难治性原发性胆汁性肝硬化的治疗

原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)是一种肝脏特异的慢性进行性自身免疫性疾病,女性发病率较高,以肝内胆汁淤积为特征,血清多种自身免疫性抗体阳性,常并发其他自身免疫性疾病.至今为止,该病病因及发病机制仍不清楚,熊去氧胆酸(urodeoxycholic acid,UDCA)是美国食品药品监督管理局批准的惟一用于治疗PBC的一线药物,以13 ～ 15 mg.kg-1.d-1的剂量长期应用可有效改善PBC患者的生物化学指标,阻止或延缓PBC早期患者的组织学进展. 一、对UDCA应答的标准及意义 关于对UDCA的应答,欧洲肝病学组关于"胆汁淤积性疾病"中PBC治疗的指南给出了两种标准:巴黎标准[1][UDCA治疗1年后血清总胆红素≤17 μmO1/L、碱性磷酸酶(ALP)≤3倍正常值上限(ULN)、AST≤2×ULN]和巴塞罗那标准[2](UDCA治疗1年后ALP下降40％或降至正常),PBC患者用UDCA治疗1年后未达到上述两种标准之一可认为"对UDCA应答不佳".目前对反映UDCA治疗后患者生物化学应答的最佳标准仍存在争议,无论应用何种标准,对UDCA的应答状况都与其远期预后、生存率及肝硬化的进展程度密切相关.     

Plasma separation and anion adsorption transiently relieve intractable pruritus in primary biliary cirrhosis

BACKGROUND/AIMS: Pruritus can be a severely disabling symptom in patients with primary biliary cirrhosis who do not respond to treatment with ursodeoxycholic acid, anion exchangers, enzyme inducers, or opiate antagonists. The aim of this study was to assess the clinical efficacy of plasma separation and anion adsorption in the treatment of intractable pruritus of cholestasis. METHODS: Three patients with primary biliary cirrhosis and intractable pruritus defined by severity of pruritus 7 on a rating scale between 0 (no pruritus) and 10 (maximal pruritus) on at least 4 of 7 days despite medical treatment were treated with plasma separation and anion adsorption on three consecutive days. Fatigue was assessed using the Fisk Fatigue Severity Score and quality of life was assessed by the PBC-40, a disease specific health related quality of life measure. RESULTS: Improvement in pruritus, fatigue, and quality of life was transiently observed in all patients. Serum bile acid levels showed no association with intensity of pruritus, and the bile acid pattern was not altered. The treatment was well tolerated by all patients. CONCLUSIONS: Plasma separation and anion adsorption seem to be a safe and effective therapeutic option for patients with primary biliary cirrhosis suffering from intractable pruritus.     

老年原发性胆汁性肝硬化患者的特点

<正>原发性胆汁性肝硬化(Primary biliary cirrhosis,PBC)是肝内中小胆管慢性进行性非化脓性炎症而导致的慢性胆汁淤积性疾病。近年来,由于早期诊断及治疗的进步,疾病的缓解率已明显提高,患者也可长期无肝硬化表现,故也有观点认为应将尚未出现肝硬化的患者命名为原发性胆汁性胆管炎(Primary biliary cholangitis),仍简称为PBC。原发性胆汁性胆管炎的命名能更客观地界定疾病,避免将     

