A Case of Autoimmune Pancreatitis Manifested by a Pseudocyst and IgG4-Associated Cholangitis

Autoimmune pancreatitis (AIP) is a benign disorder and a unique form of chronic pancreatitis with several characteristic features. A cystic formation that mimics a pseudocyst is a rare finding. There have been a few reports of AIP complicated by pancreatic cysts. We present a case of AIP with multiple pseudocysts and obstructive jaundice caused by IgG4-associated cholangitis. We initially missed the diagnosis due to the pseudocyst. Based on the computed tomography images, laboratory findings and the therapeutic response to steroids, the case was diagnosed as AIP with pseudocysts and associated cholangiopathy.     

Autoimmune paediatric liver disease

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis（AIH）,autoimmune sclerosing cholangitis（ASC）,and de novo AIH after liver transplantation.AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody（SMA/ANA,type 1） or liver kidney microsomal antibody（LKM1,type 2）.There is a female predominance in both.LKM1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity,presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both groups.The most common type of paediatric sclerosing cholangitis is ASC.The clinical,biochemical,immunological,and histological presentation of ASC is often indistinguishable from that of AIH type 1.In both,there are high IgG,non-organ specific autoantibodies,and interface hepatitis.Diagnosis is made by cholangiography.Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters,and decreased inflammatory activity on follow up liver biopsies.However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies,hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH postliver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to t     

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.     

Primary Sclerosing Cholangitis and Autoimmune Hepatitis Overlapping Syndrome Complicated by Ulcerative Colitis

The case of a 28-year-old man who had primary sclerosing cholangitis and autoimmune hepatitis overlapping syndrome (PSC-AIH OS) complicated by ulcerative colitis (UC) is reported. First, he was diagnosed with PSC complicated by UC and initially treated with ursodeoxycholic acid and mesalazine. Twenty-four months later, liver damage reappeared, and we performed a liver biopsy, which showed the features of AIH. We eventually diagnosed him with PSC-AIH OS complicated by UC. If liver damage worsens in PSC patients, PSC-AIH OS should be considered. The optimum management approach for PSC-AIH OS should be established.     

Autoimmune hepatitis in children—Impact of cirrhosis at presentation on natural history and long-term outcome

Little is known regarding the natural history of autoimmune hepatitis in children. The aims of this longitudinal cohort study were to determine the long-term prognosis of children with autoimmune hepatitis and to determine the effect of cirrhosis at presentation on survival.     

Classification and Diagnostic Criteria for IgG4-Related Sclerosing Cholangitis

IgG4-related sclerosing cholangitis (IgG4-SC) can be classified into four types based on cholangiographic findings and regions of biliary stricture. This cholangiographic classification is useful to differentiate IgG4-SC from mimickers including cholangiocarcinoma, primary sclerosing cholangitis, and pancreatic cancer. Autoimmune pancreatitis (AIP) is a valuable clue for the diagnosis of IgG4-SC because the two are frequently found in association with each other. Two sets of diagnostic criteria for IgG4-SC have been proposed. In Japan, the clinical diagnostic criteria 2020 were recently developed. These clinical diagnostic criteria include narrowing of the intrahepatic and/or extrahepatic bile duct, thickening of the bile duct wall, serological findings, pathological findings, other organ involvement, and effectiveness of steroid therapy. When these criteria are applied, IgG4-SC is initially classified as associated or not associated with AIP, and cholangiographic classification is used for differential diagnosis. In most instances, IgG4-SC can be diagnosed on the basis of clinical diagnostic criteria. However, it is challenging to diagnose isolated IgG4-SC or IgG4-SC not associated with AIP. Here, we review the classification and diagnostic criteria for IgG4-SC, specifically focusing on the clinical diagnostic criteria 2020 and a large IgG4-SC case series from a nationwide survey in Japan.     

