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Mon, Oct 21 8:04am · Understanding the Mechanism of Aging Cholangiocytes in PSC in Primary Sclerosing Cholangitis (PSC)

PSC1021

Aging (senescent) bile duct cells , i.e., cholangiocytes, demonstrate an arrest of the cell cycle, hypersecretion of inflammatory molecules and resistance to cell death. O’Hara et al., previously reported that aging of cholangiocytes is a feature in PSC patients, and that this event is regulated by a central molecular pathway (Ras signaling) as well as the transcription factor, ETS1. In a recently published manuscript, his team further explored the molecular mechanisms regulating senescent cholangiocyte resistance to cell death. Using PSC patients derived tissues and an inducible cell culture model of cholangiocyte senescence, O’Hara et al., reported that the transcription factor, ETS1, interacts with a chromatin modifying enzyme, called p300, to induce the expression of a pro-survival protein, BCL-xL, which in turn promotes senescent cholangiocyte resistance to cell death. These new exciting data suggest that ETS1 is a central regulator of the senescent cholangiocyte phenotype. This novel knowledge provides the basis for exploring new targets for the therapeutic removal of aging cholangiocyte as an approach to treat PSC.

Read the full abstract from the PSC team.

Mon, Sep 23 12:55pm · Biochemical and Imaging Biomarkers in PSC in Primary Sclerosing Cholangitis (PSC)

biomarker test

Primary Sclerosing Cholangitis (PSC) is a slowly progressing liver disease that lacks an ideal biomarker, which could predict disease progression. A biomarker is a measurable indicator of the presence or severity of a disease state. For example, body temperature is a biomarker of fever.

In this presentation, Dr. John Eaton, an Assistant Professor of Medicine and transplant Hepatologist from Mayo Clinic, discusses in detail the importance, current biomarkers of, and ongoing approaches to develop novel biomarkers for PSC.

View the full presentation from Dr. Eaton.

Mon, Sep 9 9:08am · Mayo Clinic PSC Abstracts Accepted for the 2019 Annual AASLD meeting in Primary Sclerosing Cholangitis (PSC)

AASLD Doctor with Stethoscope image

The American Association for the Study of Liver Disease (AASLD) is the leading society of scientists and health care professionals in the United States committed to preventing, diagnosing, and treating liver disease. During the annual AASLD meeting that will take place in Boston, MA (November 8-12, 2019) our group has submitted five scientific abstracts, which have being accepted for presentation. Accepted abstracts represent high caliber work, which will be shared with other scientists and health care professionals. Our work that was accepted for this meeting ranges from discovery, to translation, and to clinical application. We are very excited to share with our followers this work on PSC.

Abstract 1: Changes in Liver Stiffness Measured by Magnetic Resonance Elastography are Associated with Outcomes in Primary Sclerosing Cholangitis

Presenter: John E. Eaton, M.D.

Presentation Type: Poster Presentation
Presentation Date(s)/Time(s):

Friday, November 8: 8:00 am – 5:30 pm; Presenters Available: 12:30 – 1:30pm
Saturday, November 9: 2:00 pm–7:00 pm; Presenters Available: 5:15 – 6:15pm
Sunday, November 10: 8:00 am – 5:30 pm; Presenters Available: 12:30 – 1:30pm
Monday, November 11: 8:00 am – 5:30 pm; Presenters Available: 12:30 – 1:30pm

Location: Hynes Convention Center, Hall B

Financial Support: Chris M. Carlos and Catharine Nicole Jockisch Carlos Endowment Fund in Primary Sclerosing Cholangitis

 

Abstract 2: Therapeutic Targeting of Ductular Reactive Cells in Cholestatic Liver Disease

Presenter: Adiba I. Azad, M.D.

Presentation Type: Oral Presentation
Presentation Date/Time: Monday, November 11th at 5 p.m.

Location: Room 210, Hynes Convention Center

Financial Support: Chris M. Carlos and Catharine Nicole Jockisch Carlos Endowment Fund in Primary Sclerosing Cholangitis

 

Abstract 3: Modulation of the Intestinal Microbiome Alters Disease Progression in Germ Free Rodent Models of Primary Sclerosing Cholangitis

Presenter: Steven P. O’Hara, Ph.D.

