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Shah AA, Wigley FM. Overlooked Manifestations. SCLERODERMA 2024:587-611. [DOI: 10.1007/978-3-031-40658-4_38] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Cuomo G, Iandoli C, Galiero R, Caturano A, Di Vico C, Perretta D, Adamo PV, Ferrara R, Rinaldi L, Romano C, Sasso FC. Liver Involvement in Patients with Systemic Sclerosis: Role of Transient Elastography in the Assessment of Hepatic Fibrosis and Steatosis. Diagnostics (Basel) 2023; 13:diagnostics13101766. [PMID: 37238250 DOI: 10.3390/diagnostics13101766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/11/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023] Open
Abstract
Background Systemic sclerosis (SSc) is a rare, multisystemic disorder of connective tissue characterized by widespread inflammation, vascular abnormalities, and both skin and visceral organ fibrosis. Tissue fibrosis is the final phase of a complex biological process of immune activation and vascular damage. Objectives The aim of the study was to assess hepatic fibrosis and steatosis in SSc patients by transient elastography (TE). Methods Fifty-nine SSc patients fulfilling the 2013 ACR/EULAR classification criteria were recruited. Clinical and laboratory findings, modified Rodnan skin score (mRSS), activity index, videocapillaroscopy, echocardiography, and lung function data were analyzed. Liver stiffness (LS) was measured by transient elastography (TE), with 7 kPa used as the cut-off value for significant liver fibrosis. In addition, hepatic steatosis was evaluated by means of controlled attenuation parameter (CAP) findings. Specifically, CAP values ≥ 238 ≤ 259 dB/m were considered consistent with mild steatosis (S1), values ≥ 260 ≤ 290 dB/m were compatible with moderate steatosis (S2), and values ≥ 291 dB/m were indicative of severe steatosis (S3). Results The median age of patients was 51 years, with a median disease duration of 6 years. The median LS was 4.5 (2.9-8.3) kPa; 69.5% of patients had no evidence of fibrosis (F0); 27.1% displayed LS values between 5.2 and 7 kPa; and only 3.4% of patients had LS values > 7 kPa (F3). The median CAP value for liver steatosis was 223 dB/m (IQR: 164-343). Overall, 66.1% of patients did not show evidence of steatosis (CAP values < 238 dB/m); 15.2% showed values consistent with mild (S1) steatosis (CAP value ≥ 238 ≤ 259 dB/m); 13.5% had moderate (S2) steatosis (CAP value ≥ 260 ≤ 290 dB/m); and 5.1% were deemed to have severe steatosis (S3) due to CAP values ≥ 291 dB/m. Conclusions Although systemic sclerosis is associated with fibrosis of the skin and several organs, only 3.4% of our patient population showed evidence of marked liver fibrosis, which is the same prevalence as that expected in the general population. Therefore, fibrosis of the liver did not appear to be a significant concern in SSc patients, albeit moderate fibrosis could still be detected in a significant proportion of subjects. A prolonged follow-up may clarify whether liver fibrosis in SSc patients may still progress. Likewise, the prevalence of significant steatosis was low (5.1%) and depended on the same variables associated with fatty liver disease in the general population. TE was shown to be an easy and valuable method for detection and screening of hepatic fibrosis in SSc patients with no additional risk factors for liver disease and may be useful to assess the potential progression of liver fibrosis over time.
