儿童自身免疫性肝炎新进展

儿童自身免疫性肝病不是很常见,除了自身免疫性肝炎,还包括自身免疫性硬化性胆管炎、巨细胞肝炎伴自身免疫性溶血、肝移植后新发自身免疫性肝炎以及2个获得性自身免疫性肝病：新生儿狼疮、妊娠同种免疫性肝病(又名新生儿血色病)。涉及本年龄阶段特有的免疫系统和全身的发育特点,决定着儿童的自身免疫性肝病的种类、临床特征、预后转归可能不...     

儿童自身免疫性肝病研究进展

儿童自身免疫性肝病是指儿童患者由于自身免疫因素引起的肝脏损伤,主要包括：自身免疫性肝炎、自身免疫性硬化性胆管炎以及肝移植术后新发自身免疫性肝炎3类,其中以自身免疫性肝炎常见。到目前为止,尚无16岁以下儿童原发性胆汁性肝硬化的报道。     

Clinical analysis in 208 patients with autoimmune liver disease

目的 分析自身免疫性肝病(AILD)的临床、生化及免疫学特点.方法 选择2005年1月～ 2010年12月我院消化内科收治的自身免疫性肝病患者208例,采用回顾性分析方法收集入选患者的临床资料,分析208例自身免疫性肝病患者的临床表现、生化及免疫学特点.结果 自身免疫性肝病的发病以40岁以上女性多见,30.8％ (64/208)的患者确诊时已进展为肝硬化失代偿期,临床症状无特异性,自身免疫性肝炎患者以丙氨酸氨基转移酶(ALT)、血清免疫球蛋白G(IgG)及γ球蛋白升高更为明显(P＜0.05),而原发性胆汁性肝硬化患者以碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、血清免疫球蛋白M(IgM)升高更为明显(P＜0.05).自身免疫性肝病患者常合并1种或多种肝外自身免疫性疾病,其合并干燥综合征最为常见,自身免疫性肝炎组及原发性胆汁性肝硬化组合并干燥综合征的发生率均达30％以上.自身免疫性肝病患者均有1种或多种自身抗体阳性,其中自身免疫性肝炎组抗核抗体(ANA)阳性率为88.2％,抗线粒体抗体(AMA)阳性率为7.4％,抗线粒体抗体Ⅱ型(AMA-M2)阳性率为4.4％;原发性胆汁性肝硬化组ANA阳性率为86.6％,AMA阳性率为97.6％,AMA-M2阳性率为95.9％.自身免疫性肝炎患者主要应用糖皮质激素治疗,其中共51例(60.0％)患者单用或联用熊去氧胆酸治疗后肝脏酶学指标改善.结论 生化、免疫学、自身抗体等检查对自身免疫性肝病的诊断与鉴别诊断具有重要临床意义,熊去氧胆酸在自身免疫性肝炎的治疗中有一定的作用.     

自身免疫性肝病相关自身抗体检测的临床应用专家共识

自身免疫性肝病是一组由异常自身免疫介导的肝胆炎症性疾病,主要包括自身免疫性肝炎、原发性胆汁性胆管炎、原发性硬化性胆管炎及上述任何两种疾病主要特征同时出现的重叠综合征等。自身免疫性肝病相关自身抗体检测临床应用的标准化,有助于疾病的诊断与分类、预测预后、病情监测及发病机制的研究。     

自身免疫性肝病相关自身抗体检测的临床应用专家共识

自身免疫性肝病是一组由异常自身免疫介导的肝胆炎症性疾病, 主要包括自身免疫性肝炎、原发性胆汁性胆管炎、原发性硬化性胆管炎及上述任何两种疾病主要特征同时出现的重叠综合征等。自身免疫性肝病相关自身抗体检测临床应用的标准化, 有助于疾病的诊断与分类、预测预后、病情监测及发病机制的研究。     

自身免疫性肝炎和原发性胆汁性肝硬化重叠综合征15例临床特点分析

自身免疫性肝病是一组具有自身免疫基础的炎症性肝病,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)等,临床上确有一部分患者可同时具有上述几种疾病的临床特点,即重叠综合症.对80例自身免疫性肝病患者临床资料进行回顾性分析,发现AIH/PBC重叠综合征15例,本文对其临床特点进行分析,报道如下.     

