Journal articles: 'Primary biliary sclerosis' – Grafiati (2024)

Abstract:

Systemic sclerosis (SSc) is a complex autoimmune disease that may lead to skin and internal organ fibrosis. Based on skin involvement, two subsets of the disease are recognized (limited cutaneous SSc and diffuse cutaneous SSc). The new 2013 American College of Rheumatology/European League against Rheumatism classification criteria allow to identify SSc patients at the early stage of the disease that allows new research avenues. The aetiology of the disease is still unknown, but it has an important autoimmune basis and its association with other autoimmune diseases has been reproducibly reported. Among them, primary biliary cholangitis is considered the most common liver disease in SSc. The aim of this review is to provide an overview on recent findings about SSc associated to primary biliary cholangitis. Although the aetiology of the two diseases is still unknown, data suggest that these two disorders share the expression of fibrogenic cytokines, involved both in generation and function of T lymphocytes subpopulation (Th17 cells) and regulatory T lymphocytes. In addition, the relationships between SSc and primary biliary cholangitis may be closer as suggested by the presence of primary biliary cholangitis–specific antibodies in SSc patients and vice versa. Recent findings confirm a prevalence of overt primary biliary cholangitis in about 2% of SSc population, in particular in patients with limited cutaneous SSc and positive anticentromere antibodies. The prevalence increases if also patients with only primary biliary cholangitis–specific antibodies are considered. Data regarding SSc prevalence in primary biliary cholangitis patients have also been recently clarified. Altogether, stimulating results are moving the field forward regarding the relationships of these two autoimmune and fibrotic disorders that may belong to an overlapping entity.

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Patients with primary biliary cirrhosis (PBC) often have concurrent limited systemic sclerosis (SSc). Conversely, up to one-fourth of SSc patients are positive for PBC-specific antimitochondrial antibodies (AMA). The mechanisms responsible for the co-occurrence of these diseases are largely unknown. Genetic, epigenetic, environmental, and infectious factors appear to be important for the pathogenesis of the disease, but the hierarchy of events are not well defined. Patients with SSc and PBC have an increased morbidity and mortality compared with the general population, but whether the presence of both diseases in an affected individual worsens the prognosis and/or outcome of either disease is not clear. Some case reports suggested that the presence of SSc in PBC patents is associated with a more favorable prognosis of the liver disease, whereas others report an increased mortality in patients with PBC and SSc compared to patients with PBC alone. This paper discusses the features of patients with PBC-associated SSc. Our aims are to clarify some of the pathogenetic, diagnostic, and clinical challenges that are currently faced in the routine management of these patients. We also intend to provide some practical hints for practitioners that will assist in the early identification of patients with PBC-associated SSc.

