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Zeng X, Lv T, Li S, Chen S, Li B, Lu Z, Wang Y, Ou X, Zhao X, You H, Duan W, Jia J. Patients with AMA/anti-sp100/anti-gp210 Positivity and Cholestasis Can Manifest Conditions Beyond Primary Biliary Cholangitis. J Clin Transl Hepatol 2025; 13:200-206. [PMID: 40078201 PMCID: PMC11894394 DOI: 10.14218/jcth.2024.00374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 12/13/2024] [Accepted: 12/23/2024] [Indexed: 03/14/2025] Open
Abstract
Background and Aims The diagnostic value of primary biliary cholangitis (PBC)-specific antibodies in patients with elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels, and other identifiable causes, was unclear. Our study aimed to determine whether etiological treatments in PBC-specific antibody-positive patients could improve liver biochemical tests, thereby distinguishing them from individuals with PBC. Methods We enrolled patients who were positive for PBC-specific antibodies and elevated ALP and/or GGT levels but with other identifiable etiologies. Changes in liver biochemistry following non-ursodeoxycholic acid etiological treatments were monitored. Results A total of 155 patients with positive PBC-specific antibodies and elevated ALP and/or GGT levels due to non-PBC diseases were enrolled. Among them, 100 patients were diagnosed with non-PBC liver diseases, mainly metabolic-associated fatty liver disease, drug-induced liver injury, and autoimmune hepatitis. Additionally, 55 patients had non-liver diseases, predominantly connective tissue diseases. The median follow-up duration was 15.9 (4.7-25.6) months. Among 141 patients who completed follow-up after receiving etiological treatments, 85.1% (120/141) showed improvement in ALP and/or GGT levels, with 51.8% (73/141) achieving normalization of both ALP and GGT. However, 68 patients continued to exhibit elevated ALP and/or GGT, with 55 patients displaying isolated GGT elevation and 11 patients showing liver histological changes not consistent with PBC. Conclusions PBC-specific antibodies, along with elevated ALP and GGT levels, may occur in various non-PBC diseases. Etiological treatments may improve or even resolve cholestatic biochemistry. For these patients, initiating etiological treatment rather than immediately starting ursodeoxycholic acid therapy would be justified.
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Affiliation(s)
- Xin Zeng
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Tingting Lv
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Shuxiang Li
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Sha Chen
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Buer Li
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Zhijiao Lu
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Yu Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Xiaojuan Ou
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Xinyan Zhao
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Weijia Duan
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
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Lv H, Deng A, Chen Y, Su Z. Clinical Performance of the Line Immunoassay and Digital Liquid Chip Method for Detecting Autoimmune Liver Disease Autoantibodies. Arch Pathol Lab Med 2025; 149:271-275. [PMID: 38830630 DOI: 10.5858/arpa.2024-0057-oa] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/01/2024] [Indexed: 06/05/2024]
Abstract
CONTEXT.— The identification of autoantibodies associated with autoimmune liver disease (ALD) is crucial for diagnosis and management. Various laboratory methods have been introduced to detect autoantibody profiles. However, the variable performance of these assays may create challenges for clinicians and patients. OBJECTIVE.— To investigate the concordance rates and diagnostic performance of 2 commercially available assays, line immunoassay (LIA) and digital liquid chip method (DLCM), in patients with ALD. DESIGN.— A total of 291 serum samples were collected, consisting of 180 sera from patients with ALD and 111 sera from controls. The samples were detected through LIA and DLCM. The agreement and diagnostic performance of each assay were analyzed. RESULTS.— There was substantial to almost perfect agreement among prevalent autoantibodies (anti-mitochondrial antibody M2; antibodies against gp210, Sp100, and Ro52). Nevertheless, the Cohen κ coefficient of some uncommon autoantibodies (anti-LKM-1, anti-LC-1, and anti-SLA/LP) between the 2 methods was not ideal. LIA showed slightly better sensitivity, accuracy, and negative predictive value, while DLCM exhibited slightly higher specificity and positive predictive value. CONCLUSIONS.— LIA and DLCM demonstrated comparable performance for the detection of common ALD-related autoantibodies. LIA seemed to be more sensitive, while DLCM displayed more specificity. However, standardization of ALD autoantibody detection still faces challenges between these diverse detection systems. Comprehensive interlaboratory validation is essential to mitigate potential misunderstanding and confusion among patients and clinicians.
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Affiliation(s)
- Heye Lv
- From the Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, China (Lv, Su)
| | - Ao Deng
- the Department of Laboratory Medicine, West China Tianfu Hospital of Sichuan University, Chengdu, China (Deng, Chen)
| | - Yijun Chen
- the Department of Laboratory Medicine, West China Tianfu Hospital of Sichuan University, Chengdu, China (Deng, Chen)
| | - Zhenzhen Su
- From the Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, China (Lv, Su)
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Gambino CM, Agnello L, Calvaruso V, Giglio RV, Capodicasa L, Scazzone C, Candore G, Del Ben F, Di Marco V, Ciaccio M. Prevalence and heterogeneity of antinuclear antibody patterns in adult Italian patients with autoimmune liver diseases: Our experience. Clin Chim Acta 2025; 566:120037. [PMID: 39528068 DOI: 10.1016/j.cca.2024.120037] [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: 10/17/2024] [Revised: 11/08/2024] [Accepted: 11/08/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND AND AIM This study aims to explore the clinical significance of antinuclear antibodies (ANA) patterns in liver diseases. MATERIALS AND METHODS We included 396 patients with a request for ANA testing for suspected autoimmune liver disease (AILD). For each patient, we collected demographical, clinical, and laboratory data. RESULTS Among the patients, 33% had AILD, predominantly aiutoimmune hepatitis (AIH). The AC1 pattern was significantly more prevalent in AIH patients, while the AC21 pattern was strongly associated with primary biliary cholangitis (PBC). AC4-AC5 patterns were less frequent in AIH and PBC patients but more common in non-alcoholic hepatitis. Elevated alkaline phosphatase and gamma-glutamyl transferase levels were observed in AILD patients with AC11, AC12, and AC21 patterns. CONCLUSIONS These findings highlight the different distribution of ANA patterns in liver diseases, with specific patterns showing strong associations with distinct liver conditions.
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Affiliation(s)
- Caterina Maria Gambino
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy; Department of Laboratory Medicine, University Hospital "P. Giaccone", Palermo, Italy
| | - Luisa Agnello
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Vincenza Calvaruso
- Section of gastroenterology and Hepatology, Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Rosaria Vincenza Giglio
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy; Department of Laboratory Medicine, University Hospital "P. Giaccone", Palermo, Italy
| | - Luigi Capodicasa
- Section of gastroenterology and Hepatology, Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Concetta Scazzone
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Giuseppina Candore
- Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Fabio Del Ben
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO)-IRCCS, Aviano, Italy
| | - Vito Di Marco
- Section of gastroenterology and Hepatology, Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Marcello Ciaccio
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy; Department of Laboratory Medicine, University Hospital "P. Giaccone", Palermo, Italy.
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Sasai T, Ishikawa Y, Nakashima R, Isayama T, Tanizawa K, Handa T, Shirakashi M, Hiwa R, Tsuji H, Kitagori K, Akizuki S, Yoshifuji H, Mimori T, Morinobu A. Anti-aminoacyl tRNA synthetase antibodies showing the discrepancy between enzyme-linked immunosorbent assay and RNA-immunoprecipitation. Immunol Med 2024; 47:166-175. [PMID: 38488763 DOI: 10.1080/25785826.2024.2328918] [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: 11/07/2023] [Accepted: 03/06/2024] [Indexed: 08/23/2024] Open
Abstract
Anti-aminoacyl-tRNA synthetase (ARS) antibodies are myositis-specific antibodies associated with anti-synthetase syndrome (ASSD). Some patients are positive for anti-ARS antibodies on enzyme-linked immunosorbent assay (ELISA) but negative on RNA-immunoprecipitation (RNA-IP) (the gold standard method). Whether these patients should be considered truly positive for anti-ARS antibodies remains unclear. Therefore, we investigated the clinical characteristics of these patients and verified the authenticity of their anti-ARS positivity. Patients who were positive for anti-ARS antibodies on ELISA were divided into the non-discrepant (positive on RNA-IP, n = 52) and discrepant (negative on RNA-IP, n = 8) groups. Patient clinical characteristics were compared between the groups. For each positive individual, the authenticity of anti-ARS antibody positivity on ELISA was cross-examined using protein-IP and western blotting. All patients in the discrepant group had lung involvement, including five (63%) with interstitial lung disease. The overall survival time was significantly lower in the discrepant group than in the non-discrepant group (p < 0.05). Validation tests confirmed the presence of anti-ARS antibodies in the sera of the discrepant group but indicated different reactivity from typical anti-ARS antibodies. In conclusion, some anti-ARS antibodies are detected by ELISA but not RNA-IP. Such anti-ARS antibody discrepancies need further elucidation to attain validation of the diagnostic process in ASSD.
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Affiliation(s)
- Tsuneo Sasai
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yuki Ishikawa
- Laboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan
| | - Ran Nakashima
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Takuya Isayama
- Medical & Biological Laboratories Co., Ltd, Nagoya, Japan
| | - Kiminobu Tanizawa
- Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tomohiro Handa
- Department of Advanced Medicine for Respiratory Failure, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Mirei Shirakashi
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Ryosuke Hiwa
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hideaki Tsuji
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Koji Kitagori
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shuji Akizuki
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hajime Yoshifuji
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | | | - Akio Morinobu
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Zhang HP, Zhou Z, Chen K, Xiong LF, Wu J, Jin L. Primary biliary cholangitis has causal effects on systemic rheumatic diseases: a Mendelian randomization study. BMC Gastroenterol 2024; 24:294. [PMID: 39210292 PMCID: PMC11360496 DOI: 10.1186/s12876-024-03319-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 07/05/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND An association has been observed between primary biliary cholangitis (PBC) and systemic rheumatic diseases (SRDs) in observational studies, however the exact causal link remains unclear. We aimed to evaluate the causal effects of PBC on SRDs through Mendelian randomization (MR) analysis. METHODS The genome-wide association study (GWAS) summary data were obtained from MRC IEU OpenGWAS and FinnGen databases. Independent genetic variants for PBC were selected as instrumental variables. Inverse variance weighted was used as the main approach to evaluate the causal effects of PBC on Sjögren syndrome (SS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), mixed connective tissue disease (MCTD) and polymyositis (PM). Horizontal pleiotropy and heterogeneity were measured by MR‒Egger intercept test and Cochran's Q value, respectively. RESULTS PBC had causal effects on SS (OR = 1.177, P = 8.02e-09), RA (OR = 1.071, P = 9.80e-04), SLE (OR = 1.447, P = 1.04e-09), SSc (OR = 1.399, P = 2.52e-04), MCTD (OR = 1.306, P = 4.92e-14), and PM (OR = 1.416, P = 1.16e-04). Based on the MR‒Egger intercept tests, horizontal pleiotropy was absent (all P values > 0.05). The robustness of our results was further enhanced by the leave-one-out method. CONCLUSIONS Our research has provided new insights into PBC and SRDs, indicating casual effects on various SRDs.
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Affiliation(s)
- Hai-Ping Zhang
- Department of Gastroenterology, Hubei NO. 3 People's Hospital of Jianghan University, Wuhan, 430000, China
| | - Zhe Zhou
- Department of Radiology, The Affiliated Hospital of Wuhan Sports University, Wuhan, 430079, China
| | - Ke Chen
- Department of Gastroenterology, Hubei NO. 3 People's Hospital of Jianghan University, Wuhan, 430000, China
| | - Li-Fen Xiong
- Department of Gastroenterology, Hubei NO. 3 People's Hospital of Jianghan University, Wuhan, 430000, China
| | - Jun Wu
- Department of Gastroenterology, Hubei NO. 3 People's Hospital of Jianghan University, Wuhan, 430000, China
| | - Lei Jin
- Department of Gastroenterology, Hubei NO. 3 People's Hospital of Jianghan University, Wuhan, 430000, China.
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Drazilova S, Koky T, Macej M, Janicko M, Simkova D, Tsedendamba A, Komarova S, Jarcuska P. Pruritus, Fatigue, Osteoporosis and Dyslipoproteinemia in Pbc Patients: A Clinician’s Perspective. GASTROENTEROLOGY INSIGHTS 2024; 15:419-432. [DOI: 10.3390/gastroent15020030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2025] Open
Abstract
In this review article, we summarize the most common clinical manifestations of Primary biliary cholangitis (PBC): pruritus, fatigue, osteoporosis, and dyslipoproteinemia and discuss their impact of the patients’ quality of life. More than half of PBC patients suffer from pruritus or fatigue at the time of diagnosis. We discuss the pathophysiological aspects of the PBC clinical manifestations and treatment options. The pathophysiology of pruritus and fatigue is not adequately elucidated, but IL-31 is associated with the severity of pruritus and could be used to objectify the subjective reporting by questionnaires. Although PBC patients suffer from atherogenic dyslipidemia, they do not seem to have a higher cardiovascular risk; however, this observation needs to be clarified by further clinical studies. The second-line of PBC treatment affects pruritus severity: Obeticholic acid (OCA) worsens pruritus while fibrates improve it. Itching can be alleviated by both non-pharmacological and pharmacological approach, however the are multiple barriers to pharmacological treatment. There is no adequate treatment for fatigue today. Treatment of osteoporosis and dyslipidemia is similar for non-PBC patients; stage of liver disease should be considered in treatment. Further research to clarify the pathophysiology and to eventually discover an effective treatment to improve survival and quality of life (especially pruritus and fatigue) in PBC patients is needed.
