Immunosuppressive Agents for the Treatment of Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis

Peng, Xia; Luo, Xin; Hou, Jing-Ying; Wu, Simon; Li, Liang-Zong; Zheng, Ming‐Hua; Wang, Lingyun

doi:10.1159/000471874

Cited by 21 publications

(15 citation statements)

References 38 publications

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“…23 Patients with Crohn's disease may be more likely to receive immunomodulatory or biologic medicines than patients with ulcerative colitis or those with no IBD, although such medicines have not shown a survival detriment or benefit in PSC. 24,25 Differences in the microbiome of patients with Crohn's disease may not favor useful, disease-modifying metabolism of UDCA in some patients. Indeed, patients with PSC-Crohn's, PSC-ulcerative colitis, and PSC with no IBD each have distinct microbiota signatures, 26 with underrepresentation of Butyricicoccus in PSC-Crohn's compared with the others.…”

Section: Discussionmentioning

confidence: 99%

Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course

Deneau

Perito

Ricciuto

et al. 2019

The Journal of Pediatrics

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Objective To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis. Study design We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level <50 IU/L without experiencing portal hypertensive or dominant stricture events, liver transplantation, or death during the first year. Results We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not.

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Section: Discussionmentioning

confidence: 99%

Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course

Deneau

Perito

Ricciuto

et al. 2019

The Journal of Pediatrics

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“…Dendritic cells (DCs), macrophages, polymorphonuclear cells, angiogenic mediators, and cytokines also stimulate dismissal [21]. Many immunosuppressive agents that are used to suppress graft rejection cannot effectively inhibit immune responses and elicit many side effects [22].…”

Section: Discussionmentioning

confidence: 99%

Conditioned Medium from Adipose-Derived Stem Cell Inhibits Jurkat Cell Proliferation through TGF-β1 and p38/MAPK Pathway

Wang

Zhou

et al. 2019

Analytical Cellular Pathology

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Background. Since the first report on the immunomodulatory and immunosuppressive properties of Adipose-Derived Stem Cells (ADSCs), many studies have elucidated the underlying molecular mechanism of their suppressive activity on mixed lymphocyte reaction (MLR). However, a gap exists in our understanding of the molecular mechanism of ADSC-conditioned medium (ADSC-CM) on MLR. Methods. ADSCs were isolated from Human Adipose Tissues, and Enzyme-linked Immunosorbent Assay (ELISA) was used to identify the concentration of transforming growth factor β1 (TGF-β1) in ADSC-CM. The transcript abundance of TGF-β1, as well as that of insulin-like growth factor binding protein 3 (IGF-BP3), was evaluated using qRT-PCR on Jurkat cells cultured in ADSC-CM for 24 hours. The proliferation of the Jurkat cells was assessed using cell cycle assay. Western blotting was performed to identify potential signaling molecules involved in the ADSC-CM-induced inhibition of Jurkat cell proliferation. Results. The findings confirm that the isolated ADSCs demonstrate classic ADSC characteristics. The level of TGF-β1 was found to be low in ADSC-CM, as assessed by ELISA. Jurkat cells grown in ADSC-CM show reduced gene expression of TGF-β1 and IGF-BP3 compared with that of the control group. Furthermore, western blotting of ADSC-CM grown Jurkat cells that were blocked at the G0/G1 stage indicates that ADSC-CM decreases the protein expression of pP38 in a dose-dependent manner. Conclusion. ADSC-CM can inhibit Jurkat cell proliferation through the TGF-β1-p38 signaling pathway.

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“…Immunosuppressive agents have traditionally not been shown to offer any mortality benefit in PSC. A meta-analysis and systemic review looked at several immunosuppressive agents in the treatment of PSC and found no survival benefit or decreased necessity of liver transplantation [61]. Conversely, four children with PSC were treated with mizoribine and azathioprine, immunosuppressants, and significant benefits were noted [62].…”

Section: Primary Sclerosing Cholangitismentioning

confidence: 99%

Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma

Virani

Akers

Stephenson

et al. 2018

J Liver

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Cholestatic liver injury is characterized by damage induced on the biliary tree and cholangiocytes, the cells lining the biliary tree, thus they are termed “cholangiopathies”. Cholangiopathies include diseases such as Primary Biliary Cholangitis, Primary Sclerosing Cholangitis, Biliary Atresia and Cholangiocarcinoma. These pathologies lack viable therapies and most patients are diagnosed during late stage disease progression (with the exception of Biliary Atresia, which is found shortly after birth). The lack of therapies for these diseases has put a significant burden on the need for liver transplantation as this is the only indicative “cure” for cholangiopathies. The molecular mechanisms for cholangiopathies have been extensively studied; however, and unfortunately, the lack of effective biomarkers and therapeutics remains. In this review article we highlight the latest studies to investigate the molecular mechanisms regulating cholangiopathies and the potential therapeutics that might be discovered.

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Immunosuppressive Agents for the Treatment of Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis

Cited by 21 publications

References 38 publications

Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course

Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course

Conditioned Medium from Adipose-Derived Stem Cell Inhibits Jurkat Cell Proliferation through TGF-β1 and p38/MAPK Pathway

Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma

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