Human Amnion-Derived Mesenchymal Stromal Cells: A New Potential Treatment for Carbapenem-Resistant Enterobacterales in Decompensated Cirrhosis

Background: Spontaneous bacterial peritonitis (SBP) is a severe and often fatal infection in patients with decompensated cirrhosis and ascites. The only cure for SBP is antibiotic therapy, but the emerging problem of bacterial resistance requires novel therapeutic strategies. Human amniotic mesenchymal stromal cells (hA-MSCs) possess immunomodulatory and anti-inflammatory properties that can be harnessed as a therapy in such a context. Methods: An in vitro applications of hA-MSCs in ascitic fluid (AF) of cirrhotic patients, subsequently infected with carbapenem-resistant Enterobacterales, was performed. We evaluated the effects of hA-MSCs on bacterial load, innate immunity factors, and macrophage phenotypic expression. Results: hA-MSCs added to AF significantly reduce the proliferation of both bacterial strains at 24 h and diversely affect M1 and M2 polarization, C3a complement protein, and ficolin 3 concentrations during the course of infection, in a bacterial strain-dependent fashion. Conclusion: This study shows the potential usefulness of hA-MSC in treating ascites infected with carbapenem-resistant bacteria and lays the foundation to further investigate antibacterial and anti-inflammatory roles of hA-MSC in in vivo models.

Number of Endoscopic Sessions to Eradicate Varices Identifies High Risk of Rebleeding in Cirrhotic Patients

Background and aims: Risk stratification to identify patients with high risk of variceal rebleeding is particularly important in patients with decompensated cirrhosis. In clinical practice, eliminating gastroesphageal varices thoroughly after sequential endoscopic treatment reduces the rebleeding rate, however, no simple method has been build to predict high risk of variceal rebleeding. We conducted this study to explore the value of the number of endoscopic sessions required to eradicate gastroesphageal varices in identifying high risk of rebleeding.Patients and methods: Consecutive cirrhotic patients received sequential endoscopic therapy between January 2015 to March 2020 were enrolled. Endoscopic treatment was performed every 1-4 weeks until the eradication of varices. The primary endpoint was variceal rebleeding.Results: A total of 146 patients were included of which 60 patients received standard therapy and 86 patients underwent sequential endoscopic treatment alone. The cut-off value of the number of sequential endoscopic sessions is 3.5 times. Variceal rebleeding was significant higher in patients with endoscopic sessions > 3 times vs. ≤ 3 times (61.5% vs. 17.5%, p<0.001). Variceal rebleeding of patients with endoscopic sessions ≤3 times was significant lower than patients with > 3 times in group of standard therapy (19.6% vs. 88.9%, p<0.001) and endoscopic therapy (15.9% vs. 47.1%, p=0.028) respectively. Conclusion: The number of sequential endoscopic sessions required to eradicate the varices is related to the risk of variceal rebleeding in patients with cirrhosis. If three times of endoscopic treatment can not eradicate the varices, a more aggressive treatment such as TIPS should be seriously considered.

Autoantibody to GNAS in Early Detection of Hepatocellular Carcinoma: A Large-Scale Sample Study Combined with Verification in Serial Sera from HCC Patients

The aim of this study was to explore the value of autoantibody to GNAS in the early detection of hepatocellular carcinoma (HCC). In a large-scale sample set of 912 participants (228 cases in each of HCC, liver cirrhosis (LC), chronic hepatitis B (CHB), and normal controls (NCs) groups), autoantibody to GNAS was detected with a positive result in 47.8% of HCC patients, which was significantly higher than that in patients with LC (35.1%), CHB (19.7%), and NCs (19.7%). Further analysis showed that the frequency of autoantibody to GNAS started increasing in compensated cirrhosis patients (37.0%) with a jump in decompensated cirrhosis patients (53.2%) and reached a peak in early HCC patients (62.4%). The increasing autoantibody response to GNAS in patients at different stages was closely associated with the progression of chronic liver lesions. The result from 44 human serial sera demonstrated that 5 of 11 (45.5%) HCC patients had elevated autoantibody to GNAS before and/or at diagnosis of HCC. Moreover, 46.1% and 62.4% of high positive rates in alpha-fetoprotein (AFP) negative and early-stage HCC patients can supplement AFP in early detection of HCC. These findings suggest that autoantibody to GNAS could be used as a potential biomarker for the early detection of HCC.

A Prognostic Model of Acute-On-Chronic Liver Failure Based On Sarcopenia

Background Acute-on-chronic liver failure (ACLF) is characterized by the development of a syndrome associated with a high risk of short-term death in patients with acute decompensated cirrhosis, and better biomarkers are needed to predict such outcomes. Sarcopenia, a common complication of cirrhosis, is tightly associated with poor prognosis and increased mortality. In this study, the skeletal muscle index of ACLF patients was measured to determine whether sarcopenia combined with clinical parameters helps in identifying those at high risk of progression. Methods A total of 314 hospitalized ACLF patients were included and allocated into groups of transplantation-free survival (n = 214) or progression (n = 100) within 90 days. Muscle mass was assessed based on the skeletal muscle index. The optimal cutoff value of the AMPAS1 model (age, MELD score, platelet count, alpha-fetoprotein level, sarcopenia and more than one complication combination) for progressive prediction was identified using receiver operating characteristic (ROC) analysis. Results Sarcopenia was an independent risk factor for progression in the ACLF population (HR 3.705 95%CI 2.131-6.441, P<0.001). AMPAS1 was a good predictor, with an area under the ROC curve of 0.908, and the cutoff value for poor outcome prediction was 0.21 (sensitivity 93.2%, specificity 71.1%). Conclusion We demonstrate that sarcopenia is a simple and objective biomarker for predicting short-term prognosis in patients with ACLF. Moreover, compared to conventional prognostic scores, AMPAS1 is a better model to predict 90-day adverse outcomes in ACLF patients.