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Affiliation(s)
- Sylvia Drazilova
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Tomas Koky
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Marian Macej
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Martin Janicko
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Dagmar Simkova
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine IKEM, Videnska 1921, 140 21 Prague, Czech Republic
| | - Ariunzaya Tsedendamba
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Slavomira Komarova
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Peter Jarcuska
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
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Shurin MR, Wheeler SE. Clinical Significance of Uncommon, Non-Clinical, and Novel Autoantibodies. Immunotargets Ther 2024; 13:215-234. [PMID: 38686351 PMCID: PMC11057673 DOI: 10.2147/itt.s450184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 04/17/2024] [Indexed: 05/02/2024] Open
Abstract
Autoantibodies are a common mark of autoimmune reaction and their identification in the patients' serum, cerebrospinal fluid, or tissues is generally believed to represent diagnostic or prognostic biomarkers of autoimmune diseases or autoinflammatory conditions. Traditionally, autoantibody testing is an important part of the clinical examination of suspected patients, and in the absence of reliable T cell tests, characterization of autoantibody responses might be suitable in finding causes of specific autoimmune responses, their strength, and sometimes commencement of autoimmune disease. Autoantibodies are also useful for prognostic stratification in clinically diverse groups of patients if checked repeatedly. Antibody discoveries are continuing, with important consequences for verifying autoimmune mechanisms, diagnostic feasibility, and clinical management. Adding newly identified autoantibody-autoantigen pairs to common clinical laboratory panels should help upgrade and harmonize the identification of systemic autoimmune rheumatic disorders and other autoimmune conditions. Herein, we aim to summarize our current knowledge of uncommon and novel autoantibodies in the context of discussing their validation, diagnostic practicability, and clinical relevance. The regular updates within the field are important and well justified.
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Affiliation(s)
- Michael R Shurin
- Division of Clinical Immunopathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Sarah E Wheeler
- Division of Clinical Immunopathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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Wu Z, Li H, Xu H, Feng F, Zhang F, Zhang S, Wang L, Li Y. ChIP-seq analysis found IL21R, a target gene of GTF2I-the susceptibility gene for primary biliary cholangitis in Chinese Han. Hepatol Int 2024; 18:509-516. [PMID: 37713154 DOI: 10.1007/s12072-023-10586-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 08/17/2023] [Indexed: 09/16/2023]
Abstract
AIMS Aimed to identify a new susceptibility gene associated with primary biliary cholangitis (PBC) in Chinese Han and investigate the possible mechanism of that gene in PBC. METHODS A total of 466 PBC and 694 healthy controls (HC) were included in our study, and genotyping GTF2I gene variants by Sequenom. CD19 + B cells were isolated for Chromatin immunoprecipitation sequencing (ChIP-seq). Additionally, MEME-ChIP was utilized to perform searches for known motifs and de novo motif discovery. The GTF2I ChIP-seq of hematopoietic cell line (K562) results were obtained from ENCODE (GSE176987, GSE177691). The Genomic HyperBrowser was used to determine overlap and hierarchal clustering between ours and ENCODE datasets. RESULTS The frequency of the rs117026326 variant T allele was significantly higher in PBC patients than that in HC (20.26% compared with 13.89%, Pc = 1.09E-04). Furthermore, we observed an elevated proportion of GTF2I binding site located in the upstream and 5' UTR of genes in PBC in comparison with HC. Additionally, an in-depth analysis of IL21R region revealed that GTF2I might bind to the IL21R promoter to regulate the expression of the IL21R, with four peaks of GTF2I binding sites, including three increased binding sites in upstream, one increased binding site in 5' UTR. Motif analysis by MEME-ChIP uncovered five significant motifs. A significant overlap between our ChIP and GSE176987, GSE17769 were found by the Genomic HyperBroswer. CONCLUSIONS Our study confirmed that GTF2I was associated with PBC in Chinese Han. Furthermore, our gene function analysis indicated that IL21R may be the target gene regulated by GTF2I.
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Affiliation(s)
- Ziyan Wu
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China
| | - Haolong Li
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China
| | - Honglin Xu
- Department of Rheumatology and Clinical Immunology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Futai Feng
- Department of Rheumatology and Clinical Immunology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Fengchun Zhang
- Department of Rheumatology and Clinical Immunology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Shulan Zhang
- Department of Rheumatology and Clinical Immunology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
| | - Li Wang
- Department of Rheumatology and Clinical Immunology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
| | - Yongzhe Li
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
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Nejad SEM, Heiat M, Javanbakht M, Alavian SM, Haris MAA. Evaluation of autoimmune liver disease natural history in patients referred to Middle East Liver Diseases (MELD) center. BMC Gastroenterol 2024; 24:17. [PMID: 38178070 PMCID: PMC10768354 DOI: 10.1186/s12876-023-03105-7] [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: 07/08/2023] [Accepted: 12/19/2023] [Indexed: 01/06/2024] Open
Abstract
BACKGROUND Autoimmune liver diseases (AILD) are increasing and common forms of chronic liver disease (CLD) with different clinical responses and characteristics which can result in cirrhosis. This study aimed to investigate the natural history and characteristics of AILD in an Iranian population. METHODS Patients with AILD [Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and Overlap Syndrome (OS)] referred to Middle East Liver Diseases (MELD) center, Tehran, Iran, between January 2002 and December 2022 were included in this retrospective cohort study. The main features of natural history (the trends of liver functional tests (LFT), Auto-Antibodies, response to treatment and cirrhotic status) along with demographic data were studied. RESULTS Two hundred sixty-five patients (160 (60.4%) AIH, 37 (14.0%) PBC, 20 (7.5%) PSC, 48 (18.1%) overlap syndrome) with a median follow-up time of 5 years (IQR 4 to 8 years) were included. Baseline laboratory tests revealed that patients with AIH exhibit elevated transaminase levels. However, patients suffering from PBC and PSC displayed increased alkaline phosphatase levels. Conversely, in overlap syndrome patients, both transaminases and alkaline phosphatase were observed at high levels. Autoantibodies represented themselves as important diagnostic markers for the AIH and PBC but not for PSC. The complete response occurred in 112 (70%) of and 28 (58.4%) patients with AIH and overlap syndrome respectively and 21 patients 11 (6.9%) of AIH and 10 (20.8%) of overlap syndrome) were non-responders. Other patients in these two categories were considered as insufficient responders. On the other side, 32 (91.9%) and 8 (40%) of patients with PBC and PSC biochemically responded to Ursodeoxycholic Acid (UDCA). Unpredictably, cirrhosis regression was observed in some AIH and PBC patients. CONCLUSION Appropriate medication management for AILD patients may leads to regression from cirrhosis and improvement of manifestations; while discontinuation of medication may cause relapses. However, patient suffering from PSC showed limited response to treatment.
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Affiliation(s)
- Seyed Erfan Mehdi Nejad
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mohammad Heiat
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mohammad Javanbakht
- Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Ali Abyazi Haris
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Jin Y, Wang M, Liu Y, Xu A. Antimitochondrial antibody associated with liver cirrhosis in patients with primary biliary cholangitis. Medicine (Baltimore) 2023; 102:e35617. [PMID: 37861502 PMCID: PMC10589553 DOI: 10.1097/md.0000000000035617] [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: 08/21/2023] [Accepted: 09/21/2023] [Indexed: 10/21/2023] Open
Abstract
Antimitochondrial antibody (AMA) serves as a serological marker for diagnosing primary biliary cholangitis (PBC). However, the association between AMA and prognosis for PBC patients remains unclear. The objective of this study was to investigate the relationship between AMA and cirrhosis in PBC patients. This retrospective study enrolled 225 PBC patients, including 127 with liver cirrhosis and 98 without cirrhosis. AMA was tested by indirect immunofluorescence (IIF) with rat kidney as the substrate. AMA-M2 and M2-3E were detected by line immunoassay (LIA). The overall positivity rate for AMA detection in PBC patients was 80.9%. The positivity rates of IIF-AMA, AMA-M2, and M2-3E were significantly higher in patients with liver cirrhosis than in those without cirrhosis (73.2% vs. 52.0%, 74.0% vs. 51.0%, and 80.3% vs. 60.2%, respectively). In multivariate logistic regression, IIF-AMA (OR: 3.05, 95% CI: 1.59-5.87), AMA-M2 (OR: 3.11, 95% CI: 1.61-6.01), and M2-3E (OR: 3.29, 95% CI: 1.63-6.66) remained significantly associated with an increased incidence of liver cirrhosis. Moreover, in multinomial logistic regression, IIF-AMA (compensated cirrhosis, OR: 3.55, 95% CI: 1.49-8.44; decompensated cirrhosis, OR: 2.86, 95% CI: 1.32-6.18), AMA-M2 (compensated cirrhosis, OR: 4.74, 95% CI: 1.94-11.58; decompensated cirrhosis, OR: 2.51, 95% CI: 1.19-5.33), and M2-3E (compensated cirrhosis, OR: 4.92, 95% CI: 1.74-13.96; decompensated cirrhosis, OR: 2.91, 95% CI: 1.28-6.64) were all found to be associated with different stages of liver cirrhosis. AMA was found to be associated with the occurrence of liver cirrhosis in PBC patients. Additionally, AMA was also related to different stages of liver cirrhosis, including compensated and decompensated cirrhosis.
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Affiliation(s)
- Yujiao Jin
- Department of Clinical Laboratory, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang, China
| | - Miaochan Wang
- Department of Clinical Laboratory, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang, China
| | - Yuan Liu
- Department of Clinical Laboratory, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang, China
| | - Aifang Xu
- Department of Clinical Laboratory, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang, China
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Zhu YJ, Li J, Liu YG, Jiang Y, Cheng XJ, Han X, Wang CY, Li J. Role of biochemical markers and autoantibodies in diagnosis of early-stage primary biliary cholangitis. World J Gastroenterol 2023; 29:5075-5081. [PMID: 37753365 PMCID: PMC10518739 DOI: 10.3748/wjg.v29.i34.5075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 07/15/2023] [Accepted: 08/25/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND Primary biliary cholangitis (PBC) is a chronic progressive autoimmune cholestatic disease. The main target organ of PBC is the liver, and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis. AIM To explore the clinical characteristics of early-stage PBC, identify PBC in the early clinical stage, and promptly treat and monitor PBC. METHODS The data of 82 patients with PBC confirmed by pathology at Tianjin Second People's Hospital from January 2013 to November 2021 were collected, and the patients were divided into stage I, stage II, stage III, and stage IV according to the pathological stage. The general data, serum biochemistry, immunoglobulins, and autoimmune antibodies of patients in each stage were retrospectively analyzed. RESULTS In early-stage (stages I + II) PBC patients, 50.0% of patients had normal alanine aminotransferase (ALT) levels, and 37.5% had normal aspartate aminotransferase (AST) levels. For the remaining patients, the ALT and AST levels were mildly elevated; all of these patients had levels of < 3 times the upper limit of normal values. The AST levels were significantly different among the three groups (stages I + II vs stage III vs stage IV, P < 0.05). In the early stage, 29.2% of patients had normal alkaline phosphatase (ALP) levels. The remaining patients had different degrees of ALP elevation; 6.3% had ALP levels > 5 times the upper limit of normal value. Moreover, γ-glutamyl transferase (GGT) was more robustly elevated, as 29.2% of patients had GGT levels of > 10 times the upper limit of normal value. The ALP values among the three groups were significantly different (P < 0.05). In early stage, the jaundice index did not increase significantly, but it gradually increased with disease progression. However, the above indicators were significantly different (P < 0.05) between the early-stage group and the stage IV group. With the progression of the disease, the levels of albumin and albumin/globulin ratio tended to decrease, and the difference among the three groups was statistically significant (P < 0.05). In early-stage patients, IgM and IgG levels as well as cholesterol levels were mildly elevated, but there were no significant differences among the three groups. Triglyceride levels were normal in the early-stage group, and the differences among the three groups were statistically significant (P < 0.05). The early detection rates of anti-mitochondria antibody (AMA) and AMA-M2 were 66.7% and 45.8%, respectively. The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC. When AMA and AMA-M2 were negative, in the early stage, the highest autoantibody was anti-nuclear antibody (ANA) (92.3%), and in all ANA patterns, the highest was ANA centromere (38.5%). CONCLUSION In early-stage PBC patients, ALT and AST levels are normal or mildly elevated, GGT and ALP levels are not elevated in parallel, GGT levels are more robustly elevated, and ALP levels are normal in some patients. When AMA and AMA-M2 are negative, ANA especially ANA centromere positivity suggests the possibility of early PBC. Therefore, in the clinic, significantly elevated GGT levels with or without normal ALP levels and with ANA (particularly ANA centromere) positivity (when AMA and AMA-M2 are negative) may indicate the possibility of early PBC.
