熊去氧胆酸联合糖皮质激素治疗自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征的疗效观察

目的 观察熊去氧胆酸(UDCA)联合糖皮质激素治疗自身免疫性肝炎(AIH)-原发性胆汁性肝硬化(PBC)重叠综合征的长期疗效.方法 对19例AIH-PBC重叠综合征患者根据其初始治疗方案的不同分为初始UDCA联合激素治疗组及初始UDCA单药治疗组,根据患者肝炎病理炎症(G)和纤维化(S)程度分为病理早期组(G2S2),回顾性分析不同时间段加用激素及不同病理分期患者的疗效、生物化学应答状况和组织病理学变化情况.治疗前后数据的比较应用配对样本的t检验(正态分布)或两配对样本的Wilcoxon非参数秩和检验(非正态分布),生物化学应答率比较应用Fisher's精确检验法.结果 初始UDCA联合激素治疗组中位治疗时间为10.4(6.0～23.0)个月,治疗后ALT,AST,球蛋白、碱性磷酸酶(ALP)、γ-谷氨酰转移酶及IgG水平较治疗前明显下降(P值均<0.05);初始UDCA单药冶疗8.1(3.0～15.0)个月后,患者生物化学及免疫学指标变化差异无统计学意义(P值均>0.05),加用激素治疗10.6(6.0~24.0)个月后,ALT、AST、球蛋白,ALP及IgG水平较治疗前明显下降(P值均<0.05),与初始UDCA联合激素治疗组的ALT、IgG及ALP生物化学应答率差异无统计学意义(P值均>0.05).5例病理早期AIH-PBC重叠综合征患者出现ALT、IgG及ALP完全应答,不同病理分期患者ALT生物化学应答率差异有统计学意义(P<0.05).3例患者有治疗前后肝活组织病理检查结果,可见汇管区及界板内淋巴细胞及浆细胞的浸润明显减轻,纤维间隔的范围在一定程度有所减小.结论 对于诊断为AIH-PBC重叠综合征的患者,建议积极早期应用UDCA与糖皮质激素联合治疗.联合治疗对不同病理分期的患者都有疗效,但早期应用可能获得更佳的生物化学应答及组织学改善.     

自身免疫性肝炎和原发性胆汁性肝硬化重叠综合征的临床特征及疗效观察

目的观察自身免疫性肝炎和原发性胆汁性肝硬化(AIH-PBC)重叠综合征的临床特征及治疗效果。方法研究1:回顾分析124例PBC、57例AIH、39例AIH-PBC重叠综合征患者的临床特征;研究2:根据不同治疗方案对39例AIH-PBC重叠综合征患者进行分组疗效分析。结果在220例自身免疫性肝病患者中,AIH-PBC重叠综合征占17.73%。3组患者的性别组成差异无统计学意义,但发病年龄AIH组相似文献   

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.     

早期免疫抑制辅助UDCA对原发性胆汁性肝硬化合并自身免疫性肝炎患者疗效的影响

目的探讨早期免疫抑制辅助熊去氧胆酸(UDCA)对原发性胆汁性肝硬化(PBC)合并自身免疫性肝炎(AIH)患者治疗应答率、生化及免疫学指标的影响。方法研究对象选取我院2008年4月至2016年10月收治PBC合并AIH患者共50例,根据治疗方案不同分为对照组(25例)和观察组(25例),分别采用UDCA单用和在此基础上加用糖皮质激素辅助治疗;比较两组患者ALT应答率、ALP应答率、IgG应答率,治疗前后ALT、AST、球蛋白、总胆红素、ALP、γ-谷氨酰转肽酶、IgG及IgM水平。结果观察组患者ALT应答率、ALP应答率及IgG应答率均明显高于对照组(P0.05);观察组患者治疗后ALT、AST、球蛋白、总胆红素、ALP及γ-谷氨酰转肽酶水平均明显优于对照组、治疗前(P0.05);观察组患者治疗后IgG和IgM水平均明显优于对照组、治疗前(P0.05)。结论早期免疫抑制辅助UDCA用于PBC合并AIH患者可有效提高治疗应答率,改善生化和免疫学指标,价值优于UDCA单用。     

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.     