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Background:Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and skin as well as organ fibrosis. The lungs, skin, and gastrointestinal care frequently affected. Primary biliary cholangitis (PBC) is an autoimmune disease of the liver associated with potential progression to liver fibrosis. More recently, these two disorders have been described as an overlapping entity, especially in patients with limited, anti-centromere (CENP-B) positive SSc (1). Here, we report the first results of a pilot study of shear wave elastography (SWE) in patients with SSc and SSc/PBC compared to PBC patients.Objectives:To assess liver stiffness in patients with SSc, SSC/PBC overlap, and PBC with shear wave elastography.Methods:We analyzed a sample of 10 SSc to 11 PBC patients. In all patients, a baseline US examination of the liver and liver stiffness measurement by 2D SWE were performed using a GE logiq E10 ultrasound machine. Normal values for SWE in healthy people have recently been published (2). Liver stiffness measurement was performed according to the recommendations of the manufacturer and the recommendations of the current “EFSUMB Guideline and Recommendation on the Clinical Use of Liver Elastography” (3). In addition, age, body mass index (BMI), and antibody profiles were assessed.Results:Of 8 SSc patients without PBC, 6 were anti-CENPB pos., 1 had Scl70, and 1 Pm/Scl antibody. Median age was 59.5 (47-71). Median BMI was 23.1 (19.6-25). 1 patient had SSc/PBC overlap, 1 had hepatic steatosis. 1 was positive for CENP-B/AMA-M2 antibodies, the other patient was Scl70 positive. Median age of these 2 patients was 55.5 (55-56), BMI was 23.86 (20.9-26.8). 11 patients with PBC were positive for AMA-M2 antibodies, median age was 58 (41-78) years, BMI was 27.8 (15.8-50.3). The differences were not statistically different. Liver stiffness is expressed in kPa. Measurements had an interquartile range/median ratio <30%, indicating sufficient quality of the measurement. Liver stiffness was higher in patients with SSc/PBC overlap/hepatic steatosis (9.4±0.18, **p=0.0133) and PBC alone (7.359±2.51, **p=0.0163) compared to SSc alone (4.526±0.89 kPa). The results indicate that PBC is the main driver of liver stiffness in patients with SSc, and SSc alone may not necessarily lead to an increased liver stiffness (figure 1).Figure 1.Conclusion:Our results indicate that SWE is a useful tool in for the non-invasive assessment of liver stiffness in SSc and SSc/PBC overlap. We will further increase the sample size, especially of patients with SSc/PBC overlap. Of note, other liver diseases, such as hepatic steatosis, have to be kept in mind when SWE is performed as they may contribute to liver stiffness.References:[1]Lepri G, Randone SB, Cerinic MM, Allanore Y. Systemic sclerosis and primary biliary cholangitis: An overlapping entity?: Journal of Scleroderma and Related Disorders [Internet]. 2018 Oct 25 [cited 2020 Jun 17]; Available from: https://journals.sagepub.com/doi/10.1177/2397198318802763[2]Petzold G, Hofer J, Ellenrieder V, Neesse A, Kunsch S. Liver Stiffness Measured by 2-Dimensional Shear Wave Elastography: Prospective Evaluation of Healthy Volunteers and Patients With Liver Cirrhosis. J Ultrasound Med. 2019 Jul;38(7):1769–77.[3]Dietrich CF, Bamber J, Berzigotti A, Bota S, Cantisani V, Castera L, et al. EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version). Ultraschall Med. 2017 Aug;38(4):e48.Disclosure of Interests:Viktor Korendovych: None declared, Jan-Gerd Rademacher: None declared, Golo Petzold: None declared, PETER KORSTEN Speakers bureau: Abbvie, Pfizer, Boehringer-Ingelheim, Novartis, Chuigai, Sanofi, GSK, all unrelated., Consultant of: Abbvie, Pfizer, Boehringer-Ingelheim, Novartis, Chuigai, Sanofi, GSK, Gilead, Lilly, all unrelated., Grant/research support from: GSK, unrelated to this study.

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Background & Aim. Primary biliary cirrhosis (PBC) is frequently associated with other autoimmune diseases, including systemic sclerosis (SSc). In the last years many efforts have been dedicated to the research of widely accepted criteria for the early diagnosis of SSc. Since studies on the prevalence of early SSc in PBC patients are lacking, our aim was to investigate its hitherto unknown prevalence in a large cohort of PBC patients.Methods. We studied 80 PBC patients and 72 patients with other chronic liver diseases. Diagnostic workup included research into signs of connective tissue disease, determination of autoantibody profile, and examination of capillary abnormalities through nailfold videocapillaroscopy.Results. Ten PBC patients (12.5%) satisfied diagnostic criteria for early SSc and 5 (6.3%) had definite SSc. None of the patients in the control group were diagnosed either with early or definite SSc. No differences were observed in terms of aminotransferases, alkaline phosphatase, and liver function tests between PBC patients with and without associated SSc. Conclusions. Early SSc is significantly frequent in PBC patients. The detection of early SSc in PBC patients may lead to a prompt treatment of its complications, preventing inabilities and preserving the chance of liver transplantation.Abbreviations: ACA: anti-centromere antibodies; ACR: American College of Rheumatology; AMA: antimitochondrial antibodies; ANA: anti-nuclear antibodies; CENP-B: Centromere-protein B; ENA: extractable nuclear antigens; IIF: indirect immunofluorescence; NCM: nailfold capillary microscopy; PBC: Primary biliary cirrhosis; RP: Raynaud's phenomenon; SSc: Systemic sclerosis; UDCA: ursodeoxycholic acid.

