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Sirbe C, Simu G, Szabo I, Grama A, Pop TL. Pathogenesis of Autoimmune Hepatitis-Cellular and Molecular Mechanisms. Int J Mol Sci 2021; 22:13578. [PMID: 34948375 PMCID: PMC8703580 DOI: 10.3390/ijms222413578] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/09/2021] [Accepted: 12/14/2021] [Indexed: 02/05/2023] Open
Abstract
Pediatric autoimmune liver disorders include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is an idiopathic disease characterized by immune-mediated hepatocyte injury associated with the destruction of liver cells, causing inflammation, liver failure, and fibrosis, typically associated with autoantibodies. The etiology of AIH is not entirely unraveled, but evidence supports an intricate interaction among genetic variants, environmental factors, and epigenetic modifications. The pathogenesis of AIH comprises the interaction between specific genetic traits and molecular mimicry for disease development, impaired immunoregulatory mechanisms, including CD4+ T cell population and Treg cells, alongside other contributory roles played by CD8+ cytotoxicity and autoantibody production by B cells. These findings delineate an intricate pathway that includes gene to gene and gene to environment interactions with various drugs, viral infections, and the complex microbiome. Epigenetics emphasizes gene expression through hereditary and reversible modifications of the chromatin architecture without interfering with the DNA sequence. These alterations comprise DNA methylation, histone transformations, and non-coding small (miRNA) and long (lncRNA) RNA transcriptions. The current first-line therapy comprises prednisolone plus azathioprine to induce clinical and biochemical remission. Further understanding of the cellular and molecular mechanisms encountered in AIH may depict their impact on clinical aspects, detect biomarkers, and guide toward novel, effective, and better-targeted therapies with fewer side effects.
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Affiliation(s)
- Claudia Sirbe
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (C.S.); (T.L.P.)
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| | - Gelu Simu
- Cardiology Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
- Cardiology Department, Rehabilitation Hospital, 400066 Cluj-Napoca, Romania
| | - Iulia Szabo
- Department of Rheumatology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Alina Grama
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (C.S.); (T.L.P.)
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| | - Tudor Lucian Pop
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (C.S.); (T.L.P.)
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
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Abstract
The usage of combination antiretroviral therapy in people with HIV (PWH) has incited profound improvement in morbidity and mortality. Yet, PWH may not experience full restoration of immune function which can manifest with non-AIDS comorbidities that frequently associate with residual inflammation and can imperil quality of life or longevity. In this review, we discuss the pathogenesis underlying chronic inflammation and residual immune dysfunction in PWH, as well as potential therapeutic interventions to ameliorate them and prevent incidence or progression of non-AIDS comorbidities. Current evidence advocates that early diagnosis and prompt initiation of therapy at high CD4 counts may represent the best available approach for an improved immune recovery in PWH.
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Affiliation(s)
- Catherine W Cai
- HIV Pathogenesis Section, Laboratory of Immunoregulation, NIAID, NIH, United States
| | - Irini Sereti
- HIV Pathogenesis Section, Laboratory of Immunoregulation, NIAID, NIH, United States.
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Wang Y, Zhao N, Yang J, Wen Y. Case Report: Orbital Myositis and Myasthenia Gravis as Symptoms of Immune Reconstitution Inflammatory Syndrome in a Patient With Human Immunodeficiency Virus Infection. Front Immunol 2020; 11:595068. [PMID: 33381117 PMCID: PMC7768007 DOI: 10.3389/fimmu.2020.595068] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Accepted: 11/05/2020] [Indexed: 12/15/2022] Open
Abstract
We present a case of a 37-year-old man with HIV infection who had been on antiretroviral therapy for one year. He was admitted to our hospital with red and swollen eyes, acute onset progressive exophthalmos, and intermittent diplopia endured for 7 days. His symptoms, exam, and imaging led to a diagnosis of immune reconstitution inflammatory syndrome associated orbital myositis. His symptoms improved considerably after glucocorticoid therapy. Following a reduction in the oral prednisone dose, he re-presented with left ptosis, which rapidly progressed to bilateral ptosis. Diagnostic testing led to the diagnosis of immune mediated myasthenia gravis. Treatment with pyridostigmine bromide, prednisone, and tacrolimus was initiated. One month later, the patient's symptoms improved significantly. There was a probable association between his symptoms and autoimmune immune reconstitution inflammatory syndrome. This report highlights the importance of recognizing autoimmune disorders in human immunodeficiency virus-infected patients undergoing antiretroviral therapy. Orbital myositis and myasthenia gravis in human immunodeficiency virus-infected patients correlate closely with immunity status following a marked increase in CD4+ T cell counts.
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Affiliation(s)
- Yanli Wang
- Infectious Diseases Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Ning Zhao
- Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jun Yang
- Neurology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Ying Wen
- Infectious Diseases Department, The First Affiliated Hospital of China Medical University, Shenyang, China
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Contributing awareness of autoimmune hepatitis in HIV patients. AIDS 2019; 33:2103-2105. [PMID: 31577575 DOI: 10.1097/qad.0000000000002299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Chaiteerakij R, Sanpawat A, Avihingsanon A, Treeprasertsuk S. Autoimmune hepatitis in human immunodeficiency virus-infected patients: A case series and review of the literature. World J Gastroenterol 2019; 25:5388-5402. [PMID: 31558881 PMCID: PMC6761245 DOI: 10.3748/wjg.v25.i35.5388] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Revised: 08/14/2019] [Accepted: 08/24/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Abnormal liver chemistry is a common problem in human immunodeficiency virus (HIV)-infected patients. Common causes of abnormal liver enzymes in this population include viral hepatitis B/C or opportunistic infection, drug toxicity, and neoplasm. Autoimmune hepatitis is a rare cause of hepatitis in HIV-infected individuals; however, this condition has been increasingly reported over the past few years. CASE SUMMARY We present 13 HIV-infected patients (5 males and 8 females) who developed autoimmune hepatitis (AIH) after their immune status was restored, i.e. all patients had stable viral suppression with undetectable HIV viral loads, and median CD4+ counts of 557 cells/× 106 L. Eleven patients presented with chronic persistent elevation of aminotransferase enzyme levels. One patient presented with acute hepatitis and the other patient presented with jaundice. The median levels of aspartate aminotransferase and alanine aminotransferase enzymes were 178 and 177 U/mL, respectively. Elevation of immunoglobulin G levels was present in 11 (85%) patients. Antinuclear antibody and anti-smooth muscle antibody were positive in 11 (85%) and 5 (38%) patients. Liver biopsy was performed in all patients. They had histopathological findings compatible with AIH. The patients were started on prednisolone for remission induction, with good response. After improvement of the liver chemistry, the dose of prednisolone was tapered, and azathioprine was added as life-long maintenance therapy. At the last follow-up visit, all were doing well, without HIV viral rebound or infectious complications. CONCLUSION This report underscores the emergence of autoimmune hepatitis in the context of HIV infection.
