Early Primary Biliary Cirrhosis: A New Association with Erythema Nodosum of Unknown Origin

Primary biliary cirrhosis (PBC) is associated with immune-mediated dermatologic disorders. The association of PBC with erythema nodosum (EN) seems rare. We report two females (42 and 44 years old) with low-grade fever, arthralgias, and elevated cholestatic enzymes in the first and fatigue in the second. Patients were also suffering from typical EN lesions characterized by multiple erythematous, painful nodules over the anterior portions of their lower extremities. Clinical and extensive laboratory work up excluded all known EN causes. PBC diagnosis was established according to the cholestatic biochemical profile, anti-mitochondrial antibodies (AMA) positivity and liver histology (first), and AMA and antinuclear (ANA) PBC-specific antibodies (second). Our report may suggest that PBC could be kept in mind in EN patients of unknown aetiology and particularly, when middle-aged female patients are affected. In such cases a thorough evaluation for AMA and/or ANA PBC-specific antibodies could be helpful to achieve a correct and timely diagnosis

Variants of Primary Biliary Cholangitis: An Updated Mini-Review

Primary biliary cirrhosis (PBC) is an autoimmune cholestatic disease of the liver which affects mainly middle-aged women characterized by progressive destruction and loss of the small intrahepatic bile ducts which in turn, may lead to end-stage liver disease. The typical clinical phenotype is characterized by a middle-aged female with elevated cholestatic enzymes and positive antimitochondrial antibodies (AMA). However, apart from this typical presentation, there are important variants in everyday clinical practice. These variants include the AMA-negative PBC, the isolated AMA positivity, the AMA-positivity in patients with well-established autoimmune hepatitis (AIH), the premature ductopenic PBC variant and the PBC variant with characteristics of AIH (PBC-AIH variant). In this mini-review, we summarize and discuss the literature data and our own experience on the PBC variants highlighting also the uncertainties and a potential new era of the research agenda

An immunocompetent patient presenting with severe septic arthritis due to Ralstonia pickettii identified by molecular-based assays: a case report

Introduction: Ralstonia pickettii is an infrequent pathogen of invasive infections in healthy individuals. The microorganism is supposed to be of relatively low virulence, but can cause infections, mainly of the respiratory tract, in immunocompromised and cystic fibrosis patients. Ralstonia pickettii has also been associated with hospital outbreaks related to contamination of products used for medical care and laboratory diagnosis. Case presentation: We report here a case of septic arthritis due to Ralstonia pickettii in a female diabetic patient. The microorganism was identified from the synovial fluid by molecular-based methods, while the conventional synovial and blood cultures proved to be negative. The patient was treated by intravenous ceftazidime with complete remission of her symptoms; she was discharged 3 weeks after admission in a very good health. At follow-up examination 3 weeks later, she was still in good health condition without any sign of arthritis of the right knee and afebrile. Conclusion: In culture negative serious bacterial infections, as septic arthritis, the use of molecularbased techniques might be of outmost importance as additional and rapid diagnostic tools for the identification of the causative agent allowing a prompt and appropriate antimicrobial therapy and a favourable outcome. © 2009 Makaritsis et al; licensee Cases Network Ltd

Ocular disorders as the prevailing manifestations of antiphospholipid syndrome: a case series

