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• W4383371824 abstract "Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are cholestatic liver diseases that have significant clinical impact with debilitating symptoms and mortality. While PBC is predominantly seen in perimenopausal and postmenopausal women, men who are diagnosed with PBC have worse clinical outcomes and all-cause mortality. In contrast, 60% to 70% of patients with PSC are men; the data indicate that female sex may be an independent factor against PSC-related complications. These findings suggest a sex-dependent biological basis for these differences. Estrogen has been implicated in the pathogenesis of intrahepatic cholestasis of pregnancy and may induce cholestasis through a variety of interactions. However, it is unclear why some sexual dimorphic features may provide a protective effect despite known estrogen models that induce cholestasis. This article provides a brief introductory background and discusses the sexual dimorphism in clinical presentation in PSC and PBC. It also explores the role of estrogen signaling in pathogenesis and how it relates to intrahepatic cholestasis of pregnancy. Studies have already targeted certain molecules involved in estrogen signaling, and this review discusses these studies that identify estrogen-related receptor, estrogen receptor-α, estrogen receptor-β, farnesoid X receptor, and mast cells as possible targets, in addition to long noncoding RNA H19–induced cholestasis and sexual dimorphism. It also explores these interactions and their role in the pathogenesis of PBC and PSC. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are cholestatic liver diseases that have significant clinical impact with debilitating symptoms and mortality. While PBC is predominantly seen in perimenopausal and postmenopausal women, men who are diagnosed with PBC have worse clinical outcomes and all-cause mortality. In contrast, 60% to 70% of patients with PSC are men; the data indicate that female sex may be an independent factor against PSC-related complications. These findings suggest a sex-dependent biological basis for these differences. Estrogen has been implicated in the pathogenesis of intrahepatic cholestasis of pregnancy and may induce cholestasis through a variety of interactions. However, it is unclear why some sexual dimorphic features may provide a protective effect despite known estrogen models that induce cholestasis. This article provides a brief introductory background and discusses the sexual dimorphism in clinical presentation in PSC and PBC. It also explores the role of estrogen signaling in pathogenesis and how it relates to intrahepatic cholestasis of pregnancy. Studies have already targeted certain molecules involved in estrogen signaling, and this review discusses these studies that identify estrogen-related receptor, estrogen receptor-α, estrogen receptor-β, farnesoid X receptor, and mast cells as possible targets, in addition to long noncoding RNA H19–induced cholestasis and sexual dimorphism. It also explores these interactions and their role in the pathogenesis of PBC and PSC. Primary biliary cholangitis (PBC), previously termed primary biliary cirrhosis,1Purohit T. Cappell M.S. Primary biliary cirrhosis: pathophysiology, clinical presentation and therapy.World J Hepatol. 2015; 7: 926-941Google Scholar and primary sclerosing cholangitis (PSC) are chronic cholestatic liver diseases that primarily target cholangiocytes and can progress to end-stage liver disease over the course of years to decades.2Park J.-W. Kim J.-H. Kim S.-E. Jung J.H. Jang M.-K. Park S.-H. Lee M.-S. Kim H.-S. Suk K.T. Kim D.J. Primary biliary cholangitis and primary sclerosing cholangitis: current knowledge of pathogenesis and therapeutics.Biomedicines. 2022; 10: 1288Google Scholar,3Sarcognato S. Sacchi D. Grillo F. Cazzagon N. Fabris L. Cadamuro M. Cataldo I. Covelli C. Mangia A. Guido M. Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis.Pathologica. 2021; 113: 170-184Google Scholar Along with autoimmune hepatitis, PBC and PSC encompass the three major autoimmune pathologies that target the liver and biliary system. The etiopathogenesis of PBC and PSC is unknown, making effective therapeutic targets difficult to identify.2Park J.