良性复发性肝内胆汁淤积

良性复发性肝内胆汁淤积(benign recurrent intrahepatic cholestasis,BRIC)于1959年由Summerskill和Walshe首先提出,其特征是反复发作数周至数月的自限性严重瘙痒和黄疸.BRIC呈散发性分布,约50%的病例具有胆汁淤积家族史,遗传学研究证实,BRIC是常染色体隐性遗传病,缺损基因位于第18号染色体的长臂上:18q21-22,该基因已命名为FIC(familial in-trahepatic cholestasis)-1.     

良性复发性肝内胆汁淤积

良性复发性肝内胆汁淤积（Benign recurrent intrahepatic cholestasis,BRIC）的临床特点为持续数周至数月的反复发作性、自限性严重瘙痒和黄疸。虽然BRIC每次发作均伴有明显症状,但不会发生严重的肝损害和肝硬化。之所以使用良性复发性肝内胆汁淤积这一术语,目的在于与其他原因引起的黄疸,如Byler病相区别,因为后者是一种预后极差的严重疾病。目前对该病的病理生理学仍所知甚少,     

3例良性复发性肝内胆汁淤积症患者临床特点分析

目的 总结和分析良性复发性肝内胆汁淤积症(BRIC)患者的临床特征。方法 回顾性分析3例在复旦大学附属中山医院诊治的BRIC患者的一般情况、临床表现、实验室检查、影像学检查、病理学检查和分子遗传学检查等临床资料。结果 3例患者均为男性,首次发病年龄小于20岁,除外其他已知的可致胆汁淤积的病因;3例患者疾病均反复发作,但具有一定的自限性,发作时有黄疸和皮肤瘙痒表现,其中2例伴大便不规律、腹胀和食欲下降;实验室检查显示血清总胆红素和直接胆红素、碱性磷酸酶和总胆汁酸水平显著升高,而γ-谷氨酰转肽酶和转氨酶水平正常或轻度升高;MRCP检查均未见有肝内外胆管异常;2例肝组织病理学检查提示肝细胞明显胆汁淤积伴毛细胆管栓塞形成;3例患者均有功能预测为“潜在有害”或致病分级为“可能致病”的ATP8B1基因突变位点检出。结论 目前,BRIC病例报道较少,发病机制未完全明确,诊断较困难。临床医生应在排除其他常见肝损伤病因后,综合分析其临床表现、辅助检查和病理学检查结果进行综合临床诊断。对于临床高度怀疑BRIC的患者,应尽早行分子遗传学检查,以明确诊断,指导治疗。     

良性复发性肝内胆汁淤积症中医治疗1例

1病历简介 彭某,男,18岁。主诉：反复皮肤瘙痒、眼黄、尿黄12年,加重7天。于1997年患儿＂感冒＂后出现皮肤瘙痒、目黄、尿黄（浓茶色）,无发热、腹痛、纳差等症状,当地医院检查未明确病因,予降酶保肝退黄等治疗后病情缓解（具体用药不详）,其后未复查。     

烫伤膏治疗药物过敏严重剥脱性皮炎2例的护理

剥脱性皮炎为严重型药物性皮炎，起病急，常伴有寒战、高热，患者全身皮肤脱屑呈鳞片状或落叶状，手足部则呈手套或袜套状剥脱，炎性显著，重症患者可因全身衰竭或继发感染而死亡。我院于2005年2月和2005年8月分别收治1例药物过敏严重剥脱性皮炎患者，1例经过20余天的精心治疗和护理。疾愈出院，另1例皮炎好转后，但冈其原发病放弃治疗同家。现将此2例患者的护理体会介绍如下。     

良性复发性肝内胆汁淤积症2型1例

良性复发性肝内胆汁淤积症(BRIC)是以反复发作的自限性严重瘙痒和黄疸为特征的胆汁淤积性肝病。现报道1例BRIC 2型病例。     

良性复发性肝内胆汁淤积一例

患者,女性,52岁,山东籍,因间断性皮肤瘙痒、巩膜黄染、尿黄23年入院。患者1984年无诱因出现皮肤瘙痒、巩膜黄染、尿黄,无发热、皮疹,无消化道症状,胆红素升高,总胆红素（TBil）最高220μmol／L,经保肝、降酶及中药退黄等治疗后,肝功能恢复正常,此后未再出现皮肤瘙痒。间断复查肝功能正常。2007年3月初感皮肤瘙痒,尿黄,无其他不适,我院查肝功能示：TBil／DBil22．9／5．7μmol／L,丙氨酸氨基转移酶（ALT）245U／L、天冬氨酸氨基转移酶（AST）260U／L,查肝炎病毒、自身抗体均阴性,肝胆脾胰彩超及腹部MRI均无异常.     