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Objective.To analyze the prevalence, associations, and fine specificity of autoantibodies to primary biliary cirrhosis (PBC)-associated antigens (MIT3, Sp100, and gp210) in a cohort of Italian patients with systemic sclerosis (SSc).Methods.Sera samples from 201 patients with SSc were tested for antibodies to MIT3, gp210, and Sp100 by ELISA (the PBC screen). Anti-MIT3-positive sera were studied for IgG or IgA isotypes. All sera were analyzed by indirect immunofluorescence on HEp-2 cells and on rodent kidney/stomach/liver tissue sections in order to detect antinuclear and antimitochondrial antibodies (AMA). SSc was selected by American College of Rheumatology criteria and classified based on LeRoy’s criteria.Results.Forty-three (21.4%) sera samples were positive for PBC screen antibodies. Anti-MIT3 antibodies were detected in 36 samples, anti-Sp100 in 5, and anti-gp210 in 1 sample. The other 3 PBC screen-positive samples showed no specificity for the single antigens. PBC screen-positive patients more frequently showed a limited cutaneous SSc subtype (p = 0.04), anticentromere antibodies (ACA; p = 0.0013), elevated alkaline phosphatase (ALP) (p < 0.0001), PBC (p = 0.002), and AMA (p = 0.008). Teleangiectasia and calcinosis were less frequent in this group of patients. IgG+IgA anti-MIT3-positive patients had higher prevalence of AMA (p = 0.0035), diagnosis of PBC (p = 0.014), and increased ALP (p = 0.039), all considered biochemical markers of severe liver disease.Conclusion.PBC screen antibodies were detected in 20% of patients with SSc, strongly associated with ACA. ACA+/PBC screen+ patients had higher risk of developing PBC or elevation of ALP.

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Objective.Systemic sclerosis (SSc) is a well-established disease associated with primary biliary cholangitis (PBC). However, the original 1980 American College of Rheumatology (ACR) criteria have poor sensitivity, especially for the detection of earlier SSc in previous studies. The objective was to evaluate the prevalence of SSc in patients with PBC using more sensitive 2001 LeRoy and Medsger criteria and the 2013 ACR/European League Against Rheumatism (EULAR) classification criteria. The secondary objective was to evaluate the frequency of individual clinical features.Methods.One hundred consecutive patients with PBC without previously diagnosed SSc were recruited between 2005 and 2007 from a tertiary care gastroenterology clinic. All patients underwent a complete clinical examination, determination of SSc-specific antibodies, and a nailfold capillary microscopy. Fulfillment of the 3 different criteria sets was analyzed, along with individual disease features.Results.Of 100 patients with PBC, 1% met the ACR 1980 criteria, 22% met the 2001 LeRoy and Medsger criteria for early SSc, and 17% the 2013 ACR/EULAR criteria. Raynaud phenomenon, SSc-related antibodies, and SSc capillaroscopic patterns were the most prevalent findings, with the highest sensitivities to help guide future screening.Conclusion.Our data show a high prevalence of SSc in patients with PBC with probable underestimation by previous studies using the original ACR criteria. Comorbid SSc should be actively searched for based on newly described criteria to improve detection and increase benefits of earlier treatment.

