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Cholestasis associated Pruritus

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1. British Association of Dermatologists? guidelines for the investigation and management of generalized pruritus in adults without an underlying dermatosis

Pruritus is a common symptom in patients with various hepa- tobiliary disorders, including cholestasis of pregnancy. 138–140 The skin in hepatic pruritus is often generally hyperpigmented and excoriated. 141 The hands and feet are often the worst- affected areas. 139 Pruritus in association with fatigue at presen- tation may be a marker for more aggressive disease, for exam- ple primary biliary cholangitis. 142 There is a poor correlation between pruritus and bile acid levels, suggesting that other (...) factors may be relevant. 138,139 In patients with large bile duct obstruction, treatment is directed at restoration of biliary drainage, which is often associated with a prompt resolution of symptoms. 138,139 Nevertheless, measurement of serum bile acids may be important in detecting asymptomatic cholestasis in associa- tion with pruritus. 143 Ursodeoxycholic acid is frequently used to treat cholestasis of a range of causes, including cholestasis of pregnancy and primary biliary cholangitis. © 2017

2018 British Association of Dermatologists

2. Cholestasis associated Pruritus

Cholestasis associated Pruritus Cholestasis associated Pruritus Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer Administration 4 Cholestasis associated (...) Pruritus Cholestasis associated Pruritus Aka: Cholestasis associated Pruritus , Pruritus associated with Cholestatic Liver Disease II. Pathophysiology Bile salt protease release in skin and plasma III. Causes: Cholestasis Pancreatic carcinoma Primary biliary ( in all cases) Affects 0.5% of women in third trimester IV. Symptoms: Pruritus Intense itching worse at night Location (initial) Hands and feet Pressure areas V. Signs in areas of heavy scratching Spares midback resulting in butterfly-shaped rash

2018 FP Notebook

3. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. (PubMed)

and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth.We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated (...) Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations

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2019 Lancet

4. Cholestasis of pregnancy

Cholestasis of pregnancy Cholestasis of pregnancy - Symptoms, diagnosis and treatment | BMJ Best Practice You'll need a subscription to access all of BMJ Best Practice Search  Cholestasis of pregnancy Last reviewed: February 2019 Last updated: October 2017 Summary May be associated with an increased risk of adverse pregnancy outcomes, including premature birth, intra-uterine fetal demise, and placental abruption in severe disease. There is an increased risk of respiratory distress syndrome (...) disease with bile acid levels >40 micromol/L or severe pruritus remote from term can be treated effectively with ursodeoxycholic acid. Close fetal surveillance with delivery near term can be expected with premature delivery reserved for those with severe, worsening disease despite treatment. Definition Intrahepatic cholestasis of pregnancy (ICP) is a pruritic condition during pregnancy caused by impaired bile flow allowing bile salts to be deposited in the skin and the placenta. The cause

2017 BMJ Best Practice

5. What guidance is there available on the use of vitamin K for the management of obstetric cholestasis?

2017 Background Obstetric cholestasis (OC) or intrahepatic cholestasis of pregnancy has been described as a multifactorial condition of pregnancy characterised by intense pruritus with the absence of a skin rash, with abnormal liver function tests, neither of which have an alternative cause and both of which resolve after birth(1). It is associated with a significantly increased risk of adverse perinatal outcomes, including stillbirth (2). The use of vitamin K as part of the management of OC (...) & Gynaecology 2007; 114: 656 (6). Memtsa M, Pun S, West P et al. Consensus on the management of obstetric cholestasis: National UK Survey. BJOG: An International Journal of Obstetrics & Gynaecology 2007; 114: 910-911 (7). International Guidelines European Association for the Study of the Liver* EASL Clinical Practice Guidelines: Available through Specialist Pharmacy Service at www.sps.nhs.uk Medicines Q&As Management of cholestatic liver diseases. Journal of Hepatology 51 (2009) 237–267 Accessed via http

2017 Specialist Pharmacy Services

6. Hepatitis C virus-associated pruritus: Etiopathogenesis and therapeutic strategies (PubMed)

Hepatitis C virus-associated pruritus: Etiopathogenesis and therapeutic strategies In addition to its contributing role in the development of chronic liver diseases, chronic hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, particularly, cutaneous-based disorders including those with pruritus as a symptom. Pruritus is frequently associated with the development of chronic liver diseases such as cholestasis and chronic viral infection, and the accumulation of bile (...) potential vanilloid 1 (TRPV1) leading to the induction of pruritus by an unknown mechanism. Although the pathologic phenomenon of pruritus is common, there is no uniformly effective therapy available. Understanding the mechanisms regulating the occurrence of pruritus together with the conduction of large-scale clinical and evidence-based studies, may help to create a standard treatment protocol. This review focuses on the etiopathogenesis and treatment strategies of pruritus associated with chronic HCV