107例自身免疫性肝炎及其重叠综合征患者的临床分析

目的 分析自身免疫性肝炎(AIH)77例及其重叠综合征患者30例的临床表现、免疫学及生物化学特点及其治疗方案.方法 164例自身免疫性肝病患者中,AIH患者77例和AIH胆汁性肝硬化(PBC)重叠综合征患者30例,分析患者的临床特点、生物化学及组织学变化和治疗应答反应等. 结果 AIH患者的发病年龄高峰在50岁左右,肝功能生物化学检查结果显示为肝炎样异常,丙种球蛋白和免疫球蛋白G均明显高于正常.74%的患者抗核抗体阳性,32%的患者抗平滑肌抗体阳性,52%的患者伴发了肝外自身免疫性疾病.肝组织病理变化以界面性肝炎为主(65%),在中、重度患者则出现小叶性肝炎、玫瑰花结样改变、桥接样坏死等.AIH-PBC重叠综合征患者血清ALT、AST、γ谷氨酰转移酶、碱性磷酸酶和抗核抗体、抗线粒体抗体(AMA)/AMA-M2阳性率较高,组织学检查往往还伴有胆管的病变.60例AIH患者接受免疫抑制剂强的松龙联合硫唑嘌呤治疗第1年时,AIH治疗患者达完全缓解者42例(70%),其中26例持续缓解,16例复发(激素减量至≤10 mg/d或停药后),10例部分缓解,8例无应答.持续缓解者的AST、ALT、免疫球蛋白G、丙种球蛋白及血总胆红素水平均显著低于非持续缓解者(34例,JD值均＜0.05),此类患者撤除了硫唑嘌呤,单用激素的剂量均可维持在5～10 mg/d.AIH-PBC重叠综合征组经联合熊去氧胆酸治疗后除碱性磷酸酶和γ谷氨酰转移酶外,其余肝功能指标(ALT、AST、总胆红素)亦明显改善(P值均＜0.01).结论 AIH及AIH-PBC重叠综合征在临床上并不少见,诊断需综合临床、生物化学、免疫学和病理学等检测结果.AIH患者联合应用糖皮质激素、硫唑嘌呤达持续缓解者,可改为单用小剂量激素治疗.AIH-PBC患者加用熊去氧胆酸治疗,亦可获得较好的疗效.     

Autoimmune hepatitis-primary biliary cirrhosis concurrent with biliary stricture after liver transplantation

Although the development of de novo autoimmune liver disease after liver transplantation(LT)has been described in both children and adults,autoimmune hepatitis(AIH)-primary biliary cirrhosis(PBC)overlap syndrome has rarely been seen in liver transplant recipients.Here,we report a 50-year-old man who underwent LT for decompensated liver disease secondary to alcoholic steatohepatitis.His liver function tests became markedly abnormal 8 years after LT.Standard autoimmune serological tests were positive for anti-nuclear and antimitochondrial antibodies,and a marked biochemical response was observed to a regimen consisting of prednisone and ursodeoxycholic acid added to maintain immunosuppressant tacrolimus.Liver biopsy showed moderate bile duct lesions and periportal lymphocytes infiltrating along with light fibrosis,which confirmed the diagnosis of AIH-PBC overlap syndrome.We believe that this may be a case of post-LT de novo AIH-PBC overlap syndrome;a novel type of autoimmune overlap syndrome.     

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.     

