Histological response to combination therapy with nucleos(t)ide analogs and peginterferon alpha in treatment-naïve chronic hepatitis B patients.

Although nucleos(t)ide analog (NA) monotherapy is effective in hepatitis B virus suppression and fibrosis regression, serological response rates are not satisfactory. Studies assessing the benefits of combination therapy with NAs and peginterferon alpha (PegIFNα) in patients with chronic hepatitis B (CHB) have produced conflicting results and mainly focused on serological outcomes. Histological changes in response to combination therapy have not been evaluated in real-world practice. This study aimed to evaluate the histological changes in response to NA-PegIFNα combination therapy in CHB patients and to comprehensively compare the efficacy of NA-PegIFNα combination therapy and NA monotherapy. We conducted a retrospective analysis of data from 40 CHB patients who underwent either NA-PegIFNα combination therapy or NA monotherapy. Changes in histology at 48 weeks after treatment initiation were evaluated. Serological characteristics were also analysed and compared between the NA-PegIFNα combination therapy and NA monotherapy groups and between histological responders and nonresponders. Compared to baseline biopsies, both fibrosis staging and necroinflammatory grading scores were significantly lower in the second biopsies examined post-treatment in both groups. Nearly all patients experienced a reduction in inflammation (87.5% in both groups), but there was a subgroup of patients who exhibited either no significant improvement or fibrosis progression (33.3% and 31.2% in the NA monotherapy and NA-PegIFNα combination therapy groups, respectively). Nearly, all patients achieved ALT normalization and sustained virological response (SVR) after 48 weeks of antiviral treatment. Approximately one-third of individuals (36.8% and 30% in the two groups, respectively) achieved HBeAg loss at 48 weeks after treatment initiation. Although there were no significant differences in overall rates of histological, biochemical, virological and serological responses between the two groups, an earlier virological response and a higher cumulative SVR rate over time were observed during long-term follow-up in patients treated with NA-PegIFNα combination therapy (P = 0.0129). Trends of more rapid HBeAg loss and a higher cumulative HBeAg loss rate throughout long-term follow-up were also observed but were not statistically significant. The ALT normalization rates at 24 and 48 weeks after treatment initiation were associated with the histological response. Significant regression of fibrosis and resolution of necroinflammation were induced with either NA-PegIFNα combination therapy or NA monotherapy. Significant biochemical, virological and serological responses were observed in both groups, and the response rates at 48 weeks were similar in the two groups. Over time during long-term follow-up, the virological and serological responses were faster and superior following the combination regimen.

Histological responses of peginterferon alpha add-on therapy in patients with chronic hepatitis B with advanced liver fibrosis after long-term nucleos(t)ide analog treatment.

Although long-term antiviral treatment with nucleos(t)ide analogs (NAs) can lead to histological improvement in patients with chronic hepatitis B (CHB), a substantial proportion of patients still fail to achieve regression of fibrosis. Here, we investigated whether peginterferon alpha (Peg-IFNα） add-on therapy had benefits on fibrosis regression in patients with sustained severe fibrosis even after long-term NA treatment. We conducted a retrospective analysis of data from 50 patients with CHB receiving 48 weeks of Peg-IFNα add-on therapy. All enrolled patients had advanced fibrosis or cirrhosis (S score ≥ 3) at baseline and underwent NA treatment for at least 1 year before Peg-IFNα addition. Paired liver biopsies before and after Peg-IFNα add-on treatment and laboratory tests at baseline, 24 weeks of treatment, 48 weeks of treatment and long-term follow-up were analysed. Of the 50 patients enrolled in this study, 34 patients (68.0%) had significant regression of fibrosis, and 42 (84.0%) showed significant remission of inflammation after Peg-IFNα add-on treatment. Compared with nonresponders, patients with significant histological improvement showed faster hepatitis B surface antigen (HBsAg) decline and tended to have higher cumulative hepatitis B e antigen (HBeAg) and HBsAg loss rates during long-term follow-up. Peg-IFNα add-on therapy led to significant regression of fibrosis and resolution of inflammation in patients with advanced fibrosis after long-term NA treatment.

Biodegradable ferroelectric molecular crystal with large piezoelectric response.

Transient implantable piezoelectric materials are desirable for biosensing, drug delivery, tissue regeneration, and antimicrobial and tumor therapy. For use in the human body, they must show flexibility, biocompatibility, and biodegradability. These requirements are challenging for conventional inorganic piezoelectric oxides and piezoelectric polymers. We discovered high piezoelectricity in a molecular crystal HOCH2(CF2)3CH2OH [2,2,3,3,4,4-hexafluoropentane-1,5-diol (HFPD)] with a large piezoelectric coefficient d33 of ~138 picocoulombs per newton and piezoelectric voltage constant g33 of ~2450 × 10-3 volt-meters per newton under no poling conditions, which also exhibits good biocompatibility toward biological cells and desirable biodegradation and biosafety in physiological environments. HFPD can be composite with polyvinyl alcohol to form flexible piezoelectric films with a d33 of 34.3 picocoulombs per newton. Our material demonstrates the ability for molecular crystals to have attractive piezoelectric properties and should be of interest for applications in transient implantable electromechanical devices.

Effects of plastic residues and microplastics on soil ecosystems: A global meta-analysis.

Plastic pollution is one of the global pressing environmental problems, threatening the health of aquatic and terrestrial ecosystems. However, the influence of plastic residues and microplastics (MPs) in soil ecosystems remains unclear. We conducted a global meta-analysis to quantify the effect of plastic residues and MPs on indicators of global soil ecosystem functioning (i.e. soil physicochemical properties, plant and soil animal health, abundance and diversity of soil microorganisms). Concentrations of plastic residues and MPs were 1-2700 kg ha-1 and 0.01-600,000 mg kg-1, respectively, based on 6223 observations. Results show that plastic residues and MPs can decrease soil wetting front vertical and horizontal movement, dissolved organic carbon, and total nitrogen content of soil by 14%, 10%, 9%, and 7%, respectively. Plant height and root biomass were decreased by 13% and 14% in the presence of plastic residues and MPs, while the body mass and reproduction rate of soil animals decreased by 5% and 11%, respectively. However, soil enzyme activity increased by 7%441% in the presence of plastic residues and MPs. For soil microorganisms, plastic residues and MPs can change the abundance of several bacteria phyla and families, but the effects vary between different bacteria.