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Affiliation(s)
- Yu-Jin Zhu
- Graduate School, Tianjin Medical University, Tianjin 300041, China
| | - Jing Li
- Graduate School, Tianjin Medical University, Tianjin 300041, China
| | - Yong-Gang Liu
- Department of Pathology, Clinical School of the Second People's Hospital, Tianjin 300110, China
| | - Yong Jiang
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Xiao-Jing Cheng
- Department of Gastroenterology, Clinical School of the Second People's Hospital, Tianjin 300110, China
| | - Xu Han
- Department of Gastroenterology, Clinical School of the Second People's Hospital, Tianjin 300110, China
| | - Chun-Yan Wang
- Department of Gastroenterology, Clinical School of the Second People's Hospital, Tianjin 300110, China
| | - Jia Li
- Department of Gastroenterology, Clinical School of the Second People's Hospital, Tianjin 300110, China
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12
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Wang X, Yang Z, Ran Y, Li L, Wang B, Zhou L. Anti-gp210-positive primary biliary cholangitis: The dilemma of clinical treatment and emerging mechanisms. Ann Hepatol 2023; 28:101121. [PMID: 37302574 DOI: 10.1016/j.aohep.2023.101121] [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: 02/25/2023] [Revised: 05/16/2023] [Accepted: 05/22/2023] [Indexed: 06/13/2023]
Abstract
Anti-gp210 is the disease-specific anti-nuclear antibody (ANA) of primary biliary cholangitis (PBC). Anti-gp210-positive PBC patients have worse responses to ursodeoxycholic acid (UDCA) as compared with anti-gp210-negative patients. Moreover, anti-gp210-positive patients always present with more severe histopathologic features including lobular inflammation, interfacial hepatitis, and bile duct injury, and have a worse prognosis than their anti-gp210-negative counterparts. Previous studies have identified two antigenic epitopes recognized by anti-gp210. Although the pathogenetic mechanism of anti-gp210 production remains unclear, evidence suggests that the autoimmune response to anti-gp210 production might be due to molecular mimicry induced by bacteria or endogenous peptides. T cells and related cytokines play a critical role in the pathogenesis of PBC, however, the mechanism hasn't been fully understood. Thus, this review focuses on the clinicopathological characteristics of anti-gp210-positive PBC patients, the fundamental research of gp210 antigen, and the possible mechanism of anti-gp210 production to clarify the mechanism of anti-gp210-positive PBC and provide potential molecular targets for disease prevention and treatment in the future.
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Affiliation(s)
- Xiaoyi Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhen Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Ying Ran
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Long Li
- Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Lu Zhou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China; Department of Gastroenterology and Hepatology, People's Hospital of Hetian District, Xinjiang Uygur Autonomous Region, China.
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Medford A, Childs J, Little A, Chakraborty S, Baiocchi L, Alpini G, Glaser S. Emerging Therapeutic Strategies in The Fight Against Primary Biliary Cholangitis. J Clin Transl Hepatol 2023; 11:949-957. [PMID: 37408803 PMCID: PMC10318288 DOI: 10.14218/jcth.2022.00398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 11/29/2022] [Accepted: 01/04/2023] [Indexed: 07/03/2023] Open
Abstract
The liver has a vital role in many metabolic and regulatory processes in the body. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a chronic cholestatic autoimmune disease of the intrahepatic bile ducts associated with loss of tolerance to mitochondrial antigens. At this time there is no definitive cure for PBC; however, ursodeoxycholic acid (UDCA) has been shown to reduce injury when administered as the first line of treatment. Additional therapeutics can be given concurrently or as an alternative to UDCA to manage the symptoms and further curb disease progression. Currently, a liver transplant is the only potentially curative option when the patient has developed end-stage liver disease or intractable pruritus. This review aims to delineate the pathogenesis of primary biliary cholangitis and shed light on current therapeutic strategies in the treatment of PBC.
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Affiliation(s)
- Abigail Medford
- Department of Medical Physiology, Texas A&M University School of Medicine, Bryan, TX, USA
| | - Jonathan Childs
- Department of Medical Physiology, Texas A&M University School of Medicine, Bryan, TX, USA
| | - Ashleigh Little
- Department of Medical Physiology, Texas A&M University School of Medicine, Bryan, TX, USA
| | - Sanjukta Chakraborty
- Department of Medical Physiology, Texas A&M University School of Medicine, Bryan, TX, USA
| | | | - Gianfranco Alpini
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Shannon Glaser
- Department of Medical Physiology, Texas A&M University School of Medicine, Bryan, TX, USA
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14
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You H, Duan W, Li S, Lv T, Chen S, Lu L, Ma X, Han Y, Nan Y, Xu X, Duan Z, Wei L, Jia J, Zhuang H, Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the Diagnosis and Management of Primary Biliary Cholangitis (2021). J Clin Transl Hepatol 2023; 11:736-746. [PMID: 36969891 PMCID: PMC10037524 DOI: 10.14218/jcth.2022.00347] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 11/02/2022] [Accepted: 11/20/2022] [Indexed: 03/29/2023] Open
Abstract
In 2015, the Chinese Society of Hepatology and the Chinese Society of Gastroenterology published a consensus on primary biliary cholangitis (PBC). In the past years, numerous clinical studies have been published in the field of PBC. To guide the clinical diagnosis and management of PBC patients, the Chinese Society of Hepatology invited a panel of experts to assess the new clinical evidence and formulate the current guidelines.
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Affiliation(s)
- Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Weijia Duan
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Shuxiang Li
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Tingting Lv
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Sha Chen
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Lungen Lu
- Department of Gastroenterology, First People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiong Ma
- Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Han
- Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Yuemin Nan
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Xiaoyuan Xu
- Department of Infectious Diseases and Center for Liver Diseases, Peking University First Hospital, Beijing, China
- Correspondence to: Jidong Jia, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing 100050, China. ORCID: https://orcid.org/0000-0002-4673-8890. Tel: +86-10-63139816, Fax: +86-10-63139246, E-mail: ; Xiaoyuan Xu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China. ORCID: https://orcid.org/0000-0002-1759-4330. Tel/Fax: +86-10-83575787, E-mail:
| | - Zhongping Duan
- Artificial Liver Center, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Lai Wei
- Hepatobiliary Pancreatic Center, Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China
- Correspondence to: Jidong Jia, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing 100050, China. ORCID: https://orcid.org/0000-0002-4673-8890. Tel: +86-10-63139816, Fax: +86-10-63139246, E-mail: ; Xiaoyuan Xu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China. ORCID: https://orcid.org/0000-0002-1759-4330. Tel/Fax: +86-10-83575787, E-mail:
| | - Hui Zhuang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
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15
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Gao X, Xiao G, Yang F, Dou R, Xue M, Zhang Y, Zheng Z, Ding J. Laboratory risk factors for coexistent primary biliary cholangitis in patients with Sjögren's syndrome: a retrospective study. BMC Gastroenterol 2023; 23:220. [PMID: 37365494 DOI: 10.1186/s12876-023-02859-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Accepted: 06/19/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND Limited research exists on the laboratory characteristics of coexistent primary biliary cholangitis (PBC) and Sjögren's syndrome (SS). This study aimed to investigate the laboratory risk factors for the coexistence of PBC in patients with SS. METHODS Eighty-two patients with coexistent SS and PBC (median age 52.50 years) and 82 age- and sex-matched SS controls were retrospectively enrolled between July 2015 and July 2021. The clinical and laboratory characteristics of the two groups were compared. Laboratory risk factors for the coexistence of PBC in patients with SS were analyzed using logistic regression analysis. RESULTS Both groups had a similar prevalence of hypertension, diabetes, thyroid disease, and interstitial lung disease. Compared with the SS group, patients in the SS + PBC group had higher levels of liver enzymes, immunoglobulins M (IgM), G2, and G3 (P < 0.05). The percentage of patients with an antinuclear antibody (ANA) titre > 1:10000 in the SS + PBC group was 56.1%, higher than that in the SS group (19.5%, P < 0.05). Additionally, cytoplasmic, centromeric, and nuclear membranous patterns of ANA and positive anti-centromere antibody (ACA) were observed more frequently in the SS + PBC group (P < 0.05). Logistic regression analysis showed that elevated IgM levels, high ANA titre, cytoplasmic pattern, and ACA were independent risk factors for PBC coexistence in SS. CONCLUSIONS In addition to established risk factors, elevated IgM levels, positive ACA, and high ANA titre with cytoplasmic pattern provide clues to clinicians for the early screening and diagnosis of PBC in patients with SS.
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Affiliation(s)
- Xuan Gao
- Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China
| | - Guangzhi Xiao
- Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China
| | - Fengfan Yang
- Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China
| | - Rongrong Dou
- Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China
| | - Miao Xue
- Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China
| | - Yingying Zhang
- Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China
| | - Zhaohui Zheng
- Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China
| | - Jin Ding
- Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Rd., Xi'an, 710032, Shaanxi, China.
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16
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Dias B, Aguiar A, Morais CI, Nery FG. Correlation between individual autoantibodies and clinical features in primary biliary cholangitis: results of a retrospective longitudinal study. Eur J Gastroenterol Hepatol 2023; 35:682-689. [PMID: 37116005 DOI: 10.1097/meg.0000000000002565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Abstract
BACKGROUND AND AIMS Primary biliary cholangitis (PBC) is an immune-mediated liver disease. The immunological profile seems to relate to clinical prognosis. This study aims to determine the role of autoantibodies in the course of liver disease and in the response to ursodeoxycholic acid. METHODS Between January 2016 and December 2020, 143 patients with PBC who underwent immunological liver profile evaluation were enrolled. All data were extracted retrospectively from electronic clinical records. Chi-square test, Fisher's exact test and Mann-Whitney test were used to evaluate the relationship between autoantibodies and biochemical parameters, clinical outcomes and therapeutic response scores. A significance level of 0.05 was used. RESULTS Antimitochondrial antibodies were present in 91.6%, antiglycoprotein-210 antibody (anti-gp210) in 18.2% and anti-Sp100 in 19.6% of patients. The incidence of liver-related death was higher in patients with autoimmune hepatitis variants. The occurrence of cirrhosis or portal hypertension was not linked to the presence of any of the autoantibodies tested. No relationship was found with the probability of dying or being transplanted. Patients with anti-Sp100 antibodies had higher baseline levels of aspartate aminotransferase and alanine aminotransferase and lower immunoglobulin M levels. Patients with anti-gp210 were more likely to have a lower median transplant-free survival rate and higher median risk of liver transplant or liver-related death using the GLOBE and UK-PBC scores. CONCLUSION Our findings confirm a strong association between anti-gp210 antibodies and a worse outcome. The association between anti-Sp100 and hepatic lesions requires further elucidation.
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Affiliation(s)
- Beatriz Dias
- Instituto de Ciências Biomédicas de Abel Salazar
| | - Ana Aguiar
- Instituto de Ciências Biomédicas de Abel Salazar
- EPIUnit - Instituto De Saúde Pública, Universidade do Porto
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR)
| | - Cátia Iracema Morais
- Instituto de Ciências Biomédicas de Abel Salazar
- Serviço de Imunologia, Departamento de Patologia, Centro Hospitalar e Universitário de Santo António
| | - Filipe Gaio Nery
- Instituto de Ciências Biomédicas de Abel Salazar
- EPIUnit - Instituto De Saúde Pública, Universidade do Porto
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR)
- Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar e Universitário de Santo António, Porto, Portugal
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Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors—A 2023 Update. Int J Mol Sci 2023; 24:ijms24065643. [PMID: 36982715 PMCID: PMC10051463 DOI: 10.3390/ijms24065643] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/05/2023] [Accepted: 03/14/2023] [Indexed: 03/18/2023] Open
Abstract
With the aging of the population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly in elderly patients. Such malignancies often interfere with RA treatment. Among several therapeutic agents, immune checkpoint inhibitors (ICIs) which antagonize immunological brakes on T lymphocytes have emerged as a promising treatment option for a variety of malignancies. In parallel, evidence has accumulated that ICIs are associated with numerous immune-related adverse events (irAEs), such as hypophysitis, myocarditis, pneumonitis, and colitis. Moreover, ICIs not only exacerbate pre-existing autoimmune diseases, but also cause de novo rheumatic disease–like symptoms, such as arthritis, myositis, and vasculitis, which are currently termed rheumatic irAEs. Rheumatic irAEs differ from classical rheumatic diseases in multiple aspects, and treatment should be individualized based on the severity. Close collaboration with oncologists is critical for preventing irreversible organ damage. This review summarizes the current evidence regarding the mechanisms and management of rheumatic irAEs with focus on arthritis, myositis, and vasculitis. Based on these findings, potential therapeutic strategies against rheumatic irAEs are discussed.