Highly Increased Levels of Inter-α-inhibitor Heavy Chain 4 (ITIH4) in Autoimmune Cholestatic Liver Diseases

Background and AimsThere is an unmet need for new biomarkers to improve diagnostics and prognostics in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Inter-α-inhibitor heavy chain 4 (ITIH4) is an abundant, liver-produced protein, and its synthesis may be altered in liver diseases. We investigated whether ITIH4 plasma concentrations were affected in PBC and PSC patients.MethodsWe developed an immunoassay specific for ITIH4 and determined ITIH4 plasma concentrations in 66 PBC, 126 PSC, 92 autoimmune hepatitis (AIH), 67 chronic hepatitis C (CHC), 33 alcoholic hepatitis (AH) patients and 138 healthy controls (HCs). Hepatic ITIH4 expression was investigated by immunohistochemistry in PBC.ResultsThe mean plasma concentration of ITIH4 was almost doubled in PBC [409 µg/mL (95% CI: 388–431)] and 35% higher in PSC [308 µg/mL, (95% CI: 296–319)] compared with HCs [226 µg/mL (95% CI: 221–231); p<0.001]. In PBC patients, ITIH4 correlated with IgM (rho=0.49, p<0.001). Responders to ursodeoxycholic acid treatment (UDCA) had lower levels of ITIH4 than incomplete responders [395 µg/mL (95% CI: 364–425)] vs. 460 µg/mL (95% CI: 421–498); p=0.02]. Four weeks of UDCA treatment had no effect (p=0.19). Increased ITIH4 immunohistochemical staining was seen in a liver biopsy from a PBC patient. ITIH4 levels in AIH [224 µg/mL (95% CI: 208–241)] and HCs were similar (p=0.8). ITIH4 levels were lower in AH [199 µg/mL (95% CI: 175–223)] and CHC [202 µg/mL (192–212)] patients than in HCs (p<0.05).ConclusionsThe plasma concentration of ITIH4 was highly elevated in patients with PBC and PSC, suggesting that ITIH4 should be further investigated as a biomarker in cholestatic liver disease.     

自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征：巴黎标准诊断中国患者灵敏度低

目的 评估巴黎标准诊断中国自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征的正确性。方法 回顾性分析按巴黎标准诊断为自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征患者24例和原发性胆汁性肝硬化患者16例的临床资料,对14例部分原发性胆汁性胆管炎患者行肝穿刺检查。结果 16例自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征患者血清TBIL、ALT、GGT和IgG水平分别为（45.3±48.3）μmol/L、（236.8±71.8） U/L、（305.3±258.5） U/L和（25.3±9.9） g/l,与PBC患者【（53.4±57.8）μmol/L、（77.5±71.7） U/L、（389.2±324.3） U/L和（13.9±6.0） g/l,P<0.05】比,差异显著;两组血清ANA、AMA和AMA-M2阳性率无显著性差异（P>0.05）,仅AIH/PBC OS患者血清SMA阳性7例（43.8%）,与PBC组1例（4.2%）比较,差异有统计学意义（P<0.05）;经肝组织学检查,5例原本诊断为PBC患者修正诊断为AIH/PBC OS,他们血清ALT水平分别为40.0U/L、82.8U/L、94.1 U/L、162.1 U/L和117.2 U/L,都远远低于5倍正常值上限。结论 采取巴黎标准诊断中国自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征患者往往因为血清指标水平低而漏诊,及时行肝穿刺检查还是很必要的。     

Autoimmune liver serology：Current diagnostic and clinical challenges

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases（AiLD）,namely autoimmune hepatitis types 1 and 2（AIH-1 and 2）,primary biliary cirrhosis（PBC）,and the sclerosing cholangitis variants in adults and children.AIH-1 is specified by anti-nuclear antibody（ANA） and smooth muscle antibody（SMA）.AIH-2 is specified by antibody to liver kidney microsomal antigen type-1（anti-LKM1） and anti-liver cytosol type 1（anti-LC1）.SMA,ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation.PBC is specified by antimitochondrial antibodies（AMA） reacting with enzymes of the 2-oxo-acid dehydrogenase complexes（chiefly pyruvate dehydrogenase complex E2 subunit） and disease-specific ANA mainly react-ing with nuclear pore gp210 and nuclear body sp100.Sclerosing cholangitis presents as at least two variants,first the classical primary sclerosing cholangitis（PSC） mostly affecting adult men wherein the only（and non-specific） reactivity is an atypical perinuclear antineutro-phil cytoplasmic antibody（p-ANCA）,also termed perinuclear anti-neutrophil nuclear antibodies（p-ANNA） and second the childhood disease called autoimmune sclerosing cholangitis（ASC） with serological features resembling those of type 1 AIH.Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens,and automatedtechnologies such as ELISAs and bead assays,become available to complement（or even compete with） traditional immunofluorescence procedures.We survey for the first time global trends in quality assurance impacting as it does on（1） manufacturers/purveyors of kits and reagents,（2） diagnostic service laboratories that fulfill clinicians＇ requirements,and（3） the end-user,the physician providing patient care,who must properly interpret test results in the overall clinical context.