Presentation Type: Poster Presentation

Presentation Date(s)/Time(s):

Friday, November 8: 8:00 am – 5:30 pm; Presenters Available: 12:30 – 1:30pm
Saturday, November 9: 2:00 pm–7:00 pm; Presenters Available: 5:15 – 6:15pm
Sunday, November 10: 8:00 am – 5:30 pm; Presenters Available: 12:30 – 1:30pm
Monday, November 11: 8:00 am – 5:30 pm; Presenters Available: 12:30 – 1:30pm

Location: Hynes Convention Center, Hall B

Financial Support: DK57993, DK84567, Chris M. Carlos and Catharine Nicole Jockisch Carlos Endowment Fund in Primary Sclerosing Cholangitis

 

Abstract 4: Bile Acid Profiles Predict Hepatic Decompensation in Primary Sclerosing Cholangitis

Presenter: Omar Y. Mousa, M.B.B.S.

Presentation Type: Oral Presentation
Presentation Date/Time: Monday, November 11th at 10:45 a.m.

Location: Constitution Ballroom, Hynes Convention Center

Financial Support: DK118619, Chris M. Carlos and Catharine Nicole Jockisch Carlos Endowment Fund in Primary Sclerosing Cholangitis, and PSC Partners Seeking A Cure

 

Abstract 5: Transcription Factor, ETS1, Interacts with Histone Acetyl Transferase, p300, Promoting the Anti-Apoptotic Phenotype of Senescent Cholangiocytes via Induced Transcription of the Pro-Survival Gene, BCL2L1

Presenter: Patrick L. Splinter, M.S.

Presentation Type: Oral Presentation
Presentation Date/Time: Sunday, November 10th at 5 p.m.

Location: Room 210, Hynes Convention Center

Financial Support: DK57993 and Chris M. Carlos and Catharine Nicole Jockisch Carlos Endowment Fund in Primary Sclerosing Cholangitis

 

Read the full abstracts from the PSC team here.

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Mon, Jul 29 8:41am · IBD: A Comorbidity of PSC in Primary Sclerosing Cholangitis (PSC)

 

IBD graphic

The majority of patients with the PSC have Inflammatory Bowel Disease (IBD). The association of those two diseases is known for decades, yet the contribution of IBD in the development and outcomes of PSC remain sunclear. Morever, the presence of IBD among patients with PSC affects the medical and surgical management of these patients. Patients with PSC should understand the relationship and  impact of IBD on PSC.

In this presentation, Dr. Laura Raffals, Associate Professor of Medicine, Mayo Clinic College of Medicine provides a comprehensive review of the epidemiology, diagnosis, outcomes and management of IBD among PSC patients.

View the powerpoint presentation from Dr. Raffals

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Mon, Jul 15 10:37am · PSC and Inflammatory Bowel Disease (IBD): Women’s Health Issues in Primary Sclerosing Cholangitis (PSC)

2019-11-07 Woman with IBD

Female patients with the PSC and inflammatory bowel disease (IBD) have unique health and disease issues to deal with.

During the 15th Annual Conference of the “PSC Partners Seeking a Cure”“, Dr. Alina Allen, Assistant Professor of Medicine, Mayo Clinic College of Medicine, and Dr. Laura Raffals, Associate Professor of Medicine, Mayo Clinic College of Medicine, provided an excellent overview of the specific situations (i.e., conception, pregnancy, breastfeeding, etc) that are relevant to women with PSC and IBD and offer management approaches and advice.

View the powerpoint presentation from Dr. Allen and Dr. Raffals.

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Mon, Jul 1 4:13pm · Genes and Environment in PSC in Primary Sclerosing Cholangitis (PSC)

Gene and Environment Pic

On May 21-23, 2019, the 15th Annual Conference of the “PSC Partners Seeking a Cure” took place in Rochester, Minnesota. More than 315 patients and family members attended the meeting. We are honored and grateful that “PSC Partners Seeking a Cure” choose Rochester and Mayo Clinic as their destination for 2019. We are inspired by their mission and efforts. Starting this week and in the upcoming months we will include in our newsfeed section selected presentations of this year’s conference delivered by faculty of Mayo Clinic. A link to the first presentation’s slides, entitled: Genes and Environment in PSC, is provided below.

View the powerpoint presentation from Dr. Lazaridis

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Mon, Jun 3 9:53am · PSC literature elsewhere: Ursodeoxycholic acid therapy in pediatric PSC in Primary Sclerosing Cholangitis (PSC)

2019-05-31 Patient taking medicine

Recently, we have made the decision to include periodically in our PSC blog commentaries of selected clinical studies published by other groups. This tactic aims at keeping the followers of this blog informed about current efforts of the academic community at large to better understand and treat PSC.