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Kim KA. [Diagnosis and Treatment of Primary Biliary Cholangitis]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 81:86-90. [PMID: 36824036 DOI: 10.4166/kjg.2023.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 01/26/2023] [Accepted: 01/30/2023] [Indexed: 02/25/2023]
Abstract
Primary biliary cholangitis (PBC) is an autoimmune disease prevalent in middle-aged women and characterized by chronic cholestasis. PBC is diagnosed when at least two of the following three criteria are met: elevated alkaline phosphatase, presence of PBC-specific autoantibodies such as the anti-mitochondrial antibody or PBC-specific anti-nuclear antibodies, and non-suppurative inflammation of the interlobular bile duct after excluding other causes including drugs and biliary obstruction. The first-line treatment for PBC is ursodeoxycholic acid (UDCA, 13-15 mg/kg/day). The response to UDCA is predictive of long-term prognosis and should be evaluated 6-12 months after the UDCA treatment. The second-line treatments for PBC recommended due to an inadequate response to UDCA include obeticholic acid and fibrates. Symptoms and complications, including pruritus, sicca syndrome, and osteoporosis, should be evaluated and appropriately managed.
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Affiliation(s)
- Kyung-Ah Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
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19
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Jańczyk W, Bierła JB, Trojanowska I, Wierzbicka-Rucińska A, Cukrowska B, Socha P. Prevalence and Significance of Autoantibody Seropositivity in Children with Wilson's Disease. Diagnostics (Basel) 2023; 13:diagnostics13040768. [PMID: 36832258 PMCID: PMC9955693 DOI: 10.3390/diagnostics13040768] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/03/2023] [Accepted: 02/15/2023] [Indexed: 02/22/2023] Open
Abstract
Autoantibodies occur in healthy subjects as well as in children with Wilson's disease (WD), but their prevalence and significance are unknown. Thus, we aimed to assess the prevalence of autoantibodies and autoimmune markers, and their relationship to liver injury in WD children. The study included 74 WD and 75 healthy children as a control group. Patients with WD underwent transient elastography (TE) examinations, as well as determination of liver function tests, copper metabolism markers, and serum immunoglobulins (Ig). In the sera of the WD patients and controls, anti-nuclear (ANA), anti-smooth muscle, anti-mitochondrial, anti-parietal cell, anti-liver/kidney microsomal, anti-neutrophil cytoplasmic autoantibodies, and specific celiac antibodies were determined. Among the autoantibodies, only the prevalence of ANA in children with WD was higher than in the controls. There was no significant relationship between the presence of autoantibodies and liver steatosis or stiffness after TE. However, advanced liver stiffness (E > 8.2 kPa) was related to IgA, IgG, and gamma globulin production. The type of treatment did not influence the prevalence of autoantibodies. Our results suggest that autoimmune disturbances in WD might not be directly related to liver damage as expressed by steatosis and/or liver stiffness after TE.
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Affiliation(s)
- Wojciech Jańczyk
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
- Correspondence: ; Tel.: +48-22-8151874
| | - Joanna B. Bierła
- Department of Pathomorphology, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Ilona Trojanowska
- Department of Pathomorphology, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Aldona Wierzbicka-Rucińska
- Department of Biochemistry, Radioimmunology and Experimental Medicine, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Bożena Cukrowska
- Department of Pathomorphology, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Piotr Socha
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
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Liu HL, Yang AY, Xiong QF, Zhong YD, Liu DX, Huang P, Feng XN, Zhang Y, Yang YF. Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis. BMC Gastroenterol 2022; 22:443. [PMID: 36324070 PMCID: PMC9628093 DOI: 10.1186/s12876-022-02538-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 10/12/2022] [Indexed: 11/07/2022] Open
Abstract
Background Aberrant cytokeratin 7 expression by hepatocytes (CK7+Hs) is the hallmark characteristic of cholestasis diseases, especially in ductopenia diseases such as primary biliary cholangitis (PBC). This study attempted to evaluate the differences and relationships between the clinical and histological features of aberrant cytokeratin 7 (CK7) expression by hepatocytes in PBC patients. Methods The clinicopathological data of patients diagnosed with PBC at the Second Hospital of Nanjing between January 2016 and September 2018 were analysed with SPSS 20.0. Results Eighty-nine PBC patients who underwent liver biopsy were enrolled in this study, and 15, 29 and 45 patients had aberrant CK7 expression by hepatocytes (CK7+Hs (2 +), CK7+Hs (1 +), and CK7−Hs, respectively). There were significant differences in TB, DB, ALP, TA, IgM, interface activity, and ductopenia grade between patients with CK7−Hs and CK7+Hs (2 +) (P < 0.05). The ductopenia grade was also significantly different between patients with CK7+Hs (2 +) and CK7+Hs (1 +) according to sex (P < 0.05). Upon merging the data of CK7+Hs (2 +) and CK7+Hs (1 +) into CK7+Hs, we found significant differences in AMA, AMA-M2, anti-gp210, TB, DB, ALP, TA, IgM, fibrosis, and ductopenia grade between CK7+Hs and CK7−Hs (P < 0.05). The odds ratios (ORs) (and 95% confidence intervals (CIs)) of CK7+Hs according to anti-gp210, ductopenia grade, and interface activity were 6.413 (95% CI 1.363–30.162), 4.145 (95% CI 1.898–9.052) and 3.247 (95% CI 1.556–6.775), respectively (P < 0.05). Spearman's rank correlation according to interface activity and ductopenia grade in patients with CK7+Hs (2 + , 1 + , 0) was r = 0.359 (P = 0.001) and r = 0.396 (P < 0.001), respectively. Conclusion CK7+Hs serves as a cholestasis index of PBC and are associated with the ductopenia grade and interface activity. Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis.
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Affiliation(s)
- Hong-Li Liu
- Southeast University School of Medicine, No87 Dingjiaqiao Road, Gulou District, Nanjing, 210009, China.,The Second Hospital of Nanjing, Teaching Hospital of Southeast University, No.1 Zhongfu Road, Gulou District, Nanjing, 210003, China
| | - An-Yin Yang
- Department of Liver Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, No.1 Zhongfu Road, Gulou District, Nanjing, 210003, China
| | - Qing-Fang Xiong
- Department of Liver Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, No.1 Zhongfu Road, Gulou District, Nanjing, 210003, China
| | - Yan-Dan Zhong
- Department of Liver Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, No.1 Zhongfu Road, Gulou District, Nanjing, 210003, China
| | - Du-Xian Liu
- Department of Pathology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, No.1 Zhongfu Road, Gulou District, Nanjing, 210003, China
| | - Ping Huang
- Department of Liver Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, No.1 Zhongfu Road, Gulou District, Nanjing, 210003, China
| | - Xiao-Ning Feng
- Department of Liver Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, No.1 Zhongfu Road, Gulou District, Nanjing, 210003, China
| | - Yu Zhang
- Southeast University School of Medicine, No87 Dingjiaqiao Road, Gulou District, Nanjing, 210009, China
| | - Yong-Feng Yang
- The Second Hospital of Nanjing, Teaching Hospital of Southeast University, No.1 Zhongfu Road, Gulou District, Nanjing, 210003, China. .,Department of Liver Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, No.1 Zhongfu Road, Gulou District, Nanjing, 210003, China.
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21
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Leung KK, Hirschfield GM. Autoantibodies in Primary Biliary Cholangitis. Clin Liver Dis 2022; 26:613-627. [PMID: 36270719 DOI: 10.1016/j.cld.2022.06.004] [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: 01/31/2023]
Abstract
Primary biliary cholangitis (PBC) is a chronic immune-mediated liver disease characterized by a lymphocytic cholangitis, with subsequent cholestasis, progressive liver fibrosis, and ultimately complications arising from end-stage liver disease. Testing for autoantibodies is important in the diagnosis of PBC, as well as stratifying prognosis. This review focuses on the role of autoantibodies in the diagnosis of PBC, as well as the relationship between autoantibodies with pathophysiology and prognostication, along with a discussion regarding novel and other related disease autoantibodies.
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Affiliation(s)
- Kristel K Leung
- Department of Medicine, Division of Gastroenterology & Hepatology, University Health Network, University of Toronto, 200 Elizabeth Street, Eaton Building, 9th Floor, Toronto, Ontario M5G 2C4, Canada
| | - Gideon M Hirschfield
- Department of Medicine, Division of Gastroenterology & Hepatology, University Health Network, University of Toronto, 200 Elizabeth Street, Eaton Building, 9th Floor, Toronto, Ontario M5G 2C4, Canada.
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22
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Wang K, Li Y, Pan J, He H, Zhao Z, Guo Y, Zhang X. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models. Open Med (Wars) 2022; 17:1550-1558. [PMID: 36245703 PMCID: PMC9520330 DOI: 10.1515/med-2022-0526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 06/21/2022] [Accepted: 06/24/2022] [Indexed: 11/15/2022] Open
Abstract
Autoimmune liver diseases (AILDs) are life-threatening chronic liver diseases, mainly including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and AIH-PBC overlap syndrome (OS), which are difficult to distinguish clinically at early stages. This study aimed to establish model to achieve the purpose of the diagnosis of AIH/PBC OS in a noninvasive way. A total of 201 AILDs patients were included in this retrospective study who underwent liver biopsy during January 2011 to December 2020. Serological factors significantly associated with OS were determined by the univariate analysis. Two multivariate models based on these factors were constructed to predict the diagnosis of AIH/PBC OS using logistic regression and random forest analysis. The results showed that immunoglobulins G and M had significant importance in both models. In logistic regression model, anti-Sp100, anti-Ro-52, anti-SSA, or antinuclear antibody positivity were risk factors for OS. In random forest model, activated partial thromboplastin time and ɑ-fetoprotein level were important. To distinguish PBC and OS, the sensitivity and specificity of logistic regression model were 0.889 and 0.727, respectively, and the sensitivity and specificity of random forest model were 0.944 and 0.818, respectively. In conclusion, we established two predictive models for the diagnosis of AIH/PBC OS in a noninvasive method and they showed better performance than Paris criteria for the definition of AIH/PBC OS.
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Affiliation(s)
- Kailing Wang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Yong Li
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Jianfeng Pan
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Huifang He
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Ziyi Zhao
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Yiming Guo
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Xiaomei Zhang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410007, China
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23
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Meng J, Yang G, Li S, Luo Y, Bai Y, Deng C, Song N, Li M, Zeng X, Hu C. The clinical value of indirect immunofluorescence for screening anti-rods and rings antibodies: A retrospective study of two centers in China. Front Immunol 2022; 13:1007257. [PMID: 36238277 PMCID: PMC9552219 DOI: 10.3389/fimmu.2022.1007257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 09/08/2022] [Indexed: 11/22/2022] Open
Abstract
Objective To investigate the distribution and clinical significance of the rods and rings (RR) pattern in various diseases. Methods A total of 169,891 patients in Peking Union Medical College Hospital (PUMCH) and 29,458 patients in Inner Mongolia People’s Hospital (IMPH) from January 2018 to December 2020 were included, and the results of ANA (antinuclear antibodies) and special antibodies were analyzed retrospectively. Results The positive rates of ANA and RR patterns were 34.84%, 0.16% in PUMCH, and 44.73%, 0.23% in IMPH. Anti-RR antibodies mainly appear in adults (≥ 41 years), mostly of low or medium fluorescence titers. Isolated RR patterns were mostly presented (60.30% and 69.12%, respectively), and the RR pattern mixed with the speckled pattern was most commonly observed among patients having two or more patterns. The RR pattern existed in a variety of diseases including hepatitis C, AIDs, pulmonary diseases, nephropathy diseases, and even healthy people. The highest prevalence of the RR pattern was observed in hepatic diseases, such as hepatic dysfunction (0.79%), hepatic cirrhosis (1.05%), PBC (0.85%), and AIH (0.65%), etc. The positive rate of specific antibodies in RR pattern cases was 31.25%, and anti-Ro52 (27, 20.61%) was the most common target antibody. Conclusion The RR pattern had a low prevalence in ANAs test samples and varied in different nationalities and regions. Except for hepatitis C, it could be observed in AIDs, pulmonary diseases, nephropathy, other hepatic diseases, and even healthy people, but the positive rate was slightly higher in hepatic diseases. Its mechanism of action and clinical relevance still need clarification.