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Affiliation(s)
- Giovanna Cuomo
- Department of Precision Medicine, "Luigi Vanvitelli" University of Campania, 80138 Naples, Italy
| | - Carlo Iandoli
- Department of Precision Medicine, "Luigi Vanvitelli" University of Campania, 80138 Naples, Italy
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, "Luigi Vanvitelli" University of Campania, 80138 Naples, Italy
| | - Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, "Luigi Vanvitelli" University of Campania, 80138 Naples, Italy
| | - Claudio Di Vico
- Department of Precision Medicine, "Luigi Vanvitelli" University of Campania, 80138 Naples, Italy
| | - Danilo Perretta
- Department of Precision Medicine, "Luigi Vanvitelli" University of Campania, 80138 Naples, Italy
| | - Pier Vincenzo Adamo
- Department of Precision Medicine, "Luigi Vanvitelli" University of Campania, 80138 Naples, Italy
| | - Roberta Ferrara
- Department of Advanced Medical and Surgical Sciences, "Luigi Vanvitelli" University of Campania, 80138 Naples, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, "Luigi Vanvitelli" University of Campania, 80138 Naples, Italy
| | - Ciro Romano
- Department of Advanced Medical and Surgical Sciences, "Luigi Vanvitelli" University of Campania, 80138 Naples, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, "Luigi Vanvitelli" University of Campania, 80138 Naples, Italy
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Ahmed AM, Patel SR, Rajwana YR, Spira R. Clinical Outcomes and Inpatient Mortality Among Hospitalized Patients With Concomitant Autoimmune Hepatitis and Systemic Lupus Erythematosus. Cureus 2022; 14:e24981. [PMID: 35706720 PMCID: PMC9187263 DOI: 10.7759/cureus.24981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/23/2022] [Indexed: 12/03/2022] Open
Abstract
Background Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that is characterized by a broad disease spectrum, circulating autoantibodies, and elevated serum globulin levels. Systemic lupus erythematosus (SLE) is a chronic disease that is characterized by a high inflammatory state and is associated with multiorgan system involvement. Despite a well-known association between AIH and other autoimmune diseases, the literature is deficient on the associations between AIH-related outcomes and complications in SLE patients. This study aims to evaluate the effects of SLE on clinical outcomes and inpatient mortality in patients with AIH. Method The National Inpatient Sample (NIS) database was used to identify AIH-related hospitalizations from 2012 to 2014 using International Classification of Diseases Ninth Edition Revision (ICD-9) codes. Patients were divided into two groups, those with and without SLE. Primary outcomes were mortality, hospital charges, and length of stay (LOS). Secondary outcomes were complications associated with AIH: cirrhosis, gastrointestinal (GI) bleed, acute liver failure (ALF), cholangitis, pancreatitis, and sepsis. Chi-squared tests for categorical data and independent t-test for continuous data were used to compare outcomes. Multivariate analysis was performed to assess the primary outcomes after adjusting for confounding variables. Results There were 17,050 AIH-related hospitalizations from 2012 to 2014 and 1,115 patients had SLE. In patients with SLE and AIH, 1,035 were female with average age of 48.6. The average LOS was 6.3 days, mortality rate was 1.35%, and total hospital charges were $48,146. SLE was associated with a statistically significant lower mortality rate compared to the control. LOS, hospital cost, and CCI (Charlson Comorbidity Index) were not found to be significantly different. For secondary outcomes, SLE was statistically significant for having higher pancreatitis rates. SLE patients had statistically significant lower cholangitis, and ALF. Differences in complications such as sepsis and GI bleed were non-significant. Conclusion SLE is known to have a high inflammatory state so it was hypothesized that there would be higher rates of complications and a higher mortality rate in those with concomitant AIH. This study showed that the mortality rate was lower in SLE patients with lower rates of complications including ALF and cholangitis. We postulate that SLE patient outcomes are likely affected by the treatment regimen involved with SLE, including corticosteroids. This would provide an immunosuppressive state, limiting the autoreactivity cascade in AIH, in effect leading to better outcomes and a mortality benefit. This study identifies a lower mortality rate and lower complication rates in patients with AIH and SLE overlap as compared to patients with AIH alone and future studies are needed to confirm these associations.
