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Mihai IR, Rezus C, Burlui MA, Cardoneanu A, Macovei LA, Richter P, Bratoiu I, Rezus E. Autoimmune Liver Diseases and Rheumatoid Arthritis-Is There an Etiopathogenic Link? Int J Mol Sci 2024; 25:3848. [PMID: 38612658 PMCID: PMC11011907 DOI: 10.3390/ijms25073848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 02/28/2024] [Accepted: 03/23/2024] [Indexed: 04/14/2024] Open
Abstract
Rheumatoid arthritis (RA) is a systemic immune-mediated disease that, in addition to the articular involvement, can have extra-articular manifestations. Even though liver damage in RA is not very common, associated autoimmune liver diseases (AILDs) may occur. The most common AILD associated with RA is primary biliary cirrhosis (PBC), followed by autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). There are common underlying mechanisms that play a role in the emergence of autoimmunity and inflammation in both rheumatic and autoimmune liver diseases. Genetic studies have revealed the existence of several common disease-associated genes shared between RA and AILDs, and infectious triggers, particularly those associated with recurrent or complicated urinary tract infections, are also speculated to be potential triggers for these conditions. Moreover, these diseases share common serologic patterns characterized by the presence of specific autoantibodies and hyper-gammaglobulinemia. In this study, we focus on reviewing the association between RA and AILDs regarding the prevalence and possible etiopathogenic link.
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Affiliation(s)
- Ioana Ruxandra Mihai
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Ciprian Rezus
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- “Sfantul Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Maria Alexandra Burlui
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Anca Cardoneanu
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Luana Andreea Macovei
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Patricia Richter
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Ioana Bratoiu
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Elena Rezus
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
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Arias-de la Rosa I, Ruiz-Ponce M, Cuesta-López L, Pérez-Sánchez C, Leiva-Cepas F, Gahete MD, Navarro P, Ortega R, Cordoba J, Pérez-Pampin E, González A, Lucendo AJ, Collantes-Estévez E, López-Pedrera C, Escudero-Contreras A, Barbarroja N. Clinical features and immune mechanisms directly linked to the altered liver function in patients with rheumatoid arthritis. Eur J Intern Med 2023; 118:49-58. [PMID: 37544847 DOI: 10.1016/j.ejim.2023.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 07/28/2023] [Accepted: 08/01/2023] [Indexed: 08/08/2023]
Abstract
BACKGROUND The aim of this study was to explore the impact of arthritis on liver function using different approaches in vivo and in vitro. METHODS A cross-sectional study was performed on 330 non-obese/non-T2DM subjects: 180 RA patients, 50 NAFLD non-RA patients, and 100 healthy donors (HDs). A longitudinal study was conducted on 50 RA patients treated with methotrexate for six months. Clinical and laboratory parameters and markers of liver disease were collected. Mechanistic studies were carried out in both the CIA mouse model and hepatocytes treated with anti-citrullinated protein antibodies (ACPAs). RESULTS RA patients have an increased risk of suffering from liver disease independent of obesity or T2DM. This risk was associated with factors such as insulin resistance, autoantibodies, inflammation, and component C3. Methotrexate treatment for six months was associated with liver abnormalities in those newly-diagnosed patients having CV risk factors. ACPAs induced a defective hepatocyte function, promoting IR and inflammation. The induction of arthritis in mice caused the infiltration of immune cells in the liver and increased inflammatory, apoptotic, and fibrotic processes. CONCLUSION RA patients may experience mild to moderate liver inflammation due to the infiltration of T, B cells, and macrophages, and the action of ACPAs. This is independent of obesity or diabetes and linked to systemic inflammation, and disease activity levels. The negative effects of methotrexate on liver function could be restricted to the concomitant presence of cardiovascular risk factors.