In a retrospective study published in the Journal of Pediatrics in June 2019 (see below), Mark Deneau et al., examined the clinical factors predicting normalization of gamma glutamyltransferase (GGT) in children affected by PSC following therapy with ursodeoxycholic acid (UDCA).

In this large study, 344 PSC patients from 46 medical centers were identified with a serum GGT more than 50IU/L at the time of diagnosis who had also repeat testing one year later. Subsequently, 81 patients were excluded because they were not taking UDCA or developed complications of the disease 3 months following the diagnosis. The remaining 263 patients (60% were male with a median age of 12.1 years) were followed for a median of 5.4 years. The median dose of UDCA was 15mg/kg daily. 122 of 263 patients (46%) had normalization of GGT at 1 year. At the time of diagnosis, the group of patients that had favorable biochemical response on UDCA had a lower prevalence of Crohn’s disease, lower total bilirubin, lower aspartate aminotransferase to platelet ratio index, and greater serum albumin level. The presence of small or large duct PSC, or the concurrence of autoimmune hepatitis was not associated with normalization of GGT. The 5-year survival of patients with normalization of UDCA while on UDCA was 99% compared to 77% of patients who did not achieve normalization.

This was a large study from a diverse number of medical centers and the authors should be congratulated for this significant effort. It appears that UDCA normalizes GGT in a number of pediatric patients and these have identifiable clinically relevant factors. The study also suggests that lack of GGT normalization, while on UDCA, should make providers to discontinue therapy although compliance with this drug was unknown. The limitations of the study include its retrospective nature, the fact that it did not account for severity and duration of disease, as well as concurrent immunosuppressive therapy of the patients. In summary, this is an interesting study but we still need better objective biomarkers of PSC severity in order to improve our knowledge on treatment response in PSC patients.

The pdf of the published article can be found here.

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Mon, May 20 11:25am · Efficacy and safety of curcumin in PSC: an open label pilot study in Primary Sclerosing Cholangitis (PSC)

2019-06-04 Curcumin

In this month’s issue of the Scandinavian Journal of Gastroenterology John E. Eaton et al., reports on the results of a 12-week open-label pilot study to examine whether curcumin, a naturally occurring compound, could reduce the markers of cholestasis in patients with PSC. Curcumin is the principal curcuminoid of the rhizome turmeric (Curcuma longa) and is believed to have anti-inflammatory and anti-oxidant effects. Curcumin may function as a free radical scavenger and reduce oxidative damage through several proposed mechanisms. In two separate rodent models of cholestasis curcumin was associated with a reduction in liver enzymes and improvement in hepatic histology.

In this pilot study by John E. Eaton et al., patients with PSC and a serum alkaline phosphatase (SAP) greater than 1.5 x the upper limit of normal (ULN) received curcumin 750 mg orally twice daily for 12 weeks. The primary study endpoint was the proportion of subjects who had a reduction of SAP to less than 1.5 x ULN or a 40% reduction in SAP between baseline and week 12. Secondary study endpoints included changes in serum aspartate aminotransferase, total bilirubin, Mayo PSC risk score and self-reported health questionnaires. The authors screened 258 patients with PSC in order to enroll 15 subjects. The most common reason for subject exclusion was SAP < 1.5 x ULN (n = 98 or 38%). Curcumin did not result in a significant median (interquartile range) change in SAP x ULN [3.43 (2.10–4.32) to 2.46 (1.89–4.41), p = .36] and only 20% (3/15) of subjects achieved the primary study endpoint. There was no significant change in the secondary study endpoints. The authors did not report any serious adverse events among the enrolled patients. In summary, curcumin was well tolerated by the study participants but it was not associated with significant improvement of cholestasis or symptoms.

In this first clinical trial of curcumin among patients with PSC only 20% of the subjects, rather the target of 30%, met the primary study endpoint. Moreover, the study emphasizes that a SAP of <1.5 x ULN is common among patients with PSC. This observation, which highlights the known fluctuation of SAP during the course of PSC, makes this biomarker suboptimal as a tool to predict the progression of disease. Thus, there is an urgent need to discover more reliable biomarkers of PSC in order to better understand the disease progression and ultimately to improve its therapy.

The PDF of the published article can be found here.

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