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Clinical Relevance of Liver Involvement in the Clinical Course of Systemic Sclerosis. J Clin Med 2022; 11:jcm11040966. [PMID: 35207242 PMCID: PMC8879679 DOI: 10.3390/jcm11040966] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 02/07/2022] [Accepted: 02/09/2022] [Indexed: 02/05/2023] Open
Abstract
Liver involvement in systemic sclerosis (SSc) is rare. We evaluated the prevalence of liver fibrosis and hepatic autoimmunity in SSc patients in a retrospective observational cohort (97 SSc or mixed connective tissue disease with sclerodermic manifestations patients undergoing transient elastography, evaluating liver stiffness (LS) and controlled attenuation parameter (CAP), due to clinical indications along with biochemistry assessments and major antibodies associated to liver autoimmunity). Among them, 11 had LS ≥ 7.5 kPa and 5 showed an LS compatible with cirrhosis (LS ≥ 12.5 kPa). Predictors of LS ≥ 7.5 fibrosis were alcohol consumption (>14 or >7 alcoholic units/week for men and women, respectively), waist circumference (>102 or >88 cm for men and women, respectively), elevated alkaline phosphatase, and anti-La and anti-mitochondrial antibody (AMA) positivity. Six patients had CAP values compatible with severe steatosis (≥280 dB/m). Waist circumference, body mass index and diabetes mellitus were significant predictors of steatosis. Out of 97 patients, 19 were positive for AMA, 4 for anti-Sp100, 1 for anti-Gp210 and 7 were diagnosed with primary biliary cholangitis. Among SSc patients, hepatic fibrosis biomarkers and AMA prevalence are relatively high, suggesting the opportunity of performing a transient elastography and a screening for hepatic autoimmunity at diagnosis and/or during disease progression.
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Clinical Characteristics of Systemic Lupus Erythematosus with Cirrhosis. J Immunol Res 2020; 2020:2156762. [PMID: 32537465 PMCID: PMC7260626 DOI: 10.1155/2020/2156762] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Revised: 04/24/2020] [Accepted: 05/12/2020] [Indexed: 12/14/2022] Open
Abstract
Aim Cirrhosis is rare in systemic lupus erythematosus (SLE) patients with a poor prognosis. This study is aimed at retrospectively analyzing our single-center experience to explore the characteristics of cirrhosis in SLE patients. Methods SLE patients with cirrhosis from 2012 to 2019 were enrolled. SLE diagnosis was rigorously confirmed by a medical record review according to the revised 1997 American College of Rheumatology classification criteria for SLE. The diagnosis of liver cirrhosis was based on a combination of clinical, laboratory, and imaging criteria features. We conducted a case-control study in SLE patients complicated with the cirrhosis group and the age-, sex-, and entry-time-matched noncirrhosis group. Results A total of 21 patients with SLE cirrhosis were enrolled, 3 males and 18 females. The median age at the time of cirrhosis diagnosis was 47.3 ± 4.0 years, and the mean disease duration of SLE before cirrhosis was 4.7 ± 1.0 years. The most common initial presentation was the involvement of the hematological system in 9 patients and then skin and mucosal involvement in 5 patients, arthritis in 4 patients, and nephritis in 3 patients. Patients with cirrhosis had a significantly higher rate of hematological system involvement (thrombocytopenia and leukopenia) and worse liver function; a higher level of immune globulin G had higher mortality (p < 0.05) than patients without cirrhosis. Conclusions Cirrhosis is a rare and severe subtype of SLE with a poor prognosis. Those patients with hematological system involvement and impaired liver function should be paid more attention.
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Han HS, Ahn GR, Kim HJ, Park KY, Li K, Seo SJ. Diffuse Systemic Sclerosis in a Patient with Primary Biliary Cirrhosis and Autoimmune Hepatitis Overlap Syndrome: A Case Report. Ann Dermatol 2020; 32:69-73. [PMID: 33911712 PMCID: PMC7992632 DOI: 10.5021/ad.2020.32.1.69] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 02/05/2019] [Accepted: 02/26/2019] [Indexed: 11/08/2022] Open
Abstract
Systemic sclerosis (SSc) is a chronic systemic disease of unknown etiology characterized by vasculopathy, excessive accumulation of extracellular matrix, and fibrosis of the skin and other internal organs. Although its etiology remains elusive, approximately one third of SSc patients presents with additional autoimmune disease, which suggests that an autoimmune mechanism is a major component of the underlying pathophysiology. On the other hand, primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) are two main autoimmune liver diseases. A 41-year-old female previously diagnosed with PBC/AIH overlap syndrome presented with multiple, painful brownish to erythematous firm patches on the hands, arms, axillae, neck, abdomen, and thighs. Laboratory work-up yielded positive results for anti-nuclear antibody, anti-Ro/Sjögren's-syndrome-related antigen A autoantibodies, and perinuclear anti-neutrophil cytoplasmic antibodies while punch biopsy of her left hand showed characteristics that are consistent with scleroderma. Herein, we report the first case of a patient with diffuse cutaneous SSc and concurrent PBC/AIH overlap syndrome and suggest that this coexistence of multiple autoimmune diseases is not a coincidence but rather that a common autoimmune pathogenesis may exist.
