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Primary biliary cirrhosis

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https://www.readbyqxmd.com/read/28333129/protection-against-oxidative-stress-mediated-by-the-nrf2-keap1-axis-is-impaired-in-primary-biliary-cholangitis
#1
Urszula Wasik, Małgorzata Milkiewicz, Agnieszka Kempinska-Podhorodecka, Piotr Milkiewicz
In response to oxidative stress, nuclear factor (erythroid-derived 2)-like2 (Nrf2) induces expression of cytoprotective genes. The Nrf2 pathway is controlled by microRNAs and Kelch-like ECH-associated protein1 (Keap1). Nrf2 is stabilized when Keap1 is degraded through the autophagy pathway in a p62-dependent manner. The inhibition of autophagy causes protein accumulation, and Keap1 is inactivated by binding to p62. We investigated the role of the Nrf2/Keap1 axis in the amelioration of oxidative stress in primary biliary cholangitis (PBC)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28299343/polymorphisms-of-il12rb2-may-affect-the-natural-history-of-primary-biliary-cholangitis-a-single-centre-study
#2
Urszula Wasik, Ewa Wunsch, Gary L Norman, Eirini I Rigopoulou, Dimitrios P Bogdanos, Piotr Milkiewicz, Małgorzata Milkiewicz
Background. Recent GWAS in primary biliary cholangitis (PBC) showed strong associations with SNPs located within interleukin-12 receptor (IL12R) beta-2 (IL12RB2) gene. Aims. We assessed whether genetic variation of IL12RB2 is associated with laboratory and clinical features of PBC. Methods. Genomic DNA was isolated from 306 patients with PBC and 258 age/gender-matched controls. PBC-specific anti-mitochondrial antibodies (AMA) were tested in all subjects by ELISA. Two SNPs, rs3790567 and rs6679356, of IL12RB2 were genotyped using the MGB-TaqMan SNP assay...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28275240/polygenic-risk-assessment-reveals-pleiotropy-between-sarcoidosis-and-inflammatory-disorders-in-the-context-of-genetic-ancestry
#3
C A Lareau, C F DeWeese, I Adrianto, C J Lessard, P M Gaffney, M C Iannuzzi, B A Rybicki, A M Levin, C G Montgomery
Sarcoidosis is a complex disease of unknown etiology characterized by the presence of granulomatous inflammation. Though various immune system pathways have been implicated in disease, the relationship between the genetic determinants of sarcoidosis and other inflammatory disorders has not been characterized. Herein, we examined the degree of genetic pleiotropy common to sarcoidosis and other inflammatory disorders to identify shared pathways and disease systems pertinent to sarcoidosis onset. To achieve this, we quantify the association of common variant polygenic risk scores from nine complex inflammatory disorders with sarcoidosis risk...
March 9, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28263464/assessment-of-hepatic-impairment-and-implications-for-pharmacokinetics-of-substance-use-treatment
#4
Andrew H Talal, Charles S Venuto, Islam Younis
Although the liver is the primary site of metabolism and biliary excretion for many medications, data are limited on the liver's pharmacokinetic abilities in cirrhosis. Cirrhosis develops through collagen deposition, eventually culminating in end-stage liver disease that compromises hepatic drug metabolism. Consequently, the US Food and Drug Administration (FDA) recommends evaluating the pharmacokinetics of medications in subjects with hepatic impairment if hepatic metabolism constitutes more than 20% of their elimination or if they have a narrow therapeutic range...
March 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28263100/decreased-serum-dnase1-activity-in-patients-with-autoimmune-liver-diseases
#5
Nikolaos K Gatselis, Aigli G Vakrakou, Kalliopi Zachou, Theodoros Androutsakos, Kalliopi Azariadis, Gregorios Hatzis, Menelaos N Manoussakis, George N Dalekos
Deoxyribonuclease1 (DNase1) is involved in chromatin degradation of apoptotic cells. Its deficiency results in accumulation of self-DNA, which in turn may induce inflammation and autoimmunity. We assessed for the first time serum DNase1-activity in a large consecutive cohort of treatment-naïve patients with autoimmune liver diseases (ALD). DNase1-activity was determined by single radial enzyme-diffusion (SRED) at diagnosis of 224 patients with autoimmune hepatitis (AIH), 249 with primary biliary cirrhosis (PBC) and 36 with primary sclerosing cholangitis (PSC)...