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Affiliation(s)
- Roongruedee Chaiteerakij
- Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
| | - Anapat Sanpawat
- Department of Pathology, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
| | - Anchalee Avihingsanon
- Medical Department, The HIV Netherlands Australia Thailand Research Collaboration, Bangkok 10330, Thailand
| | - Sombat Treeprasertsuk
- Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
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Mubder M, Azab M, Jayaraj M, Cross C, Lankarani D, Dhindsa B, Pan JJ, Ohning G. Autoimmune hepatitis in patients with human immunodeficiency virus infection: A systematic review of the published literature. Medicine (Baltimore) 2019; 98:e17094. [PMID: 31517833 PMCID: PMC6750342 DOI: 10.1097/md.0000000000017094] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Liver disease in patients with HIV is common and typically has complex and multifactorial presentations that represent a major cause of morbidity and mortality. Autoimmune hepatitis (AIH) is rarely reported in patient with HIV and the disease course and clinical outcomes for treatment have not been well characterized. We are aiming to determine the patient characteristics, disease prevalence, and treatment outcomes from published articles of patients with HIV and AIH. METHOD A systematic search of PubMed, Web of Science, and Google Scholar through February 20, 2019 identified 15 studies that reported the outcomes of AIH in patients with HIV. Because of the small sample sizes and skewed distributions, resampling tests of mean differences using permutation distributions (MAXn = 10,000 permutations) were utilized; analyses were performed using R (v. 3.5.1). Categorical differences were calculated using Fisher exact test for odds ratio = 1 (equal odds), and Cramer V was calculated for effect size; analyses were completed in SPSS (v. 25). RESULTS By reviewing 15 studies reporting a total of 35 patients with AIH and HIV, male patients were found to have significantly higher aspartate transaminase and alanine transaminase levels at time of diagnosis. No other significant findings identified. The CD4 count and viral load did not show significant correlation with AIH diagnosis or its prognosis. All patients but one who presented with severe immune deficiency and responded to highly active anti-retroviral therapy received immunosuppressive treatment without side effects and achieved remission except 2 lost to follow-up and 3 expired. CONCLUSION Although rare, but AIH can develop in patients with HIV and physicians should consider it in the differential diagnosis for HIV patients presented with abnormal liver function tests, especially after excluding hepatitis C virus and drug-induced liver injury.Patients with immune deficiency disorders who present with AIH can be treated safely with steroid either as monotherapy or in combination with another immune suppressant therapy.
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Affiliation(s)
- Mohamad Mubder
- Department of Internal Medicine, University of Nevada, Las Vegas, NV
| | - Mohamed Azab
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Loma Linda University, Loma Linda, CA
| | - Mahendran Jayaraj
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nevada, Las Vegas, NV
| | | | - Daisy Lankarani
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nevada, Las Vegas, NV
| | - Banreet Dhindsa
- Department of Internal Medicine, University of Nevada, Las Vegas, NV
| | - Jen-Jung Pan
- Department of Internal medicine, Division of Gastroenterology and Hepatology, University of Arizona-College of Medicine, Phoenix, AZ
| | - Gordon Ohning
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nevada, Las Vegas, NV
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Roussel J, Pandit S, Jordan P, Boktor M, Knowles K, Dela Cruz N, Samant H. Autoimmune Hepatitis (AIH) in Acquired Immune Deficiency Syndrome (AIDS): A Case Report and Review of Literature. Case Reports Hepatol 2019; 2019:5326428. [PMID: 31281688 PMCID: PMC6590560 DOI: 10.1155/2019/5326428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Revised: 04/22/2019] [Accepted: 05/02/2019] [Indexed: 11/23/2022] Open
Abstract
The common causes of abnormal liver chemistries in human immunodeficiency virus (HIV) infected patients are multifactorial. Diagnosis of autoimmune hepatitis (AIH) in HIV infected patients is intriguing but data is scarce. Unmasking of AIH during immune reconstitution in HIV patients after starting antiretroviral therapy is reported but not with advanced acquired immunodeficiency syndrome (AIDS). Here we present a fascinating case of 32-year-old African-American man with advanced AIDS who presented with elevated transaminases. He was diagnosed with AIH before starting antiretroviral therapy and successfully treated with prednisolone and azathioprine with antiretroviral therapy despite very low CD4 count.
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Affiliation(s)
- Jordan Roussel
- Department of Internal Medicine, Louisiana State University Health Sciences Center, Shreveport, LA, USA
| | - Sudha Pandit
- Department of Gastroenterology and Hepatology, Louisiana State University Health Sciences Center, Shreveport, LA, USA
| | - Paul Jordan
- Department of Gastroenterology and Hepatology, Louisiana State University Health Sciences Center, Shreveport, LA, USA
| | - Moheb Boktor
- Department of Gastroenterology and Hepatology, Louisiana State University Health Sciences Center, Shreveport, LA, USA
| | - Kurt Knowles
- Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA, USA
| | - Nester Dela Cruz
- Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA, USA
| | - Hrishikesh Samant
- Department of Gastroenterology and Hepatology, Louisiana State University Health Sciences Center, Shreveport, LA, USA
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Webb GJ, Hirschfield GM, Krawitt EL, Gershwin ME. Cellular and Molecular Mechanisms of Autoimmune Hepatitis. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2019; 13:247-292. [PMID: 29140756 DOI: 10.1146/annurev-pathol-020117-043534] [Citation(s) in RCA: 96] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Autoimmune hepatitis is an uncommon idiopathic syndrome of immune-mediated destruction of hepatocytes, typically associated with autoantibodies. The disease etiology is incompletely understood but includes a clear association with human leukocyte antigen (HLA) variants and other non-HLA gene variants, female sex, and the environment. Pathologically, there is a CD4+ T cell-rich lymphocytic inflammatory infiltrate with variable hepatocyte necrosis and subsequent hepatic fibrosis. Attempts to understand pathogenesis are informed by several monogenetic syndromes that may include autoimmune liver injury, by several drug and environmental agents that have been identified as triggers in a minority of cases, by human studies that point toward a central role for CD4+ effector and regulatory T cells, and by animal models of the disease. Nonspecific immunosuppression is the current standard therapy. Further understanding of the disease's cellular and molecular mechanisms may assist in the design of better-targeted therapies, aid the limitation of adverse effects from therapy, and inform individualized risk assessment and prognostication.