-W. Kim J.-H. Kim S.-E. Jung J.H. Jang M.-K. Park S.-H. Lee M.-S. Kim H.-S. Suk K.T. Kim D.J. Primary biliary cholangitis and primary sclerosing cholangitis: current knowledge of pathogenesis and therapeutics.Biomedicines. 2022; 10: 1288Google Scholar The differences in sexual predominance in diagnosis and prognosis also add a layer of complexity to PBC and PSC treatment.2Park J.-W. Kim J.-H. Kim S.-E. Jung J.H. Jang M.-K. Park S.-H. Lee M.-S. Kim H.-S. Suk K.T. Kim D.J. Primary biliary cholangitis and primary sclerosing cholangitis: current knowledge of pathogenesis and therapeutics.Biomedicines. 2022; 10: 1288Google Scholar This review article discusses the sexual dimorphism in PBC and PSC,4Marchioni Beery R.M. Vaziri H. Forouhar F. Primary biliary cirrhosis and primary sclerosing cholangitis: a review featuring a women’s health perspective.J Clin Transl Hepatol. 2014; 2: 266-284Google Scholar how estrogen signaling plays a role in the pathophysiology of these diseases, and how it may be closely related to a similar cholestatic liver disorder, intrahepatic cholestasis of pregnancy (ICP), which could offer clues regarding estrogen-related pathogenesis. It also discusses multiple models that use estrogen-signaling molecules as possible therapeutic targets. PBC is a relatively rare disease, with a reported prevalence of 10 to 30 per 100,000 persons in the United States and an incidence of 2 to 3 per 100,000 persons over the last few years.5Lu M. Zhou Y. Haller I.V. Romanelli R.J. VanWormer J.J. Rodriguez C.V. Anderson H. Boscarino J.A. Schmidt M.A. Daida Y.G. Sahota A. Vincent J. Bowlus C.L. Lindor K. Zhang T. Trudeau S. Li J. Rupp L.B. Gordon S.C. Increasing prevalence of primary biliary cholangitis and reduced mortality with treatment.Clin Gastroenterol Hepatol. 2018; 16: 1342-1350Google Scholar,6Nardelli M.J. Bittencourt P.L. Cançado G.G.L. Faria L.C. Villela-Nogueira C.A. Rotman V. Silva de Abreu E. Maria Farage Osório F. Evangelista A.S. Sampaio Costa Mendes L. Ferraz de Campos Mazo D. Hyppolito E.B. de Souza Martins A. Codes L. Signorelli I.V. Perez Medina Gomide G. Agoglia L. Alexandra Pontes Ivantes C. Ferreira de Almeida E.B.V. Coral G.P. Eulira Fontes Rezende R. Lucia Gomes Ferraz M. Raquel Benedita Terrabuio D. Luiz Rachid Cançado E. Couto C.A. Clinical features and outcomes of primary sclerosing cholangitis in the highly admixed Brazilian population.Chin J Gastroenterol Hepatol. 2021; 20217746401Google Scholar PBC is believed to predominantly affect middle-aged women of European descent.2Park J.-W. Kim J.-H. Kim S.-E. Jung J.H. Jang M.-K. Park S.-H. Lee M.-S. Kim H.-S. Suk K.T. Kim D.J. Primary biliary cholangitis and primary sclerosing cholangitis: current knowledge of pathogenesis and therapeutics.Biomedicines. 2022; 10: 1288Google Scholar However, recent studies show that there may be more racial and sex diversity than previously thought.7Adejumo A.C. Akhtar D.H. Dennis B.B. Cholankeril G. Alayo Q. Ogundipe O.A. Kim D. Ahmed A. Gender and racial differences in hospitalizations for primary biliary cholangitis in the USA.Dig Dis Sci. 2021; 66: 1461-1476Google Scholar,8Lleo A. Jepsen P. Morenghi E. Carbone M. Moroni L. Battezzati P.M. Podda M. Mackay I.R. Gershwin M.E. Invernizzi P. Evolving trends in female to male incidence and male mortality of primary biliary cholangitis.Sci Rep. 2016; 625906Google Scholar European studies report a sex incidence ratio close to 4:1 female-to-male, rather than the previously reported 8 to 9:1 female-to-male ratio that is widely accepted. Male subjects with PBC likely have a higher overall mortality rate due to unclear etiology, potential underdiagnosis, and a more underlying pathophysiological process.5Lu M. Zhou Y. Haller I.V. Romanelli R.J. VanWormer J.J. Rodriguez C.V. Anderson H. Boscarino J.A. Schmidt M.A. Daida Y.G. Sahota A. Vincent J. Bowlus C.L. Lindor K. Zhang T. Trudeau S. Li J. Rupp L.B. Gordon S.C. Increasing prevalence of primary biliary cholangitis and reduced mortality with treatment.Clin Gastroenterol Hepatol. 