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Affiliation(s)
- Jingjing Meng
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
- Department of Clinical Laboratory, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guoxiang Yang
- Department of Clinical Laboratory, Inner Mongolia People’s Hospital, Hohhot, China
| | - Siting Li
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Yueming Luo
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
- Jiangmen Wuyi Hospital of Traditional Chinese Medicine (TCM) (Affiliated Jiangmen TCM Hospital of Ji’nan University), Jiangmen, China
| | - Yina Bai
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Chuiwen Deng
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Ning Song
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
- *Correspondence: Chaojun Hu, ; Xiaofeng Zeng,
| | - Chaojun Hu
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
- *Correspondence: Chaojun Hu, ; Xiaofeng Zeng,
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24
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Mijic M, Saric I, Delija B, Lalovac M, Sobocan N, Radetic E, Martincevic D, Filipec Kanizaj T. Pretransplant Evaluation and Liver Transplantation Outcome in PBC Patients. Can J Gastroenterol Hepatol 2022; 2022:7831165. [PMID: 35910038 PMCID: PMC9337972 DOI: 10.1155/2022/7831165] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 06/01/2022] [Accepted: 06/07/2022] [Indexed: 11/17/2022] Open
Abstract
Primary biliary cholangitis (PBC) is an autoimmune chronic cholestatic liver disease characterized by progressive cholangiocyte and bile duct destruction leading to fibrosis and finally to liver cirrhosis. The presence of disease-specific serological antimitochondrial antibody (AMA) together with elevated alkaline phosphatase (ALP) as a biomarker of cholestasis is sufficient for diagnosis. Ursodeoxycholic acid (UDCA) is the first treatment option for PBC. Up to 40% of patients have an incomplete response to therapy, and over time disease progresses to liver cirrhosis. Several risk scores are proposed for better evaluation of patients before and during treatment to stratify patients at increased risk of disease progression. GLOBE score and UK PBC risk score are used for the evaluation of UDCA treatment and Mayo risk score for transplant-free survival. Liver transplantation (LT) is the only treatment option for end-stage liver disease. More than 10 years after LT, 40% of patients experience recurrence of the disease. A liver biopsy is required to establish rPBC (recurrent primary biliary cholangitis). The only treatment option for rPBC is UDCA, and data show biochemical and clinical improvement, plus potential beneficial effects for use after transplantation for the prevention of rPBC development. Additional studies are required to assess the full impact of rPBC on graft and recipient survival and for treatment options for rPBC.
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Affiliation(s)
- Maja Mijic
- Department of Gastroenterology, University Hospital Merkur, Zajceva 19, Zagreb, Croatia
| | - Ivona Saric
- Department of Gastroenterology, University Hospital Merkur, Zajceva 19, Zagreb, Croatia
| | - Bozena Delija
- Department of Gastroenterology, University Hospital Merkur, Zajceva 19, Zagreb, Croatia
| | - Milos Lalovac
- Department of Gastroenterology, University Hospital Merkur, Zajceva 19, Zagreb, Croatia
| | - Nikola Sobocan
- Department of Gastroenterology, University Hospital Merkur, Zajceva 19, Zagreb, Croatia
- University of Zagreb, School of Medicine, Salata 3, Zagreb, Croatia
| | - Eva Radetic
- University of Zagreb, School of Medicine, Salata 3, Zagreb, Croatia
| | - Dora Martincevic
- University of Zagreb, School of Medicine, Salata 3, Zagreb, Croatia
| | - Tajana Filipec Kanizaj
- Department of Gastroenterology, University Hospital Merkur, Zajceva 19, Zagreb, Croatia
- University of Zagreb, School of Medicine, Salata 3, Zagreb, Croatia
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25
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Jia Y, Liu L, Deng B, Huang Y, Zhao J, Bai G. Atypical primary biliary cholangitis results in vanishing bile duct syndrome with cutaneous xanthomas: a case report. Diagn Pathol 2022; 17:57. [PMID: 35787279 PMCID: PMC9252035 DOI: 10.1186/s13000-022-01228-1] [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: 11/11/2021] [Accepted: 04/30/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Vanishing bile duct syndrome (VBDS) is a rare but potentially severe acquired chronic cholestatic liver disease. Bile duct deficiency is a reduction of bile ducts in the liver, which can eventually lead to cholestatic liver disease and progress to biliary cirrhosis. Primary biliary cholangitis (PBC) is one of the causes of bile duct deficiency. In addition, 75% of PBC patients may have dyslipidemia, and in case of secondary dyslipidemia, cutaneous xanthomas may occur. A 49-year-old woman was admitted with jaundice and multiple subcutaneous nodules. She received diagnosis of autoimmune liver disease 2 years before. Although she was treated with liver-protecting drugs, such as Essentiale and ursodeoxycholic acid, jaundice occurred repeatedly, and the color of her skin was becoming darker and more yellow. CONCLUSION This case highlights that the positivity of ANA that in PBC have a well diagnostic and prognostic significance and antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' pattern scan ca diagnose primary biliary cirrhosis accurately. Since the liver biopsy of PBC alone may not be sufficient to establish the diagnosis, serum antibodies should also be examined. PBC can also lead to intrahepatic cholestasis, which can cause dyslipidemia and cutaneous xanthomas.
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Affiliation(s)
- Yuebo Jia
- Graduate Studies, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Lin Liu
- Department of Gastroenterology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Baocheng Deng
- The First Affiliated Hospital, China Medical University, Shenyang, China
| | - Yu Huang
- Department of Gastroenterology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Jiaqi Zhao
- Graduate Studies, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Guang Bai
- Department of Gastroenterology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China.
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26
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Chang ML, Chen WT, Chan TM, Lin CY, Chang MY, Chen SC, Chien RN. Anti-Mitochondrial Antibody Titers Decrease Over Time in Primary Biliary Cholangitis Patients With Ursodeoxycholic Acid Therapeutic Response: A Cohort Study Followed Up to 28 Years. Front Immunol 2022; 13:869018. [PMID: 35663951 PMCID: PMC9160714 DOI: 10.3389/fimmu.2022.869018] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 04/19/2022] [Indexed: 11/24/2022] Open
Abstract
Background How anti-mitochondrial antibody (AMA) and liver biochemistry levels change in primary biliary cholangitis (PBC) patients treated with ursodeoxycholic acid (UDCA) remains unclear. Methods A 28-year cohort of 157 PBC patients was conducted. Patients with alkaline phosphatase (Alk-p) levels >1.67 × upper limit of normal after 1 year of UDCA treatment were considered nonresponders. Results At baseline, of 157 (mean age: 54.41 years), 136 (86.6%) were female, 51 (32.5%) had cirrhosis, and 128 (81.5%) had detectable AMAs (immunoglobulin G). UDCA nonresponders (n=61) were younger and had higher Alk-p and total bilirubin levels and cirrhosis rates than UDCA responders (n=84). Alk-p levels and cirrhosis were negatively associated with UDCA response. Regardless of cirrhosis and UDCA response, most PBC patients had decreased Alk-p and γ-glutamyltransferase levels at last follow-up (up to 28.73 years) compared with baseline levels. Patients with baseline cirrhosis (2.78 ± 2.56 vs. 6.84 ± 9.00 mg/dL, p=0.024) and UDCA nonresponders (2.54 ± 2.19 vs. 4.51 ± 6.99 mg/dL, p=0.006) had increased total bilirubin levels while patients without cirrhosis (AST: 91.5 ± 84.5 vs. 58.9 ± 43.7 U/L, p<0.001; ALT: 107.3 ± 122.5 vs. 50.7 ± 36.8 U/L, p<0.001) and UDCA responders (AST: 83.8 ± 101.3 vs. 45.58 ± 38.42 U/L, p=0.014; ALT: 95.10 ± 144.6 vs. 39.12 ± 30.65 U/L, p=0.009) had decreased aminotransferase levels. Only UDCA responders had decreased AMA titers from 1 year after UDCA treatment (p=0.028) until the last follow-up (p<0.001). Conclusions UDCA responders exhibited decreased AMA titers 1 year after treatment. Regardless of UDCA response, PBC patients showed improved cholestatic features, but only UDCA responders and patients without baseline cirrhosis exhibited attenuated hepatobiliary damage following UDCA treatment.
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Affiliation(s)
- Ming-Ling Chang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Ting Chen
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Tien-Ming Chan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Cheng-Yu Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Ming-Yu Chang
- Division of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Shiang-Chi Chen
- Department of Nursing, Taipei Medical University, Taipei, Taiwan
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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27
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COVID-19 and Autoimmune Liver Diseases. J Clin Med 2022; 11:jcm11102681. [PMID: 35628807 PMCID: PMC9143939 DOI: 10.3390/jcm11102681] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 05/06/2022] [Accepted: 05/09/2022] [Indexed: 02/06/2023] Open
Abstract
SARS-CoV-2 infection can trigger autoimmune responses, either by a systemic hyperstimulation of the immune system or molecular mimicry (or both). We here summarize the current knowledges about autoimmune liver diseases (AILDs) and COVID-19, focusing on (a) the risk of SARS-CoV-2 infection in patients affected by AILDs and/or under pharmacological treatment with immunosuppressants; (b) the capability of vaccination against SARS-CoV-2 to trigger autoimmune responses in the liver; and (c) the efficacy of vaccines against SARS-CoV-2 in patients with AILDs. Although unconclusive results have been obtained regarding the risk of being infected by SARS-CoV-2, generally indicating that all patients with chronic liver diseases have the same risk, irrespective of the etiology, the use of immunosuppressants in patients with AILDs seems to be correlated to COVID-19 severity. Few cases of autoimmune hepatitis (AIH) after SARS-CoV-2 vaccination have been reported, all characterized by a complete remission upon steroid treatment, but further evidence is needed to demonstrate the causality assessment. Humoral responses have been observed in patients with AILDs upon vaccination. In conclusion, the link between SARS-CoV-2 infection and AILDs is far to be completely elucidated. In these patients, the use of immunosuppressants has been correlated to an increase of disease severity and lower levels of antibodies upon vaccination.
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28
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Zhao XA, Wang J, Wei J, Liu J, Chen G, Wang L, Wang G, Xia J, Wu W, Yin S, Tong X, Yan X, Ding W, Xiang X, Huang R, Wu C. Gamma-glutamyl Transpeptidase to Platelet Ratio Predicts Liver Injury in Hepatitis B e Antigen-negative Chronic Hepatitis B Patients With Normal Alanine Aminotransferase. J Clin Transl Hepatol 2022; 10:247-253. [PMID: 35528978 PMCID: PMC9039718 DOI: 10.14218/jcth.2021.00151] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/24/2021] [Accepted: 06/16/2021] [Indexed: 12/07/2022] Open
Abstract
BACKGROUND AND AIMS Chronic hepatitis B virus (HBV) infection is a serious health problem worldwide. Evaluating liver injury in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) with detectable HBV DNA and normal alanine aminotransferase (ALT) is crucial to guide their clinical management. We aimed to investigate the stages of liver inflammation and fibrosis as well as the predictive accuracy of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in these patients. METHODS A total of 184 treatment-naïve HBeAg-negative CHB patients with detectable HBV DNA and normal ALT were enrolled. The Scheuer scoring system was used to classify liver inflammation and fibrosis. RESULTS The distribution of patients with different liver inflammation grades were as follows: G0, 0 (0%); G1, 97 (52.7%); G2, 68 (37.0%); G3, 12 (6.5%); and G4, 7 (3.8%). The distribution of patients with different liver fibrosis stages were as follows: S0, 22 (12.0%); S1, 72 (39.1%); S2, 42 (22.8%); S3, 19 (10.3%); and S4, 29 (15.8%). The areas under the receiver operating characteristic (AUROC) curves of GPR in predicting significant inflammation, severe inflammation, and advanced inflammation were 0.723, 0.895, and 0.952, respectively. The accuracy of GPR was significantly superior to that of ALT in predicting liver inflammation. The AUROCs of GPR in predicting significant fibrosis, severe fibrosis, and cirrhosis were 0.691, 0.780, and 0.803, respectively. The predictive accuracy of GPR was significantly higher than that of aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) in identifying advanced fibrosis and cirrhosis, and it was superior to FIB-4 but comparable to APRI in identifying significant fibrosis. CONCLUSIONS Nearly half of the HBeAg-negative CHB patients with detectable HBV DNA and normal ALT levels had significant liver inflammation or fibrosis. GPR can serve as an accurate predictor of liver inflammation and fibrosis in these patients.
