Systematic review with meta-analysis: the impact of functional cure on clinical outcomes in patients with chronic hepatitis B.

BACKGROUND: Although hepatitis B surface antigen (HBsAg) loss is considered the ideal therapeutic endpoint for the treatment of chronic hepatitis B virus (HBV) infection, its impact on clinical outcomes remains uncertain. AIM: To assess the impact of HBsAg loss on clinical outcomes following spontaneous and treatment-related HBsAg loss. METHODS: We searched PUBMED, Embase, the Cochrane library, and published abstracts through to May 2021 for studies that reported HBsAg loss, had >1 year of follow-up and reported at least one clinical outcome in adults with chronic HBV infection. RESULTS: We identified 57 studies (258 744 HBsAg-positive patients, 63 270 with HBsAg loss). Based on 24 studies including 160 598 patients with and without HBsAg loss, HBsAg loss was associated with a non-significant 23% relative risk reduction of developing hepatocellular carcinoma (HCC) compared to those who remained HBsAg-positive (RR = 0.77; 95% CI: 0.38-1.57). In subgroup meta-analysis of 10 studies, treatment-related HBsAg loss was associated with a non-significant higher pooled proportion of HCC (0.94%) compared to spontaneous HBsAg loss (0.45%). HCC development after HBsAg loss was significantly higher in males, those with underlying cirrhosis, and those with a family history of HCC. HBsAg loss was associated with lower pooled proportions of incident cirrhosis, hepatic decompensation, overall and liver-related mortality compared to no HBsAg loss. Substantial heterogeneity was noted across studies for all outcomes. CONCLUSION: HBsAg loss is associated with a reduced risk of clinical outcomes. However, several shortcomings in the published studies prevent a more definitive conclusion on the potential benefits of HBsAg loss.

Conjugation of Silver Nanoparticles With De Novo-Engineered Cationic Antimicrobial Peptides: Exploratory Proposal.

BACKGROUND: Cationic antimicrobial peptides have broad antimicrobial activity and provide a novel way of targeting multidrug-resistant bacteria in the era of increasing antimicrobial resistance. Current developments show positive prospects for antimicrobial peptides and silver nanoparticles (AgNPs) individually. OBJECTIVE: The primary objective is to propose another method for enhancing antimicrobial activity by conjugating AgNPs with cationic antimicrobial peptides, with a subsequent preliminary assessment of the minimum inhibitory concentration of multidrug-resistant bacteria. The secondary objective is to evaluate the safety of the conjugated compound and assess its viability for in vivo use. METHODS: The proposal involves 3 stages. First, WLBU2C, a modified version of the antimicrobial peptide WLBU2 with an added cysteine group, needs to be synthesized using a standard Fmoc procedure. It can then be stably conjugated with AgNPs ideally through photochemical means. Second, the WLBU2C-AgNP conjugate should be tested for antimicrobial activity according to the Clinical & Laboratory Standards Institute manual on standard minimum inhibitory concentration testing. Third, the cytotoxicity of the conjugate should be tested using cell lysis assays if the above stages are completed. RESULTS: I-TASSER (iterative threading assembly refinement) simulation revealed that the modified peptide WLBU2C has a secondary structure similar to that of the original WLBU2 peptide. No other results have been obtained at this time. CONCLUSIONS: The addition of AgNPs to already developed de novo-engineered antimicrobial peptides provides an opportunity for the development of potent antimicrobials. Future prospects include emergency last-line therapy and treatment for current difficult-to-eradicate bacterial colonization, such as in cystic fibrosis, implantable medical devices, cancer, and immunotherapy. As I do not anticipate funding at this time, I hope this proposal provides inspiration to other researchers. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/28307.