Victoria Johnson joined the MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and now HCPLive. You can reach her at vjohnson@mjhlifesciences.com

Victoria Johnson

New research has found that febuxostat use in patients with gout was associated with a significantly greater risk of mild to moderate perturbation of liver function compared to benzbromarone.

Lead investigator Wenyan Sun, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China, and colleagues identified new users of febuxostat or benzbromarone from an electronic medical record database that had liver function monitored at least 3 times in a year after initiating the study drugs. They performed propensity score matching (PSM) between the 2 groups 1:1 to match for age, sex, and pre-treatment alanine aminotransferase (ALT) and aspartate aminotransferase (AST). They also used Kaplan-Meier analysis to estimate the probability of hepatotoxicity (defined as ALT or AST >3x upper limit of normal) and calculated hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression. The investigators further performed subgroup analysis based on age, body mass index, and comorbidities.

The analysis included 2,338 participants with gout. Of these participants, 37% experienced grade 1-3 AST/ALT abnormality adverse events (AE). After PSM, 488 participants using febuxostat were matched with 488 receiving benzbromarone with a mean follow-up of 1.20 years. Sun and colleagues found that in this population, participating receiving febuxostat had an incidence of hepatotoxicity of 39.6 per 1,000 person-years and participants receiving benzbromarone had an incidence of hepatotoxicity of 16.8 per 1,000 person-years. Accordingly, febuxostat use was associated with a significantly greater risk of hepatotoxicity than benzbromarone (adjusted HR, 2.75 [95% CI, 1.28-5.91]). Participants with elevated transaminases at baseline had higher risk of hepatotoxicity. Subgroup analyses did not reveal any significant findings.

Other recent research into renal injury risk in people with gout found that monocyte-to-HDL-C ratio (MHR) was found to be correlated with gout risk and renal dysfunction severity. Lead investigator Liangyu Mi, Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China, and colleagues used data from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2016 to conduct a cross-sectional analysis to assess the correlation between MHR levels and gout. They used multiple logistic regression, subgroup analyses, and exploration of nonlinear relationships to analyze data from 7247 participants, 373 with gout.

in gout patients (0.54; standard deviation [SD], 0.31) compared to non-gout patients (0.47; SD, 0.24). After adjusting for confounding factors, MHR was significantly associated with gout risk (odds ratio [OR], 1.6 [95%CI, 1.1–2.2]; 

 = .012). They also found that after adjustments, each unit increase in MHR significantly raised the risk of gout by approximately 0.6-fold.

Furthermore, subgroup analyses revealed a positive correlation between MHR and gout risk in males, Mexican Americans(OR, 5.0 [95% CI, 1.5–17.4]; 

 = .011), and participants who were married (OR, 1.8 [95% CI, 1.2–2.8]; 

 = .008), had insufficient physical activity (OR, 1.6; 

Notably, MHR had a stronger positive association in patients who had gout with renal dysfunction (OR, 7.4 [95% CI, 2.2–25.3]; 

 = .001). Patients in the highest MHR quartile had a 1.7-fold higher prevalence of gout with renal dysfunction than the lowest quartile (OR, 2.7 [95% CI, 1.1-6.7]; 

“The findings of this study indicate a substantial positive correlation between the MHR and gout, highlighting its potential as a useful biomarker for evaluating the risk and severity of the disease and its complications. Moreover, the study reveals that MHR is linked to the progression of renal impairment in individuals with gout. These results underscore the importance of considering MHR as a valuable indicator in the management and assessment of gout-related health issues,” Mi and colleagues concluded.

Sun W, Cui L, Terkeltaub R, et al. Risk of hepatotoxicity in patients with gout treated with febuxostat or benzbromarone: a propensity score-matched cohort study. 

Published online April 7, 2025. doi: 10.1002/acr.25547

Mi L, He X, Gao J, Xu K. Monocyte-to-HDL cholesterol ratio (MHR) as a novel Indicator of gout risk. Sci Rep. 2025; 15 (12188). doi.org/10.1038/s41598-025-97373-w

Articles

Febuxostat use in gout patients is linked to a higher risk of liver function perturbation compared to benzbromarone, with a significantly greater incidence of hepatotoxicity. A study involving 2,338 participants showed febuxostat users had a hepatotoxicity incidence of 39.6 per 1,000 person-years versus 16.8 for benzbromarone users. Additionally, research indicates a correlation between monocyte-to-HDL-C ratio (MHR) and gout risk, with MHR serving as a potential biomarker for assessing gout severity and renal dysfunction. MHR is notably higher in gout patients, especially those with renal impairment.

Febuxostat was associated with a nearly 3-fold higher risk of mild to moderate perturbation of liver function than benzbromarone.

Higher Hepatotoxicity Risk With Febuxostat Over Benzbromarone in People With Gout

Heat therapy via hot water immersion relieved symptoms and improved quality of life measures in people with 

“Despite the known benefits of exercise for FM, many patients have difficult initiating or maintaining this treatment regimen due to fear avoidance of pain and rebound hyperalgesia.

