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Tatour M, Baker FA, Saadi T, Yahia A, Hazzan R. Advancements in autoimmune hepatitis epidemiology, treatment and complication - a 15-year retrospective study. Clin Res Hepatol Gastroenterol 2025; 49:102570. [PMID: 40049285 DOI: 10.1016/j.clinre.2025.102570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 03/02/2025] [Accepted: 03/03/2025] [Indexed: 03/24/2025]
Abstract
INTRODUCTION AND OBJECTIVES Autoimmune hepatitis (AIH) is a rare, heterogeneous liver disease marked by autoantibodies, hypergammaglobulinemia, and distinct histological features. Predominantly affecting women, its incidence and prevalence show significant regional variability globally. Therefore, our aim is to examine the trends of AIH and to assess its demographics, management, and disease progression using an extensive population-based database. MATERIALS AND METHODS This retrospective, population-based study analyzed data from 2.7 million adults in Clalit Health Services, focusing on autoimmune hepatitis (AIH) diagnoses between 2009 and 2023. Data reordered included demographics, clinical details, and treatment regimens. Key outcomes tracked were the development of cirrhosis and its complications. RESULTS This study included 992 AIH patients with a median age of 51.5 years, 80.4 % female, and a median follow-up of 6.1 years. Obesity was present in 23.2 %, and 10.9 % had thyroid disease. At diagnosis, 22.9 % had cirrhosis, and an additional 137 patients developed cirrhosis during follow-up, leading to a total prevalence of 36.5 %. Among cirrhotic patients, 29.9 % experienced decompensation, 25.3 % developed ascites, 9.3 % had variceal bleeding, and 10.4 % developed hepatic encephalopathy. Hepatocellular carcinoma (HCC) occurred in 5.24 % of cirrhotic patients, with an incidence rate of 6.32 cases per 1000 patient-years. Overall, 11.2 % of cirrhotic patients underwent liver transplantation. The proportion of AIH patients diagnosed with cirrhosis at the time of diagnosis significantly decreased over the study period (p = 0.0028). CONCLUSIONS This study demonstrates a decreasing trend in AIH patients diagnosed with cirrhosis, suggesting earlier detection and improved management, alongside a lower documented incidence of HCC.
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Affiliation(s)
- Mifleh Tatour
- Clalit Health Services, Nof Hagalil, Israel; Department of Family Medicine, Clalit Health Services, Afula, Israel.
| | - Fadi Abu Baker
- Department of Gastroenterology and Hepatology, Hillel Yaffe Medical Center, Hadera 38100, Israel; Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel
| | - Tarek Saadi
- Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel; Liver Unit, Rambam Health Care Campus, Haifa, Israel
| | - Ahmad Yahia
- Department of Gastroenterology and Hepatology, Emek Medical Center, Afula, Israel
| | - Rawi Hazzan
- Clalit Health Services, Nof Hagalil, Israel; Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
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Xiong A, Li S, Dou X, Yao Y. Cyclophosphamide in refractory autoimmune hepatitis and autoimmune hepatitis coexisting extrahepatic autoimmune disorders. Am J Med Sci 2024; 368:446-454. [PMID: 38876435 DOI: 10.1016/j.amjms.2024.06.007] [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: 04/01/2023] [Revised: 12/19/2023] [Accepted: 06/10/2024] [Indexed: 06/16/2024]
Abstract
INTRODUCTION AND OBJECTIVES Despite tacrolimus (TAC) or mycophenolate mofetil (MMF) for alternate approaches, a proportion of patients still required further exploration of other therapeutic options due to uncontrolled autoimmune hepatitis(AIH). The role of cyclophosphamide (CYC) for AIH has been explored in isolated case reports and small series. We present a review of CYC therapy in AIH patients. MATERIALS AND METHODS A search for studies with keywords 'autoimmune hepatitis' and 'cyclophosphamide' was performed. Data recorded included gender, age, laboratory parameters and histological findings at the time of AIH diagnosis and before initiation of CYC therapy. RESULTS We identified 13 patients across 7 studies who met criteria for study inclusion, of whom around 69.2% (9/13) were primary refractory; 30.8% (4/13) patients used CYC as rescue therapy due to their coexisting autoimmune complications. The main findings of the study were that CYC appears to have an acceptable safety profile in difficult-to-treat AIH patients, with an overall remission rate of 88.9% (8/9). The other four patients with AIH accompanied by extrahepatic autoimmune disorders also achieved remission of transaminase levels and stability of liver function after the addition of CYC. A positive response to CYC treatment was seen in 12(92.3%) patients and none of them relapsed during the follow-up. CONCLUSIONS We cautiously recommend that CYC could be a conditioning alternative to starting second-line therapy after unsuccessful intensification of first-line treatment. Pharmacogenetic methods may play a role in guiding cyclophosphamide therapy. Given our small sample size, results should be considered preliminary.
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Affiliation(s)
- AnJi Xiong
- Department of Rheumatology and Immunology, Nanchong Central Hospital, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong Hospital of Bejjing Anzhen Hospital Capital Medical University, Nanchong, Sichuan Province, China; Inflammation and Immunology Key Laboratory of Nanchong City, Nanchong, Sichuan Province, China; Nanchong Central Hospital (Nanchong Clinical Research Center), Nanchong, Sichuan Province, China.
| | - SuTing Li
- Department of Ophthalmology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province 518035, China; Shenzhen University Health Science Center, 3688 Nanhai Avenue, Shenzhen, Guangdong Province 518060, China
| | - XiaoYan Dou
- Department of Ophthalmology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province 518035, China
| | - YuFeng Yao
- Department of Ophthalmology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province 518035, China; Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong Province 515031, China
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Al-Sum HA, Alsurori SM, Alkhlassi MN, Alanazi AA, Alkhlassi IN, Alkhlassi SN. Refractory Thrombocytopenia in a 29-Year-Old Pregnant Woman With Autoimmune Hepatitis: A Case Report and Literature Review. Cureus 2023; 15:e49189. [PMID: 38130547 PMCID: PMC10734889 DOI: 10.7759/cureus.49189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/19/2023] [Indexed: 12/23/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a rare autoimmune liver disease that mostly affects women in their reproductive years, leading to impaired fertility. Nonetheless, the majority of women with well-controlled AIH have a favorable prognosis for pregnancy. This case report describes a 29-year-old pregnant woman with cirrhosis secondary to AIH who presented with severe thrombocytopenia. Her labs showed a decline in her platelet counts from 28 × 109/L before pregnancy to 20 × 109/L during pregnancy. Her abdominal ultrasound showed liver cirrhosis secondary to AIH and splenomegaly. Throughout pregnancy, various scans were performed to monitor the fetal well-being, which showed normal results. She was on a medication regimen that included nadolol of 80 mg/kg/day, prednisolone of 5 mg/kg/day, and azathioprine of 50 mg/kg/day. Due to a breech presentation, the patient was scheduled for a cesarean section. She received two courses of dexamethasone at 20 mg/day for four days within two weeks of delivery. On the day of her scheduled C-section, tranexamic acid of 1 g TID for two days was administered, and she received platelet transfusions of 12 units both before and after the procedure, with an additional 6 units administered during the procedure. Despite proper management, her platelet count remained consistently low. However, she successfully delivered a healthy baby, and the overall condition of the patient was stable.
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Affiliation(s)
- Hythem A Al-Sum
- Department of Obstetrics and Gynaecology, Division of Maternal Fetal Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, SAU
| | - Suhad M Alsurori
- Department of Obstetrics and Gynaecology, Division of Maternal Fetal Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, SAU
| | - Maha N Alkhlassi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, SAU
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Mohamed DI, Abo Nahas HH, Elshaer AM, El-Waseef DAEDA, El-Kharashi OA, Mohamed SMY, Sabry YG, Almaimani RA, Almasmoum HA, Altamimi AS, Ibrahim IAA, Alshawwa SZ, Jaremko M, Emwas AH, Saied EM. Unveiling the interplay between NSAID-induced dysbiosis and autoimmune liver disease in children: insights into the hidden gateway to autism spectrum disorders. Evidence from ex vivo, in vivo, and clinical studies. Front Cell Neurosci 2023; 17:1268126. [PMID: 38026692 PMCID: PMC10644687 DOI: 10.3389/fncel.2023.1268126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 09/28/2023] [Indexed: 12/01/2023] Open
Abstract
Autism spectrum disorders (ASD) represent a diverse group of neuropsychiatric conditions, and recent evidence has suggested a connection between ASD and microbial dysbiosis. Immune and gastrointestinal dysfunction are associated with dysbiosis, and there are indications that modulating the microbiota could improve ASD-related behaviors. Additionally, recent findings highlighted the significant impact of microbiota on the development of autoimmune liver diseases, and the occurrence of autoimmune liver disease in children with ASD is noteworthy. In the present study, we conducted both an in vivo study and a clinical study to explore the relationship between indomethacin-induced dysbiosis, autoimmune hepatitis (AIH), and the development of ASD. Our results revealed that indomethacin administration induced intestinal dysbiosis and bacterial translocation, confirmed by microbiological analysis showing positive bacterial translocation in blood cultures. Furthermore, indomethacin administration led to disturbed intestinal permeability, evidenced by the activation of the NLRP3 inflammasomes pathway and elevation of downstream biomarkers (TLR4, IL18, caspase 1). The histological analysis supported these findings, showing widened intestinal tight junctions, decreased mucosal thickness, inflammatory cell infiltrates, and collagen deposition. Additionally, the disturbance of intestinal permeability was associated with immune activation in liver tissue and the development of AIH, as indicated by altered liver function, elevated ASMA and ANA in serum, and histological markers of autoimmune hepatitis. These results indicate that NSAID-induced intestinal dysbiosis and AIH are robust triggers for ASD existence. These findings were further confirmed by conducting a clinical study that involved children with ASD, autoimmune hepatitis (AIH), and a history of NSAID intake. Children exposed to NSAIDs in early life and complicated by dysbiosis and AIH exhibited elevated serum levels of NLRP3, IL18, liver enzymes, ASMA, ANA, JAK1, and IL6. Further, the correlation analysis demonstrated a positive relationship between the measured parameters and the severity of ASD. Our findings suggest a potential link between NSAIDs, dysbiosis-induced AIH, and the development of ASD. The identified markers hold promise as indicators for early diagnosis and prognosis of ASD. This research highlights the importance of maintaining healthy gut microbiota and supports the necessity for further investigation into the role of dysbiosis and AIH in the etiology of ASD.
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Affiliation(s)
- Doaa I. Mohamed
- Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | | | - Asmaa M. Elshaer
- Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | | | - Omnyah A. El-Kharashi
- Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Soha M. Y. Mohamed
- Physiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Yasmine Gamal Sabry
- Physiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Riyad A. Almaimani
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Hussain A. Almasmoum
- Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Abdulmalik S. Altamimi
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Ibrahim Abdel Aziz Ibrahim
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Samar Z. Alshawwa
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Mariusz Jaremko
- Smart-Health Initiative and Red Sea Research Center, Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia
| | - Abdul-Hamid Emwas
- Advanced Nanofabrication Imaging and Characterization Center, King Abdullah University of Science and Technology, Core Labs, Thuwal, Saudi Arabia
| | - Essa M. Saied
- Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt
- Institute for Chemistry, Humboldt Universität zu Berlin, Berlin, Germany
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Huang Z, Nie S, Wang H, Yan W, Tian D, Liu M. The proportion of regulatory T cells in peripheral blood of patients with autoimmune hepatitis: A systematic review and meta-analysis. Int Immunopharmacol 2023; 122:110576. [PMID: 37390643 DOI: 10.1016/j.intimp.2023.110576] [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: 04/05/2023] [Revised: 06/22/2023] [Accepted: 06/23/2023] [Indexed: 07/02/2023]
Abstract
BACKGROUND Many researches have reported the impairment of regulatory T cells (Tregs) in autoimmune hepatitis (AIH), whilst the change of Tregs in peripheral blood remains controversial. We performed this systematic review and meta-analysis to clarify the numerical change of circulating Tregs in AIH patients compared with healthy individuals. METHODS Relevant studies were identified from Medline, PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, and WanFang Data. Twenty-nine studies involving 968 AIH patients and 583 healthy controls were included. Subgroup analysis stratified by Treg definition or ethnicity was performed, and analysis of active-phase AIH was conducted. RESULTS The proportions of Tregs among CD4 T cells and PBMCs were generally decreased in AIH patients compared with healthy controls. Subgroup analysis showed that circulating Tregs identified by CD4+CD25+/high, CD4+CD25+Foxp3+, CD4+CD25+/highCD127-/low, and Tregs in Asian population were decreased among CD4 T cells in AIH patients. No significant change of CD4+CD25+/highFoxp3+CD127-/low Tregs and Tregs in Caucasian population among CD4 T cells were found in AIH patients, whereas the number of studies was limited in these subgroups. Moreover, analysis of the active-phase AIH patients showed that Treg proportions were decreased generally, whereas no significant differences in Tregs/CD4 T cells were observed when markers CD4+CD25+Foxp3+, CD4+CD25+/highFoxp3+CD127-/low were used or in Caucasian population. CONCLUSIONS The proportions of Tregs among CD4 T cells and PBMCs were decreased in AIH patients compared with healthy controls generally, whereas Treg definition markers, ethnicity, and disease activity had influence on the results. Further large-scale and rigorous study is warranted.
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Affiliation(s)
- Zheng Huang
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Shangshu Nie
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Han Wang
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Wei Yan
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Dean Tian
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Mei Liu
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China.