2018; 16: 1342-1350Google Scholar,7Adejumo A.C. Akhtar D.H. Dennis B.B. Cholankeril G. Alayo Q. Ogundipe O.A. Kim D. Ahmed A. Gender and racial differences in hospitalizations for primary biliary cholangitis in the USA.Dig Dis Sci. 2021; 66: 1461-1476Google Scholar,8Lleo A. Jepsen P. Morenghi E. Carbone M. Moroni L. Battezzati P.M. Podda M. Mackay I.R. Gershwin M.E. Invernizzi P. Evolving trends in female to male incidence and male mortality of primary biliary cholangitis.Sci Rep. 2016; 625906Google Scholar PSC similarly has a sex predisposition, with male subjects being more commonly affected (up to 60%), and an average age of diagnosis close to 40 years.3Sarcognato S. Sacchi D. Grillo F. Cazzagon N. Fabris L. Cadamuro M. Cataldo I. Covelli C. Mangia A. Guido M. Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis.Pathologica. 2021; 113: 170-184Google Scholar,9Carbone M. Kodra Y. Rocchetti A. Manno V. Minelli G. Gerussi A. Ronca V. Malinverno F. Cristoferi L. Floreani A. Invernizzi P. Conti S. Taruscio D. Primary sclerosing cholangitis: burden of disease and mortality using data from the National Rare Diseases Registry in Italy.Int J Environ Res Publ Health. 2020; 17: 3095Google Scholar,10Lazaridis K.N. LaRusso N.F. Primary sclerosing cholangitis.N Engl J Med. 2016; 375: 1161-1170Google Scholar The incidence rate is close to 0 to 2 per 100,000 persons, and prevalence is increasing globally,11Mehta T.I. Weissman S. Fung B.M. Sotiriadis J. Lindor K.D. Tabibian J.H. Global incidence, prevalence and features of primary sclerosing cholangitis: a systematic review and meta-analysis.Liver Int. 2021; 41: 2418-2426Google Scholar which is likely due to more widespread advancements in both magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography for diagnosis over the last few decades.3Sarcognato S. Sacchi D. Grillo F. Cazzagon N. Fabris L. Cadamuro M. Cataldo I. Covelli C. Mangia A. Guido M. Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis.Pathologica. 2021; 113: 170-184Google Scholar,11Mehta T.I. Weissman S. Fung B.M. Sotiriadis J. Lindor K.D. Tabibian J.H. Global incidence, prevalence and features of primary sclerosing cholangitis: a systematic review and meta-analysis.Liver Int. 2021; 41: 2418-2426Google Scholar,12Boonstra K. Beuers U. Ponsioen C.Y. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review.J Hepatol. 2012; 56: 1181-1188Google Scholar The pathophysiology of PBC and PSC is still incompletely understood. However, cholangiocytes are the key cells involved in both PBC and PSC pathogenesis, and thus it is important to have a proper understanding of their function. Cholangiocytes are epithelial cells that line the bile ducts and are involved in bile formation and regulation of bile flow through the biliary tree.13Banales J.M. Huebert R.C. Karlsen T. Strazzabosco M. LaRusso N.F. Gores G.J. Cholangiocyte pathobiology.Nat Rev Gastroenterol Hepatol. 2019; 16: 269-281Google Scholar These cells play a role in tissue injury and regeneration that helps restore biliary and liver functions during damage or disease.13Banales J.M. Huebert R.C. Karlsen T. Strazzabosco M. LaRusso N.F. Gores G.J. Cholangiocyte pathobiology.Nat Rev Gastroenterol Hepatol. 2019; 16: 269-281Google Scholar,14Michalopoulos G.K. The regenerative altruism of hepatocytes and cholangiocytes.Cell Stem Cell. 2018; 23: 11-12Google Scholar PBC is secondary to a combination of genetic and environmental risk factors that lead to T cell–mediated destruction of intrahepatic, small bile ducts.2Park J.-W. Kim J.-H. Kim S.-E. Jung J.H. Jang M.-K. Park S.-H. Lee M.-S. Kim H.-S. Suk K.T. Kim D.J. Primary biliary cholangitis and primary sclerosing cholangitis: current knowledge of pathogenesis and therapeutics.Biomedicines. 2022; 10: 1288Google Scholar,3Sarcognato S. Sacchi D. Grillo F. Cazzagon N. Fabris L. Cadamuro M. Cataldo I. Covelli C. Mangia A. Guido M. Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis.Pathologica. 2021; 113: 170-184Google Scholar,15Mago S. Wu G.Y. Primary sclerosing cholangitis and primary biliary cirrhosis overlap syndrome: a review.J Clin Transl Hepatol. 2020; 8: 336-346Google Scholar PBC-mediated damage to cholangiocyte function leads to decreased bile flow or chronic cholestasis, resulting in prolonged tissue damage and fibrosis that eventually result in cirrhosis after years of cell injury.2Park J.