Plasma Exchange-Based Non-bioartificial Liver Support System Improves the Short-Term Outcomes of Patients With Hepatitis B Virus-Associated Acute-on-Chronic Liver Failure: A Multicenter Prospective Cohort Study.

Background and aims: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with extremely high short-term mortality. Whether plasma exchange (PE) improves HBV-ACLF outcomes remains controversial. Here, PE-based non-bioartificial liver support system (NB-ALSS) effects on short-term HBV-ACLF patient outcomes were investigated. Materials and methods: HBV-ACLF patients from Chinese Acute-on-chronic Liver Failure (CATCH-LIFE) cohort receiving standard medical therapy (SMT) alone or PE-based NB-ALSS in addition to SMT were allocated to SMT and SMT+PE groups, respectively; propensity score matching (PSM) was used to eliminate confounding bias. Short-term (28/90-day and 1-year) survival rates were calculated (Kaplan-Meier). Results: In total, 524 patients with HBV-ACLF were enrolled in this study; 358 received SMT alone (SMT group), and the remaining 166 received PE-based NB-ALSS in addition to SMT (SMT+PE group). PSM generated 166 pairs of cases. In the SMT+PE group, 28-day, 90-day, and 1-year survival rates were 11.90, 8.00, and 10.90%, respectively, higher than those in the SMT group. Subgroup analysis revealed that PE-based NB-ALSS had the best efficacy in patients with ACLF grade 2 or MELD scores of 30-40 (MELD grade 3). In MELD grade 3 patients who received SMT+PE, 28-day, 90-day, and 1-year survival rates were improved by 18.60, 14.20, and 20.10%, respectively. According to multivariate Cox regression analysis, PE-based NB-ALSS was the only independent protective factor for HBV-ACLF patient prognosis at 28 days, 90 days, and 1 year (28 days, HR = 0.516, p = 0.001; 90 days, HR = 0.663, p = 0.010; 1 year, HR = 0.610, p = 0.051). For those who received SMT+PE therapy, PE-based NB-ALSS therapy frequency was the only independent protective factor for short-term prognosis (28-day, HR = 0.597, p = 0.001; 90-day, HR = 0.772, p = 0.018). Conclusions: This multicenter prospective study showed that the addition of PE-based NB-ALSS to SMT improves short-term (28/90 days and 1-year) outcomes in patients with HBV-ACLF, especially in MELD grade 3 patients. Optimization of PE-based NB-ALSS may improve prognosis or even save lives among HBV-ACLF patients.

Prevalence and Clinical Significance of Portal Vein Thrombosis in Patients With Cirrhosis and Acute Decompensation.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD. METHODS: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the Chinese AcuTe on CHronic LIver FailurE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n = 2600 patients) and July 2018 through January 2019 (n = 1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD. RESULTS: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P = .04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared with patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P < .001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P < .001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT. CONCLUSIONS: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension. ClinicalTrials.gov no: NCT02457637 and NCT03641872.

Neurofilament Light Chain in Cerebrospinal Fluid and Blood as a Biomarker for Neurodegenerative Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: Neurofilament light chain (NFL) as a potential biomarker of neurodegenerative diseases has been studied in a number of studies. Thus, a comprehensive meta-analysis is warranted to assess NFL performance in neurodegenerative diseases. OBJECTIVE: To assess the performance of NFL in blood and cerebrospinal fluid (CSF) as a biomarker for neurodegenerative diseases. METHODS: A total of 36 studies with comparison of NFL level between individuals with neurodegenerative diseases and controls were retrieved from PubMed, Web of Science and Science Direct, and the ratio of means method and delta method based on the random-effect model were used to analyze the differentiation of NFL between patients and controls. RESULTS: Differentiation of CSF NFL between patients with neurodegenerative diseases and controls showed significant results. Although a few studies on blood NFL available were included in the meta-analysis, the results still showed a distinct possibility that NFL could be a potential biomarker for neurodegenerative diseases. NFL levels were increased significantly in dementias, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, and Huntington's disease. By contrast, NFL levels were not increased in Parkinson's disease (PD), although they were increased significantly in PD-related disorders (multiple system atrophy and progressive supranuclear palsy). CONCLUSIONS: In our study, in addition to PD, NFL was suggested to be a global diagnostic biomarker for neurodegenerative diseases. Moreover, it could be used in differential diagnosis of PD and PD-related disorders. However, it was worth noting that NFL was not appropriate for diagnosis or differential diagnosis without clinical symptoms and other auxiliary examinations.

Acute-on-Chronic Liver Failure in China: Rationale for Developing a Patient Registry and Baseline Characteristics.

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.

Dibasic Ammonium Phosphate Application Enhances Aromatic Compound Concentration in Bog Bilberry Syrup Wine.

A nitrogen deficiency always causes bog bilberry syrup wine to have a poor sensory feature. This study investigated the effect of nitrogen source addition on volatile compounds during bog bilberry syrup wine fermentation. The syrup was supplemented with 60, 90, 120 or 150 mg/L dibasic ammonium phosphate (DAP) before fermentation. Results showed that an increase of DAP amounts accelerated fermentation rate, increased alcohol content, and decreased sugar level. Total phenol and total flavonoid content were also enhanced with the increase of DAP amounts. A total of 91 volatile compounds were detected in the wine and their concentrations were significantly enhanced with the increase of DAP. Ethyl acetate, isoamyl acetate, phenethyl acetate, ethyl butanoate, ethyl hexanoate, ethyl octanoate, ethyl decanoate, isobutanol, isoamyl alcohol, levo-2,3-butanediol, 2-phenylethanol, meso-2,3-butanediol, isobutyric acid, hexanoic acid, and octanoic acid exhibited a significant increase of their odor activity value (OAV) with the increase of DAP amounts. Bog bilberry syrup wine possessed fruity, fatty, and caramel flavors as its major aroma, whereas a balsamic note was the least present. The increase of DAP amounts significantly improved the global aroma attributes, thereby indicating that DAP supplementation could promote wine fermentation performance and enhance the sensory quality of bog bilberry syrup wine.

[Specific immune responses to human immunodeficiency virus type 1 Gag, Tat, Rev and Nef proteins].

AIM: To investigate the features of HIV-1-Gag-, Tat-, Rev- and Nef- specific cytotoxic T-lymphocyte (CTL) responses in infected individuals in China. METHODS: The HIV-1-specific CTL responses were analyzed with an IFN-gamma ELISPOT assay by using 220 overlapping peptides spanning the entire HIV-1 Clade B (HIV-1B) and C (HIV-1C) Gag, Tat, Rev and Nef proteins consensus sequences. RESULTS: For either HIV-1B or HIV-1C, Gag and Nef were preferentially targeted by HIV-1 specific CTLs, Rev and Tat proteins were also recognized to different extent. In comparison of the immune responses between HIV-1B and HIV-1C, the magnitude and frequency were roughly identical but there were some differences in the immunodominant regions. For HIV-1B, the highest response magnitude was detected in 288-313 amino acids of Gag p24, and for HIV-1C, in 155-181 amino acids of Gag p24. The most frequently recognized region was located in 106-143 amino acids of Nef either in HIV-1B or in HIV-1C (48.1%). CONCLUSION: HIV-1-specific CTLs mainly directed against HIV-1 Gag and Nef in Chinese, and there is some difference between HIV-1B and HIV-1C. There exists the cross-recognition between the Clade B and Clade C. These data suggest that the study on HIV-1-specific CTL responses in Chinese will provide strategies for the vaccine design in China.