Sex differences in clinical presentation and prognosis in patients with primary biliary cholangitis

Abstract

Objectives: Primary biliary cholangitis (PBC) is a chronic inflammatory disease of the small intrahepatic bile ducts disproportionally affecting women. Timely diagnosis and treatment can often prevent progression to liver cirrhosis. We hypothesized PBC diagnosis in male patients is delayed and prognosis impaired. We, therefore, conducted a case–control study and compared clinical and prognostic features among male and female patients with PBC.

Materials and methods: 49 male patients with PBC treated at a German tertiary care center between 2006 and 2017 were identified and compared to 98 age-matched female controls. Prospectively collected clinical/biochemical data were analyzed retrospectively. Liver biopsies were scored in a blinded fashion. Prognostic parameters were calculated using established prognostic scores (GLOBE, PBC-UKE). Statistical analysis was performed using Mann-Whitney test and Fisher´s exact test.

Results: At PBC diagnosis, male patients reported significantly less PBC-associated symptoms as compared to female controls (34 versus 71%, p?<?.01). Compared to female patients, median time from onset of PBC-related symptoms and/or first reported elevated cholestatic biochemical parameters to PBC diagnosis was significantly increased in men (36 versus 12?months, p?=?.02). In addition, male patients underwent liver biopsy to establish PBC diagnosis more frequently, tended to show more advanced fibrosis and showed significantly poorer prognostic PBC score results. Hepatocellular carcinoma was only observed in male patients (n?=?3).

Conclusions: When compared to women, men with PBC suffer from less PBC-related symptoms, receive PBC diagnosis delayed and have a worse prognosis. Despite its rarity, the diagnosis of PBC should be considered in men with elevated cholestatic parameters.     

Impact of technical modification of endoscopic papillectomy for ampullary neoplasm on the occurrence of complications

Aim: To evaluate the usefulness of a modified technique of endoscopic papillectomy (EP) for lessening the occurrence of complications. Methods: Indications for EP were adenoma or well‐differentiated adenocarcinoma confined to the papilla of Vater (T1) without tumor spread into the bile/pancreatic duct. Sixteen patients underwent the modified technique, which consists of resection with the Endocut^® mode, followed by biliary/pancreatic sphincterotomy and stenting (Group A). Twelve patients who had undergone EP, using a cutting current, followed by pancreatic duct stenting were included as control (Group B). The frequency of complications and clinical outcomes were retrospectively compared between the two groups. Results: Sixteen patients had adenoma, and 12 had adenocarcinoma. Early complications occurred in 36% of all patients (hemorrhage, 7; cholangitis, 3; perforation, 2; cholecystitis, 1). The frequency of early complications in Group A was significantly lower than that in Group B (6% vs 75%, odds ratio [OR] 0.022, 95% confidence interval [CI], 0.0020–0.25). Late complications occurred in 18% of the patients (bile duct stone, 3; hemorrhage, 1; pancreatitis, 1). There was no significant difference in the late complication rate between Group A and Group B (19% vs 17%). Local recurrences were found in 14% of the patients, without a significant difference between Group A and Group B (19% vs 8%) during a mean follow‐up period. All recurrent tumors were successfully treated with argon plasma coagulation. Conclusions: The modified technique of EP for ampullary neoplasm contributed to lessening the occurrence of early complications. However, further refinement of this technique is necessary for improving the clinical outcome.     

Autoimmune cholangitis and cholangiocarcinoma

Autoimmune cholangitis, immunoglobulin G4‐associated cholangitis (IAC), is a part of multiorgan IgG4‐related systemic disease, which was recognized as a new clinicopathological entity in recent years. IAC is defined as a biliary stricture that responds to steroid therapy, frequently is associated with other fibrosing conditions, especially autoimmune pancreatitis and is characterized by elevation of IgG4 in serum and infiltration of IgG4 positive plasma cells in bile ducts. Since IAC shares a number of clinical, biochemical, and imaging features with cholangiocarcinoma (CCA), it is often misdiagnosed as CCA, and unnecessary surgery was performed. In this compact review, we clarify the disease of IAC, summarize criteria for diagnosis of IAC, discuss the role of CA 19‐9, and provide key information to differentiate diagnosis of IAC from CCA. IAC should be highly suspected in unexplained biliary stricture associated with increased IgG4 (in serum especially in bile) and other organ involvement (kidney, retroperitoneum etc. especially pancreas in which there are abundant IgG4‐positive plasmocytes infiltration). Correct diagnosis of IAC will avoid unnecessary surgery because IAC responds well to steroid therapy. In a word, increased IgG4 levels, other organ involvement and response to steroids are keys to distinguishing IAC from CCA.     

