Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with...Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with medications,autoimmune disorders,cancer,transplantation,and infections,the specific mechanisms of disease are not known.To date,only 4 cases of VBDS have been reported in human immunodeficiency virus(HIV) infected patients.We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases.Presentation includes hyperbilirubinemia,normal liver imaging,and negative viral and autoimmune hepatitis studies.In HIV-infected subjects,VBDS occurred at a range of CD4+ T-cell counts,in some cases following initiation or change in antiretroviral therapy.Lymphoma was associated with two cases;nevirapine,antibiotics,and viral co-infection were suggested as etiologies in the other cases.In HIV-positive patients with progressive cholestasis,early identification of VBDS and referral for transplantation may improve outcomes.展开更多
Vanishing bile duct syndrome (VBDS) refers to a group of disorders characterized by prolonged cholestasis as a result of destruction and disappearance ofintrahepatic bile ducts. Multiple etiologies have been indentifi...Vanishing bile duct syndrome (VBDS) refers to a group of disorders characterized by prolonged cholestasis as a result of destruction and disappearance ofintrahepatic bile ducts. Multiple etiologies have been indentifi ed including infections, neoplastic disorders, autoimmune conditions and drugs. The natural history of this condition is variable and may involve resolution of cholestasis or progression with irreversible damage. VBDS is extremely rare in human immunodeficiency virus (HIV)-infected patients and anti-retroviral therapy has never been implicated as a cause. We encountered a young pregnant female with HIV and VBDS secondary to anti-retroviral therapy. Here, we report her clinical course and outcome.展开更多
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic fai...BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the- counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractable pruritus that developed shortly after taking naproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS: Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.展开更多
胆管消失综合征(vanishing bile duct syndromeVBDS)病因较多,主要有先天性和遗传性疾病、缺血缺氧、肿瘤、感染、免疫紊乱、药物、特发性成人肝内胆管缺失症等因素.近年报道比较多的病因是淋巴瘤、HIV感染/AIDS和药物,有些VBDS病例较复...胆管消失综合征(vanishing bile duct syndromeVBDS)病因较多,主要有先天性和遗传性疾病、缺血缺氧、肿瘤、感染、免疫紊乱、药物、特发性成人肝内胆管缺失症等因素.近年报道比较多的病因是淋巴瘤、HIV感染/AIDS和药物,有些VBDS病例较复杂,可能不止一种因素参与.VBDS的诊断需要肝脏组织学检查,肝组织角蛋白7(cytokeratin 7,CK7)和CK19免疫组织化学检查有助于提高VBDS诊断的可靠性.VBDS的治疗主要是对症支持治疗、病因治疗、肝移植、熊去氧胆酸和免疫抑制剂的应用,糖皮质激素疗效不好或不良反应明显时可以试换用吗替麦考酚酯或他克莫司,重症病例强调包括血浆置换的综合治疗.展开更多