March 2017: Autoimmunity
https://www.readbyqxmd.com/read/28261290/prediction-of-oesophageal-varices-in-patients-with-primary-biliary-cirrhosis-by-non-invasive-markers
#6
Lili Gao, Fanping Meng, Jun Cheng, Hanwei Li, Jun Han, Weihui Zhang
INTRODUCTION: Preliminary data suggested that non-invasive methods could be useful to assess presence of oesophageal varices (OV) in liver cirrhosis. The primary objectives were to investigate non-invasive markers for diagnosing and grading OV in patients with primary biliary cirrhosis. MATERIAL AND METHODS: This study included a total of 106 consecutive treatment-naive patients with primary biliary cirrhosis (PBC). Results of physical examination, blood tests, and abdominal ultrasound scan (USS) were measured...
March 1, 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28255561/genetic-contribution-to-the-pathogenesis-of-primary-biliary-cholangitis
#7
REVIEW
Satoru Joshita, Takeji Umemura, Eiji Tanaka, Masao Ota
Formerly termed primary biliary cirrhosis, primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease characterized by the presence of antimitochondrial antibodies. Ursodeoxycholic acid (UDCA) therapy is the most effective and approved treatment for PBC and leads to a favorable outcome in the vast majority of cases. Although the etiology of PBC has not yet been elucidated, human leukocyte antigen (HLA) class II alleles have been consistently associated with disease onset for decades...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28249274/the-emerging-role-of-soluble-adenylyl-cyclase-in-primary-biliary-cholangitis
#8
Jung-Chin Chang, Ulrich Beuers, Ronald P J Oude Elferink
BACKGROUND: Primary biliary cholangitis (PBC; previously referred to as primary biliary cirrhosis) is a chronic fibrosing cholangiopathy with the signature of an autoimmune disease and features of intrahepatic cholestasis. Immunosuppressing treatments are largely unsuccessful. Responsiveness to ursodeoxycholic acid and reduced expression of anion exchanger 2 (AE2) on canalicular membranes and small bile ducts underline the importance of bicarbonate transportation in its disease mechanism...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249264/bile-acids-and-deregulated-cholangiocyte-autophagy-in-primary-biliary-cholangitis
#9
Motoko Sasaki, Yasuni Nakanuma
BACKGROUND: Primary biliary cholangitis (PBC) is characterized by a high prevalence of serum anti-mitochondrial antibodies against the E2 subunit of the pyruvate dehydrogenase complex and bile duct lesions called chronic non-suppurative destructive cholangitis (CNSDC) in small bile ducts, eventually followed by extensive bile duct loss and biliary cirrhosis. Macroautophagy (a major type of autophagy) is a process of cellular self-digestion that plays a critical role in energy homeostasis and in the cytoprotection to various stresses...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28229620/successful-infliximab-therapy-in-a-patient-with-comorbid-spondyloarthritis-primary-biliary-cirrhosis-and-generalized-morphea
#10
Hatice Resorlu, Sevilay Kılıc, Selda Isık, Ferhat Gokmen
The patient in this report was diagnosed simultaneously with primary biliary cirrhosis (PBC), spondyloarthritis, and generalized morphea and was started on infliximab therapy. In addition to an improvement in clinical symptoms with this therapy, an improvement was also observed in laboratory parameters such as cholestatic enzymes, C-reactive protein, and erythrocyte sedimentation rate. Infliximab was well tolerated in this 56-year-old patient. However, further studies must be performed in order to clarify the therapeutic role of TNF-α blockers in, PBC and generalized morphea...
