BACKGROUND: The role of gastrointestinal microbiome in health and disease is increasingly appreciated. A significant amount of evidence clearly points to a dysbiosis manifest in inflammatory bowel disease (IBD) when compared to healthy controls. Less understood is the microbiome profile in autoimmune liver disease (AILD). Both adult and paediatric data indicate a distinct microbial signature in patients with IBD and co-existent primary sclerosing cholangitis (PSC), which is unique and different compared to the microbial signature that exists in patients with IBD alone. However, there is limited information on the microbiome make-up of patients with parenchymal liver disease, with or without IBD.
METHODS: The present study sought to compare the microbiome of children with IBD, to those with IBD-AILD, those with AILD alone and those of healthy controls.
RESULTS: Results from this work indicate that children with AILD have a microbiome profile that mirrors healthy controls.
CONCLUSIONS: Those with IBD-AILD and IBD have similar microbiome profiles which are distinct from AILD alone and healthy controls. This suggests that the dysbiosis in these groups is primarily due to IBD rather than AILD.

UNASSIGNED: Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare malignant tumor. The incidence rate of PSCCT is less than 1%. However, the diagnosis and treatment of PSCCT are limited. Surgical resection is considered to be one of the few effective intervention methods. In this article, we reported a case of taking tyrosine kinase inhibitors (TKIs) combined with immune checkpoint inhibitors (ICIs) for PSCCT.
UNASSIGNED: An 80-year-old male was admitted to our hospital with dyspnea, cough, wheezing, and hoarseness for a giant thyroid mass. He underwent bronchoscopy and tracheal stent implantation to alleviate the respiratory obstruction. Then he accepted right partial thyroid and right lymph node biopsy. Postoperative pathology revealed squamous cell carcinoma. Subsequently, he underwent an endoscopy to exclude upper gastrointestinal squamous cell carcinoma. Finally, he was diagnosed with PSCCT. The patient was tentatively treated with a combination of Anlotinib and Sintilimab. After two courses, the tumor volume significantly reduced in MRI images and shrank further after five courses of combined treatment. Unfortunately, the patient died of fulminant liver failure and autoimmune liver disease after 5-month-treatment.
UNASSIGNED: TKIs combined with ICIs may be an effective and novel way for PSCCT treatment, but immune-related complications, especially liver damage, should be cared.

UNASSIGNED: The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti-B cell activating factor, belimumab. The first three patients had concomitant Sjögren\'s disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren\'s disease.
UNASSIGNED: To retrospectively investigate treatment response in six patients with AIH or PBC with or without concomitant Sjögren\'s disease treated with the anti-BAFF therapy belimumab at the University Hospital in Bern, Switzerland.
UNASSIGNED: In all three patients with AIH, belimumab improved disease control and helped by-pass or reduce problematic side effects from corticosteroids and calcineurin inhibitors. In PBC patients (n = 3), there was no clear improvement of liver function tests, despite reduction or normalization of IgM. All patients with concomitant Sjögren\'s disease (n = 3) had an improvement of sicca symptoms and two out of three patients experienced an initially marked reduction in fatigue, which lessened over time.
UNASSIGNED: Belimumab may be a promising treatment option for patients with AIH and further investigations are needed. In PBC however, response was not convincing. The effects on sicca symptoms and fatigue were encouraging.

Acute hepatitis presenting with blood eosinophilia are scarcely reported. Different clinical courses of autoimmune hepatitis (AIH) have been associated with acute hepatitis with eosinophilia, however it is still unclear if the latter is a common manifestation of different autoimmune diseases, part of a similar spectrum of eosinophil-associated liver injury or even a trigger to AIH. We report a case of a 32 years old woman who presented with subacute hepatitis, peripheral eosinophilia, hypergammaglobulinemia and liver biopsy suggestive of AIH. The role of eosinophils in autoimmune liver diseases deserves further studies in order to clarify its physiopathology aspects.

Inflammatory rheumatic diseases (IRD) and autoimmune liver diseases (AILD) share many similarities regarding epidemiology, genetics, immunology and therapeutic regimens, so it is not surprising that approximately 20% of patients with AILD are diagnosed with an IRD as well. Clinical features and biochemical hallmarks of IRD and AILD often intertwine and cross diagnostic criteria. Therefore, the real distinction of underlying disorders in a patient with these comorbidities may be challenging. The present report is the first report of simultaneously developed juvenile dermatomyositis (JDM) and autoimmune sclerosing cholangitis (ASC) with both entities fulfilling the latest guidelines for a definite diagnosis. Both of these diagnoses are difficult to definitely establish since ASC has a similar serologic profile as autoimmune hepatitis and liver histological analysis is frequently non-specific, whereas clinically amyopathic JDM diagnosis depends mostly on classical dermatological symptoms, while the rest of the diagnostic criteria, including the necessity for skin or muscle biopsy and the presence of myositis specific antibodies, are still not uniformed. In spite of these challenges, our patient clearly met European League Against Rheumatism/American College of Rheumatology classification criteria for CAJDM and The European Society for Pediatric Gastroenterology, Hepatology and Nutrition diagnostic criteria for ASC. Since elevated serum transaminases, the presence of serum antinuclear antibodies and hypergammaglobulinemia could be explained as a part of both JDM and ASC, the underlying pathophysiology remains debatable. Intriguingly, JDM and ASC share genetic predisposition including human leukocyte antigen allele DRB1*0301 and tumor necrosis factor α 308A allele. Furthermore, both humoral and cellular components of the adaptive immune system contribute to the pathogenesis of JDM and ASC. Moreover, recent findings indicate that the loss of the CD28 expression on T-cells plays a significant role in their pathogenesis along with the Th17 immune pathway. Despite these common features that suggest shared autoimmunity, AILD and autoimmune myositis are traditionally studied and managed independently. The lack of therapies that target the underlying cause results in a high rate of adverse events due to unspecific immunosuppressive therapy. Shared autoimmunity is an ideal area to develop new, targeted immunotherapy that would hopefully be beneficial for more than one disease.

Primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome is frequently associated with extrahepatic autoimmune disorders. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disease that is characterized by complement-mediated hemolysis due to erythrocyte membrane defects. However, autoimmune liver disease was not previously reported to be associated with PNH. A 37-year-old female patient was referred to our hospital with elevated liver enzymes and hematuria. On the basis of the symptoms and results of laboratory tests, radiographic studies, and pathologic results, she was diagnosed with PBC-AIH overlap syndrome and PNH. She was treated with a combination of ursodeoxycholic acid and prednisolone. The patient was symptom-free, with laboratory findings within near-normal range. The patient had recovered well at the 24-month follow-up evaluation. While we acknowledge that this was a single case, these findings expand our knowledge of immunological diseases that are associated with PNH and suggest an immune-mediated pathogenic pathway between PNH and PBC-AIH overlap syndrome. The combination of ursodeoxycholic acid and prednisolone can achieve therapeutic success. Routine follow-up of these patients is necessary to document disease progression.

UNASSIGNED: In children overlap of autoimmune hepatitis (AIH) and primary sclerosing cholangitis is labelled as autoimmune sclerosing cholangitis (ASC). The only prospective pediatric study showed a high prevalence of ASC by using endoscopic retrograde cholangiopancreatography. Aims of our study were to find the prevalence of ASC by using magnetic resonance cholangiography (MRC) in AIH and in non-AIH cirrhosis and to compare clinical presentation and outcome of AIH and ASC.
UNASSIGNED: Prospectively we did MRC in 38 children with AIH (cases) and 19 disease controls (Wilson disease). Multiple biliary strictures with proximal dilatation on MRC were taken as definitive changes of ASC. Detail clinical, laboratory parameters, liver histopathology and treatment outcome were recorded.
UNASSIGNED: The median age of cases was 11.5 (3-18) years, 22 (57.9%) were girls and 28 (73.7%) were diagnosed as type 1 AIH. MRC was done in 11 children (28.9%) at the time of diagnosis and in 27 (71.1%) after a median follow-up of 2.5 (0.3-10) years. Abnormal MRC changes were seen in 14/38 (36.8%) of AIH and 8/19 (42.1%) of controls. However, definite changes of ASC were present in four (10.5%) children in AIH and none in controls. None of the clinical, laboratory, histological parameters and treatment response were significantly different between ASC and AIH groups.
UNASSIGNED: The prevalence of ASC in children with AIH was just 10.5%. We suggest MRC in select group with cholestatic features, inflammatory bowel disease and in those who showed poor response to immunosuppression instead of all children with AIH.

Introduction and aim: The aim of this study was to investigate the outcome of a paediatric onset of inflammatory bowel disease (IBD) in a cohort of subjects with primary sclerosing cholangitis (PSC) and in a matched-age population-based control group without PSC. Methods: We identified 28 IBD-PSC cases (median age at IBD diagnosis 12.5 years, 25-75th: 10-16 years) and selected three IBD controls for each case matched for age and year of IBD diagnosis. All data regarding the gastrointestinal tract and liver were collected at diagnosis and at last follow-up (median 15 years). Results: At diagnosis the prevalence of pancolitis was similar between the groups (78% and 79%, respectively p = -.30), but histologic inflammation was milder in IBD-PSC (61% vs 30%, p = .06). At last follow-up (median age 29 years) pancolitis was less frequent (6% and 33%, respectively p = .04) and the remission higher (76% and 47%, respectively p = .08) in IBD-PSC patients than in IBD patients. Panproctolectomy (32% in IBD-PSC and 34% in IBD, p = 1.0) and the rate of pouchitis (62% and 70%, respectively p = .8) were similar. Conclusions: The outcome of paediatric onset IBD in patients with PSC in adulthood seems to be comparable to those with IBD only.

Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease (CLD). It presents with varied clinical features from acute hepatitis to CLDs like chronic viral hepatitis and alcoholic liver disease, making it difficult to diagnose in the absence of a high index of suspicion and adequate laboratory support. Autoantibody-mediated hepatocyte injury is the major feature of AIH. We present a 44 year old woman with recurrent jaundice, ascites, splenomegaly, coagulopathy, negative chronic viral hepatitis screening, elevated IgG and positive anti-smooth muscle antibody. The patient responded well to immunosuppressive therapy. This report brings to the fore the need for physicians to maintain a high index of suspicion and thoroughly evaluate all CLD cases of seemingly \'unknown\' etiology for AIH in order to prevent progression to end-stageliver- disease, since the disease is highly amenable to immunosuppressive therapy.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are both autoimmune cholestatic liver disease and the association of these two conditions in the same patient is very rare. We report the case of a female patient presenting with a cholestatic liver disease and a panel of autoantibodies specific for PBC, including antibodies to mitochondrial E2-pyruvate dehydrogenase, gp-210 and Sp-100. Beside these findings, the liver biopsy revealed concentric fibrosis of small biliary ducts and the magnetic resonance cholangiography presented no abnormal findings. Diagnosis of small duct PSC/PBC overlapping was done. No description of this association was found in the literature. Clinical and serological features of this unusual finding are discussed.