Researchers led by Christopher P. Holstege, MD, director of UVA Health’s Blue Ridge Poison Center, examined reports submitted to U.S. poison centers from 2000 through 2024. When the data were adjusted for population growth, the rate of reported xenobiotic-related liver injury rose from 10.9 cases per million people to 52.9 cases per million. That represents an increase of almost 400 percent. The study does not mean that every liver injury in the country was captured, because poison center records reflect calls made by the public and health professionals rather than a complete national registry. However, poison centers are an important source of real-time toxicological surveillance, allowing scientists to detect changes in exposure patterns before they become visible in slower-moving health statistics.

More than 80 percent of the reported cases required inpatient medical care, suggesting that many of the exposures were clinically serious rather than minor or transient reactions. The liver is particularly vulnerable to toxic substances because it receives blood from the digestive tract and is responsible for chemically modifying, storing and eliminating a vast range of compounds. During this process, enzymes can convert an otherwise harmless substance into a reactive metabolite capable of damaging liver cells. Injury may begin with inflammation or cellular stress and progress to impaired bile flow, widespread hepatocyte death, acute liver failure and, in the most severe cases, the need for transplantation.

Medications accounted for the majority of the injuries recorded in the study, with acetaminophen emerging as the most frequently implicated substance. The drug is widely used to reduce pain and fever and is present in hundreds of prescription and nonprescription products. Under normal conditions, the liver safely processes most acetaminophen through chemical pathways that produce inactive compounds. A smaller fraction is converted into a reactive metabolite known as N-acetyl-p-benzoquinone imine, or NAPQI. The body normally neutralizes NAPQI with the antioxidant glutathione, but excessive doses can deplete glutathione and allow the metabolite to attack liver proteins and cellular structures.

The study found that liver injuries associated with acetaminophen-containing combination prescription products fell sharply—by approximately 60 to 85 percent—after the U.S. Food and Drug Administration limited the amount of acetaminophen permitted in those medicines. The decline suggests that regulatory action reduced the risk created by products that combined acetaminophen with other active ingredients, particularly when patients were unaware that multiple medicines contained the same pain reliever. At the same time, injuries linked to acetaminophen taken by itself increased steadily over the period studied. That pattern indicates that the drug remains a major source of toxic exposure even as one category of combination products has become safer.

Women had higher rates of acetaminophen-associated liver injury than men, while suspected suicide was the most common reason for exposure in both sexes. The data point to the importance of distinguishing accidental medication errors from intentional overdoses, because the medical response, prevention strategies and public health interventions differ substantially. Accidental exposure can occur when patients take several products with overlapping ingredients, misunderstand dosing instructions or use more than recommended while attempting to control severe pain or fever. Intentional ingestion requires rapid emergency assessment as well as mental health support. In either situation, early treatment is critical because symptoms may be mild or absent during the first stage of acetaminophen poisoning.

Alcohol was the second most common contributor to reported liver injuries, although it occurred far less frequently than acetaminophen-related cases. Alcohol-associated injuries were reported more often among men than women, but exposures increased in both groups during the COVID-19 pandemic. Alcohol can injure the liver through several overlapping mechanisms, including the accumulation of toxic metabolic products, oxidative stress, disruption of fat metabolism and activation of inflammatory pathways. Repeated heavy exposure can lead to fatty liver, alcoholic hepatitis and scarring, while a particularly large exposure or combination with other toxic substances may produce acute injury. The pandemic-era increase observed in poison center reports mirrors broader concerns about changes in alcohol consumption and substance use during periods of social disruption.

The researchers also documented rising reports involving stimulants, illicit drugs, herbal and dietary supplements and environmental toxins. These categories were less common than acetaminophen and alcohol, but they reflect a growing challenge for clinicians and poison specialists: the chemical landscape of consumer exposure is constantly changing. Supplements may contain concentrated botanical compounds, undisclosed pharmaceuticals or contaminants, and their formulations can vary between products and batches. Stimulants and street drugs may be mixed with other substances that increase toxicity, while environmental chemicals can affect the liver through metabolic activation or prolonged low-level exposure. Because many emerging products are not subject to the same premarket testing as approved medicines, identifying the exact substance and dose can be difficult during an emergency.

Holstege said the findings underscore the need for consumers to follow clinical advice and pharmaceutical label instructions, while exercising particular caution with unregulated or newly emerging substances. The results also demonstrate how poison centers can function as an early-warning system for public health. Their records can reveal shifts in drug-related harm, identify vulnerable populations and show whether a policy change is associated with a meaningful reduction in poisoning. Still, the study’s observational design cannot prove that every increase resulted from a single cause. Changes in calling behavior, awareness of poison center services, clinical recognition, product availability and patterns of intentional self-harm may all influence the numbers. Even with those limitations, the scale and persistence of the increase point to a widening need for medication safety education, clearer labeling, careful supplement oversight and rapid access to toxicology expertise.

