Pharmacological interventions for primary sclerosing cholangitis: an attempted network meta-analysis.
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ABSTRACT:
SUBMITTER: Saffioti F
PROVIDER: S-EPMC6464655 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Publications
Pharmacological interventions for primary sclerosing cholangitis: an attempted network meta-analysis.
Saffioti Francesca F Gurusamy Kurinchi Selvan KS Hawkins Neil N Toon Clare D CD Tsochatzis Emmanuel E Davidson Brian R BR Thorburn Douglas D
The Cochrane database of systematic reviews 20170328
<h4>Background</h4>Primary sclerosing cholangitis is a chronic cholestatic liver disease that is associated with both hepatobiliary and colorectal malignancies, which can result in liver cirrhosis and its complications. The optimal pharmacological treatment for patients with primary sclerosing cholangitis remains controversial.<h4>Objectives</h4>To assess the comparative benefits and harms of different pharmacological interventions in people with primary sclerosing cholangitis by performing a ne ...[more]
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| S-EPMC6464620 | biostudies-literature
Project description:Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis, and often requires liver transplantation (LT). PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40. Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC. PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD. When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue. The etiology of PSC is poorly understood, but an increasing body of evidence supports the concept of cholangiocyte injury as a result of environmental exposure and an abnormal immune response in genetically susceptible individuals. PSC is a progressive disease, yet no effective medical therapy for halting disease progression has been identified. Management of PSC is mainly focused on treatment of symptoms and addressing complications. PSC can be complicated by bacterial cholangitis, dominant strictures (DSs), gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy. CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC. LT is currently the only life-extending therapeutic approach for eligible patients with end-stage PSC, ultimately required in approximately 40% of patients. LT secondary to PSC has an excellent outcome compared to other LT indications, although the disease can recur and result in morbidity post-transplant.
| S-EPMC7829069 | biostudies-literature
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| S-EPMC5553912 | biostudies-literature
Project description:ObjectivesTherapies for treatment of patients with primary sclerosing cholangitis (PSC) include administration of ursodeoxycholic acid (UDCA) alone, or combination with metronidazole (MTZ) or mycophenolate mofetil (MMF), respectively. However, the optimum regimen still remains inconclusive. We aimed to compare interventions in terms of patient mortality or liver transplantation (MOLT), progression of liver histological stage (POLHS), serum bilirubin, alkaline phosphatase (ALP) levels and adverse events (AE).MethodsWe searched PubMed, Embase and the Cochrane Library for randomized controlled trials until 31, Jan 2015. We estimated hazard ratios (HRs), odds ratios (ORs) and mean difference (MD) between treatments on clinical outcomes. Sensitivity analyses based on the dose of UDCA, quality of trials or treatment duration were also performed.ResultsTen RCTs were included. Compared with UDCA plus MTZ, UDCA (HR 0.28, 95%CI 0.01-3.41), UDCA plus MMF (HR 0.08, 95%CI 0.00-4.18), or OBS (HR 0.28, 95%CI 0.01-3.98) all provided an increased risk of MOLT. UDCA provided a significant reduction in bilirubin and ALP levels compared with OBS (MD -13.92, P < 0.001; MD -484.34, P < 0.001; respectively). With respect to POLHS, although differing not significantly, UDCA plus MTZ had a tendency to improve LHS more than UDCA (OR 1.33), UDCA plus MMF (OR 3.24) or OBS (OR 1.08). Additionally, UDCA plus MTZ (MD -544.66, P < 0.001) showed a significant reduction in ALP levels compared with OBS, but appeared to be associated with more AEs compared with UDCA (OR 5.09), UDCA plus MMF (OR 4.80) or OBS (OR 7.21).ConclusionsMTZ plus UDCA was the most effective therapy in survival rates and liver histological progression.
| S-EPMC4694950 | biostudies-literature
Project description:Primary sclerosing cholangitis (PSC) represents a chronic cholestatic liver disease with fibroobliterative sclerosis of intra- and/or extrahepatic bile ducts, eventually leading to biliary cirrhosis. The association with human leukocyte antigen (HLA) and non-HLA haplotypes and the presence of autoantibodies in sera of PSC patients support a crucial role for immune-mediated mechanisms in the initiation and progression of PSC. The strong clinical association between PSC and inflammatory bowel diseases led to intriguing pathogenetic concepts, in which the inflamed gut with translocation of bacterial products and homing of gut-primed memory T lymphocytes via aberrantly expressed adhesion molecules plays a fundamental role. Genetically or chemically modified bile composition was shown to induce sclerosing cholangitis and liver fibrosis in a number of animal models ("toxic bile concept"). The potential role of vascular injury with ischemia of bile duct epithelium cells in the development of sclerosing cholangitis is supported by animal models of endothelial cell injury showing close morphological similarities with human PSC.