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Affiliation(s)
- I Arias-de la Rosa
- Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain.
| | - M Ruiz-Ponce
- Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain
| | - L Cuesta-López
- Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain
| | - C Pérez-Sánchez
- Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain
| | - F Leiva-Cepas
- Deparment of Pathology, Reina Sofia University Hospital, Cordoba, Spain; Department of Morphological Sciences, Section of Histology, Faculty of Medicine and Nursing, Cordoba, Spain
| | - M D Gahete
- Department of Cell Biology, Physiology, and Immunology, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, CIBERobn, Cordoba, Spain
| | - P Navarro
- Department of Gastroenterology. Hospital General de Tomelloso, Spain; Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Spain
| | - R Ortega
- Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain
| | - J Cordoba
- Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, Chicago, IL, USA
| | - E Pérez-Pampin
- Experimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigación Sanitaria - Hospital Clínico Universitario de Santiago (IDIS), Santiago de Compostela, Galicia, Spain
| | - A González
- Experimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigación Sanitaria - Hospital Clínico Universitario de Santiago (IDIS), Santiago de Compostela, Galicia, Spain
| | - A J Lucendo
- Department of Gastroenterology. Hospital General de Tomelloso, Spain; Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Spain; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - E Collantes-Estévez
- Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain
| | - Ch López-Pedrera
- Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain
| | - A Escudero-Contreras
- Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain
| | - N Barbarroja
- Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain.
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Barbarroja N, Ruiz-Ponce M, Cuesta-López L, Pérez-Sánchez C, López-Pedrera C, Arias-de la Rosa I, Collantes-Estévez E. Nonalcoholic fatty liver disease in inflammatory arthritis: Relationship with cardiovascular risk. Front Immunol 2022; 13:997270. [PMID: 36211332 PMCID: PMC9539434 DOI: 10.3389/fimmu.2022.997270] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 09/07/2022] [Indexed: 11/13/2022] Open
Abstract
Liver disease is one of the most important causes of morbidity and mortality worldwide whose prevalence is dramatically increasing. The first sign of hepatic damage is inflammation which could be accompanied by the accumulation of fat called non-alcoholic fatty liver disease (NAFLD), causing damage in the hepatocytes. This stage can progress to fibrosis where the accumulation of fibrotic tissue replaces healthy tissue reducing liver function. The next stage is cirrhosis, a late phase of fibrosis where a high percentage of liver tissue has been replaced by fibrotic tissue and liver functionality is substantially impaired. There is a close interplay of cardiovascular disease (CVD) and hepatic alterations, where different mechanisms mediating this relation between the liver and systemic vasculature have been described. In chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in which the CVD risk is high, hepatic alterations seem to be more prevalent compared to the general population and other rheumatic disorders. The pathogenic mechanisms involved in the development of this comorbidity are still unraveled, although chronic inflammation, autoimmunity, treatments, and metabolic deregulation seem to have an important role. In this review, we will discuss the involvement of liver disease in the cardiovascular risk associated with inflammatory arthritis, the pathogenic mechanisms, and the recognized factors involved. Likewise, monitoring of the liver disease risk in routine clinical practice through both, classical and novel techniques and indexes will be exposed. Finally, we will examine the latest controversies that have been raised about the effects of the current therapies used to control the inflammation in RA and PsA, in the liver damage of those patients, such as methotrexate, leflunomide or biologics.
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Chegni H, Heidarvand M. The in vitro effects of vitamin 1, 25(OH) 2 D3 on expression of cytokines: In new-onset systemic lupus erythematosus patients. Lupus 2022; 31:939-943. [PMID: 35485195 DOI: 10.1177/09612033221098533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a variety of factors in the immune system. Awareness of the role of cytokines in SLE has led to new clinical perspectives in its pathogenesis; therefore, the aim of this study was to investigate the effect of vitamin 1, 25(OH) 2 D3 (D3) on the expression of IL-2, IL-4, IL-5, IL-10, and IFN-γ cytokines in patients with lupus. METHODS A total of 65 new-onset SLE patients were enrolled in the study. After peripheral blood mononuclear cell isolation, the lymphocytes of each patient were divided into two groups, one treated with a concentration of 50 μmol vitamin D3 (test) and the other untreated with vitamin D3 (control), were cultured. After 24 hours, the cultured cells were collected and the expressions of IL-2, IL-4, IL-5, IL-10, and IFN-γ genes were analyzed by RT-qPCR. RESULTS It was observed that vitamin D3 reduced expression of IFN-γ, IL-4, IL-5, and IL-10 genes by 73, 50, 37, and 29%, respectively, and increased IL-2 gene expression by 31% (p ≤ 0.05). CONCLUSION With different patterns of cytokine changes in patients with lupus in different studies, it seems that the pattern of cytokine changes is largely dependent on the phase of the disease and with this study it can be concluded that vitamin D3 administration at the time of diagnosis and in the early stages and before starting treatment have different effects from its administration in the acute stage of the disease, which requires further studies to prove. It seems that in patients with systemic lupus erythematosus, vitamin D should be administered taking into account the phase of the disease.