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Affiliation(s)
- Xiang-An Zhao
- Department of Gastroenterology, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jie Wei
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Guangmei Chen
- Department of Infectious Diseases, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Li Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Guiyang Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Weihua Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Weimao Ding
- Department of Hepatology, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Xiaoxing Xiang
- Department of Gastroenterology, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Correspondence to: Chao Wu and Rui Huang, Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, Jiangsu 210008, China. ORCID: https://orcid.org/0000-0002-1657-010X (CW), https://orcid.org/0000-0002-3189-7960 (RH). Tel: +86-25-8310-5890 (CW), +86-25-8310-6666-20201 (RH), Fax: +86-25-8330-7115 (CW), +86-25-8330-7115 (RH), E-mail: (CW), (RH)
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Correspondence to: Chao Wu and Rui Huang, Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, Jiangsu 210008, China. ORCID: https://orcid.org/0000-0002-1657-010X (CW), https://orcid.org/0000-0002-3189-7960 (RH). Tel: +86-25-8310-5890 (CW), +86-25-8310-6666-20201 (RH), Fax: +86-25-8330-7115 (CW), +86-25-8330-7115 (RH), E-mail: (CW), (RH)
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Bauer A, Habior A. Concentration of Serum Matrix Metalloproteinase-3 in Patients With Primary Biliary Cholangitis. Front Immunol 2022; 13:885229. [PMID: 35529854 PMCID: PMC9072739 DOI: 10.3389/fimmu.2022.885229] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 03/29/2022] [Indexed: 11/13/2022] Open
Abstract
Background and AimsMetalloproteinases (MMPs) are involved in many distinct processes in the liver. Matrix metalloproteinase-3 (MMP-3) plays an important role in connective tissue remodeling, degradation of collagen (types II, III, IV, IX, and X), proteoglycans, fibronectin, laminin, and elastin. In addition, MMP-3 can also activate other MMPs such as MMP-1, MMP-7, and MMP-9. Primary biliary cholangitis (PBC) is a cholestatic, autoimmune liver disease, characterized by the progressive destruction of intrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and liver failure. Fibrosis is the result of an imbalance between production and degradation of the extracellular matrix surrounding hepatocytes. Our aim in the present study was to determine whether the measurement of serum MMP-3 is clinically useful for assessing ongoing liver fibrosis in patients with PBC.MethodsThe MMP-3 concentration was determined in 182 PBC patients and 80 non-PBC controls using a commercially available ELISA kit.ResultsHigher concentrations of MMP-3 were found in 61% of PBC patients. PBC subjects had greater MMP-3 levels than controls: 68.9 ± 62.6 vs 21.3 ± 7.4 ng/mL, p < 0.001 for healthy subjects; 68.9 ± 62.6 vs 22.7 ± 7.6 ng/mL, p = 0.022 for autoimmune hepatitis controls; and 68.9 ± 62.6 vs 37.2 ± 17.4 ng/mL, p = 0.002 for primary sclerosing cholangitis controls. The serum MMP-3 concentration was significantly elevated in patients with higher bilirubin concentration (107.6 ± 85.8 vs 61.6 ± 46.1 ng/mL, p < 0.001) and was correlated with the level of antimitochondrial antibodies specific for PBC. The concentration of MMP-3 in sera of PBC patients was also found to correlate with the state of liver fibrosis (OR = 4.3; p < 0.01).ConclusionsOur study demonstrated significantly higher MMP-3 levels in PBC patients than in healthy and pathological controls. Increased MMP-3 concentrations were positively correlated with various clinical and immunological parameters, and advanced liver fibrosis. The level of MMP-3 was associated with hepatic dysfunction and could play a role in the pathophysiology of hepatic fibrosis in PBC.
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Affiliation(s)
- Alicja Bauer
- Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Warsaw, Poland
- *Correspondence: Alicja Bauer,
| | - Andrzej Habior
- Department of Gastroenterology, Hepatology and Clinical Oncology Centre of Postgraduate Medical Education, Warsaw, Poland
- Clinic of Polish Gastroenterology Foundation, Warsaw, Poland
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Wu Z, Xu H, Zhang S. AC-X: Characteristic Antinuclear Antibody Patterns of Two Anti-Mi-2 Autoantibody-Positive Dermatomyositis Patients—A Case Report. Front Immunol 2022; 13:857030. [PMID: 35371082 PMCID: PMC8967955 DOI: 10.3389/fimmu.2022.857030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 02/21/2022] [Indexed: 11/13/2022] Open
Abstract
Here we reported two anti-Mi-2 autoantibody-positive dermatomyositis (DM) patients with a characteristic antinuclear antibody (ANA) immunofluorescence pattern. Autoantibodes were screened by indirect immunofluorescence (IIF) on HEp-2 cells (Euroimmun, Lübeck, Germany) and confirmed by line immunoblot (ANA Profile 3—Euroimmun, Germany). These two patients were positive for ANA (speckled, titer 1:320), followed by confirmation of positive anti-Mi-2α and anti-Mi-2β positive and negative for all other antibodies. We found a characteristic ANA pattern of the anti-Mi-2 antibody that differed from the AC-4 pattern, especially in the morphology of mitotic cells (metaphase, anaphase, and telophase). Thus, we would like to suggest reporting this characteristic antinuclear antibody pattern as a new AC type, as AC-X.
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Presence of Serum Antinuclear Antibodies Does Not Impact Outcomes in HBV-Related Acute-on-Chronic Liver Failure. Can J Gastroenterol Hepatol 2022; 2022:7981338. [PMID: 35223685 PMCID: PMC8881176 DOI: 10.1155/2022/7981338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 01/16/2022] [Accepted: 01/26/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND The aim of this study was to provide new insights into the prevalence of positive antinuclear antibody (ANA) in patients with HBV-related acute-on-chronic liver failure (ACLF) and its impact on clinical outcomes. METHODS A total of 116 patients with HBV-related ACLF treated at three clinical centers were retrospectively recruited. Serum concentrations of ANA were detected using the enzyme-linked immunosorbent assay kit. Multiple nuclear dots, rim-like, and centromere patterns of ANA were detected using indirect immunofluorescence assay on HEp-2 cells. RESULTS Among the 116 patients with HBV-related ACLF, 17 (14.66%) were ANA positive. Most patients in both ANA positive and negative groups were males (88.2% and 83.8%). Patients with negative ANA had a higher international normalized ratio, model for end-stage liver disease (MELD), and MELD-sodium scores than those with positive ANA (all P < 0.05). Multiple nuclear dot pattern was detected in half of the patients (8/17, 47.06%), rim-like/membranous pattern was found in six patients, and centromere pattern was detected in the last three patients. For patients with ANA (+), IgM was lower, and it was positively correlated with IgG. For patients with ANA (-), C3 was positively correlated with C4, and both C3 and C4 were negatively correlated with INR and MELD (all P < 0.05). In addition, TBIL, INR, WBC, and PLT, but not ANA, resulted as independent risk factors associated with 90-day mortality. CONCLUSION Positive ANA is frequent in HBV-related ACLF, and it does not seem to be associated with poor outcomes, but the pathogenesis of ACLF may be different between ANA (+) and ANA (-) groups.
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You H, Ma X, Efe C, Wang G, Jeong SH, Abe K, Duan W, Chen S, Kong Y, Zhang D, Wei L, Wang FS, Lin HC, Yang JM, Tanwandee T, Gani RA, Payawal DA, Sharma BC, Hou J, Yokosuka O, Dokmeci AK, Crawford D, Kao JH, Piratvisuth T, Suh DJ, Lesmana LA, Sollano J, Lau G, Sarin SK, Omata M, Tanaka A, Jia J. APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis. Hepatol Int 2022; 16:1-23. [PMID: 35119627 PMCID: PMC8843914 DOI: 10.1007/s12072-021-10276-6] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 11/08/2021] [Indexed: 12/14/2022]
Affiliation(s)
- Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing, Mainland, China
| | - Xiong Ma
- Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University, Shanghai, Mainland, China
| | - Cumali Efe
- Department of Gastroenterology, Gazi Yaşargil Education and Research Hospital, Diyarbakir, Turkey
| | - Guiqiang Wang
- Department of Infectious Diseases and Center for Liver Diseases, Peking University First Hospital, Beijing, Mainland, China
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Weijia Duan
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing, Mainland, China
| | - Sha Chen
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing, Mainland, China
| | - Yuanyuan Kong
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland, China
| | - Dong Zhang
- Experimental and Translational Research Center, Beijing Clinical Research Institute, Beijing, Mainland, China
| | - Lai Wei
- Hepatobiliary Pancreatic Center, Tsinghua Changgung Hospital, Tsinghua University, Beijing, Mainland, China
| | - Fu-Sheng Wang
- Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospial, Beijing, Mainland, China
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jin Mo Yang
- Division of Hepatology, Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, South Korea
| | - Tawesak Tanwandee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Rino A. Gani
- Department of Internal Medicine, Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta, Indonesia
| | - Diana A. Payawal
- Department of Medicine, Fatima University Medical Center, Manila, Philippines
| | | | - Jinlin Hou
- Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, Mainland, China
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - A. Kadir Dokmeci
- Department of Medicine, Ankara University School of Medicine, Ankara, Turkey
| | - Darrell Crawford
- School of Medicine, University of Queensland, Brisbane, Australia
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Teerha Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Faculty of Medicine, Prince of Songkla University, Hatyai, Thailand
| | - Dong Jin Suh
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, South Korea
| | | | - Jose Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - George Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong SAR, China
| | - Shiv K. Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Tokyo, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing, Mainland, China
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van Beers JJBC, Koek GH, Damoiseaux JGMC. The Role of Autoantibodies in the Diagnosis of Autoimmune Liver Disease: Lessons Learned from Clinical Practice. J Appl Lab Med 2022; 7:259-267. [PMID: 34996079 DOI: 10.1093/jalm/jfab099] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 07/29/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are autoimmune liver diseases associated with distinct autoantibodies. Diagnosis is based upon clinical, serological, and histopathology findings. The role of autoantibodies in the diagnosis of these autoimmune liver diseases, with the focus on PBC and AIH, will be discussed. CONTENT When AIH or PBC is suspected, testing for multiple autoantibodies can be requested. In this mini-review, the different ways in which autoantibodies can be tested (indirect immunofluorescence and antigen-specific tests) in the context of PBC and AIH are discussed, as well as the pitfalls in interpreting the test results. SUMMARY For appropriate interpretation of test results, an important prerequisite is that the doctor knows which test is used in the laboratory of choice and that the laboratory specialist is aware of what the doctor wants to test for. Good communication between clinician and laboratory specialist can, therefore, aid in the diagnosis of autoimmune liver diseases.
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Affiliation(s)
- Joyce J B C van Beers
- Department of Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Ger H Koek
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Jan G M C Damoiseaux
- Department of Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands
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OUP accepted manuscript. J Appl Lab Med 2022; 7:814-815. [DOI: 10.1093/jalm/jfac014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 01/29/2022] [Indexed: 11/14/2022]
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Zeng Y, Dai Y, Zhou Z, Yu X, Shi D. Hepatotoxicity-Related Adverse Effects of Proton Pump Inhibitors: A Cross-Sectional Study of Signal Mining and Analysis of the FDA Adverse Event Report System Database. Front Med (Lausanne) 2021; 8:648164. [PMID: 34869400 PMCID: PMC8636138 DOI: 10.3389/fmed.2021.648164] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 10/25/2021] [Indexed: 12/21/2022] Open
Abstract
Background and Objectives: Mounting evidence demonstrates that proton pump inhibitors (PPIs) are associated with a number of adverse effects. However, the literatures about hepatotoxicity-related adverse effects (HRAEs) of PPIs are mostly case reports and a few clinical studies. Methods: We evaluated the association between PPIs and HAREs using the reporting odd ratio (ROR) for mining the adverse event report signals in the FDA Adverse Event Reporting System (FAERS) database. Results: There were 23,825 reports of PPIs as primary suspect drug or second suspect drug, of which 3,253 reports were HRAEs. The top five HRAE signals caused by PPIs were hepatitis cholestatic, cholestasis, fulminant hepatitis, subacute hepatic failure, and acute hepatitis. We also summarized the signals of the HRAEs caused by each PPI. The simultaneous signals were cholestasis and hepatitis cholestatic. For the cholestasis signal, esomeprazole showed an ROR of 21.556 (95% CI 17.592–26.413); pantoprazole showed the highest ROR of 22.611 (95% CI 17.794–28.733) in the hepatic cholestatic signal; lansoprazole was the only PPI with expression in the coma hepatic signal, with an ROR of 10.424 (95% CI 3.340–32.532). By analyzing the reports of pantoprazole-induced hepatic encephalopathy, we found that patients aged over 65 years and males reported the highest rate. And from the combination of drugs and indications of drugs, no significant results were obtained. Conclusions: The RORs of signals of “cholestasis” were generally higher than those of “hepatocellular injury.” And the signals about “cholestasis” in HRAE caused by PPIs are more reported.
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Affiliation(s)
- Yifan Zeng
- Computer Technology and Information Centre, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ying Dai
- Department of Pharmacy, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ziye Zhou
- Department of Pharmacy, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xuben Yu
- Department of Pharmacy, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Dawei Shi
- Department of Pharmacy, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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Balderramo D, Mattos AZ, Mulqui V, Chiesa T, Plácido-Damián Z, Abarca J, Bolomo A, Carlino Y, Bombassaro IZ, Wiltgen D, Castillo LT, Díaz K, Acuña J, Manero E, Prieto J, Carrera E, Díaz-Ferrer J, Debes JD. Abnormal Liver Tests during Hospitalization Predict Mortality in Patients with COVID-19: A Multicenter Study from South America. Can J Gastroenterol Hepatol 2021; 2021:1622533. [PMID: 34621710 PMCID: PMC8492276 DOI: 10.1155/2021/1622533] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 09/15/2021] [Accepted: 09/22/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The role of liver function tests (LFT) as prognostic factors in patients admitted with COVID-19 has not been fully investigated, particularly outside resource-rich countries. We aimed at evaluating the prognostic value of abnormal LFT on admission and during hospitalization of patients with COVID-19. METHODS We performed a retrospective study that included 298 adult patients hospitalized for COVID-19, between 05/2020 and 02/2021, in 6 hospitals from 5 countries in South America. We analyzed demographic and comorbid variables and laboratory tests on admission and during hospitalization. LFT over twice the upper limit of normal (ALEx2) were also evaluated in relation to a variety of factors on admission and during hospitalization. De novo-ALEx2 was defined as the presence of ALEx2 at one week of hospitalization in patients without ALEx2 on admission. Patients were followed until hospital discharge or death. Multivariable analysis was used to evaluate the association between ALEx2 on admission and during hospitalization and mortality. RESULTS Of the total of 298 patients, 60% were male, with a mean age of 60 years, and 74% of patients had at least one comorbidity. Of those, 137 (46%) patients were transferred to the intensive care unit and 66 (22.1%) patients died during hospitalization. ALEx2 on admission was present in 87 (29.2%) patients and was found to be independently associated with 1-week mortality (odds ratio (OR) = 3.55; 95% confidence interval (95%CI) 1.05-12.05). Moreover, 84 (39.8%) out of 211 patients without ALEx2 at admission developed de novo-ALEx2, which was independently associated with mortality during second week of hospitalization (OR = 6.09; 95%CI 1.28-29) and overall mortality (OR = 2.93, 95%CI 1.05-8.19). CONCLUSIONS A moderate elevation of LFT during admission was associated with a poor short-term prognosis in patients hospitalized with COVID-19. In addition, moderate elevation of LFT at one week of hospitalization was an independent risk factor for overall mortality in these patients.
