Search

Background: Peroxisome proliferator-activated receptor (PPAR) agonists are recognised as a promising treatment for primary biliary cholangitis (PBC). However, the effects and safety of these agonists on PBC remain unexplored. Our study aimed to investigate the efficacy and safety of PPAR agonists in treating PBC. Methods: We searched Cochrane Library, and Web of Science, PubMed, and Embase databases from inception to 15 March 2024 for randomised controlled studies (RCTs) that enrolled individuals with PBC treated with PPAR agonists compared with placebo. The primary outcomes were biochemical response and normalization of the alkaline phosphatase (ALP) level. Results: Eight RCTs involving 869 participants in total were included. The metaanalysis revealed that compared to placebo, PPAR agonists increased the rate of biochemical response (RR: 5.53; 95% CI: 3.79, 8.06) and normalization of the ALP level (RR: 17.18; 95% CI: 5.61, 52.61). In addition, PPAR agonists can also reduce alanine aminotransferase (ALT) (MD: -12.69 U/L; 95% CI: -18.03, -7.35), aspartate aminotransferase (AST) (MD: -4.18 U/L; 95% CI: -7.28, -1.08), ALP (MD: -142.95 U/L; 95% CI: -167.29, -118.60), γ-glutamyltransferase (GGT) (MD: -63.03 U/L; 95% CI: -92.08, -33.98), and total cholesterol (TC) levels (SMD: -0.71; 95% CI: -1.38, -0.04), and there was no significant difference in overall adverse reactions (RR: 0.99; 95% CI: 0.92, 1.05), serious adverse reactions (RR: 1.10; 95% CI: 0.70, 1.72) between the two groups. Conclusion: PPAR agonists are safe and well-tolerated in patients with PBC and are effective in improving the rate of biochemical response and related biomarkers. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease characterized by the destruction of the small intrahepatic bile ducts, which can progress to liver cirrhosis. The gold standard in the treatment of PBC is ursodeoxycholic acid (UDCA), which is indicated in all patients with PBC because it improves not only biochemical parameters but also patients' survival. An important milestone in the identification of patients at risk is the assessment of biochemical response to UDCA. Patients who respond to treatment have a lower incidence of hepatic events and better prognosis than patients who do not. Several scoring systems can be used to assess the response and identify non-responders who will benefit from second-line treatment. Obeticholic acid (OCA) is currently the only approved second-line treatment for PBC, which is effective for non-responders to UDCA therapy or patients, who have not tolerated UDCA therapy. However, OCA is contraindicated in advanced liver cirrhosis and portal hypertension. Moreover, pruritus may be a limiting factor for the administration of OCA. Fibrates have shown promising data supporting their use in non-responders to UDCA because they improve the biochemical parameters and elastographic findings and have possible antipruritic effects. Therefore, the idea of a triple treatment seems interesting. Clinical research is focusing on several other groups of drugs: peroxisome proliferator-activated receptor (PPAR) δ- and α/δ agonists, non-steroidal farnesoid X receptor agonists, fibroblast growth factor 19 modulators, and inhibitors of nicotinamide adenine dinucleotide phosphate oxidase 1 and 4. [ABSTRACT FROM AUTHOR]

Background and aimsCurrent treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier.MethodsFive hundred sixty-nine patients with an average of 59 months (Median: 53; IQR:32-79) follow-up periods were randomly divided into either the training (70%) or the validation cohort (30%). The efficiency of different combinations of total bilirubin (TBIL), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcomes was assessed at 1, 3 or 6 month after the initiation of UDCA therapy. The endpoints were defined as adverse outcomes, including liver-related death, liver transplantation and complications of cirrhosis. Adverse outcome-free survival was compared using various published criteria and a proposed new criterion.ResultsA new criterion of evaluating UDCA responses at 1 month was established as: ALP ≤ 2.5 × upper limit of normal (ULN) and AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi'an criterion). The 5 year adverse outcome-free survival rate of UDCA responders, defined by Xi'an criterion, was 97%, which was significantly higher than that of those non-responders (64%). An accurate distinguishing high-risk patients' capacity of Xi'an criterion was confirmed in both early and late-stage PBC.ConclusionsXi'an criterion has a similar or even higher ability to distinguish high-risk PBC patients than other published criteria. Xi'an criterion can facilitate early identification of patients requiring new therapeutic approaches.