抗结核药致剥脱性皮炎13例护理体会

剥脱性皮炎是一种累及全身或几乎全身皮肤的红斑鳞屑性皮肤病[1].起病急,常伴有寒战、高热,患者全身皮肤脱屑呈鳞片状或落叶状,手足部则呈手套或袜套状剥脱,炎性显著,重症患者可因全身衰竭或继发感染而死亡.药源性剥脱性皮炎是严重的药疹之一,现将我院收治的13例抗结核药所致剥脱性皮炎护理体会整理如下.     

氟达拉滨致全身剥脱性皮炎1例护理体会

我科于2008年1月收治1例慢性淋巴细胞白血病（CLL）患者,应用氟达拉滨导致全身剥脱性皮炎型药疹,经及时发现积极治疗和护理,取得较好效果。现将护理体会报告如下。     

Successfully treated intractable pruritus with rifampin in a case of benign recurrent intrahepatic cholestasis

A 56-year-old gentleman with benign recurrent intrahepatic cholestasis (BRIC) suffered from recurrent episodes of pruritus for over 40 years. The treatment prescribed, namely cholestyramine, was minimally effective. However, rifampin 150 mg b.i.d promptly and completely relieved his severe pruritus. The diagnosis of BRIC, being a rare condition, may go unrecognized. The severity of the lifelong episodes of intermittent cholestasis with pruritus in BRIC may be extremely distressing to the affected patient. Administration of rifampin during the acute episode of severe pruritus led to a marked improvement in his quality of life.     

Treatment of pruritus with Prometheus dialysis and absorption system in a patient with benign recurrent intrahepatic cholestasis

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disorder characterized by recurrent episodes of jaundice and itching. Episodes of cholestasis last variously from 1 week to several months, may start at any age and usually resolve spontaneously. No effective treatment has been found as yet. We report a case of genetically proven BRIC in a male patient who developed three episodes of pruritus and jaundice at the age of 14, 16 and 19 years. During the third episode, he did not respond to pharmacological medical therapy, and fractionated plasma separation and absorption (FPSA, Prometheus) was performed to manage intractable pruritus. The treatment immediately alleviated pruritus, lowered serum bilirubin concentration and induced sustained remission in the 5‐year follow up. FPSA seems to be a safe and effective way of treatment for BRIC in patients with severe pruritus and prolonged jaundice.     

Description of two new ABCB11 mutations responsible for type 2 benign recurrent intrahepatic cholestasis in a French-Canadian family

Benign recurrent intrahepatic cholestasis is a rare clinical entity that is caused by mutations in the canalicular transport genes. The present report describes two individuals from the same family whose symptoms were typical of the clinical characteristics of type 2 benign recurrent intrahepatic cholestasis. Sequencing of the ABCB11 gene revealed two previously unreported mutations that predict the absence of expression of the protein. The clinical presentation of the current cases are discussed, as are the differential diagnosis and genetic characteristics of the hereditary cholestatic disorders, overemphasizing the possibility of making a definite genetic diagnosis.     

Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11

BACKGROUND & AIMS: Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BRIC) are hereditary liver disorders; PFIC is characterized by severe progressive liver disease whereas BRIC patients have intermittent attacks of cholestasis without permanent liver damage. Mutations in ATP8B1 are present in PFIC type 1 and in a subset of BRIC patients. We hypothesized that a genetically distinct form of BRIC is associated with mutations in ABCB11. This gene encodes the bile salt export pump (BSEP) and is mutated in PFIC type 2. METHODS: Patients from 20 families were included; all had a normal ATP8B1 sequence. Sequencing of all 27 coding exons including the splice junctions of ABCB11 revealed 8 distinct mutations in 11 patients from 8 different families: one homozygous missense mutation (E297G) previously described in PFIC2 patients, 6 novel missense mutations, and one putative splice site mutation. RESULTS: In 12 families, no mutations in ATB8B1 or ABCB11 were detected. Pancreatitis is a known extrahepatic symptom in BRIC caused by ATP8B1 mutations, but was not present in BRIC patients with mutations in ABCB11. In contrast, cholelithiasis was observed in 7 of 11 BRIC patients with mutations in ABCB11, but has not been described in ATP8B1-affected BRIC patients. CONCLUSIONS: Mutations in ABCB11 are associated with BRIC, and consistent with the genetic classification of PFIC into 2 subtypes, we propose that this disorder be named BRIC type 2.     