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Affiliation(s)
- Hamid Chegni
- Department of Medical Laboratory Sciences, 556492School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Heidarvand
- Department of Immunology, Faculty of Medical Sciences, 48455Isfahan University of Medical Science, Tehran, Iran
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Halabi H, AlDabbagh A, Alamoudi A. Gastrointestinal Manifestations of Rheumatic Diseases. SKILLS IN RHEUMATOLOGY 2021:475-499. [DOI: 10.1007/978-981-15-8323-0_23] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
AbstractSLE may involve any part of the gastrointestinal (GI) tract as well as the liver.
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Abstract
Liver involvement in rheumatic diseases may occur as a primary liver disease, primary rheumatic disease with hepatic manifestations or antirheumatic drug-induced liver disease. The aim of our article is to underline the importance of monitoring and control of the level of aminotransferases and cholestatic enzymes in rheumatic disorders. Some of the rheumatic diseases with constantly elevated liver enzymes need to be investigated in consideration of concomitant primary autoimmune liver disease (such as autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis) or drug hepatotoxicity. Also, we should be aware of hepatitis B reactivation or hepatitis C flare when immunosuppressants are used.
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Afzal W, Haghi M, Hasni SA, Newman KA. Lupus hepatitis, more than just elevated liver enzymes. Scand J Rheumatol 2020; 49:427-433. [PMID: 32942921 DOI: 10.1080/03009742.2020.1744712] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Systemic lupus erythematosus (SLE), a multisystem autoimmune inflammatory disease, may involve any organs, including the liver. Liver involvement in SLE is not part of the American College of Rheumatology criteria and is relatively rare. Liver disease is usually mild, manifesting as subtle elevation of liver enzymes. Jaundice and hepatomegaly can be seen in some patients; advanced liver disease with cirrhosis is extremely rare. Precise pathology remains obscure. SLE may cause non-specific changes, including hepatocellular, cholestatic, or vascular changes. Alcohol, drugs, viral infections, metabolic disorders, autoimmune hepatitis, and other common causes of liver dysfunction should be excluded. Corticosteroids may expedite the recovery process, but may lead to non-alcoholic fatty liver disease and liver damage. Several large-scale multicentre studies have shown that liver involvement is not the major cause of morbidity and mortality in SLE patients. In this review, we discuss the pathogenesis, diagnosis, differential diagnosis, clinical manifestations, management, complications, and prognosis of lupus hepatitis.
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Affiliation(s)
- W Afzal
- Sanford School of Medicine, University of South Dakota , Sioux Falls, SD, USA
| | - M Haghi
- Department of Internal Medicine, Coney Island Hospital , Brooklyn, NY, USA
| | - S A Hasni
- National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD, USA
| | - K A Newman
- School of Medicine, Eisenhower Medical Center, University of California , Rancho Mirage, CA, USA
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Yang QB, He YL, Peng CM, Qing YF, He Q, Zhou JG. Systemic lupus erythematosus complicated by noncirrhotic portal hypertension: A case report and review of literature. World J Clin Cases 2018; 6:688-693. [PMID: 30430127 PMCID: PMC6232573 DOI: 10.12998/wjcc.v6.i13.688] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Revised: 09/01/2018] [Accepted: 10/09/2018] [Indexed: 02/05/2023] Open
Abstract
A 48 year-old Chinese woman suffering from polyarthritis, irregular fever and trichomadesis was admitted to the hospital. A diagnosis of systemic lupus erythematosus (SLE) was made based on polyarthritis, pancytopenia, reduced complement 3, multiple positive autoantibodies, a positive Coomb’s test and protein in her urine. In addition, splenomegaly was detected during physical examination and confirmed by abdominal ultrasonography and magnetic resonance imaging, indicating that the patient had SLE and portal hypertension. Further negative investigations ruled out the possibility of cirrhosis. The patient was diagnosed with active SLE complicated by noncirrhotic portal hypertension (NCPH) without liver histopathology, due to the patient’s refusal for liver biopsy. Portal vein diameter and splenomegaly decreased following treatment with methylprednisolone, hydroxychloroquine and metoprolol tartrate. To date, SLE complicated by NCPH has rarely been reported, as it is under-recognized clinically as well as pathologically. Here we describe a case of SLE complicated by NCPH and review the literature for its characteristics, which may contribute to improving the recognition of NCPH and reducing missed and delayed diagnosis of this disorder.
