Effects of Age and Sex of Response to Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary Biliary Cholangitis

Cheung, Angela; Lammers, Wim J. E. P.; Perez, Carla Fiorella Murillo; Buuren, Henk R. van; Gulamhusein, Aliya; Trivedi, Palak; Lazaridis, Konstantinos N.; Ponsioen, Cyriel Y.; Floreani, Annarosa; Hirschfield, Gideon; Corpechot, Christophe; Mayo, Marlyn J.; Invernizzi, Pietro; Battezzati, Pier Maria; Parés, Albert; Nevens, Frederik; Thorburn, Douglas; Mason, Andrew L.; Carbone, Marco; Kowdley, Kris V.; Bruns, Tony; Dalekos, George Ν.; Gatselis, Nikolaos; Verhelst, Xavier; Lindor, Keith D.; Lleo, Ana; Poupon, Raoul; Janssen, Harry L.A.; Hansen, Bettina E.

doi:10.1016/j.cgh.2018.12.028

Cited by 63 publications

(57 citation statements)

References 24 publications

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“…All these patients were deemed at risk of disease progression on the basis of presence of cirrhosis or young age at diagnosis, both of which have been robustly demonstrated to be associated with poor outcomes in PBC. ( 5,11‐13 ) . This highlights that risk in PBC is multifactorial and relates to biochemical response to UDCA in part but also to age and fibrosis stage.…”

Section: Discussionmentioning

confidence: 99%

Real‐World Effectiveness of Obeticholic Acid in Patients with Primary Biliary Cholangitis

et al. 2020

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Patients with primary biliary cholangitis (PBC) with incomplete response to ursodeoxycholic acid are at risk of disease progression and need additional therapy. Obeticholic acid (OCA) was approved in Canada in May 2017, but its effectiveness in a real‐world setting has not been described. We sought to describe our experience with OCA in a Canadian cohort. OCA‐naive patients treated at two Canadian centers were included. Clinical and biochemical data were collected at OCA initiation and during follow‐up. Primary outcomes were changes in serum alkaline phosphatase (ALP), gamma‐glutamyl transferase (GGT), and total bilirubin (TB) over the duration of therapy. Secondary outcomes were changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), immunoglobulin M (IgM), platelets, and albumin; and achievement of the primary endpoint of the original phase 3 study that led to OCA approval (A Placebo‐Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis [POISE]), dose reductions, discontinuations, and tolerability. Repeated‐measures models were used to assess changes in biochemistry over time. Sixty‐four patients were included; 4 carried a diagnosis of overlap with autoimmune hepatitis. Mean age was 54.6 years, median ALP was 250 U/L, TB was 13 µmol/L, platelet count was 225 × 109/L, and 24% had liver stiffness measurements ≥16.9 kPa. There was a significant reduction in mean ALP of 55 U/L (P < 0.001), GGT of 138 U/L (P < 0.001), ALT of 11.9 U/L (P < 0.001), AST of 5.7 U/L (P < 0.05), and IgM of 0.70 g/L (P < 0.001) over 12 months; TB remained stable (P = 0.98). Forty‐four patients met POISE‐inclusion criteria, 39% (n = 17) of whom had 12‐month biochemical measurements. In this subset, 18% (n = 3/17) met the 12‐month POISE primary endpoint, but considering follow‐up to 19 months, 43% achieved this target (n = 9/21). Pruritus was the most commonly reported complaint. Conclusion: Use of OCA was associated with improvement in biochemical surrogates of outcome in PBC in a real‐world setting.

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Section: Discussionmentioning

confidence: 99%

Real‐World Effectiveness of Obeticholic Acid in Patients with Primary Biliary Cholangitis

et al. 2020

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“…A more severe disease course in young patients affected by primary biliary cholangitis (PBC) has been recently confirmed in a large retrospective study, showing increased risk of treatment failure, liver transplantation, and death. 26 In primary sclerosing cholangitis (PSC), older age at diagnosis was strongly associated with increased risk of cholangiocarcinoma (21% patient-years for patients older than 60 years). 27 Finally, important considerations have been recently raised also for liver transplantation in elderly patients, given organ shortage and a possible increased risk of complications in these categories of patients.…”

Section: Influence Of Aging In Hepatobiliary Diseasesmentioning

confidence: 99%

Aging and the Biological Response to Liver Injury

et al. 2019

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Interest in understanding the aging process has recently risen in the scientific community. Aging, commonly defined as the functional decline in the function of organs and tissues, is indeed the major risk factor for the development of many chronic diseases, such as cardiovascular diseases, pathologies of nervous system, or cancer. To date, the influence of aging in the pathophysiology of liver and biliary diseases is not fully understood. Although liver cells have a high regenerative capacity, hepatocytes and cholangiocytes undergo extensive molecular changes in response to aging. Following time-dependent damage induced by aging, liver cells initially activate compensatory mechanisms that, if hyperstimulated, may lead to the decline of regenerative capacity and the development of pathologies. A deeper understanding of molecular aging has undoubtedly the potential to improve the clinical management of patients, possibly unveiling new pathways for selective drug treatment.

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“…Cholestatic liver diseases are profoundly influenced by patient age. A more severe disease course in young patients affected PBC has been recently observed in a large retrospective study, showing increased risk of treatment failure, liver transplantation and death (80). In PSC, the age at diagnosis increase the risk of develop cholangiocarcinoma (21% for patients older than 60 years) (81).…”

Section: Cholangiocytes and Cholangiopathies: Focus On Psc And Pbcmentioning

confidence: 89%

Aging-Related Molecular Pathways in Chronic Cholestatic Conditions

et al. 2020

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Aging is commonly defined as the time-dependent functional decline of organs and tissues. Average life expectancy has increased considerably over the past century and is estimated to increase even further, consequently also the interest in understanding the aging processes. Although aging is not a disease, it is the major risk factor for the development of many chronic diseases. Pathologies, such as Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC) are cholestatic liver diseases characterized by chronic inflammation, biliary damage and ultimately liver fibrosis, targeting specifically cholangiocytes. To date, the influence of aging in these biliary diseases is not fully understood. Currently, liver transplantation is the only solution because of lacking in efficiently therapies. Although liver cells have a high regenerative capacity, they undergo extensive molecular changes in response to aging. Following time-dependent damage induced by aging, the cells initially activate protective compensatory processes that, if hyperstimulated, can lead to the decline of regenerative ability and the development of pathologies. Recent studies have introduced novel therapeutic tools for cholangiopathies that have showed to have promising potential as novel therapies for PSC and PBC and for the development of new drugs. The recent advancements in understanding of molecular aging have undoubtedly the potential to unveil new pathways for selective drug treatments, but further studies are needed to deepen their knowledge.

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Effects of Age and Sex of Response to Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary Biliary Cholangitis

Abstract: had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of data analyses.Study concept and design: All authors.

Cited by 63 publications

References 24 publications

Real‐World Effectiveness of Obeticholic Acid in Patients with Primary Biliary Cholangitis

Real‐World Effectiveness of Obeticholic Acid in Patients with Primary Biliary Cholangitis

Aging and the Biological Response to Liver Injury

Aging-Related Molecular Pathways in Chronic Cholestatic Conditions

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