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Ursodeoxycholic acid treatment of vanishing bile duct syndromes

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World Journal of Gastroenterology 2006年第22期12卷 3487-3495页

作者： Thomas Pusi ulrich beuers Department of Medicine Ⅱ Klinikum Grosshadern University of MunichGermany

Vanishing bile duct syndromes （VBDS） are characterized by progressive loss of small intrahepatic ducts caused by a variety of different diseases leading to chronic cholestasis, cirrhosis, and premature death from liver failure. The majority of adult patients with VBDS suffer from primary biliary cirrhosis （PBC） and primary sclerosing cholangitis （PSC）. Ursodeoxycholic acid （UDCA）, a hydrophilic dihydroxy bile acid, is the only drug currently approved for the treatment of patients with PBC, and anticholestatic effects have been reported for several other cholestatic syndromes. Several potential mechanisms of action of UDCA have been proposed including stimulation of hepatobiliary secretion, inhibition of apoptosis and protection of cholangiocytes against toxic effects of hydrophobic bile acids.

关键词： Cholestasis Primary biliary cirrhosis Primary sclerosing cholangitis Secretion Signaling Transport Ursodeoxycholic acid Vanishing bile duct syndrome

Predictors of premature delivery in patients with intrahepatic cholestasis of pregnancy

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World Journal of Gastroenterology 2007年第46期13卷 6226-6230页

作者： Jurate Kondrackiene ulrich beuers Rimantas Zalinkevicius Horst-Dietmar Tauschel Vladas Gintautas Limas Kupcinskas Department of Gastroenterology Kaunas University of MedicineKaunasLithuania Department of Gastroenterology and Hepatology Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands Institute of Endocrinology Kaunas University of MedicineKaunasLithuania Dr.Falk Pharma GmbH FreiburgGermany Department of Obstetrics and Gynecology Kaunas University of MedicineKaunasLithuania

AIM： To evaluate the predictive value of clinical symptoms and biochemical parameters for prematurity in intrahepatic cholestasis of pregnancy （ICP）. METHODS： Sixty symptomatic patients with ICP were included in this retrospective analysis. Preterm delivery was defined as delivery before 37 wk gestation. Predictors of preterm delivery were disclosed by binary multivariate logistic regression analysis. RESULTS： Mean time of delivery was 38.1 ± 1.7 wk. No stillbirths occurred. Premature delivery was observed in eight （13.3%） patients. Total fasting serum bile acids were higher （47.8 ±15.2 vs 41.0 ± 10.0 μmol/L, P 〈 0.05）, and pruritus tended to start earlier （29.0 ± 3.9 vs 31.6 ± 3.3 wk, P = 0.057） in patients with premature delivery when compared to those with term delivery. Binary multivariate logistic regression analysis revealed that early onset of pruritus （OR 1.70, 95% CI 1.23-2.95, P = 0.038） and serum bile acid （OR 2.13, 95% CI 1.13-3.25, P = 0.013） were independent predictors of preterm delivery. CONCLUSION： Early onset of pruritus and high levels of serum bile acids predict preterm delivery in ICP, and define a subgroup of patients at risk for poor neonatal outcome.

关键词： Intrahepatic cholestasis Delivery Pregnancy

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胆汁淤积症的肝外表现

德国医学 2000年第4期17卷 216-217页

作者： ulrich beuers 郝连杰 Department of Medicine Ⅱ Klinikum GrosshademUniversity of MunichD-81377 MunichGermany 同济医科大学附属同济医院

严重的胆汁淤积症主要表现为胆汁淤积肝外症状,最常报道的症状是瘙痒和乏力。约半数慢性胆汁淤积症病人产生骨质减少性骨病,导致严重活动能力丧失。本文将集中讨论慢性胆汁淤积症3个主要肝外表现的发病机理和治疗。瘙痒瘙痒是惹起病人... 详细信息

严重的胆汁淤积症主要表现为胆汁淤积肝外症状,最常报道的症状是瘙痒和乏力。约半数慢性胆汁淤积症病人产生骨质减少性骨病,导致严重活动能力丧失。本文将集中讨论慢性胆汁淤积症3个主要肝外表现的发病机理和治疗。瘙痒瘙痒是惹起病人抓伤的不适感,在一天内胆汁淤积症瘙痒的程度不同,研究胆汁淤积病人抓痒活动的强度,可以用固定在病人手指甲上的抓痒记录器测出。有意义的是抓痒活动在中午和下午的开始达到最高峰,而据胆汁淤积症病人的主诉瘙痒感在夜间最强。

关键词：胆汁淤积症肝外表现瘙痒疲乏骨质疏松

Functional assessment of liver regeneration after major hepatectomy

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Hepatobiliary Surgery and Nutrition 2022年第4期11卷 530-538页