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van den Beukel MD, Stoelinga AEC, van der Meer AJ, van der Meulen S, Zhang L, Tushuizen ME, van Hoek B, Trouw LA. Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment. Front Med (Lausanne) 2023; 10:1195747. [PMID: 37564051 PMCID: PMC10411548 DOI: 10.3389/fmed.2023.1195747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 06/14/2023] [Indexed: 08/12/2023] Open
Abstract
Background (Auto)immune mediated and cholestatic liver disease (AILD) includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Especially AIH is characterized by the presence of autoantibodies and elevated serum immunoglobulins. In rheumatoid arthritis, autoantibodies against post-translational modifications (PTMs) such as citrullination (Cit) and carbamylation (CarP) are used as diagnostic and prognostic markers, respectively. We studied the presence of six anti-PTM antibodies in patients with the three AILDs and non-AILD. Methods Antibodies against six PTMs (malondialdehyde-acetaldehyde adducts (MAA), advanced glycation end-products (AGE), CarP, acetylation (AL), Cit, and nitration (NT)) were tested in sera of patients with AILD (n = 106), non-AILD (n = 101) and compared with healthy controls (HC) (n = 100). Levels and positivity were correlated with clinical and biochemical features in a well-defined cohort of untreated AIH patients. Results Anti-PTM antibodies were more often detectable in sera from AILD patients compared with HCs (anti-MAA: 67.9% vs. 2.0%, anti-AGE: 36.8% vs. 4.0%, anti-CarP: 47.2% vs. 5.0% and anti-AL: 18.9% vs. 5.0%). In untreated AIH, time to complete biochemical response (CBR) was associated with anti-MAA, anti-AGE, anti-CarP and anti-AL antibodies. Significantly more patients with at least three anti-PTM antibodies attained CBR at 12 months of treatment (13 vs. 3 p = 0.01). Conclusion Anti-PTM antibodies are frequently present in AILD. The presence of anti-MAA, anti-AGE and anti-CarP antibodies correlates with the presence of AIH within this cohort. In AIH, harboring at least three anti-PTM antibody responses is positively associated with CBR. Determination of anti-PTM antibodies in liver disease may have diagnostic and prognostic value.
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Affiliation(s)
| | - Anna E. C. Stoelinga
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands
| | - Adriaan J. van der Meer
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands
| | - Stef van der Meulen
- Department of Immunology, Leiden University Medical Center, Leiden, Netherlands
| | - Lu Zhang
- Department of Immunology, Leiden University Medical Center, Leiden, Netherlands
| | - Maarten E. Tushuizen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands
| | - Leendert A. Trouw
- Department of Immunology, Leiden University Medical Center, Leiden, Netherlands
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Khakwani A, Trivedi M, Afzal M, Kahlon P, Khola, Patel P, Chirumamilla PC, Vohra RR, Ratheesh R, Mathew M, Abdin ZU, Nazir Z. Use of Balloon Occluded Retrograde Transvenous Obliteration (BRTO) for Treatment of Gastric Varices: A Narrative Review. Cureus 2023; 15:e38233. [PMID: 37257163 PMCID: PMC10225054 DOI: 10.7759/cureus.38233] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/28/2023] [Indexed: 06/02/2023] Open
Abstract
Gastric Varices occur as a result of portal hypertension. Balloon Retrograde Transvenous Obliteration (BRTO) is a modality for managing gastric varices. The ultimate goal of this review is to promote the broader adoption of BRTO in managing gastric varices and to promote further research to improve patient outcomes. Before this study, an electronic literature search was undertaken based on identified concepts, keywords, and other pertinent descriptions. Search databases were developed and included "Gastric varices" AND "BRTO" OR "intervention" OR "treatment" OR "procedure" OR "glue" OR "adhesive". The databases selected and thoroughly searched were PubMed, Cochrane Library and ScienceDirect. Following the first search, 274 articles were found in total. By applying inclusion criteria of full-text articles and a period of fewer than five years, the database was reduced to 37 articles, which was then further filtered to include only articles on adults over 19 years old, leaving a total count of 17 articles. BRTO is a relatively simple procedure to perform once the essential skill is attained and helpful in both emergency and elective management of gastric varices. Its use still needs to be improved by the unavailability and lack of skills. However, there are side effects associated with BRTO as it causes elevation of portal hypertension, recurrent bleeding, hemoglobinuria and pain post procedure. This review emphasizes the need for further research in this field, focusing on refining patient selection criteria, improving the technical aspect of the procedure and enhancing long-term outcomes.
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Affiliation(s)
- Anum Khakwani
- Internal Medicine/Gastroenterology, Nishtar Medical University, Multan, PAK
| | - Manan Trivedi
- Department of Surgery, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai, IND
| | - Maham Afzal
- Medicine and Surgery, Shalamar Medical and Dental College, Lahore, PAK
| | - Puneet Kahlon
- Medicine, American International Medical University, Gros Islet, LCA
| | - Khola
- Internal Medicine, Shalamar Medical and Dental College, Lahore, PAK
| | - Parakh Patel
- Medicine, American International Medical University, Gros Islet, LCA
| | | | - Rimsha R Vohra
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Rani Ratheesh
- Internal Medicine, Dr MGR Medical University, Tamilnadu, IND
| | - Midhun Mathew
- Department of Internal Medicine, Pennsylvania Hospital, Philadelphia, USA
| | - Zain U Abdin
- Medicine, District Head Quarter Hospital, Faisalabad, PAK
| | - Zahra Nazir
- Internal Medicine/Clinical Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Sakulsaengprapha V, Wasuwanich P, Naraparaju G, Korotkaya Y, Thawillarp S, Oshima K, Karwowski C, Scheimann AO, Karnsakul W. Applicability of International Autoimmune Hepatitis Group (IAIHG) Scoring System for Autoimmune Hepatitis in Pediatrics. BIOLOGY 2023; 12:479. [PMID: 36979170 PMCID: PMC10045027 DOI: 10.3390/biology12030479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/17/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023]
Abstract
INTRODUCTION Many hepatologic pathologies mimic autoimmune hepatitis (AIH). Researchers developed the International Autoimmune Hepatitis Group (IAIHG) scoring system to compensate for the lack of specific diagnostic tests for AIH. The scoring system was not designed with pediatric patients in mind, so there are limits to its pediatric use. Additionally, there is limited information on the value of a liver biopsy in conjunction with its use. METHODS In this retrospective study, we evaluated the effect of liver biopsy scores on the IAIHG scoring system in patients that were 0-18 years old with suspected AIH. We also analyzed demographic data and laboratory values associated with a final AIH diagnosis. RESULTS We found that interface hepatitis and predominant plasma cells found during the biopsy were significantly associated with a final AIH diagnosis. We also found that abnormal laboratory values were associated with an AIH diagnosis. We found that IAIHG scores calculated post-liver biopsy showed a greater area under the receiver operating characteristic curve (AUROC) of 0.95, which was compared to 0.88 for the scores calculated before a liver biopsy. Including biopsy metrics lowered the optimized cutoff score and test specificity. CONCLUSION Incorporating liver histopathological features improved the performance of the IAIHG scoring system. Further studies to identify other potential elements in liver histology may improve the performance metrics of the IAIHG test in the pediatric population.
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Affiliation(s)
- Vorada Sakulsaengprapha
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (V.S.); (G.N.); (Y.K.); (C.K.); (A.O.S.)
| | - Paul Wasuwanich
- College of Medicine, University of Florida, Gainesville, FL 32610, USA;
| | - Gayathri Naraparaju
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (V.S.); (G.N.); (Y.K.); (C.K.); (A.O.S.)
| | - Yelena Korotkaya
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (V.S.); (G.N.); (Y.K.); (C.K.); (A.O.S.)
| | - Supharerk Thawillarp
- Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA;
| | - Kiyoko Oshima
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;
| | - Christine Karwowski
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (V.S.); (G.N.); (Y.K.); (C.K.); (A.O.S.)
| | - Ann O. Scheimann
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (V.S.); (G.N.); (Y.K.); (C.K.); (A.O.S.)
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; (V.S.); (G.N.); (Y.K.); (C.K.); (A.O.S.)
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Clinical Characteristics of Autoimmune Hepatitis in a Middle Eastern Population: A Tertiary Care Center Experience. J Clin Med 2023; 12:jcm12020629. [PMID: 36675558 PMCID: PMC9861091 DOI: 10.3390/jcm12020629] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 01/07/2023] [Accepted: 01/11/2023] [Indexed: 01/15/2023] Open
Abstract
Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease of uncertain cause, and its manifestations appear to vary by race and ethnicity. The literature on AIH in the Middle East, including Jordan, is scarce; therefore, this study aimed to determine the clinical characteristics of AIH in an understudied population. This retrospective chart review study was conducted on AIH patients who presented to Jordan University Hospital over a seven-year period (2014-2020). Retrieved data included sociodemographics, liver function tests, autoimmune serologic markers, viral hepatitis serology, findings on liver biopsies, treatment regimens, post-therapy outcomes and treatment-related complications. The total number of AIH patients included in the study was 30, divided as follows: type 1 AIH (n = 17, 56.7%), type 2 AIH (n = 2, 6.7%), seronegative AIH (n = 9, 30.0%), and two patients who had AIH-primary biliary cirrhosis overlap syndrome (6.7%). The mean age at diagnosis was 44 years (standard deviation: 17 years), with a female predominance (n = 25, 83.3%). Acute presentation was seen among 18 patients (60.0%). Mild to moderate fibrosis (F1 and F2 on METAVIR scoring system) without cirrhosis was observed among patients who underwent liver biopsies (10/19, 52.6%). The majority of patients (73.3%) were initially treated with prednisone, with azathioprine combination in 16.7% of the patients. At 6 months post initial treatment, twenty patients (66.7%) achieved biochemical remission, four patients had incomplete response, two patients failed to improve (one died during the induction of remission period due to AIH-related complications), and four patients were lost to follow-up. This study provided an updated overview of AIH in Jordan. The results showed typical female predominance, and interestingly high rates of acute presentation and seronegative disease. Future longitudinal studies are recommended to address the nature and long-term prognosis of AIH in Jordan.
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Ueda K, Aizawa Y, Kinoshita C, Nagano T, Ishida J, Saeki C, Oikawa T, Harada T, Hokari A, Saruta M. Centrilobular zonal necrosis is a unique subtype of autoimmune hepatitis: A cohort study. Medicine (Baltimore) 2022; 101:e29484. [PMID: 35866813 PMCID: PMC9302312 DOI: 10.1097/md.0000000000029484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 04/12/2022] [Accepted: 05/02/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUNDS Centrilobular zonal necrosis (CZN) is described as a histological feature present in a small number of autoimmune hepatitis (CZN-AIH) patients. CZN may be detected in the absence of significant interface hepatitis, which is the most important histological finding of AIH. The clinical and histopathological spectra of CZN-AIH were not homogeneous, and the concept of CZN-AIH as a distinctive subtype of AIH remains controversial, due to the rarity of CZN-AIH and the ambiguous definition of CZN. METHODS To elucidate the clinical and immunogenetic features of CZN-AIH, a total of 102 biopsy samples of AIH, obtained at The Jikei University Katsushika Medical Center and Jikei University Hospital from 2000 to 2018, were reviewed. The 32 patients whose biopsies showed CZN were selected as the CZN-AIH group, and the remaining 70 were grouped as the non-CZN-AIH controls (control AIH). Data on clinical, histopathologic, and immunogenetic features were statistically compared between the CZN-AIH and the control AIH group. Additionally, the impact of the onset pattern (acute or chronic) and coexistent significant interface hepatitis in CZN-AIH was determined. RESULTS In CZN-AIH, the frequency of acute-onset cases was significantly higher than that in control AIH (56.2% vs 32.9%; P < .05), and the number of cases with moderate-to-severe interface hepatitis in liver histology was significantly lower (37.5% vs 87.1%; P < .001). Compared to the control AIH, cases of CZN-AIH had lower immunoglobulin G level (P < .001), lower antinuclear antibodies titer (P < .001), and lower AIH score (P < .001). The immunogenetic disproportionate distribution of HLA-DR phenotypes in control AIH (increased HLA-DR4 and decreased HLA-DR9) was not found in CZN-AIH. Moreover, CZN-AIH was less frequently relapsed (P < .05). For the acute-onset CZN-AIH cases, the clinical features were hardly indistinguishable from the chronic CZN-AIH cases. Similarly, the existence of interface hepatitis did not influence on the pathophysiology of CZN-AIH. Moreover, the acute-onset CZN-AIH cases is clinically distinguishable from acute-onset control AIH. CONCLUSION CZN can characterize as a distinct AIH subtype, regardless of onset-pattern or coexistence of significant interface hepatitis. To further strengthen this hypothesis, collection of more CZN-AIH cases is needed.
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Affiliation(s)
- Kaoru Ueda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Katsushika Medical Center, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Yoshio Aizawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Katsushika Medical Center, Tokyo, Japan
| | - Chika Kinoshita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Katsushika Medical Center, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Tomohisa Nagano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Katsushika Medical Center, Tokyo, Japan
| | - Jinya Ishida
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Tsunekazu Oikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Toru Harada
- Division of Pathology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Atsushi Hokari
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Katsushika Medical Center, Tokyo, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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11
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Acute Hepatitis A-Induced Autoimmune Hepatitis: A Case Report and Literature Review. Medicina (B Aires) 2022; 58:medicina58070845. [PMID: 35888564 PMCID: PMC9325281 DOI: 10.3390/medicina58070845] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 06/22/2022] [Accepted: 06/23/2022] [Indexed: 11/30/2022] Open
Abstract
Introduction: The pathogenesis of autoimmune hepatitis (AIH) is little known. Previous case reports suggest that several viral hepatitis, including hepatitis A, can trigger AIH. Patient: A 55-year-old female showed general weakness and jaundice. The patient was diagnosed with acute hepatitis A and discharged after 14 days of hospitalization with improving liver function. However, blood tests performed 6 days after discharge revealed an increase in liver enzymes and high serum titers of an anti-nuclear antibody and immunoglobulin G. She was readmitted for liver biopsy. Diagnosis: Liver biopsy showed acute hepatitis A along with AIH. According to the revised international autoimmune hepatitis group scoring system, her score was 14 and she was diagnosed as AIH induced by acute hepatitis A. Intervention: Conservative treatments with crystalloid (Lactated Ringer’s Solution), ursodeoxycholic acid, and silymarin were administered. Outcomes: The patient has been followed up on an outpatient basis and neither symptom recurrence nor an increase in liver enzymes has been reported thus far. Lessons: After the treatment of acute hepatitis A, liver function needs to be carefully monitored over time, and the possibility of autoimmune hepatitis should be considered when liver enzymes increases.