目的探讨与药物性胆管消失综合征((drug?vanishing bile duct syndrome,D?VBDS)预后相关的临床、病理组织学及肝生化学特点。方法采用回顾性研究方法选取2003年1月至2017年12月石家庄市第五医院经肝穿刺病理明确诊断为D?VBDS的45例病人...目的探讨与药物性胆管消失综合征((drug?vanishing bile duct syndrome,D?VBDS)预后相关的临床、病理组织学及肝生化学特点。方法采用回顾性研究方法选取2003年1月至2017年12月石家庄市第五医院经肝穿刺病理明确诊断为D?VBDS的45例病人,根据再次追踪随访的肝生化指标及临床症状体征情况,将其分为预后转归好与差分为两组,对比分析两组病人的性别构成、发病年龄、用药史、病理形态学特点及血清学指标等数据,并对病理形态学特点进行半定量评分。结果31例D?VBDS病人预后较好,14例D?VBDS病人预后较差。两组在性别构成(χ^2=0.106,P=0.745)及发病年龄(t=2.988,P=0.394)比较,均差异无统计学意义(P>0.05),均以40~60岁女性最多见。中药及中成药是引起D?VBDS最主要的药物(51.1%),其次为阿奇霉素(11.1%)及解热镇痛药(9.0%)。肝生化各指标高峰值比较,预后差组总胆红素(TBil)、直接胆红素(DBil)、总胆汁酸(TBA)、球蛋白(GLB)、总胆固醇(TG)(t=6.436,P=0.000;t=5.847,P=0.000;t=3.569,P=0.033;t=2.381,P=0.031;t=2.328,P=0.041)水平明显高于预后好组,白蛋白(ALB)、胆碱酯酶(CHE)(t=2.445,P=0.020;t=3.003,P=0.012)水平明显低于预后好组,差异有统计学意义(P<0.05)。两组病理形态学特点对比显示,汇管区炎症和纤维化、胆盐淤积、细胆管增生及毛细胆管淤胆评分(t=2.437,P=0.017;t=4.416,P=0.001;t=4.214,P=0.001;t=3.050,P=0.006;t=2.716,P=0.009)两组差异有统计学意义(P<0.05)。结论影响D?VBDS预后的因素与胆管损伤的级别、范围、胆管再生修复状况等因素有关。血清TBil、DBil、TBA、TC、GLB水平的持续升高及ALB、CHE水平持续降低可作为预测预后的肝生化学指标。肝组织中汇管区炎症和纤维化程度、胆盐淤积程度、细胆管增生程度及毛细胆管淤胆程度为与预后相关的病理形态学特点,肝穿组织病理检查结果仍是明确诊断及判断预后的金标准。展开更多
肝内胆管缺失是指肝内胆管数量的减少或消失,是胆管树基本病理改变之一。免疫紊乱、肿瘤、感染、药物、缺血、遗传等因素都有可能引起胆管缺失。临床上,通过肝活组织检查,在10个及以上门管区的标本里,发现50%以上的小叶间胆管缺失,即可...肝内胆管缺失是指肝内胆管数量的减少或消失,是胆管树基本病理改变之一。免疫紊乱、肿瘤、感染、药物、缺血、遗传等因素都有可能引起胆管缺失。临床上,通过肝活组织检查,在10个及以上门管区的标本里,发现50%以上的小叶间胆管缺失,即可确诊[1]。胆管缺失的预后取决于病因和损伤程度。晚期出现不可逆的广泛胆管缺失甚至胆管消失时,该病理综合征称为胆管消失综合征(vanishing bile duct syndrome,VBDS),仅发生在0.5%小胆管病[2]。随后,可进展至广泛的胆管纤维化或肝硬化。有趣的是,也有部分患者表现为胆管上皮细胞再生,在数月或数年后得到恢复。本文总结了胆管缺失发病的分子机制,并重点强调近年来免疫介导的胆管病和胆管缺失的研究进展。展开更多
基金Supported by The Intramural Research Programs of the National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Diseases
文摘Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with medications,autoimmune disorders,cancer,transplantation,and infections,the specific mechanisms of disease are not known.To date,only 4 cases of VBDS have been reported in human immunodeficiency virus(HIV) infected patients.We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases.Presentation includes hyperbilirubinemia,normal liver imaging,and negative viral and autoimmune hepatitis studies.In HIV-infected subjects,VBDS occurred at a range of CD4+ T-cell counts,in some cases following initiation or change in antiretroviral therapy.Lymphoma was associated with two cases;nevirapine,antibiotics,and viral co-infection were suggested as etiologies in the other cases.In HIV-positive patients with progressive cholestasis,early identification of VBDS and referral for transplantation may improve outcomes.
文摘Vanishing bile duct syndrome (VBDS) refers to a group of disorders characterized by prolonged cholestasis as a result of destruction and disappearance ofintrahepatic bile ducts. Multiple etiologies have been indentifi ed including infections, neoplastic disorders, autoimmune conditions and drugs. The natural history of this condition is variable and may involve resolution of cholestasis or progression with irreversible damage. VBDS is extremely rare in human immunodeficiency virus (HIV)-infected patients and anti-retroviral therapy has never been implicated as a cause. We encountered a young pregnant female with HIV and VBDS secondary to anti-retroviral therapy. Here, we report her clinical course and outcome.
文摘BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the- counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractable pruritus that developed shortly after taking naproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS: Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.