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Affiliation(s)
- G J Webb
- National Institute for Health Research Liver Biomedical Research Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom; ,
| | - G M Hirschfield
- National Institute for Health Research Liver Biomedical Research Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom; ,
| | - E L Krawitt
- Department of Medicine, University of Vermont, Burlington, Vermont 05405, USA; .,Department of Medicine, Dartmouth College, Hanover, New Hampshire 03755, USA
| | - M E Gershwin
- Division of Rheumatology, Allergy, and Clinical Immunology, School of Medicine, University of California, Davis, California 95817, USA;
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Kim H, Kwon JH, Kim YH, Nam SW, Lee JY, Jang JW. Favorable effect of corticosteroids in treating acute-on-chronic liver failure underlying chronic hepatitis B. Clin Mol Hepatol 2018; 24:430-435. [PMID: 29172397 PMCID: PMC6313026 DOI: 10.3350/cmh.2017.0016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 07/04/2017] [Accepted: 08/08/2017] [Indexed: 11/05/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) occurs in the presence of a chronic liver disease or cirrhosis, and often results from exacerbation of chronic hepatitis B (CHB). The efficacy of corticosteroid treatment in ACLF patients with underlying CHB remains unclear. We report the case of a 50-year-old woman who experienced ACLF due to CHB exacerbation and was treated with a combination of corticosteroids and nucleot(s)ide analogue (NUC). The patient showed rapid decompensation due to CHB exacerbation. Three months of antiviral therapy produced no improvement in liver function. Combination therapy with corticosteroids and NUC was started, which did result in improvement of liver function. This case shows that the combined therapy of corticosteroids and NUC can be effective in treating ACLF due to CHB exacerbation.
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Affiliation(s)
- Hyeji Kim
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary’s Hospital, Incheon, Korea
| | - Jung Hyun Kwon
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary’s Hospital, Incheon, Korea
| | - Yong Hee Kim
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary’s Hospital, Incheon, Korea
| | - Soon Woo Nam
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary’s Hospital, Incheon, Korea
| | - Jong Yul Lee
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary’s Hospital, Incheon, Korea
| | - Jeong Won Jang
- Department of Internal Medicine, The Catholic University of Korea Seoul St. Mary’s Hospital, Seoul, Korea
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Mathew T, Avati A, D'Souza D, Therambil M, Baptist AA, Shaji A, Nadig R, Rockey SM, Parry G. HIV infection associated neuromyelitis optica spectrum disorder: Clinical features, imaging findings, management and outcomes. Mult Scler Relat Disord 2018; 27:289-293. [PMID: 30448469 DOI: 10.1016/j.msard.2018.11.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 11/03/2018] [Accepted: 11/12/2018] [Indexed: 11/25/2022]
Abstract
INTRODUCTION HIV Infection associated NMOSD (HIV-NMOSD) is a recently recognized entity. Management of patients with HIV-NMOSD is a challenge. Here we report our own experience of HIV-NMOSD along with a complete review of all the cases of HIV-NMOSD reported in literature. OBJECTIVE Describe the clinical features, radiological findings, treatment patterns and outcomes in patients with HIV-NMOSD. METHODS The details of all cases of HIV- NMOSD were searched from our NMOSD registry. A literature search was also done using the terms NMO, NMOSD and HIV infection in PUBMED, Google Scholar and EMBASE. The details of all the reported cases and cases from our registry were collected and analyzed. RESULTS Six cases of HIV-NMOSD were identified from the literature and one from our registry. There were four males and three females with age ranging from 8 years to 49 years. Duration of HIV infection ranged from newly detected to 15 years. Optic neuritis followed by myelitis was the commonest presentation, occurring in 5 out of 7 patients. 3 patients were anti-aquaporin 4 antibody positive while 3 were negative and in one anti- aquaporin 4 antibody assay was not done. All patients received immunomodulatory treatment. 5/7 patients had poor recovery from acute attacks but no patient had further relapses while on immunomodulatory treatment and antiretroviral therapy. CONCLUSION HIV associated NMOSD is a recently recognized entity. A high index of suspicion is needed to diagnose these patients. In all patients with HIV infection presenting with optic neuritis or/and myelitis, anti aquaporin 4 antibody status should be checked and in all patients of NMOSD, HIV infection should be ruled out.
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Affiliation(s)
- Thomas Mathew
- Department of Neurology, St. John's Medical College Hospital, Sarjapura Road, Bengaluru, Karnataka 560034, India.
| | - Amrutha Avati
- Department of Neurology, St. John's Medical College Hospital, Sarjapura Road, Bengaluru, Karnataka 560034, India
| | - Delon D'Souza
- Department of Neurology, St. John's Medical College Hospital, Sarjapura Road, Bengaluru, Karnataka 560034, India
| | - Manjusha Therambil
- Department of Neurology, St. John's Medical College Hospital, Sarjapura Road, Bengaluru, Karnataka 560034, India
| | - Anita Angela Baptist
- Department of Neurology, St. John's Medical College Hospital, Sarjapura Road, Bengaluru, Karnataka 560034, India
| | - Asha Shaji
- Department of Neurology, St. John's Medical College Hospital, Sarjapura Road, Bengaluru, Karnataka 560034, India
| | - Raghunandan Nadig
- Department of Neurology, St. John's Medical College Hospital, Sarjapura Road, Bengaluru, Karnataka 560034, India
| | - Smitha Mary Rockey
- Department of Microbiology, St. John's Medical College Hospital, Sarjapura Road, Bengaluru, Karnataka 560034, India
| | - Gareth Parry
- Department of Neurology, St. John's Medical College Hospital, Sarjapura Road, Bengaluru, Karnataka 560034, India
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Rodrigues EM, Fernandes R, Susin R, Fior B. Immune reconstitution inflammatory syndrome as a cause of autoimmune hepatitis and acute liver failure. Rev Bras Ter Intensiva 2018; 29:382-385. [PMID: 29044307 PMCID: PMC5632982 DOI: 10.5935/0103-507x.20170053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 01/02/2017] [Indexed: 12/18/2022] Open
Abstract
Acute liver failure is a rare syndrome with high mortality and is often diagnosed
late. Intensivist physicians play fundamental roles in the diagnostic suspicion
and the management of the multiple-organic dysfunctions characteristic of this
entity. Immune reconstitution inflammatory syndrome is an entity that is
characterized by the paradoxical worsening of the patient's previous condition,
after the initiation of antiretrovirals, triggered against either pathogens
present in the host or autoantigens. Autoimmune hepatitis has recently been
described as one of these autoimmune manifestations. The authors report the
first case with evolution to acute liver failure and death within a few days
after the development of encephalopathy, review the cases of autoimmune
hepatitis described and comment on the therapeutic possibilities in this
context.
