Triple therapy with ursodeoxycholic acid, budesonide and mycophenolate mofetil in patients with features of severe primary biliary cirrhosis not responding to ursodeoxycholic acid alone

Rabahi, N.; Chrétien, Yves; Gaouar, Farid; Wendum, Dominique; Serfaty, Lawrence; Chazouillères, Olivier; Corpechot, Christophe; Poupon, R.

doi:10.1016/j.gcb.2010.02.004

Cited by 51 publications

(39 citation statements)

References 25 publications

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“…In a pilot trial including 22 non-responders to UDCA, with a mean duration of 46 months, budesonide failed to add any additional benefit to UDCA; moreover, it was shown that budesonide could aggravate underlying osteopenic bone disease [84]. In a small pilot study including 15 patients with PBC (with a suboptimal response to UDCA), budesonide was administered in combination with both UDCA and MMF; patients also received supplementation with calcium and vitamin D. A normalization of liver enzymes was obtained in 41% of cases [86]. It should be stressed, however, that budesonide is contraindicated in cirrhosis due to its potential to induce portal vein thrombosis [88].…”

Section: Introductionmentioning

confidence: 99%

Proposed therapies in primary biliary cholangitis

Floreani

Sun

Zou

et al. 2016

Expert Review of Gastroenterology & Hepatology

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Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a model autoimmune disease with chronic cholestasis characterized by the hallmark of anti-mitochondrial antibodies and treated with ursodeoxycholic acid (UDCA). However, approximately 20-40% of patients incompletely respond to UDCA and have an increased risk of disease progression. Although there have been significant advances in the immunobiology of PBC, these have yet to be translated into newer therapeutic modalities. Current approaches to controlling the immune response include broad immunosuppression with corticosteroids as well as targeted therapies directed against T and B cells. In contrast, ameliorating cholestasis is the focus of other therapies in development, including obeticholic acid. In this article the authors will discuss ongoing clinical trials and, in particular, the rationale for choosing agents that may effectively target the aberrant immune response.

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Section: Introductionmentioning

confidence: 99%

Proposed therapies in primary biliary cholangitis

Floreani

Sun

Zou

et al. 2016

Expert Review of Gastroenterology & Hepatology

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“…Treble treatment with budesonide (6 mg/d), UDCA (13-15 mg/kg per day), and mycophenolate mofetil (1.5 g/d) may afford an advantage in non-cirrhotic PBC patients with characteristics of serious illness without biochemical response to UDCA[169]. Combination therapy of budesonide (6 mg/d) and UDCA (15 mg/kg per day) was able to ameliorate the plasma biochemical index of hepatic function and hepatic histology, particularly in PBC patients with hepatic fibrosis (grade I-III), whereas the treatment effectiveness of UDCA alone was principally on lab results[170].…”

Section: Therapy Of Pbcmentioning

confidence: 99%

Recent advances in the diagnosis and treatment of primary biliary cholangitis

Huang¹

2016

WJH

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Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies (including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies (anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies (anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and anti-diastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients.

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“…A significant 128 loss of bone mass has been reported, despite the significant increase of the Mayo risk score [33] . A triple regimen, including mycophenolate mofetil along with UDCA and budesonide for 3 years in 15 patients with suboptimal response to UDCA and significant interface hepatitis in liver biopsy, resulted in an improvement of liver biochemistries and histological activity and fibrosis as well [35] . The 2 patients who failed to achieve total or partial biochemical response had severe ductopenia, extensive fibrosis and the highest bilirubin level.…”

Section: Prednisolone and Budesonidementioning

confidence: 99%

Therapy of Primary Biliary Cirrhosis: Novel Approaches for Patients with Suboptimal Response to Ursodeoxycholic Acid

Parés¹

2015

Dig Dis

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Primary biliary cirrhosis (PBC) is a chronic cholestatic disease of presumed autoimmune pathogenesis, characterized by the inflammation and damage of the intrahepatic intermediate and small bile ducts, which eventually results in cirrhosis. A number of randomized and observational and pilot studies using several agents were carried out in the 80s, but no clear results or even harmful effects were reported. Over the past 2 decades, increasing evidence indicates that ursodeoxycholic acid (UDCA) - 13 to 16 mg/kg/day - is the treatment of choice for patients with PBC. Biochemical response to UDCA, assessed at 1 year, clearly predicts the long-term outcome, since in UDCA, responders survival is similar to that estimated for the matched control population. However, about 40% of patients have incomplete biochemical response and increased risk of progression and decreased survival free of transplantation. Patients with suboptimal biochemical response to UDCA outline the group in whom further single or combined treatments with UDCA are needed. Accordingly, data on the effect of fibrates alone or in combination with UDCA, and budesonide in combination with UDCA have been reported. The combined treatment of UDCA and fibrates in patients without optimal biochemical response to UDCA improves the degree of cholestasis and may minimize the long-term management of these patients. The results of the combined therapy of UDCA with budesonide are appealing but they should be established in large randomized trials. The effect of new agents such obeticholic acid are promising, since the addition of this farnesoide-X-receptor agonist bile acid in patients with stable UDCA dosage and increased alkaline phosphatase levels results in an improvement of cholestasis as compared to placebo, with a parallel decrease of aminotransferases and immunoglobulin M, as well as one surrogate marker of bile acid synthesis. New molecular therapies are currently being investigated.

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Triple therapy with ursodeoxycholic acid, budesonide and mycophenolate mofetil in patients with features of severe primary biliary cirrhosis not responding to ursodeoxycholic acid alone

Cited by 51 publications

References 25 publications

Proposed therapies in primary biliary cholangitis

Proposed therapies in primary biliary cholangitis

Recent advances in the diagnosis and treatment of primary biliary cholangitis

Therapy of Primary Biliary Cirrhosis: Novel Approaches for Patients with Suboptimal Response to Ursodeoxycholic Acid

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