-W. Kim J.-H. Kim S.-E. Jung J.H. Jang M.-K. Park S.-H. Lee M.-S. Kim H.-S. Suk K.T. Kim D.J. Primary biliary cholangitis and primary sclerosing cholangitis: current knowledge of pathogenesis and therapeutics.Biomedicines. 2022; 10: 1288Google Scholar,12Boonstra K. Beuers U. Ponsioen C.Y. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review.J Hepatol. 2012; 56: 1181-1188Google Scholar,13Banales J.M. Huebert R.C. Karlsen T. Strazzabosco M. LaRusso N.F. Gores G.J. Cholangiocyte pathobiology.Nat Rev Gastroenterol Hepatol. 2019; 16: 269-281Google Scholar PSC pathogenesis is also a combination of genetic, environmental, and dietary risk factors.15Mago S. Wu G.Y. Primary sclerosing cholangitis and primary biliary cirrhosis overlap syndrome: a review.J Clin Transl Hepatol. 2020; 8: 336-346Google Scholar Human leukocyte antigen (HLA) genes I and II, specifically HLA-B and HLA-DRB1,16Næss S. Lie B.A. Melum E. Olsson M. Hov J.R. Croucher P.J.P. Hampe J. Thorsby E. Bergquist A. Traherne J.A. Schrumpf E. Boberg K.M. Schreiber S. Franke A. Karlsen T.H. Refinement of the MHC risk map in a Scandinavian primary sclerosing cholangitis population.PLoS One. 2014; 9e114486Google Scholar are particularly high risk at chromosome 6p21. A strong HLA association suggests that the adaptive immune system plays a significant role in pathogenesis. Certain studies theorize an autoimmune response, although the putative antigen in PSC is still unknown. Results of some genome-wide studies suggest that single nucleotide polymorphisms in the chromosome 6 region are linked to PSC. However, data are preliminary, and larger sample sizes are needed.17Karlsen T.H. Folseraas T. Thorburn D. Vesterhus M. Primary sclerosing cholangitis—a comprehensive review.J Hepatol. 2017; 67: 1298-1323Google Scholar Genes in the IL-2 pathway are also likely to contribute to PSC pathogenesis in certain patient populations.3Sarcognato S. Sacchi D. Grillo F. Cazzagon N. Fabris L. Cadamuro M. Cataldo I. Covelli C. Mangia A. Guido M. Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis.Pathologica. 2021; 113: 170-184Google Scholar,9Carbone M. Kodra Y. Rocchetti A. Manno V. Minelli G. Gerussi A. Ronca V. Malinverno F. Cristoferi L. Floreani A. Invernizzi P. Conti S. Taruscio D. Primary sclerosing cholangitis: burden of disease and mortality using data from the National Rare Diseases Registry in Italy.Int J Environ Res Publ Health. 2020; 17: 3095Google Scholar Interestingly, a gut microbiota hypothesis was suggested due to the high co-incidence of ulcerative colitis in patients with PSC. It is proposed that gut microbes may migrate through the portal system to the liver and biliary tract and cause an abnormal cholangiocyte response, including dysregulated proliferation and senescence. The T-cell gut hypothesis suggests that gut microbes stimulate an intestinal T-cell response, which results in T-cell migration to the liver and biliary system, and then eventual immune-mediated cholangiocyte destruction.3Sarcognato S. Sacchi D. Grillo F. Cazzagon N. Fabris L. Cadamuro M. Cataldo I. Covelli C. Mangia A. Guido M. Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis.Pathologica. 2021; 113: 170-184Google Scholar Ongoing research is targeted at fully understanding the pathogenesis of both cholangiopathies.3Sarcognato S. Sacchi D. Grillo F. Cazzagon N. Fabris L. Cadamuro M. Cataldo I. Covelli C. Mangia A. Guido M. Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis.Pathologica. 2021; 113: 170-184Google Scholar,10Lazaridis K.N. LaRusso N.F. Primary sclerosing cholangitis.N Engl J Med. 2016; 375: 1161-1170Google Scholar Up to one-half of patients with PBC are asymptomatic at the time of diagnosis. The most common symptoms by far are fatigue, jaundice, and pruritus, likely secondary to chronic cholestasis. Cholestasis also increases the risk of infectious processes such as cholangitis and biliary obstruction in general. Therefore, patients often present with abdominal pain, which is typically right-sided.1Purohit T. Cappell M.S. Primary biliary cirrhosis: pathophysiology, clinical presentation and therapy.World J Hepatol. 