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Affiliation(s)
- Hye Sung Han
- Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea
| | - Ga Ram Ahn
- Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea
| | - Hyung Joon Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Kui Young Park
- Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea
| | - Kapsok Li
- Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea
| | - Seong Jun Seo
- Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea
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Guo R, Zhang T, Meng X, Lin Z, Lin J, Gong Y, Liu X, Yu Y, Zhao G, Ding X, Chen X, Lu L. Lymphocyte mass cytometry identifies a CD3-CD4+ cell subset with a potential role in psoriasis. JCI Insight 2019; 4:125306. [PMID: 30747724 DOI: 10.1172/jci.insight.125306] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Accepted: 02/05/2019] [Indexed: 02/05/2023] Open
Abstract
Psoriasis (PS) is a systemic, immune-mediated inflammatory disorder. However, the whole lymphocyte compartment and the potential pathologies of PS have not been fully characterized. In the present study, we examined whole lymphocyte subsets and signal transduction proteins using high-dimensional single-cell mass cytometry and a bioinformatics pipeline for an in-depth characterization of the immune cell subsets and protein profiles involved in pathways in the peripheral blood of patients with PS. We identified 15 major immune cell populations in T cell lineages and characterized various CD3+CD4+ Th and CD3+CD8+ T cytotoxic cell populations simultaneously across 24 leukocyte markers and 7 proteins related to the signal transduction pathways. High-dimensional analysis identified 3 new subsets that are abundant in PS peripheral blood, resembling CD3-CD4+ lymphoid tissue inducer cells, Tc17 cells, and CD8+CXCR3+ Tregs. We confirmed the CD3-CD4+ cells, and their features and functions, in an independent PS cohort. The use of single-cell mass cytometry allows systemic-level characterization of lymphocyte subpopulations and dysregulated signaling pathways in the blood of patients with PS, identifying abnormalities of different immune cell subsets. We validated that the CD3-CD4+ cells had elevated OX40 and decreased FRA2 expression, which were positively associated with the PS area and severity index.
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Affiliation(s)
- Ruru Guo
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ting Zhang
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Xinyu Meng
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhen Lin
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinran Lin
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yu Gong
- Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | | | - Yuetian Yu
- Department of Critical Care Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guilin Zhao
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Xianting Ding
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaoxiang Chen
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Liangjing Lu
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Haridy J, Sood S, Nicoll A. Reply. Clin Gastroenterol Hepatol 2018; 16:149-150. [PMID: 28893680 DOI: 10.1016/j.cgh.2017.08.051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Revised: 08/31/2017] [Accepted: 08/31/2017] [Indexed: 02/07/2023]
Affiliation(s)
- James Haridy
- Department of Gastroenterology and Hepatology, University of Melbourne, The Royal Melbourne Hospital, Melbourne, Australia
| | - Siddharth Sood
- Department of Gastroenterology and Hepatology, University of Melbourne, The Royal Melbourne Hospital, Melbourne, Australia
| | - Amanda Nicoll
- Department of Gastroenterology and Hepatology, University of Melbourne, The Royal Melbourne Hospital, Melbourne, Australia; Department of Gastroenterology, Eastern Health, Melbourne, Australia; Monash University, Melbourne, Australia
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Lally EV, Shah AA, Wigley FM. Overlooked Manifestations. SCLERODERMA 2017:533-550. [DOI: 10.1007/978-3-319-31407-5_38] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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10
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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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Vierling JM. Autoimmune Hepatitis and Overlap Syndromes: Diagnosis and Management. Clin Gastroenterol Hepatol 2015; 13:2088-108. [PMID: 26284592 DOI: 10.1016/j.cgh.2015.08.012] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Revised: 08/11/2015] [Accepted: 08/11/2015] [Indexed: 12/14/2022]
Affiliation(s)
- John M Vierling
- Departments of Medicine and Surgery, Baylor College of Medicine, Baylor-St Luke's Medical Center, Houston, Texas.