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2017 World Journal of Gastroenterology

7. Prognostic and mechanistic potential of progesterone sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum. (PubMed)

Prognostic and mechanistic potential of progesterone sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum. A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated (...) pregnancy = 29/100), demonstrating that all three progesterone sulfates are prognostic for ICP. Concentrations of progesterone sulfates were associated with itch severity and, in combination with autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of first-trimester samples all progesterone sulfates were significantly elevated in serum from low-risk asymptomatic women who

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2015 Hepatology

8. Is ursodeoxycholic acid effective for intrahepatic cholestasis of pregnancy?

Is ursodeoxycholic acid effective for intrahepatic cholestasis of pregnancy? Intrahepatic cholestasis of pregnancy is a condition associated with fetal morbidity and mortality. Ursodeoxycholic acid has been proposed as a treatment alternative, but its use remains controversial. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including eight randomized trials. We combined the evidence using meta-analysis and generated (...) a summary of findings table following the GRADE approach. We concluded ursodeoxycholic acid reduces prematurity risk and need for admission in neonatal intensive care units. It might also reduce maternal pruritus.

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2017 Medwave

9. The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC. (PubMed)

-treated patients. Rates of grade 2 or 3 pruritus were 14% with 100 mg, 20% with 30 mg, and 40% with placebo. Conclusion: In this 12-week, randomized, placebo-controlled study, cilofexor was well tolerated and led to significant improvements in liver biochemistries and markers of cholestasis in patients with PSC.© 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases. (...) The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC. Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a phase II double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor agonist in patients without cirrhosis with large-duct PSC. Patients were randomized to receive cilofexor 100 mg (n = 22), 30 mg (n = 20

2019 Hepatology

10. Severe and protracted cholestasis in 44 young men taking bodybuilding supplements: assessment of genetic, clinical and chemical risk factors. (PubMed)

Severe and protracted cholestasis in 44 young men taking bodybuilding supplements: assessment of genetic, clinical and chemical risk factors. Bodybuilding supplements can cause a profound cholestatic syndrome.To describe the drug-Induced liver injury network's experience with liver injury due to bodybuilding supplements.Liver injury pattern, severity and outcomes, potential genetic associations, and exposure to anabolic steroids by product analysis were analysed in prospectively enrolled (...) ). Liver biopsy (59% of subjects) demonstrated a mild hepatitis and profound cholestasis in most without bile duct injury, loss or fibrosis. Seventy-one per cent were hospitalised, and none died or required liver transplantation. In some, chemical analysis revealed anabolic steroid controlled substances not listed on the label. No enrichment of genetic variants associated with cholestatic syndromes was found, although mutations in ABCB11 (present in up to 20%) were significantly different than

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2019 Alimentary Pharmacology & Therapeutics

11. Pruritus Secondary to Primary Biliary Cholangitis: A Review of the Pathophysiology and Management with Phototherapy. (PubMed)

Pruritus Secondary to Primary Biliary Cholangitis: A Review of the Pathophysiology and Management with Phototherapy. Primary biliary cholangitis (PBC) is an autoimmune hepatobiliary disorder characterised by destruction of liver bile ducts leading to intrahepatic cholestasis. It is a disease associated with significant morbidity, and is characterised in particular, by intractable pruritus for which treatments are often unsuccessful. Although used in clinical practice by dermatologists in the UK (...) , the evidence base for phototherapy in this condition is not well documented. Case studies have reported on the clinical outcome of phototherapy in cholestatic pruritus which are summarised in this review. In addition, this review considers recent studies that provide insight into the pathophysiology of itch in PBC; these include the role of bile salts, autotaxin and specific receptors including G-protein-coupled bile acid receptor, Gpbar1 (TGR5) and the nuclear transcription factor farnesoid X receptor

2019 British Journal of Dermatology

12. Cholestasis associated Pruritus

Cholestasis associated Pruritus Cholestasis associated Pruritus Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer Administration 4 Cholestasis associated (...) Pruritus Cholestasis associated Pruritus Aka: Cholestasis associated Pruritus , Pruritus associated with Cholestatic Liver Disease II. Pathophysiology Bile salt protease release in skin and plasma III. Causes: Cholestasis Pancreatic carcinoma Primary biliary ( in all cases) Affects 0.5% of women in third trimester IV. Symptoms: Pruritus Intense itching worse at night Location (initial) Hands and feet Pressure areas V. Signs in areas of heavy scratching Spares midback resulting in butterfly-shaped rash