2015; 7: 926-941Google Scholar Up to 75% of patients with PBC are diagnosed with other autoimmune pathologies (eg, Hashimoto thyroiditis, Graves’ disease, Sjogren syndrome), leading to incidental diagnosis of PBC. It is hypothesized that co-diagnosis with other autoimmune disorders could be secondary to epithelial antigen cross-reactivity.15Mago S. Wu G.Y. Primary sclerosing cholangitis and primary biliary cirrhosis overlap syndrome: a review.J Clin Transl Hepatol. 2020; 8: 336-346Google Scholar As with PBC, most patients with PSC have no symptoms at the time of diagnosis but may have chronic elevation in some liver function laboratory test results. The patients who do have symptoms (up to 50%) most commonly present with hepatomegaly and splenomegaly in addition to fatigue and pruritus (closer to 10%).3Sarcognato S. Sacchi D. Grillo F. Cazzagon N. Fabris L. Cadamuro M. Cataldo I. Covelli C. Mangia A. Guido M. Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis.Pathologica. 2021; 113: 170-184Google Scholar,9Carbone M. Kodra Y. Rocchetti A. Manno V. Minelli G. Gerussi A. Ronca V. Malinverno F. Cristoferi L. Floreani A. Invernizzi P. Conti S. Taruscio D. Primary sclerosing cholangitis: burden of disease and mortality using data from the National Rare Diseases Registry in Italy.Int J Environ Res Publ Health. 2020; 17: 3095Google Scholar,10Lazaridis K.N. LaRusso N.F. Primary sclerosing cholangitis.N Engl J Med. 2016; 375: 1161-1170Google Scholar PBC can usually be diagnosed with elevated alkaline phosphatase levels in addition to a positive anti-mitochondrial antibody test result. Although anti-mitochondrial antibody–negative PBC can be seen, it is exceedingly rare, occurring in less than 5% of patients with PBC.3Sarcognato S. Sacchi D. Grillo F. Cazzagon N. Fabris L. Cadamuro M. Cataldo I. Covelli C. Mangia A. Guido M. Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis.Pathologica. 2021; 113: 170-184Google Scholar Persistent alkaline phosphatase elevations, indicative of cholestasis, for longer than 6 months is considered diagnostic for PSC. Findings can be confirmed with either endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography that display the characteristic bile duct stricturing, and a biopsy is not needed for a presumed PSC diagnosis.3Sarcognato S. Sacchi D. Grillo F. Cazzagon N. Fabris L. Cadamuro M. Cataldo I. Covelli C. Mangia A. Guido M. Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis.Pathologica. 2021; 113: 170-184Google Scholar,4Marchioni Beery R.M. Vaziri H. Forouhar F. Primary biliary cirrhosis and primary sclerosing cholangitis: a review featuring a women’s health perspective.J Clin Transl Hepatol. 2014; 2: 266-284Google Scholar,9Carbone M. Kodra Y. Rocchetti A. Manno V. Minelli G. Gerussi A. Ronca V. Malinverno F. Cristoferi L. Floreani A. Invernizzi P. Conti S. Taruscio D. Primary sclerosing cholangitis: burden of disease and mortality using data from the National Rare Diseases Registry in Italy.Int J Environ Res Publ Health. 2020; 17: 3095Google Scholar,18Rabiee A. Silveira M.G. Primary sclerosing cholangitis.Transl Gastroenterol Hepatol. 2021; 6: 29Google Scholar,19Trivedi P.J. Hirschfield G.M. Recent advances in clinical practice: epidemiology of autoimmune liver diseases.Gut. 2021; 70: 1989-2003Google Scholar Due to the nature of cholangiopathy epidemiology data, there is interest in the clinical differences and outcomes stratified according to race, age, and—most importantly for the purpose of the current article—sex. In a study by Abdulkarim et al,20Abdulkarim M. Zenouzi R. Sebode M. Schulz L. Quaas A. Lohse A.W. Schramm C. Weiler-Normann C. Sex differences in clinical presentation and prognosis in patients with primary biliary cholangitis.Scand J Gastroenterol. 2019; 54: 1391-1396Google Scholar only about 15% of male subjects reported more than one typical PBC symptom (eg, jaundice, pruritus, fatigue). Comparatively, 56% of female subjects reported more than one of those symptoms. However, studies also show that many men did not undergo a diagnostic PBC workup despite typical PBC-like symptoms and liver laboratory abnormalities, attributed mainly to the belief that PBC predominantly affects women. This, along with other factors, likely contributed to the delayed diagnosis of PBC in men (36 months after initial symptoms versus 12 months in women).21Podda M. Selmi C. Lleo A. Moroni L. Invernizzi P. The limitations and hidden gems of the epidemiology of primary biliary cirrhosis.J Autoimmun. 