干扰素α与阿德福韦酯不同联合方法治疗HBeAg阳性慢性乙型肝炎的疗效

目的 观察IFNα联合阿德福韦酯(ADV)治疗HBeAg阳性慢性乙型肝炎(CHB)的临床疗效,探讨理想的联合治疗方案.方法 2005年1月至2009年6月纳入河北医科大学第三医院HBeAg阳性CHB患者156例.56例患者HBV DNA≥1×107拷贝/mL、或纤维化分期≥S3、或既往单药治疗失败(复发)者,予以初始IFNα联合ADV治疗;52例未达上述指标患者接受初始IFNα单药治疗.24周时依据患者HBV DNA、HBeAg、HBsAg变化调整治疗方案:16例取得早期应答的初始IFNα联合ADV治疗组患者调整为IFNα单药维持治疗,其余患者与初始IFNα单药治疗组未达到早期应答者共同接受IFNα联合ADV治疗.另选48例作为标准治疗组,接受全程IFNα单药治疗.48周时复评全部患者HBV DNA、HBeAg、HBsAg定量,并决定是否延长疗程.最终于72周评估患者疗效、安全性、耐药复发等,数据行卡方检验.结果 治疗24周,初始IFNα联合ADV治疗组早期应答率达28.6%,其中HBV DNA阴转率、ALT复常率(53.6%,62.5%)与初始IFNα单药治疗组(32.7%,x2=4.78;40.4%,x2=5.21)、标准治疗组(27.1%,x2=5.28;37.5%,x2=6.46)比较,差异均有统计学意义(均P<0.05),且HBeAg阴转率较标准治疗组更高(39.3%比18.8%,x2=7.48,P<0.05).48周时,初始IFNα联合ADV治疗组16例取得早期应答者停用ADV后,5例HBeAg复阳,3例病毒学反弹;HBV DNA阴转率为73.2%,HBeAg转换率为41.1%,HBsAg清除率为12.5%.其中96例接受不同联合方法治疗的患者HBV DNA阴转率、HBeAg转换率、HBsAg清除率分别为65.6%、33.3%和8.3%.72周时不同联合方法治疗组患者整体复发率与标准治疗组相当,HBsAg清除率上升2.7%.结论 IFNa联合ADV抗病毒治疗对提高应答率优势明显.结合患者基线特征、治疗反应,制订不同联合方案,不失为当前CHB抗病毒优化治疗理想策略之一.

Abstract：

Objective To investigate the efficacy of interferon α(IFNα)and adefovir dipivoxil (ADV)combination therapy in HBeAg positive chronic hepatitis B(CHB)patients and to explore the optimized strategy for individualized treatment.Methods A total of 156 HBeAg positive CHB patients were enrolled in the study from January 2005 to June 2009 in the Third Affiliated Hospital of Hebei Medical University.Fifty-six CHB patients with hepatitis B virus(HBV)DNA≥1 X 107copy/mLand/or liver fibrosis stage≥S3,or previous monotherapy failure(relapse)were treated with initial IFNα and ADV combination therapy.Fifty-two patients who didn't meet any of the above baseline characteristics received initial IFNα monotherapy.The remaining 48 patients treated with IFNα monotherapy for full treatment duration were considered as control.At week 24 of treatment,the treatment regimens were adjusted according to quantitative changes of HBV DNA,HBeAg and HBsAg:16 patients who achieved early response in group of initial IFNα and ADV combination therapy subsequently received IFNα monotherapy,the other patients in group of initial combination therapy together with patients who did not achieved early response in group of initial IFNα monotherapy subsequently received IFNα and ADV combination treatment.The HBV DNA levels,HBeAg and HBsAg titers were detected at the end of 48 weeks of treatment to determine the treatment duration.The treatment efficacy,safety,drug resistance and relapse rates were finally evaluated at week 72.All data were analyzed using chi square test.Results At week 24,the early response rate in group of initial combination therapy was 28.6%,and the HBV DNA negative rate and alanine aminotransferase(ALT)normalization rate were significantly higher than those in groups of initial IFNα monotherapy and control(53.6%vs 32.7%vs 27.1%and 62.5%vs 40.4%vs 37.5%,respectively,P<0.05);in addition,HBeAg loss rate was higher than control group(39.3%vs 18.8%,x2=7.48;P<0.05).At week 48,five of 16 patients who achieved early response developed HBeAg reversion and three cases accompanied with virological breakthrough in group of initial combination therapy after switching to IFNα monotherapy,while the rates of HBV DNA negative,HBeAg seroconversion and HBsAg clearance were 73.2%,41.1%and 12.5%,respectively.The HBV DNA negative rate,HBeAg seroconversion rate and HBsAg clearance rate in 96 patients Who had received different combination treatment regimens were 65.6%,33.3%and 8.3%,respectively.At week 72,the relapse rate in individualized treatment group was comparable to those in control group,while HBsAg clearance rate increased 2.7%in individualized treatment group.Conclusions IFNα and ADV combination treatment could improve early biochemical and virological responses.Individualized treatment strategy based on baseline characteristics and treatment responses may be helpful for optimizing antiviral treatment in CHB patients.     