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Clinical Characteristics of Concomitant Systemic Lupus Erythematosus and Primary Biliary Cirrhosis: A Literature Review. J Immunol Res 2015; 2015:713728. [PMID: 26090497 PMCID: PMC4452083 DOI: 10.1155/2015/713728] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Accepted: 01/17/2015] [Indexed: 12/14/2022] Open
Abstract
Although autoimmune diseases often coexist, concomitant cases of systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) are uncommon. In this review paper, 34 cases of SLE with concomitant PBC found in English and Japanese scientific literature and Japanese proceedings were reviewed and summarized, including cases with liver dysfunction complicated by SLE. Of the 34 reported concomitant cases of SLE and PBC, 97.1% (33/34) were females, and PBC was diagnosed initially in 69.0% (20/29), except for five cases in which both SLE and PBC were simultaneously diagnosed. Sjögren's syndrome was the most common autoimmune disease complicating concomitant SLE and PBC (23.5%, 8/34). Five deaths have been reported: two elderly patients died of liver failure because of the worsening of PBC, and another two patients died from pulmonary infection associated with SLE pharmacotherapy. It is uncertain whether concomitant cases occur by chance or share a common immunological or genetic basis.
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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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Abstract
BACKGROUND Primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome is used to describe the coexistence of both diseases, with either a sequential or a simultaneous presentation in the same patient. Available studies have focused on the simultaneous form, whereas there is limited information on sequential PBC-AIH. We carried out a retrospective study of patients who sequentially developed PBC-AIH overlap syndrome. METHODS The medical data of 1065 patients diagnosed with PBC (n=483) and AIH (n=582) were retrospectively analyzed. RESULTS A sequential development of PBC-AIH was observed in 19 (1.8%) patients after a mean of 6.5 (1-14) years of follow-up. AIH developed in 12 (2.5%) PBC patients, whereas PBC occurred in seven (1.2%) patients with AIH. The baseline serologic and histological findings of patients who developed PBC-AIH were similar to those of patients with typical PBC or AIH. Eighteen patients were treated with a combination of ursodeoxycholic acid (UDCA) and immunosuppression after the diagnosis of PBC-AIH was established. One patient showed a spontaneous resolution of hepatitic flare under UDCA therapy. Biochemical remission was achieved in 16 patients, whereas three progressed to decompensated cirrhosis and required liver transplantation. CONCLUSION The sequential overlap of PBC-AIH can occur during the follow-up of patients with pure PBC or AIH. In our cohort, we could not identify any factors that predicted the development of this rare condition. The combination of UDCA and immunosuppression seems to be an appropriate therapy in the setting of PBC-AIH.
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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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Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome developed in a patient with vitiligo and Hashimoto thyroiditis. Eur J Gastroenterol Hepatol 2013. [PMID: 23196727 DOI: 10.1097/meg.0b013e328359493e] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Efe C. Drug induced autoimmune hepatitis and TNF-α blocking agents: is there a real relationship? Autoimmun Rev 2012; 12:337-9. [PMID: 22841985 DOI: 10.1016/j.autrev.2012.03.010] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2012] [Accepted: 03/02/2012] [Indexed: 02/06/2023]
Abstract
Hepatotoxicity is an expected side effect of tumour necrosis factor-α (anti-TNF-α) blocking agents including, infliximab, etanercept and adalimumab. Although mild to moderate elevations of liver enzymes have been recognised after the use of these agents, severe hepatitis is rarely reported. Reactivation of viral hepatitis and drug induced liver injury is two main causes of liver dysfunction in these patients. A broad spectrum, ranging from minor immunological alterations to systemic autoimmune disease, has been reported during treatment with anti-TNF-α. Therefore, in recent studies TNF-α blocking agents have been considered a potential cause of drug induced autoimmune hepatitis. Taking into account the advances in the field of hepatology, this review summarizes the general characteristics of anti-TNF-α induced liver injury and autoimmune hepatitis.