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12
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Chen Y, Hua X, Huang B, Karsten S, You Z, Li B, Li Y, Li Y, Liang J, Zhang J, Wei Y, Chen R, Lyu Z, Xiao X, Lian M, Wei J, Fang J, Miao Q, Wang Q, Berglung UW, Tang R, Helleday T, Ma X. MutT Homolog 1 Inhibitor Karonudib Attenuates Autoimmune Hepatitis by Inhibiting DNA Repair in Activated T Cells. Hepatol Commun 2022; 6:1016-1031. [PMID: 34894107 PMCID: PMC9035570 DOI: 10.1002/hep4.1862] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 10/16/2021] [Accepted: 10/26/2021] [Indexed: 12/30/2022] Open
Abstract
Autoimmune hepatitis (AIH) is an inflammatory liver disease driven by the hyperactivation of various intrahepatic antigen-specific T cells due to a breach of immune tolerance. Studies in immunometabolism demonstrate that activated T cells harbor increased levels of reactive oxygen species that cause oxidative DNA damage. In this study, we assessed the potential of DNA damage repair enzyme MutT homolog 1 (MTH1) as a therapeutic target in AIH and karonudib as a novel drug for patients with AIH. We report herein that MTH1 expression was significantly increased in liver samples from patients with AIH compared to patients with chronic hepatitis B and nonalcoholic fatty liver disease and from healthy controls. In addition, the expression of MTH1 was positively correlated with AIH disease severity. We further found abundant T cells that expressed MTH1 in AIH. Next, we found that karonudib significantly altered T-cell receptor signaling in human T cells and robustly inhibited proliferation of human T cells in vitro. Interestingly, our data reflected a preferential inhibition of DNA damage repair in activated T cells by karonudib. Moreover, MTH1 was required to develop liver inflammation and damage because specific deletion of MTH1 in T cells ameliorated liver injury in the concanavalin A (Con A)-induced hepatitis model by inhibiting T-cell activation and proliferation. Lastly, we validated the protective effect of karonudib on the Con A-induced hepatitis model. Conclusion: MTH1 functions as a critical regulator in the development of AIH, and its inhibition in activated T cells reduces liver inflammation and damage.
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Affiliation(s)
- Yong Chen
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Xiangwei Hua
- Department of Thyroid Breast OncologyShanghai East Hospital, School of Medicine, Tongji University School of MedicineShanghaiChina
- Science for Life LaboratoryDepartment of Oncology and PathologyKarolinska InstitutetStockholmSweden
- Department of Liver Surgery and Liver Transplantation CenterRenji HospitalSchool of MedicineShanghaiChina
| | - Bingyuan Huang
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Stella Karsten
- Science for Life LaboratoryDepartment of Oncology and PathologyKarolinska InstitutetStockholmSweden
| | - Zhengrui You
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Bo Li
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - You Li
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Yikang Li
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Jubo Liang
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Jun Zhang
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Yiran Wei
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Ruiling Chen
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Zhuwan Lyu
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Xiao Xiao
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Min Lian
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Jue Wei
- Department of GastroenterologyShanghai Tongren HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina
| | - Jingyuan Fang
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Qi Miao
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Qixia Wang
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Ulrika Warpman Berglung
- Science for Life LaboratoryDepartment of Oncology and PathologyKarolinska InstitutetStockholmSweden
| | - Ruqi Tang
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
| | - Thomas Helleday
- Science for Life LaboratoryDepartment of Oncology and PathologyKarolinska InstitutetStockholmSweden
- Weston Park Cancer CentreDepartment of Oncology and MetabolismUniversity of SheffieldSheffieldUnited Kingdom
| | - Xiong Ma
- Division of Gastroenterology and HepatologyKey Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghaiChina
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13
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Thomas-Dupont P, Grube-Pagola P, Izaguirre-Hernández IY, Hernández-Flores KG, Sánchez-Marce EE, Cano-Contreras AD, Remes-Troche JM, Vivanco-Cid H. Development of a New Murine Model of Type 2 Autoimmune Hepatitis Using a Human Liver Protein. THE AMERICAN JOURNAL OF PATHOLOGY 2022; 192:21-30. [PMID: 34717895 DOI: 10.1016/j.ajpath.2021.10.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 09/13/2021] [Accepted: 10/04/2021] [Indexed: 11/17/2022]
Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver characterized by parenchymal destruction, hypergammaglobulinemia, specific autoantibody production, and hepatic fibrosis and necrosis. Murine models of AIH have been described; however, little is known about the immunologic mechanisms of tissue destruction. In this study, a new murine model of type 2 AIH was developed using recombinant human cytochrome P450 (CYP) 2D6 emulsified with complete Freund's adjuvant (CFA). BALB/c mice were immunized with 2 μg/mL i.p. of CYP2D6 in CFA. The control group received CFA or phosphate-buffered saline alone. Alanine aminotransferase activity, autoantibody production, IgG concentrations, histologic damage, and specific T-cell response were evaluated. Persistent AIH, characterized by cellular infiltration, hepatic fibrosis, elevated alanine aminotransferase, and the production of anti-liver kidney microsomal antibody type 1 developed in CFA/CYP2D6-immunized mice. These mice presented high levels of IgG and its subclasses IgG1, IgG2a, and IgG2b against liver self-proteins. Interestingly, IL-2+ and interferon γ-positive Cyp2d6-specific T cells were present in greater concentrations in mice immunized with CFA/CYP2D6 compared with control. Immunization with CFA, in combination with a natural human autoantigen like CYP2D6, was demonstrated to break tolerance, resulting in a chronic form of autoimmune-related liver damage. This murine model of type 2 AIH is expected to be instrumental in understanding the immunologic mechanisms of the pathogenesis of this autoimmune liver disease.
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Affiliation(s)
- Pablo Thomas-Dupont
- Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | - Peter Grube-Pagola
- Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | | | | | - Elvis E Sánchez-Marce
- Hospital Regional de Alta Especialidad de Veracruz, Servicios de Salud de Veracruz, Veracruz, México
| | - Ana D Cano-Contreras
- Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | - José M Remes-Troche
- Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | - Héctor Vivanco-Cid
- Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México.
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14
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Patel AM, Liu YS, Davies SP, Brown RM, Kelly DA, Scheel-Toellner D, Reynolds GM, Stamataki Z. The Role of B Cells in Adult and Paediatric Liver Injury. Front Immunol 2021; 12:729143. [PMID: 34630404 PMCID: PMC8495195 DOI: 10.3389/fimmu.2021.729143] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 08/16/2021] [Indexed: 12/16/2022] Open
Abstract
B lymphocytes are multitasking cells that direct the immune response by producing pro- or anti-inflammatory cytokines, by presenting processed antigen for T cell activation and co-stimulation, and by turning into antibody-secreting cells. These functions are important to control infection in the liver but can also exacerbate tissue damage and fibrosis as part of persistent inflammation that can lead to end stage disease requiring a transplant. In transplantation, immunosuppression increases the incidence of lymphoma and often this is of B cell origin. In this review we bring together information on liver B cell biology from different liver diseases, including alcohol-related and metabolic fatty liver disease, autoimmune hepatitis, primary biliary and primary sclerosing cholangitis, viral hepatitis and, in infants, biliary atresia. We also discuss the impact of B cell depletion therapy in the liver setting. Taken together, our analysis shows that B cells are important in the pathogenesis of liver diseases and that further research is necessary to fully characterise the human liver B cell compartment.
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Affiliation(s)
- Arzoo M. Patel
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Yuxin S. Liu
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Scott P. Davies
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Rachel M. Brown
- Department of Histopathology, Queen Elizabeth Hospital, Birmingham Women’s and Children’s National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
| | - Deirdre A. Kelly
- The Liver Unit, Birmingham Women’s and Children’s Hospital and the University of Birmingham, Birmingham, United Kingdom
| | - Dagmar Scheel-Toellner
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Gary M. Reynolds
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- The Liver Unit, Birmingham Women’s and Children’s Hospital and the University of Birmingham, Birmingham, United Kingdom
| | - Zania Stamataki
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
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15
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Liu G, Zhao W, Bai J, Cui J, Liang H, Lu B. Formononetin protects against concanavalin-A-induced autoimmune hepatitis in mice through its anti-apoptotic and anti-inflammatory properties. Biochem Cell Biol 2021; 99:231-240. [PMID: 33749318 DOI: 10.1139/bcb-2020-0197] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that seriously threatens the health of humans globally. Formononetin (FMN) is a natural herb extract with multiple biological functions. In this study, an experimental model of AIH was established in mice through the use of concanavalin A (ConA). To investigate the effects of FMN on ConA-induced hepatitis, the mice were pretreated with 50 or 100 mg/kg body mass of FMN. The results show that FMN alleviated ConA-induced liver injury of mice in a dose-dependent manner. Moreover, pretreatment with FMN inhibited the apoptosis of hepatocytes in the ConA-treated mice through downregulating the expression of pro-apoptotic proteins (Bax, cleaved caspase 9, and cleaved caspase 3) and upregulating the expression of anti-apoptotic protein (Bcl-2). It was also found that the levels of proinflammatory cytokines were greatly reduced in the serum and liver tissues of mice pretreated with FMN. Further studies showed that FMN reduced the level of phosphorylated nuclear factor kappa B (p-NF-κB) p65 and enhanced the level of IκBα (inhibitor of NF-κB), suggesting that FMN inhibits the activation of the NF-κB signaling pathway. In addition, FMN inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Therefore, FMN could be a promising agent for the treatment of AIH.
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Affiliation(s)
- Guangwei Liu
- Spleen, Stomach and Hepatobiliary Department, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450004, P.R. China
| | - Wenxia Zhao
- Spleen, Stomach and Hepatobiliary Department, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450004, P.R. China
| | - Jiameng Bai
- Spleen, Stomach and Hepatobiliary Department, Henan University of Chinese Medicine, Zhengzhou 450046, P.R. China
| | - Jianjiao Cui
- Spleen, Stomach and Hepatobiliary Department, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450004, P.R. China
| | - Haowei Liang
- Spleen, Stomach and Hepatobiliary Department, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450004, P.R. China
| | - Baoping Lu
- School of Basic Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, P.R. China
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16
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Fedrizzi RS, Coral GP, Mattos AAD, Mattos ÂZD, Tovo CV. EVALUATION OF PATIENTS WITH AUTOIMMUNE HEPATITIS IN A SPECIALIZED OUTPATIENT CLINIC IN SOUTHERN BRAZIL. ARQUIVOS DE GASTROENTEROLOGIA 2021; 57:361-365. [PMID: 33237214 DOI: 10.1590/s0004-2803.202000000-69] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by necroinflammation and autoimmune etiology. Studies evaluating the characteristics of patients with AIH are scarce in Brazil. OBJECTIVE Our objective was to evaluate the profile of patients with AIH in a specialized center in Southern Brazil and to verify factors related to treatment response. METHODS this was a retrospective cohort study, which analyzed demographic, epidemiological, clinical, laboratory, and histologic data. Patients with AIH diagnosed according to the criteria of the International Autoimmune Hepatitis Group (IAIHG) were included. In liver biopsies, the degree of fibrosis, histological activity, presence of hepatocyte rosettes, plasma cell infiltrates, and confluent necrosis were evaluated. In the statistical analysis, the significance level was 5%. RESULTS Forty adults patients diagnosed with AIH were included. The evaluated population predominantly consisted of women (75.0%) and the average age at diagnosis was 44.2 years. The association with extrahepatic autoimmune diseases occurred in 20.0% of cases. Clinically, 35.0% of patients presented with acute onset hepatitis, 37.5% with cirrhosis, and 27.5% with other forms of presentation. The most common clinical manifestation was jaundice (47.5%). Thirty-five patients were treated, and of these, 97.1% used prednisone combined with azathioprine. The average treatment time was 2.7 years. Response to treatment was complete or partial in 30 (85.7%) and absent in 5 (14.3%) patients. There was no statistically significant difference when evaluating response to treatment in relation to forms of presentation, histological findings, and the presence of autoantibodies. Regarding fibrosis, regression was observed in 18.75% of the cases. CONCLUSION Most patients with AIH were young at presentation and of female sex. The association with extrahepatic autoimmune diseases and cirrhosis at presentation was seen in a considerable proportion of patients. Treatment was effective, but there were no clinical, histological or serological parameters capable of predicting treatment response.
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Affiliation(s)
- Renata S Fedrizzi
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brasil
| | - Gabriela P Coral
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brasil
| | - Angelo A de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brasil
| | - Ângelo Z de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brasil
| | - Cristiane V Tovo
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brasil
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Comparison of the Effects of TIPS versus BRTO on Bleeding Gastric Varices: A Meta-Analysis. Can J Gastroenterol Hepatol 2020; 2020:5143013. [PMID: 32104670 PMCID: PMC7036113 DOI: 10.1155/2020/5143013] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 11/15/2019] [Accepted: 12/03/2019] [Indexed: 12/11/2022] Open
Abstract
UNLABELLED Background and Aim. Upper gastrointestinal bleeding is a threat to patients with gastric varices (GVs). Previous studies have concluded that both transjugular intrahepatic portosystemic shunt (TIPS) and balloon-occluded retrograde transvenous obliteration (BRTO) are effective treatments for patients with GV. We aimed to compare the efficiency and outcomes of these two procedures in GV patients through meta-analysis. METHODS The PubMed, Cochrane Library, EMBASE, and Web of Science databases were searched using the keywords: GV, bleeding, TIPS, and BRTO to identify relevant randomized controlled trials and cohort studies. The overall survival (OS) rate, imminent haemostasis rate, rebleeding rate, technical success rate, procedure complication rate (hepatic encephalopathy and aggravated ascites), and Child-Pugh score were evaluated. Randomized clinical trials and cohort studies comparing TIPS and BRTO for GV due to portal hypertension were included in our meta-analysis. Two independent reviewers performed data extraction and assessed the study quality. A meta-analysis was performed to calculate risk ratios (RRs), mean differences (MDs), and 95% CIs using random effects models. RESULTS A total of nine studies fulfilled the inclusion criteria. There was a significant difference between TIPS and BRTO in the OS rate (RR, 0.81 (95% CI, 0.66 to 0.98); P=0.03) and rebleeding rate (RR, 2.61 (95% CI, 1.75 to 3.90); P=0.03) and rebleeding rate (RR, 2.61 (95% CI, 1.75 to 3.90); P=0.03) and rebleeding rate (RR, 2.61 (95% CI, 1.75 to 3.90); P=0.03) and rebleeding rate (RR, 2.61 (95% CI, 1.75 to 3.90); P=0.03) and rebleeding rate (RR, 2.61 (95% CI, 1.75 to 3.90); P=0.03) and rebleeding rate (RR, 2.61 (95% CI, 1.75 to 3.90); P=0.03) and rebleeding rate (RR, 2.61 (95% CI, 1.75 to 3.90). CONCLUSIONS In this meta-analysis, BRTO brought more benefits to patients, with a higher OS rate and lower rebleeding rate. BRTO is a feasible method for GVB.