Expanding etiology of progressive familial intrahepatic cholestasis

BACKGROUND Progressive familial intrahepatic cholestasis(PFIC) refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes, resulting in a hepatocellular form of cholestasis. While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause, recent scientific advancements have uncovered multiple specific responsible proteins. The variety of identified defects has resulted in an ever-broadening phenotypic spectrum, ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis, explore the expanding knowledge base of genetic based diseases in this field, and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines. We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding, diagnosis, and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC. English only articles were accessed in full. The manual search included references of retrieved articles.We extracted data on disease characteristics, associations with other diseases, and treatment. Data was summarized and presented in text, figure, and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults. A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8 B1), BSEP(ABCB11), and MDR3(ABCB4) transporter deficiencies, as well as more recently described gene mutations--TJP2(TJP2), FXR(NR1 H4), MYO5 B(MYO5 B), and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.     

Atypical causes of cholestasis

Cholestatic liver disease consists of a variety of disorders. Primary sclerosing cholangitis and primary biliary cirrhosis are the most commonly recognized cholestatic liver disease in the adult population, while biliary atresia and Alagille syndrome are commonly recognized in the pediatric population. In infants, the causes are usually congenital or inherited. Even though jaundice is a hallmark of cholestasis, it is not always seen in adult patients with chronic liver disease. Patients can have “silent” progressive cholestatic liver disease for years prior to development of symptoms such as jaundice and pruritus. In this review, we will discuss some of the atypical causes of cholestatic liver disease such as benign recurrent intrahepatic cholestasis, progressive familial intrahepatic cholestasis, Alagille Syndrome, biliary atresia, total parenteral nutrition induced cholestasis and cholestasis secondary to drug induced liver injury.     

Nonsense variant of ATP8B1 gene in heterozygosis and benign recurrent intrahepatic cholestasis: A case report and review of literature

BACKGROUND Benign recurrent intrahepatic cholestasis is a genetic disorder with recurrent cholestatic jaundice due to ATP8B1 and ABCB11 gene mutations encoding for hepato-canalicular transporters. Herein, we firstly provide the evidence that a nonsense variant of ATP8B1 gene(c.1558AT) in heterozygous form is involved in BRIC pathogenesis.CASE SUMMARY A 29-year-old male showed severe jaundice and laboratory tests consistent with intrahepatic cholestasis despite normal gamma-glutamyltranspeptidase. Acute and chronic liver diseases with viral, metabolic and autoimmune etiology were excluded. Normal intra/extra-hepatic bile ducts were demonstrated by magnetic resonance. Liver biopsy showed: Cholestasis in the centrilobular and intermediate zones with bile plugs and intra-hepatocyte pigment, Kupffer's cell activation/hyperplasia and preserved biliary ducts. Being satisfied benign recurrent intrahepatic cholestasis diagnostic criteria, ATP8B1 and ABCB11 gene analysis was performed. Surprisingly, we found a novel nonsense variant of ATP8B1 gene(c.1558AT) in heterozygosis. The variant was confirmed by Sanger sequencing following a standard protocol and tested for familial segregation,showing a maternal inheritance. Immunohistochemistry confirmed a significant reduction of mutated gene related protein(familial intrahepatic cholestasis 1).The patient was treated with ursodeoxycholic acid 15 mg/kg per day and colestyramine 8 g daily with total bilirubin decrease and normalization at the 6~(th) and 12~(th) mo.CONCLUSION A genetic abnormality, different from those already known, could be involved in familial intrahepatic cholestatic disorders and/or pro-cholestatic genetic predisposition, thus encouraging further mutation detection in this field.     

Successful treatment with colestimide for a bout of cholestasis in a Japanese patient with benign recurrent intrahepatic cholestasis caused by ATP8B1 mutation

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive disorder characterized by bouts of cholestasis that resolve spontaneously without leaving considerable liver damage. Most of BRIC patients have mutations in ATP8B1 gene coding FIC1 protein. It has been suggested that an imbalance between the gut absorption of bile acids and the liver excretion possibly causes the development of cholestasis. We encountered a Japanese woman patient with familial intrahepatic cholestasis type 1 (FIC1) deficiency manifesting BRIC, in whom a rapid and gross elevation of serum total bile acid (TBA) level preceded that of serum total bilirubin level. Interestingly, the early administration of colestimide prevented the development of hyperbilirubinemia along with the additional elevation of serum TBA level. This case suggests that FIC1 deficiency causes an imbalance between the gut absorption of bile acids and the liver excretion leading to cholestasis, and raised the possibility that colestimide may be used as an optional treatment for BRIC.