自身免疫性肝病诊断与治疗进展

自身免疫性肝病是一组由自身免疫介导的慢性肝胆系统损伤性疾病,主要包括自身免疫性肝炎、原发性胆汁性肝硬化及原发性硬化性胆管炎.本文就自身免疫性肝病的诊断与治疗进展进行综述.     

原发性胆汁性肝硬化-自身免疫性肝炎重叠综合征5例

自身免疫性肝病主要包括自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)、原发性硬化性胆管炎(PSC).在临床诊治过程中,我们有时会发现2种或3种自身免疫性肝病在同一患者身上会有重叠的表现,在诊断和治疗过程中可能发生困难.为此,将在临床上所见的5例加以介绍,引起注意.     

献礼建党百年, 助力健康中国——我国第一部自身免疫性肝病诊治指南正式发布

自身免疫性肝病是因自身免疫紊乱导致肝脏细胞受损而产生的慢性肝病, 主要包括自身免疫性肝炎、原发性胆汁性胆管炎、原发性硬化性胆管炎和IgG4相关硬化性胆管炎等。2015年, 中华医学会肝脏病学分会针对自身免疫性肝炎、原发性胆汁性胆管炎、原发性硬化性胆管炎和胆汁淤积性肝病分别推出了诊疗共识, 这是我国自身免疫性肝病临床诊治的重要里程碑事件。近年来, 国内外研究进展迅速, 有必要以更高的循证标准制定疾病指南, 为疾病的规范化诊治提供依据和准则。2021年7月, 中华医学会肝脏病学分会自身免疫性肝病学组召开学术年会, 会议期间举行了自身免疫性肝病指南撰写启动会。经过多次讨论和修改, 于2021年12月首发于《中华内科杂志》。     

自身免疫性肝病的治疗

临床上常见的自身免疫性肝病包括自身免疫性肝炎(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 cholangitis,PSC)以及重叠综合征.本文简单介绍自身免疫性肝病的治疗,以供临床医生参考.     

Lymphocytic (microscopic) colitis

Lymphocytic colitis, formerly called microscopic colitis, is a clinicopathologic syndrome with chronic watery diarrhea and diffuse mucosal inflammatory changes with prominent intraepithelial lymphocytes. The 18 lymphocytic colitis patients studied presented with chronic watery diarrhea at a mean age of 53.8±17 years (±1 SD). Roentgenographic, endoscopic, and culture data were not diagnostic. In patients tested, there was a high prevalence of arthritis (82%) and autoantibodies (50%) but no increase in frequency of histocompatibility antigens associated with well-defined autoimmune disease (DR3, B8). Lymphocytic colitis patients were compared to 21 patients with collagenous colitis. Similarities included age, symptomatology, and nondiagnostic radiographic and endoscopic studies. However, the sex distribution was statistically different, with an equal male-to-female ratio in lymphocytic colitis and female predominance (80%) in collagenous colitis. Other differences included dissimilar histocompatibility phenotypes and collagen band on biopsies of collagenous but not lymphocytic colitis. These findings suggest that lymphocytic and collagenous colitis may be related yet distinct disorders.Presented in part at The National Foundation for Ileitis and Colitis Seminar in Ft. Lauderdale, Florida, October 1987.Supported in part by The Harvey M. and Lyn P. Meyerhoff Digestive Disease-Inflammatory Bowel Disease Center, The National Foundation for Ileitis and Colitis, and by an institutional grant from The Johns Hopkins University School of Medicine.Dr. Lazenby is a recipient of a fellowship from The National Foundation for Ileitis and Colitis.     