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Affiliation(s)
- Edison Moraes Rodrigues
- Grupo de Transplante Hepático, Irmandade da Santa Casa de Misericórdia de Porto Alegre - Porto Alegre (RS), Brasil.,Unidade de Terapia Intensiva de Transplantes, Hospital Dom Vicente Scherer, Irmandade da Santa Casa de Misericórdia de Porto Alegre - Porto Alegre (RS), Brasil.,Rede Institucional de Pesquisa e Inovação em Medicina Intensiva, Irmandade da Santa Casa de Misericórdia de Porto Alegre - Porto Alegre (RS), Brasil
| | - Rogério Fernandes
- Grupo de Transplante Hepático, Irmandade da Santa Casa de Misericórdia de Porto Alegre - Porto Alegre (RS), Brasil
| | - Ruth Susin
- Unidade de Terapia Intensiva de Transplantes, Hospital Dom Vicente Scherer, Irmandade da Santa Casa de Misericórdia de Porto Alegre - Porto Alegre (RS), Brasil
| | - Bárbara Fior
- Hospital de Clínicas de Porto Alegre - Porto Alegre (RS), Brasil
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Onyekonwu CL, Chukwuka CJ, Nwandu A, Patel D. Vitiligo immune reconstitution inflammatory syndrome (IRIS)—An incidental finding in a tertiary teaching hospital in southeast Nigeria. JAAD Case Rep 2018; 4:145-148. [PMID: 29387768 PMCID: PMC5789520 DOI: 10.1016/j.jdcr.2017.09.030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Affiliation(s)
- Chinwe Laura Onyekonwu
- Sub-Department of Dermatology, College of Medicine, University of Nigeria, Ituku-Ozalla, Enugu, Nigeria
- Correspondence to: Chinwe Laura Onyekonwu, FMCP, MPH, Sub-Department of Dermatology, College of Medicine, University of Nigeria, Ituku-Ozalla, PO Box 4409, Enugu, Nigeria.Sub-Department of DermatologyCollege of MedicineUniversity of Nigeria, Ituku-OzallaPO Box 4409EnuguNigeria
| | - Chinwe Judith Chukwuka
- Department of Medicine, College of Medicine, University of Nigeria, Ituku-Ozalla, Enugu, Nigeria
| | - Anthea Nwandu
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Devang Patel
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland
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Ofori E, Ramai D, Ona MA, Reddy M. Autoimmune hepatitis in the setting of human immunodeficiency virus infection: A case series. World J Hepatol 2017; 9:1367-1371. [PMID: 29359021 PMCID: PMC5756727 DOI: 10.4254/wjh.v9.i36.1367] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 11/16/2017] [Accepted: 12/06/2017] [Indexed: 02/06/2023] Open
Abstract
Liver injury in the setting of human immunodeficiency virus (HIV) infection is more commonly attributed to viral hepatitis or highly active antiretroviral treatment (HAART) toxicity. The severity of liver injury is an important cause of morbidity and mortality. The emergence of autoimmune diseases, particularly autoimmune hepatitis (AIH) in the setting of HIV infection, is rare. Previous reports indicate that elevated liver enzymes are a common denominator amongst these patients. We present two patients with HIV infection, on HAART, with virological suppression. Both patients presented with elevated liver enzymes, and following liver biopsies, were diagnosed with AIH. The clinical course of these patients underscore the therapeutic value of corticosteroids, and in some cases, addition of immunosuppression for AIH treatment.
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Affiliation(s)
- Emmanuel Ofori
- Division of Gastroenterology and Hepatology, the Brooklyn Hospital Center, Academic Affiliate of the Icahn School of Medicine at Mount Sinai, Clinical Affiliate of the Mount Sinai Hospital, Brooklyn, NY 11201, United States
| | - Daryl Ramai
- Division of Gastroenterology and Hepatology, the Brooklyn Hospital Center, Academic Affiliate of the Icahn School of Medicine at Mount Sinai, Clinical Affiliate of the Mount Sinai Hospital, Brooklyn, NY 11201, United States.
| | - Mel A Ona
- Division of Advanced Endoscopy, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Madhavi Reddy
- Division of Gastroenterology and Hepatology, the Brooklyn Hospital Center, Academic Affiliate of the Icahn School of Medicine at Mount Sinai, Clinical Affiliate of the Mount Sinai Hospital, Brooklyn, NY 11201, United States
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Noreña I, Morantes-Caballero JA, Garcés A, Gómez BJ, Rodríguez G, Saavedra C, Otero W. Autoimmune hepatitis in human immunodeficiency virus infection: Case report and literature review. World J Clin Infect Dis 2017; 7:50-57. [DOI: 10.5495/wjcid.v7.i4.50] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 08/02/2017] [Accepted: 09/13/2017] [Indexed: 02/06/2023] Open
Abstract
The infection due to human immunodeficiency virus (HIV) is characterized by the progressive reduction of CD4+ T lymphocytes and the compromise of other cell lines of the immune system, resulting in immunosuppression. In this context, autoimmune diseases could be considered contradictory, however, cases of autoimmune diseases during this infection have been described, including autoimmune hepatitis (AIH), which is uncommon and has few case reports within medical literature, none of them from Latin America. In this case report where a patient with an HIV infection on combined antiretroviral treatment developed acute elevation of transaminases, hyperbilirubinemia, and deterioration in hepatic synthetic function. Although initially an antiretroviral drug-induced liver injury was suspected, during the study a diagnosis of autoimmune hepatitis was proven, which required treatment with corticosteroid and azathioprine, obtaining a satisfactory response and managing to continue the antiretroviral therapy. Autoimmune diseases in HIV infection must be taken into account. In the case of hepatitis in patients with HIV on antiretroviral treatment, the differentiation between viral hepatitis caused by autoimmune diseases or medications is essential to establish an adequate treatment, and avoid the suspension of the antiretroviral therapy.
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Affiliation(s)
- Ivan Noreña
- Infectious Diseases Section, Department of Internal Medicine, Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia, Bogotá 11321, Colombia
| | - Jairo A Morantes-Caballero
- Department of Internal Medicine, Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia, Bogotá 11321, Colombia
| | - Andrés Garcés
- Department of Internal Medicine, Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia, Bogotá 11321, Colombia
| | - Brian José Gómez
- Department of Internal Medicine, Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia, Bogotá 11321, Colombia
| | - Gabriel Rodríguez
- Infectious Diseases Section, Department of Internal Medicine, Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia, Bogotá 11321, Colombia
| | - Carlos Saavedra
- Infectious Diseases Section, Department of Internal Medicine, Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia, Bogotá 11321, Colombia
| | - William Otero
- Gastroenterology Section, Department of Internal Medicine, Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia, Bogotá 11321, Colombia
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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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Virot E, Duclos A, Adelaide L, Miailhes P, Hot A, Ferry T, Seve P. Autoimmune diseases and HIV infection: A cross-sectional study. Medicine (Baltimore) 2017; 96:e5769. [PMID: 28121924 PMCID: PMC5287948 DOI: 10.1097/md.0000000000005769] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
To describe the clinical manifestations, treatments, prognosis, and prevalence of autoimmune diseases (ADs) in human immunodeficiency virus (HIV)-infected patients.All HIV-infected patients managed in the Infectious Diseases Department of the Lyon University Hospitals, France, between January 2003 and December 2013 and presenting an AD were retrospectively included.Thirty-six ADs were found among 5186 HIV-infected patients which represents a prevalence of 0.69% including immune thrombocytopenic purpura (n = 15), inflammatory myositis (IM) (n = 4), sarcoidosis (n = 4), Guillain-Barré syndrome (GBS) (n = 4), myasthenia gravis (n = 2), Graves' disease (n = 2), and 1 case of each following conditions: systemic lupus erythematosus, rheumatoid arthritis, autoimmune hepatitis, Hashimoto thyroiditis and autoimmune hemolytic anemia. One patient presented 2 ADs. Thirty patients were known to be HIV-infected when they developed an AD. The AD preceded HIV infection in 2 patients. GBS and HIV infection were diagnosed simultaneously in 3 cases. At AD diagnosis, CD4 T lymphocytes count were higher than 350/mm in 63% of patients, between 200 and 350/mm in 19% and less than 200/mm in 19%. Twenty patients benefited from immunosuppressant treatments, with a good tolerance.ADs during HIV infection are uncommon in this large French cohort. Immune thrombocytopenic purpura, sarcoidosis, IM, and GBS appear to be more frequent than in the general population. Immunosuppressant treatments seem to be effective and well tolerated.