Introduction: Antiphospholipid syndrome is an autoimmune disorder characterized by either a history of vascular thrombosis (one or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ) or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The systemic features of the syndrome are characterized by large variability depending on the affected organ(s). Among them, neurological and behavioural disturbances, dermatological features as livedo reticularis and renal, ocular, liver or valvular heart manifestations have been reported in antiphospholipid syndrome patients. However, studies on the frequency and clinical presentation of the ocular manifestations as the prevailing (first) sign of antiphospholipid syndrome in patients suffering from "unexplained" ocular disease are missing. Herein, we present three cases suffering from unexplained ocular disease as first manifestation of antiphospholipid syndrome. Case presentation: All the three patients were referred to our department because of unexplained ocular features from the anterior or posterior segment and unexplained neuroophthalmologic symptoms. The first patient had bilateral retinal occlusive disease, the second and the third patient had unilateral nonarteritic anterior ischemic optic neuropathy with macular oedema. Moderate to high levels of antiphospholipid antibodies were detected in all of them at baseline as well as 6 to 12 weeks after initial testing confirming the presence of antiphospholipid antibodies. Anticoagulant treatment with acenocoumarol was instituted resulting in stabilization and/or improvement of ocular signs in all of them. Conclusion: Due to the important diagnostic and therapeutic implications of antiphospholipid syndrome, the possibility of ocular features as the first clinical manifestation of antiphospholipid syndrome should be kept in mind of the physicians particularly in patients with no evident risk factors for ocular disease. In this case, prompt anticoagulant treatment and close follow-up seem to be essential for vision salvation and stabilization. © 2009 Tsironi et al; licensee BioMed Central Ltd

Efficacy and safety of palliative treatment in patients with autoimmune liver disease-associated hepatocellular carcinoma

Introduction and Objectives: Autoimmune liver diseases (AILD) are rare causes hepatocellular carcinoma (HCC), and data on the efficacy and tolerability of anti-tumor therapies are scarce. This pan-European study aimed to assess outcomes in AILD-HCC patients treated with tyrosine kinase inhibitors (TKIs) or transarterial chemoembolization (TACE) compared with patients with more common HCC etiologies, including viral, alcoholic or non-alcoholic fatty liver disease. / Materials and Methods: 107 patients with HCC-AILD (AIH:55; PBC:52) treated at 13 European centres between 1996 and 2020 were included. 65 received TACE and 28 received TKI therapy. 43 (66 %) were female (median age 73 years) with HCC tumor stage BCLC A (34 %), B (46 %), C (9 %) or D (11 %). For each treatment type, propensity score matching was used to match AILD to non-AILD-HCC on a 1:1 basis, yielding in a final cohort of 130 TACE and 56 TKI patients for comparative analyses of median overall survival (mOS) and treatment tolerability. / Results: HCC-AILD patients showed comparable mOS to controls for both TACE (19.5 vs. 22.1 months, p = 0.9) and TKI (15.4 vs. 15.1 months, p = 0.5). Adverse events were less frequent in AILD-HCC patients than controls (33 % % vs. 62 %, p = 0.003). For TKIs, there were no significant differences in adverse events (73% vs. 86%, p = 0.2) or interruption rates (44% vs. 36 %, p = 0.7). / Conclusions: In summary, this study demonstrates comparable mOS for AILD-HCC patients undergoing local and systemic treatments, with better tolerability than HCC of other causes. TKIs remain important therapeutic options for AILD-HCC patients, particularly given their exclusion from recent immunotherapy trials

Unusual cardiovascular complications of brucellosis presenting in two men: two case reports and a review of the literature

Introduction: Brucellosis is a zoonosis with worldwide distribution, which is particularly endemic in many countries of the Mediterranean basin. Cardiovascular complications of this disease, such as endocarditis, myocarditis and pericarditis, are very rare, with even fewer cases of myocarditis or asymptomatic pericardial effusion in the absence of concomitant endocarditis being reported. Case presentation: We report two cases of brucellosis in two Caucasian men, aged 17 and 34 years old, with myocarditis and asymptomatic pericardial effusion, respectively. Of note, neither patient had concomitant endocarditis. The disease was confirmed serologically and by blood cultures. Both patients recovered completely after receiving appropriate antibiotic treatment without any sign of relapse during a follow-up of 12 months. Conclusion: These two cases emphasize that in endemic areas Brucella can be considered as a potentially causative agent of idiopathic pericardial effusion or myocarditis, even in the absence of concomitant endocarditis. This possibility could be taken into account particularly in cases where contraction of brucellosis is possible, such as occupational exposure or consumption of unpasteurized dairy products. © 2011 Gatselis et al; licensee BioMed Central Ltd

Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis

\ua9 2024 The Author(s)Background & Aims: In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain. Methods: We conducted an international retrospective cohort study among patients with PBC treated with ursodeoxycholic acid and followed by vibration-controlled transient elastography between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation, or death, was quantified using the hazard ratio and its confidence interval. Results: A total of 6362 LSMs were performed in 3078 patients (2007 on ursodeoxycholic acid alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1000 person-years). LSM progressed in 59% of patients (mean, 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (P < .001). For example, the adjusted hazard ratios (95% confidence interval) associated with a 20% annual variation in LSM were 2.13 (1.89–2.45) for the increase and 0.40 (0.33–0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or liver transplantation was considered. Conclusions: Tracking longitudinal changes in LSM using vibration-controlled transient elastography provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate end point in PBC clinical trials

Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

\ua9 2022 The Authors. Background & Aims: Autoimmune hepatitis (AIH) has been well characterised and codified through the development of diagnostic criteria. These criteria have been adapted and simplified and are widely used in clinical practice. However, there is a need to update and precisely define the criteria for both treatment response and treatment. Methods: A systematic review was performed and a modified Delphi consensus process was used to identify and redefine the response criteria in autoimmune hepatitis. Results: The consensus process initiated by the International Autoimmune Hepatitis Group proposes that the term ‘complete biochemical response’ defined as ‘normalization of serum transaminases and IgG below the upper limit of normal’ be adopted to include a time point at 6 months after initiation of treatment. An insufficient response by 6 months was a failure to meet the above definition. Non-response was defined as ‘<50% decrease of serum transaminases within 4 weeks after initiation of treatment’. Remission is defined as liver histology with a Hepatitis Activity Index <4/18. Intolerance to treatment was agreed to stand for ‘any adverse event possibly related to treatment leading to potential drug discontinuation’. Conclusions: These definitions provide a simple and reproducible framework to define treatment response and non-response, irrespective of the therapeutic intervention. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable inter-study comparisons. Future prospective database studies are needed to validate these endpoints. Lay summary: Consensus among international experts on response criteria and endpoints in autoimmune hepatitis is lacking. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable the comparison of results between clinical trials. Therefore, the International Autoimmune Hepatitis Group (IAIHG) herein presents a statement on 5 agreed response criteria and endpoints: complete biochemical response, insufficient response, non-response, remission, and intolerance to treatment, which can be used to guide future reporting

