胆汁淤积性肝病继发皮肤瘙痒中西医诊疗研究进展

瘙痒常见于慢性胆汁淤积性肝胆疾病,也可伴发于几乎所有其他种类肝病。既往研究的胆汁淤积所致瘙痒的潜在致痒源有胆盐、组胺、孕酮代谢产物、内源性阿片类物质和溶血磷脂酸。中医认为血热血淤是引起胆汁淤积性瘙痒的主要原因。然而,胆汁淤积性瘙痒的确切发病机制尚不明确,现有的止痒治疗方法仅可使部分患者症状得以缓解。本文旨在回顾最近相关研究,对胆汁淤积性瘙痒的中西医病机、病理和治疗现状予以概述。     

浅谈胆汁淤积性肝病瘙痒的治疗

正胆汁淤积性肝病导致的瘙痒症状对患者来说常常难以忍受,临床上也缺乏有效的治疗手段。尽管大部分胆汁淤积性肝病都会引起瘙痒,包括原发性胆汁性胆管炎(PBC)、原发性硬化性胆管炎(PSC)、妊娠肝内胆汁淤积症(ICP)、遗传性或药物性胆汁淤积,在研究瘙痒症时我们仍把重点放在PBC。据统计,70%PBC患者存在瘙痒症状,而其中只有极少部分症状严重,这些人通常对药物治疗无应答[1]。现有的临床推荐治疗药     

胆汁淤积性肝病相关并发症的处理

正胆汁淤积性肝病(cholestatic liver disease,CLD)是指由肝脏原因引起的胆汁形成、分泌和(或)排泄障碍,使胆汁流淤积于肝胆系统而不能正常地流向肠道的疾病,临床上种类较多,如原发性胆汁性胆管炎(PBC)、原发性硬化性胆管炎(PSC)、药物性胆汁淤积等。CLD常见的并发症有瘙痒、疲劳、骨质疏松、认知障碍和脂溶性维生素缺乏等。1瘙痒1.1瘙痒的定义及其发病机制瘙痒是包括原发性胆汁性肝硬化(PBC)和PSC等胆汁淤积性肝病患者的常见症状~([1]),是指皮肤产生的一种刺激且不愉快的感觉,并容易激发搔抓     

原发性胆汁性肝硬化的治疗进展

原发性胆汁性肝硬化的治疗主要包括针对胆汁淤积的熊去氧胆酸、针对免疫异常发病机制的糖皮质激素或免疫抑制剂以及针对瘙痒症状、骨质疏松等并发症的对症治疗,终末期患者适合肝移植治疗.本文就原发性胆汁性肝硬化的治疗进展做一综述.     

胆汁淤积性肝病疲劳的发生机制、评估和治疗

胆汁淤积性肝病的典型肝外表现有瘙痒、脂肪泻、脂溶性维生素缺乏及代谢性骨病。近年来，人们开始注意到这类疾病中的疲劳也是一个明显的症状。由于其是非特异性症状，且缺乏客观的评估方法，所以直到现在仍然被大家所忽视。此外，目前对疲劳的发病机制及其治疗依旧不清楚。疲劳是一个复杂的症状，包括持续的衰竭感觉，正常工作能力缺失，心理和生理功能的下降。现在，由于患有原发性胆汁性肝硬化的患者在早期就得到诊断，了解疲劳症状的基本发病机制显得尤为重要。     

胆汁淤积性肝病相关皮肤瘙痒的机制和治疗进展

胆汁淤积性肝病如原发性胆汁性肝硬化、原发性硬化性胆管炎和妊娠期肝内胆汁淤积症,很常见的一个临床表现是皮肤瘙痒.其确切的发病机制仍不清楚,几种介质可能在其发病机制中发挥了一定作用,如溶血磷脂酸、胆盐、阿片类物质、组胺和孕酮的代谢产物.我们对其发病机制和治疗的研究进展作一综述,以便更好的认识和治疗胆汁淤积患者的皮肤瘙痒.     

原发性胆汁性胆管炎的药物治疗进展

原发性胆汁性胆管炎是一种病因及发病机制尚不明确的胆汁淤积性肝病。熊去氧胆酸和奥贝胆酸是美国食品药品监督管理局批准使用的治疗药物,两者均有减轻肝内胆汁淤积的作用,但仍有部分患者对其治疗无生化应答,亟需探索新的治疗药物或方法。贝特类药物、免疫抑制剂及中医药对原发性胆汁性胆管炎患者有一定疗效,但临床安全性及作用机制尚需进一步研究。     

原发性胆汁性胆管炎相关瘙痒症的管理

原发性胆汁性胆管炎(PBC)是一种进行性肝内胆汁淤积性自身免疫性疾病,瘙痒可见于60%~70%的PBC患者,并严重影响患者的生活质量。改善PBC患者的瘙痒症状对提高患者的生活质量有着重要意义。主要总结了PBC的发病机制、PBC相关瘙痒症的治疗进展。     