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Affiliation(s)
- Emilie Virot
- Département de Médecine Interne, Hôpital de la Croix-Rousse, Hospices Civils de Lyon
| | - Antoine Duclos
- Pôle Information Médicale Evaluation Recherche des Hospices Civils de Lyon
| | - Leopold Adelaide
- Département de Maladies Infectieuses, Hôpital de la Croix-Rousse, Hospices Civils de Lyon
| | - Patrick Miailhes
- Département de Maladies Infectieuses, Hôpital de la Croix-Rousse, Hospices Civils de Lyon
| | - Arnaud Hot
- Université de Lyon, Université Lyon 1
- Département de Médecine Interne, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Tristan Ferry
- Département de Maladies Infectieuses, Hôpital de la Croix-Rousse, Hospices Civils de Lyon
- Université de Lyon, Université Lyon 1
| | - Pascal Seve
- Département de Médecine Interne, Hôpital de la Croix-Rousse, Hospices Civils de Lyon
- Université de Lyon, Université Lyon 1
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Kaleidoscope of autoimmune diseases in HIV infection. Rheumatol Int 2016; 36:1481-1491. [DOI: 10.1007/s00296-016-3555-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 08/13/2016] [Indexed: 12/23/2022]
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Murunga E, Andersson M, Rensburg CV. Autoimmune hepatitis: a manifestation of immune reconstitution inflammatory syndrome in HIV infected patients? Scand J Gastroenterol 2016; 51:814-8. [PMID: 27000683 DOI: 10.3109/00365521.2016.1157888] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To describe a case series of patients presenting with autoimmune hepatitis after initiation of antiretroviral therapy. MATERIALS AND METHODS The demographics, clinical and laboratory features, and therapeutic response of HIV-infected patients on antiretroviral therapy presenting to our Division between November 2011 and November 2014 with elevated liver enzymes, were analysed. RESULTS Nine patients with elevated liver enzymes, immunoglobulin G and autoimmune markers in keeping with autoimmune hepatitis were identified. All were anti-hepatitis C virus negative. One patient was hepatitis B surface antigen positive but his hepatitis B viral load was undetectable. All patients denied using any traditional herbal remedies. Liver histology was consistent with autoimmune hepatitis showing interface hepatitis and infiltrates of lymphocytes and plasma cells. Diagnosis was made according to the Autoimmune Hepatitis Group Scoring Systems. All patients were started on 15-20 mg of oral prednisone with clinical and biochemical improvement after 1-6 weeks. CONCLUSIONS Immune reconstitution related autoimmune hepatitis should be considered in the differential diagnosis of hepatitis in the HIV-infected patient on antiretroviral therapy. Liver biopsy should be performed and the diagnosis confirmed using scoring systems developed by the Autoimmune Hepatitis Group. Timely treatment with prednisone and other agents for autoimmune hepatitis is indicated, and can be lifesaving in acute liver failure.
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Affiliation(s)
- Eric Murunga
- a Division of Gastroenterology , Stellenbosch University Medical School , Cape Town , South Africa
| | - Monique Andersson
- b Division of Infectious Diseases , Stellenbosch University Medical School , Cape Town , South Africa
| | - Christo van Rensburg
- a Division of Gastroenterology , Stellenbosch University Medical School , Cape Town , South Africa
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Affiliation(s)
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- EASL office, 7 Rue Daubin, CH 1203 Geneva, Switzerland,
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Gatselis NK, Zachou K, Koukoulis GK, Dalekos GN. Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics. World J Gastroenterol 2015; 21:60-83. [PMID: 25574080 PMCID: PMC4284362 DOI: 10.3748/wjg.v21.i1.60] [Citation(s) in RCA: 128] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Revised: 10/30/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient.
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Moura MC, Pereira E, Braz V, Eloy C, Lopes J, Carneiro F, Araújo JP. Autoimmune hepatitis in a patient infected by HIV-1 and under highly active antiretroviral treatment: Case report and literature review. World J Immunol 2014; 4:194-198. [DOI: 10.5411/wji.v4.i3.194] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2014] [Revised: 10/12/2014] [Accepted: 10/29/2014] [Indexed: 02/05/2023] Open
Abstract
Liver disease has recently been described as an important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). Liver test changes are useful surrogates of the burden of liver disease. Previous studies have shown that transaminase elevations are frequent among these patients. The cause of those changes is harder to establish in HIV-patients. We present a 61-year-old caucasian male, diagnosed with HIV type 1 infection since 1998, under highly active antiretroviral treatment (HAART), with virological suppression and immunological recovery. He presented in a follow-up laboratory workup high values of transaminases, arthralgia at the hip joints and hepatomegaly. Liver function tests were normal. The antibodies to hepatitis viruses were negative. However, autoimmune study and liver biopsy were compatible with autoimmune hepatitis (AIH). The AIH is a rare diagnosis in HIV-infected patients perhaps because the elevation of transaminases and changes in liver function tests are often associated to HAART or to other possible liver diseases, namely viral hepatitis and non-alcoholic steatohepatitis. The diagnosis may be underestimated. There are no specific recommendations available for the treatment of HIV-associated AIH although the immunosupression with slower tapering seems the most reasonable approach.
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Abstract
Thyroid abnormalities and nonthyroidal illness complicate human immunodeficiency virus (HIV) infection. Among the effects that result from HIV and other opportunistic infections, distinctive features of HIV infection include early lowering of reverse tri-iodothyromine (T3) levels, with normal free T3 levels. Later, some patients develop an isolated low free thyroxine level. After highly active antiretroviral therapy, the immune system reconstitutes in a way that leads to dysregulation of the autoimmune response and the appearance of Graves disease in 1% to 2% of patients. Opportunistic thyroid infections with unusual organisms are most commonly asymptomatic, but can lead to acute or subacute thyroiditis.
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Affiliation(s)
- Anthony P Weetman
- Department of Human Metabolism, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK.