2013; 46: 81-87Google Scholar The outcomes of these disparities lead to men having advanced liver disease and sequelae of cirrhosis, including spontaneous bacterial peritonitis, severe jaundice, and acute liver failure by the time of official diagnosis20Abdulkarim M. Zenouzi R. Sebode M. Schulz L. Quaas A. Lohse A.W. Schramm C. Weiler-Normann C. Sex differences in clinical presentation and prognosis in patients with primary biliary cholangitis.Scand J Gastroenterol. 2019; 54: 1391-1396Google Scholar,22Gatselis N.K. Zachou K. Lygoura V. Azariadis K. Arvaniti P. Spyrou E. Papadamou G. Koukoulis G.K. Dalekos G.N. Rigopoulou E.I. Geoepidemiology, clinical manifestations and outcome of primary biliary cholangitis in Greece.Eur J Intern Med. 2017; 42: 81-88Google Scholar,23Marschall H.-U. Henriksson I. Lindberg S. Söderdahl F. Thuresson M. Wahlin S. Ludvigsson J.F. Incidence, prevalence, and outcome of primary biliary cholangitis in a nationwide Swedish population-based cohort.Sci Rep. 2019; 911525Google Scholar Lleo et al8Lleo A. Jepsen P. Morenghi E. Carbone M. Moroni L. Battezzati P.M. Podda M. Mackay I.R. Gershwin M.E. Invernizzi P. Evolving trends in female to male incidence and male mortality of primary biliary cholangitis.Sci Rep. 2016; 625906Google Scholar, 24Sayiner M. Golabi P. Stepanova M. Younossi I. Nader F. Racila A. Younossi Z.M. Primary biliary cholangitis in Medicare population: the impact on mortality and resource use.Hepatology. 2019; 69: 237-244Google Scholar reported that male subjects have higher all-cause mortality in Italian and Danish populations, and data from Sayiner et al8Lleo A. Jepsen P. Morenghi E. Carbone M. Moroni L. Battezzati P.M. Podda M. Mackay I.R. Gershwin M.E. Invernizzi P. Evolving trends in female to male incidence and male mortality of primary biliary cholangitis.Sci Rep. 2016; 625906Google Scholar, 24Sayiner M. Golabi P. Stepanova M. Younossi I. Nader F. Racila A. Younossi Z.M. Primary biliary cholangitis in Medicare population: the impact on mortality and resource use.Hepatology. 2019; 69: 237-244Google Scholar also endorse similar results for a US population. Far fewer data are available that analyze sex differences in PSC.11Mehta T.I. Weissman S. Fung B.M. Sotiriadis J. Lindor K.D. Tabibian J.H. Global incidence, prevalence and features of primary sclerosing cholangitis: a systematic review and meta-analysis.Liver Int. 2021; 41: 2418-2426Google Scholar Ulcerative colitis is commonly seen with PSC as a concomitant disease process, and Invernizzi et al6Nardelli M.J. Bittencourt P.L. Cançado G.G.L. Faria L.C. Villela-Nogueira C.A. Rotman V. Silva de Abreu E. Maria Farage Osório F. Evangelista A.S. Sampaio Costa Mendes L. Ferraz de Campos Mazo D. Hyppolito E.B. de Souza Martins A. Codes L. Signorelli I.V. Perez Medina Gomide G. Agoglia L. Alexandra Pontes Ivantes C. Ferreira de Almeida E.B.V. Coral G.P. Eulira Fontes Rezende R. Lucia Gomes Ferraz M. Raquel Benedita Terrabuio D. Luiz Rachid Cançado E. Couto C.A. Clinical features and outcomes of primary sclerosing cholangitis in the highly admixed Brazilian population.Chin J Gastroenterol Hepatol. 2021; 20217746401Google Scholar, 9Carbone M. Kodra Y. Rocchetti A. Manno V. Minelli G. Gerussi A. Ronca V. Malinverno F. Cristoferi L. Floreani A. Invernizzi P. Conti S. Taruscio D. Primary sclerosing cholangitis: burden of disease and mortality using data from the National Rare Diseases Registry in Italy.Int J Environ Res Publ Health. 