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Affiliation(s)
- Qi-Bin Yang
- Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Yong-Long He
- Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Clinical Medical School, Chengdu University of Traditional Chinese Medicine, Chengdu 610000, Sichuan Province, China
| | - Chun-Mei Peng
- Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Yu-Feng Qing
- Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Qi He
- Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Jing-Guo Zhou
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610000, Sichuan Province, China
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Abstract
Liver disease in children occurs via a multitude of primary illnesses such as autoimmune hepatopathy, biliary atresia, and nonalcoholic fatty liver disease. However, jaundice, hepatitis, and alterations in liver tests can often be a manifestation of systemic diseases. The liver is involved in many critical functions such as circulation, immunity, toxin clearance, and metabolism; when the heart, lungs, gastrointestinal tract, immune system, or endocrine systems are compromised, the liver will be affected. This article reviews common causes of liver injury as well as highlights key associations that should not be missed when diagnosing and managing children with liver disease. Becoming familiar with patterns of liver injury and arranging clues in the context of a thorough history and physical examination can help providers navigate the broad differential diagnosis of secondary liver disease. [Pediatr Ann. 2018;47(11):e458-e464.].
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Diego and Giorgina Vergani: The two hearts of translational autoimmunity. J Autoimmun 2016; 66:1-6. [DOI: 10.1016/j.jaut.2015.11.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 11/30/2015] [Indexed: 12/18/2022]
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Spectrum of Histomorphologic Findings in Liver in Patients with SLE: A Review. HEPATITIS RESEARCH AND TREATMENT 2014; 2014:562979. [PMID: 25136456 PMCID: PMC4130189 DOI: 10.1155/2014/562979] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/02/2014] [Accepted: 07/03/2014] [Indexed: 12/19/2022]
Abstract
Collagen vascular diseases (CVDs) like systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjogren syndrome (SS), and scleroderma are immunologically mediated disorders that typically have multisystem involvement. Although clinically significant liver involvement is rare, liver enzyme abnormalities are common in these patients. The reported prevalence of hepatic involvement in SLE, histopathologic findings, and its significance is very variable in the existing literature. It is important to be familiar with the causes of hepatic involvement in SLE along with histomorphological features which aid in distinguishing hepatitis of SLE from other hepatic causes as they would alter the patient management and disease course. Histopathology of liver in SLE shows a wide morphological spectrum commonly due to a coexisting pathology. Drug induced hepatitis, viral etiology, and autoimmune overlap should be excluded before attributing the changes to SLE itself. Common histopathologic findings in SLE include fatty liver, portal inflammation, and vascular changes like hemangioma, congestion, nodular regenerative hyperplasia, arteritis, and abnormal vessels in portal tracts.
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Bessone F, Poles N, Roma MG. Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis. World J Hepatol 2014; 6:394-409. [PMID: 25018850 PMCID: PMC4081614 DOI: 10.4254/wjh.v6.i6.394] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Revised: 03/08/2014] [Accepted: 05/14/2014] [Indexed: 02/06/2023] Open
Abstract
Systemic lupus erythematosus (SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows: (1) immunological comorbilities (overlap syndromes); (2) non-immunological comorbilities associated to SLE; and (3) a putative liver damage induced by SLE itself, referred to as "lupus hepatitis". In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus (e.g., autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis.