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Affiliation(s)
- Cumali Efe
- Hacettepe University, Department of Gastroenterology, Turkey.
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Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome and associated extrahepatic autoimmune diseases. Eur J Gastroenterol Hepatol 2012; 24:531-4. [PMID: 22465972 DOI: 10.1097/meg.0b013e328350f95b] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AIM To assess the prevalence of concurrent extrahepatic autoimmune diseases in patients with autoimmune hepatitis (AIH)/primary biliary cirrhosis (PBC) overlap syndrome and applicability of the 'mosaic of autoimmunity' in these patients. METHODS The medical data of 71 AIH/PBC overlap patients were evaluated for associated autoimmune diseases. RESULTS In the study population, 31 (43.6%) patients had extrahepatic autoimmune diseases, including autoimmune thyroid diseases (13 patients, 18.3%), Sjögren syndrome (six patients, 8.4%), celiac disease (three patients, 4.2%), psoriasis (three patients, 4.2%), rheumatoid arthritis (three patients, 4.2%), vitiligo (two patients, 2.8%), and systemic lupus erythematosus (two patients, 2.8%). Autoimmune hemolytic anemia, antiphospholipid syndrome, multiple sclerosis, membranous glomerulonephritis, sarcoidosis, systemic sclerosis, and temporal arteritis were identified in one patient each (1.4%). A total of 181 autoimmune disease diagnoses were found in our patients. Among them, 40 patients (56.4%) had two, 23 (32.3%) had three, and eight (11.3%) had four diagnosed autoimmune diseases. CONCLUSION A large number of autoimmune diseases were associated with AIH/PBC overlap patients. Therefore, extended screening for existing autoimmune diseases during the routine assessment of these patients is recommended. Our study suggests that the concept of 'mosaic of autoimmunity' is a valid clinical entity that is applicable to patients with AIH/PBC overlap syndrome.
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Abstract
Autoimmune hepatitis is a chronic liver disease characterized by elevated aminotransferase levels, autoantibodies, increased γ-globulin or IgG levels and biopsy evidence of interface hepatitis. Recent advances include new practice guidelines that redefine criteria for remission to require complete biochemical and histological normalization on therapy; comparisons between the revised original and simplified diagnostic scoring systems; refined characterization of autoantibodies and their diagnostic performance parameters; proof of the safety and efficacy of combination budesonide and azathioprine therapy for non-cirrhotic patients; scrutiny of overlap syndromes; further analyses of the outcomes of orthotopic liver transplantation and the diagnosis and treatment of recurrent and de novo autoimmune hepatitis after transplantation. Anticipated consequences of the application of the new definition of therapeutic remission include a reduction in the proportion of patients achieving remission with conventional immunosuppression regimens and a corresponding increase in the need for alternative therapies.
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Piga M, Vacca A, Porru G, Garau P, Cauli A, Mathieu A. Two different clinical subsets of lupus hepatitis exist. Mimicking primary autoimmune liver diseases or part of their spectrum? Lupus 2011; 20:1450-1. [PMID: 21951946 DOI: 10.1177/0961203311411352] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Selmi C, De Santis M, Gershwin ME. Liver involvement in subjects with rheumatic disease. Arthritis Res Ther 2011; 13:226. [PMID: 21722332 PMCID: PMC3218873 DOI: 10.1186/ar3319] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The liver is often overlooked as a target organ, with pathology either secondary to an underlying disease or due to the toxicity of therapies and the medical complications of extrahepatic diseases. It is thus important for the clinical rheumatologist to be aware of the diagnostic procedure to monitor liver injury. Indeed, systemic rheumatologic diseases may be associated with liver abnormalities secondary to the presence of a coexisting autoimmune liver disease (particularly primary biliary cirrhosis or autoimmune hepatitis), the direct involvement of the liver parenchyma, or the impact of medical treatments (particularly methotrexate) on the liver. In addition, the rheumatologist should be aware of the impact of immunosuppressive agents on underlying viral infections, particularly viral hepatitis. We review herein the data on the role of the liver in the clinical management of systemic rheumatic diseases.