中国人原发性胆汁性肝硬化的前瞻性研究

目的对自1958年至2001年确诊的40例原发性胆汁性肝硬化(PBC)病人作较详细的前瞻性观察,以唤起国内同道的注意.方法从1958年诊断第1例起,至今已收集了40例,对其临床过程作了长期的随访.诊断标准(1)临床表现和肝生化检查符合淤胆;(2)除外其他原因的肝内或肝外淤胆;(3)血清抗线粒体抗体阳性;(4)肝活检符合PBC的组织学改变;(5)经1年以上随访,符合PBC的自然病程.结果自1958年至2001年共确诊PBC 40例,1958～1990年间仅9例,余者在1991～2001年间诊断.29例系上海市常住户口,8例系来自外地,另3例系外籍华人.本组发病时平均年龄为(47.9±9.1)岁,确诊时年龄为(51.5±9.8)岁.女性39例,男性仅1例.本病起病隐匿和缓慢,不易觉察.有14例发病时无明显症状,系在体检时发现肝功能(LFL)异常或高血脂就诊.初起时主诉为乏力、皮肤搔痒、尿深和轻度黄疸.PBC的临床表现随着病程的进展而变化,一般病程大于5年或以上,往往有黄疸、眼睑黄疣、肝脾肿大、肝掌和蜘蛛痣.长期黄疸病人脸色呈黄色、黄褐色或黑色.起病时LFL的异常率如下ALP 97.5%,GGT 95%,ALT80%,AST 70%,高胆红素血症52%.免疫荧光法测线粒体抗体20例,其中17例阳性;酶免疫法M2抗体试验测定31例,30例阳性,1例阴性;IgM增高者为88.6%.28例有肝组织学资料.病理学分期Ⅱ期8例,Ⅲ期12例,Ⅳ期8例.并发病自身免疫性肝炎2例,口眼干燥征7例,Ⅱ型糖尿病4例,类风湿性关节炎4例,自身免疫性溶血性贫血、甲状腺功能亢进、多肌炎和自身免疫性胃炎各1例.治疗单用皮质激素、氨甲蝶呤或秋水仙碱无效,16例应用熊去氧胆酸12个月以上,12例有明显缓解.随访和转归8例死亡,死亡原因为肝衰竭和(或)上消化道大出血,29例仍存活,3例失访,平均存活期为9.17年.结论PBC在中国人中并非罕见,提高本病的早期诊断,给予有效治疗,可改进预后和生存质量.     

Primary biliary cirrhosis

Primary biliary cirrhosis is a chronic autoimmune inflammatory disease of the liver with a striking female preponderance. It has an insidious onset and typically affects middle-aged women. The disease manifests gradually with symptoms of fatigue, pruritis, and increased alkaline phosphatase levels on laboratory evaluation. The hallmark of the disease is the circulating antimitochondrial antibody. Histology is characterized by inflammation of the bile ducts, destruction of cholangiocytes, and subsequent cholestasis, progressing to biliary cirrhosis. The standard treatment for primary biliary cirrhosis is ursodeoxycholic acid, which improves survival, but the disease can still lead to cirrhosis and liver failure over decades.     

熊去氧胆酸及其联合激素和免疫抑制剂治疗原发性胆汁性肝硬化的临床观察

目的 观察熊去氧胆酸(UDCA)、UDCA联合泼尼松龙、UDCA联合硫唑嘌呤3种方案治疗对原发性胆汁性肝硬化(PBC)的疗效,并评价影响疗效的危险因素.方法 82例初诊PBC患者随机分为单用UDCA(U组,28例)、UDCA联合泼尼松龙(UP组,27例)、UDCA联合硫唑嘌呤(UA组,27例)3个治疗组,在治疗第0、3、6、12个月采集临床、实验室资料及药物不良反应.主要采用重复测量的方差分析和COX回归进行统计学处理.结果 UP组患者较U组及UA组在乏力和瘙痒程度上有明显改善(P=0.015和P=0.037),U组、UA组无改善.3组患者治疗后丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、总胆红素、直接胆红素(DBIL)和IgM均下降,组内比较差异有统计学意义(P＜0.05),3组间比较差异无统计学意义(P＞0.05).发生疾病进展的患者Mayo危险性评分高(P=0.018)、凝血酶原时间(PT)延长(P=0.042).UP组血糖升高2例、满月脸5例、多毛1例;UA组白细胞下降2例,胆绞痛1例,U组未出现药物不良反应.ALP、GGT、总胆固醇基线水平高是生化缓解的危险因素(P=0.015).总胆红素、DBIL、总胆汁酸增高、PT延长不利于肝生化缓解(P=0.075).结论 3种方案对PBC患者肝脏生化指标、IgM的改善作用相近,UDCA联合泼尼松龙方案可减轻乏力、瘙痒症状,单用UDCA方案不良反应发生率最低.Mayo危险性评分高、PT延长的患者疾病易进展;高水平的ALP、GGT、总胆固醇是生化缓解的危险因素;高水平的总胆红素、DBIL、总胆汁酸、PT不利于生化缓解.