2015 FP Notebook

13. Intrahepatic Cholestasis of Pregnancy: A Review of Diagnosis and Management. (PubMed)

Intrahepatic Cholestasis of Pregnancy: A Review of Diagnosis and Management. Intrahepatic cholestasis of pregnancy (ICP) complicates approximately 0.2% to 2% of pregnancies and can lead to increased fetal risks in pregnancy.This review aims to increase the knowledge of women's health care providers regarding the diagnosis, management, and fetal risks associated with ICP.The diagnosis of ICP is based on symptoms of pruritus that typically include the palms and soles, as well as elevated bile (...) pruritus symptoms, as well as biochemical tests, but no treatment has been shown to definitively improve fetal outcomes.Providers should be aware of the signs and symptoms of ICP and provide accurate diagnosis and management of affected women. Women with a diagnosis of ICP should be treated with ursodeoxycholic acid to improve maternal symptoms. Given the increased risk of stillbirth in the setting of ICP, delivery may be considered at 37 weeks' gestation.

2018 Obstetrical & Gynecological Survey

14. Ursodeoxycholic acid versus placebo in the treatment of women with intrahepatic cholestasis of pregnancy (ICP) to improve perinatal outcomes: protocol for a randomised controlled trial (PITCHES) (PubMed)

Ursodeoxycholic acid versus placebo in the treatment of women with intrahepatic cholestasis of pregnancy (ICP) to improve perinatal outcomes: protocol for a randomised controlled trial (PITCHES) Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder specific to pregnancy and presents with maternal pruritus, raised concentrations of serum bile acids and abnormal liver function tests. ICP is associated with increased rates of spontaneous and iatrogenic preterm labour, fetal (...) hypoxia, meconium-stained amniotic fluid and intrauterine death. Some clinicians treat ICP with ursodeoxycholic acid (UDCA) to improve maternal pruritus and biochemical abnormalities. However, there are currently no data to support the use of UDCA to improve pregnancy outcome as none of the trials performed to date have been powered to address this question.The PITCHES trial is a triple-masked, placebo-controlled randomised trial, to evaluate UDCA versus placebo in women with ICP between 20 + 0 to 40

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2018 Trials

15. Severe renal Fanconi and management strategies in Arthrogryposis-Renal dysfunction-Cholestasis syndrome: a case report. (PubMed)

Severe renal Fanconi and management strategies in Arthrogryposis-Renal dysfunction-Cholestasis syndrome: a case report. Arthrogryposis-Renal dysfunction-Cholestasis syndrome (ARC, MIM#208085) is a rare multisystem disease due to mutations in the VPS33B and VIPAR genes, both involved in maintaining apical-basolateral cell polarity. The correlation between mutations and phenotype in the ARC Syndrome is not well described. We report on a 6 year old patient who presented with severe renal Fanconi (...) as first manifestation of ARC related to a combined de novo mutation in the VPS33B gene.A 6 year old girl presented during the first year of life with severe renal Fanconi as the first manifestation of ARC-Syndrome. This case presents all defining features of ARC syndrome (including liver, skin and articular manifestations) with predominantly renal impairment at presentation. This novel mutation may be associated with a pronounced renal phenotype in ARC. Furthermore, we report on the successful use

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2018 BMC Nephrology

16. Pruritus (PDQ®): Health Professional Version

sensation. It is thought that spinal modulation of afferent stimuli (Gate theory) and central mechanisms may play a role in the relief of itch.[ ] Hypothesized pathogenesis of pruritus associated with underlying disease states are varied. Biliary, hepatic, renal, and malignant diseases are thought to produce pruritus through circulating toxic substances. Histamine released from circulating basophils and the release of leukopeptidase from white blood cells may trigger pruritus associated with lymphomas (...) . [ ] Duque MI, Thevarajah S, Chan YH, et al.: Uremic pruritus is associated with higher kt/V and serum calcium concentration. Clin Nephrol 66 (3): 184-91, 2006. [ ] Rishe E, Azarm A, Bergasa NV: Itch in primary biliary cirrhosis: a patients' perspective. Acta Derm Venereol 88 (1): 34-7, 2008. [ ] Cribier B, Samain F, Vetter D, et al.: Systematic cutaneous examination in hepatitis C virus infected patients. Acta Derm Venereol 78 (5): 355-7, 1998. [ ] Oaklander AL, Bowsher D, Galer B, et al.: Herpes zoster