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Affiliation(s)
- Fernando Bessone
- Fernando Bessone, Natalia Poles, Gastroenterology and Hepatology Department, University of Rosario School of Medicine, Rosario 2000, Argentina
| | - Natalia Poles
- Fernando Bessone, Natalia Poles, Gastroenterology and Hepatology Department, University of Rosario School of Medicine, Rosario 2000, Argentina
| | - Marcelo G Roma
- Fernando Bessone, Natalia Poles, Gastroenterology and Hepatology Department, University of Rosario School of Medicine, Rosario 2000, Argentina
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De Santis M, Crotti C, Selmi C. Liver abnormalities in connective tissue diseases. Best Pract Res Clin Gastroenterol 2013; 27:543-51. [PMID: 24090941 DOI: 10.1016/j.bpg.2013.06.016] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Accepted: 06/28/2013] [Indexed: 01/31/2023]
Abstract
The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd-Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.
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Affiliation(s)
- Maria De Santis
- Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy; BIOMETRA Department, University of Milan, Milan, Italy
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Jiménez-Encarnación E, Ríos G, Muñoz-Mirabal A, Vilá LM. Euforia-induced acute hepatitis in a patient with scleroderma. BMJ Case Rep 2012; 2012:bcr-2012-006907. [PMID: 23257938 DOI: 10.1136/bcr-2012-006907] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Euforia, a supplement containing a variety of natural ingredients, is widely used as an antioxidant and anti-inflammatory formula. It is not approved by the US Food and Drug Administration and its side effects are unknown. We report a 45-year-old woman with limited systemic sclerosis who presented with jaundice and marked elevation of serum transaminases. One month before, she started taking Euforia juice. A liver biopsy disclosed submassive hepatocellular necrosis with histopathological changes consistent with toxic hepatitis. The patient's symptoms resolved with cessation of Euforia. Six months later, she persisted with abnormal liver function tests, but these resolved 18 months after discontinuation of Euforia. The mechanism by which Euforia causes liver injury is unknown. Some ingredients contained in this supplement (green tea, Aloe vera, noni and goji) are linked to hepatic injury. To our knowledge, this is the first report of hepatotoxicity associated with Euforia.
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Affiliation(s)
- Esther Jiménez-Encarnación
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
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Huang D, Aghdassi E, Su J, Mosko J, Hirschfield GM, Gladman DD, Urowitz MB, Fortin PR. Prevalence and risk factors for liver biochemical abnormalities in Canadian patients with systemic lupus erythematosus. J Rheumatol 2011; 39:254-61. [PMID: 22174205 DOI: 10.3899/jrheum.110310] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To determine the prevalence of abnormal liver enzymes in patients with systemic lupus erythematosus (SLE) and whether further investigations were done, and the differences in SLE-related and/or metabolic factors in patients with and without liver biochemical abnormalities. METHOD Patients from the University of Toronto Lupus Clinic who met at least 4 of the American College of Rheumatology classification criteria for SLE and had 1.5 times the upper limit for aspartate transaminase or alanine transaminase on 2 consecutive visits within a 2-year period were matched with controls for age, sex, and SLE duration. Demographic, clinical, and laboratory data were extracted at the time of the first appearance of liver enzyme abnormality for the cases and at the reference point for the controls. RESULTS From the 1533 patients reviewed, 134 (8.7%) met the inclusion criteria. Thirty of these patients were evaluated by a hepatologist, 75 had imaging studies (41 were done specifically for liver investigation), and 13 had liver biopsies. Results based on these investigations showed 31 fatty livers, 35 cases of drug-induced hepatotoxicity, 10 autoimmune etiologies, and 3 cases of viral hepatitis. Compared to controls, cases were higher in body mass index, anti-dsDNA antibody, prevalence of hypertension, antiphospholipid syndrome, and use of immunosuppressive medication, especially azathioprine and methotrexate; they were lower in IgM. CONCLUSION Metabolic abnormalities such as obesity and hypertension and hepatotoxic effects of medication used to treat SLE may contribute more than SLE-related factors to liver biochemical abnormalities in patients with SLE.
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Affiliation(s)
- Darryl Huang
- Division of Health Care and Outcome Research, Toronto Western Research Institute, Toronto, Ontario, Canada
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Ohira H, Abe K, Takahashi A. Involvement of the liver in rheumatic diseases. Clin J Gastroenterol 2011; 5:9-14. [DOI: 10.1007/s12328-011-0271-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2011] [Accepted: 11/10/2011] [Indexed: 01/15/2023]
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