Diagnosis of autoimmune pancreatitis using endoscopic ultrasonography

Background  Revised clinical criteria for autoimmune pancreatitis (AIP) have been proposed by the Research Committee of Intractable Disease of the Pancreas and the Japan Pancreas Society. These criteria require distinguishing AIP from neoplastic lesions. However, this can be difficult, and patients often undergo surgery on the basis of suspected pancreatic cancer (PC). Methods  AIP was diagnosed in 25 patients at the Aichi Cancer Center Hospital (ACCH) according to the revised AIP criteria. In each patient, endoscopic ultrasonography (EUS) was used to describe the conventional pancreatic parenchymal and ductal features of chronic pancreatitis (Sahai criteria), and other abnormal features, namely, diffuse hypoechoic areas (DHAs), diffuse enlargement (DE), focal hypoechoic areas (FHAs), focal enlargement, bile duct wall thickening (BWT), lymphadenopathy, and peripancreatic hypoechoic margins (PHMs). We compared these features between 25 patients with AIP and 30 patients with pancreatic cancer resected at ACCH. Results  Few conventional EUS features of chronic pancreatitis (CP) were seen in patients with AIP (mean, 2.0 features). Frequencies of DHA, DE, BWT, and PHM were significantly higher in AIP than in PC. DHAs, DE, and FHAs resolved after steroid treatment. Conclusions  Novel EUS features of AIP are useful in distinguishing AIP from PC and for following the effects of steroid therapy.     

Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine

Abstract. Chao C, Klein NP, Velicer CM, Sy LS, Slezak JM, Takhar H, Ackerson B, Cheetham TC, Hansen J, Deosaransingh K, Emery M, Liaw K‐L, Jacobsen SJ (Kaiser Permanente Southern California, Pasadena, CA; Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, CA; Merck Research Laboratories, Upper Gwynedd, PA; South Bay Medical Center, Kaiser Permanente Southern California, Los Angeles, CA; and Kaiser Permanente Southern California, Downey, CA, USA). Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med 2012; 271 : 193–203. Objective. An observational safety study of the quadrivalent human papillomavirus vaccine (HPV4) in women was conducted. This report presents findings from autoimmune surveillance. Design. Subjects were followed for 180 days after each HPV4 dose for new diagnoses of 16 prespecified autoimmune conditions. Setting. Two managed care organizations in California. Subjects. Number of 189 629 women who received ≥1 dose of HPV4 between 08/2006 and 03/2008. Outcome. Potential new‐onset autoimmune condition cases amongst HPV4 recipients were identified by electronic medical records. Medical records of those with ≥12‐month health plan membership prior to vaccination were reviewed by clinicians to confirm the diagnosis and determine the date of disease onset. The incidence of each autoimmune condition was estimated for unvaccinated women at one study site using multiple imputations and compared with that observed in vaccinated women. Incidence rate ratios (IRR) were calculated. Findings were reviewed by an independent Safety Review Committee (SRC). Results. Overall, 1014 potential new‐onset cases were electronically identified; 719 were eligible for case review; 31–40% were confirmed as new onset. Of these, no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition. None of the estimated IRR was significantly elevated except Hashimoto’s disease [IRR = 1.29, 95% confidence interval: 1.08–1.56]. Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions. The SRC and the investigators identified no autoimmune safety concerns in this study. Conclusions. No autoimmune safety signal was found in women vaccinated with HPV4.     

Thyroid dysfunction in primary biliary cirrhosis,primary sclerosing cholangitis and non‐alcoholic fatty liver disease

Background/Aims: Primary biliary cirrhosis (PBC) is frequently associated with autoimmune diseases, including thyroid disease, although it is uncertain that this association is higher than in other liver diseases. Methods: We compared the prevalence and incidence of thyroid dysfunction (TD) in a series of patients with PBC (n=67) with patients with primary sclerosing cholangitis (PSC) (n=79) and non‐alcoholic fatty liver disease (NAFLD) (n=97) seen in a tertiary referral centre who had previously participated in clinical trials. Results: At initial evaluation, prevalence of TD in PBC was 13% compared with 11% in PSC (P=0.71) and 25% in NAFLD (P=0.08). Incidence of TD was 2.9 patients per 100 person‐years in PBC compared with 2.1 patients per 100 person‐years in PSC (P=0.57) and 1.8 patients per 100 person‐years in non‐alcoholic liver disease (P=0.45). Older age, female gender, biochemical abnormalities and concurrent autoimmune disorders were not predictive of the development of TD. Conclusions: TD was unexpectedly as common in patients with PBC as in patients with PSC and NAFLD, yet significantly more common than expected in the general population. Further investigation of thyroid disease in PSC and NAFLD is warranted.     