36例原发性胆汁性肝硬化的临床特征分析

目的探讨原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)患者的临床特征,以提高对PBC的诊断与治疗水平。方法对具有完整资料的36例PBC的一般资料、从出现症状或肝功改变到确诊的时间、临床表现、血清化学指标、免疫学、影像学、病理学改变及治疗转归等进行回顾性分析。结果本组36例PBC患者中女性33例(91.7%)。从出现症状或肝功改变至确诊的平均时间为18.95个月,最长82个月。临床表现主要为乏力(80.6%)、皮肤瘙痒(69.4%);最主要的体征为黄疸(61.1%)和脾大(61.1%);AMA/AMA-M2阳性率达91.67%;r-谷胺酰转肽酶(GGT)、总胆红素(TBIL)、直接胆红素(DBIL)和血清白蛋白(ALB)在不同的临床分期中差异有统计学意义(P<0.05)。肝硬化前期组经熊去氧胆酸(UDCA)治疗前后肝功的对比差异有统计学意义(P<0.05),而肝硬化期组此项对比差异无统计学意义(P>0.05)。结论 PBC以中年女性多见,高滴度AMA及AMA-M2亚型是诊断PBC的主要指标。肝硬化期GGT、TBIL和DBIL的水平明显高于肝硬化前期,而ALB水平反而明显降低。该病病程较长,在早期主要表现为原发性胆汁性胆管炎,需较长时间才发展为原发性胆汁性肝硬化。以UDCA为主的综合治疗能够明显改善早期患者的症状和血清胆汁淤积指标。因此早期发现、早期治疗效果较好。     

经皮肝穿刺胆道引流治疗急性梗阻性化脓性胆管炎合并感染性休克的疗效分析

目的 评价经皮肝穿刺胆道引流(PTCD)治疗急性梗阻性化脓性胆管炎(AOSC)合并感染性休克的临床效果.方法 回顾性分析2010年12月-2015年12月收治的79例AOSC合并感染性休克患者的临床资料,并总结其治疗经验.结果 79例患者均行PTCD,穿刺成功率100％,无明显手术相关并发症发生.75例患者于经皮肝穿刺胆道引流管置入术后3～7 d感染性休克症状消失,4例患者于住院期间死上.75例患者中62例患者于病情稳定后根据梗阻原因行二期手术或双介入手术治疗,2例患者于病情稳定后拒绝二次手术治疗,11例患者不能二期手术或双介入手术带管生存,平均4.7个月.结论 对合并感染性休克的AOSC患者行急症PTCD治疗不仅可以快速退黄减压,降低病死率,而且可以改善休克症状,为二期手术或双介入手术治疗创造机会和条件,是一种安全有效的治疗方式.     

超声引导PTCD在急性梗阻性化脓性胆管炎的应用价值

目的探讨急性梗阻性化脓性胆管炎的治疗方法,床旁急诊超声引导经皮肝穿刺胆道引流术(percutaneous transhepatic cholangial drainage,PTCD)在该病中的应用价值。方法收集2011年5月至201 5年6月海南省农垦总医院63例急性梗阻性化脓性胆管炎病人的临床资料,回顾分析床旁急诊超声引导PTCD的治疗效果。结果超声引导PTCD成功率为100%;引流量为250~830 ml/d,平均为(530±68)ml/d;引流后血常规及肝功能检查结果显示,与术前比较,白细胞计数(WBC)、血清总胆红素(TBIL)、血清直接胆红素(DBIL)、丙氨酸转氨酶(ALT)指标显著下降,血小板计数(BPC)上升,体温正常,差异均有统计学意义(P0.01)。症状改善58例(92%),死亡5例(8%),无引流管脱落,无腹腔内出血、胆道出血、气胸、胆漏等并发症发生。结论床旁急诊超声引导PTCD,能快速有效引流,操作方便、简单,创伤小,并发症少,安全性高,能为解除病因手术安全性创造条件。     

