Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.

Clinical utility of two-dimensional shear-wave elastography in monitoring disease course in autoimmune hepatitis-primary biliary cholangitis overlap syndrome

BACKGROUND Autoimmune hepatitis-primary biliary cholangitis(AIH-PBC)overlap syndrome has a worse prognosis than AIH or PBC alone.Therefore,accurately staging liver fibrosis and dynamically monitoring disease progression are essential.AIM To investigate the performance of two-dimensional shear-wave elastography(2DSWE)for noninvasively staging liver fibrosis and assessing the clinical utility of repeated 2D-SWE for monitoring treatment response in AIH-PBC overlap syndrome.METHODS A total of 148 patients diagnosed with AIH-PBC overlap syndrome were retrospectively enrolled.Among them,82 patients had a 2D-SWE follow-up time of more than 1 year.The Scheuer scoring system was used to evaluate stages of hepatic inflammation and liver fibrosis.The performance of 2D-SWE for staging liver fibrosis was evaluated with the liver biopsy.Changes in liver stiffness(LS)measured by 2D-SWE in patients with or without complete biochemical remission were evaluated.RESULTS LS value was strongly correlated with liver fibrosis stage(Spearman r=0.84,P<0.0001).The areas under the receiver operating characteristic curves of LS for diagnosing significant fibrosis(≥S2),severe fibrosis(≥S3),and cirrhosis(S4)were 0.91,0.97,and 0.96,respectively.Patients with complete biochemical remission had a considerable decrease in LS values(P<0.0001).More importantly,the declined LS in patients with S0-S2 was significantly lower than that in patients with S3-S4(P=0.0002).In contrast,patients who failed to achieve biochemical remission had a slight but not significant decrease in LS(P=0.37).CONCLUSION LS measured by 2D-SWE is an accurate and reliable method in assessing liver fibrosis,especially for diagnosing severe fibrosis(≥3)and monitoring treatment response in patients with AIH-PBC overlap syndrome.

Serum metabolic profiling of targeted bile acids reveals potentially novel biomarkers for primary biliary cholangitis and autoimmune hepatitis

BACKGROUND Primary biliary cholangitis(PBC)and autoimmune hepatitis(AIH)are two unexplained immune diseases.The golden standard for diagnosis of these diseases requires a liver biopsy.Liver biopsy is not widely accepted by patients because of its invasive nature,and atypical liver histology can confuse diagnosis.In view of the lack of effective diagnostic markers for PBC and AIH,combined with the increasingly mature metabolomics technologies,including full-contour metabolomics and target.AIM To determine non-invasive,reliable,and sensitive biochemical markers for the differential diagnosis of PBC and AIH.METHODS Serum samples from 54 patients with PBC,26 patients with AIH and 30 healthy controls were analyzed by Ultra-high performance liquid chromatographytandem mass spectrometry serum metabolomics.The metabolites and metabolic pathways were identified,and the metabolic changes,metabolic pathways and inter-group differences between PBC and AIH were analyzed.Fifteen kinds of target metabolites of bile acids(BAs)were quantitatively analyzed by SRM,and the differential metabolites related to the diagnosis of PBC were screened by receiver operating characteristic curve analysis.RESULTS We found the changes in the levels of amino acids,BAs,organic acids,phospholipids,choline,sugar,and sugar alcohols in patients with PBC and AIH.Furthermore,the SRM assay of BAs revealed the increased levels of chenodeoxycholic acid,lithocholic acid(LCA),taurolithocholic acid(TLCA),and LCA+TLCA in the PBC group compared with those in the AIH group.The levels of BAs may be used as biomarkers to differentiate PBC from AIH diseases.The levels of glycochenodeoxycholic acid,glycochenodeoxycholic sulfate,and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class,which was correlated with the severity of disease.CONCLUSION The results demonstrated that the levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.