Objective To investigate the value of baseline red cell distribution width (RDW) and alkaline phosphatase (ALP) level after ursodeoxycholic acid (UDCA) treatment for one month in predicting the response to UDCA treatment in patients with primary biliary cholangitis (PBC) . Methods A retrospective analysis was performed for the data of 127 patients with PBC who were diagnosed in Department of Hepatology, The Third People’s Hospital of Jiangsu University, from January 2015 to July 2022, with data collected at baseline, after one month of treatment, and after one year of follow-up. Based on the Paris-I criteria, the patients were divided into good response group and poor response group, and the two groups were analyzed in terms of clinical and laboratory features and their association with response to UDCA. The Logistic regression method was used to investigate the independent risk factors for response to UDCA treatment. The area under the ROC curve (AUC) was used to determine the optimal cut-off values of related indicators； the patients were divided into two groups based on such values, and the two groups were compared in terms of baseline indicators and response. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Results Compared with the good response group, the poor response group had significantly higher levels of total bilirubin, aspartate aminotransferase/alanine aminotransferase, ALP, RDW, and RDW-CV at baseline and a significantly higher level of ALP after one month of UDCA treatment (Z=−4.792, −3.697, −2.399, −4.102, −3.220, and −4.236, all P<0.05) . Compared with the good response group, the poor response group had significantly lower levels of albumin, hemoglobin, lymphocytes, hematocrit, and body mass index at baseline (Z=−3.592, −3.603, −2.602, −3.829, −2.432, all P<0.05), as well as significantly lower levels of prealbumin, albumin/ globulin ratio, apolipoprotein A, and free triiodothyronine at baseline (t=4.530, 3.402, 3.485, and 3.639, all P<0.001) . Compared with the poor response group, the good response group had a significantly lower proportion of patients with liver cirrhosis, gallstones/cholecystitis, or anemia (χ² =20.815, 3.892, and 12.283, all P<0.05) . Baseline RDW (odds ratio ［OR］= 1.157, 95% confidence interval ［CI］：1.028—1.301, P=0.015) and ALP level after one month of treatment (OR=1.012, 95%CI： 1.005—1.020, P=0.002) were independent risk factors for response to UDCA, with an AUC of 0.713 and 0.720, respectively. The patients with baseline RDW≥upper limit of normal (ULN) and ALP≥2.2×ULN after one month of UDCA treatment had a lower UDCA response rate (42.6% vs 8.2%, χ² =20.813, P<0.001) . Conclusion Patients with baseline RDW≥ULN and ALP≥2.2× ULN after one month of UDCA treatment tend to have a low biochemical response rate to UDCA. [ABSTRACT FROM AUTHOR]

Aims: Ursodeoxycholic acid is the first‐line treatment for primary biliary cholangitis, and treatment response is one of the factors predicting the outcome. To prescribe alternative therapies, clinicians might need additional information before deciphering the treatment response to ursodeoxycholic acid, contributing to a better patient prognosis. In this study, we developed and validated machine learning (ML) algorithms to predict treatment responses using pretreatment data. Methods: This multicenter cohort study included collecting datasets from two data samples. Data 1 included 245 patients from 18 hospitals for ML development, and was divided into (i) training and (ii) development sets. Data 2 (iii: test set) included 51 patients from our hospital for validation. An extreme gradient boosted tree predicted the treatment response in the ML model. The area under the curve was used to evaluate the efficacy of the algorithm. Results: Data 1 showed that patients complying with the Paris II treatment response had significantly lower serum alkaline phosphatase and total bilirubin levels than those who did not respond. Three factors, total bilirubin, total protein, and alanine aminotransferase levels were selected as essential variables for prediction. Data 2 showed that patients complying with the Paris II criteria had significantly high prothrombin time and low total bilirubin levels. The area under the curve of extreme gradient boosted tree was good for (ii) (0.811) and (iii) (0.856). Conclusions: We demonstrated the efficacy of ML in predicting the treatment response for patients with primary biliary cholangitis. Early identification of cases requiring additional treatment with our novel ML model may improve prognosis. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Primary biliary cholangitis (PBC) is often overlapping with other autoimmune conditions, including systemic lupus erythematosus (SLE). Since the concomitant PBC and SLE are rare, the impacts of SLE on the response and prognosis in ursodeoxycholic acid (UDCA)–treated patients with PBC remain unclear. Methods: A PBC database of 769 patients at West China hospital was used to identify 26 patients with concomitant PBC and SLE. The clinical and biochemical characteristics of these patients were collected and analyzed. Propensity score matching was used to compensate for the differences in age, total bilirubin, and alkaline phosphatase. The biochemical responses and prognoses were compared between the patients with and without concomitant SLE. Results: The female-to-male ratio was 25:1 in the PBC patients with concomitant SLE. Compared with the group with PBC alone, the median hemoglobin and albumin values in the PBC-SLE group at the time of diagnosis of PBC were lower (both P < 0.05). After treatment, the group with PBC alone showed lower alanine aminotransferase and glutamyltransferase values and aspartate aminotransferase/platelet ratio indices at the final visit (all P < 0.05). The Kaplan-Meier estimate showed that the adverse event–free survival did not differ between the patients with and without concomitant SLE (P = 0.564). Conclusion: The results of this retrospective, single-center study suggested that the concomitant SLE status might have a negative impact on the biochemical responses to the treatment, while the effect of concomitant SLE on PBC progression remains to be further defined. Key Points • The prevalence of SLE in the PBC population being in a large PBC cohort was as low as 3.4%. • Compared with PBC-SLE group, the group with PBC alone showed lower alanine aminotransferase and glutamyltransferase values and aspartate aminotransferase/platelet ratio indices at the final visit, indicating that the concomitant SLE may have a negative impact on the biochemical responses to the treatment of PBC. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis(PBC) is an immune-mediated chronic and progressive intrahepatic cholestasis disease. Treatment with ursodeoxycholic acid(UDCA) can significantly improve the prognosis of patients with PBC, but some patients still have poor response to UDCA, which is the main risk factor for disease progression. Several evaluation models and scoring systems based on biochemical response have been applied to screen out patients with poor response in clinical practice. Integrated traditional Chinese and Western medicine therapy for PBC has certain advantages in improving the symptoms, liver biochemistry, fibrosis indices, and biochemical response rate of PBC patients and thus holds promise for clinical application; however, further improvement is needed for experimental design and efficacy evaluation. [ABSTRACT FROM AUTHOR]