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Tu H, Chen D, Cai C, Du Q, Lin H, Pan T, Sheng L, Xu Y, Teng T, Tu J, Lin Z, Wang X, Wang R, Xu L, Chen Y. microRNA-143-3p attenuated development of hepatic fibrosis in autoimmune hepatitis through regulation of TAK1 phosphorylation. J Cell Mol Med 2020; 24:1256-1267. [PMID: 31808606 PMCID: PMC6991639 DOI: 10.1111/jcmm.14750] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 09/12/2019] [Accepted: 09/24/2019] [Indexed: 12/11/2022] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic liver disease due to autoimmune system attacks hepatocytes and causes inflammation and fibrosis. Intracellular signalling and miRNA may play an important role in regulation of liver injury. This study aimed to investigate the potential roles of microRNA 143 in a murine AIH model and a hepatocyte injury model. Murine AIH model was induced by hepatic antigen S100, and hepatocyte injury model was induced by LPS. Mice and AML12 cells were separated into six groups with or without the treatment of miRNA-143. Inflammation and fibrosis as well as gene expression were examined by different cellular and molecular techniques. The model was successfully established with the elevation of ALT and AST as well as inflammatory and fibrotic markers. Infection or transfection of mir-143 in mice or hepatocytes significantly attenuated the development of alleviation of hepatocyte injury. Moreover, the study demonstrated phosphorylation of TAK1-mediated miRNA-143 regulation of hepatic inflammation and fibrosis as well as hepatocyte injury. Our studies demonstrated a significant role of miRNA-143 in attenuation of liver injury in AIH mice and hepatocytes. miRNA-143 regulates inflammation and fibrosis through its regulation of TAK1 phosphorylation, which warrants TAK1 as a target for the development of new therapeutic strategy of autoimmune hepatitis.
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Affiliation(s)
- Hanxiao Tu
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
| | - Dazhi Chen
- Department of GastroenterologyThe First Hospital of Peking UniversityBeiJingChina
| | - Chao Cai
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
| | - Qianjing Du
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
| | - Hongwei Lin
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
| | - Tongtong Pan
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
| | - Lina Sheng
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
- Department of Infectious DiseasesThe Affiliated Yiwu Central Hospital of Wenzhou Medical UniversityYiwuChina
| | - Yuedong Xu
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
| | - Teng Teng
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
| | - Jingjing Tu
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
| | - Zhuo Lin
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
| | - Xiaodong Wang
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
| | - Rui Wang
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
| | - Lanman Xu
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
- Department of Infectious Diseases and Liver DiseasesNingbo Medical Center Lihuili HospitalNingboChina
- Department of Infectious Diseases and Liver DiseasesThe Affiliated Lihuili Hospital of Ningbo UniversityNingboChina
| | - Yongping Chen
- Department of Infectious DiseasesWenzhou Key Laboratory of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityHepatology Institute of Wenzhou Medical UniversityWenzhouChina
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Lian M, Zhang J, Zhao L, Chen X, Peng Y, Wang Q, Chen S, Ma X. Interleukin-35 Regulates Immune Microenvironment of Autoimmune Hepatitis Through Inducing the Expansion of Myeloid-Derived Suppressor Cells. Front Immunol 2019; 10:2577. [PMID: 31787974 PMCID: PMC6854006 DOI: 10.3389/fimmu.2019.02577] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Accepted: 10/17/2019] [Indexed: 12/26/2022] Open
Abstract
Interleukin-35 (IL-35) is a novel anti-inflammatory cytokine of IL12 cytokine family, however, the role of IL-35 in patients with AIH and its effect on myeloid-derived suppressor cells (MDSCs) has not yet been analyzed. The expression of IL-35 subunits (p35 and EBI3) in liver tissues was quantified by immunochemistry and its correlation with clinical parameters was explored in patients with AIH. The expression of MDSCs and IL-35 receptor (gp130 and IL-12Rβ2) were analyzed using flow cytometry and confocal staining. Besides, we utilized in vitro culture to explore the role of IL-35 on MDSCs expansion and activation. We found that the elevated expression of both IL-35 subunits (EBI3 and p35) in liver tissue was positively associated with degrees of hepatic inflammatory and fibrosis in patients with AIH. Furthermore, the expression of EBI3 in liver was positively correlated with patient age, serum IgG levels and serum AST, and was negatively correlated with hemoglobin and albumin. Moreover, our results showed that ratio of MDSC in peripheral blood increased significantly in AIH patients as compared with healthy controls. Further study showed that CD33, a representative marker of MDSCs, co-localized well with gp130 and IL12Rβ2, suggesting MDSCs as target cell for IL-35. Consistently, MDSCs from AIH displayed a substantial higher abundance of gp130 and IL12Rβ2 and were expanded by IL-35 in vitro. IL-35-induced MDSCs showed a significant increase in Nitric oxide (NO) production but not reactive oxygen species (ROS). Conclusions: IL-35 might play an important role in AIH by regulating MDSCs and it could provide new insights into the therapy of AIH.
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Affiliation(s)
- Min Lian
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Jun Zhang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Li Zhao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xiang Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Yanshen Peng
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Qixia Wang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Shengliang Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xiong Ma
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
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Chapman RW, Aspinall RJ, Trivedi P, Wright G, Heneghan M. Challenges in the use of corticosteroids in the management of autoimmune hepatitis. Br J Hosp Med (Lond) 2019; 80:594-599. [PMID: 31589514 DOI: 10.12968/hmed.2019.80.10.594] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Autoimmune hepatitis is widely assumed by health-care professionals to be a disease that is easily controlled through the use of corticosteroids and immunosuppressants but recent studies in the UK indicate highly variable treatment regimens and often unsatisfactory treatment outcomes, such as dependence on long-term high-dose steroids and ongoing need for liver transplantation in some cases. The therapeutic use of the systemically acting corticosteroid prednisolone results in unacceptable side effects in many patients. Recent evidence suggests that it is not always necessary to use high-dose steroids (>0.5 mg/kg/d) to attain remission; and side effects may also be minimised through more targeted therapy with the less systemically-absorbed corticosteroid, budesonide. The authors offer advice on the stratification of treatment for these patients and suggest changes to improve the services available for people with autoimmune hepatitis in the UK.
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Affiliation(s)
- Roger W Chapman
- Consultant Hepatologist, John Radcliffe Hospital, University of Oxford, Oxford
| | | | - Palak Trivedi
- Consultant Hepatologist and Clinician Scientist, NIHR Birmingham BRC, University of Birmingham, Birmingham
| | - Gavin Wright
- Consultant Hepatologist/Gastroenterologist, Basildon & Thurrock University Hospital, Basildon, Essex
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Incidence, prevalence, and causes of death of patients with autoimmune hepatitis: A nationwide register-based cohort study in Finland. Dig Liver Dis 2019; 51:1294-1299. [PMID: 30850346 DOI: 10.1016/j.dld.2019.01.015] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 01/08/2019] [Accepted: 01/27/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Epidemiological studies of autoimmune hepatitis are scarce and often based on single centre registries. AIMS We conducted a nationwide register study of incidence, prevalence, survival, and causes of death of autoimmune hepatitis patients in Finland. METHODS Autoimmune hepatitis cases 1995-2015 were retrieved from the national database of special reimbursements for drugs costs. Data on causes of death were retrieved from Statistics Finland. RESULTS After incomplete registration of AIH during the first years, the incidence of autoimmune hepatitis stabilised to 1.1/100,000 person-years (1.6 in women and 0.52 in men) in 2008-2015. The prevalence of autoimmune hepatitis at the end of 2015 was 14.3/100,000, 23.0/100,000 in women and 6.6/100,000 in men. The all-cause standardized mortality ratio (SMR) of autoimmune hepatitis patients was 1.81 (95% confidence interval (CI) 1.47-2.20). The SMR was increased in all age groups and in both sexes. The SMR for hepatocellular carcinoma was 20.6 (95% CI 10.3-36.8), and for digestive diseases in overall 13.5 (95% CI 8.2-20.8), constituting mainly from autoimmune hepatitis and liver cirrhosis. CONCLUSION Incidence of autoimmune hepatitis has remained stable, with clear female predominance. Autoimmune hepatitis is associated with a markedly increased risk of death with hepatocellular cancer forming the greatest risk.
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Zipprich A. Rheumatologie und Hepatologie: Diagnostik und Therapie von
autoimmunen Lebererkrankungen. AKTUEL RHEUMATOL 2019. [DOI: 10.1055/a-0885-9314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
ZusammenfassungUnter autoimmunen Lebererkrankungen werden im klassischen Sinne 3 verschiedene
Entitäten, die Autoimmune Hepatitis (AIH), die Primär biliäre Cholangitis (PBC)
und die Primär sklerosierende Cholangitis (PSC) verstanden. Der nachfolgende
Übersichtartikel fokusiert auf die Diagnostik und die Therapie dieser 3
autoimmunen Lebererkrankungen und gibt eine Übersicht zu möglichen zusätzlich
assoziierten Autoimmunerkrankungen.
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Palle SK, Naik KB, McCracken CE, Kolachala VL, Romero R, Gupta NA. Racial disparities in presentation and outcomes of paediatric autoimmune hepatitis. Liver Int 2019; 39:976-984. [PMID: 30802337 DOI: 10.1111/liv.14081] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 02/12/2019] [Accepted: 02/19/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Most studies on autoimmune hepatitis (AIH) in children are in predominantly Caucasian cohorts. Paediatric AIH in African Americans (AA) is understudied, with a dearth of clinical predictors of outcome, often leading to serious complications and even mortality. The aim of the study was to define disease presentation, progression, response to therapy and outcomes in paediatric AIH in a well-defined, large, single centre, demographically diverse population. METHODS We conducted a review of patients with AIH who were followed at this tertiary liver transplant centre. Clinical and laboratory covariates were assessed with regard to disease presentation, progression and outcomes in AA vs Non-AA children. RESULTS African Americans patients constituted 42% of this cohort. At 1-year follow-up, AA children were receiving significantly higher doses of steroids compared to non-AA. More AA presented with end-stage liver disease (ESLD) with high immunoglobulin G and GGT:platelet ratio. After adjusting for other risk factor variables like gender, age at presentation and ESLD, AA children were at 4.5 times higher risk for significant outcome liver transplant/death within the first 12 months of presentation. Post-transplant, recurrent AIH was seen in 50% of AA vs 8% in non-AA. CONCLUSIONS African American patients with AIH are more likely to present with ESLD and have an increased early risk for transplantation with high likelihood of disease recurrence post-transplantation. Studies are needed to delineate factors such as inherent biology, genetics and access to care. Early referral and tailored immunosuppressive regimens are required for AA patients with AIH.
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Affiliation(s)
- Sirish K Palle
- Transplant Services, Children's Healthcare of Atlanta (CHOA), Atlanta, Georgia.,Department of Pediatrics, Emory University (EU) School of Medicine (SOM), Atlanta, Georgia
| | - Kushal B Naik
- Transplant Services, Children's Healthcare of Atlanta (CHOA), Atlanta, Georgia.,Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Courtney E McCracken
- Department of Pediatrics, Emory University (EU) School of Medicine (SOM), Atlanta, Georgia
| | - Vasantha L Kolachala
- Department of Pediatrics, Emory University (EU) School of Medicine (SOM), Atlanta, Georgia
| | - Rene Romero
- Transplant Services, Children's Healthcare of Atlanta (CHOA), Atlanta, Georgia.,Department of Pediatrics, Emory University (EU) School of Medicine (SOM), Atlanta, Georgia
| | - Nitika A Gupta
- Transplant Services, Children's Healthcare of Atlanta (CHOA), Atlanta, Georgia.,Department of Pediatrics, Emory University (EU) School of Medicine (SOM), Atlanta, Georgia
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24
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Nicoll AJ, Roberts SK, Lim R, Mitchell J, Weltman M, George J, Wigg A, Stuart K, Gow P, MacQuillan G, Tse E, Levy M, Sood S, Zekry A, Cheng W, Mitchell J, Skoien R, Sievert W, Strasser SI, McCaughan GW. Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels. Aliment Pharmacol Ther 2019; 49:1314-1322. [PMID: 30972807 DOI: 10.1111/apt.15248] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 12/15/2018] [Accepted: 03/12/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). AIM To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. METHODS We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. RESULTS A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG; P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre-treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. CONCLUSION Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre-treatment IgG levels.
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Ebadi M, Bhanji RA, Mazurak VC, Lytvyak E, Mason A, Czaja AJ, Montano-Loza AJ. Severe vitamin D deficiency is a prognostic biomarker in autoimmune hepatitis. Aliment Pharmacol Ther 2019; 49:173-182. [PMID: 30484857 DOI: 10.1111/apt.15029] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 07/30/2018] [Accepted: 09/30/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Vitamin D deficiency has been implicated in the outcome of chronic liver disease. AIM To determine the frequency of severe vitamin D deficiency in autoimmune hepatitis (AIH), assess its association with treatment non-response, and evaluate the relationship between vitamin D status and liver-related mortality and need for transplantation. METHODS Two hundred and nine patients were evaluated by liver tissue examination at presentation. Serum vitamin D levels were determined, and serum levels <25 nmol/L (10 ng/mL) were considered severely deficient. Treatment non-response was defined as non-normalised aspartate aminotransferase/alanine aminotransferase and immunoglobulin G levels during conventional immunosuppressive therapy. Univariate and multivariate analyses were performed using binary logistic regression and Cox proportional hazards model. RESULTS The mean vitamin D level was 60 ± 38 nmol/L (range, 3-263 nmol/L), and 42 patients (20%) had severe vitamin D deficiency. Treatment non-response was more common in patients with severe vitamin D deficiency than in patients without (59% vs 41%, P = 0.04). Severe vitamin D deficiency was also independently associated with a higher risk of developing cirrhosis (HR 3.40; 95% CI 1.30-8.87, P = 0.01) and liver-related mortality or requirement for liver transplantation (LT; HR 5.26, 95% CI, 1.54-18.0, P = 0.008). Patients with persistent severe deficiency following vitamin D supplementation continued to have poor outcomes. CONCLUSIONS Severe vitamin D deficiency is associated with treatment non-response, progression to cirrhosis, and liver-related death or need for LT. Severe vitamin D deficiency is a prognostic biomarker in AIH.
