Treatment of primary biliary cirrhosis: Is there more to offer than ursodeoxycholic acid?
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ABSTRACT:
SUBMITTER: Pares A
PROVIDER: S-EPMC6567861 | biostudies-literature | 2014 Feb
REPOSITORIES: biostudies-literature
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Treatment of primary biliary cirrhosis: Is there more to offer than ursodeoxycholic acid?
Clinical liver disease 20140201 2
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Project description:Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. We have previously reported that augmented expression of lysosome-associated membrane protein 2 (LAMP-2) was correlated with the severity of PBC. This study aimed to determine whether serum LAMP-2 could serve as a predictor of biochemical response to UDCA. The efficiency of serum LAMP-2 to predict biochemical response was assessed after 1 year of UDCA treatment in PBC patients by a retrospective analysis. We found that the basal serum LAMP-2 level was increased in PBC, especially in patients with stage III-IV (p = 0.010) or TBIL > 1 mg/dL (p = 0.014). Baseline serum LAMP-2 was higher in non-responders than that in responders, but the difference was statistically insignificant. However, after UDCA treatment, serum LAMP-2 level decreased prominently in the first 3 months, which was more obvious in responders. Further studies showed that the 35% decline of LAMP-2 after treatment for 3 months could be stated as an indicator of UDCA response with the sensitivity of 62.9% and specificity of 75.0% by Paris criteria. Meanwhile the specificity and sensitivity were identified as 63.5% and 64.1% by Barcelona criteria. Together, a decline in LAMP-2 might help to predict the response to UDCA.
| S-EPMC4403591 | biostudies-other
Project description:IntroductionPatients with cirrhosis and men have been under-represented in most studies examining the clinical benefit of response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC). The aim of this study was to study the association of UDCA response and liver-related death or transplantation, hepatic decompensation, and hepatocellular carcinoma (HCC) in patients with PBC cirrhosis.MethodsWe conducted a retrospective cohort study of veterans, predominantly men, with PBC and compensated cirrhosis to assess the association of UDCA response with the development of all-cause and liver-related mortality or transplantation, hepatic decompensation, and HCC using competing risk time-updating Cox proportional hazards models.ResultsWe identified 501 subjects with PBC and compensated cirrhosis, including 287 UDCA responders (1,692.8 patient-years [PY] of follow-up) and 214 partial responders (838.9 PY of follow-up). The unadjusted rates of hepatic decompensation (3.8 vs 7.9 per 100 PY, P < 0.0001) and liver-related death or transplantation (3.7 vs 6.2 per 100 PY, P < 0.0001) were lower in UDCA responders compared with partial responders. UDCA response was associated with a lower risk of hepatic decompensation (subhazard ratio [sHR] 0.54, 95% confidence interval [CI] 0.31-0.95, P = 0.03), death from any cause or transplantation (adjusted hazard ratio 0.49, 95% CI 0.33-0.72, P = 0.0002), and liver-related death or transplantation (sHR 0.40, 95% CI 0.24-0.67, P = 0.0004), but not HCC (sHR 0.39, 95% CI 0.60-2.55, P = 0.32). In a sensitivity analysis, the presence of portal hypertension was associated with the highest UDCA-associated effect.DiscussionUDCA response is associated with a reduction in decompensation, all-cause, and liver-related death or transplantation in a cohort of predominantly male patients with cirrhosis, with the highest benefit in patients with portal hypertension.
| S-EPMC8410631 | biostudies-literature
Project description:A systems model was developed to describe the metabolism and disposition of ursodeoxycholic acid (UDCA) and its conjugates in healthy subjects based on pharmacokinetic (PK) data from published studies in order to study the distribution of oral UDCA and potential interactions influencing therapeutic effects upon interruption of its enterohepatic recirculation. The base model was empirically adapted to patients with primary biliary cirrhosis (PBC) based on current understanding of disease pathophysiology and clinical measurements. Simulations were performed for patients with PBC under two competing hypotheses: one for inhibition of ileal absorption of both UDCA and conjugates and the other only of conjugates. The simulations predicted distinctly different bile acid distribution patterns in plasma and bile. The UDCA model adapted to patients with PBC provides a platform to investigate a complex therapeutic drug interaction among UDCA, UDCA conjugates, and inhibition of ileal bile acid transport in this rare disease population.
| S-EPMC4999605 | biostudies-literature
Project description:ObjectiveUrsodeoxycholic acid is the priority drug of primary biliary cirrhosis (PBC) and is usually combined with traditional Chinese medicine. This study aimed to systematically evaluate the benefits of integrated Chinese and western interventions for PBC.MethodsSearched the randomized controlled trials in PubMed, Web of Science, CNKI, CBM, Wanfang, VIP databases. The Cochrane risk of bias tool was used for methodological quality assessment and all data analysis was performed using Revman5.3 and Stata14.2 software.Result30 randomized controlled trials involving 10 interventions with a total of 1948 participants were included. Identified the direct and indirect evidence of trials, and used network meta analyses ranked the benefits of different interventions based on pairwise meta analysis. The primary outcom was clinical efficacy rate. Secondary outcome was liver function, including alkaline phosphataseand total bilirubin.ConclusionThe conclusion of this systematic review provide credible evidence - based for the relative advantages of integrated Chinese and western interventions for PBC.