熊去氧胆酸联合糖皮质激素治疗原发性胆汁性肝硬化伴自身免疫性肝炎特征的疗效观察

目的回顾性研究熊去氧胆酸(ursodeoxycholic acid,UDCA)联合糖皮质激素治疗原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)伴自身免疫性肝炎(autoimmune hepatitis,AIH)特征的临床疗效.方法根据不同治疗方案回顾性的将31例PBC伴AIH特征的患者分为单用UDCA组和UDCA联合糖皮质激素组,根据患者肝脏病理炎症(G)、纤维化(S)程度分为两组:炎症程度≤G2,纤维化程度≤S2为病理早期组,炎症程度G2、纤维化程度S2为病理晚期组.回顾性分析不同方案治疗前后的血生化指标、免疫球蛋白指标、肝脏组织病理学变化及应答状况等方面的改变.结果治疗后两组生化指标碱性磷酸酶(alkaline phosphatase,ALP)、γ-谷氨酰转肽酶(γ-glutamyl transferase,GGT)及免疫球蛋白M(immunoglobulin M,IgM)水平均较治疗前有所下降,其中ALP、IgM改善有统计学意义(P0.05).联合治疗组的谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶、GGT、ALP、球蛋白、免疫球蛋白较基线水平明显改善.不同治疗组在ALT、免疫球蛋白G、ALP的生化学应答率上无统计学意义(P0.05),但联合治疗组应答率更高.不同病理分期患者ALP应答率有统计学意义(P0.05).联合治疗组患者的肝组织炎症程度或纤维化的程度及范围及胆管损害较治疗前有明显改善.结论对于PBC伴AIH特征的患者,需尽早明确诊断,建议在UDCA的基础治疗上积极加用糖皮质激素,更好地控制疾病的进展.     

中晚期自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征的临床病理研究

目的探讨中晚期自身免疫性肝炎-原发性胆汁性肝硬化（AIH-PBC）重叠综合征的临床病理特征及治疗直答。方法对具有肝穿刺标本的11例PBC-AIH重叠综合征和13例PBC（Seheuer分期3、4期）患者进行比较，重点分析AIH-PBC重叠综合征的临床、病理特点及治疗应答。结果两组患者的性别、年龄、病程、症状无显著差异；AIH-PBC重叠综合征患者的丙氨酸氨基转移酶、天冬氨酸氨基转移酶、γ-球蛋白、免疫球蛋白IgG以及抗核抗体或抗平滑肌抗体阳性率明显高于PBC（P〈0．05）。肝组织学见汇管区与肝腺泡内以单个核细胞为主的较多炎细胞浸润，其中易见浆细胞的聚积性浸润。可见不同时期小胆管损伤或毛细胆管反应性增生并侵蚀肝界板；重叠综合征患者经熊去氧胆酸治疗可使肝功能改善，与PBC患者无明显差异。结论中晚期AIH-PBC重叠综合征临床、血清学及组织病理学表现出AIH和PBC双重特征，UDCA治疗有助于血生化指标的改善。     