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis

Background: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.Fil: Efe, Cumali. Harran University Hospita; TurquíaFil: Lammert, Craig. University School of Medicine Indianapolis; Estados UnidosFil: Taşçılar, Koray. Universitat Erlangen-Nuremberg; AlemaniaFil: Dhanasekaran, Renumathy. University of Stanford; Estados UnidosFil: Ebik, Berat. Gazi Yasargil Education And Research Hospital; TurquíaFil: Higuera de la Tijera, Fatima. Hospital General de México; MéxicoFil: Calışkan, Ali R.. No especifíca;Fil: Peralta, Mirta. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Gerussi, Alessio. Università degli Studi di Milano; ItaliaFil: Massoumi, Hatef. No especifíca;Fil: Catana, Andreea M.. Harvard Medical School; Estados UnidosFil: Purnak, Tugrul. University of Texas; Estados UnidosFil: Rigamonti, Cristina. Università del Piemonte Orientale ; ItaliaFil: Aldana, Andres J. G.. Fundacion Santa Fe de Bogota; ColombiaFil: Khakoo, Nidah. Miami University; Estados UnidosFil: Nazal, Leyla. Clinica Las Condes; ChileFil: Frager, Shalom. Montefiore Medical Center; Estados UnidosFil: Demir, Nurhan. Haseki Training And Research Hospital; TurquíaFil: Irak, Kader. Kanuni Sultan Suleyman Training And Research Hospital; TurquíaFil: Melekoğlu Ellik, Zeynep. Ankara University Medical Faculty; TurquíaFil: Kacmaz, Hüseyin. Adıyaman University; TurquíaFil: Balaban, Yasemin. Hacettepe University; TurquíaFil: Atay, Kadri. No especifíca;Fil: Eren, Fatih. No especifíca;Fil: Alvares da-Silva, Mario R.. Universidade Federal do Rio Grande do Sul; BrasilFil: Cristoferi, Laura. Università degli Studi di Milano; ItaliaFil: Urzua, Álvaro. Universidad de Chile; ChileFil: Eşkazan, Tuğçe. Cerrahpaşa School of Medicine; TurquíaFil: Magro, Bianca. No especifíca;Fil: Snijders, Romee. No especifíca;Fil: Barutçu, Sezgin. No especifíca;Fil: Lytvyak, Ellina. University of Alberta; CanadáFil: Zazueta, Godolfino M.. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Demirezer Bolat, Aylin. Ankara City Hospital; TurquíaFil: Aydın, Mesut. Van Yuzuncu Yil University; TurquíaFil: Amorós Martín, Alexandra Noemí. No especifíca;Fil: De Martin, Eleonora. No especifíca;Fil: Ekin, Nazım. No especifíca;Fil: Yıldırım, Sümeyra. No especifíca;Fil: Yavuz, Ahmet. No especifíca;Fil: Bıyık, Murat. Necmettin Erbakan University; TurquíaFil: Narro, Graciela C.. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Bıyık, Murat. Uludag University; TurquíaFil: Kıyıcı, Murat. No especifíca;Fil: Kahramanoğlu Aksoy, Evrim. No especifíca;Fil: Vincent, Maria. No especifíca;Fil: Carr, Rotonya M.. University of Pennsylvania; Estados UnidosFil: Günşar, Fulya. No especifíca;Fil: Reyes, Eira C.. Hepatology Unit. Hospital Militar Central de México; MéxicoFil: Harputluoğlu, Murat. Inönü University School of Medicine; TurquíaFil: Aloman, Costica. Rush University Medical Center; Estados UnidosFil: Gatselis, Nikolaos K.. University Hospital Of Larissa; GreciaFil: Üstündağ, Yücel. No especifíca;Fil: Brahm, Javier. Clinica Las Condes; ChileFil: Vargas, Nataly C. E.. Hospital Nacional Almanzor Aguinaga Asenjo; PerúFil: Güzelbulut, Fatih. No especifíca;Fil: Garcia, Sandro R.. Hospital Iv Víctor Lazarte Echegaray; PerúFil: Aguirre, Jonathan. Hospital Angeles del Pedregal; MéxicoFil: Anders, Margarita. Hospital Alemán; ArgentinaFil: Ratusnu, Natalia. Hospital Regional de Ushuaia; ArgentinaFil: Hatemi, Ibrahim. No especifíca;Fil: Mendizabal, Manuel. Universidad Austral; ArgentinaFil: Floreani, Annarosa. Università di Padova; ItaliaFil: Fagiuoli, Stefano. No especifíca;Fil: Silva, Marcelo. Universidad Austral; ArgentinaFil: Idilman, Ramazan. No especifíca;Fil: Satapathy, Sanjaya K.. No especifíca;Fil: Silveira, Marina. University of Yale. School of Medicine; Estados UnidosFil: Drenth, Joost P. H.. No especifíca;Fil: Dalekos, George N.. No especifíca;Fil: N.Assis, David. University of Yale. School of Medicine; Estados UnidosFil: Björnsson, Einar. No especifíca;Fil: Boyer, James L.. University of Yale. School of Medicine; Estados UnidosFil: Yoshida, Eric M.. University of British Columbia; CanadáFil: Invernizzi, Pietro. Università degli Studi di Milano; ItaliaFil: Levy, Cynthia. University of Miami; Estados UnidosFil: Montano Loza, Aldo J.. University of Alberta; CanadáFil: Schiano, Thomas D.. No especifíca;Fil: Ridruejo, Ezequiel. Universidad Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Wahlin, Staffan. No especifíca