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Affiliation(s)
- Maryam Ebadi
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - Rahima A Bhanji
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - Vera C Mazurak
- Division of Human Nutrition, University of Alberta, Edmonton, AB, Canada
| | - Ellina Lytvyak
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - Andrew Mason
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
| | - Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - Aldo J Montano-Loza
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
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26
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Incidence and Clinical Features of Autoimmune Hepatitis in the Province of Santa Fe (Argentina). J Pediatr Gastroenterol Nutr 2018; 67:e107-e110. [PMID: 30095578 DOI: 10.1097/mpg.0000000000002122] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJETIVES The aim of the study is to investigate the incidence and clinical features of autoimmune hepatitis (AIH) in children from the province of Santa Fe, Argentina, for 10 years. METHODS From the records of all of the pediatric hepatologists in the province of Santa Fe, Argentina, we reviewed the clinical charts of patients <18 years who were diagnosed with AIH (simplified score >6 points) and followed between January 2003 and December 2013. Population data were extracted from the 2010 national census. Values were expressed as percentages and median ± interquartile range. Mann-Whitney U test was used for comparison between the groups. RESULTS Sixty-seven patients fulfilled inclusion criteria, from which 11 (16%) were later reclassified as having "autoimmune sclerosing cholangitis" according to biochemical, histological, and radiological findings. A final sample of 56 patients (39 F) with AIH was analyzed, giving an annual incidence of 0.56/100,000. Median age at presentation was 8 (5.7-11) years, and the median follow-up was 4 (2-7) years. Type 1 AIH was diagnosed in 89%. An acute presentation was observed in 53%, while 13 (23%) showed cirrhosis on initial biopsy. Prednisone (87%) and azathioprine (60%) were the most common drugs prescribed. At the end of follow-up, 53/56 (95%) were alive, including 4 patients (7%) who underwent liver transplantation. CONCLUSIONS AIH has an estimated incidence of 0.56/100,000 per year in children from the province of Santa Fe (Argentina). Overall survival rate was 95%. A subgroup of patients diagnosed as AIH develops predominant biliary disease and should be better classified as autoimmune sclerosing cholangitis.
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Aljumah AA, Al Jarallah B, Albenmousa A, Al Khathlan A, Al Zanbagi A, Al Quaiz M, Al-Judaibi B, Nabrawi K, Al Hamoudi W, Alghamdi M, Fallatah H. The Saudi association for the study of liver diseases and transplantation clinical practice guidelines for management of autoimmune hepatitis. Saudi J Gastroenterol 2018; 24:S1-S20. [PMID: 30264737 PMCID: PMC6305081 DOI: 10.4103/sjg.sjg_159_18] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Abdulrahman A. Aljumah
- Division of Hepatology, Hepatobiliary Sciences and Organ Transplant Center, King Abdulaziz Medical City and King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Badr Al Jarallah
- Department of Medicine, Division of Gastroenterology, Al Qassim University, Al Qassim, Saudi Arabia
| | - Ali Albenmousa
- Department of Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Abdullah Al Khathlan
- Department of Medicine, Division of Gastroenterology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Adnan Al Zanbagi
- Department of Medicine, Division of Gastroenterology, King Abdullah Medical City, Makkah, Saudi Arabia
| | - Mohammed Al Quaiz
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Bandar Al-Judaibi
- Department of Medicine, University of Rochester, Rochester City, New York State, USA
| | - Khalid Nabrawi
- Department of Internal Medicine, Aseer Central Hospital, Abha, Saudi Arabia
| | - Waleed Al Hamoudi
- Department of Medicine, Division of Gastroenterology, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Alghamdi
- Department of Internal Medicine, King Fahad Military Medical City, Dhahran, Saudi Arabia
| | - Hind Fallatah
- Department of Medicine, Division of Gastroenterology and Hepatology, King Abdulaziz University, Jeddah, Saudi Arabia
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Abdel-Razik A, Mousa N, Shabana W, Refaey M, Elzehery R, Elhelaly R, Zalata K, Abdelsalam M, Eldeeb AA, Awad M, Elgamal A, Attia A, El-Wakeel N, Eldars W. Rifaximin in nonalcoholic fatty liver disease: hit multiple targets with a single shot. Eur J Gastroenterol Hepatol 2018; 30:1237-1246. [PMID: 30096092 DOI: 10.1097/meg.0000000000001232] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS The pathogenesis of nonalcoholic fatty liver disease (NAFLD) may include increased insulin resistance, upregulation of proinflammatory cytokines, lipopolysaccharide, and BMI. Rifaximin is a minimally absorbable antibiotic that might act against a broad spectrum of gut bacteria. This study aimed to investigate the effects of rifaximin on NAFLD. PATIENTS AND METHODS Fifty participants with biopsy-proven nonalcoholic steatohepatitis (NASH) were registered in this multicentric, double-blind, randomized, placebo-controlled study. BMI, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, lipid profile, serum endotoxin, homeostatic model assessment, toll-like receptor-4, interleukin-10 (IL-10), IL-6, tumor necrosis factor-α, and cytokeratin-18 (CK-18) levels were evaluated at baseline and at 1, 3, and 6 months of rifaximin therapy (1100 mg/day). RESULTS Patients were randomized into two groups (rifaximin group; n=25 and placebo group; n=25). After 6 months of rifaximin therapy, patients with NASH showed a significant reduction in homeostatic model assessment, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, endotoxin, toll-like receptor-4, IL-6, tumor necrosis factor-α, CK-18, and NAFLD-liver fat score (all P<0.05), but no changes in the lipid profile; moreover, there was a mild nonstatistically significant reduction of BMI. However, in the placebo group, there was no significant difference in these variables at baseline and after therapy. CONCLUSION Rifaximin therapy appears to be effective and safe in modifying NASH through reduction of serum endotoxin and improvement of insulin resistance, proinflammatory cytokines, CK-18, and NAFLD-liver fat score.
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Affiliation(s)
| | | | | | - Mohamed Refaey
- Department of Tropical Medicine, Faculty of Medicine, Zagazig University, Zagazig City
| | | | | | | | | | | | | | | | - Ahmed Attia
- Department of Hepatology, National Liver Institute, Menoufia University, Shebeen El-kom, Egypt
| | - Niveen El-Wakeel
- Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura City
| | - Waleed Eldars
- Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura City
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O'Brien CB, Barnea ER, Martin P, Levy C, Sharabi E, Bhamidimarri KR, Martin E, Arosemena L, Schiff ER. Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Trial of Synthetic Preimplantation Factor in Autoimmune Hepatitis. Hepatol Commun 2018; 2:1235-1246. [PMID: 30411073 PMCID: PMC6218676 DOI: 10.1002/hep4.1239] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 07/09/2018] [Indexed: 12/16/2022] Open
Abstract
Preimplantation factor (PIF) is an evolutionary conserved peptide secreted by viable embryos which promotes maternal tolerance without immune suppression. Synthetic PIF (sPIF) replicates native peptide activity. The aim of this study was to conduct the first‐in‐human trial of the safety, tolerability, and pharmacokinetics of sPIF in patients with autoimmune hepatitis (AIH). We performed a randomized, double‐blind, placebo‐controlled, prospective phase I clinical trial. Patients were adults with documented AIH with compensated chronic liver disease. Diagnosis of AIH was confirmed by either a pretreatment International Criteria for the Diagnosis of AIH score of 15 or more, or a posttreatment score of 17 or more. Patients were divided into three dosing cohorts (0.1, 0.5, or 1.0 mg/kg) of 6 patients in each group. Three patients in each group had normal liver tests and 3 patients had abnormal liver tests. They were randomized to receive a single, subcutaneous dose of either sPIF or a matching placebo. Eighteen patients were enrolled, and all successfully completed the trial. There were no clinically significant adverse events and all doses were well tolerated. Ascending doses of sPIF produced a linear increase in the respective serum levels with a half‐life of 90 minutes. There were no grade 2, 3 or 4 laboratory abnormalities. No patient developed detectable anti‐sPIF antibodies. Conclusion: This first‐in‐human trial of the safety and pharmacokinetics of sPIF (a novel biologic immune modulatory agent) demonstrated both excellent safety and tolerability. The data support further studies of multiple ascending doses of sPIF in autoimmune hepatitis and potentially other autoimmune disorders.
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Affiliation(s)
| | | | - Paul Martin
- University of Miami Schiff Center for Liver Diseases Miami Florida
| | - Cynthia Levy
- University of Miami Schiff Center for Liver Diseases Miami Florida
| | - Eden Sharabi
- Northwestern University Medical School Chicago Illinois
| | | | - Eric Martin
- University of Miami Schiff Center for Liver Diseases Miami Florida
| | | | - Eugene R Schiff
- University of Miami Schiff Center for Liver Diseases Miami Florida
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30
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Minghui Z, Kunhua H, Yunwen B, Hongmei L, Jing L, Shaowen W, Longqiaozi S, Chaohui D. Analysis of Differentially Expressed Proteins Involved in Autoimmune Cirrhosis and Normal Serum by iTRAQ Proteomics. Proteomics Clin Appl 2018; 13:e1700153. [PMID: 29999587 PMCID: PMC6585725 DOI: 10.1002/prca.201700153] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Revised: 04/20/2018] [Indexed: 12/15/2022]
Abstract
PURPOSE In order to study the candidate biomarkers in autoimmune cirrhosis (AIC). EXPERIMENTAL DESIGN Isobaric tags are first implemented for relative and absolute quantitation technology on proteins prepared from serum obtained from AIC and normal controls. Proteins found to be differentially expressed are identified with liquid chromatography electrospray ionization tandem mass spectrometry by using a Q Exactive classic ion trap mass spectrometer. RESULTS 108 proteins (32 upregulated and 76 downregulated proteins) are identified from AIC samples, compared with the normal controls. Gene Ontology enrichment analysis, KEGG pathway analysis, and protein-protein interaction map by STRING show that they associate with multiple functional groups, including ion binding activity, peptidase activity, and enzyme regulator activity. Finally, the von Willebrand factor, insulin-like growth factor-binding protein complex acid labile subunit, transthyretin, adiponectin proteins are identified with western blot as candidate biomarkers for AIC. CONCLUSIONS AND CLINICAL RELEVANCE These findings offer a comprehensive profile of the AIC proteome about candidate biomarkers and provide a useful basis for further analysis of the pathogenic mechanism of AIC.
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Affiliation(s)
- Zheng Minghui
- Department of Clinical Laboratory, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China
| | - Hu Kunhua
- Proteomics Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China
| | - Bao Yunwen
- Department of Clinical Laboratory, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China
| | - Lu Hongmei
- The Second Clinical Medical College, Guangdong Medical University, Dongguan, 523808, China
| | - Li Jing
- Department of Clinical Laboratory, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China
| | - Wu Shaowen
- Department of Clinical Laboratory, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China
| | - Sun Longqiaozi
- Department of Clinical Laboratory, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China
| | - Duan Chaohui
- Department of Clinical Laboratory, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China
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Rizvi S, Gawrieh S. Autoimmune Hepatitis in the Elderly: Diagnosis and Pharmacologic Management. Drugs Aging 2018; 35:589-602. [PMID: 29971609 DOI: 10.1007/s40266-018-0556-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Autoimmune hepatitis (AIH) may present as acute or chronic hepatitis in the elderly. Advanced hepatic fibrosis and cirrhosis are common on first presentation in this population. In this review, we discuss the presentation, approach to diagnosis and management of AIH in the elderly. As polypharmacy is common in the elderly, careful medication use history is essential for detecting drug-induced AIH-like hepatitis. Steroid-sparing or minimizing therapeutic regimens are preferred to treat AIH in the elderly. For the purpose of induction, budesonide or lower dose prednisone in combination with azathioprine (AZA) regimens are preferred over high-dose prednisone monotherapy due to the higher risk of side effects of the later in the elderly. The goal of maintenance therapy should be to achieve full biochemical and histologic remission. Bone density monitoring and interventions to prevent steroid-related bone disease should be implemented throughout the course of the disease. Liver transplantation should be considered in the elderly patient with liver failure or early hepatocellular carcinoma if there are no significant comorbidities or compromise in functional status.
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Affiliation(s)
- Syed Rizvi
- Gastroenterology and Hepatology Division, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI, 53226, USA.
| | - Samer Gawrieh
- Gastroenterology and Hepatology Division, Indiana University School of Medicine, 702 Rotary Cir, Indianapolis, IN, 46202-5175, USA.
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Kalra A, Burton JR, Forman LM. Pro: Steroids Can Be Withdrawn After Transplant in Recipients With Autoimmune Hepatitis. Liver Transpl 2018; 24:1109-1112. [PMID: 29923302 DOI: 10.1002/lt.25206] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 03/19/2018] [Accepted: 03/31/2018] [Indexed: 02/07/2023]
Abstract
Corticosteroids have been a mainstay of immunosuppression following liver transplantation. However, evolution in the field of transplant immunology has produced steroid-free options, resulting in most transplant centers weaning steroids after transplant within days to months-an evidence-based management decision. Patients with autoimmune hepatitis (AIH), however, receive corticosteroids prior to transplant. This raises the question of whether these patients should also be weaned from corticosteroids. In this review, we discuss the benefits of avoiding steroid use in this population of patients-an approach that not only avoids the adverse effects of corticosteroids but does so without risking graft failure from recurrent AIH or from acute cellular rejection.