Clinicopathological features of 11 cases of chronic hepatitis B infection complicated with primary biliary cholangitis

BACKGROUND Only a few cases of chronic hepatitis B(CHB)with primary biliary cholangitis(PBC)have been reported based on histological evidence from liver biopsies.AIM To observe the clinicopathological features and outcomes of 11 patients with CHB infection complicated by PBC.METHODS Eleven patients with CHB and PBC who underwent liver biopsy at the Zhenjiang Third Hospital,affiliated with Jiangsu University,and Wuxi Fifth People’s Hospital,from January 2005 to September 2020,were selected.All patients initially visited our hospital with CHB and were pathologically diagnosed with CHB and PBC.RESULTS Only five had elevated alkaline phosphatase levels,nine were positive for antimitochondrial antibody(AMA)-M2,and two were negative for AMA-M2.Two had jaundice and pruritus symptoms,10 had mildly abnormal liver function,and one had severely elevated bilirubin and liver enzyme levels.The pathological characteristics of CHB complicated by PBC overlapped with those of PBCautoimmune hepatitis(AIH).When necroinflammation of the portal area is not obvious,the pathological features of PBC are predominant,similar to the features of PBC alone.When the interface is severe,biliangitis will occur,with a large number of ductular reactions in zone 3.Unlike the PBC-AIH overlap pathology,this pathology is characterized by a small amount of plasma cell infiltration.Unlike PBC,lobulitis is often observed.CONCLUSION This is the first large case series to show that the rare pathological features of CHB with PBC are similar to those of PBC-AIH and small duct injury was observed.

False positive anti-hepatitis A virus immunoglobulin M in autoimmune hepatitis/primary biliary cholangitis overlap syndrome:A case report

BACKGROUND Autoimmune hepatitis(AIH)is an immune-mediated liver disease affecting all age groups.Associations between hepatitis A virus(HAV)and AIH have been described for many years.Herein,we report a case of an AIH/primary biliary cholangitis(PBC)overlap syndrome with anti-HAV immunoglobulin M(IgM)false positivity.CASE SUMMARY A 55-year-old man was admitted with manifestations of anorexia and jaundice along with weakness.He had marked transaminitis and hyperbilirubinemia.Viral serology was positive for HAV IgM and negative for others.Autoantibody screening was positive for anti-mitochondria antibody but negative for others.Abdominal ultrasound imaging was normal.He was diagnosed with acute hepatitis A.After symptomatic treatment,liver function tests gradually recovered.Several months later,his anti-HAV IgM positivity persisted and transaminase and bilirubin levels were also more than 10 times above of the upper limit of normal.Liver histology was prominent,and HAV RNA was negative.Therefore,AIH/primary biliary cholangitis(PBC)overlap syndrome diagnosis was made based on the“Paris Criteria”.The patient was successfully treated by immunosuppression.CONCLUSION This case highlights that autoimmune diseases or chronic or acute infections,may cause a false-positive anti-HAV IgM result because of cross-reacting antibodies.Therefore,the detection of IgM should not be the only method for the diagnosis of acute HAV infection.HAV nucleic acid amplification tests should be employed to confirm the diagnosis.

Performance of transient elastography in assessing liver fibrosis in patients with autoimmune hepatitis-primary biliary cholangitis overlap syndrome

AIM To investigate the performance of transient elastography(TE) for diagnosis of fibrosis in patients with autoimmune hepatitis-primary biliary cholangitis(AIHPBC) overlap syndrome.METHODS A total of 70 patients with biopsy-proven AIH-PBC overlap syndrome were included. Spearman correlation test was used to analyze the correlation of liver stiffness measurement(LSM) and fibrosis stage. Independent samples Student's t-test or one-way analysis of variance was used to compare quantitative variables. Receiver operating characteristics(ROC) curve was used to calculate the optimal cut-off values of LSM for predicting individual fibrosis stages. A comparison on the diagnostic accuracy for severe fibrosis was made between LSM and other serological scores.RESULTS Patients with AIH-PBC overlap syndrome had higher median LSM than healthy controls(11.3 ± 6.4 k Pa vs 4.3 ± 1.4 k Pa, P < 0.01). LSM was significantly correlated with fibrosis stage(r = 0.756, P < 0.01). LSM values increased gradually with an increased fibrosis stage. The areas under the ROC curves of LSM for stages F ≥ 2, F ≥ 3, and F4 were 0.837(95%CI: 0.729-0.914), 0.910(0.817-0.965), and 0.966(0.893-0.995), respectively. The optimal cut-off values of LSM for fibrosis stages F ≥ 2, F ≥ 3, and F4 were 6.55, 10.50, and 14.45 k Pa, respectively. LSM was significantly superior to fibrosis-4, glutaglumyl-transferase/platelet ratio, and aspartate aminotransferase-to-platelet ratio index scores in detecting severe fibrosis(F ≥ 3)(0.910 vs 0.715, P < 0.01; 0.910 vs 0.649, P < 0.01; 0.910 vs 0.616, P < 0.01, respectively).CONCLUSION TE can accurately detect hepatic fibrosis as a noninvasive method in patients with AIH-PBC overlap syndrome.

