Predicting outcome in primary biliary cirrhosis

Lammers, Willem J; Kowdley, Kris V.; Buuren, Henk R. van

doi:10.1016/s1665-2681(19)30838-5

Cited by 47 publications

(45 citation statements)

References 88 publications

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“…Understanding the behavior of ALP as a biomarker in PSC is of interest, and parallels interest in PBC. In PBC, dichotomous risk scores have C statistics of approximately 0.6, with the dynamic scores reporting C statistics of 0.8 and above . Although in PSC, the serum ALP was not associated with short‐term outcome, the prognostic importance as a longer‐term predictor of clinical events is highlighted by its inclusion in our long‐term risk score.…”

Section: Discussionmentioning

confidence: 88%

Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis and Development and Validation of a Risk Scoring System

Goode¹,

Clark²,

Mells³

et al. 2019

Hepatology

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We sought to identify factors that are predictive of liver transplantation or death in patients with primary sclerosing cholangitis (PSC), and to develop and validate a contemporaneous risk score for use in a real‐world clinical setting. Analyzing data from 1,001 patients recruited to the UK‐PSC research cohort, we evaluated clinical variables for their association with 2‐year and 10‐year outcome through Cox‐proportional hazards and C‐statistic analyses. We generated risk scores for short‐term and long‐term outcome prediction, validating their use in two independent cohorts totaling 451 patients. Thirty‐six percent of the derivation cohort were transplanted or died over a cumulative follow‐up of 7,904 years. Serum alkaline phosphatase of at least 2.4 × upper limit of normal at 1 year after diagnosis was predictive of 10‐year outcome (hazard ratio [HR] = 3.05; C = 0.63; median transplant‐free survival 63 versus 108 months; P < 0.0001), as was the presence of extrahepatic biliary disease (HR = 1.45; P = 0.01). We developed two risk scoring systems based on age, values of bilirubin, alkaline phosphatase, albumin, platelets, presence of extrahepatic biliary disease, and variceal hemorrhage, which predicted 2‐year and 10‐year outcomes with good discrimination (C statistic = 0.81 and 0.80, respectively). Both UK‐PSC risk scores were well‐validated in our external cohort and outperformed the Mayo Clinic and aspartate aminotransferase‐to‐platelet ratio index (APRI) scores (C statistic = 0.75 and 0.63, respectively). Although heterozygosity for the previously validated human leukocyte antigen (HLA)‐DR*03:01 risk allele predicted increased risk of adverse outcome (HR = 1.33; P = 0.001), its addition did not improve the predictive accuracy of the UK‐PSC risk scores. Conclusion: Our analyses, based on a detailed clinical evaluation of a large representative cohort of participants with PSC, furthers our understanding of clinical risk markers and reports the development and validation of a real‐world scoring system to identify those patients most likely to die or require liver transplantation.

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Section: Discussionmentioning

confidence: 88%

Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis and Development and Validation of a Risk Scoring System

Goode¹,

Clark²,

Mells³

et al. 2019

Hepatology

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“…The secondary outcome was appearance of cirrhosis‐related symptoms and liver‐related events and overall survival. The severity or prognosis of PBC was evaluated using proposed scoring systems, namely, the UK‐PBC‐risk score for development of liver failure requiring liver transplantation and the GLOBE scores for the estimated transplant‐free survival …”

Section: Methodsmentioning

confidence: 99%

“…The severity or prognosis of PBC was evaluated using proposed scoring systems, namely, the UK-PBC-risk score for development of liver failure requiring liver transplantation and the GLOBE scores for the estimated transplant-free survival. 14,[25][26][27] Statistical analyses. Continuous variables are presented as mean ± SD, and categorical variables are presented as numbers and percentages.…”

Section: Methodsmentioning

confidence: 99%

IgM response is a prognostic biomarker of primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate

Takano

Saeki

Oikawa

et al. 2019

J of Gastro and Hepatol

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Background and Aim Primary biliary cholangitis (PBC) patients who are refractory to ursodeoxycholic acid (UDCA) are at risk for progression to cirrhosis and liver failure. Bezafibrate could be an alternative second‐line therapeutic option in these patients. This study aimed to evaluate the long‐term outcome(s) of combined UDCA and bezafibrate therapy in UDCA‐refractory PBC patients and identify prognostic factors. Methods Among 445 patients treated with UDCA, 150 patients inadequately responded to UDCA monotherapy and received long‐term UDCA plus bezafibrate (median, 15 years). Data from these patients were used for this retrospective analysis. Results Combination therapy resulted in significant improvements in serum biochemistry and liver transplantation risk estimated using the UK‐PBC‐risk and the GLOBE scores. The cumulative normalization rates of alkaline phosphatase, gamma‐glutamyltransferase, and immunoglobulin M (IgM) were significantly higher in patients without cirrhosis‐related symptoms or liver‐related events than in those with them. Overall, IgM constantly emerged as a significant factor associated with cirrhosis‐related symptoms and liver‐related events at all time points. Cumulative survival rates were significantly lower in patients with IgM ≥ 240 mg/dL than in patients with IgM < 240 mg/dL. Thus, normalization of IgM levels was a good surrogate predictor of long‐term prognosis. None of the patients discontinued combination therapy due to any adverse events during the follow‐up period. Conclusions Our findings point to the beneficial effects of long‐term UDCA plus bezafibrate combination therapy for UDCA‐refractory PBC patients, and IgM response can be a useful predictive biomarker of long‐term clinical outcomes.

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“…Currently, the drugs used to treat ICH are very limited, and ursodeoxycholic acid (UDCA) is a drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of cholestasis. Nevertheless, the curative effects of UDCA are far from satisfactory, the complete response of some patients is not good and the clinical application of UDCA in infants is narrow due to the limited indications for the disease spectrum (Lammers et al, 2014). Despite the unclear pathogenesis of ICH, regardless of the aetiology, the outcomes of ICH are liver cirrhosis or liver failure if there are no effective treatments (Li et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Li-Dan-He-Ji Improves Infantile Cholestasis Hepatopathy Through Inhibiting Calcium-Sensing Receptor-Mediated Hepatocyte Apoptosis

et al. 2020

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in the intracellular calcium concentration ([Ca 2+ ] i ) and ROS levels and attenuated the dissipation of the mitochondria membrane potential in the TCDC-induced primary hepatocytes. The opposite results were obtained from the TCDC-induced primary hepatocytes treated with an agonist of CaSR (GdCl 3 ) plus forsythoside-A, emodin or chlorogenic acid. Based on the results from in vivo and in vitro studies, LDHJ functions as an antagonist of CaSR to regulate hepatocyte apoptosis in cholestasis through the mitochondrial pathway and mitogen-activated protein kinase pathway.

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Predicting outcome in primary biliary cirrhosis

Cited by 47 publications

References 88 publications

Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis and Development and Validation of a Risk Scoring System

Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis and Development and Validation of a Risk Scoring System

IgM response is a prognostic biomarker of primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate

Li-Dan-He-Ji Improves Infantile Cholestasis Hepatopathy Through Inhibiting Calcium-Sensing Receptor-Mediated Hepatocyte Apoptosis

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