2020; 17: 3095Google Scholar, 25Invernizzi F. Cilla M. Trapani S. Guarino M. Cossiga V. Gambato M. Morelli M.C. Morisco F. Burra P. Floreani A. Special Interest Group Gender in Hepatology of the Italian Association for the Study of the Liver (AISF): Gender and autoimmune liver diseases: relevant aspects in clinical practice.J Pers Med. 2022; 12: 925Google Scholar found that it is less commonly seen in women with PSC versus male PSC patients (48% versus 61%). However, data sets from Brazil and Europe show no significant difference between clinical presentation symptoms in male and female subjects.6Nardelli M.J. Bittencourt P.L. Cançado G.G.L. Faria L.C. Villela-Nogueira C.A. Rotman V. Silva de Abreu E. Maria Farage Osório F. Evangelista A.S. Sampaio Costa Mendes L. Ferraz de Campos Mazo D. Hyppolito E.B. de Souza Martins A. Codes L. Signorelli I.V. Perez Medina Gomide G. Agoglia L. Alexandra Pontes Ivantes C. Ferreira de Almeida E.B.V. Coral G.P. Eulira Fontes Rezende R. Lucia Gomes Ferraz M. Raquel Benedita Terrabuio D. Luiz Rachid Cançado E. Couto C.A. Clinical features and outcomes of primary sclerosing cholangitis in the highly admixed Brazilian population.Chin J Gastroenterol Hepatol. 2021; 20217746401Google Scholar,9Carbone M. Kodra Y. Rocchetti A. Manno V. Minelli G. Gerussi A. Ronca V. Malinverno F. Cristoferi L. Floreani A. Invernizzi P. Conti S. Taruscio D. Primary sclerosing cholangitis: burden of disease and mortality using data from the National Rare Diseases Registry in Italy.Int J Environ Res Publ Health. 2020; 17: 3095Google Scholar Despite these findings, female sex is an independent factor against cirrhotic complications with advanced PSC (spontaneous bacterial peritonitis, hepatic encephalopathy, hepatocellular carcinoma), and female subjects also have higher significant transplant-free survival rates compared with men.9Carbone M. Kodra Y. Rocchetti A. Manno V. Minelli G. Gerussi A. Ronca V. Malinverno F. Cristoferi L. Floreani A. Invernizzi P. Conti S. Taruscio D. Primary sclerosing cholangitis: burden of disease and mortality using data from the National Rare Diseases Registry in Italy.Int J Environ Res Publ Health. 2020; 17: 3095Google Scholar,25Invernizzi F. Cilla M. Trapani S. Guarino M. Cossiga V. Gambato M. Morelli M.C. Morisco F. Burra P. Floreani A. Special Interest Group Gender in Hepatology of the Italian Association for the Study of the Liver (AISF): Gender and autoimmune liver diseases: relevant aspects in clinical practice.J Pers Med. 2022; 12: 925Google Scholar,26John B.V. Aitcheson G. Schwartz K.B. Khakoo N.S. Dahman B. Deng Y. Goldberg D. Martin P. Taddei T.H. Levy C. Kaplan D.E. Male sex is associated with higher rates of liver-related mortality in primary biliary cholangitis and cirrhosis.Hepatology. 2021; 74: 879-891Google Scholar There are many hypotheses as to why men and postmenopausal women appear to have poorer outcomes with cholangiopathies. One such explanation is that sex hormones, particularly estrogen, may play a key role in cholangiocyte regulation and proliferation, and estrogens likely have a complex dual role, as cholestasis, cholangiopathy, and liver disease still occurs in those who take supplemental estrogen.27Hamilton K.J. Hewitt S.C. Arao Y. Korach K.S. Estrogen hormone biology.Curr Top Dev Biol. 2017; 125: 109-146Google Scholar To understand how estrogen plays a role in cholangiocyte function, it is important to know the synthesis and regulation of estrogen signaling. The hypothalamus secretes gonadotropin-releasing hormone, which subsequently acts on the anterior pituitary to secrete follicle-stimulating hormone and luteinizing hormone. Follicle-stimulating hormone can then stimulate either granulosa or Sertoli cells to synthesize aromatase.27Hamilton K.J. Hewitt S.C. Arao Y. Korach K.S. Estrogen hormone biology.Curr Top Dev Biol. 2017; 125: 109-146Google Scholar In women, the granulosa cells are found in the ovaries, which is where aromatase can convert androgens or the intermediates such as dehydroepiandrosterone into estrogen.27Hamilton K.J. Hewitt S.C. Arao Y. Korach K.S. Estrogen hormone biology.Curr Top Dev Biol. 2017; 125: 109-146Google Scholar,28Kumar A. Banerjee A. Singh D. Thakur G. Kasarpalkar N. Gavali S. Gadkar S. Madan T. Mahale S.D. Balasinor N.H. Sachdeva G. Estradiol: a steroid with multiple facets.Horm Metab Res. 2018; 50: 359-374Google Scholar Dehydroepiandrosterone is derived from cholesterol and is a widely available steroid hormone found in many organs of the human body, including the liver. There are three main subtypes of estrogen: estrone, estradiol (E2), and estriol. E2 is the most biologic" @default.
