PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC

Kruk, Beata; Liebe, Roman; Milkiewicz, Małgorzata; Raszeja‐Wyszomirska, Joanna; Lammert, Frank; Milkiewicz, Piotr; Krawczyk, Marcin

doi:10.1371/journal.pone.0202942

Cited by 8 publications

(11 citation statements)

References 24 publications

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“…From these, 129 articles were selected for full‐text assessment. Ultimately, 25 studies 12,17–40 were included in this meta‐analysis, containing 17 452 PSC patients. The proportion of female patients was 37.1% (95% CI 35.1–39.1%).…”

Section: Resultsmentioning

confidence: 99%

Prevalence of inflammatory bowel disease in patients with primary sclerosing cholangitis: A systematic review and meta‐analysis

Zhang

Gao²,

et al. 2022

Liver International

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Background and Aim: Previous studies have established an association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC). The disease burden of IBD in PSC patients was not well estimated. The study aimed to quantify the pooled prevalence of IBD in PSC and to investigate whether subtypes of PSC and sex influence the prevalence of IBD.Methods: PubMed, Embase, and Web of Science were searched through November 2021 for studies reporting data on IBD among PSC patients. The outcomes were the prevalence of IBD in patients with PSC, as well as the association (odds ratio [OR]) of IBD in PSC according to subtype and sex. Results:Based on the analysis of 25 studies, the prevalence of IBD in patients with PSC was 71.1% (95% CI 68.2-75.1%), most commonly in UC (55.9%, 95% CI 52.5-59.3%). The pooled prevalence of IBD was 76.9% in Australia (95% CI 71.2-82.6%, 1 study), 75.9% (95% CI 69.5-82.3%, 4 studies) in North America, 70.9% (95% CI 65.8-76.0%, 17 studies) in Europe and 67.0% (95% CI 57.9-76.0%, 2 studies) in Asia. Male PSC patients had a higher prevalence of IBD (OR 1.67, 95% CI 1.52-1.83) and UC (OR 2.02, 95% CI 1.56-2.63) and a lower prevalence of CD (OR 0.77, 95% CI 0.67-0.88) than female patients. Large duct PSC patients had a higher prevalence of IBD (OR 2.57, 95% CI 2.03-3.25) and UC (OR 4.51,) than small duct PSC patients.

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Section: Resultsmentioning

confidence: 99%

Prevalence of inflammatory bowel disease in patients with primary sclerosing cholangitis: A systematic review and meta‐analysis

Zhang

Gao²,

et al. 2022

Liver International

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“…6、ALD represents the alcoholic fatty liver disease. M.Krawczyk [9] 2017 Kleiner Score case 68/20/2 control 164/38/3 0-1 2-3 N.Akuta [10] 2016 Brunt Score case 41/13/1 control 63/20/1 0-2 3-4 B. Kruk [11] 2018 Diagnostic criteria for cirrhosis case50/5/0 control 107/16/0 No YES C.Manchiero [12] 2017 Metavir Score case 46/12/0 control 215/17/0 0-2 3-4 U.Vespasiani-Gentilucci [13] 2018…”

Section: Search Resultsmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted October 14, 2020. ; https://doi.org/10.1101/2020.10.11.20210690 doi: medRxiv preprint in patients M.Krawczyk [9] 2017 Kleiner Score case 68/20/2 control 164/38/3 0-1 2-3 N.Akuta [10] 2016 Brunt Score case 41/13/1 control 63/20/1 0-2 3-4 B. Kruk [11] 2018 U.Vespasiani-Gentilucci [13] 2018…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

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Association between TM6SF2 rs58542926 T/C gene polymorphism and significant liver fibrosis: A meta-analysis

Mei

Zhang

Tang

et al. 2020

Preprint

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Aim: To further explore the association between Transmembrane 6 superfamily member 2(TM6SF2) rs58542926 T/C gene polymorphism and hepatic fibrosis. Materials and Methods: In this study the MEDLINE, PubMed, EMBASE, and CENTRAL databases were queried from inception to March 21, 2020. According to inclusion and exclusion criteria; case control studies assessing the relationship between TM6SF2 rs58542926 T/C gene polymorphism and significant liver fibrosis were selected. NOS scale was used to evaluate the included literature. Stata 12.0 software was used for data analysis. Results: In this meta analysis: a total of 7 articles, including 2286 patients were included. Statistical analysis showed that the TM6SF2 gene polymorphism was associated with significant liver fibrosis in the allele contrast, recessive dominant models (T vs. C, OR=1.292, 95%CI 1.035-1.611, P=0.023; TT vs. CT+CC, OR=2.829, 95%CI 1.101-7.267, P=0.031). No significant publication bias was found after Egger′s test.

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“… 35 In male patients with PSC with bile duct stenosis requiring intervention, the PNPLA3 I148M variant may be a risk factor for reduced survival 36 while another study found no impact. 37 Knockdown/inhibition of PNPLA3 variants is currently receiving considerable attention as novel treatment strategy for NASH. 38 Variants of the ABCB4 gene encoding the hepatobiliary phosphatiylcholine floppase not only confer risk of bile duct injury and cholestatic liver disease by altering bile toxicity, 39 but large-scale whole-genome sequencing uncovered a common ABCB4 variant as a general risk factor for elevated aminotransferases and higher impact variants as potential determinants of early-onset gallstone disease, cholestasis of pregnancy, liver cirrhosis and hepatobiliary cancer.…”

Section: Shared Pathogenetic Principles As Targets For Therapeutic Interventionsmentioning

confidence: 99%

Novel therapeutic targets for cholestatic and fatty liver disease

Trauner

Fuchs

2021

Gut

107

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Cholestatic and non-alcoholic fatty liver disease (NAFLD) share several key pathophysiological mechanisms which can be targeted by novel therapeutic concepts that are currently developed for both areas. Nuclear receptors (NRs) are ligand-activated transcriptional regulators of key metabolic processes including hepatic lipid and glucose metabolism, energy expenditure and bile acid (BA) homoeostasis, as well as inflammation, fibrosis and cellular proliferation. Dysregulation of these processes contributes to the pathogenesis and progression of cholestatic as well as fatty liver disease, placing NRs at the forefront of novel therapeutic approaches. This includes BA and fatty acid activated NRs such as farnesoid-X receptor (FXR) and peroxisome proliferator-activated receptors, respectively, for which high affinity therapeutic ligands targeting specific or multiple isoforms have been developed. Moreover, novel liver-specific ligands for thyroid hormone receptor beta 1 complete the spectrum of currently available NR-targeted drugs. Apart from FXR ligands, BA signalling can be targeted by mimetics of FXR-activated fibroblast growth factor 19, modulation of their enterohepatic circulation through uptake inhibitors in hepatocytes and enterocytes, as well as novel BA derivatives undergoing cholehepatic shunting (instead of enterohepatic circulation). Other therapeutic approaches more directly target inflammation and/or fibrosis as critical events of disease progression. Combination strategies synergistically targeting metabolic disturbances, inflammation and fibrosis may be ultimately necessary for successful treatment of these complex and multifactorial disorders.

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PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC

Cited by 8 publications

References 24 publications

Prevalence of inflammatory bowel disease in patients with primary sclerosing cholangitis: A systematic review and meta‐analysis

Prevalence of inflammatory bowel disease in patients with primary sclerosing cholangitis: A systematic review and meta‐analysis

Association between TM6SF2 rs58542926 T/C gene polymorphism and significant liver fibrosis: A meta-analysis

Novel therapeutic targets for cholestatic and fatty liver disease

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