 Thus, there exists is a need for a passive, non-pharmaceutical intervention that could help to reduce pain, improve physical functioning, and lead to a better quality of life,” lead investigator Andrea Chadwick, MD, MSc, associate professor, Department of Anesthesiology, Pain, and Perioperative Medicine, University of Kansas School of Medicine, and colleagues wrote.

The study screened 62 participants and enrolled 11, all of which were female, and 3 of which withdrew, 1 for health issues unrelated to the study and 2 due to the COVID-19 pandemic. The remaining 8 participants completed the study, undergoing 4 weeks of heat therapy via hot water immersion with no adverse events.

Investigators found that the participants’ Brief Pain Inventory (BPI) average and worst pain severity scores were significantly reduced post-intervention (

.035, respectively). Participants also experienced statistically significant reductions (

.035) in Fibromyalgia Impact Questionnaire (FIQ-R) post heat therapy and significant improvements in PROMIS Physical Function 8b questionnaire and in the PROMIS sleep-related impairment (

 =.014) and PROMIS sleep-related impairment (SRI) questionnaire (

.042), with no changes in depression or anxiety. These findings altogether demonstrated significant improvements in overall impact of fibromyalgia symptoms, physical function, and sleep-related impairment.

Chadwick and colleagues also found a statistically significant reduction in HSP90 levels, increase in number of extracellular vesicles, and induction of HSP40 and HSC70 blood levels.

Participants reported reduced subjective pain and symptom impact, though FMness scores did not significantly change in the 8-person sample. Pressure pain threshold and tolerance values showed upward trends, but changes were not statistically significant. Conditioned pain modulation (CPM) could only be completed in 3 of 8 patients due to pain intolerance; of those, 2 showed improved CPM magnitude, though this was also not statistically significant.

“As a whole, these findings suggest that heat therapy via hot water immersion may be an effective non-pharmaceutical intervention for patients with FM and that its analgesic benefits may be due to decreases in HSP 90 and increases in HSP 40 and 72 – which although in our study did not show significant changes in inflammatory cytokines, have been associated with improvements in inflammation. Further large-scale, well-powered studies are needed to confirm our preliminary clinical and translational results,” Chadwick and colleagues concluded.

The investigators encouraged further research, acknowledging the study’s very small sample size as a key limitation. Another limitation was indetectable concentrations of inflammatory cytokines in serum via multiplex testing, whereas future studies should utilize an ex-vivo whole blood lipopolysaccharide stimulation model so toll-like receptor 4 global cytokine chemokine release can be scored and measured, they wrote.

Chadwick AL, Shi C, McMillan M, Miller J, Hu J, Geiger PC. The impact of a heat therapy intervention on pain and fibromyalgia symptoms in patients with fibromyalgia: a pilot study. 

 2025;6:1526491. Published 2025 Mar 13. doi:10.3389/fpain.2025.1526491

Kregel KC. Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. 

(1985). (2002) 92(5):2177–86. 10.1152/japplphysiol.01267.2001

A pilot study explored the effects of heat therapy via hot water immersion on fibromyalgia patients, revealing significant improvements in pain severity, physical function, and sleep-related impairment. The study involved 11 female participants, with 8 completing the intervention without adverse events. Results indicated reductions in pain scores and fibromyalgia impact, alongside changes in heat shock protein levels. Despite promising findings, the study's small sample size and limitations in cytokine measurement necessitate further research to validate these preliminary results and explore the underlying mechanisms of heat therapy's analgesic effects.

Participants experienced significant improvements in pain, sleep, and physical function.

Heat Therapy Seems Promising for Fibromyalgia Symptoms in Small Study

Medical science research is constantly evolving, and HCPLive remains dedicated to highlighting the experts behind these advancements. Over the past year alone, the dynamic field of respiratory health has seen a wide range of research efforts focused on conditions that impact breathing and overall quality of life for patients.

, HCPLive’s quarterly newsletter spotlighting pulmonary investigators supported by the American Lung Association Research Institute, features some of the latest progress in pulmonary research. Each issue—accessible on HCPLive.com and via our email newsletter—offers expert insights into the development of research with the potential to change clinical practice.

 includes written articles and video interviews featuring investigators discussing their latest work on conditions like chronic obstructive pulmonary disease (COPD), asthma, rare interstitial lung diseases, and respiratory viruses. Much like 

, a collaborative series from HCPLive and the American Lung Association, 

 aims to cover a wide range of topics across the field of pulmonology.

The following summary represents a preview of authors and their research featured in our second issue.

Peter Miller, MD, PhD, is an Assistant Professor of Medicine at Massachusetts General Hospital and Harvard Medical School. Miller discussed his research looking into clonal hematopoiesis (CH), particularly involving somatic mutations in the ASXL1 gene, which has emerged as a novel, non-traditional risk factor for chronic obstructive pulmonary disease (COPD).

