Adefovir is usually applied for therapy of chronic hepatitis B (CHB), but its effectiveness after cessation is still unknown. This study was to evaluate the effectiveness of adefovir treatment with strict cessation criteria in hepatitis B e antigen (HBeAg)-negative patients and to identify potentially important factors. One hundred forty-five HBeAg-negative CHB patients who had received adefovir treatment for at least 24 months and for whom serum hepatitis B virus (HBV) DNA had remained undetectable for at least 18 months before cessation were included. They were followed up monthly during the first four months and at 3-month or 6-month intervals thereafter. Patients with ≥10(4) copies of HBV DNA per mL were defined as relapsed. In total, 95 patients relapsed within the follow-up time, and more than 93% relapsed within 12 months after adefovir cessation. Cumulative relapse rates at months 6, 12, 24, 36, 48 and 60 were 53.8%, 61.4%, 65.5%, 65.5%, 65.5% and 65.5%, respectively. Age was the only factor associated with relapse, with lower relapse rates in younger patients shown by Cox regression analysis. HBsAg seroconversion occurred in 12 patients, and none of them relapsed during follow-up. The effectiveness of adefovir therapy does not persist in HBeAg-negative CHB patients, even when strict cessation criteria are applied, except for patients aged ≤ 25 years. HBsAg seroconversion is the ideal endpoint of adefovir treatment.
Objective We aimed to compare the cumulative efficacy and resistance of ADV monotherapy, ADV add-on LAM (ADV + LAM), ADV and ETV (ADV + ETV) combination therapy in LAM-resistant patients. Methods Ninety-one adult CHB patients with LAM-resistance mutations (YMDD) were identified. Of these 91, 29 patients were treated with ADV monotherapy, 30 were treated with ADV + LAM and 32 were treated with ADV + ETV combination therapy, for at least 24 months. Results The mean serum HBV-DNA decreases from baseline at 3, 6, 12, and 24 months were -3.23, -4.41, -5.32, and -5.58 log10IU/mL in the ADV + ETV combination therapy groups, respectively; the most significant among the three treatment groups (p<0.01). The rate of HBV-DNA PCR undetectability (<60 IU/mL) at 6 months in ADV + ETV combination therapy was 78.1%; also the most significant among the three treatment groups (p=0.024). Viral breakthrough and genotypic mutations were detected in 8 (27.6%) and 4 (13.3%) patients in the ADV monotherapy and ADV+LAM therapy groups, respectively; whereas no case of viral breakthrough and genotypic resistance was detected in the ADV+ETV combination therapy group after 24 months (p<0.05). Conclusion ADV + ETV combination therapy demonstrated faster and significantly greater suppression of HBV DNA compared with ADV add-on LAM combination therapy for patients with LAM-resistance mutations. ADV + ETV was superior to ADV + LAM in achieving initial virological response and long-term suppression activity against HBV. ADV + ETV combination therapy was the most effective to refrain from selecting HBV strains with cross-resistance to three NAs (LAM, ADV and ETV) for LAM-resistance patients.
BackgroundGut microbiota plays a key role in the development of sarcopenia via the ‘gut‐muscle’ axis, and probiotics‐based therapy might be a strategy for sarcopenia. Fecal microbiota transplantation from young donors (yFMT) has attracted much attention because of its probiotic function. However, whether or not yFMT is effective for sarcopenia in old recipients is largely unknown. Thus, we aimed to investigate the effect and mechanism of yFMT on age‐related sarcopenia.MethodsThe fecal microbiota of either young (12 weeks) or old (88 weeks) donor rats was transplanted into aged recipient rats for 8 weeks. Then, muscle mass, muscle strength, muscle function, muscle atrophy, and muscle regeneration capacity were measured. Analysis of fecal 16 s rRNA, serum non‐targeted metabolomic, gut barrier integrity, and muscle transcriptome was conducted to elucidate the interaction between gut microbiota and skeletal muscles.ResultsAs evaluated by magnetic resonance imaging examination, grip strength test (P < 0.01), rotarod test (P < 0.05), and exhaustive running test (P < 0.05), we found that yFMT mitigated muscle mass loss, muscle strength weakness, and muscle function impairment in aged rats. yFMT also countered age‐related atrophy and poor regeneration capacity in fast‐ and slow‐switch muscles, which were manifested by the decrease in slow‐switch myofibres (both P < 0.01) and muscle interstitial fibrosis (both P < 0.05) and the increase in the cross‐section area of myofibres (both P < 0.001), fast‐switch myofibres (both P < 0.01), and muscle satellite cells (both P < 0.001). In addition, yFMT ameliorated age‐related dysbiosis of gut microbiota and metabolites by promoting the production of beneficial bacteria and metabolites—Akkermansia, Lactococcus, Lactobacillus, γ‐glutamyltyrosine, 3R‐hydroxy‐butanoic acid, and methoxyacetic acid and inhibiting the production of deleterious bacteria and metabolites—Family_XIII_AD3011_group, Collinsella, indoxyl sulfate, indole‐3‐carboxilic acid‐O‐sulphate, and trimethylamine N‐oxide. Also, yFMT prevented age‐related destruction of gut barrier integrity by increasing the density of goblet cells (P < 0.0001) and the expression levels of mucin‐2 (P < 0.0001) and tight junctional proteins (all P < 0.05). Meanwhile, yFMT attenuated age‐related impairment of mitochondrial biogenesis and function in fast‐ and slow‐switch muscles. Correlation analysis revealed that yFMT‐induced alterations of gut microbiota and metabolites might be closely related to mitochondria‐related genes and sarcopenia‐related phenotypes.ConclusionsyFMT could reshape the dysbiosis of gut microbiota and metabolites, maintain gut barrier integrity, and improve muscle mitochondrial dysfunction, eventually alleviating sarcopenia in aged rats. yFMT might be a new therapeutic strategy for age‐related sarcopenia.
Biomaterial‐associated microbial infection is one of the most frequent and severe complications associated with the use of biomaterials in medical devices. In previous studies, we developed new fluorinated polyphosphazenes, poly[bis(octafluoropentoxy) phosphazene] (OFP) and crosslinkable OFP (X‐OFP), and demonstrated the inhibition of bacterial adhesion and biofilm formation, thereby controlling microbial infection. In this study, two additional fluorinated polyphosphazenes (PPs, defined as LS02 and LS03) with fluorophenoxy‐substituted side groups, 4‐fluorophenoxy and 4‐(trifluoromethyl)phenoxy, respectively, based on X‐OFP general structure, were synthesized and applied as coatings on stainless steel. The linkage of fluorophenoxy groups to the P‐N backbone of PPs was found to increase the surface stiffness and significantly reduced Staphylococcus bacterial adhesion and inhibited biofilm formation. It also significantly reduced microbial infection compared to OFP, our prior X‐OFPs or poly[bis(trifluoroethoxy) phosphazene] (TFE). The biofilm experiments show that the newly synthesized PPs LS02 and LS03 are biofilm free up to 28 days. Plasma coagulation and platelet adhesion/activation experiments also demonstrated that new PPs containing fluorophenoxy side groups are hemocompatible. The development of new crosslinkable fluorinated PPs containing fluorophenoxy‐substituted side groups provides a new generation of polyphosphazene materials for medical devices with improved resistance to microbial infections and thrombosis formation.
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