UVA Health’s Blue Ridge Poison Center provides free, confidential guidance around the clock for suspected poison exposures, including medication overdoses and possible liver-toxic substances. The center can be reached in the United States at 1-800-222-1222. People should not wait for symptoms before seeking advice, particularly after a suspected acetaminophen overdose, because serious liver injury can develop while early warning signs remain subtle. The new study, published in Clinical Gastroenterology and Hepatology, was authored by Eleanor Blair Towers, Christopher P. Holstege, Scott Schmalzried and Rita Farah. The researchers reported that they had no financial interest in the work.

Subject of Research: People

Web References: https://makingofmedicine.virginia.edu/

References: Clinical Gastroenterology and Hepatology

Image Credits: UVA Health

Keywords: liver injury, acetaminophen, poisoning, xenobiotics, poison centers, medication safety, alcohol-related liver disease, dietary supplements, toxicology, UVA Health

Latin America’s unique epidemiological profile for SLD is shaped by an alarming rise in obesity and type 2 diabetes prevalence. These metabolic conditions act as cornerstones in MASLD pathogenesis, precipitating hepatic steatosis and fostering a milieu conducive to inflammation and fibrosis. Compounding this metabolic burden is a high prevalence of harmful alcohol use, which independently contributes to hepatic injury and worsens clinical outcomes in patients harboring steatotic livers. The concomitant presence of these risk factors defines the region’s mounting challenge in managing this multifaceted liver pathology.

Genetic predisposition also plays a pivotal role in the heightened vulnerability of Latin American populations to SLD. Particularly notable is the high frequency of deleterious variants in the PNPLA3 gene, which encodes the patatin-like phospholipase domain-containing protein 3 enzyme. This variant has been shown to significantly predispose individuals to fat accumulation in hepatocytes, disease progression, and the development of advanced liver pathology, including steatohepatitis and hepatocellular carcinoma. The genetic landscape thus interacts synergistically with metabolic and alcohol-related insults, accelerating the trajectory from benign steatosis to life-threatening liver disease.

Clinically, the consequences of this confluence are dire. Patients with SLD are at increased risk not only for the progression to nonalcoholic steatohepatitis (NASH) or alcoholic steatohepatitis but also for advanced fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). These advanced manifestations herald significant morbidity and mortality, imposing a growing burden on healthcare systems ill-equipped to meet these challenges. In Latin America, the epidemiological shift towards higher rates of metabolic dysfunction and alcohol-related liver injury portends an impending rise in liver-related complications that will demand urgent public health attention.

Despite the evident clinical and epidemiological weight of SLD in Latin America, the region grapples with structural health-system deficiencies that undermine effective disease management. Fragmented healthcare delivery systems compromise continuity and quality of care, while limited availability of hepatology specialists constrains diagnosis accuracy and therapeutic interventions. Furthermore, the scarcity of advanced diagnostic tools such as transient elastography and histological expertise impairs early detection and staging of liver disease, leading to delayed treatment and poorer outcomes.

Therapeutic options remain comparatively limited, and access to emerging treatment modalities is often restricted by economic and infrastructural barriers. This constraint is exacerbated by low rates of participation in clinical trials, which hinders the development of evidence-based, region-specific management strategies. The lack of robust clinical research tailored to Latin American populations leaves clinicians reliant on data generated from predominantly European or North American cohorts, which may not fully capture the genetic and environmental nuances influencing disease progression locally.

The current state of research and surveillance in Latin America highlights significant knowledge gaps that must be addressed to curb the escalating burden of SLD. Comprehensive epidemiological studies are urgently needed to delineate the true prevalence and natural history of MASLD and ALD in diverse populations across the continent. Moreover, improved surveillance mechanisms would enable timely identification of at-risk individuals and facilitate monitoring of disease progression, thereby informing targeted interventions and resource allocation.

Prevention strategies focused on mitigating metabolic risk factors—such as obesity and diabetes—are paramount. Public health initiatives promoting healthy diets, physical activity, and metabolic health optimization could play a substantial role in reducing the incidence of MASLD. Simultaneously, harm reduction policies aimed at curbing harmful alcohol consumption are crucial to attenuate the impact of ALD and the overlapping metabolic-alcohol-related liver disease subtype that compounds clinical complexity.

Health system strengthening is critical to mounting an effective response to the SLD epidemic. Investments in hepatology training and capacity building can expand the specialist workforce necessary to manage complex liver disease cases. Enhancing access to diagnostic and therapeutic technologies, including non-invasive fibrosis assessment tools and novel pharmacological treatments, would enable earlier diagnosis and improved clinical management. Such improvements would also facilitate greater inclusion of Latin American populations in clinical trials, ensuring that advancements in liver disease treatment are both applicable and accessible to this high-risk region.