Abstract：

Objective The aims of this study were to compare the clinical and laboratory responses to ursodeoxycholic acid (UDCA) monotherapy with the combination therapy of UDCA plus prednisolone/azathioprine in primary biliary cirrhosis(PBC),and to investigate the risk factors affecting the therapeutic responses.Methods Eighty-two patients with untreated PBC were divided randomly into three groups.Group U (28 patients) received UDCA alone,group UP(27 patients) received UDCA and pr ednisolone,while group UA (27 patients ) received UDCA and azathioprine.The clinical and laboratory data were recorded after treated for 3,6 and 12 months.Repeated measures ANOVA and COX regression model were used for statistical analysis.Results Fatigue and pruritus were improved only in group UP(P=0.015 and P=0.037 respectively).Alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),gamma-glutamyl transferase (GGT),total bilirubin (TBIL),direct bilirubin (DBIL) and IgM in the 3 groups were decreased (P＜0.05),while there was no statistical significant difference between the three groups (P＞0.05).The patients with disease progression had higher Mayo risk score (MRS) (P=0.018) and prolonged prothrombin time (PT)(P=0.042).In group UP,side-effect associated with glucocorticosteroids occurred in eight patients while there was no side-effect in group U.High baseline levels of ALP、GGT and CHO were risk factors for biochemical remission(P=0.015).The increase of DBIL,TBIL,total bile acid(TBA) and PT did not contribute to the prediction of biochemical remission ( P=0.075 ).Conclusion There are no differences among the three groups in the improvement of hepatic biochemical data and IgM.The combination therapy of UDCA with prednisolone could relieve fatigue and itching.The disease of patients with higher Mayo risk score and prolonged PT tend to progress.High baseline levels of ALP,GGT and CHO are risk factors for biochemical remission.High baseline levels of TBIL,DBIL,TBA and PT could not predict biochemical remission.The incidence of adverse effect is lowest when treated with UDCA alone.     

ABCB4 disease: Many faces of one gene deficiency

ATP-binding cassette (ABC) subfamily B member 4 (ABCB4), also known as multidrug resistance protein 3 (MDR3), encoded by ABCB4, is involved in biliary phospholipid secretion, protecting hepatobiliary system from deleterious detergent and lithogenic properties of the bile. ABCB4 mutations altering canalicular ABCB4 protein function and expression may have variable clinical presentation and predispose to several human liver diseases. Well-established phenotypes of ABCB4 deficit are: progressive familial intrahepatic cholestasis type 3, gallbladder disease 1 (syn. low phospholipid associated cholelithiasis syndrome), high ɣ-glutamyl transferase intrahepatic cholestasis of pregnancy, chronic cholangiopathy, and adult biliary fibrosis/cirrhosis. Moreover, ABCB4 aberrations may be involved in some cases of drug induced cholestasis, transient neonatal cholestasis, and parenteral nutrition-associated liver disease. Recently, genome-wide association studies have documented occurrence of malignant tumours, predominantly hepatobiliary malignancies, in patients with ABCB4/MDR3 deficit.The patient's age at the time of the first presentation of cholestatic disease, as well as the severity of liver disorder and response to treatment are related to the ABCB4 allelic status. Mutational analysis of ABCB4 in patients and their families should be considered in all individuals with cholestasis of unknown aetiology, regardless of age and/or time of onset of the first symptoms.     

中等剂量熊去氧胆酸治疗原发性胆汁性肝硬化的系统评价

目的评价长期应用中等剂量熊去氧胆酸治疗原发性胆汁性肝硬化的疗效及安全性。方法对全世界关于中等剂量(13～15mg·kg-1·g-1)熊去氧胆酸与安慰剂对照治疗原发性胆汁性肝硬化的随机对照试验进行系统评价。结果共纳入7项随机对照试验,累计1038例患者。熊去氧胆酸能显著改善患者的肝功能生化检测指标,但不能改善疲劳和瘙痒等症状。病程Ⅰ至Ⅱ期的患者治疗2年后肝脏组织学显著好于对照组(P=0.03),但分析所有患者时差异无统计学意义(P=0.08)。荟萃分析显示治疗组与对照组间死亡率(OR0.99,95%可信区间0.62～1.58)、肝病相关死亡率(1.05,0.53～2.05)、肝移植率(0.87,0.53～1.41)、死亡和(或)肝移植率(0.92,0.64～1.31)和肝功能失代偿率(0.94,0.60～1.49)差异无统计学意义。结论熊去氧胆酸能有效改善肝功能,但不能改善症状,也无足够证据支持熊去氧胆酸能延长患者的生存期。早期患者及早并长期应用熊去氧胆酸可能延缓肝脏组织学进展。     

