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Medscape
02-06-2025
- Business
- Medscape
Metabolic Issues May Affect Liver Fibrosis in Hepatitis B
Patients with untreated chronic hepatitis B who had metabolic comorbidities were at a higher risk for advanced liver fibrosis and were less likely to see improvement with antiviral therapy than those without such comorbidities. METHODOLOGY: Researchers investigated the association between the presence of concurrent metabolic comorbidities and the severity of liver fibrosis in 3179 patients with untreated chronic hepatitis B (median age, 37 years; 72.2% men) using data from two tertiary clinics in the Netherlands and Canada and six global clinical trials. All patients underwent an initial liver biopsy, and 1307 of the patients enrolled in the clinical trials underwent a second biopsy 48-72 weeks after starting antiviral therapy. Biopsies were analyzed by experienced pathologists. Advanced fibrosis was defined as having METAVIR stages F3-F4, and nonadvanced fibrosis as having METAVIR stages F0-F2. Progression or regression of fibrosis was determined by an increase or decrease in fibrosis of at least one METAVIR stage from baseline, respectively. The presence of metabolic comorbidities (overweight, hypertension, diabetes, and dyslipidemia) was assessed using chart reviews and patient histories. TAKEAWAY: At baseline, metabolic comorbidities were present in 54.8% of patients, and advanced fibrosis was present in 24.4% of patients. The presence of metabolic comorbidities was independently associated with an increased risk for advanced fibrosis (adjusted odds ratio [aOR] for one comorbidity, 1.115; aOR for two or more comorbidities, 1.627; P = .006). = .006). The presence of metabolic comorbidities was also independently associated with reduced odds of regression from advanced to nonadvanced fibrosis after initiating antiviral therapy (aOR for one comorbidity, 0.79; aOR for two or more comorbidities, 0.26; P = .025). = .025). Progression to advanced fibrosis during antiviral therapy was observed in 9.8% of patients with one metabolic comorbidity and 14.3% of those with two or more metabolic comorbidities compared with 4.6% of those without metabolic comorbidities ( P = .001). IN PRACTICE: 'These findings provide solid support for the recently published World Health Organization HBV [hepatitis B virus] guideline, which underlines the importance of identifying and managing metabolic comorbidities in CHB [chronic hepatitis B] patients, as these comorbidities increase the risk of fibrosis progression and HCC [hepatocellular carcinoma] development,' the study authors wrote. SOURCE: The study, led by Lisa M. van Velsen, MD, Department of Gastroenterology & Hepatology, Erasmus Medical Center in Rotterdam, the Netherlands, was published online in Clinical Gastroenterology and Hepatology . LIMITATIONS: Information on hepatic steatosis was unavailable for the clinical trial patients. The presence of metabolic comorbidities was determined on the basis of a retrospective review of medical histories and medications, potentially leading to underdiagnosis of the conditions. Changes or development of metabolic comorbidities during follow-up could not be accounted for. DISCLOSURES: This study was sponsored by the Foundation for Liver and Gastrointestinal Research, and the data for the analyses were shared by Roche and Gilead Sciences. Several authors reported receiving research support or grants, consulting and/or speaking fees, honoraria, or contracts from pharmaceutical and biotechnology companies, including Roche and Gilead Sciences. One author reported being employed by Roche, and two authors reported being employed by Gilead Sciences.