| S-EPMC3236286 | biostudies-literature
Project description:Background and objective: Pruritus is a common complication in patients with primary biliary cholangitis (PBC). The pathogenesis is not clear, and also the precise therapeutic measures remain alluring. In order to systematically evaluate the efficacy and safety of drug interventions in the treatment of pruritus associated with PBC, this systemic review and meta-analysis was conducted. Methods: The randomized controlled trials (RCTs) on drug interventions in the treatment of pruritus associated with primary cholangitis were searched in the electronic databases of PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov. Two researchers independently screened the literature, extracted and integrated the data, and assessed the bias risk of the selected literature, according to the Cochrane handbook. Finally, the STATA 15.0 software was used for the meta-analysis. Results: A total of 23 RCTs involving 2,194 patients were studied, that included 12 pharmacological interventions. In terms of itching relief, compared with placebo, UDCA, methotrexate and GSK2330672 had a definite effect in improving pruritus (pruritus remission rate before and after treatment, p < 0.05). In terms of serum indexes, compared with placebo group, UDCA, OCA, rifampicin, cyclosporine, NGM282, seladelpar and colchicine may improve blood alkaline phosphatase (ALP) (p < 0.05), but only rifampicin showed low heterogeneity. UDCA, bezafibrate, OCA, rifampicin, NGM282 and others may improve blood γ-glutamyl transpeptidase (γ-GGT) (p < 0.05), but due to the high heterogeneity and the limitation of research samples, a clear conclusion cannot be drawn. In terms of adverse events, except high (>15 mg/kg/day) and low doses (<13 mg/kg/day) of UDCA increased the incidence of adverse events, there were no risk of increasing the incidence of adverse events compared with placebo (p > 0.05), and a moderate dose of UDCA (13-15 mg/kg/day) and malotilate (1,500 mg/day) may also help in reducing the incidence of adverse events (p < 0.05). Conclusion: UDCA, methotrexate and GSK2330672 may relieve itching in patients with PBC, but there is a lack of robust evidence to support their effect on ALP or γ-GGT. Due to the heterogeneity in the published studies, based on the present review, we cannot explicitly recommend any specific drug for the treatment of PBC-related pruritus. Systematic Review Registration: link-https://osf.io/2g8ya, identifier 10.17605/OSF.IO/2G8YA.
| S-EPMC9631940 | biostudies-literature
Project description:BackgroundPrimary sclerosing cholangitis is a chronic liver disease associated with significant morbidity, mortality, and healthcare utilization. We conducted a systematic review and meta-analysis of population-based studies of the incidence and prevalence of primary sclerosing cholangitis.MethodsMedline and Embase were systematically searched to identify population-based studies of a defined geographic area and reported the incidence or prevalence of primary sclerosing cholangitis in the general population. Meta-analyses, using random-effects, were performed to calculate overall and country-specific incidence (per 100 000 persons/year) and prevalence rates (per 100 000 persons) with 95% confidence intervals.ResultsThe 14 studies on incidence and the 12 for prevalence originated from North America, Asia, Europe, and Oceania. Incidence and prevalence rates of primary sclerosing cholangitis were 0.87 (95% confidence interval, 0.59-1.29) and 13.53 (95% confidence interval, 10.20-17.94) per 100 000 persons, respectively.ConclusionsBoth the prevalence and incidence of primary sclerosing cholangitis is low in the general population. Future studies on the incidence and prevalence of primary sclerosing cholangitis in the general population should be directed at Asia, Africa, and Latin America to allow for a more robust assessment of the global epidemiology of primary sclerosing cholangitis.
| S-EPMC11532590 | biostudies-literature
Project description:Background and aimsWhile endoscopic retrograde cholangiopancreatography (ERCP) is a valuable diagnostic and therapeutic tool in primary sclerosing cholangitis (PSC), there is conflicting data on associated adverse events. The aims of this systematic review and meta-analysis are to (1) compare ERCP-related adverse events in patients with and without PSC and (2) determine risk factors for ERCP-related adverse events in PSC.MethodsEmbase, PubMed, and CENTRAL were searched between January 1, 2000, and May 12, 2021. Eligible studies included adults with PSC undergoing ERCP and reported at least one ERCP-related adverse event (cholangitis, pancreatitis, bleeding, and perforation) or an associated risk factor. The risk of bias was assessed with the Newcastle-Ottawa scale and Cochrane Risk of Bias 2. Raw event rates were used to calculate odds ratios (ORs) and then pooled using random-effects models.ResultsTwenty studies met eligibility criteria, of which four were included in a meta-analysis comparing post-ERCP adverse events in patients with PSC (n = 715) to those without PSC (n = 9979). We found a significant threefold increase in the 30-day odds of cholangitis in PSC compared to those without (OR 3.263, 95% CI 1.076-9.896; p=0.037). However, there were no significant differences in post-ERCP pancreatitis (PEP), bleeding, or perforation. Due to limitations in primary data, only risk factors contributing to PEP could be analyzed. Accidental passage of the guidewire into the pancreatic duct (OR 7.444, 95% CI 3.328-16.651; p < 0.001; I 2 = 65.0%) and biliary sphincterotomy (OR 4.802, 95% CI 1.916-12.033; p=0.001; I 2 = 73.1%) were associated with higher odds of PEP in a second meta-analysis including five studies.ConclusionsIn the context of limited comparative data and heterogeneity, PSC patients undergoing ERCP have higher odds of cholangitis despite the majority receiving antibiotics. Additionally, accidental wire passage and biliary sphincterotomy increased the odds of PEP. Future studies on ERCP-related risks and preventive strategies are needed.
| S-EPMC9334029 | biostudies-literature
Project description:Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography-related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary SC.
| S-EPMC8240333 | biostudies-literature