细胞毒性T细胞穿入现象在原发性胆汁性胆管炎中的表现及意义*

目的:研究原发性胆汁性胆管炎(primary biliary cholangitis,PBC)中发生CD8+细胞毒性T细胞(cytotoxic T lymphocyte,CTL)穿入现象及其意义。方法:收集53例PBC患者肝穿刺标本,采用H&E染色和免疫荧光染色方法,在光学显微镜和激光共聚焦显微镜下观察PBC肝组织中CTL的穿入及穿入宿主细胞的类型,并分析与病程的关系。结果:53例PBC患者中10例(18.9%)发生淋巴细胞穿入肝细胞,15例(28.3%)发生淋巴细胞穿入胆管上皮,仅1例患者同时存在淋巴细胞穿入肝细胞和胆管上皮细胞。免疫荧光染色证实穿入的淋巴细胞是CD8阳性细胞毒性T细胞(CTL)。早期PBC患者中4例(22.2%)、晚期PBC患者中6例(17.1%)发生CTL穿入肝细胞,两组差异无统计学意义(P>0.05)。早期PBC患者中9例(50.0%)、晚期PBC患者中6例(17.1%)发生CTL穿入胆管上皮,两组差异有统计学意义(Z=2.52,P<0.05)。结论:在PBC肝组织中,CTL可穿入肝细胞和胆管上皮细胞,CTL穿入胆管上皮细胞并导致其发生凋亡可能是PBC发病过程中胆管损伤的机制之一。     

Recurrence of primary sclerosing cholangitis after liver transplantation is associated with specific changes in the gut microbiome pretransplant – a pilot study

Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation (LT). Up to 25% of patients experience recurrence of PSC (rPSC) after LT, which is associated with significant morbidity and mortality. To date, it is not possible to predict which patients are at risk for rPSC. The aetiology of PSC is complex and is speculated to involve translocation of intestinal bacteria to the liver, because of its frequent co-occurrence with inflammatory bowel diseases (IBD). Here, we investigate whether the mucosal intestinal microbiome of PSC patients (n = 97) at time of first LT can identify those patients who will develop rPSC. 16S gene sequencing of bacterial DNA isolated from formalin-fixed paraffin-embedded biopsies showed that PSC patients with Crohn’s disease (n = 15) have a reduced microbial diversity and that inflammation of the mucosa is associated with beta-diversity changes and feature differences. No differences in alpha- or beta diversity were observed between patients with rPSC (n = 14) and without rPSC (n = 83). However, many over-represented bacterial features were detected in patients with rPSC, while surprisingly, those without recurrence of disease were characterized by an increased presence of the Gammaproteobacteria Shigella. This pilot study warrants further investigation into bacterial differences between rPSC and non-rPSC patients.     

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

Background and AimsPrimary 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).MethodsThe 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.ResultsA 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.ConclusionsPBC/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.     

PTBD联合二期PTCSL术治疗急性胆管炎伴胆总管结石患者疗效及安全性评价*

目的 探讨采用经皮肝穿刺胆道引流术(PTBD)联合二期经皮经肝胆道镜取石术(PTCSL)治疗急性胆管炎伴胆总管结石患者的疗效及其安全性。方法 2017年5月～2020年5月常州市第七人民医院收治的急性胆管炎伴胆总管结石患者75例,均急诊接受PTBD手术治疗。在术后2～4 w,其中39例观察组患者接受二期PTCSL术治疗,另36例对照组接受腹腔镜胆囊切除术(LC)、腹腔镜胆道探查取石术(LCBDE)和T管引流术治疗。随访1年。结果 术后,观察组肛门排气时间、引流管留置时间分别为(19.6±3.3)h和(7.8±1.2) h,与对照组的(20.4±3.5) h和(8.1±1.3) h比,差异均无统计学意义(P>0.05),而观察组手术时间和住院日分别为(86.9±14.1)min和(9.5±1.5)d,均显著短于对照组[分别为(124.6±19.8)min和(11.4±1.9)d,P<0.05];在术后24 h,观察组疼痛评分(2.1±0.3)分,显著低于对照组[(3.6±0.6)分,P<0.05];术后,观察组切口感染、胆漏、胰腺炎和胆道出血等并发症发生率为15.4%,与对照组的13.9%比,差异无统计学意义(P>0.05);随访发现,观察组结石残余和结石复发发生率分别为7.7%和15.4%,与对照组的8.3%和11.1%比,差异均无统计学意义(P>0.05)。结论 本研究采用的两套手术方案治疗急性胆管炎伴胆总管结石患者均安全、有效,但采用二期PTCSL术治疗能够缩短手术时间和住院时间,减轻术后疼痛反应,似更合适。