February 23, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28226189/equitable-distribution-in-rare-indications-for-liver-transplantation-the-dilemma-of-the-too-small-tablecloth-continues
#11
Andreas A Schnitzbauer, Wolf O Bechstein
Primary biliary cholangitis (formerly known as primary biliary cirrhosis) has been a classic indication for liver transplantation for more than thirty years (1). Due to the changing epidemiology of liver diseases combined with the universal lack of post-mortal grafts, the question of prioritizing allocation amongst sick patients competing for these rare grafts on the waiting list remains an unresolved challenge. In their UNOS database analysis Ashwani Singal and coworkers focus on wait-list mortality for a nowadays rare indication for liver transplantation: primary biliary cholangitis (PBC) (2)...
February 22, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28225291/-a-contribution-to-the-differential-diagnostics-of-sclerosing-cholangitides
#12
Martin Blaho, Petr Dítě, Martina Bojková, Martin Rydlo, Tomáš Kupka, Pavel Svoboda, Pavel Klvaňa, Arnošt Martínek
Sclerosing cholangitides represent a group of chronic biliary obstructive diseases which include primary sclerosing cholangitis (PSC), IgG4 associated sclerosing cholangitis (IgG4-SC) and secondary sclerosing cholangitis (SSC). The manifestations of the diseases are similar, but their asymptomatic course is also frequent. IgG4-SC belongs to the group of IgG4 associated diseases and it is the most frequently related to type 1 autoimmune pancreatitis. Diagnosing of IgG4-SC is based on typical histopathological images, shape changes revealed by diagnostic imaging, serological tests, concurrent impairment of other organs and response to therapy, where IgG4-SC responds well to treatment with corticoids, whereas the only possibility for the remaining units is endoscopic intervention or liver transplantation...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28223722/to-screen-or-not-to-screen-celiac-antibodies-in-liver-diseases
#13
REVIEW
Janaína Luz Narciso-Schiavon, Leonardo Lucca Schiavon
Celiac disease (CD) is a systemic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. The typical symptoms are anemia, diarrhea, fatigue, weight loss, and abdominal pain. CD has been reported in patients with primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, aminotransferase elevations, nonalcoholic fatty liver disease, hepatitis B, hepatitis C, portal hypertension and liver cirrhosis. We evaluate recommendations for active screening for CD in patients with liver diseases, and the effect of a gluten-free diet in these different settings...
February 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28215616/incidence-and-determinants-of-hepatocellular-carcinoma-in-autoimmune-hepatitis-a-systematic-review-and-meta-analysis
#14
REVIEW
Aylin Tansel, Lior H Katz, Hashem B El-Serag, Aaron P Thrift, Mayur Parepally, Mohammad H Shakhatreh, Fasiha Kanwal
BACKGROUND: The risk of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH) is unclear. We conducted a systematic review and meta-analysis of the incidence of HCC and associated risk factors among patients with AIH. METHODS: We searched PubMed, Embase, and reference lists from relevant articles through June 2016 to identify cohort studies that examined the incidence of HCC in patients with AIH. We used random effects models to estimate pooled incidence rates overall and in subgroup of patients with cirrhosis...
February 12, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28203139/spontaneous-splenic-infarcts-in-a-cirrhotic-patient-with-primary-biliary-cirrhosis
#15
Fredy Nehme, Kyle Rowe, Ahmad Haris, Imad Nassif
Spontaneous splenic infarction has been rarely reported as a complication of cirrhosis and portal hypertension. We describe the case of a 67-year-old female with past medical history of primary biliary cirrhosis presenting for a 1-day history of left upper quadrant pain. Investigations were in favor of splenic infarcts secondary to portal hypertension. The patient improved with conservative management and no recurrence was noted on further follow-up. Splenic infarction must be kept in mind when a patient with cirrhosis presents with left upper quadrant abdominal pain without a clear source...