作者： Fadi Rassam Pim B.Olthof Bart Takkenberg Marc G.Besselink Olivier R.Busch Joris I.Erdmann Rutger-Jan Swijnenburg Krijn Pvan Lienden ulrich H.beuers Roelof J.Bennink Thomas Mvan Gulik Department of Surgery Cancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamThe Netherlands Department of Gastroenterology&Hepatology Amsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands Departments of Radiology and Nuclear Medicine Cancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands

Background: Liver regeneration is crucial to restore the functional liver mass after liver resection. The aim of this study was to evaluate the early postoperative changes in remnant liver function, volume and liver stiffness after major liver resection and their correlation with postoperative outcomes. Methods: Patients undergoing major liver resection (≥3 segments) between February and November 2018 underwent both functional assessment using technetium-99m mebrofenin hepatobiliary scintigraphy (HBS) and CT-volumetry of the (future) remnant liver on preoperative day 1, the 5th postoperative day, and 4-6 weeks after resection. At the same time points, patients underwent transient elastography (TE) for the assessment of liver stiffness. Severe postoperative complications (Clavien-Dindo ≥ 3A) and mortality were correlated with the functional and volumetric increases of the remnant liver. Liver failure was graded according to the International Study Group of Liver Surgery (ISGLS) criteria. Results: A total of 18 patients were included of whom 10 (56%) had severe complications and one patient (5%) developed liver failure. Function and volume of the remnant liver had increased by the 5th postoperative day from 6.9 (5.4-10.9) to 9.6 (6.7-13.8) %/min/m2, P=0.004 and from 795.5 (538.3-1,037.5) to 1,080.0 (854.0-1,283.3) mL, P<0.001, respectively. After 4-6 weeks, remnant liver volume had further increased [from 1,080.0 (854.0-1,283.3) to 1,222.0 (1,016.0-1,380.5) mL, P=0.035], however, liver function did not show any significant, further increase [from 9.6 (6.7-13.8) to 10.9 (8.8-13.6) %/min/m2, P=0.177]. Liver elasticity of the future remnant liver (FRL) increased [from 10.8 (5.7-18.7) to 17.5 (12.4-22.6) kPa, P=0.018] and gradually recovered after 4-6 weeks to a median of 10.9 (5.7-18.8) kPa (T3 vs. T4, P=0.079). Patients who had severe postoperative complications did not show a significant increase in liver function on the 5th postoperative day (P=0.203), despite increas

关键词： Hepatobiliary scintigraphy(HBS) liver resection liver regeneration posthepatectomy liver failure liver function test

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肝脏重叠综合征（下）

传染病网络动态 2005年第11期 25-28页

作者： ulrich beuers 刘妍（编译）审校（杨月）

在最近十年，儿童和成人均报道过一定数量的AIH—PSC重叠综合征。年轻的自身免疫性肝病患者中存在相当部分的AIH-PSC重叠综合征。文献检索显示依据组织学检测结果，在AIH患者中AIH—PSC重叠综合征占6％，事实上，应用AIH评分对113例PSC... 详细信息

在最近十年，儿童和成人均报道过一定数量的AIH—PSC重叠综合征。年轻的自身免疫性肝病患者中存在相当部分的AIH-PSC重叠综合征。文献检索显示依据组织学检测结果，在AIH患者中AIH—PSC重叠综合征占6％，事实上，应用AIH评分对113例PSC患者进行回顾性评价，可以诊断重叠综合征的占8％。相反的，在另一组2儿例PSC患者中，只有1．4％符合AIH—PSC重叠综合征的诊断标准。两组数据年龄的差异、自身抗体的范围都是要考虑的，因此数据的复杂程度导致了不同的结果。

关键词：重叠综合征肝病患者肝脏 PSC AIH 自身免疫性回顾性评价检测结果文献检索自身抗体

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肝脏重叠综合征（上）

传染病网络动态 2005年第10期 26-28页

作者： ulrich beuers 刘妍（编译）杨月（审校）

“重叠综合征”被引入肝脏是描述不同形式的自身免疫性肝病，包括自身免疫性肝炎（AIH）、原发性胆汁性肝硬化（PBC）和原发性硬化性胆管炎（PSC）。对于这些重叠综合征，是不同形式的实体或是自身免疫性肝病的多样表现还有争论。

关键词：重叠综合征肝脏自身免疫性肝病原发性硬化性胆管炎原发性胆汁性肝硬化自身免疫性肝炎

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原发性胆汁性肝硬化的临床表现

肝脏 2008年第1期13卷 57-58页

作者： U. beuers 刘光华（译） Department of Gastroenterology ＆ Hepatology Academic Medical CenterUniv. of Amsterdam The Netherlands 不详