2016 PDQ - NCI's Comprehensive Cancer Database

17. Obstetric Cholestasis

an alternative cause and both of which resolve after birth. Most authorities accept elevations of any of a wide range of LFTs beyond pregnancy-specific limits. 4 Investigations to exclude other causes of pruritus and of abnormal LFTs should be performed. The clinical importance of obstetric cholestasis lies in the potential fetal risks, which may include spontaneous preterm birth,iatrogenic preterm birth and fetal death.There can also be maternal morbidity in association with the intense pruritus (...) Obstetric Cholestasis Obstetric Cholestasis Green–top Guideline No. 43 April 2011© Royal College of Obstetricians and Gynaecologists 2 of 14 RCOG Green-top Guideline No.43 Obstetric Cholestasis This is the second edition of this guideline.The first edition was published in 2006 under the same title. 1. Purpose and scope This guideline summarises the evidence for the fetal risks associated with obstetric cholestasis and provides guidance on the different management choices and the options

2011 Royal College of Obstetricians and Gynaecologists

18. A Drug Regimen for Progressive Familial Cholestasis Type 2. (PubMed)

A Drug Regimen for Progressive Familial Cholestasis Type 2. Progressive familial cholestasis type 2 is caused by a genetically determined absence or reduction in the activity of the bile salt export pump (BSEP). Reduction or absence of BSEP activity causes a failure of bile salt excretion, leading to accumulation of bile salts in hepatocytes and subsequent hepatic damage. Clinically, patients are jaundiced, suffer from severe intractable pruritus, and evidence progressive liver dysfunction (...) . A low level of serum γ-glutamyl transpeptidase, when associated with the described signs and symptoms, is often an early identifier of this condition. Treatment options to date include liver transplantation and the use of biliary diversion. We report a multidrug regimen of 4-phenylbutyrate, oxcarbazepine, and maralixibat (an experimental drug owned by Shire Pharmaceuticals, Dublin, Republic of Ireland) that completely controlled symptoms in 2 siblings with partial loss of BSEP activity.Copyright ©

2017 Pediatrics

19. [Meta-analysis of Yinzhihuang oral liquid in treatment of intrahepatic cholestasis of pregnancy]. (PubMed)

[Meta-analysis of Yinzhihuang oral liquid in treatment of intrahepatic cholestasis of pregnancy]. To systematically review the clinical efficacy and safety of Yinzhihuang oral liquid in the treatment of intrahepatic cholestasis of pregnancy(ICP). Literatures published by June 2016 were searched in databases, such as Medline, Pubmed, Cochrane Library, China National Knowledge Infrastructure(CNKI), Chinese Scientific Journals Full-text Database(VIP), Chinese biomedical literature database(CBM (...) ), and Wanfang Database. Randomized controlled trials(RCT) of Yinzhihuang oral liquid were collected according to the inclusion criteria, and the methodological quality of selected literatures was evaluated. The Meta-analysis was conducted by using RevMan 5.3 software. A total of 7 RCTs involving 711 patients were included. The results of Meta-analysis showed that, compared with control group, Yinzhihuang oral liquid significantly alleviated pruritus symptoms[MD=-0.68, 95%CI(-0.95,-041), P<0.000 01], reduced

2017 Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica

20. norUrsodeoxycholic Acid Improves Cholestasis in Primary Sclerosing Cholangitis. (PubMed)

norUrsodeoxycholic Acid Improves Cholestasis in Primary Sclerosing Cholangitis. Primary sclerosing cholangitis (PSC) represents a devastating bile duct disease, currently lacking effective medical therapy. 24-norursodeoxycholic acid (norUDCA) is a side chain-shortened C23 homologue of UDCA and has shown potent anti-cholestatic, anti-inflammatory and anti-fibrotic properties in a preclinical PSC mouse model. A randomized controlled trial, including 38 centers from 12 European countries (...) . There was no difference in reported pruritus between treatment and placebo groups.norUDCA significantly reduced ALP values dose-dependently in all treatment arms. The safety profile of norUDCA was excellent and comparable to placebo. Consequently, these results justify a phase III trial of norUDCA in PSC patients. Lay summary: Effective medical therapy for primary sclerosing cholangitis (PSC) is urgently needed. In this phase II clinical study in PSC patients, a side chain-shortened derivative of ursodeoxycholic acid

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2017 Journal of Hepatology

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