assay (Sansure, Changsha, Hunan, China) was evaluated and the clinical performance of this assay was also analyzed.Methods: Traceability of the Sansure HCV RNA assay to the WHO international standard for HCV (genotype 1a) was detected across multiple centers. Reproducibility, accuracy (the differences of observed average concentrations and expected concentrations) and precision were assessed using series dilutions of World HCV RNA performance panel WWHV303-02 (HCV-1b), WWHV303-04(HCV-2a), WWHV303-11(HCV-3a) and WWHV303-19 (HCV-6a). In addition, both Sansure HCV RNA and CAP/CTM HCV (Roche, Branchburg, NJ, USA) assays were used to detect HCV RNA in 346 EDTA anti-coagulated plasma samples from previous HCV-infected patients, during and after antiviral therapy.Results: The Sansure assay showed good traceability by agreeing with the HCV-1a WHO standard across all five concentrations tested (25, 50, 100, 1000, 10,000 IU/ml). The differences between observed average concentrations and expected concentrations were all within 0.2 log10 IU/ml. HCV WWHV303 standards across 4 HCV genotypes (1b, 2a, 3a and 6a) were used for evaluation of reproducibility and the accuracy of the test were all within 0.2 log10 IU/ml. The inter-assay variations across the above 4 HCV genotypes were all less than 0.03 on each evaluated concentration, indicating good precision of Sansure HCV RNA assay. In clinical practice, concordant results were determined in 99.42% (344/346) samples (215 positive and 129 negative samples). Two specimens with negative HCV RNA results by Sansure assay were detected positive by CAP/CTM HCV test. Correlation analysis indicated a significantly positive correlation in detected HCV RNA concentrations (r = 0.9439, P < 0.0001). HCV RNA levels in 95.35% (205/215) specimens were within mean difference ± 1.96 SD as tested by both assays.Conclusions: With the advantages of traceability, reproducibility and lower price, Sansure HCV RNA assay represented an alternative option for HCV RNA detection in hospital and medical institution in China. [ABSTRACT FROM AUTHOR]