Mathematical Model Reveals HDV RNA Dynamics and HBV Reactivation During Lonafarnib Therapy
Researchers developed a mathematical model to characterize how hepatitis delta virus (HDV) RNA, hepatitis B virus (HBV) DNA, and hepatitis B surface antigen (HBsAg) change during lonafarnib-based therapy in 15 coinfected patients. Lonafarnib targets HDV but not HBV, making it a useful tool for studying how the two viruses interact kinetically. The findings reveal that HDV suppression can paradoxically increase HBV replication, with important implications for combination therapy design.
A preprint posted to arXiv presents a detailed kinetic analysis of viral dynamics in 15 HBV/HDV coinfected patients treated with lonafarnib (LNF), an investigational drug that inhibits HDV but not HBV. The model estimated an HDV RNA serum half-life of approximately 1.26 days and found that lonafarnib achieved roughly 94% efficacy in blocking HDV RNA production during the first phase of viral decline. Lonafarnib monotherapy frequently produced only a flat or partial response and was associated with viral breakthrough, while combination regimens with ritonavir or pegylated interferon-alpha (PEG-IFN-α) produced more sustained biphasic HDV declines without breakthrough. Notably, all treatment arms except LNF plus PEG-IFN-α had at least one patient experience an increase in HBV DNA on-treatment, which the model attributed to a median four-fold rise in HBV DNA production rate once HDV fell below an inhibitory threshold — suggesting HDV normally suppresses HBV replication. HBsAg levels remained stable throughout, consistent with the model's finding of a constant pool of HBsAg-producing cells. These results provide quantitative mechanistic insight into the interplay between HDV and HBV and may help guide the optimization of combination antiviral strategies.
What's missing
As a preprint, this study has not yet undergone formal peer review. The sample size is small (n=15), limiting statistical power and generalizability. The study does not report long-term virological outcomes or sustained virological response rates after treatment cessation. The inhibitory threshold at which HDV suppresses HBV was inferred indirectly rather than measured directly.
What different sources said
- arXiv physicsCenter
Mathematical Modeling of HDV RNA, HBV DNA, and HBsAg Dynamics during Lonafarnib-Based Therapy: Insights from the LOWR HDV-1 Study
Related
Gut Bacteria Enzyme Found to Break Down Heat-Processed Food Compounds, Producing Novel Biogenic Amines
Researchers have discovered that an enzyme in common gut bacteria can degrade N-epsilon-carboxymethyllysine (CML), a compound formed during thermal food processing, producing previously unknown biogenic amines. The enzyme, ornithine decarboxylase SpeC from enterobacteria, acts on CML and related modified lysine derivatives through a low-level 'underground' catalytic activity. This finding suggests a previously unrecognized communication axis between thermally processed dietary compounds and gut microbial physiology, with potential implications for host health.
Full-Length Gene Sequencing Reveals Two Distinct Bacterial Communities in Black-Legged Ticks Expanding Into Canada
Researchers used Oxford Nanopore full-length 16S rRNA gene sequencing to characterize the microbiome of Ixodes scapularis black-legged ticks collected in Nova Scotia, Canada, distinguishing between tick-adapted bacteria and environmentally acquired bacteria. The study comes as I. scapularis — the primary vector of Lyme disease — is rapidly expanding northward into Canada due to climate change. The findings suggest that environmentally derived bacteria in tick microbiomes are not mere contamination, which has implications for how tick microbiome data is collected and interpreted across surveillance studies.
Study Identifies Metabolic Link Between Cell Envelope Stress and Biofilm Formation in Bacteria
Researchers have discovered that the metabolite acetyl-CoA directly inhibits enzymes that degrade the bacterial signaling molecule c-di-GMP, connecting cell envelope biosynthesis stress to biofilm formation in Pseudomonas aeruginosa. The study found that sub-inhibitory concentrations of antibiotics targeting early peptidoglycan biosynthesis — but not other antibiotic classes — elevate c-di-GMP levels by reducing phosphodiesterase activity, with acetyl-CoA competing for the enzyme active site. Because the relevant enzyme domain is broadly conserved across bacterial species, this checkpoint mechanism may be widespread and could have implications for understanding antibiotic-induced biofilm responses.