文摘胆管消失综合征(vanishing bile duct syndromeVBDS)病因较多,主要有先天性和遗传性疾病、缺血缺氧、肿瘤、感染、免疫紊乱、药物、特发性成人肝内胆管缺失症等因素.近年报道比较多的病因是淋巴瘤、HIV感染/AIDS和药物,有些VBDS病例较复杂,可能不止一种因素参与.VBDS的诊断需要肝脏组织学检查,肝组织角蛋白7(cytokeratin 7,CK7)和CK19免疫组织化学检查有助于提高VBDS诊断的可靠性.VBDS的治疗主要是对症支持治疗、病因治疗、肝移植、熊去氧胆酸和免疫抑制剂的应用,糖皮质激素疗效不好或不良反应明显时可以试换用吗替麦考酚酯或他克莫司,重症病例强调包括血浆置换的综合治疗.
文摘目的探讨与药物性胆管消失综合征((drug?vanishing bile duct syndrome,D?VBDS)预后相关的临床、病理组织学及肝生化学特点。方法采用回顾性研究方法选取2003年1月至2017年12月石家庄市第五医院经肝穿刺病理明确诊断为D?VBDS的45例病人,根据再次追踪随访的肝生化指标及临床症状体征情况,将其分为预后转归好与差分为两组,对比分析两组病人的性别构成、发病年龄、用药史、病理形态学特点及血清学指标等数据,并对病理形态学特点进行半定量评分。结果31例D?VBDS病人预后较好,14例D?VBDS病人预后较差。两组在性别构成(χ^2=0.106,P=0.745)及发病年龄(t=2.988,P=0.394)比较,均差异无统计学意义(P>0.05),均以40~60岁女性最多见。中药及中成药是引起D?VBDS最主要的药物(51.1%),其次为阿奇霉素(11.1%)及解热镇痛药(9.0%)。肝生化各指标高峰值比较,预后差组总胆红素(TBil)、直接胆红素(DBil)、总胆汁酸(TBA)、球蛋白(GLB)、总胆固醇(TG)(t=6.436,P=0.000;t=5.847,P=0.000;t=3.569,P=0.033;t=2.381,P=0.031;t=2.328,P=0.041)水平明显高于预后好组,白蛋白(ALB)、胆碱酯酶(CHE)(t=2.445,P=0.020;t=3.003,P=0.012)水平明显低于预后好组,差异有统计学意义(P<0.05)。两组病理形态学特点对比显示,汇管区炎症和纤维化、胆盐淤积、细胆管增生及毛细胆管淤胆评分(t=2.437,P=0.017;t=4.416,P=0.001;t=4.214,P=0.001;t=3.050,P=0.006;t=2.716,P=0.009)两组差异有统计学意义(P<0.05)。结论影响D?VBDS预后的因素与胆管损伤的级别、范围、胆管再生修复状况等因素有关。血清TBil、DBil、TBA、TC、GLB水平的持续升高及ALB、CHE水平持续降低可作为预测预后的肝生化学指标。肝组织中汇管区炎症和纤维化程度、胆盐淤积程度、细胆管增生程度及毛细胆管淤胆程度为与预后相关的病理形态学特点,肝穿组织病理检查结果仍是明确诊断及判断预后的金标准。
文摘肝内胆管缺失是指肝内胆管数量的减少或消失,是胆管树基本病理改变之一。免疫紊乱、肿瘤、感染、药物、缺血、遗传等因素都有可能引起胆管缺失。临床上,通过肝活组织检查,在10个及以上门管区的标本里,发现50%以上的小叶间胆管缺失,即可确诊[1]。胆管缺失的预后取决于病因和损伤程度。晚期出现不可逆的广泛胆管缺失甚至胆管消失时,该病理综合征称为胆管消失综合征(vanishing bile duct syndrome,VBDS),仅发生在0.5%小胆管病[2]。随后,可进展至广泛的胆管纤维化或肝硬化。有趣的是,也有部分患者表现为胆管上皮细胞再生,在数月或数年后得到恢复。本文总结了胆管缺失发病的分子机制,并重点强调近年来免疫介导的胆管病和胆管缺失的研究进展。