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• W4383371824 title "Sex-Dependent Differences in Cholestasis" @default.
• W4383371824 cites W1580834849 @default.
• W4383371824 cites W1860026848 @default.
• W4383371824 cites W1976482077 @default.
• W4383371824 cites W1983754538 @default.
• W4383371824 cites W2003422299 @default.
• W4383371824 cites W2005913737 @default.
• W4383371824 cites W2016202086 @default.
• W4383371824 cites W2034819949 @default.
• W4383371824 cites W2044126226 @default.
• W4383371824 cites W2073055866 @default.
• W4383371824 cites W2087357579 @default.
• W4383371824 cites W2104761060 @default.
• W4383371824 cites W2112930872 @default.
• W4383371824 cites W2119795893 @default.
• W4383371824 cites W2121717560 @default.
• W4383371824 cites W2126220199 @default.
• W4383371824 cites W2178270601 @default.
• W4383371824 cites W2243188229 @default.
• W4383371824 cites W2315775322 @default.
• W4383371824 cites W2335873537 @default.
• W4383371824 cites W2344881746 @default.
• W4383371824 cites W2406168974 @default.
• W4383371824 cites W2417383068 @default.
• W4383371824 cites W2546705606 @default.
• W4383371824 cites W2583201344 @default.
• W4383371824 cites W2593311731 @default.
• W4383371824 cites W2616598259 @default.
• W4383371824 cites W2745107259 @default.
• W4383371824 cites W2777791186 @default.
• W4383371824 cites W2792120461 @default.
• W4383371824 cites W2809183114 @default.
• W4383371824 cites W2829125471 @default.
• W4383371824 cites W2884037904 @default.
• W4383371824 cites W2893198872 @default.
• W4383371824 cites W2907622015 @default.
• W4383371824 cites W2912717368 @default.
• W4383371824 cites W2917000227 @default.
• W4383371824 cites W2964683056 @default.
• W4383371824 cites W2988688775 @default.
• W4383371824 cites W2989612982 @default.
• W4383371824 cites W2991147339 @default.
• W4383371824 cites W2991168139 @default.
• W4383371824 cites W3011987578 @default.
• W4383371824 cites W3023357194 @default.
• W4383371824 cites W3034223876 @default.
• W4383371824 cites W3044367060 @default.
• W4383371824 cites W3046690279 @default.
• W4383371824 cites W3080654265 @default.
• W4383371824 cites W3101096440 @default.
• W4383371824 cites W3101994443 @default.
• W4383371824 cites W3130961991 @default.
• W4383371824 cites W3144026819 @default.
• W4383371824 cites W3172171371 @default.
• W4383371824 cites W3178832754 @default.
• W4383371824 cites W3182225677 @default.
• W4383371824 cites W3182945548 @default.
• W4383371824 cites W3190465468 @default.
• W4383371824 cites W3194858063 @default.
• W4383371824 cites W3197612695 @default.
• W4383371824 cites W3204242597 @default.
• W4383371824 cites W3213272676 @default.
• W4383371824 cites W3214186206 @default.
• W4383371824 cites W4211088821 @default.
• W4383371824 cites W4220972930 @default.
• W4383371824 cites W4281720261 @default.
• W4383371824 cites W4281846872 @default.
• W4383371824 cites W4307137826 @default.
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