164例自身免疫性肝病临床分析

目的 分析比较自身免疫性肝炎（autoimmune hepatitis，AIH）、原发性胆汁性肝硬化（primary biliary cirrhosis，PBC）、原发性硬化性胆管炎（primary sclerosing cholangltis）及其重叠综合征的临床特点、生化特征和治疗反应，提高对自身免疫性肝病的认识。方法对77例AIH患者、46例PBC患者、11例PSC患者和30例PBC-AIH重叠综合征患者的临床及实验室检查资料进行回顾性分析。结果除PSC外，大多数自身免疫性肝病多发于中年女性，从出现症状到明确诊断平均需要2．5年。AIH、PBC-AIH重叠患者具有较高的转氨酶，PBC、PSC具有较明显的GGT、ALP升高。临床表现上AIH、PBC、PSC、AIH-PBC黄疸发生率分别为84％、78％、90％和67％，皮肤瘙痒的发生率分别为43％、56％、81％和60％。PSC和AIH-PBC具有较高的AIH评分，27％的PSC患者和33％AIH-PBC的评分达到可能的AIH。合理应用UDCA和免疫抑制剂可使90％的PBC和AIH患者症状在六个月内得到缓解、肝功能恢复明显改善。结论 AIH、PBC-AIH的肝功能异常以转氨酶升高为主，PBC、PSC以胆汁淤积为主。应用AIH评分系统诊断可能的AIH时应注意鉴别PSC及其它自身免疫性肝病。UDCA和免疫抑制剂可改善绝大多数患者的症状和肝功能异常。     

Long term outcome and response to therapy of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome

BACKGROUND/AIMS: Whether primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome requires immunosuppressive therapy in addition to ursodeoxycholic acid (UDCA) is a controversial issue. METHODS: Seventeen patients with simultaneous form of strictly defined overlap were followed for 7.5 years. First-line treatment was UDCA alone (UDCA) in 11 and combination of immunosuppressors and UDCA (UDCA + IS) in 6. RESULTS: Characteristics at presentation were not significantly different between the 2 groups. In the UDCA + IS group (f-up 7.3 years), biochemical response in terms of AIH features (ALT<2ULN and IgG < 16 g/L) was achieved in 4/6 and fibrosis did not progress. In the UDCA group, biochemical response was observed in three patients together with stable or decreased fibrosis (f-up 4.5 years) whereas the eight others were non-responders with increased fibrosis in four (f-up 1.6 years). Seven of these eight patients subsequently received combined therapy for 3 years. Biochemical response was obtained in 6/7 and no further increase of fibrosis was demonstrated. Overall, fibrosis progression in non-cirrhotic patients occurred more frequently under UDCA monotherapy (4/8) than under combined therapy (0/6) (P = 0.04). CONCLUSIONS: Combination of UDCA and immunosuppressors appears to be the best therapeutic option for strictly defined PBC-AIH overlap syndrome.     

自身免疫性肝病重叠综合征的临床治疗探讨

目的探讨自身免疫性肝病重叠综合征的治疗方法,提高治疗的有效性与安全性。方法 32例自身免疫性肝炎（AIH）-原发性胆汁性肝硬化（PBC）重叠综合征患者,均给予强的松（0.5mg.kg-1.d-1）联合熊去氧胆酸（UDCA,15 mg.kg-1.d-1）治疗,回顾性分析治疗前、后不同时段患者疾病状态的变化,评价临床疗效。结果所有患者症状、体征明显减轻,生化指标、肝脏病理损害均明显改善,与入院前比较差异有统计学意义（P〈0.01或P〈0.05）。IgG、IgM、抗平滑肌抗体（SMA）、抗线粒体抗体（AMA）治疗前后无明显变化,差异无统计学意义（P〉0.05）。结论强的松联合UDCA短期内能明显减轻AIH-PBC患者的临床症状、体征,改善生化学和肝组织学指标,提高患者生存质量,治疗安全有效。     

