Biochemical response to ursodeoxycholic acid among PBC patients: a nationwide population-based study

Örnolfsson, Kristjan T.; Lund, Sigrún H.; Ólafsson, Sigurđur; Bergmann, Ottar M.; Bjõrnsson, Einar

doi:10.1080/00365521.2019.1606931

Cited by 22 publications

(17 citation statements)

References 26 publications

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“…Furthermore, a potential selection bias cannot be excluded, as all patients were recruited from two independent tertiary care centers and a selection of more severe cases did probably occur, which likely explains the increased proportion of patients with end‐stage liver disease and the decreased proportion of patients responding adequately to UDCA treatment at 12 months after the initiation of therapy. However, the UDCA response rates in our PBC cohort were in line with previous observations in comparable selected and unselected PBC cohorts, which have recently been summarized . Previous genome‐wide association studies did not show a major role of CHRM3 in PBC or PSC, suggesting that the impact of CHRM3 polymorphisms might be rather limited in these diseases.…”

Section: Discussionsupporting

confidence: 91%

Evaluation of muscarinic acetylcholine receptor type 3 gene polymorphisms in patients with primary biliary cholangitis and primary sclerosing cholangitis

Greverath

Leicht

Chamorro

et al. 2019

Hepatology Research

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Aim Muscarinic acetylcholine receptor type 3‐mediated signaling might be involved in the pathogenesis of chronic inflammatory biliary diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). The aim of the present study was to investigate the prevalence of five well‐characterized specific single‐nucleotide polymorphisms within the muscarinic acetylcholine receptor type 3 gene, CHRM3 (rs11578320, rs6690809, rs6429157, rs7548522, and rs4620530), in patients with PBC and PSC. Patients with chronic hepatitis C (CHC) and healthy individuals served as control cohorts. In the PBC cohort, baseline characteristics and response to ursodeoxycholic acid therapy applying established response criteria at 12 months after the initiation of treatment were evaluated according to the underlying CHRM3 genotype. Methods CHRM3 genotyping was carried out in 306 PBC patients, 205 PSC patients, 208 CHC patients, and 240 healthy controls from two independent German tertiary care university centers in Berlin and Leipzig, Germany. Results CHRM3 rs4620530 proportions in patients with PBC significantly differed from patients with PSC (P = 0.005), CHC (P = 0.009), and healthy controls (P = 0.008), primarily due to a substantial overrepresentation of the T allele in PBC (49.3% in PBC vs. 39.8% in PSC, 35.7% in CHC, and 40% in healthy controls), indicating a potential association of the rs4620530 T allele with PBC (OR 1.461, 95% CI 1.147–1.861, P = 0.002). Further analysis showed no association of CHRM3 single‐nucleotide polymorphism rs4620530 with baseline characteristics and ursodeoxycholic acid treatment response in PBC. Conclusion CHRM3 single‐nucleotide polymorphism rs4620530 might confer an increased genetic risk for the development of PBC.

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Section: Discussionsupporting

confidence: 91%

Evaluation of muscarinic acetylcholine receptor type 3 gene polymorphisms in patients with primary biliary cholangitis and primary sclerosing cholangitis

Greverath

Leicht

Chamorro

et al. 2019

Hepatology Research

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“…PBC, primary biliary cholangitis. and a 3-fold increase in age-adjusted mortality (40). At this time, clinicians are encouraged to use 2 liver biochemistries as the anchor for clinical judgment when determining candidates for second-line therapy in PBC: ALP and bilirubin levels (5,41,42).…”

Section: Definition Of An Inadequate Biochemical Response To Udcamentioning

confidence: 99%

“…Response to UDCA has historically been assessed after 12 months of treatment according to various binary response criteria and quantitative prognostic scores. Lack of biochemical response is reported in 25%–50% of treated patients ( 39 ) and has been associated with a >5-fold increase in risk of progression to cirrhosis and a 3-fold increase in age-adjusted mortality ( 40 ). At this time, clinicians are encouraged to use 2 liver biochemistries as the anchor for clinical judgment when determining candidates for second-line therapy in PBC: ALP and bilirubin levels ( 5 , 41 , 42 ).…”

Section: Clinical Implications Of New Data On the Management Of Pbcmentioning

confidence: 99%

Application of the Latest Advances in Evidence-Based Medicine in Primary Biliary Cholangitis

et al. 2022

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Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune liver disease that can progress to end-stage liver disease and its complications. A previous expert review panel collaborated on a consensus document for gastroenterologists and other healthcare professionals regarding the care of patients with PBC. Subsequently, there have been several recent important developments in the diagnosis, treatment, and monitoring of patients with PBC. These include updates to prognostic models on risk stratification, new noninvasive tools for staging of disease, updates to the appropriate use of and long-term treatment results with obeticholic acid as a second-line treatment, the emerging therapeutic role of fibrates, and the advancement of investigational agents for managing PBC. In this updated expert consensus document, we provide updates on staging, the use of noninvasive prognostic tools, and a treatment algorithm to provide evidence-based and practical tools for clinicians who manage PBC, with the ultimate goal to improve the long-term outcomes for patients with this chronic liver disease.

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“…Patients who achieve treatment response to UDCA therapy in the early stage of the disease have survival rates comparable with the general population [ 9 ], and a relatively modest improvement in overall survival is related to a proportion of patients who fail to achieve treatment response. Based on the published data, treatment response is achieved in 46%–74% of all treated patients [ 10 ]. Notably, despite its suboptimal efficacy, UDCA remains the first-line treatment option for PBC.…”

Section: Introductionmentioning

confidence: 99%

External Validation of UDCA Response Score in Slovak and Croatian Patients with Primary Biliary Cholangitis

Gazda

Janíčko

Dražilová

et al. 2021

Canadian Journal of Gastroenterology and Hepatology

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Background. Ursodeoxycholic acid response score (URS) is a prognostic model that estimates the baseline probability of treatment response after 12 months of ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cholangitis (PBC). Aim. To independently evaluate the predictive performance of the URS model. Methods. We used a cohort of Slovak and Croatian treatment-naïve PBC patients to quantify the discrimination ability using the area under receiver operating characteristic curve (AUROC) and its 95% confidence interval (CI). Furthermore, we evaluated the calibration using calibration belts. The primary outcome was treatment response after 12 months of UDCA therapy defined as values of alkaline phosphatase ≤1.67 × upper limit of normal. Results. One hundred and ninety-four patients were included. Median pretreatment age was 56 years (interquartile range 49–62). Treatment response was achieved in 79.38% of patients. AUROC of the URS was 0.81 (95% CI 0.73–0.88) and the calibration belt revealed that response rates were correctly estimated by predicted probabilities. Conclusion. Our results confirm that the URS can be used in treatment-naïve PBC patients for estimating the treatment response probability after 12 months of UDCA therapy.

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Biochemical response to ursodeoxycholic acid among PBC patients: a nationwide population-based study

Cited by 22 publications

References 26 publications

Evaluation of muscarinic acetylcholine receptor type 3 gene polymorphisms in patients with primary biliary cholangitis and primary sclerosing cholangitis

Evaluation of muscarinic acetylcholine receptor type 3 gene polymorphisms in patients with primary biliary cholangitis and primary sclerosing cholangitis

Application of the Latest Advances in Evidence-Based Medicine in Primary Biliary Cholangitis

External Validation of UDCA Response Score in Slovak and Croatian Patients with Primary Biliary Cholangitis

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