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Affiliation(s)
- Domingo Balderramo
- Gastroenterology Department, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
| | - Angelo Z. Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
| | - Victoria Mulqui
- Gastroenterology Department, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
- Internal Medicine Department, Hospital Pablo Soria, San Salvador de Jujuy, Argentina
| | - Talita Chiesa
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
| | - Zuly Plácido-Damián
- Gastroenterology Department, Hospital Nacional Edgardo Rebagliati Martins-Essalud, School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru
| | - Jaysoom Abarca
- Department of Gastroenterology, Hospital Especialidades Eugenio Espejo, Universidad San Francisco de Quito, Quito, Ecuador
| | - Andrea Bolomo
- Gastroenterology Department, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
| | - Yanina Carlino
- Gastroenterology Department, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
| | - Isadora Z. Bombassaro
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
| | - Denusa Wiltgen
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
- Internal Medicine Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
| | - Laura Tenorio Castillo
- Gastroenterology Department, Hospital Nacional Edgardo Rebagliati Martins-Essalud, School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru
| | - Karina Díaz
- Department of Gastroenterology, Hospital Especialidades Eugenio Espejo, Universidad San Francisco de Quito, Quito, Ecuador
| | - Johana Acuña
- Department of Gastroenterology, Hospital Especialidades Eugenio Espejo, Universidad San Francisco de Quito, Quito, Ecuador
| | - Estela Manero
- Internal Medicine Department, Hospital Pablo Soria, San Salvador de Jujuy, Argentina
| | - Jhon Prieto
- Centro de Enfermedades Hepaticas y Digestivas, Bogota, Colombia
| | - Enrique Carrera
- Department of Gastroenterology, Hospital Especialidades Eugenio Espejo, Universidad San Francisco de Quito, Quito, Ecuador
| | - Javier Díaz-Ferrer
- Gastroenterology Department, Hospital Nacional Edgardo Rebagliati Martins-Essalud, School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru
| | - Jose D. Debes
- Department of Medicine, University of Minnesota, Minneapolis, USA
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Beenet L. Profile of Hepatobiliary Dysfunction in Hematopoietic Stem Cell Transplant Recipients: Autoimmune Diseases Also Contribute. J Clin Exp Hepatol 2021; 11:630-631. [PMID: 34511827 PMCID: PMC8414322 DOI: 10.1016/j.jceh.2021.03.017] [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: 03/05/2021] [Accepted: 03/31/2021] [Indexed: 12/12/2022] Open
Affiliation(s)
- Linda Beenet
- Department of Pathology & Laboratory Medicine, University of California Los Angeles (UCLA) Technology Center for Genomics & Bioinformatics, Los Angeles, CA, United States
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Wilhelmi M. Diagnostic significance of uncommon antinuclear antibodies. Clin Biochem 2021; 94:83. [PMID: 33891921 DOI: 10.1016/j.clinbiochem.2021.04.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 04/13/2021] [Indexed: 11/16/2022]
Affiliation(s)
- Markus Wilhelmi
- Medical Clinic I, Gastroenterology and Hepatology, Nutritional Medicine University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
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Granito A, Muratori L, Tovoli F, Muratori P. Autoantibodies to speckled protein family in primary biliary cholangitis. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2021; 17:35. [PMID: 33789734 PMCID: PMC8011120 DOI: 10.1186/s13223-021-00539-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 03/17/2021] [Indexed: 02/07/2023]
Abstract
The autoantibody profile of primary biliary cholangitis (PBC) includes antinuclear antibodies (ANA) which are detectable by indirect immunofluorescence in more than 50% of PBC patients. One of the two immunofluorescence patterns which are historically considered "PBC-specific" is the so-called "multiple nuclear dots" (MND) targeting nuclear body proteins such as Sp100, Sp140, Sp140L proteins, promyelocytic leukemia protein (PML) and small ubiquitin-related modifier proteins (SUMO). It has been hypothesized a role of nuclear body protein alterations in immune disorders such as PBC, thus suggesting novel and more refined therapeutic approaches.
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Affiliation(s)
- Alessandro Granito
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138, Bologna, Italy.
- Center for the Study, Treatment of Autoimmune Diseases of the Liver, Biliary System, Bologna, Italy.
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy.
| | - Luigi Muratori
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138, Bologna, Italy
- Center for the Study, Treatment of Autoimmune Diseases of the Liver, Biliary System, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138, Bologna, Italy
- Center for the Study, Treatment of Autoimmune Diseases of the Liver, Biliary System, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Paolo Muratori
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138, Bologna, Italy
- Center for the Study, Treatment of Autoimmune Diseases of the Liver, Biliary System, Bologna, Italy
- Department for the Science of the Quality of Life (QUVI), Alma Mater Studiorum, University of Bologna, Bologna, Italy
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Wilhelmi M. Clinical and serological prognostic markers in primary biliary cholangitis. Clin Mol Hepatol 2021; 27:360-361. [PMID: 33752318 PMCID: PMC8046621 DOI: 10.3350/cmh.2021.0088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 03/22/2021] [Indexed: 11/24/2022] Open
Affiliation(s)
- Markus Wilhelmi
- Department of Gastroenterology, Hepatology, and Nutritional Medicine (Medicine Clinic I), University Hospital Frankfurt, Frankfurt am Main, Germany
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Xiang X, Yang X, Shen M, Huang C, Liu Y, Fan X, Yang L. Ursodeoxycholic Acid at 18-22 mg/kg/d Showed a Promising Capacity for Treating Refractory Primary Biliary Cholangitis. Can J Gastroenterol Hepatol 2021; 2021:6691425. [PMID: 33542908 PMCID: PMC7843178 DOI: 10.1155/2021/6691425] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 01/13/2021] [Accepted: 01/15/2021] [Indexed: 02/05/2023] Open
Abstract
Aim To compare the response between the current recommended dosage 13-15 mg/kg/d and 20 mg/kg/d dose of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) patients who do not respond completely to a standard dose of UDCA. Methods We included 73 patients with poor response and randomized them into two groups to investigate whether increasing the dosage of UDCA was beneficial to nonresponders. Patients assigned to the 13-15 mg/kg/d group continued with standard therapy, and participants in the 18-22 mg/kg/d group switched to the higher dosage (18-22 mg/kg/d), with a follow-up of 12 months for both groups. The primary endpoints were the rate of response at 6 months and drug side effects. Results According to the Paris 2 criteria, patients receiving 18-22 mg/kg/d UDCA achieved a response rate of 59.4% compared with 36.1% in the standard dosage group (P=0.046) at 6 months, respectively. At 12 months, the high-UDCA-dosage group achieved a response rate of 59.4% compared with 47.2% in the standard dosage group (P=0.295), respectively. Additionally, the risk score predicted by the UK-PBC model was lower in high-dosage UDCA-treated patients than in the standard dosage group (all P < 0.05). Side effects include diarrhea, nausea and vomiting, rash, and newly developed high blood pressure, which were mild and tolerated. Conclusions Patients treated with the high UDCA dosage showed some advantages over those who continued the standard dosage in terms of biochemical remission and disease progression, indicating that standard therapy with UDCA for 6 months and then another 1 year with high UDCA dosage for nonresponders could be a treatment option before second-line therapy is recommended.
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Affiliation(s)
- Xinyu Xiang
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoli Yang
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Mengyi Shen
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, West China Hospital, Sichuan University, Chengdu, China
| | - Chen Huang
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, West China Hospital, Sichuan University, Chengdu, China
| | - Yifeng Liu
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoli Fan
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, West China Hospital, Sichuan University, Chengdu, China
| | - Li Yang
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, West China Hospital, Sichuan University, Chengdu, China
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Response Rate and Impact on Lipid Profiles of Obeticholic Acid Treatment for Patients with Primary Biliary Cholangitis: A Meta-Analysis. Can J Gastroenterol Hepatol 2021; 2021:8829510. [PMID: 33511089 PMCID: PMC7822683 DOI: 10.1155/2021/8829510] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 12/16/2020] [Accepted: 12/30/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Up to 40% of patients with primary biliary cholangitis (PBC) have an inadequate response to ursodeoxycholic acid (UDCA). Obeticholic acid (OCA) is considered the addition of treatment, but the response rate based on commonly referenced biochemical response criteria and lipids' impact was unclear. Previous studies reported inconsistency results partially due to small sample size. Therefore, we performed a meta-analysis and aimed to explore OCA treatment's response rate and effect on lipids' profiles in PBC patients. METHODS We performed PubMed, Embase, and Cochrane controlled trials register (updated to JUN 2019) databases and manual bibliographical searches for randomized controlled trials reporting on OCA treatment in PBC patients. Two researchers independently extracted data and assessed the risk of bias of studies. We calculated risk ratio (RR) for the overall complete response rate, and the standardized mean difference (SMD) for the serum lipids changes after OCA treatment, all with 95% confidence intervals (CIs) using fixed-effects models. We registered this meta-analysis with PROSPERO (registration number: CRD42020148550). RESULTS Three trials, with 265 patients, were selected for the analysis. OCA was superior to placebo in PBC patients (RR, 1.48; 95% CI, 1.15-1.90). OCA's pooled treatment response rate was 65% (95% CI, 56%-74%), corresponding to Paris I criteria. Besides, OCA significantly decreased total cholesterol (P=0.02) with no heterogeneity (P=0.87, I 2 = 0%) and high-density lipoprotein levels (P < 0.05) with no heterogeneity (P=0.82, I 2 = 0%). CONCLUSIONS This meta-analysis demonstrated that OCA was a promising additional treatment for PBC patients and might reduce serum cholesterol levels. The longer follow-up studies are needed to give more evidence.
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Meta-Analysis of Antinuclear Antibodies in the Diagnosis of Antimitochondrial Antibody-Negative Primary Biliary Cholangitis. Gastroenterol Res Pract 2019; 2019:8959103. [PMID: 31281353 PMCID: PMC6590611 DOI: 10.1155/2019/8959103] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 04/18/2019] [Accepted: 05/27/2019] [Indexed: 12/14/2022] Open
Abstract
Objective The diagnostic value of antinuclear antibodies (ANAs) including anti-gp210 and anti-sp100 for primary biliary cholangitis/cirrhosis (PBC) has been widely reported. However, their diagnostic performances for antimitochondrial antibody- (AMA-) negative PBC were less well elucidated. Therefore, the aim of the current meta-analysis was to evaluate the diagnostic accuracy of ANAs in patients with AMA-negative PBC. Materials and Methods Literature on the diagnostic value of biomarkers for AMA-negative PBC was systematically searched in PubMed, MEDLINE, EMBASE, and the Cochrane Library. The qualities of the retrieved studies were assessed by the Quality Assessment of Diagnostic Accuracy Studies-version 2 (QUADAS-2) scale. Pooled sensitivity and specificity of the biomarkers were calculated with random-effects models. The areas under the summary receiver operating characteristic (AUSROC) curves were used to evaluate the overall diagnostic performance of ANAs. Results A total of 11 studies (400 AMA-negative PBC patients and 6217 controls) were finally included in the meta-analysis. ANAs had an overall sensitivity of 27% (95% CI: 20%, 35%) and specificity of 98% (95% CI: 97%, 99%). The pooled sensitivities for anti-gp210 and anti-sp100 were 23% (95% CI: 13%, 37%) and 25% (95% CI: 13%, 43%), respectively, and their specificities were 99% (95% CI: 97%, 100%) and 97% (95% CI: 93%, 98%), respectively. Conclusions ANAs exhibited high specificity but low sensitivity and therefore could be used as reliable biomarkers to reduce the necessity of liver histology.
