Virus-like particles encapsulating HBV-RNA represent a serum biomarker for assessing viral replication activity in clinical practice. However, baseline levels of serum HBV-RNA and their associations with viral replicative intermediates and liver disease in phases of chronic hepatitis B remain unknown. In this cross-sectional study, 102 patients were categorized into immune-tolerant (IT), HBeAg-positive immune active (HBeAg+IA), inactive carrier (IC) and HBeAg-negative immune active (HBeAg-IA) phases. HBV-RNA in serum samples and in 66 paired liver biopsies were quantified and correlated with serum ALT levels, histopathological scores and the levels of other viral replicative intermediates. Mean levels of serum HBV-RNA differed among phases, with the highest levels among IT (6.78 ± 0.83 log copies mL ) patients, followed by HBeAg+IA (5.73 ± 1.16 log copies mL ), HBeAg-IA (4.52 ± 1.25 log copies mL ) and IC (2.96 ± 0.40 log copies mL ) patients. Serum HBV-RNA levels correlated with HBV DNA in all phases, although correlations with other viral replicative intermediates weakened or disappeared when cases were stratified into phases. Distinct compositions of viral products were found among phases: the ratio of HBsAg to serum HBV-RNA was highest in IC patients, while the ratio of serum HBV-RNA to intrahepatic HBV-RNA and the ratio of intrahepatic HBV-DNA to intrahepatic HBV-RNA were significantly higher in IT patients. In conclusion, baseline levels of HBV-RNA and the composition of viral replicative intermediates differ significantly across the natural course of chronic HBV infection. These findings shed light on the nature of viral replication and pathogenesis of disease among different phases of chronic HBV infection.
High levels of low-density lipoprotein cholesterol (LDL-C) enhance platelet activation, whereas high levels of high-density lipoprotein cholesterol (HDL-C) exert a cardioprotective effect. However, the effects on platelet activation of high levels of LDL-C combined with low levels of HDL-C (HLC) have not yet been reported. We aimed to evaluate the platelet activation marker of HLC patients and investigate the antiplatelet effect of atorvastatin on this population. Forty-eight patients with high levels of LDL-C were enrolled. Among these, 23 had HLC and the other 25 had high levels of LDL-C combined with normal levels of HDL-C (HNC). A total of 35 normocholesterolemic (NOMC) volunteers were included as controls. Whole blood flow cytometry and platelet aggregation measurements were performed on all participants to detect the following platelet activation markers: CD62p (P-selectin), PAC-1 (GPIIb/IIIa), and maximal platelet aggregation (MPAG). A daily dose of 20 mg atorvastatin was administered to patients with high levels of LDL-C, and the above assessments were obtained at baseline and after 1 and 2 months of treatment. The expression of platelets CD62p and PAC-1 was increased in HNC patients compared to NOMC volunteers (P<0.01 and P<0.05). Furthermore, the surface expression of platelets CD62p and PAC-1 was greater among HLC patients than among HNC patients (P<0.01 and P<0.05). Although the expression of CD62p and PAC-1 decreased significantly after atorvastatin treatment, it remained higher in the HLC group than in the HNC group (P<0.05 and P=0.116). The reduction of HDL-C further increased platelet activation in patients with high levels of LDL-C. Platelet activation remained higher among HLC patients regardless of atorvastatin treatment.
MicroRNAs (miRNAs) were recently reported to play an important role in hepatitis B virus (HBV) infection and related diseases. We evaluated the correlation between serum miRNA-125b, viral replication and liver necroinflammation in Chinese patients with chronic hepatitis B (CHB) infection. Serum miRNA-125b levels in samples from 211 CHB patients were determined by RT-PCR. Liver biopsies were collected from 138 patients. Serum miRNA-125b, miRNA-122 and miRNA-124 levels were determined. Correlations between serum miRNA-125b, viral replication and liver necroinflammation were analysed. The receiver operating characteristic (ROC) curve was used to assess the discriminating power of serum miRNA-125b to grade liver necroinflammation (G). HepG2.2.15 cells were transfected with miRNA-125b mimics. Intracellular viral core DNA was extracted and analysed by Southern blot. We found that serum miRNA-125b was positively correlated with the serum HBV DNA level. HBV replication capacity increased after transfection with miRNA-125b mimics. Patients with CHB with moderate-to-severe liver necroinflammation (G ≥2) showed significantly higher (p <0.001) serum miRNA-125b levels than those with G <2. In patients with alanine transaminase levels less than twice the upper limit of normal, serum miRNA-125b combined with miRNA-124 yielded an area under the ROC curve of 0.816, with 70.4% sensitivity and 84.9% specificity to discriminate the grade of liver necroinflammation (G ≥2). Hence, we concluded that miRNA-125b may enhance HBV replication. Serum miRNA-125b correlates with viral load. Serum miRNA-125b alone or combined with miRNA-124 has the potential to discriminate grades of liver necroinflammation, particularly in Chinese patients with CHB who have normal or mildly increased alanine transaminase levels.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.