Objective: To assess the proportion of PBC patients with a biochemical response to ursodeoxycholic acid (UDCA) in a population-based cohort and the association of biochemical response with outcomes. Methods: All patients diagnosed with PBC in Iceland from 1991–2015 were identified. Patients taking UDCA for an adequate period of time were analyzed for treatment response according to the Barcelona, Paris I, Paris II and Toronto criteria and outcomes. Results: Overall 182 females and 40 males were diagnosed with PBC and 135 patients were treated with UDCA. Overall 99 (73%) patients had adequate data on UDCA treatment and results of liver tests to assess biochemical response according to the Barcelona criteria, 95 (70%) according to the Toronto criterion and 85 (63%) according to the Paris I and II criteria. In all 74% (n = 63), 67% (n = 64), 54% (n = 53) and 46% (n = 39) responded to treatment according to the Paris I, Toronto, Barcelona and Paris II criteria. Among nonresponders according to the Paris I, Toronto, Paris II and Barcelona criteria, 50%, 39%, 33% and 30% developed cirrhosis versus 10%, 6%, 5% and 11% of responders, HR 5.36 (p =.002), 6.61 (p =.002), 10.94 (p =.003) and 2.21(p =.11), respectively. Age-adjusted mortality was significantly lower among responders according to the Paris I and Paris II criteria, HR 0.33 (p =.02) and 0.31 (p =.02), respectively. Conclusion: Development of cirrhosis and higher mortality was significantly associated with a lack of biochemical response to UDCA. Frequent development of cirrhosis and increased mortality in nonresponders underlines the need for a more effective therapy than UDCA for this sizeable subgroup of patients. [ABSTRACT FROM AUTHOR]

Non-invasive predictors for the development of cirrhosis-related conditions are needed for patients with primary biliary cholangitis (PBC). We investigated the association between cytokeratin-18 fragments (M30 and M65) and liver histology, treatment response and the development of cirrhosis-related conditions in patients with PBC. We retrospectively reviewed the clinical data of 111 individuals with biopsy-proven PBC. Serum M30 and M65 levels were measured using stored sera. M30 were significantly decreased after treatment, but there was no significant change in the M65 levels. M65 was significantly higher in non-responders according to the Paris-I and Paris-II definitions. In the multivariate analysis, high levels of M65 were significantly associated with advanced Scheuer stage (odds ratio 5.86; 95% confidence interval 0.55-22.2; P = 0.009) and with the development of cirrhosis-related conditions (hazard ratio 3.94; 95% confidence interval: 1.06-14.5, P = 0.039). Among PBC patients without cirrhosis, those with high serum M65 levels at baseline were at higher risk of developing cirrhosis-related conditions (log-rank test; P = 0.001). High levels of serum M65 may be a non-invasive and early predictor of the development of cirrhosis-related conditions in PBC patients. Our findings may help initiate therapies earlier for those at risk for cirrhosis. [ABSTRACT FROM AUTHOR]