Characteristics and Inpatient Outcomes of Primary Biliary Cholangitis and Autoimmune Hepatitis Overlap Syndrome

Background and Aims:Primary biliary cholangitis(PBC)and autoimmune hepatitis(AIH)are hepatobiliary diseases of presumed immune-mediated origin that have been shown to overlap.The aim of this retrospective trial was to use national data to examine the characteristics and outcomes of patients hospitalized with overlapping PBC and AIH(PBC/AIH).Methods:The National Inpatient Sample was used to identify hospitalized adult patients with PBC,AIH,and PBC/AIH from 2010 to 2014 by International Classification of Diseases-Ninth Edition Revision codes;patients with hepatitis B virus and hepatitis C virus infection were excluded.Primary outcomes measures were in-hospital outcomes that included mortality,respiratory failure,septic shock,length of stay,and total hospital charges.Secondary outcomes were the clinical characteristics of PBC/AIH,including the comorbid extrahepatic autoimmune disease pattern and complications of cirrhosis.Results:A total of 3,478 patients with PBC/AIH were included in the study.PBC/AIH was associated with higher rates of Sjögren’s syndrome(p<0.001;p<0.001),lower rates of Crohn’s disease(p<0.05;p<0.05),and higher rates of cirrhosis-related complications when compared to PBC or AIH alone.There were similar rates of mortality between the PBC/AIH,PBC,and AIH groups.The PBC/AIH group had higher rates of septic shock when compared to the PBC group(p<0.05)and AIH group(p<0.05)after adjusting for possible confounders.Conclusions:PBC/AIH is associated with a lower rate of Crohn’s disease,a higher rate of Sjögren’s syndrome,higher rates of cirrhosis-related complications,and significantly increased risk of septic shock compared to PBC and AIH individually.

Hepatobiliary and pancreatic disorders in celiac disease

A variety of hepatic and biliary tract disorders may complicate the clinical course of celiac disease. Some of these have been hypothesized to share common genetic factors or have a common immunopathogenesis, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune forms of hepatitis or cholangitis. Other hepatic changes in celiac disease may be associated with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma. Finally, pancreatic exocrine function may be impaired in celiac disease and represent a cause of treatment failure.

Role of albumin-bilirubin score in non-malignant liver disease

The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.

抗核抗体谱对AIH-PBC OS及单纯AIH患者激素应答的影响

目的探讨抗核抗体谱(ANAs)对自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征(AIH-PBC OS)及单纯AIH患者半年内激素应答的影响。方法回顾性分析2018年1月-2021年12月兰州大学第一医院收治的77例自身免疫性肝病(AILD)患者的资料,其中AIH-PBC OS组46例,单纯AIH组31例。均经肝穿刺活检组织病理检查确诊,并行糖皮质激素治疗。比较两组患者的一般临床特征、肝穿刺相关指标、自身抗体及免疫球蛋白指标,以及患者使用糖皮质激素初始及6个月内复查的生化及免疫球蛋白指标,根据谷草转氨酶(AST)、谷丙转氨酶(ALT)及免疫球蛋白G(IgG)水平评估治疗6个月内的激素应答情况,采用多因素有序logistic分析ANAs对两组患者激素应答结果的影响。结果ANAs阳性及阴性AILD患者中,AIH-PBC OS及单纯AIH患者占比均无统计学差异(55.6%vs.44.4%,65.6%vs.34.4%,P>0.05)。46例AIH-PBC OS患者中,ANAs阳性组25例,ANAs阴性组21例。ANAs阳性组半年内激素完全应答率低于ANAs阴性组(44.0%vs.76.2%),而激素不应答率高于ANAs阴性组(20.0%vs.0),差异有统计学意义(P<0.05)。31例单纯AIH患者中,ANAs阳性组20例,ANAs阴性组11例。两组患者半年内激素应答结果差异无统计学意义(P>0.05)。多因素有序logistic分析结果显示,AIHPBC OS患者中,ANAs阳性者半年内激素不应答的可能性较大,差异有统计学意义(P<0.05)。而单纯AIH患者中ANAs类型对激素应答结果无明显影响(P>0.05)。结论在AIH-PBC OS患者中,ANAs阳性者半年内激素应答结果欠佳;在单纯AIH患者中,ANAs对激素应答结果无明显影响。