Medscape
23-05-2025
- Health
- Medscape
Cold Sore Virus Implicated in Alzheimer's Disease
Herpes simplex virus 1 (HSV-1) infection is associated with an increased risk of developing Alzheimer's disease (AD), but treating the viral infection may offer protection, a new study found. In a matched case-control study of nearly 700,000 older adults, HSV-1 was more common in those with AD, and antiviral therapy for HSV-1 was associated with a lower risk of developing AD. However, the authors and outside experts cautioned that no firm conclusions can be drawn from this observational study and called for more research. The study was published online on May 20 in BMJ Open . It was funded by Gilead Sciences, which is actively involved in the research and development of treatments for HSV. Mixed Data HSV-1, a common virus that causes cold sores, affects more than two thirds of the global population younger than 50 years. An association between HSV-1 and AD has been reported previously, albeit with conflicting results across various studies. One recent Taiwanese cohort study found that symptomatic HSV infection was associated with a threefold increased risk of developing dementia. Antiherpetic medication reduced the risk by 90%. However, a study of US veterans failed to link HSV infection with an increased risk for dementia. Although, like the Taiwanese findings, antiherpetic medication was associated with a protective effect against dementia. To investigate further, researchers led by Yunhao Liu, PhD, data scientist with Gilead Sciences, used the IQVIA PharMetrics Plus claims database to match 344,628 people with AD to an equal number of control individuals without AD. Compared with 823 (0.24%) control individuals without an AD diagnosis, 1507 (0.44%) individuals diagnosed with AD had a history of HSV-1. Among those with AD, nearly two thirds were women (65%), their mean age was 73 years, and they tended to have more coexisting conditions. After adjusting for relevant confounding factors, the likelihood of an HSV-1 diagnosis was 80% higher in those with AD (adjusted odds ratio [aOR], 1.80; 95% CI, 1.65-1.96). In a stratified analysis, the association of HSV-1 with AD was more pronounced in older age groups — with an aOR of 2.10 in those aged 75 years or older vs an aOR of 1.14 in those aged 50-70 years. 'These findings are consistent with studies suggesting that the neurodegenerative impact of HSV-1 becomes more apparent with age and cumulative exposures,' the authors noted. Among the 2330 adults with a history of HSV-1, 931 (40%) were treated with antiherpetic medication, which was associated with a 17% reduced risk for AD compared with no treatment (adjusted hazard ratio [aHR], 0.83; 95% CI, 0.74-0.92). 'While the molecular mechanisms remain to be fully elucidated, these results are indicative of a possible role for antiherpetic therapy in mitigating dementia risk,' the authors wrote. Caveats and Cautionary Notes F. Perry Wilson, MD, Yale School of Medicine, New Haven, Connecticut, and Medscape's Impact Factor commentator, noted in a recent commentary that studies that use administrative data have limitations and said the author's suggestion that antiherpetic therapies are potentially protective for AD-related dementia 'feels like a bit of a leap to me at this point.' On the other hand, Wilson said, 'for those who suffer from cold sores, a study like this may push you a bit toward treatment, at least during an outbreak. Short-term valacyclovir is relatively safe and reduces the duration of the cold sore by about a day, which is nice. But if it reduces your risk of dementia as well, well, it might be a no-brainer.' Several outside experts also weighed in on the study in a statement from the UK nonprofit Science Media Centre. Sheona Scales, PhD, director of research at Alzheimer's Research UK, Cambridge, England, cautioned that 'despite the large sample size, this research has limitations partly due to only using health records and administrative claims data.' 'Most people infected with HSV-1 don't have any symptoms, so some infections might not have been recorded. Infections predating the information recorded are also not available. Although cases were matched with controls, diagnosing Alzheimer's disease, especially in the early stages, remains a challenge,' Scales commented. While the study found that some people receiving medicines to treat HSV-1 infections had a lower risk for AD, 'a lot more work is needed to unpick this,' she added. 'We know there are 14 established risk factors for dementia, and there's not enough evidence to include infections in this list. This study doesn't tell us if infections are causing the risk, it only shows an association. Further research is needed to understand what the underlying biology around this is,' Scales said. Tara Spires-Jones, PhD, director of the Centre for Discovery Brain Sciences at The University of Edinburgh, Edinburgh, Scotland, said the study adds to a growing body of data linking HSV-1 and other viral infections to the risk for AD. However, 'it is important to note that HSV-1 infection, which is extremely common in the population, is by no means a guarantee that someone will develop Alzheimer's,' Spires-Jones noted. 'Why viral infections may increase risk of dementia is not fully understood, but the most likely explanation is that infections increase inflammation in the body and contribute to age-related brain inflammation. More research is needed to understand the best way to protect our brains from Alzheimer's disease as we age, including a better understanding of links between viral infection and Alzheimer's risk,' Spires-Jones said. Richard Oakley, PhD, director of Research and Innovation at Alzheimer's Society, London, England, cautioned that the study 'doesn't prove that cold sores cause Alzheimer's disease, or that antivirals prevent it. Much more research is needed to explore exactly how viruses might be involved and before we can draw firm conclusions.'