熊去氧胆酸治疗老年原发性胆汁性肝硬化的临床研究

目的探讨老年原发性胆汁肝硬化（PBC）的临床特征、诊断和治疗效果。方法将66例诊断为PBC的病人分为老年组40例,中年组26例,比较两组的临床表现、生化免疫指标（碱性磷酸酶：ALP、谷氨酰转肽酶：GGT、抗线粒体抗体：AMA）。两组病例均给予口服熊去氧胆酸（UDCA：优思弗）治疗,服药8W后比较疗效。结果90％病人因体检发现ALP、GGT升高就诊,治疗前两组患者的ALP、GGT升高程度差异无统计学意义（P〉0．05）。非特异性皮肤瘙痒是老年PBC患者的主要表现,中年组患者中88．5％无症状,明显高于老年组的37．5％;口服优思弗8W后,两组ALP、GGT均较治疗前明显程度降低（P〈0．05）。老年组中3例肝硬化患者服用优思弗后,其症状、体征及ALP、GGT均无改善,2例死亡。服药后两组患者乏力、皮肤瘙痒症状均无改善,影像学也无变化。结论：（1）PBC早期缺乏特异症状;（2）AMA对PBC诊断有重要意义,ALP、GGT的升高早于黄疸、肝肿大出现。（3）应重视体检中无法解释的ALP、GGT异常升高。（4）UDCA对早期原发性胆汁肝硬化疗效满意。（5）老龄可能是影响PBC患者预后的因素之一。     

Secondary bile acids and the biliary epithelia: The good and the bad

The biliary tract has been considered for several decades a passive system just leading the hepatic bile to the intestine. Nowadays several researches demonstrated an important role of biliary epithelia (i.e. cholangiocytes) in bile formation. The study of biliary processes therefore maintains a continuous interest since the possible important implications regarding chronic cholestatic human diseases, such as primary biliary cholangitis or primary sclerosing cholangitis. Bile acids (BAs), produced by the liver, are the most represented organic molecules in bile. The physiologic importance of BAs was initially attributed to their behavior as natural detergents but several studies now demonstrate they are also important signaling molecules. In this minireview the effect of BAs on the biliary epithelia are reported focusing in particular on secondary (deriving by bacterial manipulation of primary molecules) ones. This class of BAs is demonstrated to have relevant biological effects, ranging from toxic to therapeutic ones. In this family ursodeoxycholic and lithocholic acid present the most interesting features. The molecular mechanisms linking ursodeoxycholic acid to its beneficial effects on the biliary tract are discussed in details as well as data on the processes leading to lithocholic damage. These findings suggest that expansion of research in the field of BAs/cholangiocytes interaction may increase our understanding of cholestatic diseases and should be helpful in designing more effective therapies for biliary disorders.     

Patterns of serum lipids derangements and cardiovascular risk assessment in patients with primary biliary cholangitis