慢性乙型肝炎合并原发性胆汁性胆管炎的临床特点

目的观察24例慢性乙型肝炎(chronic hepatitis B,CHB)合并原发性胆汁性胆管炎(primary biliary cholangitis,PBC)患者的临床特征和预后。方法选取2010年1月至2022年12月在首都医科大学附属北京佑安医院就诊的CHB合并PBC患者。所有患者最初均因CHB就诊于我院。结果24例患者中女16例,男8例,女性占比66.7%,13例出现黄染或皮肤瘙痒症状,16例肝功能异常,以碱性磷酸酶(alkaline phosphatase,ALP)和r-谷氨酰转肽酶(r-Glutamyl transpeptidase,γ-GT)升高为主,24例患者抗线粒体抗体阳性。24例患者接受抗病毒和熊去氧胆酸治疗后,ALP和γ-GT水平明显下降(P=0.003,P=0.004)。结论CHB合并PBC患者接受抗病毒和熊去氧胆酸治疗后,不影响其生化应答及预后。

Predictors of survival in autoimmune liver disease overlap syndromes

BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is unclear.AIM To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death.METHODS Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap(AIH-PBC)or autoimmune hepatitis and primary sclerosing cholangitis overlap(AIH-PSC)and were identified from three tertiary centres for this cohort study.Liver-related death or transplantation(liver-related mortality)was determined using a population-based data linkage system.Prognostic scores for liver-related death were compared for accuracy[including liver outcome score(LOS),Hepascore,Mayo Score,model for end-stage liver disease(MELD)score and MELD incorporated with serum sodium(MELD-Na)score].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepascore was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBC,27%AIH-PSC).There was no significant difference in survival between AIH-PBC and AIH-PSC.LOS was a significant predictor of liver-related mortality(P<0.05)in patients with AIH-PBC(n=14)but not AIH-PSC(n=8).A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients(P=0.012,log-rank test,100%sensitivity,77.8%specificity)(Harrell's C-statistic 0.867).The MELD score,MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group.CONCLUSION Survival in the rare,AILDOS is unclear.The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients.Further trials investigating predictors of survival in AILDOS are required.

多种无创检测指标预测自身免疫性肝病患者肝硬化效能比较

目的评估无创检测指标诊断自身免疫性肝病(AILDs)患者肝硬化的效能。方法2017年4月~2020年9月我院诊治的自身免疫性肝炎(AIH)患者93例和自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征(AIH-PBC OS)患者37例,均接受肝活检,并常规检测获得门冬氨酸氨基转移酶/血小板计数比值(APRI)、基于4因子的纤维化指数(FIB-4)、门冬氨酸氨基转移酶-丙氨酸氨基转移酶(AAR)和肝脏硬度检测(LSM),绘制受试者工作特征曲线(ROC),并计算曲线下面积(AUROC),评估诊断效能。结果肝组织病理学检查显示,在AIH患者中,发现肝硬化21例(22.6%),在AIH-PBC OS患者中,发现肝硬化6例(16.2%);无论在AIH组还是AIH-PBC OS组,肝硬化患者LSM、FIB-4和AAR都显著高于非肝硬化组(P<0.05);LSM、FIB-4和AAR诊断AIH患者肝硬化的截断点分别为17.7 kPa、3.6和1.1,其诊断的AUC分别为0.876、0.783和0.745;LSM、FIB-4和AAR诊断AIH-PBC OS患者肝硬化的截断点分别为22.9 kPa、7.7和1.0,其诊断的AUC分别为0.989、0.914和0.833,均以LSM的诊断效能最高。结论无创检测指标LSM、FIB-4和AAR诊断AILDs患者肝硬化具有很大的临床应用价值,适合普查和筛查。