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Affiliation(s)
- Avash Kalra
- Division of Gastroenterology and Hepatology, University of Colorado, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - James R Burton
- Division of Gastroenterology and Hepatology, University of Colorado, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Lisa M Forman
- Division of Gastroenterology and Hepatology, University of Colorado, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO
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Tang HH, Li HL, Li YX, You Y, Guan YY, Zhang SL, Liu LX, Bao WL, Zhou Y, Shen XY. Protective effects of a traditional Chinese herbal formula Jiang-Xian HuGan on Concanavalin A-induced mouse hepatitis via NF-κB and Nrf2 signaling pathways. JOURNAL OF ETHNOPHARMACOLOGY 2018; 217:118-125. [PMID: 29421593 DOI: 10.1016/j.jep.2018.02.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 01/31/2018] [Accepted: 02/03/2018] [Indexed: 05/21/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Jiang-Xian HuGan (JXHG) formulated by five natural products including Freshwater clam (Corbicula fluminea), Curcuma longa L., Ligustrum lucidum, Eclipta prostrata (L.) L. and Paeonia lactiflora Pall., has exhibited a great hepatoprotective effect. AIM OF THIS STUDY We investigated the effect of JXHG on concanavalin A (ConA)-induced acute live injury in mice, and to elucidate its underlying molecular mechanisms. MATERIALS AND METHODS Jiangkanling Capsule (900 mg/kg), low-dose JXHG (LJXHG, 700 mg/kg), high-dose JXHG (HJXHG, 1400 mg/kg) were administered to mice by oral gavage daily for 20 days prior to a single intravenous injection of ConA (20 mg/kg). Liver injury was evaluated by measuring the serum levels of enzymes and cytokines as well as liver histological analysis. We also measured the hepatic expression of cytokines at mRNA levels and the proteins related to NF-κB and Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways. RESULT Our results showed that JXHG pretreatment significantly alleviated ConA-induced live injury as evidenced by decreased serum levels of glutamic-pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST), and reduced hepatocyte apoptosis and mortality. Furthermore, JXHG was able to significantly reduce the serum levels of proinflammatory cytokines, down-regulate the mRNA expression of interleukin-6 (IL-6) and interferon-γ (IFN-γ), and up-regulate IL-10 as well as superoxide-dimutase-1 (SOD1), glutathione reductase (GSR) and Glutathione peroxidase 2 (GPX2) mRNA in the liver tissues after Con A injection. In addition, JXHG pretreatment dramatically suppressed the phosphorylation of NF-κB p65 (p65), increased Nrf2 expression, and decreased the expression ratio of cleaved caspase-3/caspase-3 in liver tissues. CONCLUSION These results suggest that JXHG protects against ConA-induced acute live injury through inhibiting NF-κB mediated inflammatory pathway and promoting Nrf2 mediated anti-oxidative stress signaling pathway.
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Affiliation(s)
- Huan-Huan Tang
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China; Department of Pharmacology, School of Pharmacy, Guilin Medical University, No. 109 Huanchengbei Road Two, Guilin 541004, China
| | - Hai-Long Li
- Infinitus R&D Center, Infinitus (China) Company Ltd, No.19, Sicheng Road, The First Floor of HongTai Zhihui Valley, Tianhe Area, Guangzhou 510663, China
| | - Yue-Xuan Li
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Yan You
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Yun-Yun Guan
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Su-Lin Zhang
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Li-Xin Liu
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Wei-Lian Bao
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Yong Zhou
- Infinitus R&D Center, Infinitus (China) Company Ltd, No.19, Sicheng Road, The First Floor of HongTai Zhihui Valley, Tianhe Area, Guangzhou 510663, China.
| | - Xiao-Yan Shen
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China.
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Arcos-Machancoses JV, Molera Busoms C, Julio Tatis E, Victoria Bovo M, Quintero Bernabeu J, Juampérez Goñi J, Crujeiras Martínez V, Martin de Carpi J. Accuracy of the 2008 Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Children. Pediatr Gastroenterol Hepatol Nutr 2018; 21:118-126. [PMID: 29713609 PMCID: PMC5915689 DOI: 10.5223/pghn.2018.21.2.118] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/28/2017] [Accepted: 12/18/2017] [Indexed: 02/07/2023] Open
Abstract
PURPOSE Classical criteria for diagnosis of autoimmune hepatitis (AIH) are intended as research tool and are difficult to apply at patient's bedside. We aimed to study the accuracy of simplified criteria and the concordance with the expert diagnosis based on the original criteria. METHODS A cohort of children under study for liver disorder was selected through consecutive sampling to obtain the prevalence of AIH within the group of differential diagnoses. AIH was defined, based on classical criteria, through committee review of medical reports. Validity indicators of the simplified criteria were obtained in an intention to diagnose approach. Optimal cut-off and the area under the receiver operating characteristic (ROC) curve were calculated. RESULTS Out of 212 cases reviewed, 47.2% were AIH. For the optimal cut-off (6 points), the simplified criteria showed a sensitivity of 72.0% and a specificity of 96.4%, with a 94.7% positive and a 79.4% negative predictive value. The area under the ROC curve was 94.3%. There was a good agreement in the pre-treatment concordance between the classical and the simplified criteria (kappa index, 0.775). CONCLUSION Simplified criteria provide a moderate sensitivity for the diagnosis of AIH, but may help in indicating treatment in cases under suspicion with 6 or more points.
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Affiliation(s)
| | - Cristina Molera Busoms
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
| | - Ecaterina Julio Tatis
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain
| | - María Victoria Bovo
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain
| | - Jesús Quintero Bernabeu
- Department of Pediatric Gastroenterology and Hepatology, Vall d'Hebron Hospital (VHH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
| | - Javier Juampérez Goñi
- Department of Pediatric Gastroenterology and Hepatology, Vall d'Hebron Hospital (VHH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
| | - Vanessa Crujeiras Martínez
- Department of Pediatric Gastroenterology and Hepatology, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, Spain
| | - Javier Martin de Carpi
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
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Nguyen HH, Shaheen AA, Baeza N, Lytvyak E, Urbanski SJ, Mason AL, Norman GL, Fritzler MJ, Swain MG. Evaluation of classical and novel autoantibodies for the diagnosis of Primary Biliary Cholangitis-Autoimmune Hepatitis Overlap Syndrome (PBC-AIH OS). PLoS One 2018; 13:e0193960. [PMID: 29554146 PMCID: PMC5858776 DOI: 10.1371/journal.pone.0193960] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Accepted: 02/21/2018] [Indexed: 01/28/2023] Open
Abstract
Background and aims Up to 20% of Primary Biliary Cholangitis (PBC) patients are estimated to have features that overlap with Autoimmune Hepatitis (AIH). Patients with PBC-AIH overlap syndrome (PBC-AIH OS) have been reported to exhibit suboptimal responses to ursodeoxycholic acid therapy, and are more likely to progress to cirrhosis. Anti-double stranded DNA (anti-dsDNA) and anti-p53 have been previously suggested to be potential autoantibodies for identifying patients with PBC-AIH OS. In our well defined PBC patient cohorts, a comprehensive assessment of various classical and novel autoantibodies was evaluated for their utility in identifying PBC-AIH OS patients. Methods PBC-AIH OS was classified according to the Paris criteria and PBC as per the European Association for the Study of the Liver guidelines. Biobanked serum samples from 197 patients at the University of Calgary Liver Unit and the University of Alberta were analyzed for classical and novel autoantibodies. Anti-dsDNA was measured by the Crithidia luciliae immunofluorescence (CLIFT) assay (1:20 dilution) and chemiluminescence (CIA: QUANTA Flash®, Inova Diagnostics, San Diego). Anti-p53, anti-Ro52/TRIM21, anti-YB 1, anti-GW182, anti-Ge-1, and anti-Ago 2 were measured by either an addressable laser bead immunoassay (ALBIA) or line immunoassay (LIA). Autoantibodies against MIT3, gp210, sp100, LKM1, SLA, and the novel autoantibodies Hexokinase-1 (HK-1), and Kelch like protein 12 (KLHL-12) were measured using QUANTA Lite® ELISA assays. We applied non-parametric methods to compare the biomarkers frequencies between study groups. We used multivariate adjusted models and AUROC to compare the diagnostic accuracy of the different autoantibodies alone or in combination with serum biochemistry. Results 16 out of 197 PBC patients (8.1%) were classified as PBC-AIH OS. Compared to PBC patients, PBC-AIH OS patients were similar in age (median: 59 vs. 63, P = 0.21) and female predominance (94% vs. 89%, P = 1.00). Anti-dsDNA-by CLIFT (37.5% in PBC-AIH OS vs 9.9% in PBC alone, P <0.01) was the only autoantibody associated with PBC-AIH OS; a finding consistent with previous reports. Significant elevation in serum ALT (62 IU/L in PBC-AIH OS vs 37 IU/L in PBC alone, P < 0.01), and serum IgG (17.6 g/L in OS vs 12.1 g/L in PBC alone, P <0.01) were observed in patients with PBC-AIH OS receiving medical/immunosuppressive therapy. In a multivariate model, positive anti-dsDNA by CLIFT, ALT and IgG were significant predictors of PBC-AIH OS with an area under the receiver operator curve (AUROC) value of 0.84. Conclusions Consistent with previous findings, the presence of anti-dsDNA by CLIFT is associated with PBC-AIH OS. Contrary to previous reports, anti-p53 was not associated with PBC-AIH OS. Our comprehensive evaluation of various classical and novel autoantibody biomarkers including Ro52/TRIM21, anti-p53, anti-KLHL-12 and anti-HK-1 were not significantly associated with PBC-AIH OS. Our findings highlight the ongoing need for the research and development of new autoantibody biomarkers to aid in the diagnosis of PBC-AIH OS.
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Affiliation(s)
- Henry H. Nguyen
- University of Calgary Division of Gastroenterology and Hepatology. Hospital Dr NW, Calgary, Alberta Canada
| | - Abdel Aziz Shaheen
- University of Calgary Division of Gastroenterology and Hepatology. Hospital Dr NW, Calgary, Alberta Canada
| | - Natalia Baeza
- University of Calgary Department of Medicine. Hospital Drive NW Calgary, Alberta, Canada
| | - Ellina Lytvyak
- University of Alberta Division of Gastroenterology. Zeidler Ledcor Centre Edmonton, Alberta Canada
| | - Stefan J. Urbanski
- University of Calgary Department of Pathology & Laboratory Medicine. Calgary, Alberta Canada
| | - Andrew L. Mason
- University of Alberta Division of Gastroenterology. Zeidler Ledcor Centre Edmonton, Alberta Canada
| | - Gary L. Norman
- Inova Diagnostics. San Diego, CA, United States of America
| | - Marvin J. Fritzler
- University of Calgary Department of Medicine. Hospital Drive NW Calgary, Alberta, Canada
| | - Mark G. Swain
- University of Calgary Division of Gastroenterology and Hepatology. Hospital Dr NW, Calgary, Alberta Canada
- * E-mail:
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Roberts SK, Lim R, Strasser S, Nicoll A, Gazzola A, Mitchell J, Siow W, Khoo T, Hamarneh Z, Weltman M, Gow P, Janko N, Tse E, Mishra G, Cheng EH, Levy M, Cheng W, Sood S, Skoien R, Mitchell J, Zekry A, George J, MacQuillan G, Wigg A, Stuart K, Sievert W, McCaughan G. Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy. Clin Gastroenterol Hepatol 2018; 16:268-277. [PMID: 29050991 DOI: 10.1016/j.cgh.2017.09.063] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Revised: 08/18/2017] [Accepted: 09/25/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about outcomes of patients with autoimmune hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and safety of mycophenolate mofetil in patients failed by or intolerant to corticosteroids, with or without azathioprine. METHODS We performed a retrospective study of 105 patients with AIH who received mycophenolate mofetil therapy after an inadequate response or intolerance to standard therapy (98% received combination therapy with corticosteroids plus thiopurines). Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network. We reviewed records for baseline demographic features and characteristics of liver disease, initial therapy, mycophenolate mofetil indications, treatment outcome, and side effects. The primary outcome was biochemical remission, defined as levels of alanine and aspartate transferase and IgG level within the normal reference range, with or without normal liver histology within the first 2 years of treatment. RESULTS The indication for mycophenolate mofetil therapy was non-response to treatment for 40% of cases and intolerance to therapy for 60%. Overall, 63 patients (60%) achieved biochemical remission following a median 12 weeks treatment with mycophenolate mofetil. The proportion of patients who achieved biochemical remission was similar between patients receiving mycophenolate mofetil for non-response to standard therapy (57%) and patients with intolerance to standard therapy (62%). However, a lower proportion of patients with cirrhosis achieved biochemical remission (47%) than patients without cirrhosis (6%) (P = .07). Serious adverse events occurred in 3 patients (2.7%) including 1 death, and 10 patients (9.2%) discontinued mycophenolate mofetil because of adverse events. CONCLUSION In this retrospective study of patients with AIH who received mycophenolate mofetil as a rescue therapy, we found the drug to be well tolerated and moderately effective, inducing biochemical remission in 60% of subjects. Rates of response are lower and rates of infection are higher in patients with AIH and cirrhosis. Prospective studies of mycophenolate mofetil are warranted for this population.
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Affiliation(s)
| | - Ricky Lim
- Royal Prince Alfred Hospital, Sydney
| | - Simone Strasser
- Royal Prince Alfred Hospital, Sydney; Centenary Research Institute, Sydney
| | - Amanda Nicoll
- Eastern Health, Box Hill Hospital, and Monash University, Box Hill
| | | | | | - Way Siow
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney
| | | | | | | | | | - Natasha Janko
- The Alfred, Melbourne; Eastern Health, Box Hill Hospital, and Monash University, Box Hill
| | | | - Gauri Mishra
- Monash Medical Centre and Monash University, Melbourne
| | | | | | | | | | | | | | | | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney
| | | | | | | | | | - Geoffrey McCaughan
- Royal Prince Alfred Hospital, Sydney; Centenary Research Institute, Sydney
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Zhang W, Zhou Y, Li X, Xu X, Chen Y, Zhu R, Yin L. Macrophage-targeting and reactive oxygen species (ROS)-responsive nanopolyplexes mediate anti-inflammatory siRNA delivery against acute liver failure (ALF). Biomater Sci 2018; 6:1986-1993. [DOI: 10.1039/c8bm00389k] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Macrophage-targeting and ROS-degradable nanopolyplexes were developed to realize efficient TNF-α siRNA delivery toward the treatment of acute liver failure.