January 2017: Case Reports in Gastroenterology
https://www.readbyqxmd.com/read/28197333/a-case-of-primary-biliary-cirrhosis-mimicking-acute-hepatitis-b-in-the-clinic-republic-of-korea
#16
Woo Hyuk Kwon, Hong Min Park, Jeong Jun Park, Sung Hoon Lee, Yong Kyu Lee
Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic autoimmune liver disease characterized by progressive bile duct injury. The most common symptoms of this disease include fatigue and pruritus. The diagnosis of PBC is based on cholestatic biochemical liver tests, presence of antimitochondrial antibodies, and characteristic histological biopsy findings. We report a case of a patient with PBS, who was initially suspected to be in the window period of hepatitis B by a private doctor in a local clinic based on the detection of isolated immunoglobulin M antibody against hepatitis B core antigen...
January 2017: Korean Journal of Family Medicine
https://www.readbyqxmd.com/read/28187190/widespread-gli-expression-but-limited-canonical-hedgehog-signaling-restricted-to-the-ductular-reaction-in-human-chronic-liver-disease
#17
Candice Alexandra Grzelak, Nicholas David Sigglekow, Janina Elke Eleonore Tirnitz-Parker, Elizabeth Jane Hamson, Alessandra Warren, Bharvi Maneck, Jinbiao Chen, Bramilla Patkunanathan, Jade Boland, Robert Cheng, Nicholas Adam Shackel, Devanshi Seth, David Geoffrey Bowen, Luciano Gastón Martelotto, D Neil Watkins, Geoffrey William McCaughan
Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations...
2017: PloS One
https://www.readbyqxmd.com/read/28127155/the-histone-modification-code-in-the-pathogenesis-of-autoimmune-diseases
#18
REVIEW
Yasuto Araki, Toshihide Mimura
Autoimmune diseases are chronic inflammatory disorders caused by a loss of self-tolerance, which is characterized by the appearance of autoantibodies and/or autoreactive lymphocytes and the impaired suppressive function of regulatory T cells. The pathogenesis of autoimmune diseases is extremely complex and remains largely unknown. Recent advances indicate that environmental factors trigger autoimmune diseases in genetically predisposed individuals. In addition, accumulating results have indicated a potential role of epigenetic mechanisms, such as histone modifications, in the development of autoimmune diseases...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28114749/risk-of-secondary-osteoporosis-due-to-lobular-cholestasis-in-non-cirrhotic-primary-biliary-cholangitis
#19
Anna Seki, Fusao Ikeda, Hirokazu Miyatake, Koichi Takaguchi, Shosaku Hayashi, Toshiya Osawa, Shin-Ichi Fujioka, Ryoji Tanaka, Masaharu Ando, Hiroyuki Seki, Yoshiaki Iwasaki, Kazuhide Yamamoto, Hiroyuki Okada
BACKGROUND AND AIM: It remains unclear whether primary biliary cholangitis (PBC) represents a risk factor for secondary osteoporosis. METHODS: A case-control study was conducted to examine bone mineral density and bone turnover markers in middle-aged postmenopausal PBC patients without liver cirrhosis. We compared the incidence of low bone mineral density between propensity-score matched subgroups of PBC patients and healthy controls, and investigated the mechanisms underlying unbalanced bone turnover in terms of the associations between bone turnover markers and PBC-specific histological findings...
January 23, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28073410/-correlation-of-fibrotouch-and-fibroscan-with-the-stage-of-primary-biliary-cirrhosis
#20
Y G Zhang, S X Zhao, G D Zhou, W C Li, W G Ren, H J Du, R Q Wang, Y M Nan
Objective: To investigate the diagnostic value of FibroTouch and FibroScan for the stage of primary biliary cirrhosis (PBC). Methods: A total of 66 PBC patients who visited our hospital from January 2014 to March 2016 were enrolled, and all the patients underwent liver biopsy and FibroTouch and FibroScan tests. Liver stiffness measurement (LSM) was used to assess fibrosis degree, and the receiver operating characteristic (ROC) curve was used to compare the cut-off values, sensitivities, and specificities of these two methods in determining fibrosis stage...
December 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
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