青海地区自身免疫性肝病重叠综合征患者的抗线粒体抗体差异分析

目的总结青海省自身免疫性肝病重叠患者的临床及病理特征,提高临床诊治水平。方法回顾性分析2017年12月—2022年12月青海省人民医院首次确诊为自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征的患者共85例,抗线粒体抗体阳性为A组共58例,抗线粒体抗体阴性为B组27例。分析一般临床特征、合并疾病情况、血清生化学指标、免疫学指标、肝组织的病理情况;计量资料符合正态分布的采用x±s表示,组间比较采用独立样本t检验;不符合正态分布的计量资料采用M(P_(25),P_(75))表示,组间比较采用Wilcoxon秩和检验;计数资料采用构成比(%)表示,组间比较采用χ^(2)检验。结果A、B两组患者在性别、年龄、总胆红素、γ-谷氨酰基转移酶、碱性磷酸酶、免疫球蛋白G的水平及抗Ro52抗体、抗SSA抗体检出率、干燥综合征患病率、肝脏病理炎症分级、肝脏病理纤维化分级的比较上无统计学差异(P>0.05);在丙氨酸氨基转移酶[(115.41±76.63)比(255.90±244.90)U/L]、免疫球蛋白M[4.05(2.75,5.43)比1.99(1.41,3.51)g/L]水平、抗核抗体-G(χ^(2)=9.67)、自身免疫性甲状腺疾病(χ^(2)=5.74)患病率的组间比较差异有统计学意义(P<0.05)。结论A组患者丙氨酸氨基转移酶、免疫球蛋白M及抗核抗体-G水平更高,B组患自身免疫性甲状腺疾病比例更高;两组病理组织学的炎症分级及纤维化分级以中重度为主,提示患者发病隐匿,病程漫长,确诊时病情分期较晚;如确诊为自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征患者,建议完善甲状腺疾病的检查。

Graves病合并自身免疫性肝病1例并文献复习

甲状腺功能亢进症导致肝损伤的原因有甲状腺激素增多引起的损伤、抗甲状腺药物治疗引起的药物性肝损伤(DILI)及可能合并的其他肝脏疾病等[1,2]。Graves病(Graves'disease,GD)是一种全身性自身免疫性疾病,也是甲状腺功能亢进症最常见的表现形式。2010年一项研究报道,另一种自身免疫性疾病,如类风湿关节炎、恶性贫血、系统性红斑狼疮等在GD患者的发生率为9.7%,在桥本甲状腺炎的发病率为14.3%[3]。近年来,部分文献报道了GD合并自身免疫性肝病,尤其是自身免疫性肝炎(autoimmune hepatitis,AIH),但合并原发性胆汁性胆管炎(primary biliary cholangitis,PBC)或合并重叠综合征(overlap syndrome,OS)的情况还比较少见。本文报道了1例GD患者在治疗期间反复出现肝功能异常,经肝活检组织病理学检查证实其合并PBC-AIH OS,经积极治疗后病情明显缓解。

原发性胆汁性胆管炎-自身免疫性肝炎重叠综合征合并肺隐球菌病1例报告

自身免疫性肝病重叠综合征表现为患者出现一种以上的自身免疫性肝病的生化、免疫、组织学或胆管造影特征,常需联合使用免疫抑制剂治疗。肺隐球菌病是一种由新型隐球菌或格特隐球菌引起的侵袭性肺真菌病,易在免疫功能低下患者中发生。本病例为1例重叠综合征,在免疫抑制治疗过程中发现并治疗肺隐球菌病,在抗真菌治疗过程中肝功能出现异常,根据患者的肝功能情况,评估了更换抗真菌药物的可行性,综合考虑后制定了在密切监测肝功能的情况下,积极治疗新型隐球菌感染的治疗策略,避免了感染的进展。提示在启动免疫抑制治疗前,除了全面评估全身感染灶,对于可疑感染灶也必须保持监测。