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Affiliation(s)
- Wenxin Zhang
- Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices
- Institute of Functional Nano and Soft Materials (FUNSOM)
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Soochow University
- Suzhou 215123
| | - Yang Zhou
- Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices
- Institute of Functional Nano and Soft Materials (FUNSOM)
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Soochow University
- Suzhou 215123
| | - Xudong Li
- Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices
- Institute of Functional Nano and Soft Materials (FUNSOM)
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Soochow University
- Suzhou 215123
| | - Xin Xu
- Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices
- Institute of Functional Nano and Soft Materials (FUNSOM)
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Soochow University
- Suzhou 215123
| | - Yongbing Chen
- Department of Thoracic Surgery
- the Second Affiliated Hospital of Soochow University
- Suzhou 215004
- P.R. China
| | - Rongying Zhu
- Department of Thoracic Surgery
- the Second Affiliated Hospital of Soochow University
- Suzhou 215004
- P.R. China
| | - Lichen Yin
- Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices
- Institute of Functional Nano and Soft Materials (FUNSOM)
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Soochow University
- Suzhou 215123
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Sun W, Wu HY, Chen S. Influence of TBX21 T-1993C variant on autoimmune hepatitis development by Yin-Yang 1 binding. World J Gastroenterol 2017; 23:8500-8511. [PMID: 29358858 PMCID: PMC5752710 DOI: 10.3748/wjg.v23.i48.8500] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 10/15/2017] [Accepted: 11/07/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigated the mechanism of the association between the TBX21 T-1993C promoter polymorphism and autoimmune hepatitis type 1 (AIH-1) development.
METHODS In vivo, In vivo, and reporter analyses were performed to determine the function of transcription factors binding to the T-1993C element of the TBX21 promoter in human CD4+ T and B cell lines. Flow cytometry and quantitative real-time PCR were used to analyze T-box transcription factor (T-bet) and interferon-γ (IFN-γ) expressions in CD4+ T cells, B cells and monocytes from the peripheral blood of AIH-1 patients including 5-1993TC and 15-1993TT genotype carriers, and healthy controls including 10-1993TC and 25-1993TT genotype carriers. Furthermore, a range of biochemical indices was measured simultaneously in the blood of AIH-1 patients.
RESULTS TBX21-1993C allele created a strong Yin-Yang 1 (YY1)-binding site and decreased transcriptional activity of TBX21 promoter in human CD4+ T and B cells. Higher levels of T-bet and IFN-γ were detected in the circulating CD4+ T cells and B cells of AIH-1 patients carrying the TBX21-1993 TT genotype compared with the patients carrying the -1993 TC genotype and controls with the -1993 TC genotype. T-bet expression levels of circulating T cells and B cells were positively correlated with AIH-1 disease activity. Knockdown of YY1 with siRNA caused increased expression of T-bet and IFN-γ in peripheral blood mononuclear cells in AIH-1 patients.
CONCLUSION The repression of TBX21 expression by high-affinity binding of YY1 to the -1993C allele may contribute to a decreased development of AIH-1 via suppression of type 1 immunity.
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Affiliation(s)
- Wei Sun
- Institute of Infectious Diseases, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China
| | - Hong-Yan Wu
- Nuclear Medicine Department, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China
| | - Song Chen
- Institute of Infectious Diseases, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China
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Acharya GK, Liao HI, Frunza-Stefan S, Patel R, Khaing M. Autoimmune Hepatitis: Diagnostic Dilemma When It Is Disguised as Iron Overload Syndrome. J Clin Exp Hepatol 2017; 7:269-273. [PMID: 28970716 PMCID: PMC5620361 DOI: 10.1016/j.jceh.2017.03.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2016] [Accepted: 03/01/2017] [Indexed: 02/08/2023] Open
Abstract
Elevated serum ferritin level is a common finding in iron overload syndrome, autoimmune and viral hepatitis, alcoholic and nonalcoholic fatty liver diseases. High transferrin saturation is not a common finding in above diseases except for iron overload syndrome. We encountered a challenging case of 73-year-old female who presented with yellowish discoloration of skin, dark color urine and dull abdominal pain. Initial laboratory tests reported mild anemia; elevated bilirubin, liver enzymes, and transferrin saturation. We came to the final diagnosis of autoimmune hepatitis after extensive workups. Autoimmune hepatitis is a rare disease, and the diagnosis can be further complicated by a similar presentation of iron overload syndrome. Markedly elevated transferrin saturation can simulate iron overload syndrome, but a liver biopsy can guide physicians to navigate the diagnosis.
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Key Words
- AIH, autoimmune hepatitis
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- AMA, antimicrosomal antibody
- ANA, antinuclear antibody
- AST, aspartate aminotransferase
- Autoimmune disease
- Autoimmune hepatitis
- BUN, blood urea nitrogen
- CMV, cytomegalovirus
- CT, computed tomography
- Diagnostic dilemma
- EBV, Epstein–Barr virus
- ESR, erythrocyte sedimentation rate
- HHC, hereditary hemochromatosis
- HLA, human leukocyte antigen
- INR, international normalized ratio
- Ig, immunoglobulin
- Iron overload syndrome
- LDH, lactate dehydrogenase
- LFT, liver function test
- MRI, magnetic resonance imaging
- PT, prothrombin time
- PTT, partial thromboplastin time
- PTU, propylthiouracil
- RBC, red blood cell
- TIBC, total iron binding capacity
- Transferrin saturation
- WBC, white blood cell
- anti-LKM, anti-liver kidney microsomal
- anti-SMA, anti-smooth muscle antibody
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Affiliation(s)
- Gyanendra K. Acharya
- The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
- Address for correspondence: Gyanendra Kumar Acharya, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.The University of Texas MD Anderson Cancer Center1515 Holcombe BlvdHoustonTX77030USA
| | - Hung-I Liao
- Wyckoff Heights Medical Center, 374 Stockholm Street, Brooklyn, NY 11237, USA
| | | | - Ronakkumar Patel
- Wyckoff Heights Medical Center, 374 Stockholm Street, Brooklyn, NY 11237, USA
| | - Moe Khaing
- Wyckoff Heights Medical Center, 374 Stockholm Street, Brooklyn, NY 11237, USA
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40
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Tansel A, Katz LH, El-Serag HB, Thrift AP, Parepally M, Shakhatreh MH, Kanwal F. Incidence and Determinants of Hepatocellular Carcinoma in Autoimmune Hepatitis: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2017; 15:1207-1217.e4. [PMID: 28215616 PMCID: PMC5522646 DOI: 10.1016/j.cgh.2017.02.006] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 01/31/2017] [Accepted: 02/06/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The risk of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH) is unclear. We conducted a systematic review and meta-analysis of the incidence of HCC and associated risk factors among patients with AIH. METHODS We searched PubMed, Embase, and reference lists from relevant articles through June 2016 to identify cohort studies that examined the incidence of HCC in patients with AIH. We used random effects models to estimate pooled incidence rates overall and in subgroup of patients with cirrhosis. The between-study heterogeneity was assessed using I2 statistic. RESULTS A total of 25 studies (20 papers and 5 abstracts), including 6528 patients, met the eligibility criteria. The median cohort size was 170 patients with AIH (range, 25-1721 patients), followed for a median of 8.0 years (range, 3.3-16.0 years). The pooled incidence rate for HCC in patients with AIH was 3.06 per 1000 patient-years (95% confidence interval, 2.22-4.23; I2 = 51.5%; P = .002). The pooled incidence of HCC in patients with cirrhosis at AIH diagnosis was 10.07 per 1000 patient-years (95% confidence interval, 6.89-14.70; I2 = 48.8%; P = .015). In addition, 92 of 93 patients who had HCC had evidence of cirrhosis before or at the time of their HCC diagnosis. The risk of HCC seems to be lower in patients with AIH and cirrhosis than that reported for patients with cirrhosis from hepatitis B, hepatitis C, or primary biliary cholangitis. CONCLUSIONS Based on the increased risked of HCC shown in this meta-analysis, there may be a role for HCC surveillance in patients with AIH and cirrhosis.
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Affiliation(s)
- Aylin Tansel
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas.
| | - Lior H Katz
- The Department of Gastroenterology, Sheba Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Hashomer, Israel
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Aaron P Thrift
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Mayur Parepally
- Division of Gastroenterology and Nutrition, Department of Medicine, Loyola University Medical Center, Chicago, Illinois
| | - Mohammad H Shakhatreh
- Section of Gastroenterology and Hepatology, Virginia Tech Carilion School of Medicine and Research Institute, Roanoke, Virginia
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
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Guedes ALV, Andrade AR, Nunes VS, Lima FR, de Mello ES, Ono SK, Terrabuio DRB, Cançado ELR. Histological remission of autoimmune hepatitis after the addition of allopurinol and azathioprine dose reduction. AUTOPSY AND CASE REPORTS 2017; 7:35-42. [PMID: 28740837 PMCID: PMC5507567 DOI: 10.4322/acr.2017.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Accepted: 06/02/2017] [Indexed: 12/30/2022] Open
Abstract
The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite. The addition of allopurinol shifts the metabolism of thiopurine towards 6-thioguanine, improving the immunosuppressive effect. We present the case of a 51-year-old female with autoimmune hepatitis who had a biochemical response after azathioprine and prednisone treatment without histological remission, and who preferentially shunted to 6-MMP. After the addition of allopurinol, the patient’s 6-thioguanine levels increased, and she reached histological remission with a reduction of 67% of the original dose of azathioprine. The patient did not develop clinical manifestations as a consequence of her increased immunosuppressive state. We also review the relevant literature related to this issue. In conclusion, the addition of allopurinol to thiopurine seems to be an option for those patients who do not reach histological remission and who have a skewed thiopurine metabolite profile.
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Affiliation(s)
- Ana Luiza Vilar Guedes
- University of São Paulo, School of Medicine, Department of Gastroenterology. São Paulo, SP, Brazil
| | - Adriana Ribas Andrade
- University of São Paulo, School of Medicine, Department of Gastroenterology. São Paulo, SP, Brazil
| | - Vinicius Santos Nunes
- University of São Paulo, School of Medicine, Department of Gastroenterology. São Paulo, SP, Brazil
| | - Fabiana Roberto Lima
- University of São Paulo, School of Medicine, Department of Pathology. São Paulo, SP, Brazil
| | | | - Suzane Kioko Ono
- University of São Paulo, School of Medicine, Department of Gastroenterology. São Paulo, SP, Brazil
| | | | - Eduardo Luiz Rachid Cançado
- University of São Paulo, School of Medicine, Department of Gastroenterology. São Paulo, SP, Brazil.,University of São Paulo, Institute of Tropical Medicine of São Paulo. São Paulo, SP, Brazil
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Abdel-Razik A, Mousa N, Elalfy H, Sheta TF, Awad M, Abdelsalam M, Elhelaly R, Elzehery R, Gouda NS, Eldars W. A Novel Combination of C-Reactive Protein and Vascular Endothelial Growth Factor in Differential Diagnosis of Ascites. J Gastrointest Cancer 2017; 48:50-57. [PMID: 27614744 DOI: 10.1007/s12029-016-9873-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Ascites with unknown cause remains a diagnostic challenge, which needs novel noninvasive biomarkers for the precise diagnosis. We aimed to evaluate the ascitic fluid and serum C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) as diagnostic markers in the differential diagnosis of malignant and benign ascites. METHODS In this prospective work, 315 consecutive patients with ascites were studied. Ascitic fluid and serum levels of CRP and VEGF were evaluated by using an enzyme-linked immunosorbent assay. RESULTS Patients were divided into a benign ascites group (group 1) (n = 256) and a malignant ascites group (group 2) (n = 59). Ascitic and serum CRP were significantly elevated in malignant ascites than benign ascites group [5.08 (3.62-6.58) vs. 1.82 (0.64-3.86) ng/ml; P < 0.001 and 12.7 (8.55-17.05) vs. 5.94 (2.57-10.64) ng/ml; P < 0.001], respectively. Ascitic and serum VEGF were significantly increased in malignant ascites than benign ascites patients [0.68 (0.39-0.96) vs. 0.41 (0.25-0.83) ng/ml; P < 0.001 and 0.74 (0.41-1.08) vs. 0.54 (0.23-0.86) ng/ml; P < 0.001], respectively. At a cutoff value of 7.3 and 0.63 ng/ml, serum CRP and VEGF had specificity (77.3 and 89.5 %) and sensitivity (83.1 and 94.9 %) for detecting malignant ascites [area under the curve (AUC) 0.821, 0.921], respectively. At a cutoff value of 2.5 and 0.57 ng/ml, ascitic CRP and VEGF had specificity (81.6 and 85.5 %) and sensitivity (84.7 and 91.5 %) for detecting malignant ascites (AUC 0.842, 0.894), respectively. CONCLUSION Elevated ascitic fluid and serum CRP and VEGF values were related to the malignant ascites.