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Brady GF, Kwan R, Cunha JB, Elenbaas JS, Omary MB. Lamins and Lamin-Associated Proteins in Gastrointestinal Health and Disease. Gastroenterology 2018; 154:1602-1619.e1. [PMID: 29549040 PMCID: PMC6038707 DOI: 10.1053/j.gastro.2018.03.026] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 03/04/2018] [Accepted: 03/06/2018] [Indexed: 02/07/2023]
Abstract
The nuclear lamina is a multi-protein lattice composed of A- and B-type lamins and their associated proteins. This protein lattice associates with heterochromatin and integral inner nuclear membrane proteins, providing links among the genome, nucleoskeleton, and cytoskeleton. In the 1990s, mutations in EMD and LMNA were linked to Emery-Dreifuss muscular dystrophy. Since then, the number of diseases attributed to nuclear lamina defects, including laminopathies and other disorders, has increased to include more than 20 distinct genetic syndromes. Studies of patients and mouse genetic models have pointed to important roles for lamins and their associated proteins in the function of gastrointestinal organs, including liver and pancreas. We review the interactions and functions of the lamina in relation to the nuclear envelope and genome, the ways in which its dysfunction is thought to contribute to human disease, and possible avenues for targeted therapies.
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Affiliation(s)
- Graham F. Brady
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan,Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan,To whom correspondence should be addressed: University of Michigan Medical School, Division of Gastroenterology, Department of Internal Medicine, 1137 Catherine St., Ann Arbor, MI 48109-5622.
| | - Raymond Kwan
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan
| | - Juliana Bragazzi Cunha
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan
| | - Jared S. Elenbaas
- Medical Scientist Training Program, Washington University, St Louis, Missouri
| | - M. Bishr Omary
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan,Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan,Ǻbo Akademi University, Turku, Finland
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de Liso F, Matinato C, Ronchi M, Maiavacca R. The diagnostic accuracy of biomarkers for diagnosis of primary biliary cholangitis (PBC) in anti-mitochondrial antibody (AMA)-negative PBC patients: a review of literature. Clin Chem Lab Med 2017; 56:25-31. [PMID: 28731850 DOI: 10.1515/cclm-2017-0249] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 06/09/2017] [Indexed: 02/01/2023]
Abstract
Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is an autoimmune disease of the liver characterized by anti-mitochondrial antibodies (AMA) in 90%-95% of patients. The aim of this study was to evaluate the diagnostic value of several serum biomarkers in patients with PBC but negative for AMA. Some antinuclear antibodies (ANA) pattern, detected by indirect immunofluorescence (IIF), such as multiple nuclear dot (MND) and rim-like patterns are well-known to be specific for PBC. The corresponding nuclear antigens are the components of the nuclear pore complex (Gp210 for rim-like pattern) and Sp100, PML proteins (for MND pattern) detectable by immunoblotting and ELISA methods. More recently, new biomarkers have been evaluated in order to improve the diagnostic sensitivity, such as kelch-like 12 (KLHL12) and hexokinase-1. Considering these different serum biomarkers, studies evaluating their diagnostic role in AMA-negative PBC patients compared to AMA-positive ones and controls were included in this review. Pooled sensitivity and specificity were 37% and 85%, respectively. The overall PPV and NPV mean values were 45% and 83%. Even if all biomarkers are very specific for PBC, the overall sensitivity was poor and therefore is necessary to identify a marker with a greater sensitivity for PBC in AMA-negative patients.
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Ozaslan E, Efe C, Gokbulut Ozaslan N. The diagnosis of antimitochondrial antibody-negative primary biliary cholangitis. Clin Res Hepatol Gastroenterol 2016; 40:553-561. [PMID: 27567165 DOI: 10.1016/j.clinre.2016.06.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Revised: 06/12/2016] [Accepted: 06/23/2016] [Indexed: 02/04/2023]
Abstract
Autoimmune liver diseases are heterogenous disorders that share largely non-specific clinical, serological and pathological features. The correct diagnosis requires discriminative features which are highly specific, for example high-titer antimitochondrial antibodies (AMA) and florid duct lesion in primary biliary cholangitis (PBC). However, the imperfect sensitivities of these characteristic features and abuse of scoring systems led to many artificial diagnoses such as overlap syndromes and outliers for example "autoimmune cholangitis" which is now called as "AMA-negative PBC". Patients lacking detectable AMA (up to 20% in indirect immunofluorescence - IF), but otherwise presenting signs and symptoms of PBC should be regarded as affected by "AMA-negative PBC" because they seem to follow a natural history similar to that of their AMA positive counterparts. The complementary use of IF, ELISA and immunoblotting have disclosed that the majority of patients initially considered AMA-negative are in fact AMA positive. Moreover, the use of PBC-specific ANA's like Gp210 and sp100 have diminished the AMA-negative cases (if truly exists!) to less than 5%. The histological spectrum of PBC includes typical florid duct lesions and/or compatible features such as non-specific hepatitic and biliary findings. In the absence of florid duct lesion and AMA positivity, histology alone cannot differentiate PBC from other biliary disorders. However, the analysis of compatible histological features with the clinical, serological and imaging findings usually points to a specific diagnosis. In this review, we present serological, clinical and pathological pitfalls regarding AMA-negative PBC including illustrative cases and a diagnostic algorithm.
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Affiliation(s)
- Ersan Ozaslan
- Numune Education and Research Hospital, Department of Gastroenterology, Ankara, Turkey.
| | - Cumali Efe
- Batman State Hospital, Department of Gastroenterology, Batman, Turkey
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Cancado ELR, Harriz M. The Importance of Autoantibody Detection in Primary Biliary Cirrhosis. Front Immunol 2015; 6:309. [PMID: 26157439 PMCID: PMC4477174 DOI: 10.3389/fimmu.2015.00309] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2015] [Accepted: 05/29/2015] [Indexed: 01/27/2023] Open
Affiliation(s)
- Eduardo Luiz Rachid Cancado
- Department of Gastroenterology, Clinical Gastroenterology and Clinical Hepatology of Hospital das Clinicas, University of São Paulo School of Medicine , São Paulo , Brazil ; Laboratory of Immunopathology of Schistosomiasis, Institute of Tropical Medicine, University of São Paulo , São Paulo , Brazil ; Laboratory of Tropical Gastroenterology and Hepatology, Institute of Tropical Medicine , São Paulo , Brazil
| | - Michelle Harriz
- Department of Gastroenterology, Clinical Gastroenterology and Clinical Hepatology of Hospital das Clinicas, University of São Paulo School of Medicine , São Paulo , Brazil
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Quarneti C, Muratori P, Lalanne C, Fabbri A, Menichella R, Granito A, Masi C, Lenzi M, Cassani F, Pappas G, Muratori L. Fatigue and pruritus at onset identify a more aggressive subset of primary biliary cirrhosis. Liver Int 2015; 35:636-641. [PMID: 24698666 DOI: 10.1111/liv.12560] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2014] [Accepted: 03/28/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS In recent years, primary biliary cirrhosis is mostly diagnosed in patients who are asymptomatic; however, a proportion of cases still present with typical complaints such as fatigue and/or pruritus. We compared biochemical, histological and immunological features of patients with or without fatigue and/or pruritus at onset to see whether the different clinical presentation may eventually impact on disease progression. METHODS We analysed the Bologna cohort of 216 patients with primary biliary cirrhosis referred to our Centre between 1997 and 2007, according to symptomatic (fatigue and/or pruritus) or asymptomatic presentation. Clinical, biochemical, histological and immunological feature at diagnosis, response to ursodeoxycholic acid and progression of the disorder were compared after a mean follow-up of 81 ± 75 months. RESULTS At diagnosis, symptomatic patients were significantly more often women (98.6% vs. 87.2%, P = 0.004), younger (mean age 49 ± 12 vs. 55 ± 12 years, P = 0.003) and with more pronounced biochemical activity, as indicated by higher alkaline phosphatase (mean 2.93 ± 2 vs. 2.12, P = 0.002) and aminotransferase (mean 1.92 ± 1 vs. 1.47 ± 1.27, P = 0.014) levels, whereas histological stage and autoantibody profile were similar. Symptomatic patients were less likely to respond to ursodeoxycholic acid therapy (63% vs. 81%, P = 0.006) and developed more often cirrhosis and its complications (31% vs. 13%, P = 0.004). CONCLUSIONS Fatigue and/or pruritus at onset identify a subset of patients with primary biliary cirrhosis who preferentially are women, younger, with a particularly active disease, less responsive to ursodeoxycholic acid treatment, and more inclined to evolve to cirrhosis and its complications.
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Affiliation(s)
- Chiara Quarneti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Azienda Ospedaliera Universitaria Sant'Orsola-Malpighi, Bologna, Italy
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Li BA, Liu J, Hou J, Tang J, Zhang J, Xu J, Song YJ, Liu AX, Zhao J, Guo JX, Chen L, Wang H, Yang LH, Lu J, Mao YL. Autoantibodies in Chinese patients with chronic hepatitis B: Prevalence and clinical associations. World J Gastroenterol 2015; 21:283-291. [PMID: 25574103 PMCID: PMC4284347 DOI: 10.3748/wjg.v21.i1.283] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Revised: 07/02/2014] [Accepted: 08/28/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prevalence of autoantibodies and their associations with clinical features in Chinese patients with chronic hepatitis B (CHB).
METHODS: A total of 325 Chinese patients with CHB were enrolled in this retrospective, hospital-based study. Patients with chronic hepatitis C (CHC), autoimmune hepatitis (AIH), or primary biliary cirrhosis (PBC) were included, with healthy donors acting as controls. A panel of autoantibodies that serologically define AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay. The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies (ANA-H), smooth-muscle antibodies, anti-liver kidney microsome type 1, anti-liver cytosolic antigen type 1, and anti-soluble liver antigen/liver pancreas; the PBC-related antibodies were characterized by ANA-nuclear dots/membranous rim-like, anti-mitochondrial antibodies-M2 (AMA-M2), anti-BPO (recombinant antigen targeted by AMA-M2), anti-Sp100, anti-promyelocytic leukemia protein (anti-PML), and anti-gp210. The dichotomization of clustering was used to unequivocally designate the AIH or PBC profiles for each case. Anti-Ro52 antibodies were also tested.
RESULTS: The prevalence of any autoantibody in CHB amounted to 58.2%, which was similar to the 66.2% prevalence in CHC, significantly higher than the 6.7% in the healthy controls (P < 0.001), and lower than the 100% found in AIH and PBC (P = 0.004 and P < 0.001, respectively). There were more anti-PML and anti-gp210 antibodies among the CHB patients than the CHC patients (11.1% vs 0%, P = 0.003; 12.6% vs 0%, P < 0.001, respectively). The prevalence and titer of AMA, anti-BPO, anti-PML, and anti-gp210 were higher in PBC than in those with CHB. Among the CHB patients, the prevalence of ANA, especially ANA-H, was significantly lower in patients with compensated and decompensated cirrhosis compared with patients without cirrhosis. Thirty-eight cases of hepatocellular carcinoma (HCC) in CHB showed a significant difference compared with non-HCC patients in the prevalence of anti-PML (0% vs 12.5%, P = 0.013). Dichotomization of the autoantibodies revealed that the PBC profile was more prevalent in patients with CHB than in those with CHC, and that it was strongly correlated with both compensated and decompensated cirrhosis. In contrast, the prevalence of the AIH profile was significantly higher in non-cirrhosis patients with CHB than in those with compensated cirrhosis (18.5% vs 8.2%, P = 0.039). Moreover, the AIH profile was also closely associated with hepatitis B e-antigen positivity.
CONCLUSION: ANA-H could be an indicator of early-stage CHB. Dichotomizing the autoantibody profiles revealed that the PBC profile is strongly associated with cirrhosis in CHB.
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MESH Headings
- Adult
- Asian People
- Autoantibodies/blood
- Biomarkers/blood
- Carcinoma, Hepatocellular/blood
- Carcinoma, Hepatocellular/ethnology
- Carcinoma, Hepatocellular/immunology
- Carcinoma, Hepatocellular/virology
- China/epidemiology
- Diagnosis, Differential
- Female
- Hepatitis B e Antigens/blood
- Hepatitis B, Chronic/blood
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/ethnology
- Hepatitis B, Chronic/immunology
- Hepatitis, Autoimmune/blood
- Hepatitis, Autoimmune/ethnology
- Hepatitis, Autoimmune/immunology
- Humans
- Liver Cirrhosis/blood
- Liver Cirrhosis/ethnology
- Liver Cirrhosis/immunology
- Liver Cirrhosis/virology
- Liver Cirrhosis, Biliary/blood
- Liver Cirrhosis, Biliary/ethnology
- Liver Cirrhosis, Biliary/immunology
- Liver Neoplasms/blood
- Liver Neoplasms/ethnology
- Liver Neoplasms/immunology
- Liver Neoplasms/virology
- Male
- Middle Aged
- Predictive Value of Tests
- Prevalence
- Retrospective Studies
- Seroepidemiologic Studies
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Villalta D, Sorrentino MC, Girolami E, Tampoia M, Alessio MG, Brusca I, Daves M, Porcelli B, Barberio G, Bizzaro N. Autoantibody profiling of patients with primary biliary cirrhosis using a multiplexed line-blot assay. Clin Chim Acta 2015; 438:135-8. [DOI: 10.1016/j.cca.2014.08.024] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Revised: 08/19/2014] [Accepted: 08/20/2014] [Indexed: 12/18/2022]
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