自身免疫性肝炎和原发性胆汁性胆管炎患者甲状腺功能变化及其对治疗应答的影响

目的分析自身免疫性肝炎(AIH)和原发性胆汁性胆管炎(PBC)患者甲状腺功能、抗甲状腺抗体变化及其对治疗应答的影响。方法2020年1月~2022年1月我院诊治的AIH患者30例、PBC患者28例和同期健康体检者32例,分别给予患者标准的免疫抑制或熊去氧胆酸治疗。常规检测血清三碘甲状腺原氨酸(T3)、四碘甲状腺原氨酸(T4)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)水平,采用放射受体法检测血清抗甲状腺素受体抗体(TRAb)、抗甲状腺过氧化物酶抗体(TPO-Ab)、抗甲状腺球蛋白抗体(TGAb)、甲状腺素结合球蛋白(TBG)和甲状腺球蛋白(TG)。结果AIH组血清FT3和FT4水平分别为(4.2±0.2)pmol/L和(13.8±1.9)pmol/L,PBC组分别为(4.3±0.3)pmol/L和(13.9±1.3)pmol/L,均显著低于健康人【分别为(4.9±0.6)pmol/L和(15.9±4.2)pmol/L,P<0.05】,而AIH组和PBC组血清TSH水平分别为(3.8±1.2)mIU/L和(3.7±0.5)mIU/L,均显著高于健康人【(2.6±0.5)mIU/L,P<0.05】;AIH组血清TPO-Ab和TG阳性率分别为33.3%和26.7%,PBC组分别为39.3%和25.0%,均显著高于健康人的9.4%和3.1%(P<0.05);经过1年的治疗,AIH组生化学应答率为66.7%,PBC组为75.0%;两种疾病应答组血清FT3和FT4水平显著高于未应答组,而血清TSH水平及TPO-Ab和TG阳性率显著低于未应答组,差异有统计学意义(P<0.05)。结论AIH和PBC患者都可能存在甲状腺功能减退,并影响治疗应答,临床应予以重视筛查和处理。

自身免疫性肝炎和原发性胆汁性胆管炎患者血清胆汁酸成分变化及其对治疗应答的影响

目的研究自身免疫性肝炎(AIH)和原发性胆汁性胆管炎(PBC)患者血清胆汁酸(BAs)成分变化及其对治疗应答的影响。方法2020年1月~2023年1月我院诊治的28例AIH患者和55例PBC患者,分别接受醋酸泼尼松或熊去氧胆酸胶囊治疗。采用液相色谱-质谱联用法(LC-MS/MS)检测血清BAs成分,包括游离胆酸(CA)、去氧胆酸(DCA)、鹅去氧胆酸(CDCA)、熊去氧胆酸(UDCA)和石胆酸(LCA),甘氨结合型BAs包括糖胆酸(GCA)、糖去氧胆酸(GDCA)、糖去氧胆酸(GCDCA)和糖去氧胆酸(GUDCA)和牛磺结合型BAs包括牛磺酸胆酸(TCA)、牛磺酸去氧胆酸(TDCA)、牛磺酸去氧胆酸(TCDCA)和牛磺酸石胆酸(TLCA)。结果在治疗6个月末,AIH患者获得应答20例(71.4%),PBC患者获得应答42例(76.4%);AIH应答组血清CA、CDCA、UDCA和LCA分别为(1.6±0.5)ng/ml、(2.6±0.4)ng/ml、(2.0±0.3)ng/ml和(0.7±0.4)ng/ml,均显著低于未应答组【分别为(2.4±0.7)ng/ml、(2.9±0.4)ng/ml、(2.4±1.0)ng/ml和(0.9±0.7)ng/ml,P<0.05】,血清GCA、GDCA、GCDCA和GUDCA水平分别为(1.3±0.5)ng/ml、(2.6±0.3)ng/ml、(2.9±0.3)ng/ml和(1.6±0.5)ng/ml,均显著低于未应答组【分别为(3.0±1.0)ng/ml、(3.2±0.6)ng/ml、(3.8±0.8)ng/ml和(2.6±1.2)ng/ml,P<0.05】,血清TCA、TDCA、TCDCA和TLCA水平分别为(0.5±0.1)ng/ml、(2.6±0.2)ng/ml、(2.5±0.3)ng/ml和(0.1±0.0)ng/ml,均显著低于未应答组【分别为(2.1±1.2)ng/ml、(3.3±0.6)ng/ml、(2.7±0.4)ng/ml和(0.4±0.1)ng/ml,P<0.05】;PBC应答组血清CA、CDCA、UDCA和LCA水平分别为(1.7±0.4)ng/ml、(2.7±0.4)ng/ml、(2.1±0.4)ng/ml和(0.8±0.4)ng/ml,均显著低于未应答组【分别为(2.3±0.9)ng/ml、(3.0±0.4)ng/ml、(2.5±0.7)ng/ml和(1.3±0.7)ng/ml,P<0.05】,血清GCA、GDCA、GCDCA和GUDCA水平分别为(1.4±0.7)ng/ml、(2.6±0.4)ng/ml、(3.0±0.5)ng/ml和(2.0±0.9)ng/ml,均显著低于未应答组【分别为(2.9±0.9)ng/ml、(3.2±0.5)ng/ml、(3.8±0.7)ng/ml和(3.0±1.1)ng/ml,P<0.05】,血清TCA、TDCA、TCDCA和TLCA水平分别为(0.5±0.2)ng/ml、(2.7±0.3)ng/ml、(2.5±0.4)ng/ml和(0.2±0.1)ng/ml,均显著低于未应答组【分别为(2.1±0.9)ng/ml、(3.2±0.5)ng/ml、(2.8±0.4)ng/ml和(0.5±0.2)ng/ml,P<0.05】。结论虽然PBC和AIH患者血清BAs水平有显著性差异,但血清Bas水平升高或在治疗过程中不下降者,可能影响对治疗的应答,其机制还有待于探讨。