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Iordache L, Launay O, Bouchaud O, Jeantils V, Goujard C, Boue F, Cacoub P, Hanslik T, Mahr A, Lambotte O, Fain O. Autoimmune diseases in HIV-infected patients: 52 cases and literature review. Autoimmun Rev 2014; 13:850-7. [PMID: 24747058 DOI: 10.1016/j.autrev.2014.04.005] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Accepted: 04/04/2014] [Indexed: 12/12/2022]
Abstract
OBJECTIVES 1) To describe autoimmune diseases (AD) in HIV-infected people; and 2) to perform a literature review concerning this issue. DESIGN 52 HIV-infected patients that presented an AD in 14 medical departments in Paris and Ile-de-France area were retrospectively included in this study. RESULTS The ADs were vasculitis (11), immune cytopenias (8), rheumatic diseases (8), lupus (7), sarcoidosis (7), thyroid diseases (6), hepatic diseases (5), and antiphospholipid syndrome (4). Four patients presented 2 ADs. In 5 patients the AD preceded HIV infection, in 14 HIV infection was diagnosed at the same time as the AD and 34 were HIV-infected when they developed an AD. 40 ADs (80%) occurred in patients with a CD4 T lymphocyte count of more than 200/mm(3). Cases of autoimmune hemolytic anemia occurred only in patients severely immunodepressed. In five patients (a vasculitis case, a sarcoidosis case, three thyroid disease cases) the AD presented as a form of immune restoration inflammatory syndrome (IRIS). Some ADs allowed HIV-infection diagnosis at a stage of moderate immune deficiency (vasculitis, antiphospholipid syndrome, immune thrombocytopenia). 37 patients received immunosuppressant treatments with good tolerance. These results confirm in a large series of patients previous data concerning autoimmune diseases occurrence in HIV-infected people. CONCLUSION In the HAART era, when HIV-infected people are treated more and more early, autoimmune diseases can occur, mainly at the phase of immunological recovery. HIV infection should not limit immunosuppressant treatment use.
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Affiliation(s)
- Laura Iordache
- Internal Medicine Department, Jean Verdier Hospital, Avenue du 14 Juillet, 93140 Bondy, France.
| | - Odile Launay
- Clinical Investigation Centre, Cochin Hospital, 27 rue du Fbg St.-Jacques, 75014 Paris, France
| | - Olivier Bouchaud
- Infectious Diseases Department, Avicenne Hospital, 125 rue de Stalingrad, 93009 Bobigny, France
| | - Vincent Jeantils
- Infectious Diseases Department, Jean Verdier Hospital, Avenue du 14 Juillet, 93140 Bondy, France
| | - Cécile Goujard
- Internal Medicine Department, Kremlin Bicetre Hospital, 78 rue du Général Leclerc, 94270 Le Kremlin-Bicetre, France
| | - Francois Boue
- Internal Medicine Department, Antoine Béclère Hospital, 157 rue de la Porte de Trivaux, 92140 Clamart, France
| | - Patrice Cacoub
- Internal Medicine and Clinical Immunology Department, Pitié-Salpétrière Hospital, 47-83 bd de l'Hopital, 75013 Paris, France; Hospital-University Department I2B, Sorbonne Universités, UPMC Paris 6 University, UMR 7211, F-75005, Paris, France; INSERM, UMR S959, F-75013, Paris, France; CNRS, UMR 7211, F-75005, Paris, France
| | - Thomas Hanslik
- Internal Medicine Department, Ambroise Paré Hospital, 9 Avenue Charles-de-Gaulle, 92100 Boulogne Billancourt, France
| | - Alfred Mahr
- Internal Medicine Department, St. Louis Hospital, 1 Avenue Claude-Vellefaux, 75010 Paris, France
| | - Olivier Lambotte
- Internal Medicine Department, Kremlin Bicetre Hospital, 78 rue du Général Leclerc, 94270 Le Kremlin-Bicetre, France
| | - Olivier Fain
- Internal Medicine Department, Jean Verdier Hospital, Avenue du 14 Juillet, 93140 Bondy, France
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Zachou K, Muratori P, Koukoulis GK, Granito A, Gatselis N, Fabbri A, Dalekos GN, Muratori L. Review article: autoimmune hepatitis -- current management and challenges. Aliment Pharmacol Ther 2013; 38:887-913. [PMID: 24010812 DOI: 10.1111/apt.12470] [Citation(s) in RCA: 121] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Revised: 03/22/2013] [Accepted: 08/12/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a disease of unknown aetiology characterised by interface hepatitis, hypergammaglobulinaemia, circulating autoantibodies and a favourable response to immunosuppression. AIM To review recent advancements in understanding aetiopathogenesis, clinical, serological and histological features, diagnostic criteria and treatment strategies of AIH. METHODS Published studies on AIH extracted mainly from PubMed during the last 15 years. RESULTS Autoimmune hepatitis has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations are variable ranging from no symptoms to severe acute hepatitis and only seldom to fulminant hepatic failure. Autoimmune attack is perpetuated, possibly via molecular mimicry mechanisms, and favoured by the impaired control of regulatory T-cells. A typical laboratory finding is hypergammaglobulinaemia with selective elevation of IgG, although in 15-25% of patients - particularly children, elderly and acute cases - IgG levels are normal. Liver histology and autoantibodies, although not pathognomonic, still remain the hallmark for diagnosis. Immunosuppressive treatment is mandatory and life-saving; however, to meet strict response criteria, the conventional therapy with prednisolone with or without azathioprine is far from ideal. CONCLUSIONS Autoimmune hepatitis remains a major diagnostic and therapeutic challenge. The clinician, the hepato-pathologist and the laboratory personnel need to become more familiar with different expressions of the disease, interpretation of liver histology and autoimmune serology. According to the strict definition of treatment response issued by the 2010 AASLD guidelines, many patients are nonresponders to conventional treatment. Newer immunosuppressive agents targeting pathogenetic mechanisms can improve patient management, which needs to be tailored on a case-by-case basis.
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Affiliation(s)
- K Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, Thessaly University, Larissa, Greece
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Caplan M, Trivedi A, McLaughlin M, Hebou A, Kleiner DE, Heller T, Morse CG. Primary Biliary Cirrhosis Overlapping with Autoimmune Hepatitis in an HIV-Infected Patient on Antiretroviral Therapy. JOURNAL OF INTERDISCIPLINARY HISTOPATHOLOGY 2013; 1:270-273. [PMID: 26807302 PMCID: PMC4723101 DOI: 10.5455/jihp.20130624104921] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Liver disease in HIV-infected patients is complex and multifactorial. Drug toxicity and infections are common causes of elevations in liver-associated enzymes. Immune reconstitution and unmasking of autoimmune disease may also play a role, particularly in the era of effective combination antiretroviral therapy. In this case report, we describe the first reported biopsy-confirmed case of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome presenting in an HIV-infected patient following initiation of antiretroviral therapy.
