Author Interviews, Gastrointestinal Disease, Hepatitis - Liver Disease / 13.05.2025
Role of Genetic Research in Advancing PSC Treatment
MedicalResearch.com discussion with:
Dr. Bertus Eksteen PhD, MBChB, FRCP
Founder of the Calgary PSC Clinic
Member of the Calgary Liver Unit and the Southern Alberta Liver Transplant Clinic
Aspen Woods Clinic
Calgary, Canada
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Dr. Bertus Eksteen[/caption]
Primary sclerosing cholangitis (PSC) is a liver disease characterized by progressive inflammation and scarring of the bile ducts. PSC still has no known cause or cure and often leads to liver failure or cancer. For patients and clinicians, the lack of answers is deeply frustrating. But that's beginning to change.
Thanks to genetic research, we’re uncovering clues about PSC’s origins—and why it behaves differently from patient to patient. By learning more about the genomic underpinnings of PSC, researchers can create new treatment targets, devise risk profiles for early diagnosis, and even develop better clinical tools for detecting the disease in its earliest stages.
And that path forward doesn’t just start with new treatments — it begins in the lab.
Dr. Bertus Eksteen[/caption]
Primary sclerosing cholangitis (PSC) is a liver disease characterized by progressive inflammation and scarring of the bile ducts. PSC still has no known cause or cure and often leads to liver failure or cancer. For patients and clinicians, the lack of answers is deeply frustrating. But that's beginning to change.
Thanks to genetic research, we’re uncovering clues about PSC’s origins—and why it behaves differently from patient to patient. By learning more about the genomic underpinnings of PSC, researchers can create new treatment targets, devise risk profiles for early diagnosis, and even develop better clinical tools for detecting the disease in its earliest stages.
And that path forward doesn’t just start with new treatments — it begins in the lab.
Dr. Moyland[/caption]
Cynthia Moylan, MD
Associate Professor of Medicine,
Division of Gastroenterology
Duke University Health System
MedicalResearch.com: What is the background for this study?
Response: Metabolic dysfunction can lead to several health problems including metabolic dysfunction associated steatotic liver disease (MASLD), is driven by different factors, including: a person’s behavioral or lifestyle factors, environmental factors, and genetics. Limited research exists regarding genetic , epigenetic, or other factors that might impact development of metabolic dysfunction and MASLD. Our group has previously shown that alterations in DNA methylation (a type of epigenetic change), identifiable both in liver tissue and in blood, associate with MASLD and its progression to more severe liver disease. Whether DNA methylation that impacts imprinted gene expression also associates with metabolic dysfunction and MASLD risk remains largely unknown.
In this project, we explored imprinted genes: imprinting is a normal process that regulates genes by silencing one parental copy (either the maternal or the paternal) so that only one copy is expressed. Imprinting is an important biological process for development and has a disproportionate impact on disease - in fact, imprinted genes are hypothesized to affect 1-6% of the human genome. We sought to explore how altered DNA methylation of imprint control regions (ICRs) that help ‘control’ these imprinted genes might impact development of metabolic dysfunction in children (and hence potentially even in adults).
Dr. van der Velde[/caption]
Jeroen van der Velde, PhD
Leiden University Medical Center
Dept. Clinical Epidemiology, C7-102
Leiden, The Netherlands
MedicalResearch.com: What is the background for this study?
Response: We hypothesized that, in addition to the amount of physical activity, the pattern in which physical activity is accumulated over the day is relevant for metabolic health.
Several studies previously showed beneficial effects of interrupting sedentary periods with short periods of activity (breaks in sedentary time) on glucose control. In addition, very recently it has been argued that the timing of physical activity during the day may be relevant for metabolic health. This was mainly shown in animal studies and intervention studies with supervised high intensity exercise training in men with impaired glucose control or type 2 diabetes. If timing of physical activity matters in a ‘free-living’ setting in the general population is largely unknown.
Therefore, our aim was to investigate associations of timing of physical activity and breaks in sedentary time with liver fat content and insulin resistance in a middle-aged population.
Dr. Midya[/caption]
Dania Valvi, MD MPH PhD
Assistant Professor
Department of Environmental Medicine and Public Health
Co-Director, MS in Epidemiology
Icahn School of Medicine at Mount Sinai
Email: dania.valvi@mssm.edu
MedicalResearch.com: What is the background for this study?
Response: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children in the U.S., Europe and other world regions, currently affecting 1 in every 10 children, and 1 in every 3 children with obesity in the U.S. The rate of pediatric NAFLD has more than doubled in recent decades following the epidemic rates also noted for childhood obesity. There is increasing interest in the role that environmental chemical exposures may play in NAFLD etiology, since several animal studies have shown that prenatal exposures to endocrine-disrupting chemicals (EDCs) cause liver injury and damage; but, until now, the potential effects of prenatal EDC mixture exposures in pediatric NAFLD had not been studied.
Dr. LaMoreaux[/caption]
Brian LaMoreaux, M.D., M.S.
Medical Director, Medical Affairs
Horizon Therapeutics
MedicalResearch.com: What is the background for this study?
Response: Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD) but the relationship to fibrosis remains uncertain. Moreover, it is not known whether lowering serum urate will affect the course of NAFLD.
Dr. Hui Wang[/caption]
Prof Hui Wang PhD
Wuhan University
China
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We started our work in the adverse outcome of maternal caffeine intake during pregnancy about 15 years ago. Then, we found that prenatal caffeine intake could result in nonalcoholic fatty liver disease in the offspring. However, the underlying mechanism was unclear.
So, we start the current work, and found that hat maternal caffeine intake disrupts liver development before and after birth, which might be the trigger of the adult non-alcoholic fatty liver disease in the offspring rats. Moreover, we further found that the fetal programming of liver glucocorticoid – insulin like growth factor 1 axis, a new endocrine axis first reported by our team, might participate in such process.