Management of Evans syndrome

Evans syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA) with a positive direct antiglobulin test (DAT) in the absence of known underlying aetiology. This condition generally runs a chronic course and is characterised by frequent exacerbations and remissions. First-line therapy is usually corticosteroids and/or intravenous immunoglobulin, to which most patients respond; however, relapse is frequent. Options for second-line therapy include immunosuppressive drugs, especially ciclosporin or mycophenolate mofetil; vincristine; danazol or a combination of these agents. More recently a small number of patients have been treated with rituximab, which induces remission in the majority although such responses are often sustained for <12 months and the long-term effects in children are unclear. Splenectomy may also be considered although long-term remissions are less frequent than in uncomplicated ITP. For very severe and refractory cases stem cell transplantation (SCT) offers the only chance of long-term cure. The limited data available suggest that allogeneic SCT may be superior to autologous SCT but both carry risks of severe morbidity and of transplant-related mortality. Cure following reduced-intensity conditioning has now been reported and should be considered for younger patients in the context of controlled clinical trials.     

Recurrent hypoglycemia,a rare case of insulin autoimmune syndrome in a young African American male

Insulin autoimmune syndrome (IAS) is an uncommon cause of spontaneous hypoglycemia from hyperinsulinemia due to autoantibodies against endogenous insulin (Jian-Ping Chu, 2016). These individuals have no prior exposure to exogenous insulin. We report a case of a 35-year-old African American male, who presented to Vaughn Regional Medical Center in Selma, AL, after he was found to have seizures from hypoglycemia, with a blood sugar of 63 on presentation. He was never diagnosed with diabetes in the past, nor did he have a history of seizure disorder. He continued to be hypoglycemic during the initial period of his hospital stay. His fasting insulin level was 27 mIU/l (normal is less than 25, with presence of insulin autoantibodies (IAA), and a negative workup otherwise. This led us to include IAS as one of our differentials for his hypoglycemia.     

Autoimmune serology in liver disease: methodology and interpretation

Abstract   Accurate measurement of levels of autoantibodies in serum is critical for the diagnosis of autoimmune hepatitis. The major reactivities include anti-nuclear antibody (ANA), smooth muscle antibody (SMA), antibody to liver kidney microsomes type-1 (anti-LKM1); other relevant reactivities include antibodies to liver cytosol 1 (anti-LC1), soluble liver antigen (anti-SLA), and neutrophil cytoplasmic antigens (ANCA). In addition to the classical indirect immunofluorescence technique, automatic assays based on recombinant antigens are now available, which allow detection of antibodies not visible on immunofluorescence, like anti-SLA, and assist in the interpretation of at times problematic immunofluorescence patterns, like anti-LKM1 or anti-LC1.     

Idiopathic autoimmune thrombocytopenia and neutropenia in siblings

Familial incidences of autoimmune disorders involving red cells, white cells and platelets are rare. Two cases of autoimmune neutropenia and thrombocytopenia occurring in two adult brothers are reported here. One patient showed prompt recovery of white cells with steroids but needed IV IgG+ splenectomy for durable platelet recovery. His brother required splenectomy for durable recovery of white cells and platelets as he showed transient recovery with steroids and IV IgG.     

Autoimmune hepatitis in a demographically isolated area of Australia

Background: Previous studies describing autoimmune hepatitis (AIH) come from liver transplant centres in which a skewed distribution of cases may give a misleading picture of the incidence of AIH and its natural history. This series describes AIH in a stable and demographically discrete population of patients in the Australian Capital Territory (ACT) and the surrounding region. Methods: In 42 patients with type 1 AIH (point prevalence 8 per 100 000 population), clinical, laboratory and histological features at presentation, response to initial therapy, details of maintenance therapy and outcome were recorded. Results: Consistent with other publications, the male‐to‐female ratio was 1:3, mean age at presentation was 53 years and 24% had cirrhosis at diagnosis. Most patients (86%) responded to initial therapy and 67% went into long‐term remission. One patient died from liver failure and none required liver transplantation. Azathioprine was included in the treatment regimen in 74% of cases with doses generally <2 mg/kg. Azathioprine dose greater than or equal to 2 mg/kg was associated with better clinical outcome, but this did not reach statistical significance. A higher proportion of female patients had cirrhosis at presentation (9/10 vs 1/10; P= 0.24). Conclusion: In this Australian community‐based study, type 1 AIH was primarily a disease of later life, responded to conventional immunosuppressive therapy and generally has a good prognosis. Further study of the use of azathioprine is warranted to determine the optimal dose.