胆汁淤积性疲劳

胆汁淤积性肝病的典型表现有瘙痒、脂肪泻和代谢性骨病[1]。近年发现疲劳也是这类疾病中的一个明显症状,超过40%的原发性胆汁性肝硬化(PBC)患者感觉到中到重度疲劳[2]。这里疲劳是一种包括持续的衰竭感觉、正常工作能力的缺失以及心理和生理功能下降的复杂症状。在缺乏胆汁淤积性肝病和肝功能衰竭的症状时,疲劳被看作是胆汁淤积性肝病中一个最常见的虚弱症状,伴随疲劳而导致的社会功能障碍影响着患者的生活质量[3]。因此了解疲劳症状的     

间充质干细胞在原发性胆汁性胆管炎中的研究

原发性胆汁性胆管炎是一种慢性自身免疫性胆汁淤积性肝病。近年来研究发现,鉴于间充质干细胞具有免疫调节、抗纤维化和肝细胞分化的特性,正在成为治疗肝脏疾病的新方式,并且越来越多的证据表明间充质干细胞对原发性胆汁性胆管炎的治疗有积极作用。本文从原发性胆汁性胆管炎的发病机制以及间充质干细胞治疗原发性胆汁性胆管炎的作用机制、研究进展等方面展开叙述。间充质干细胞治疗原发性胆汁性胆管炎的前景十分广阔,值得进一步研究。     

Pathophysiology and current management of pruritus in liver disease

Pruritus is frequently reported by patients with cholestatic hepatobiliary diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy and hereditary cholestatic syndromes, but may accompany almost any other liver disease. Increased concentrations of bile salts, histamine, progesterone metabolites or endogenous opioids have been controversially discussed as potential pruritogens in cholestasis in the past. Most recently, novel insights unravelled lysophosphatidic acid (LPA), a potent neuronal activator, as a potential pruritogen in pruritus of cholestasis. Nevertheless, the pathogenesis of pruritus in cholestasis is still not clearly defined and current antipruritic treatment strategies provide relief only in a part of the affected patients. Based on recent experimental and clinical findings, this review outlines the actual insight in pathogenesis of pruritus in cholestasis and summarizes evidence-based and experimental therapeutic interventions for cholestatic patients suffering from itch.     

Pathogenesis and management of pruritus in cholestatic liver disease

Patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis and intrahepatic cholestasis of pregnancy commonly complain of pruritus. The underlying pathogenesis remains obscure with several mediators possibly playing an important role; these include lysophosphatidic acid, bile salts, opioids, histamine and progesterone metabolites. We describe in this review novel insights into the pathogenesis and management of pruritus in patients with cholestasis.     

LIVER DISEASE IN PREGNANCY,WITH PARTICULAR EMPHASIS ON THE CHOLESTATIC SYNDROMES

This review is primarily concerned with the ætiology, pathology, clinical features, differential diagnosis, pathogenesis and treatment of obstetric cholestasis and pruritus of pregnancy. The exact mechanism of the pruritus, jaundice and deranged biochemical state in these disorders is discussed in the light of advances in our understanding of bile salt metabolism and a recent and more acceptable concept of the pathogenesis of cholestasis. The incidence, ætiology and clinical features of cholestasis following oral contraceptives are outlined in detail, and the relationship of these changes to the cholestatic syndrome in the third trimester is discussed. Other hepatic disorders which appear to be related to pregnancy are also briefly reviewed. Biochemical derangements of hepatic function in pregnant women without underlying hepatic disease are considered in detail.     

Pruritus in chronic cholestatic liver disease

Pruritus is a troublesome complication in patients with cholestatic liver disease. Several links to its pathogenesis have been proposed, including the role of bile acids, endogenous opioid and serotonins, and lysophosphatidic acid. The management of pruritus in cholestasis is challenging. Medical treatment of the underlying cholestatic condition may provide benefit. Extracorporeal albumin dialysis can be pursued for those who have a poor quality of life and failed the various therapeutic interventions, while awaiting liver transplantation. Experimental interventions, and the management of pruritus in certain conditions such as intrahepatic cholestasis of pregnancy and benign recurrent intrahepatic cholestasis, are also briefly reviewed.     

Management of Pruritus in Primary Biliary Cholangitis: A Narrative Review

Primary biliary cholangitis is an autoimmune condition characterized by destruction of intrahepatic bile ducts. It causes debilitating symptoms that dramatically affect the patient's quality of life. Pruritus affects 60% to 70% of individuals with primary biliary cholangitis and leads to sleep disturbances, fatigue, depression, and suicidal ideation. A complete search was performed with studies from PubMed, EMBASE, Web of Science, Cochrane database, Countway Library, and CINAHL with specific search terms. This narrative review was prepared after a comprehensive literature review. Treating patients with cholestatic pruritus is challenging and may have a profound impact on quality of life. The standard of therapy for primary biliary cholangitis, ursodeoxycholic acid, does not have a beneficial effect in cholestatic pruritus. Patients often do not respond to conventional therapies such as cholestyramine, rifampicin, opioid antagonists, and sertraline. These therapies lack long-term efficacy and have side effects. Patients who have not responded to these initial treatments can be considered for experimental therapies or clinical trials. This review outlines the current and emerging treatment modalities for patients with primary biliary cholangitis who have pruritus.     