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Affiliation(s)
- Margaret Caplan
- Clinical Research Directorate/CMRP, SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick, MD, USA
| | - Apurva Trivedi
- Liver Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD, USA
| | - Mary McLaughlin
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | | | - David E Kleiner
- Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD, USA
| | - Caryn G Morse
- Critical Care Medicine Department, NIH Clinical Center, Bethesda, MD, USA
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Hagel S, Bruns T, Herrmann A, Tannapfel A, Stallmach A. Autoimmune hepatitis in an HIV-infected patient: an intriguing association. Int J STD AIDS 2013; 23:448-50. [PMID: 22807544 DOI: 10.1258/ijsa.2009.009337] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Abnormal levels of liver enzymes are common in HIV-infected patients and may be caused by multiple factors, including co-infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) infection and in the majority of cases by antiretroviral drug-related liver injury. This report, however, describes a patient with HIV infection and abnormal liver function tests where further diagnostics revealed concomitant autoimmune hepatitis (AIH). The association of immune dysfunction in patients with HIV infection/AIDS and the development of autoimmune diseases is intriguing. The precise mechanism causing the emergence or unmasking of autoimmune conditions in HIV infection remains unclear, but it is important to demonstrate that autoimmune diseases do occur in HIV-infected patients. Therefore, clinicians should include AIH in the differential diagnosis of increased liver enzymes when there is no improvement despite changing antiretroviral therapy.
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Affiliation(s)
- S Hagel
- Division of Gastroenterology, Hepatology and Infectious Diseases, Department of Internal Medicine II, Friedrich-Schiller-University, Erlanger Allee 101, 07747 Jena, Germany.
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Defo D, Kouotou E, Bissek A, Mboua J. Vitiligo régressif au début d’un traitement antirétroviral : syndrome de reconstitution immunitaire ? Ann Dermatol Venereol 2012. [DOI: 10.1016/j.annder.2012.06.049] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Abstract
Autoimmune hepatitis (AIH) is characterized by a T-cell rich infiltrate associated with lobular and interface hepatitis, hypergammaglobulinemia and production of autoantibodies. Genetic risk is linked to the HLA particularly DRB1*0301 and DRB1*0401 alleles in North American and European Caucasian populations. It has recently been suggested that functional deficiencies in CD4(+)CD25(+)CD127(low)FOXP3(+) regulatory T cells contribute to the breakdown of immune tolerance that results in AIH. Most patients respond to immunosuppressive therapy with corticosteroids and can be maintained in remission by low-dose corticosteroid treatment and/or azathioprine. For those who progress to end-stage disease liver transplantation is an effective treatment although it is associated with recurrence. In the future it is likely that biological therapies will allow more targeted therapy designed to switch the balance to immune regulation and thereby restore immune homeostasis. Although treatment for many cases is relatively straightforward and successful problems are encountered in those who fail to respond to standard treatment, are unable to tolerate it or relapse. In such cases alternative therapies should be considered. In addition treatment is complicated in some patients by comorbidity and special care is required during and after pregnancy. We will discuss the current and future therapeutic options for patients with difficult to treat AIH.
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Affiliation(s)
- Richard Parker
- Centre for Liver Research & Birmingham NIHR Biomedical Research Liver Centre, School of Infection and Immunity, MRC Centre for Immune Regulation, Institute for Biomedical Research, Medical School, University of Birmingham, Birmingham, UK
| | - Ye Htun Oo
- Centre for Liver Research & Birmingham NIHR Biomedical Research Liver Centre, School of Infection and Immunity, MRC Centre for Immune Regulation, Institute for Biomedical Research, Medical School, University of Birmingham, Birmingham, UK
| | - David H. Adams
- Centre for Liver Research & Birmingham NIHR Biomedical Research Liver Centre, School of Infection and Immunity, MRC Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK
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Abstract
OBJECTIVE To describe incidence of immune reconstitution inflammatory syndrome (IRIS) and its association with mortality in a large multisite US HIV-infected cohort applying an objective, comprehensive definition. DESIGN We studied 2,610 patients seen during 1996-2007 who initiated or resumed highly active combination antiretroviral therapy (cART) and, during the next 6 months, demonstrated a decline in plasma HIV-RNA viral load of at least 0.5 log(10) copies/ml or an increase of at least 50% in CD4 cell count per microliter. We defined IRIS as the diagnosis of a type B or C condition [as per the Centers for Disease Control and Prevention (CDC) 1993 AIDS case definition] or any new mucocutaneous disorder during this same 6-month period. METHODS We assessed the incidence of IRIS and evaluated risk factors for IRIS using conditional logistic regression and for all-cause mortality using proportional hazards models. RESULTS We identified 370 cases of IRIS (in 276 patients). Median and nadir CD4 cell counts at cART initiation were 90 and 43 cells/μl, respectively; median viral load was 2.7 log(10) copies/ml. The most common IRIS-defining diagnoses were candidiasis (all forms), cytomegalovirus infection, disseminated Mycobacterium avium intracellulare, Pneumocystis pneumonia, varicella zoster, Kaposi's sarcoma and non-Hodgkin lymphoma. Only one case of Mycobacterium tuberculosis was observed. IRIS was independently associated with CD4 cell count less than 50 cells/μl vs. at least 200 cells/μl [odds ratio (OR) 5.0] and a viral load of at least 5.0 log(10) copies vs. less than 4.0 log(10) copies (OR 2.3). IRIS with a type B-defining or type C-defining diagnosis approximately doubled the risk for all-cause mortality. CONCLUSION In this large US-based HIV-infected cohort, IRIS occurred in 10.6% of patients who responded to effective ART and contributed to increased mortality.
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Daas H, Khatib R, Nasser H, Kamran F, Higgins M, Saravolatz L. Human immunodeficiency virus infection and autoimmune hepatitis during highly active anti-retroviral treatment: a case report and review of the literature. J Med Case Rep 2011; 5:233. [PMID: 21702972 PMCID: PMC3141694 DOI: 10.1186/1752-1947-5-233] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2010] [Accepted: 06/25/2011] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION The emergence of hepatic injury in patients with human immunodeficiency virus infection during highly active therapy presents a diagnostic dilemma. It may represent treatment side effects or autoimmune disorders, such as autoimmune hepatitis, emerging during immune restoration. CASE PRESENTATION We present the case of a 42-year-old African-American woman with human immunodeficiency virus infection who presented to our emergency department with severe abdominal pain and was found to have autoimmune hepatitis. A review of the literature revealed 12 reported cases of autoimmune hepatitis in adults with human immunodeficiency virus infection, only three of whom were diagnosed after highly active anti-retroviral treatment was initiated. All four cases (including our patient) were women, and one had a history of other autoimmune disorders. In our patient (the one patient case we are reporting), a liver biopsy revealed interface hepatitis, necrosis with lymphocytes and plasma cell infiltrates and variable degrees of fibrosis. All four cases required treatment with corticosteroids and/or other immune modulating agents and responded well. CONCLUSION Our review suggests that autoimmune hepatitis is a rare disorder which usually develops in women about six to eight months after commencing highly active anti-retroviral treatment during the recovery of CD4 lymphocytes. It represents either re-emergence of a pre-existing condition that was unrecognized or a de novo manifestation during immune reconstitution.
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Affiliation(s)
- Hanady Daas
- Department of Internal Medicine, Division of Infectious Diseases, St John Hospital & Medical Center, 19251 Mack Avenue, Suite 340, Grosse Pointe Woods, MI 48236, USA.