熊去氧胆酸治疗无重叠和有重叠特征原发性胆汁性肝硬化的疗效及生存分析

目的观察熊去氧胆酸（ursodeoxyeholicacid,UDCA）对具有自身免疫性肝炎（autoimmunehepatitis,AIH）重叠特征的原发性胆汁性肝硬化（Drimarybiliarycirrhosis．PBC）和单纯PBC患者的疗效以及对生存期的影响。方法回顾性分析20例因PBC死亡的患者,以患者死亡为研究终点,采用简化评分标准进行分组。其中12例诊断可能为AIH,将此12例具重叠特征和8例无重叠特征的PBC患者分别进行研究,分析2组在UDCA初治及研究终点时的临床特征、UDCA治疗的生化学应答及生存期情况。结果2组在UDCA治疗基线的PLT、ALP、GGT、ALT、AST、ALB、TBIL、TBA、CRE、PT、INR水平及梅奥风险评分差异均无统计学意义,而抗核抗体或抗平滑肌抗体≥1：80的阳性率、血清球蛋白或IgG／〉1．1倍正常值上限的百分比及AIH治疗前的简化评分差异均有统计学意义。UDCA治疗后有重叠特征组的生存时间为（24．4＋16．5）个月,中位生存时间为22．0个月;无重叠特征组生存时间为（60．6＋43-3）个月,中位生存时间为50．5个月。采用Kaplan-Meier生存分析显示,重叠特征组经过UDCA治疗后预后较差,Log-rank检验结果显示2组生存时间差异有统计学意义。在导致死亡的原因中,2组发病率差异均无统计学意义,但数据显示上消化道出血仍为主要死亡原因。结论对于巴黎标准不能确诊而简化评分标准可确诊的AIH—PBC患者,单纯UDCA治疗预后差,生存时间较无重叠特征的PBC患者短。     

Primary biliary cirrhosis and autoimmune hepatitis overlap syndrome: therapeutic features in 5 patients

Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two different liver diseases, however diagnosis criteria of these two affections can be found in a same patient. The aim of this study is to relate the clinical, serologic and histologic features of patients presenting the overlap syndrome, AIH-PBC, defined by the presence of at least of two main criteria of each disease and to evaluate their response to therapy. PATIENTS AND METHODS: This was a retrospective study concerning patients presenting overlap syndrome diagnosed between January 1998 and December 2001. These patients had been treated with ursodesoxycholic acid (AUDC) or prednisone and azathioprine or a combination of these three products. Clinical and biological criteria were used to assess response to therapy. RESULTS: Five patients fulfilled the diagnostic criteria of overlap syndrome. All patients were females, the median age was 38 years (range: 19-65 years). Three patients were treated by UDCA, a clinical and biological response was noted in only one patient. Two patients were treated by prednisone and azathioprine without any remission. Three patients were treated by a combination of these three products with a good response in two cases. CONCLUSION: Optimal treatment for overlap AIH-PBC syndrome remains to be determined. Treatment with UDCA or immunosuppressor alone is not efficient. A combination of these drugs should be evaluated in further studies.     

自身免疫性肝病重叠综合征的诊断和治疗

自身免疫性肝病（AILD）是一组以肝脏病理损害和肝功能异常为主要表现的自身免疫性疾病,可分为自身免疫性肝炎（AIH）、原发性胆汁性肝硬化（PBC）和原发性硬化性胆管炎（PSC）,重叠综合征指同时具有其中两种疾病的临床和病理表现。重叠综合征相对少见,主要包括AIH—PBC和AIH—PSC。由于重叠综合征在临床表现、血清学和组织学方面综合了两种AILD的特点,其诊断和治疗有一定难度并存在争议。对其临床表现以及诊断和治疗方案进行深入研究有助于对该病的认识和防治。