自身免疫性肝炎合并原发性胆汁性胆管炎继发耶氏肺孢子菌肺炎患者的药学监护

自身免疫性肝炎(AIH)合并原发性胆汁性胆管炎(PBC)继发耶氏肺孢子菌肺炎1例女性患者,因“间断皮肤瘙痒8年,间断发热20 d”入院。患者3个月前被诊断为PBC合并AIH,经激素治疗后好转出院,院外持续规律口服激素治疗。此次入院诊断为呼吸窘迫综合征、重症肺炎、PBC、AIH。患者入院后经验性给予哌拉西林钠/他唑巴坦钠抗感染治疗,后经支气管肺泡灌洗液二代基因测序提示耶氏肺孢子菌感染。临床药师通过查阅相关文献建议给予甲氧苄啶-磺胺甲噁唑联合卡泊芬净治疗,同时监测患者用药疗效及可能出现的不良反应,根据患者的实际情况调整治疗方案,对患者进行用药、生活饮食等指导。经积极有效的治疗后患者的症状得到有效控制,好转出院。自身免疫性肝病是继发耶氏肺孢子菌肺炎的高危因素,致死率高。临床药师需通过综合研判患者的疾病状况、用药情况及检测结果,协同临床医师制定合理化、个体化的药物治疗方案,以提高药物治疗的安全性、有效性和经济性。此外,与医师建立良好的沟通,提高了患者对药师的信任,同时临床药师积极参与危重患者的药学管理有助于为患者安全有效的治疗提供保障,改善其临床预后。

自身免疫性肝病患者SH2B3基因Rs3184504单核苷酸多态性分析

目的探讨自身免疫性肝病(AILD)患者SH2B衔接蛋白3(SH2B3)基因中Rs3184504单核苷酸多态性(SNP)变化。方法2017年6月~2023年10月我院收治的58例自身免疫性肝炎(AIH)、62例原发性胆汁性胆管炎(PBC)患者和同期体检的60例健康人,采用PCR法检测SH2B3基因中Rs3184504位点多态性。应用Logistic回归分析SH2B3基因Rs3184504单核苷酸多态性与AIH或PBC的患病风险度。结果AIH组SH2B3基因Rs3184504位点中TT基因型和等位基因T占比分别为53.4%和66.4%,PBC组分别为54.8%和69.4%,均显著高于健康人(分别为16.7%和26.7%,P<0.05),而AIH组和PBC组SH2B3基因Rs3184504位点中CC基因型分别为20.7%和16.1%,均显著低于健康人的63.3%(P<0.05);Logistic回归分析显示,相对于SH2B3基因Rs3184504位点中CC基因型携带者,TT基因型携带者AIH患病风险提高了2.529倍(OR=2.529,P<0.05),相对于SH2B3基因Rs3184504位点中CC基因型携带者,CT基因型携带者PBC患病风险提高了2.812倍(OR=2.812,P<0.05),TT基因型携带者PBC患病风险提高了2.370倍(OR=2.370,P<0.05)。结论AILD与SH2B3基因中Rs3184504单核苷酸多态性变化有关,其中TT基因是AIH易感基因型,CT和TT基因型是PBC易感基因型,携带T等位基因的患者发生AILD的风险增加。