原发性胆汁性肝硬化（PBC）多发于中年女性，具有脏器特异性，该病由免疫介导、多以破坏肝内小胆管为特征的自身免疫性疾病，最终可发展为肝纤维化和肝硬化。PBC的诊断要点有：（1）肝内胆汁淤积的血清酶谱表现；（2）血清IgM升高；（3... 详细信息

原发性胆汁性肝硬化（PBC）多发于中年女性，具有脏器特异性，该病由免疫介导、多以破坏肝内小胆管为特征的自身免疫性疾病，最终可发展为肝纤维化和肝硬化。PBC的诊断要点有：（1）肝内胆汁淤积的血清酶谱表现；（2）血清IgM升高；（3）免疫荧光法检测的抗线粒体抗体（AMA）阳性；通过ELISA或免疫印迹法检测的PBC特征性抗体AMA的M2阳性；（4）肝内中小胆管的破坏或缺损。

关键词：原发性胆汁性肝硬化临床表现肝内胆汁淤积抗线粒体抗体自身免疫性疾病脏器特异性血清IgM 免疫荧光法

熊脱氧胆酸和考来烯胺治疗妊娠期肝内胆汁淤积症的功效与安全性比较

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世界核心医学期刊文摘（胃肠病学分册） 2006年第2期2卷 36-37页

作者： Kondrackiene J. beuers U. Kupcinskas L. 陈云茹 Department of Gastroenterology Kaunas University of Medicine Eiveniu Street 250009 Kaunas Lithuania Dr.

Background & Aims: Treatment of intrahepatic cholestasis of pregnancy with ursodeoxycholic acid appears promising, but data are limited so far. The aim of this randomized study was to evaluate the efficacy and safety of ursodeoxycholic acid in comparison with cholestyramine. Methods: Eighty-four symptomatic patients with intrahepatic choles-tasis of pregnancywere randomized to receive either ursodeoxycholic acid, 8- 10 mg/kg body weight daily (n = 42), or cholestyramine, 8 g daily (n = 42), for 14 days. The primary end point was a reduction of pruritus by more than 50% after 14 days of treatment as evaluated by a pruritus score. Secondary end points were outcome of pregnancy, reduction of serum aminotransferase activities and serum bile acid levels, and drug safety. Intention-to-treat analysis was applied. Results: Pruritus was more effectively reduced by ursodeoxycholic acid than cholestyramine (66.6% vs 19.0% , respectively; P < .005). Babies were delivered significantly closer to term by patients treated with ursodeoxycholic acid than those treated with cholestyramine (38.7 ± 1.7 vs 37.4 ± 1.5 weeks, respectively, P < .05). Serum alanine and aspartate aminotransferase activities were markedly reduced by 78.5% and 73.8% , respectively, after ursodeoxycholic acid, but by only 21.4% , each, after cholestyramine therapy (P < .01 vs ursodeoxycholic acid). Endogenous serum bile acid levels decreased by 59.5% and 19.0% , respectively (P < .02). Ursodeoxycholic acid, but not cholestyramine was free of adverse effects. Conclusions: Ursodeoxycholic acid is safe and more effective than cholestyramine in intrahepatic cholestasis of pregnancy.

关键词：考来烯胺熊脱氧胆酸血清丙氨酸血清胆汁酸氨基转移酶足月分娩评分表瘙痒症本项内源

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原发性胆汁性肝硬化的药物治疗

肝脏 2008年第1期13卷 58-58页

作者： U. beuers 倪鎏达（译） Department of Gastroenterology ＆ Hepatology Academic Medical CenterUniv. of Amsterdam The Netherlands 不详

熊去氧胆酸（UDCA）已被广泛用于原发性胆汁性肝硬化（PBC）的治疗。80年代后期和90年代初期的随机对照试验证实，UDCA能有效改善PBC患者血清生化指标。2000年首次报道UDCA有效阻止PBC组织学进展。早期meta分析曾怀疑UDCA治疗PBC的益处... 详细信息

熊去氧胆酸（UDCA）已被广泛用于原发性胆汁性肝硬化（PBC）的治疗。80年代后期和90年代初期的随机对照试验证实，UDCA能有效改善PBC患者血清生化指标。2000年首次报道UDCA有效阻止PBC组织学进展。早期meta分析曾怀疑UDCA治疗PBC的益处，但由于其治疗时间较短和剂量不足而受质疑。最近，三组长达20年以上的队列研究表明，采用适当剂量UDCA（每日13～15mg／kg）治疗组织学为1～2期的早期患者.

关键词：原发性胆汁性肝硬化药物治疗 UDCA治疗随机对照试验血清生化指标 meta分析剂量不足熊去氧胆酸