A network meta-analysis of the efficacy and side effects of udca-based therapies for primary sclerosing cholangitis

Zhu, Gui‐Qi; Shi, Ke‐Qing; Huang, Guiqian; Wang, Liren; Ying, Lin; Braddock, Martin; Chen, Yongping; Zhou, Mengtao; Zheng, Ming‐Hua

doi:10.18632/oncotarget.5610

Cited by 22 publications

(10 citation statements)

References 47 publications

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“…These results are consistent with our previous findings showing that UDCA aggravates liver injury in ANIT-treated model mice via the induction of BSEP ( Zhang et al, 2018 ). Thus, induction of Yinchen to BSEP expression may be deleterious in obstructive cholestasis, such as PSC with segmental biliary obstruction ( Roma et al, 2011 ; Zhu et al, 2015 ) and cholangiocarcinoma with bile duct blockage. However, our recent findings indicate that Yinchen can alleviate liver injury in 1% CA-induced cholestatic model mice via the induction of BSEP (data not shown), suggesting that Yinchen can induce BSEP to treat cholestasis when the bile duct is not obstructed.…”

Section: Discussionmentioning

confidence: 99%

Effect of Different Ratios of Yinchen and Gancao Decoction on ANIT-Treated Cholestatic Liver Injury in Mice and Its Potential Underlying Mechanism

Wang

et al. 2021

Front. Pharmacol.

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Cholestasis is a pathological state that leads to serious liver disease; however, therapeutic options remain limited. Yinchen and Gancao are often used in combination at different ratios in traditional Chinese formulae for the treatment of jaundice and cholestasis. In the present study, we investigated the effect of decoctions containing different ratios of Yinchen and Gancao (YGD) on alpha-naphthyl isothiocyanate (ANIT)-treated intrahepatic cholestasis (IC) in mice, and further explored the underlying mechanism. Treatment with 0:4 and 1:4 YGD significantly reduced plasma total bile acid (TBA), total bilirubin (TBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities; decreased unconjugated and conjugated bile acid levels; and improved hepatocyte necrosis and inflammatory cells recruitment to hepatic sinusoids. Moreover, the expression levels of Toll-like receptor 4 (TLR4), interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), C-C ligand 2 (CCL2), and C-X-C ligand 2 (CXCL2) in the liver were significantly reduced. However, treatment with 4:1 and 4:0 YGD increased plasma TBA, TBIL, AST, ALT, and ALP activities and aggravated liver cell injury and inflammation. Moreover, the mRNA expression of the bile salt export pump (BSEP) in the liver was significantly increased in mice treated with 4:0 YGD. The present study demonstrates that YGD containing a high proportion of Gancao, which inhibits the TLR4/NF-κB pathway and reduces the inflammatory response, had protective effects against ANIT-treated IC in mice. However, YGD containing a high proportion of Yinchen aggravated the ANIT-treated IC in mice, which may be related to upregulation of BSEP and boosting bile acid regurgitation from damage cholangiocytes to liver in ANIT-treated IC mice.

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Section: Discussionmentioning

confidence: 99%

Effect of Different Ratios of Yinchen and Gancao Decoction on ANIT-Treated Cholestatic Liver Injury in Mice and Its Potential Underlying Mechanism

Wang

et al. 2021

Front. Pharmacol.

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“…It is more hydrophilic than its structural analog, chenodeoxycholic acid, contributing in part to its beneficial effects and reduced bile acid‐induced hepatotoxicity . Unfortunately, various trials have failed to show the same beneficial effects in PSC despite some improvements in liver biochemistry . In some instances, high‐dose UDCA has even been harmful …”

Section: Clinical Trials: Translating Precision Medicine Into Practicementioning

confidence: 99%

Precision medicine in primary sclerosing cholangitis

Maurice

Thorburn

2019

J of Digest Diseases

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Primary sclerosing cholangitis is a rare, complex autoimmune disease in relatively young patients. There is currently no treatment for the disease, resulting in high rates of advanced liver disease leading to death or liver transplantation. However, advances have been made in our understanding of the pathophysiological mechanisms of the disease, particularly from breakthroughs in the underlying genetics. Moreover, large international collaborations have generated important clinical data that have given greater detail on the different disease phenotypes and natural history, generating new risk prediction models. As a result, drug development may be designed to target specific disease mechanisms at known points of the disease natural history. Therefore, more drugs are entering phase II and III development, giving hope that soon patient‐specific treatments may be available to treat this difficult disease.

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“…Bosch et al 29 suggested that preventive administration of UDCA after liver transplantation for PBC patients reduces risk of recurrence. UDCA, as well, helps improve liver functions but has less benefit in improving prognosis for patients with primary sclerosing cholangitis (PSC) 30,31…”

Section: Therapeutic Roles Of Bas Signaling In Chronic Liver Diseasesmentioning

confidence: 99%

Therapeutic Roles of Bile Acid Signaling in Chronic Liver Diseases

2018

Journal of Clinical and Translational Hepatology

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Bile acids (BAs) are the major metabolic product of cholesterol, having detergent-like activities and being responsible for absorption of lipid and lipid-soluble vitamins. In addition, it has been increasingly recognized that BAs are important signaling molecules, regulating energy metabolism and immunity. Under physiological circumstances, synthesis and transport of BAs are precisely regulated to maintain bile acid homeostasis. Disruption of bile acid homeostasis results in pathological cholestasis and metabolic liver diseases. During the last decades, BAs have been gradually recognized as an important therapeutic target for novel treatment in chronic liver diseases. This review will provide an update on the current understanding of synthesis, transport and regulation of BAs, with a focus on the therapeutic roles of bile acid signaling in chronic liver diseases.

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A network meta-analysis of the efficacy and side effects of udca-based therapies for primary sclerosing cholangitis

Abstract: ABSTRACT

Cited by 22 publications

References 47 publications

Effect of Different Ratios of Yinchen and Gancao Decoction on ANIT-Treated Cholestatic Liver Injury in Mice and Its Potential Underlying Mechanism

Effect of Different Ratios of Yinchen and Gancao Decoction on ANIT-Treated Cholestatic Liver Injury in Mice and Its Potential Underlying Mechanism

Precision medicine in primary sclerosing cholangitis

Therapeutic Roles of Bile Acid Signaling in Chronic Liver Diseases

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