Recent advances in the management of pruritus in chronic liver diseases

Tajiri, Kazuto; Shimizu, Yukihiro

doi:10.3748/wjg.v23.i19.3418

Cited by 39 publications

(35 citation statements)

References 111 publications

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“…Patients with PBC may be asymptomatic or present with a variety of symptoms, most commonly fatigue and/or pruritus 2 17. Pruritus, or itchy skin, affects up to 70% of patients with PBC and can interfere with daily life; because it is often worse at night, pruritus may prevent or disrupt sleep, increasing fatigue and affecting patient quality of life (QoL) 18–20. PBC-related pruritus often manifests in the limbs, causing itch on the palms and feet, as well as on the arms and legs 19.…”

Section: Introductionmentioning

confidence: 99%

“…Pruritus, or itchy skin, affects up to 70% of patients with PBC and can interfere with daily life; because it is often worse at night, pruritus may prevent or disrupt sleep, increasing fatigue and affecting patient quality of life (QoL) 18–20. PBC-related pruritus often manifests in the limbs, causing itch on the palms and feet, as well as on the arms and legs 19. It can range from mild to severe and can intensify in warmer temperatures 19.…”

Section: Introductionmentioning

confidence: 99%

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Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel

Pate

Gutierrez²,

Frenette

et al. 2019

BMJ Open Gastroenterol

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Background and aimsThis article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment.MethodsIn May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice.ResultsThese recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms.ConclusionsPruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel

Pate

Gutierrez²,

Frenette

et al. 2019

BMJ Open Gastroenterol

View full text Add to dashboard Cite

show abstract

“…Chronic itch, or pruritus, is a severe and potentially debilitating clinical feature associated with many dermatological and systemic conditions 1 , severely affecting quality of life and potentially leading to lassitude, fatigue, and even depression and suicidal tendencies 2 . The most well-characterized itch receptors are the H1 and H4 histamine receptors (HRH1 and HRH4) 3 .…”

Section: Introductionmentioning

confidence: 99%

“…Although antihistamines, which act by inhibiting histamine receptors, are generally effective at relieving itch symptoms induced by inflammation and allergens, these compounds are usually ineffective at treating chronic itch caused by systemic diseases and most skin disorders. To date, no effective treatment is available for treating histamine-resistant itch 2 .…”

Section: Introductionmentioning

confidence: 99%

MRGPRX4 is a novel bile acid receptor in cholestatic itch

Zhao

Liu

et al. 2019

Preprint

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Patients with liver diseases often suffer from chronic itch or pruritus, yet the itch-causing pruritogen(s) and their cognate receptor(s) remain largely elusive. Using transcriptomics and GPCR activation assays, we found that an orphan, primate specific MRGPRX4 is expressed in human dorsal root ganglia (hDRG) and selectively activated by bile acids. In situ hybridization and immunohistochemistry revealed that MRGPRX4 is expressed in ∼7% of hDRG neurons and co-localizes with HRH1, a known itch-inducing GPCR. Bile acids elicited a robust Ca2+ response in a subset of cultured hDRG neurons, and intradermal injection of bile acids and an MRGPRX4 specific agonist induced significant itch in healthy human subjects. Surprisingly, application of agonist for TGR5, a known sequence conserved bile acid receptor previously implicated in cholestatic itch, failed to elicit Ca2+ response in cultured hDRG neurons, nor did it induce pruritus in human subjects. In situ hybridization and immunostaining results revealed that hTGR5 is selectively expressed in satellite glial cells, unlike mTGR5 (in mouse DRG neurons), likely accounting for the inter-species difference functionally. Finally, we found that patients with cholestatic itch have significantly higher plasma bile acid levels compared to non-itchy patients and the bile acid levels significantly decreased after itch relief. This elevated bile acid level in itchy patients is sufficient to activate MRGPRX4. Taken together, our data strongly suggest that MRGPRX4 is a novel bile acid receptor that likely underlies cholestatic itch, providing a promising new drug target for anti-itch therapies.

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“…[1][2][3][4][5][6][7] The accumulation of bile acids in the sera and tissues as a consequence of chronic liver injury in patients with CLD is considered to be one of the major causes of pruritus. 7 Pruritus is associated with difficulty in falling asleep, middle awakening and loss of sufficient sleepiness.…”

Section: Introductionmentioning

confidence: 99%

Effect of nalfurafine hydrochloride in patients with chronic liver disease with refractory pruritus on sleep disorders: a study protocol for single-arm, prospective, interventional study

Nishikawa

Enomoto

Iwata

et al. 2017

BMJ Open Gastroenterol

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IntroductionChronic liver disease (CLD)-related pruritus manifests as cholestasis symptoms, which can cause severe itches in the whole body and significantly decrease quality of daily activities and sleep. The actigram, which documents movement by means of an accelerometer, has been demonstrated to be useful for assessing sleep quality. Nalfurafine hydrochloride, which is a selective κ-opioid receptor agonist, exerts its antipruritic efficacies through a novel mechanism. We aimed to prospectively examine the effect of nalfurafine hydrochloride on sleep quality for patients with CLD with pruritus utilising actigram.Methods and analysisThis study will be a single-centre, prospective, interventional, single-arm study. Our study participants are subjects whose pruritus was confirmed to be uncontrollable by antihistamines or antiallergics within 6 months before informed consent (IC). Evaluation time points using actigram will be (1) before administration of testing drug; (2) after 1 week; (3) after 4 weeks (primary endpoint); and (4) every 4 weeks thereafter. The follow-up period will be 6 months. We will prospectively assess and compare changes in sleep quality in patients with CLD with pruritus undergoing nalfurafine hydrochloride therapy using actigram. Quantitative variables will be compared by paired t-test.Ethics and disseminationThis study has received approval from the Institutional Review Board at Hyogo College of Medicine (approval no 2325). The study protocol, IC form and other documents were reviewed and approved. Final data will be publicly disseminated regardless of the results. A report releasing study results will be submitted in an appropriate journal.Trial registration numberUMIN000028161; Pre-results.

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Recent advances in the management of pruritus in chronic liver diseases

Cited by 39 publications

References 111 publications

Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel

Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel

MRGPRX4 is a novel bile acid receptor in cholestatic itch

Effect of nalfurafine hydrochloride in patients with chronic liver disease with refractory pruritus on sleep disorders: a study protocol for single-arm, prospective, interventional study

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