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Background:Anti-centromere antibodies (ACA) are detected in the serum of patients with various autoimmune diseases including Sjögren’s syndrome (SjS), systemic sclerosis (SSc) and primary biliary cholangitis (PBC). ACA positivity is correlated with clinical manifestations such as Raynaud’s phenomenon and sclerodactyly and these features are commonly seen across diseases. Although CENPB is thought to be the major antigen against ACA, autoimmune features of other centromere proteins have not been fully evaluated.Objectives:The aim of this study is to elucidate centromere autoantigens comprehensively and clarify their association with pathogenesis of SjS, SSc and PBC.Methods:A centromere protein library was created by cloning 6 single proteins and 10 complexes consisting of 35 proteins belonging to human centromere region. The centromere antigens were immobilized on beads and incubated in the serum of patients with SjS (n = 86), SSc (n = 35), PBC (n = 10), patients with two or more diseases above (n = 44), and healthy volunteers (n = 68). Autoantibodies to each centromere protein were analyzed by flow cytometry.Results:Patients had a wide variety of antibodies against most of centromere antigens including 4 newly identified autoantigens. The hierarchical clustering of each antigen distinguished 2 antigen clusters. The reactivity of autoantibodies against a centromere protein of one cluster was mutually correlated regardless of disease types, indicating that these proteins/protein complexes might be the target of ACA. In addition, our method enabled us to detect sera reacted against multiple centromere antigens in some of the ACA-negative patients with existing methods.Conclusion:We identified 4 novel centromere autoantigens and our data suggested that the main target of ACA was the protein complex rather than a single specific antigen in SjS, SSc and PBC patients. Using the combination of centromere proteins may be useful to detect ACA with higher sensitivity.References:[1]Fritzler MJ, Rattner JB, Luft LM, Edworthy SM, Casiano CA, Peebles C, Mahler M. Historical perspectives on the discovery and elucidation of autoantibodies to centromere proteins (CENP) and the emerging importance of antibodies to CENP-F. Autoimmun Rev. 2011;10:194-200.Disclosure of Interests:Nobuhiko Kajio: None declared, Masaru Takesh*ta: None declared, Katsuya Suzuki: None declared, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd.

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A 57-year-old woman with rheumatoid arthritis (RA) and limited systemic sclerosis (lSSc) was suspected to have lymphadenopathy and primary biliary cirrhosis (PBC). Lymph node biopsy showed reactive follicular lymphadenopathy with intrafollicular plasmacyte infiltration that was interleukin-6 positive by immunohistostaining. Because of gradually worsening arthritis, tocilizumab was administered and arthritis improved markedly. Interestingly, lymphadenopathy and PBC improved simultaneously. This suggested that interleukin-6 might play an important role in reactive lymphadenopathy and PBC associated with RA/lSSc.

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AbstractManagement of malignant bile duct obstruction is both a clinically important and technically challenging aspect of caring for patients with advanced malignancy. Bile duct obstruction can be caused by extrinsic compression, intrinsic tumor/stone/debris, or by biliary ischemia, inflammation, and sclerosis. Common indications for biliary intervention include lowering the serum bilirubin level for chemotherapy, ameliorating pruritus, treating cholangitis or bile leak, and providing access for bile duct biopsy or other adjuvant therapies. In some institutions, biliary drainage may also be considered prior to hepatic or pancreatic resection. Prior to undertaking biliary intervention, it is essential to have high-quality cross-sectional imaging to determine the level of obstruction, the presence of filling defects or atrophy, and status of the portal vein. High bile duct obstruction, which we consider to be obstruction above, at, or just below the confluence (Bismuth classifications IV, III, II, and some I), is optimally managed percutaneously rather than endoscopically because interventional radiologists can target specific ducts for drainage and can typically avoid introducing enteric contents into isolated undrained bile ducts. Options for biliary drainage include external or internal/external catheters and stents. In the setting of high obstruction, placement of a catheter or stent above the ampulla, preserving the function of the sphincter of Oddi, may lower the risk of future cholangitis by preventing enteric contamination of the biliary tree. Placement of a primary suprapapillary stent without a catheter, when possible, is the procedure most likely to keep the biliary tree sterile.

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Background and Objectives: Laboratory liver abnormalities can be observed in patients affected with polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA), especially with a cholestatic pattern. The first objective of our review article is to discuss the potential link between antimitochondrial antibodies (AMA) and/or primary biliary cholangitis (PBC) and PMR/GCA, according to the evidences of literature. The second objective is to discuss the association of PMR/GCA with the other rheumatic diseases having PBC as a common manifestation. Materials and Methods: A literature search was performed on PubMed and Medline (OVID interface) using these terms: polymyalgia rheumatica, giant cell arteritis, antimitochondrial antibodies, primary biliary cholangitis, primary Sjogren’s syndrome, systemic sclerosis, and systemic lupus erythematosus. The search was restricted to all studies and case reports published in any language. Reviews, conference abstracts, comments, and non-original articles were excluded; however, each review’s reference list was scanned for additional publications meeting this study’s aim. When papers reported data partially presented in previous articles, we referred to the most recent published data. Results and Conclusions: Our literature search highlighted that cases reporting an association between AMA, PBC and PMR/GCA were very uncommon; AMA antigenic specificity had never been detected and biopsy-proven PBC was reported only in one patient with PMR/GCA. Finally, the association of PMR/GCA with autoimmune rheumatic diseases in which PBC is relatively common was anecdotal.