Policymakers must prioritize the implementation of comprehensive liver health policies that integrate prevention, early detection, and treatment within broader health system frameworks. Cross-sector collaboration involving public health authorities, academic institutions, and international organizations can galvanize efforts to reduce the morbidity and mortality associated with SLD. Such coordination is essential to bridge existing gaps in care and research and to foster sustainable, population-level health improvements.

It is imperative to recognize the multifactorial nature of SLD and its interwoven etiologies—metabolic derailments, alcohol misuse, and genetic susceptibility—that jointly magnify disease impact in Latin America. This complexity demands a multifaceted, evidence-based approach encompassing public health interventions, clinical management advances, and research innovations. Only through such concerted actions can the escalating tide of steatotic liver disease be stemmed, averting widespread liver failure and cancer that threaten the well-being of millions.

Emerging research has also begun to illuminate molecular pathways underpinning SLD, revealing potential therapeutic targets. For instance, the PNPLA3 I148M variant disrupts normal lipid remodeling processes in hepatocytes, leading to pathological triglyceride accumulation. Targeting pathways related to lipid metabolism and inflammation could yield novel treatments tailored to genetically predisposed populations. Furthermore, understanding the epigenetic and environmental modulators of gene expression may open avenues for personalized medicine approaches in SLD care.

Future directions in tackling the SLD crisis in Latin America must incorporate the development and validation of non-invasive biomarkers to supplant liver biopsy, currently the gold standard but limited by invasiveness and accessibility issues. Advanced imaging techniques and serum markers could revolutionize disease staging and monitoring, facilitating large-scale screening and surveillance initiatives. Integration of such tools into primary care settings offers the potential to democratize liver health assessment and prompt earlier clinical intervention.

The integration of digital health technologies, including telemedicine and electronic health records, represents another frontier for improving liver disease management in resource-constrained environments. These technologies can extend hepatology expertise beyond urban centers, enable remote monitoring of disease progression, and foster patient engagement in lifestyle modifications. Tailored digital platforms designed for Latin American populations could enhance adherence to preventive measures and treatment regimens, thereby improving overall outcomes.

Addressing socio-economic determinants of health is also integral to attenuating the SLD burden in Latin America. Poverty, educational disparities, and limited access to nutritious foods intersect with the metabolic and behavioral risk factors driving liver disease. Public policies that encompass social welfare, food security, and health literacy initiatives can create an enabling environment for sustained liver health improvements and lower disease incidence at a population level.

The synthesis of current knowledge underscores an urgent call to action to confront the burgeoning SLD epidemic in Latin America. Comprehensive strategies that integrate molecular research, clinical innovation, public health initiatives, and health system reforms are imperative. Through collaborative, region-specific efforts bolstered by global support, there lies a promising path to mitigate this formidable liver health challenge and improve quality of life for millions affected across Latin America.

Subject of Research: Steatotic liver disease epidemiology, clinical burden, and management in Latin America

Article Title: Steatotic liver disease in Latin America: current views and perspectives

Article References: Idalsoaga, F., Díaz, L.A., Barrera, F. et al. Steatotic liver disease in Latin America: current views and perspectives. Nat Rev Gastroenterol Hepatol (2026). https://doi.org/10.1038/s41575-026-01219-3

Image Credits: AI Generated

PFOS belongs to the notorious group of so-called “forever chemicals,” which garnered attention due to their widespread presence and extreme persistence in the environment and human tissues. Unlike many pollutants that break down relatively quickly, PFAS compounds resist natural degradation processes, leading to bioaccumulation throughout ecosystems and within the bodies of living organisms. PFOS, in particular, has been extensively used in an array of consumer products, ranging from non-stick cookware and stain-resistant fabrics to fast-food packaging and firefighting foams. This ubiquitous use has resulted in near-universal exposure, with recent data suggesting that about 95% of Americans carry measurable levels of PFAS in their bloodstream.

Alcohol consumption, a leading cause of liver disease worldwide, remains a major public health challenge. The World Health Organization attributes nearly three million deaths annually to alcohol-related causes, with liver disease constituting a substantial portion of this toll. In the United States alone, excessive alcohol use is responsible for approximately 95,000 deaths each year, rendering it a foremost preventable cause of mortality. Yet, the variation in liver disease outcomes among individuals with similar alcohol intake has evaded comprehensive explanation, prompting researchers to explore other contributory factors influencing liver vulnerability.