Introduction and objectivesPrimary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease that disrupts the cholesterol metabolism. Our aim was to investigate the frequency of dyslipidemias and to evaluate the risk of cardiovascular events in a historic cohort of patients with PBC.PatientsAll patients attended from 2000 to 2009 with histological diagnosis of PBC were included and were compared with healthy controls. The 10-year cardiovascular risk was estimated by the Framingham risk score.ResultsFifty four patients with PBC were included and compared to 106 controls. Differences in total cholesterol (263.8 ± 123.9 mg/dl vs. 199.6 ± 40, p = 0.0001), LDL-cholesterol (179.3 ± 114.8 vs. 126.8 ± 34.7, p = 0.0001), HDL-cholesterol (62.4 ± 36.2 mg/dl vs. 47.3 ± 12.3, p = 0.0001) and triglycerides (149.1 ± 59.1 mg/dl vs. 126.4 ± 55.4, p = 0.001) were found. Hypercholesterolemia (>240 mg/dl) was found in 52.4% of the patients with PBC vs. 11% in the control group, high LDL-cholesterol (160–189 mg/dl) in 45.2% of the patients with PBC vs. 10% in controls and hyperalphalipoproteinemia (HDL-cholesterol >60 mg/dl) in 45.2% of the patients with PBC vs. 16% in controls. The 10-year cardiovascular risk was 5.3% ± 5.9 in the patients with PBC and 4.1% ± 5.7 in the control group (p = 0.723, IC 95% = 0.637–1.104). Only one cardiovascular event (stroke) in a patient with PBC was registered in a mean follow up time of 57.9 ± 36.5 months.ConclusionsMarked derangements in serum lipids and a high frequency of dyslipidemias are found in patients with PBC, however, these do not increase the risk of cardiovascular events.     

Abordaje del paciente con colestasis y síndrome ictérico. Posicionamiento científico conjunto AMH,AMG, AMEG

The term cholestasis refers to bile acid retention, whether within the hepatocyte or in the bile ducts of any caliber. Biochemically, it is defined by a level of alkaline phosphatase that is 1.67-times higher than the upper limit of normal. Cholestatic diseases can be associated with an inflammatory process of the liver that destroys hepatocytes (hepatitis), with jaundice (yellowing of the skin and mucus membranes, associated with elevated serum bilirubin levels), or with both, albeit the three concepts should not be considered synonymous. Cholestatic diseases can be classified as intrahepatic or extrahepatic, depending on their etiology. Knowing the cause of the condition is important for choosing the adequate diagnostic studies and appropriate treatment in each case. A complete medical history, together with a thorough physical examination and basic initial studies, such as liver ultrasound and liver function tests, aid the clinician in deciding which path to follow, when managing the patient with cholestasis. In a joint effort, the Asociación Mexicana de Hepatología (AMH), the Asociación Mexicana de Gastroenterología (AMG) and the Asociación Mexicana de Endoscopia Gastrointestinal (AMEG) developed the first Mexican scientific position statement on said theme.     

Pathogenic role of oxidative and nitrosative stress in primary biliary cirrhosis

Primary biliary cirrhosis is a multifactor autoimmune disease characterized by hepatic and systemic manifestations,with immune system dysregulation and abnormalities in the hepatic metabolism of bile salts,lipids,and nutrients,as well as destruction of membrane lipids and mitochondrial dysfunction.Both oxidative and nitrosative stress are associated with ongoing manifestations of the disease.In particular,abnormalities in nitric oxide metabolism and thiol oxidation already occur at early stages,thus leading to the hypothesis that these biochemical events play a pathogenic role in primary biliary cirrhosis.Moreover,the association of these metabolic abnormalities with the progression of the disease may indicate some biochemical parameters as early diagnostic markers of disease evolution,and may open up the potential for pharmacological intervention to inhibit intra-and extra-cellular stress events for resuming hepatocellular functions.The following paragraphs summarize the current knowledge by outlining molecular mechanisms of the disease related to these stress events.     