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Affiliation(s)
- Carlo Selmi
- Department of Medicine and Autoimmunity and Metabolism Unit, IRCCS-Istituto Clinico Humanitas, University of Milan, via. A. Manzoni 56, 20089 Rozzano (MI), Italy
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Efe C, Purnak T, Ozaslan E, Ozbalkan Z, Karaaslan Y, Altiparmak E, Muratori P, Wahlin S. Autoimmune liver disease in patients with systemic lupus erythematosus: a retrospective analysis of 147 cases. Scand J Gastroenterol 2011; 46:732-7. [PMID: 21348808 DOI: 10.3109/00365521.2011.558114] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE We aimed to investigate the characteristics of autoimmune liver disease (AILD) developed in patients with systemic lupus erythematosus (SLE), including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and the AIH/PBC overlap syndrome. We also evaluated the accuracy of diagnostic criteria and scoring systems for AILD in SLE. METHODS A retrospective analysis of patients attending the rheumatology and gastroenterology clinics in Ankara, Turkey, between 1999 and 2010. SLE patients with elevated liver enzymes were investigated for liver diseases. RESULTS A total of 147 SLE patients were identified and 36 of them had liver enzyme abnormalities. AILD was diagnosed in 4.7% of all SLE patients, in 19.4% of those with elevated liver enzymes. Of patients with liver enzyme abnormalities, 72.3% fulfilled the criteria for AIH proposed by the International Autoimmune Hepatitis Group (IAIHG), whereas 66.7% had AIH by using the simplified criteria. Yet, only 13.8% of these patients had liver biopsy findings consistent with AIH. Patients with AILD were treated with conventional therapy including ursodeoxycholic acid, prednisolone, azathioprine or combinations of these. Treatment failure and subsequent advanced liver disease developed in one patient. CONCLUSIONS AILD may occur during the course of SLE. Due to biochemical similarities between AIH and SLE, AIH could be considered very probable by using both IAIHG scoring system and simplified criteria. For definitive diagnosis of AIH, liver biopsy should be performed in all SLE patients with chronic enzyme abnormalities. The response to therapy is favorable in these patients, and early diagnosis is important for preventing advanced liver disease.
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Affiliation(s)
- Cumali Efe
- Department of Internal Medicine, Ankara Numune Research and Education Hospital, Ankara, Turkey.
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Efe C, Purnak T, Ozaslan E, Ozbalkan Z. The importance of autoimmune hepatitis and primary biliary cirrhosis in patients with systemic lupus erythematosus. Lupus 2011; 20:112. [PMID: 21233150 DOI: 10.1177/0961203310389098] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Overlap syndrome and connective tissue diseases. Dig Dis Sci 2011; 56:268-9. [PMID: 21042852 DOI: 10.1007/s10620-010-1463-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Efe C, Purnak T, Ozaslan E. Systemic lupus erythematosus and autoimmune hepatitis. Rheumatol Int 2010; 31:419. [PMID: 20665028 DOI: 10.1007/s00296-010-1581-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2010] [Accepted: 07/14/2010] [Indexed: 11/28/2022]
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Efe C, Purnak T, Ozaslan E, Ozbalkan Z. Systemic sclerosis and autoimmune hepatitis. Clin Rheumatol 2010; 29:695. [PMID: 20373122 DOI: 10.1007/s10067-010-1440-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2010] [Accepted: 03/15/2010] [Indexed: 12/01/2022]
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