The University of Louisville study, conducted collaboratively with researchers from Boston University and the University of Massachusetts Lowell, utilized advanced animal models that simulate chronic and binge drinking scenarios, akin to patterns observed in human alcohol consumption. These models allowed the team to carefully investigate the interactive effects of PFOS and alcohol on liver health under controlled conditions replicating real-world exposure levels. Crucially, this combinatorial approach illuminated mechanisms by which PFOS amplifies alcohol-induced hepatic injury.

One of the pivotal findings was that co-exposure to PFOS and alcohol dramatically heightened the accumulation of fat within liver cells, a hallmark of steatosis that precedes more severe liver pathology. Concurrently, biochemical markers indicative of liver damage surged significantly compared to exposure to either substance alone. Through gene expression analyses, the study uncovered upregulation of molecular pathways associated with oxidative stress, inflammation, and early cancer development. These data paint a mechanistic picture wherein PFOS disrupts the liver’s normal metabolic and protective functions, effectively undermining the organ’s adaptive resilience against alcohol-related insults.

Scientists also observed that PFOS interferes with hepatic lipid metabolism. The chemical appears to impair the liver’s ability to efficiently process and export fats, fostering an environment conducive to metabolic dysregulation. This metabolic disturbance contributes to a feed-forward cycle of liver injury and inflammation, setting the stage for progressive liver disease. Importantly, PFOS notably concentrated within the liver, with approximately 60% of the total chemical burden residing in hepatic tissue. This targeted accumulation underscores the potential for PFOS to directly exacerbate alcohol’s toxic effects in this vital organ.

The implications of these discoveries extend beyond basic science, signaling urgent public health considerations. With PFAS chemicals pervasive in consumer products and environmental reservoirs, many individuals who consume alcohol are inadvertently subjected to joint exposures that may increase their risk of developing liver disease. Given that only about a third of heavy drinkers develop severe liver pathology, integrating environmental toxicant exposure into risk assessment models could refine our understanding of disease heterogeneity and guide targeted interventions.

The interplay between alcohol and PFOS also opens new avenues for therapeutic exploration. By identifying key molecular pathways perturbed by combined exposure, researchers can investigate novel drug targets aimed at bolstering liver defenses or mitigating damage. Such treatments, if successfully developed, could prove transformative for millions affected by the dual burden of alcohol use and environmental chemical exposure. Moreover, the study raises critical questions about gender differences, genetic predisposition, and differing PFAS compounds, topics currently under investigation by the research team to unpack the complexity of liver disease etiology.

This research serves as a clarion call for stronger regulatory measures surrounding PFAS chemicals. Despite growing recognition of their environmental persistence and health risks, regulatory frameworks have lagged in effectively limiting exposure. The findings underscore the need for policies that not only address direct chemical toxicity but also consider the subtle interactions between lifestyle factors and environmental pollutants that collectively undermine human health.

In light of these findings, individuals can take precautionary steps to reduce their PFAS exposure, potentially alleviating some of the compounded risk to liver health. Choosing alternatives to non-stick cookware, opting for PFAS-free household products, using water filtration systems in contaminated areas, and minimizing consumption of packaged fast foods known to contain PFAS-laden materials are practical strategies. Such actions may help curb the silent and insidious impact of these chemicals, complementing broader public health efforts to reduce alcohol-related harm.

Ultimately, this research highlights the intricate web of factors influencing liver disease and challenges simplistic models focused solely on alcohol consumption. It urges a paradigm shift toward a more holistic view incorporating environmental toxicants, genetics, lifestyle, and microbial factors. By advancing our understanding of these multifaceted interactions, science moves closer to unraveling the longstanding mystery of differential liver disease outcomes and opens the prospect of precision medicine approaches tailored to individual risk profiles.

As the scientific community continues to dissect these complex relationships, the study from the University of Louisville stands as a pioneering example of integrative research blending toxicology, environmental health, and hepatology. It not only deepens comprehension of liver disease pathology but also emphasizes the critical need to consider our modern chemical environment as a powerful modifier of health beyond traditional clinical factors. The full implications of this work, especially in guiding public policy and clinical practice, will unfold in the coming years as further investigations and translational studies build on this foundation.

Subject of Research: Animals
Article Title: Perfluorooctane sulfonate exposure and alcohol-associated liver disease severity in a mouse chronic-binge ethanol feeding model
News Publication Date: 10-May-2025
Web References:

• https://academic.oup.com/toxsci/advance-article/doi/10.1093/toxsci/kfaf066/812834
• https://www.niehs.nih.gov/health/topics/agents/pfc
• https://www.who.int/health-topics/alcohol#tab=tab_1
• https://pmc.ncbi.nlm.nih.gov/articles/PMC3214974/

References: DOI: 10.1093/toxsci/kfaf066/812834

Keywords

Environmental toxicology, Steatohepatitis, Alcoholism