AIMTo evaluate the differences in acute kidney injury (AKI) between acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) patients.METHODSDuring the period from December 2015 to July 2017, 280 patients with hepatitis B virus (HBV)-related ACLF (HBV-ACLF) and 132 patients with HBV-related DC (HBV-DC) who were admitted to our center were recruited consecutively into an observational study. Urine specimens were collected from all subjects and the levels of five urinary tubular injury biomarkers were detected,including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver-type fatty acid binding protein (L-FABP), cystatin C (CysC), and kidney injury molecule-1 (KIM-1). Simultaneously, the patient demographics, occurrence and progression of AKI, and response to terlipressin therapy were recorded. All patients were followed up for 3 mo or until death after enrollment.RESULTSAKI occurred in 71 and 28 of HBV-ACLF and HBV-DC patients, respectively (25.4% vs 21.2%, P = 0.358). Among all patients, the levels of four urinary biomarkers (NGAL, CysC, L-FABP, IL-18) were significantly elevated in patients with HBV-ACLF and AKI (ACLF-AKI), compared with that in patients with HBV-DC and AKI (DC-AKI) or those without AKI. There was a higher proportion of patients with AKI progression in ACLF-AKI patients than in DC-AKI patients (49.3% vs 17.9%, P = 0.013). Forty-three patients with ACLF-AKI and 19 patients with DC-AKI were treated with terlipressin. The response rate of ACLF-AKI patients was significantly lower than that of patients with DC-AKI (32.6% vs 57.9%, P = 0.018). Furthermore, patients with ACLF-AKI had the lowest 90 d survival rates among all groups (P < 0.001).CONCLUSIONAKI in ACLF patients is more likely associated with structural kidney injury, and is more progressive, with a poorer response to terlipressin treatment and a worse prognosis than that in DC patients.
Background Interferon alpha (IFN-α) has been proven effective in treating chronic hepatitis B (CHB) due to its capability to suppress hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) covalently closed circular DNA (cccDNA). However, the underlying mechanisms are blurred. Methods We investigated the antiviral activities of exosomes from responders and non-responders to pegylated IFN-α (PegIFN-α) as well as the supernatants of IFN-α-treated THP-1 (the human leukemia monocyte cell line) derived macrophages. Then the expression profiles of exosomal microRNAs (miRNAs) were analyzed using miRNA sequencing. The luciferase reporter assay was used to locate the binding position of HBV genomic sequence targeted by the identified miRNA. Results Exosomes from PegIFN-α treated patients particularly responders as well as the supernatants of IFN-α-treated macrophages exhibited anti-HBV activities as manifested by the suppression of HBsAg, hepatitis B e antigen (HBeAg), HBV DNA and cccDNA levels in HBV related cell lines. PegIFN-α treatment upregulated exosomal hsa-miR-193a-5p, hsa-miR-25-5p, and hsa-miR-574-5p that could partially inhibit HBV replication and transcription. Hsa-miR-574-5p reduced pgRNA and polymerase mRNA levels by binding to the 2750-2757 position of HBV genomic sequence. Conclusions Exosomes can transfer IFN-α-related miRNAs from macrophages to HBV-infected hepatocytes, and exhibit antiviral activities against HBV replication and expression.
Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT04365634.ContextDiabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear.ObjectiveWe aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients.Design and MethodsIn this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups.ResultsCompared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL‐2R, IL‐6, IL‐8, IL‐10, and TNF‐α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF‐α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8+ T cells and NK cells than survivors.ConclusionThe elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8+ T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.
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