| S-EPMC7668450 | biostudies-literature
Project description:BackgroundPrimary biliary cirrhosis (PBC) is a chronic and progressive cholestasis liver disease. Bile salt export pump (BSEP) is the predominant bile salt efflux system of hepatocytes. BSEP gene has been attached great importance in the susceptibility of PBC and the response rate of ursodeoxycholic acid (UDCA) treatment of PBC patients.MethodsIn this study, TaqMan assay was used to genotype four variants of BSEP, and the Barcelona criteria were used for evaluating the response rate of UDCA treatment.ResultsVariant A allele of BSEP rs473351 (dominant model, OR = 2.063; 95% CI, 1.254-3.393; P = 0.004) was highly associated with PBC susceptibility. On the contrary, variant A allele of BSEP rs2287618 (dominant model, OR = 0.617; 95% CI, 0.411-0.928; P = 0.020) provided a protective role and Barcelona evaluation criterion indicated that the frequency of variant allele at BSEP rs2287618 was significantly decreased in UDCA-responsive PBC patients (P = 0.021).ConclusionThese results suggested that BSEP rs473351 was closely associated with the susceptibility of PBC and if people with BSEP rs2287618 were diagnosed as PBC, the UDCA treatment was not satisfactory. Larger studies with mixed ethnicity subjects and stratified by clinical and subclinical characteristics are needed to validate our findings.
| S-EPMC4216684 | biostudies-literature
Project description:Aim: Up to 40% of patients with primary biliary cholangitis (PBC) will have a suboptimal biochemical response to ursodeoxycholic acid (UDCA), which can be improved by the addition of fibrates. This exploratory study aims to evaluate the long-term real-life biochemical response of different fibrates, including ciprofibrate, in subjects with UDCA-unresponsive PBC. Methods: The Brazilian Cholestasis Study Group multicenter database was reviewed to assess the response rates to UDCA plus fibrates in patients with UDCA-unresponsive PBC 1 and 2 years after treatment initiation by different validated criteria. Results: In total, 27 patients (100% women, mean age 48.9 ± 9.2 years) with PBC were included. Overall response rates to fibrates by each validated criterion varied from 39 to 60% and 39-76% at 12 and 24 months after treatment combination, respectively. Combination therapy resulted in a significant decrease in ALT and ALP only after 2 years, while GGT significantly improved in the first year of treatment. Treatment response rates at 1 and 2 years appear to be comparable between ciprofibrate and bezafibrate using all available criteria. Conclusion: Our findings endorse the efficacy of fibrate add-on treatment in PBC patients with suboptimal response to UDCA. Ciprofibrate appears to be at least as effective as bezafibrate and should be assessed in large clinical trials as a possibly new, cheaper, and promising option for treatment of UDCA-unresponsive PBC patients.
| S-EPMC8811361 | biostudies-literature
Project description:Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with ursodeoxycholic acid (UDCA) as first-line treatment. Poor response to UDCA is associated with a higher risk of progressing to cirrhosis, but the underlying mechanisms are unclear. UDCA modulates the composition of primary and bacterial-derived bile acids (BAs). We characterized the phenotypic response to UDCA based on BA and bacterial profiles of PBC patients treated with UDCA. Patients from the UK-PBC cohort (n = 419) treated with UDCA for a minimum of 12-months were assessed using the Barcelona dynamic response criteria. BAs from serum, urine, and feces were analyzed using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry and fecal bacterial composition measured using 16S rRNA gene sequencing. We identified 191 non-responders, 212 responders, and a subgroup of responders with persistently elevated liver biomarkers (n = 16). Responders had higher fecal secondary and tertiary BAs than non-responders and lower urinary bile acid abundances, with the exception of 12-dehydrocholic acid, which was higher in responders. The sub-group of responders with poor liver function showed lower alpha-diversity evenness, lower abundance of fecal secondary and tertiary BAs than the other groups and lower levels of phyla with BA-deconjugation capacity (Actinobacteriota/Actinomycetota, Desulfobacterota, Verrucomicrobiota) compared to responders. UDCA dynamic response was associated with an increased capacity to generate oxo-/epimerized secondary BAs. 12-dehydrocholic acid is a potential biomarker of treatment response. Lower alpha-diversity and lower abundance of bacteria with BA deconjugation capacity might be associated with an incomplete response to treatment in some patients.
| S-EPMC10190197 | biostudies-literature
Project description:Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9-10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13-15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC.
| S-EPMC2758170 | biostudies-literature
Project description:The United Kingdom-Primary Biliary Cholangitis (UK-PBC) risk scores are a set of prognostic models that estimate the risk of end-stage liver disease in patients with PBC at 5-, 10- and 15-year intervals. They have not been externally validated outside the United Kingdom. In this retrospective, external validation study, data were abstracted from outpatient charts and discrimination and calibration of the UK-PBC risk scores were assessed. A total of 464 patients with PBC treated with ursodeoxycholic acid were included. The median diagnosis age was 52.4 years, and 88% were female patients. The cumulative incidence of events was 6%, 9%, and 15% at 5, 10, and 15 years, respectively. Concordance (c-statistic) was 0.88, 0.85, and 0.84 using the 5-, 10- and 15-year risk scores, respectively, which was slightly lower than values observed in the United Kingdom validation cohort. Using the 5-year risk score, more events were observed than predicted (25 versus 16.8; P = 0.046); using the 10-year risk score, there was no difference between the observed and predicted number of events (35 versus 44.9; P = 0.14); conversely, using the 15-year risk score, fewer events were observed than predicted (46 versus 67.5; P = 0.009). Limiting evaluation by the 15-year UK-PBC risk score to those with >10 years of follow-up demonstrated no difference between observed and predicted events. Using the 5-year risk score, patients within the highest quartile had statistically significant worse event-free survival compared to the rest of the cohort: 82% versus 98% at 5 years, 73% versus 97% at 10 years, and 58% versus 93% at 15 years. Conclusion: In patients assessed at a North American tertiary medical center, the UK-PBC risk score had excellent discrimination and was reasonably calibrated both in the short and long term. (Hepatology Communications 2018;2:676-682).
| S-EPMC5983113 | biostudies-literature