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AbstractBile leaks are rare but potentially devastating iatrogenic or posttraumatic complications. This is being diagnosed more frequently since the advent of laparoscopic cholecystectomy and propensity toward nonsurgical management in select trauma patients. Timely recognition and accurate characterization of a bile leak is crucial for favorable patient outcomes and involves a multimodal imaging approach. Management is driven by the type and extent of the biliary injury and requires multidisciplinary cooperation between interventional radiologists, endoscopists, and hepatobiliary/transplant surgeons. Interventional radiologists have a vital role in both the diagnosis and management of bile leaks. Percutaneous interventional procedures aid in the characterization of a bile leak and in its initial management via drainage of fluid collections. Most bile leaks resolve with decompression of the biliary system which is routinely done via endoscopic retrograde cholangiopancreaticography. Some bile leaks can be definitively treated percutaneously while others necessitate surgical repair. The primary principle of percutaneous management is flow diversion away from the site of a leak with the placement of transhepatic biliary drainage catheters. While this can be accomplished with relative ease in some cases, others call for more advanced techniques. Bile duct embolization or sclerosis may also be required in cases where a leaking bile duct is isolated from the main biliary tree.

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CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV) infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1) CD8+ T-cell deficiency, (2) primary EBV infection, (3) decreased CD8+ T-cell control of EBV, (4) increased EBV load and increased anti-EBV antibodies, (5) EBV infection in the target organ, (6) clonal expansion of EBV-infected autoreactive B cells in the target organ, (7) infiltration of autoreactive T cells into the target organ, and (8) development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.

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Background:Primary biliary cirrhosis (PBC) is a rare slowly progressive autoimmune disease characterized by inflammatory destruction and fibrosis of intrahepatic bile ducts. It is known to coexist together with rheumatological conditions such as Sjögren’s syndrome (SS) and systemic sclerosis (SSc). There is a wide range in reported prevalence of disease overlap with these entities; however, the exact prevalence rates remain unclear.Objectives:The objectives were to determine the prevalence of: 1) PBC in patients with SS and SSc (and the subsets of limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc)), 2) SSc and SS in patients with PBC, and 3) to analyze changes in frequency over time. SSc occurs in 3/10,000 and PBC in 4-40/10,000 but these rare autoimmune diseases are known to coexist together. We speculated that there could be more cases diagnosed due to increasing availability of standardized antibody tests such as ANA, centromere antibodies, ENA and mitochondrial antibodies.Methods:A systematic review of the literature was performed using Medline, EMBASE, CINAHL, and the Cochrane Library databases up till June 16, 2020. Only full text articles in the English language with at least 40 patients were included. Cohorts, case series, cross-sectional studies, correspondences and registries with reported prevalence rates of both PBC in patients with SS and SSc as well as SSc and SS in patients with PBC were included. Data on frequency of co-existent diseases was studied by year of publication to determine if prevalence changed over time using linear regression. We used the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist to assess the quality of the studies.Results:Of 2876 citations identified, 67 were included in the analysis (n=33 for PBC, 15 for SSc, 18 for SS and 1 for SSc/SS). STROBE checklist scores ranged from 7-21. The prevalence of PBC was 5% in patients with SSc. Within the subsets, the prevalence of PBC in lcSSc was 8% and in dcSSc was 1%. In patients with SS, the prevalence of PBC was 4%. The prevalence of SSc overall in those with PBC was 5% and, within the subsets was 6% in lcSSc and 0% in dcSSc. The prevalence of SS in PBC was 18%. There was also no significant association between year of publication and prevalence. There was a lack of standardized definitions so misclassification may have occurred.Conclusion:PBC is increased in SSc but mostly in the lcSSc subset. SS in PBC is common at nearly 1 in 5. Over the years, there was no change in the prevalence of PBC in SSc indicating stability over time.Acknowledgements:Meagan Stanley, Western University Librarian.Disclosure of Interests:None declared.