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Affiliation(s)
- Ahmed Abdel-Razik
- Tropical Medicine Department, Faculty of Medicine, Mansoura University-Egypt, Mansoura, 35516, Egypt.
| | - Nasser Mousa
- Tropical Medicine Department, Faculty of Medicine, Mansoura University-Egypt, Mansoura, 35516, Egypt
| | - Hatem Elalfy
- Tropical Medicine Department, Faculty of Medicine, Mansoura University-Egypt, Mansoura, 35516, Egypt
| | - Tarek Fouad Sheta
- Internal Medicine Department, Faculty of Medicine, Mansoura University-Egypt, Mansoura, Egypt
| | - Mahmoud Awad
- Internal Medicine Department, Faculty of Medicine, Mansoura University-Egypt, Mansoura, Egypt
| | - Mostafa Abdelsalam
- Nephrology and Dialysis Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University-Egypt, Mansoura, Egypt
| | - Rania Elhelaly
- Clinical Pathology Department, Faculty of Medicine, Mansoura University-Egypt, Mansoura, Egypt
| | - Rasha Elzehery
- Clinical Pathology Department, Faculty of Medicine, Mansoura University-Egypt, Mansoura, Egypt
| | - Nawal S Gouda
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University-Egypt, Mansoura, Egypt
| | - Waleed Eldars
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University-Egypt, Mansoura, Egypt
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43
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Liver transplantation for acute liver failure. Cir Esp 2017; 95:181-189. [PMID: 28433231 DOI: 10.1016/j.ciresp.2017.01.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2016] [Revised: 01/11/2017] [Accepted: 01/19/2017] [Indexed: 12/16/2022]
Abstract
Before liver transplantation became widely applicable as a treatment option, the mortality rate for acute liver failure was as high as 85%. Today, acute liver failure is a relatively common transplant indication in some settings, but the results of liver transplantation in this context appear to be worse than those for chronic forms of liver disease. In this review, we discuss the indications and contraindications for urgent liver transplantation. In particular, we consider the roles of auxiliary, ABO-incompatible, and urgent living donor liver transplantation and address the management of a «status 1» patient with total hepatectomy and portocaval shunt for toxic liver syndrome.
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44
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Adiga A, Nugent K. Lupus Hepatitis and Autoimmune Hepatitis (Lupoid Hepatitis). Am J Med Sci 2017; 353:329-335. [DOI: 10.1016/j.amjms.2016.10.014] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 09/23/2016] [Accepted: 10/31/2016] [Indexed: 12/21/2022]
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Puustinen L, Boyd S, Mustonen H, Arkkila P, Arola J, Färkkilä M. Prognostic value of clinical variables and liver histology for development of fibrosis and cirrhosis in autoimmune hepatitis. Scand J Gastroenterol 2017; 52:321-327. [PMID: 27846740 DOI: 10.1080/00365521.2016.1253768] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE In autoimmune hepatitis, data on the prognostic value of baseline liver biopsy and the sequential histology is controversial. Our aim was to evaluate the prognostic value of clinical variables and biopsy at the time of diagnosis and during the disease course. MATERIALS AND METHODS All 98 patients in our hospital during 1995-2012 were included. Sequential biopsies were available in 66 patients. Analyses based on clinical and histological variables were performed to find parameters predicting the progression of fibrosis, and development of cirrhosis. RESULTS At the time of diagnosis, 7% were cirrhotic. Fibrosis progressed in 28 (42%) patients, remained stable in 26 (39%) and resolved in 12 (18%) patients. Findings which predicted fibrosis progression, were baseline total inflammation (odds ratio 1.7, 95% CI 1.01-2.8), cumulative total inflammation (1.8, 95% CI 1.01-3.2, rosette formation (2.8, 95% CI 1.1-7.1), absence of pericholangitis (0.4, 95% CI 0.1-1.0) and necrosis (1.4, 95% CI 1.0-2.0). Risk factors for the development of cirrhosis were cholestasis (4.6, 95% CI 1.2-16.9), interphase inflammation (3.4, 95% CI 1.1-10.4), and necrosis (3.3, 95% CI 1.2-9.7). In a cumulative model, cumulative total inflammation (4.5, 95% CI 1.4-15.0), necrosis (6.7, 95% CI 1.3-34.6), or cumulative immunoglobulin G load (61.8, 95% CI 2.0-1954.3) were risk factors. None of the patients with histological pericholangitis or granulomas developed cirrhosis. CONCLUSIONS The histology provides prognostic information regarding progression of fibrosis or the development of cirrhosis. The total cumulative inflammatory activity predicts the progression of fibrosis, whereas baseline fibrosis, interphase inflammation, cholestasis, necrosis, as well as the cumulative total inflammation and cumulative immunoglobulin G, are risk factors for cirrhosis.
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Affiliation(s)
- Lauri Puustinen
- a Clinic of Gastroenterology, Department of Medicine , Helsinki University Hospital , Helsinki , Finland
| | - Sonja Boyd
- b Department of Pathology , Haartman Institute and Huslab, Helsinki University Hospital , Helsinki , Finland
| | - Harri Mustonen
- c Department of Surgery , Helsinki University Hospital, University of Helsinki , Helsinki , Finland
| | - Perttu Arkkila
- a Clinic of Gastroenterology, Department of Medicine , Helsinki University Hospital , Helsinki , Finland
| | - Johanna Arola
- b Department of Pathology , Haartman Institute and Huslab, Helsinki University Hospital , Helsinki , Finland
| | - Martti Färkkilä
- a Clinic of Gastroenterology, Department of Medicine , Helsinki University Hospital , Helsinki , Finland.,d Department of Gastroenterology , University of Helsinki , Helsinki , Finland
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Deswal S, Srivastava A. Role of Allopurinol in Optimizing Thiopurine Therapy in Patients with Autoimmune Hepatitis: A Review. J Clin Exp Hepatol 2017; 7:55-62. [PMID: 28348471 PMCID: PMC5357743 DOI: 10.1016/j.jceh.2017.01.115] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Accepted: 01/29/2017] [Indexed: 12/12/2022] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic immune mediated liver disease characterized by elevated transaminases, hyper gammaglobulinemia, presence of autoantibodies and interface hepatitis in the absence of a known etiology of liver disease. Thiopurines (azathioprine [AZA]/6-mercaptopurine [6MP]) and steroids remain the first line of treatment of AIH in both children and adults. However, a small proportion of AIH patients are either non-responders or develop side effects with AZA. The metabolism of AZA is complex and mediated by multiple enzymes. After absorption and getting converted to 6MP, it is converted to 6-thiouric acid, 6-methyl mercaptopurine (6MMP) and 6-thioguanine (6TG) by different enzymes. Elevated 6MMP levels are associated with hepatotoxicity and also poor efficacy due to simultaneous lower levels of 6TG, which is the active drug metabolite related to both efficacy and myelosuppression. Allopurinol, a xanthine oxidase inhibitor shifts the metabolism of AZA away from 6MMP toward 6TG. This combination of allopurinol with reduced dose of AZA is an alternative to more expensive and toxic second line therapy to induce remission in patients with AIH. This article discusses the mechanism of action of allopurinol in inducing response to AZA, reviews the published literature on this combination therapy and gives guidelines on the use of allopurinol in patients with AIH.
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Key Words
- 6-MTIMP, 6-methyl thioinosine monophosphate
- 6MMP, 6-methyl mercaptopurine
- 6MP, 6-mercaptopurine
- 6TG, 6-thioguanine
- AIH, autoimmune hepatitis
- ANA, antinuclear antibody
- AZA, azathioprine
- HGPRT, hypoxanthine guanine phosphoribosyl transferase
- IBD, inflammatory bowel disease
- IgG, immunoglobulin G
- LC, liver cytosol
- LKM, liver kidney microsomal
- PBC, primary biliary cirrhosis
- PSC, primary sclerosing cholangitis
- SMA, smooth muscle antibody
- TIMP, thioinosine monophosphate
- TPMT, thiopurine methyltransferase
- XO, xanthine oxidase
- allopurinol
- autoimmune hepatitis
- azathioprine
- hepatotoxicity
- overlap syndrome
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Affiliation(s)
- Shivani Deswal
- Department of Pediatrics, PGIMER and Dr RML Hospital, New Delhi, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
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Kia L, Beattie A, Green RM. Autoimmune hepatitis in patients with human immunodeficiency virus (HIV): Case reports of a rare, but important diagnosis with therapeutic implications. Medicine (Baltimore) 2017; 96:e6011. [PMID: 28207511 PMCID: PMC5319500 DOI: 10.1097/md.0000000000006011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
RATIONALE Chronic liver disease is a major cause of morbidity and mortality in patients with HIV. However, autoimmune hepatitis (AIH) in patients with HIV has rarely been reported. Our aim was to evaluate a cohort of patients with HIV and AIH and identify clinical presentations and outcomes. PATIENT CONCERNS Management of autoimmune hepatitis in context of human immunodeficiency virus, long-term outcomes, and safety in setting of underlying immunocompromised state. DIAGNOSES Autoimmune Hepatitis, Human Immunodeficiency Virus, Hepatotoxicity, Liver Injury, Liver Transplantation. INTERVENTIONS We retrospectively reviewed the charts of patients with HIV and AIH based on histological, serologic, biochemical demographic, and clinical data. OUTCOMES Five patients were identified with autoimmune hepatitis; 4 of 5 were women, and all were African or African-American. The age at the time of AIH diagnosis was 46.6 ± 13.4 years. All patients acquired HIV sexually and all had CD4 counts >250 cells/uL (456-1011 cells/uL) and undetectable HIV viral loads at the time of AIH diagnosis. One patient presented with acute liver failure necessitating liver transplantation and developed AIH posttransplantation. At the time of diagnosis, the AST were 350 ± 448 U/L, ALT 247 ± 190 U/L, bilirubin 7 ± 12 mg/dL, and alkaline phosphatase 126 ± 53 U/L. All patients had histologic evidence of AIH on liver biopsies. Patients were successfully treated with prednisone and azathioprine, without a decrease in CD4 <250 cells/uL, infectious complications or significant side effects. LESSONS AIH occurs in patients with well-controlled HIV. In our patient cohort, immunosuppressive therapy with prednisone and azathioprine was safe and effective in inducing remission, without significant complications or development of opportunistic infections.
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Affiliation(s)
- Leila Kia
- Division of Gastroenterology and Hepatology, Department of Medicine
| | - Adam Beattie
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Richard M. Green
- Division of Gastroenterology and Hepatology, Department of Medicine
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Jhee JH, Kim HJ, Kang W, Kim S, Kim DY. A case of autoimmune hepatitis combined with Graves' disease. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 65:48-51. [PMID: 25603854 DOI: 10.4166/kjg.2015.65.1.48] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg during a period of 2 weeks. Laboratory tests showed elevated levels of liver enzymes (AST 1,282 IU/L, ALT 1,119 IU/L) and total bilirubin (6.4 mg/dL); negative for hepatitis virus infection; elevated serum levels of triiodothyronine (T3, 3.60 ng/dL), free thyroxine (fT4, 3.82 ng/dL), and lowered serum level of thyroid stimulating hormone (TSH, <0.025 μIU/mL); and positive for thyroid stimulating antibody and anti-mitochondrial antibody (AMA). The liver biopsy findings were consistent with autoimmune hepatitis (AIH). Accordingly, oral steroid therapy was started with 60 mg of prednisolone under the impression of AIH associated with Graves' disease. After a week of steroid therapy, the clinical manifestation showed significant improvement, with normalization of both liver and thyroid functions. Diagnosis of the liver condition of patients who present with hyperthyroidism and liver dysfunction is important, so that appropriate therapy can be promptly initiated.
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Affiliation(s)
- Jong Hyun Jhee
- Departments of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Ju Kim
- Departments of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Wonseok Kang
- Departments of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sewha Kim
- Departments of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Do Young Kim
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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Abstract
Autoimmune hepatitis (AIH) is an uncommon, chronic inflammatory, and relapsing liver disease of unknown origin that may lead to liver cirrhosis, hepatocellular carcinoma, liver transplantation, or death. AIH occurs in all age groups and races but can frequently manifest as acute fulminant hepatitis. Clinical presentation of AIH can have features similar to primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC), and these diseases may coexist leading to overlap syndromes. Although histological diagnosis is necessary, imaging features often can demonstrate characteristics that may be helpful to distinguish these diseases. Imaging features of AIH are those of chronic liver disease, and imaging plays important role in detection of complications and ruling out other possible causes of chronic liver disease. Emerging techniques such as elastography provide non-invasive options for diagnosis of significant fibrosis and cirrhosis during clinical follow-up as well as assessment of response to treatment. In this study, we will describe imaging findings in AIH and overlap syndromes.
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Abdel-Razik A, Eldars W, Elhelaly R, Elzehery R. C-reactive protein and insulin-like growth factor-1 in differential diagnosis of ascites. J Gastroenterol Hepatol 2016; 31:1868-1873. [PMID: 27010362 DOI: 10.1111/jgh.13386] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/12/2016] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIM Insulin-like growth factor-1 (IGF-1) and C-reactive protein (CRP) are produced mainly by the liver; the output of these markers in response to inflammatory processes may be affected in patients with hepatic dysfunction. This may explain the differences in IGF-1 and CRP values in patients with non-portal and portal hypertension ascites. We aimed to evaluate serum and ascitic fluid IGF-1 and CRP as diagnostic markers in the differential diagnosis of benign and malignant ascites. METHODS In this prospective study, 398 consecutive patients with ascites were included. Serum and ascitic fluid levels of IGF-1 and CRP were measured using an enzyme-linked immunosorbent assay. RESULTS Patients were divided into group 1, due to benign ascites (n = 324), and group 2, due to malignant ascites (n = 74). Serum and ascitic IGF-1 were significantly increased in malignant ascites than benign ascites group [305 ± 65.7 ng/mL vs 95 ± 53.8 ng/mL; P < 0.001 and 288 ± 54.7 ng/mL vs 83.2 ± 36.7 ng/mL; P < 0.001], respectively. Serum and ascitic CRP were significantly higher in malignant ascites than benign ascites patients [12.8 ± 6.3 mg/mL vs 6.1 ± 4.9 mg/mL; P < 0.001 and 5.1 ± 2.2 mg/mL vs 1.6 ± 1.3 mg/mL; P < 0.001], respectively. At a cutoff value of 309.4 ng/mL and 7.8 mg/mL, serum IGF-1 and CRP had (95.1%, 81%) sensitivity and (88.6%, 75.5%) specificity for detecting malignant ascites [area under the curve: 0.932, 0.845], respectively. At a cutoff value of 291.6 ng/mL and 2.6 mg/mL, ascitic IGF-1 and CRP had (94.6%, 84%) sensitivity and (83.2%, 80.3%) specificity for detecting malignant ascites (area under the curve: 0.911, 0.893) correspondingly. CONCLUSION Elevated serum and ascitic fluid IGF-1 and CRP levels were associated with malignant ascites.
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Affiliation(s)
- Ahmed Abdel-Razik
- Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Waleed Eldars
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Rania Elhelaly
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Rasha Elzehery
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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