泼尼松龙联合熊去氧胆酸治疗原发性胆汁性肝硬化患者疗效初步研究

目的 评价泼尼松龙联合熊去氧胆酸（UDCA）治疗原发性胆汁肝硬化（PBC）患者的疗效,寻找治疗PBC的有效方案。方法 2010年1月~2015年12月我院治疗的106例PBC患者,随机分为观察组和对照组,每组53例。给予对照组患者UDCA 13~15 mg·kg^-1·d^-1口服,观察组在对照组治疗的基础上再给予泼尼松龙口服并逐步减少激素剂量。在治疗前和治疗后3个月、6个月和12个月,观察患者临床表现和检测血清主要生化指标和免疫球蛋白IgM、IgG、IgA。结果 在治疗后,观察组和对照组患者临床症状均有所改善,观察组患者的乏力、皮肤瘙痒症状明显改善（P<0.05）;在治疗后,两组患者血清ALP、GGT和TBIL水平较治疗前均有明显改善（P<0.05）,且两组患者在治疗3个月时上述指标下降较快,观察组改善程度明显优于对照组（P<0.05）,在治疗6个月和12个月时,两组上述指标改善程度不明显（P>0.05）,两组患者血清ALB水平在治疗前后无明显变化（P>0.05）,且在不同治疗时段亦无显著性差异（P>0.05）;治疗后,两组患者血清IgM水平明显下降（P<0.05）,并且在治疗3个月时观察组较对照组下降程度较大,差异显著（P<0.05）,在6个月和12个月时,两组免疫球蛋白水平改善程度差异不明显（P>0.05）,两组患者血清IgA和IgG水平在治疗前后无显著性差异（P>0.05）。结论 泼尼松龙联合UDCA在短期内可以改善PBC患者临床表现、主要生化指标以及IgM水平,但其远期疗效还有待观察。     

熊去氧胆酸治疗原发性胆汁性肝硬化患者早期应答预测1年疗效

目的 探讨早期预测熊去氧胆酸(UDCA)治疗原发性胆汁性肝硬化(PBC)患者疗效的方法.方法 回顾性分析26例PBC患者的临床资料,他们接受常规剂量的UDCA治疗,分别在3个月、6个月和9个月观察疗效,以血清ALP降低＞40％为应答标准,采用受试者工作特征(ROC)曲线下面积和Bland-Altman图分析一致性来预测1年时的疗效.结果 本组患者治疗3个月应答者9例(34.6％),6个月应答者9例(34.6％),9个月应答者14例(53.8％),1年应答者15例(57.7％);3个月内应答者ROC曲线下面积(0.83,p=0.004,95％CI 0.66～1.01)能较好判断患者1年的疗效,Bland-Altman一致性分析发现3个月应答者和12个月应答者ALP降低百分比的差值较好地分布在95％一致性界限内;3个月应答者与不应答者的年龄和入组时生化指标间无显著性差异.结论 PBC患者服用UDCA 3个月时血清ALP的下降水平可判断1年后的疗效.     

随机对照试验研究熊去氧胆酸治疗原发性胆汁性肝硬化患者的疗效及安全性*

目的 评价熊去氧胆酸（UDCA）治疗原发性胆汁性肝硬化（PBC）患者的疗效和安全性。方法 本研究采用随机平行对照试验设计方案,将90例PBC患者随机分为试验组和对照组,每组45例。两组受试者均给予保肝支持疗法,试验组受试者在此基础上给予UDCA 250 mg口服,3次/d;给予对照组受试者泼尼松治疗。两组均治疗4 w。常规检测血清总胆红素（TBIL）,丙氨酸氨基转移酶（ALT）,天冬氨酸氨基转移酶（AST）,碱性磷酸酶（ALP）,总胆汁酸（TBA） 和γ-谷氨酰转肽酶（GGT）。记录治疗期间受试者的不良反应发生情况。结果 在治疗4 w末,试验组受试者血清T-BIL、ALT、AST、ALP和GGT水平分别为（34.19±16.88） μmol/L、（48.58±23.31） U/L、（37.27±18.33） U/L、（104.51±43.55） U/L和（82.68±33.34） U/L,均显著低于对照组的（67.35±31.10） μmol/L、（85.27±31.88） U/L、（73.55±15.71） U/L、（197.09±52.36） U/L 和（131.66±37.58） U/L（P<0.01）;试验组受试者血清TBA为（20.27±9.11） μmol/L,显著高于对照组的（3.27±1.89） μmol/L（P<0.01）;两组不良反应发生率比较,如便秘（P=0.29）、头痛（P=0.29）、头晕（P=0.50）、心动过速（P=0.50）、恶心（P=0.33）和呕吐（P=0.50）等,均无显著性相差。结论 UDCA治疗PBC患者的疗效优于泼尼松,且该药的不良反应较少,受试者可以耐受。     