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Background:studies have shown that anticentromere antibody (ACA) positivity in primary Sjogren’s syndrome (pSS) is associated with autoimmune liver diseases, most often primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) [1, 2, 3], but detailed characteristics of the frequency and severity of liver disease in these patients is not presented in the literature.Objectives:to identify the frequency, structure and characterize the course of autoimmune liver diseases in pSS+ACA.Methods:we observe 82 patients with pSS+ACA. The diagnosis of pSS was established on the basis of Russian 2001 criteria, SSc was excluded based on the ACR/EULAR 2013 criteria [4]. 18 of 82 patients (22%) had a persistent increase in alkaline phosphatase, 11 of them were positive for antimitochondrial antibodies (AMA) and, according to the recommendations of the American Association for the Study of Liver Diseases [5], they were diagnosed with PBC. 7 of 18 patients were AMA-negative, 2 of them had a liver biopsy and the diagnosis of AMA-negative PBC was confirmed, 4 patients who did not have a liver biopsy and 1 patient with hepatitis B were excluded from the study. Also, in 6 of 64 patients without signs of liver damage, an increase in AMA was detected, in 1 of them a liver biopsy was performed and the diagnosis of PBC was confirmed. Thus, the group of patients with pSS+ACA and autoimmune liver diseases included 19 patients: 12 patients with AMA-positive PBC, 2 patients with AMA-negative PBC, and 5 patients with asymptomatic AMA positivity.Results:The median follow-up for 19 patients with pSS+ACA and autoimmune liver diseases was 4 years. AMA were detected in 89.5% of patients, an increase in IgM - in 42.1%, an increase in ALT / AST - 63.2%, a decrease in albumin, prothrombin index and cytopenia - 15.8% (were associated with the development of liver cirrhosis). In most cases, the clinical course of liver disease was characterized by an asymptomatic, slowly progressing course, with no signs of progression during observation. Cirrhosis and portal hypertension were detected in 15.8% of patients, hepatic encephalopathy - in 10.5%. Liver biopsy was performed in 9 patients, PBC was diagnosed in all cases (overlap syndrome with AIH was established in 3 cases). Assessment of PBC histological stages showed signs of stage 1 in 5 patients, stage 2 in 1 patient, stage 3 in 3 patients. Observation of 5 patients with stage 1 PBC and 5 AMA-positive patients without signs of liver damage (median follow-up was 2 years), showed the absence of clinical, laboratory and instrumental progression of liver disease, which is why we believe that these patients have epithelitis of the biliary ducts as manifestation of glandular lesions in pSS, but not PBC.Conclusion:autoimmune liver diseases in pSS+ACA are detected in 23.2% of patients, most of whom develop PBC and epitheliitis of the biliary ducts with the same frequency, less often overlap syndrome of PBC and AIH, and characterized by a mild, slowly progressing course and rarely lead to liver cirrhosis.References:[1]Masako Kita et al. Abnormal Liver Function in Patients with Sjogren’s Syndrome. Acta Med. Nagasaki 41: 31-37.[2]Baldini, Chiara et al. “Overlap of ACA-positive systemic sclerosis and Sjögren’s syndrome: a distinct clinical entity with mild organ involvement but at high risk of lymphoma.” Clinical and experimental rheumatology vol. 31,2 (2013): 272-80.[3]Bournia, Vasiliki-Kalliopi K et al. “Anticentromere antibody positive Sjögren’s Syndrome: a retrospective descriptive analysis.” Arthritis research & therapy vol. 12,2 (2010): R47. doi:10.1186/ar2958.[4]van den Hoogen, Frank et al. “2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative.” Arthritis and rheumatism vol. 65,11 (2013): 2737-47. doi:10.1002/art.38098.[5]Lindor, Keith D et al. “Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases.” Hepatology (Baltimore, Md.) vol. 69,1 (2019): 394-419. doi:10.1002/hep.30145.Disclosure of Interests:None declared

Abstract:

Background:Systemic sclerosis (SSc) is a chronic, connective tissue disease with an autoimmune pattern characterized by inflammation, fibrosis and microcirculation changes leading to internal organs malfunctions. The gastrointestinal tract (GIT) is affected in up to 90% of patients with SSc. Any part of the GIT from the mouth to the anus can be affected. There are few descriptive studies about SSc-related GIT involvement.Objectives:We aimed to characterize the GIT involvement in patients with SSc.Methods:This retrospective study included all patients from SSc cohort of our autoimmune diseases unit in a tertiary referral centre. All patients fulfilled SSc criteria proposed by the American College of Rheumatology. All subjects’ histories were evaluated. Laboratory and imaging results were obtained from the hospital files. Patients with digestive manifestations were compared with patients without GIT involvement. Chi2 and t-student were used, using the statistical package SPSS25.0.Results:83 subjects with SSc were included, 68 (81,9%) of them were women. The mean age at the onset of SSc was 62,1 ± 15,3 years (range 26-89) with a mean follow-up of 9,6 ± 7,4 years. 80,7% of patients had limited SSc, 12% diffuse SSc, 4.8% SSc sine scleroderma and 2,4% early SSc. Considering the immunological profile 12 (14,5%) had Scl70 antibodies, 49 (59%) anticentromere and 21 (25,3%) had ANA antibodies without specificity for anti-Scl70 or anticentromere. 37,3% patients had lung involvement, 20,5% scleroderma and 30,1% digital ulcers. 79,5% of SSc patients were treated with proton pump inhibitors or H2 blockers. 53 (63,9%) patients with SSc had GIT involvement. In 11 patients (20,7%) digestive involvement was diagnosed before SSc (mean 26,2 months). Esophageal involvement occurred in 83%, gastric involvement in 28,3%, intestine involvement in 24,5% and liver and biliary tree involvement in 26,4%. See table 1. No significant differences in age, sex, SSc subtype, autoantibody profile, lung involvement, skin disease, mortality and therapy were observed between patients with or without GIT manifestations. There were no deaths associated with GIT involvement. The most common pharmacologic therapy used was proton pump inhibitors (86,8%), domperidone (20,8%) and antibiotic rotation (17%).EsophagealGastricIntestinalLiver and biliary tree44/53 (83%)15/53 (28,3%)12/53 (24,5%)14/53 (26,4%)Esophageal motility disorder 8 (15,1%)Gastroparesis 6 (11,3%)Small bacterial overgrowth 7 (13,2%)Primary biliary cholangitis 9 (17%)Gastroesophageal reflux 40 (75,5%)Abdominal pain /nausea 10 (18,9%)Colonic inertia 1 (1,9%)Autoimmune hepatitis 3 (5,7%)Dysphagia 11 (20,8%)Subacute gastritis 7 (13,2%)Diarrhea 6 (11,3%)Cholestatic liver enzymes 11 (20,8%)Flatulence / abdominal discomfort 6 (11,3%)Cirrhosis 2 (3,8%)Conclusion:Almost two thirds of our cohort of SSc have symptomatic gastrointestinal disease. GIT manifestations are heterogeneous. Symptoms are non-specific and overlapping for a particular anatomical site. Esophagus is the most commonly affected. More than seventy-five per cent of patients experience symptoms of gastroesophageal reflux. We did not find differences among patients with and without SSc GIT disease. 17% of patients had a Reynold’s syndrome.References:[1]Alastal Y et al. Gastrointestinal manifestations associated with systemic sclerosis: results from the nationwide inpatient simple. Ann Gastroenterol 2017; 30 (5): 1-6.[2]Savarino E et al. Gastrointestinal motility disorder assessment in systemic sclerosis. Rheumatology. 2013; 52(6):1095–100.[3]Steen VD et al. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis and rheumatism. 2000; 43(11):2437–44.Disclosure of Interests:None declared

Abstract:

Objective.To investigate the diagnostic accuracy of antimitochondrial antibodies (AMA), sp100, and gp210 antibodies for primary biliary cirrhosis (PBC) in a large population of patients with systemic sclerosis (SSc); to examine concordance of these antibodies with subsets of SSc. Further, to assess the association of SSc-related antibodies with hepatic parameter abnormalities.Methods.We obtained medical records to verify the diagnoses of SSc and PBC. Sera from all participants were examined for the presence of SSc- and PBC-related antibodies, as well as for abnormalities in hepatic parameters.Results.We examined 817 patients with SSc, of whom 16 (2%) had confirmed PBC. The sensitivity and specificity of AMA by a MIT3 ELISA for PBC were 81.3% and 94.6%, respectively. Sp100 had a sensitivity and specificity of 31.3% and 97.4%, respectively, while gp210 had an even lower sensitivity. We were able to detect all PBC cases using AMA(MIT3) and sp100 as a combined marker, resulting in a significantly improved sensitivity of 100% (p = 0.042) with an incremental decrease in specificity to 92.6%. Independent of AMA or sp100 status, there was an association of anticentromere B (CENP-B) and anti-topoisomerase antibodies (ATA) with higher alkaline phosphatase levels (p = 0.051 and p = 0.003, respectively) while anti-RNA polymerase III (anti-RNAP) was associated with lower alkaline phosphatase levels (p = 0.019) among the patients with SSc.Conclusion.Utilization of AMA(MIT3) and sp100 antibodies as a combined diagnostic marker leads to an improved detection of PBC in patients with SSc. CENP-B and ATA are associated with alkaline phosphatase elevation.

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AbstractBackgroundSystemic sclerosis (SSc) and primary biliary cholangitis (PBC) are autoimmune diseases that may occur concomitantly and are both strongly associated with disease-specific autoantibodies. This study investigated the prevalence and fine specificity of PBC-specific serology (PBC-Ab) and associations with the SSc-subtypes and SSc-specific antibodies as well as the association with cholestatic liver enzymes. Furthermore, three different techniques for the detection of PBC-Ab were compared.MethodsSerum of 184 Belgian SSc patients with a known SSc-antibody profile, was analyzed for PBC-Ab (antimitochondrial antibodies [AMA], anti-Gp210, anti-Sp100 and anti-PML) using indirect immunofluorescence (IIF) analysis on human epithelioma-2000 (HEp-2000) cells (ANA-IIF, Immunoconcepts) and liver-kidney-stomach tissue sections (IIF-LKS) (Menarini), and a line immunoblot (LB) (EuroImmun). Alkaline phosphatase/γ-glutamyl transferase (ALP/GGT) were evaluated at time of first sampling (t0) and after 3 years of follow-up (t3).ResultsPBC-Ab were present in 13% of patients and significantly correlated with centromere antibodies (anti-CENP-B), but not correlated with the limited cutaneous SSc subgroup (lcSSc). The most frequent reactivities were AMA (11%, with 9% AMA-M2) and Sp-100 antibodies (5%), showing a major overlap. There was no relevant association between the presence of PBC-Ab and ALP or GGT elevation at t0 nor at t3. Detection of AMA with IIF-LKS is comparable to LB. ANA-IIF screening was less sensitive compared to LB.ConclusionsA wide range of PBC-Ab is detectable in SSc in the absence of cholestatic liver enzyme elevations, even after 3 years of follow-up. However, as these antibodies may precede PBC-disease up to 10 years further prospective follow-up of our cohort will be necessary.

Abstract:

Chlamydia trachomatis and C. pneumoniae are members of the Chlamydiaceae family of obligate intracellular bacteria. The former causes diseases predominantly at the mucosal epithelial layer of the urogenital or eye, leading to pelvic inflammatory diseases or blindness; while the latter is a major causative agent for pulmonary infection. On top of these well-described diseases at the respective primary infection sites, Chlamydia are notoriously known to migrate and cause pathologies at remote sites of a host. One such example is the sexually acquired reactive arthritis that often occurs at few weeks after genital C. trachomatis infection. C. pneumoniae, on the other hand, has been implicated in an extensive list of chronic inflammatory diseases which include atherosclerosis, multiple sclerosis, Alzheimer’s disease, asthma, and primary biliary cirrhosis. This review summarizes the Chlamydia infection associated diseases at the secondary sites of infection, and describes the potential mechanisms involved in the disease migration and pathogenesis.