Miller and colleagues conducted large-scale genetic epidemiology studies across multiple biobanks to quantify the association between ASXL1-mutant CH and COPD, identifying genetic modifiers that may amplify disease risk and characterize related clinical phenotypes. Using mouse models, they confirmed that these mutations promote COPD pathogenesis through enhanced inflammation, and they are evaluating anti-inflammatory therapies as potential interventions.

Uncovering the Link Between Clonal Hematopoiesis and Chronic Obstructive Pulmonary Disease

Divay Chandra, MD, MSc, is an associate professor in the Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, at University of Pittsburgh in Pennsylvania. Chandra is exploring lithium's potential as a disease-modifying therapy for COPD, for which no therapies currently exist that modify disease progression, and known risk factors like smoking account for only about half of total disease burden.

Chandra and his team are investigating lithium for its ability to activate WNT/β-catenin signaling, a key pathway in lung repair. Their research found that lithium reduces emphysema in mouse models, correlates with less severe emphysema in human cohorts, and induces reparative signaling in human lung tissue and they are looking to further correlate circulating lithium levels with disease severity.

Exploring Lithium as a Potential Disease-Modifying Therapy for Emphysema

William Zhang, MD, Assistant Professor of Medicine at Weill Cornell Medicine, is investigating abnormal iron homeostasis in alveolar macrophages that may play a role in COPD pathogenesis.

Zhang investigated the role of iron dysregulation in alveolar macrophages (AMs) as a potential contributor to COPD pathogenesis and exacerbation risk. Using cigarette smoke-exposed mouse models, single-cell RNA sequencing, and a transgenic model with macrophage-specific NCOA4 depletion, his team demonstrated that disrupted iron homeostasis alters AM function and may contribute to emphysema, but also found that limiting iron access may impair infection defense.

Abnormal Iron Homeostasis in Alveolar Macrophages: Implications for COPD Pathogenesis

Jaime Hook, MD, is an Assistant Professor, Division of Pulmonary, Critical Care, and Sleep Medicine, Departments of Medicine and Microbiology, Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai. Hook is seeking to bolster alveolar defense against 

Her team investigated how influenza disrupts innate alveolar defenses by inhibiting CFTR-mediated liquid secretion and activating ENaC-driven absorption, creating an absorptive microenvironment that facilitates bacterial stabilization and lethal coinfection. They demonstrated that the CFTR potentiator ivacaftor restores alveolar secretion and protects against death in flu-infected mice, and identified alveolar type 1 cells as key contributors to liquid secretion and alveolar defense.

Developing New Treatments for Influenza That Target the Lung – Not the Virus

, you will find something similar to what this quartet of featured authors provided: a multifaceted package of perspectives on the innovations and solutions pushing pulmonology ever forward. We hope you enjoy our latest series.

In this summary, we highlight the latest issue of our pulmonology research quarterly newsletter powered by the American Lung Association Research Institute.


Welcome Back to The Respiratory Report - 3rd Edition

This interview in the latest issue of The Respiratory Report features Jamie Hook, MD, discussing research into targeting the lung and not the virus to treat influenza.

Bolstering Alveolar Defense to Treat Complicated Influenza

Influenza is a major cause of global mortality and a frequent cause of pandemics, with death often resulting from secondary pneumonia by inhaled 

 (SA), especially in children. New research is uncovering how influenza infection disrupts lung defenses and opens the door to deadly bacterial co-infections with SA.

Jaime Hook, MD, Assistant Professor, Division of Pulmonary, Critical Care, and Sleep Medicine, Departments of Medicine and Microbiology, Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, and her team are studying new therapeutic approaches for influenza lung infection that protect against fatal SA coinfection. 

Hook spoke in the third issue of The Respiratory Report, a quarterly newsletter from 

 that is powered by the American Lung Association Research Institute, on her team’s current research in this area.

Her team found that influenza impairs alveolar defense by blocking CFTR-dependent liquid secretion and activating ENaC-driven absorption, creating an absorptive environment that allows inhaled 

 to cause fatal lung injury and were able to rescue alveolar wall liquid secretion and protect against SA-induced lung injury with the CFTR potentiator drug ivacaftor.

"These findings support CFTR potentiator therapy as a new treatment strategy for flu, SA coinfection, and they also inform the design of new CFTR potentiating therapies that might have more precise alveolar sites of action,  better drug efficacy, fewer side effects, and perhaps resilience in the face of new pandemic viruses and new viral and bacterial mutations that threaten the efficacy of existing drugs," Hook said.

To learn more about Hook's research, view the interview above or read her contribution to the third issue of The Respiratory Report here:

Developing new treatments for influenza that target the lung – not the virus

Videos

This interview in the latest issue of The Respiratory Report features Jamie Hook, MD, discussing research into targeting the lung and not the virus to treat influenza.