原发性胆汁性肝硬化患者对熊去氧胆酸应答欠佳的影响因素

目的 观察对熊去氧胆酸应答欠佳的原发性胆汁性肝硬化(PBC)患者的临床特点.方法 回顾性研究经熊去氧胆酸治疗1年以上的38例PBC患者,分析其在确诊时的性别、年龄及就诊时主要主诉;治疗前及治疗1年后的肝功能生化指标(血清ALT、AST、ALP、Y-谷氨酰转肽酶、总胆红素、白蛋白和球蛋白等);治疗前免疫学指标(IgG、IgM、血清抗核抗体和抗线粒体抗体).计量资料比较采用独立样本均数的t检验或近似法t'检验,计数资料的比较用Fisher's Exact Test.结果 38例PBC患者中,应答欠佳组患者17例,主要就诊原因为出现肝病相关症状,包括皮肤、巩膜黄染(41.1%),乏力、纳差(23.5%),下肢水肿、腹胀(11.7%)等.较好应答组患者21例,主要就诊原因为体检肝功能异常(33.3%).实验室检查结果显示,应答欠佳组与较好应答组相比,基线总胆红素[(40.15±25.08)μmol/L比(18.07±8.73)μmol/L]、碱性磷酸酶[(498.60±277.50)U/L比(313.70±182.10)U/L]、ALT[(105.60±69.22)U/L比(65.84±37.11)U/L]、AST[(113.80±54.24)U/L比(62.52±26.22)U/L]、球蛋白[(40.64±8.82)g/L比(33.06±5.01)g/L]和IgG[(19.52±4.44)g/L比(15.18±4.06)g/L]均较高,差异有统计学意义(t值分别为3.428、2.315、2.180、3.532、2.386和3.021,P值均＜0.05).结论 PBC患者中,因肝病相关症状就诊者、肝脏生物化学指标明显异常者以及自身免疫特征较多者,可能对熊去氧胆酸的应答欠佳.

Abstract：

Objective To observe the characteristics of primary biliary cirrhosis (PBC) with a suboptimal biochemical response to ursodeoxycholic acid.Methods A total of 38 Chinse PBC patients (5male patients,33 female patients,average age 55 years old) with treatment of ursodeoxycholic acid in our hospital from January 1999 to January 2009 were erolled and studied retrospectively.Results 17 suboptimal biochemical responders mainly presented with liver diseases related symptoms including jaundice (41.1%),fatigue,anorexia (23.5%),edema and abdominal distension (11.7%).21 good biochemical responders mainly presented with abnormal liver function tests without symptoms.The suboptimal biochemical responders had significantly higher baseline levels of total serum bilirubin,alkaline phosphatase,alanine aminotransferase,aspartate aminotransferase,immunoglobulin G and globulin as compared to the good biochemical responsers.There were no differences in gender,age and the dose of UDCA.Conclusion PBC patients with liver diseases related symptoms,marked abnormal liver tests and characteristics of autoimmune hepatitis may have a suboptimal biochemical response to ursodeoxycholic acid treatment.     

Epidemiology of primary biliary cholangitis in Italy: Evidence from a real-world database

BackgroundPrimary biliary cholangitis is an autoimmune disease affecting the interlobular bile ducts. Limited information is available on its epidemiology and treatment in Italy.AimsTo describe primary biliary cholangitis epidemiology and investigate treatment patterns for Italian patients with this disease.MethodsElectronic medical records from 900 general practitioners (part of the QuintilesIMS™ Longitudinal Patient Databases) were examined. Demographics were compared with those from the Italian National Institute of Statistics dataset. The International Classification of Diseases, Ninth Revision, biliary cirrhosis code 571.6 was used for diagnosis, and data on comorbidities, concomitant medications, medical examinations, specialist referrals, and treatments were collected.ResultsThis dataset was representative of the Italian population. Point prevalence of primary biliary cholangitis was calculated as 27.90 per 100,000 and incidence as 5.31 per 100,000 inhabitants/year. Some associations between the disease and comorbidities were sex specific. The most common laboratory assays requested were for liver enzymes, and the majority of patients were not referred to a specialist. Ursodeoxycholic acid was the most common therapy.ConclusionThis can be used as a benchmark for monitoring and identifying unmet needs to improve treatment in Italy.