Long-term efficacy of sertraline as a treatment for cholestatic pruritus in patients with primary biliary cirrhosis

OBJECTIVES: Generalized pruritus is a common complication of cholestatic liver diseases, although its pathogenesis remains elusive. Current treatments are often inadequate and may be poorly tolerated, so the clinician is sometimes faced with a patient in misery and no good therapeutic options. Because, in our experience, several patients with primary biliary cirrhosis (PBC) claimed that sertraline had improved their pruritus, we sought to determine whether sertraline use was associated with changes in pruritus medications or self-reported severity of pruritus in a large cohort of patients with PBC. METHODS: The self-reported severity of pruritus was followed prospectively in 40 patients with PBC for a mean of 7.5 +/- 1.3 yr. These data were then retrospectively examined to determine the effect of sertraline on pruritus in all subjects who had received sertraline at some time during the study. RESULTS: For 28 of 32 patients with pruritus, itching was stable or fluctuated slightly over the follow-up period. No patient experienced rapid progression of pruritus, and four patients experienced a sustained resolution of their pruritus. Ten subjects started sertraline and continued it long enough (>6 months) to determine its lasting effect on pruritus. Three of these individuals did not have significant pruritus before or after sertraline. Of the seven patients with pruritus, six (86%) recorded a significant reduction or resolution of pruritus in their weekly diaries and also decreased or completely stopped other medications for pruritus. CONCLUSIONS: Sertraline use is associated with an improvement in cholestatic pruritus. This novel observation implies that serotonergic fibers are important in regulating the perception of itch.     

老年瘙痒症病理机制研究进展

老年瘙痒症发生的病理机制尚未完全阐明。角质细胞间脂质成分改变、膜丝聚蛋白结构不完整、天然保湿因子水平降低、pH值变化及雌激素水平降低等均可导致皮肤屏障功能受损, 并在皮肤瘙痒症的发病中起着重要作用。免疫衰老形成的炎性环境、神经的退行性改变与病理性损伤被认为是介导该病发生的自然病因。此外, 一些系统性疾病(如慢性肾脏疾病、胆汁淤积性疾病、糖尿病, 恶性肿瘤等)也与老年瘙痒症的发生、发展相关。深入阐明老年瘙痒症发生的病理机制, 可为防病治病提供有益的诊疗思路。     

Sertraline as a first-line treatment for cholestatic pruritus

Pruritus is frequently the most debilitating symptom of cholestatic liver diseases. Moreover, existing therapies are often ineffective. Recent small, retrospective case series reports suggest that serotonin reuptake inhibitors can improve pruritus. This study was undertaken to establish the dose of sertraline and to evaluate its efficacy for cholestatic pruritus. Twenty one subjects with chronic pruritus due to liver disease (including primary biliary cirrhosis, primary sclerosing cholangitis, chronic hepatitis C, and postnecrotic cirrhosis) initially underwent an open-label, dose escalation to determine the dose with optimal efficacy and tolerability. After a washout period, 12 of the subjects entered a randomized, double-blind, placebo-controlled trial. Participants quantified their pruritus using a 0-10 visual analog scale, and pruritus was assessed for distribution, timing, degree of disability, and physical evidence of scratching. The optimum sertraline dose (75-100 mg/day) was well tolerated. In the controlled portion of the study, itch scores improved in patients taking sertraline, but worsened in patients taking placebo (P=0.009). Changes in itch distribution, duration, direction, and physical evidence of scratching paralleled changes in the visual analog pruritus score. CONCLUSION: Sertraline seems to be an effective, well-tolerated treatment for pruritus due to chronic liver disease. These results suggest that serotonergic pathways are important in the perception of itch.     

Effect of oral naltrexone on pruritus in cholestatic patients

AIM:To determine the efficacy and potential complica-tions of oral naltrexone used in the treatment of pruritusin cholestatic patients and to compare them with otherstudies.METHODS:Thirty-four enrolled cholestatic patientscomplaining of pruritus were studied.In the initial phase,pruritus scores during day and night were evaluated.Sub-sequently,patients were given a placebo for one weekfollowed by naltrexone for one week.In each therapeuticcourse(placebo or naltrexone)day and night pruritusscores were distinguished by a visual analogue scale(VAS)system and recorded in patients'questionnaires.RESULTS:Both naltrexone and placebo decreased VASscores significantly.Naltrexone was more effective thanplacebo in decreasing VAS scores.Both day and nightscores of pruritus decreased by half of the value priorto therapy in thirteen patients(38%).Daytime pruritusimproved completely in two patients(5.9%),but no im-provement in the nighttime values was observed in anypatient.Sixteen patients(47%)suffered from naltrexonecomplications,eleven(32%)of them were related to itswithdrawal.Complications were often mild.In the caseof withdrawal,the complication was transient(withinthe first 24-28 h of therapy)and self-limited.We had tocease the drug in two cases(5.9%)because of severewithdrawal symptoms. CONCLUSION:Naltrexone can be used in the treatmentof pruritus in cholestatic patients and is a safe drugshowing few,mild and self-limited complications.