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Mital D, MacFaul G. The ill, jaundiced patient: a triple whammy and the importance of waiting for all results. Clin Med (Lond) 2011; 11:91-2. [PMID: 21404796 PMCID: PMC5873816 DOI: 10.7861/clinmedicine.11-1-91] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
There are many causes of raised liver function tests in HIV infection. This lesson discusses a case where autoimmune hepatitis, acute hepatitis B and acute toxoplasmosis were diagnosed in a lady presenting with abdominal pain and jaundice. Oral steroids for autoimmune hepatitis may have worsened the clinical picture as her hepatitis serology was not available at the time. This lesson highlights the importance of waiting for all serology results to return in an ill jaundiced patient before deciding on active management and treatment
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Affiliation(s)
- D Mital
- Milton Keynes NHS Foundation Trust.
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Abstract
Reconstitution Graves' disease occurs in three settings. First, bone marrow transplantation from a donor with Graves' disease may cause this disease to appear in the recipient, as a result of adoptive immunity, although disordered immunoregulation secondary to graft-versus-host disease may also play a role. Second, alemtuzumab treatment for multiple sclerosis leads to the development of Graves' disease in up to a third of patients during the phase of naive T-cell expansion, which follows therapeutic lymphocyte depletion. Other reconstitution autoimmune phenomena, including immune thrombocytopaenic purpura, are also recognised after alemtuzumab administration. Finally, reconstitution Graves' disease may occur during a similar phase of CD4(+) T-cell expansion, which follows highly active antiretroviral therapy for human immunodeficiency virus infection. Again, this complication is part of a broader spectrum of immunoregulatory disturbances, which can arise after immune reconstitution. The mechanisms responsible for reconstitution Graves' disease are at present unclear, but may include a relative bias towards a Th2-mediated immune response and reduced competition for autoreactive lymphocytes to expand during the time when recovery from lymphopenia commences.
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Affiliation(s)
- Anthony Weetman
- School of Medicine, Beech Hill Road, Sheffield, S10 2RX, UK.
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Abstract
PURPOSE OF REVIEW This review focuses on some of the recent advances in the understanding of HIV immunopathogenesis and the diagnosis and treatment of several autoimmune conditions associated with HIV in the era of potent antiretroviral therapy. RECENT FINDINGS Chronic immune activation with progressive immune exhaustion are central features of HIV pathogenesis. The role of self-reactive T cells in the generation and maintenance of this process has recently been described. The understanding of the impact of immune dysregulation on the generation of autoimmune phenomena in HIV infection remains incomplete. The diagnosis of autoimmune diseases in the context of HIV is often difficult due to similarities in clinical presentations and laboratory markers. The antiretroviral therapy-associated immune reconstitution syndrome can present as autoimmune disease. SUMMARY The cause, frequency and prognosis of autoimmune conditions associated with HIV infection remain somewhat uncertain. Their management is often empirical with the use of novel immunosuppressive medication.
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Reyes-Corcho A, Bouza-Jiménez Y. [Human immunodeficiency virus and AIDS-associated immune reconstitution syndrome. State of the art]. Enferm Infecc Microbiol Clin 2009; 28:110-21. [PMID: 19632745 DOI: 10.1016/j.eimc.2009.03.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2008] [Revised: 03/20/2009] [Accepted: 03/27/2009] [Indexed: 01/27/2023]
Abstract
Since the arrival of highly active antiretroviral therapy (HAART), immune reconstitution syndrome (IRS) has become an increasingly more frequent complication in patients with human immunodeficiency virus (HIV) infection. This article presents a review of the available evidence on this subject, indexed in MEDLINE-PUBMED, BVS-BIREME, and BioMed Central. The review covers the definition, epidemiology, classification, and diagnostic criteria related to IRS. In addition, the clinical particularities of the most frequent etiologies are described, and a proposal for a therapeutic approach is formulated. The prognosis and future implications of this syndrome in the epidemiology of some infectious illnesses in the HIV-positive population are included. Several unresolved aspects are mentioned, such as those related to the pathophysiology of the condition, use of biomarkers for the diagnosis, and the need for evidence-based therapeutic algorithms to enable standardization of treatment for these patients.
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Affiliation(s)
- Andrés Reyes-Corcho
- Servicio de Enfermedades Infecciosas, Hospital Universitario Dr. Gustavo Aldereguía Lima, Cienfuegos, Cuba
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George MP, Kannass M, Huang L, Sciurba FC, Morris A. Respiratory symptoms and airway obstruction in HIV-infected subjects in the HAART era. PLoS One 2009; 4:e6328. [PMID: 19621086 PMCID: PMC2709444 DOI: 10.1371/journal.pone.0006328] [Citation(s) in RCA: 124] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2009] [Accepted: 06/18/2009] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Prevalence and risk factors for respiratory symptoms and airway obstruction in HIV-infected subjects in the era of highly active antiretroviral therapy (HAART) are unknown. We evaluated respiratory symptoms and measured airway obstruction to identify the impact of HAART and other risk factors on respiratory symptoms and pulmonary function. METHODOLOGY/PRINCIPAL FINDINGS Two hundred thirty-four HIV-infected adults without acute respiratory symptoms were recruited from an HIV clinic. All subjects were interviewed and performed spirometry. Multivariate linear and logistic regressions were performed to determine predictors of respiratory symptoms, forced expiratory volume in one second (FEV(1)) percent predicted, and FEV(1)/forced vital capacity (FEV(1)/FVC). Thirty-one percent of subjects reported at least one respiratory symptom. Smoking status (current or former versus never) (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.41-5.22, p = 0.003), higher log plasma HIV viral levels (OR = 1.12, 95%CI = 1.02-1.24, p = 0.02), and lower FEV(1)/FVC (OR = 1.06 for every 0.01 decrease in FEV(1)/FVC, 95%CI = 1.02-1.14, p = 0.001) were independent predictors of respiratory symptoms. Age (p = 0.04), pack-year smoking history (p<0.001), previous bacterial pneumonia (p = 0.007), and HAART use (p = 0.04) were independent predictors of decreased FEV(1)/FVC. CONCLUSIONS/SIGNIFICANCE Respiratory symptoms remain common in HIV-infected subjects, especially in those with a smoking history. Subjects who were older, had a greater pack-year history of smoking, or previous bacterial pneumonia had lower FEV(1)/FVC ratios. Interestingly, use of HAART was independently associated with a decreased FEV(1)/FVC, possibly secondary to an immune response to subclinical infections, increased autoimmunity, or other factors associated with HAART use.
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Affiliation(s)
- M. Patricia George
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
| | - Mouhamed Kannass
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California and Will Rogers Pulmonary Research Institute, Los Angeles, California, United States of America
| | - Laurence Huang
- Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America
| | - Frank C. Sciurba
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
| | - Alison Morris
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California and Will Rogers Pulmonary Research Institute, Los Angeles, California, United States of America
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Vispo E, Maida I, Moreno A, Barreiro P, Soriano V. Autoimmune hepatitis induced by pegylated interferon in an HIV-infected patient with chronic hepatitis C. J Antimicrob Chemother 2008; 62:1470-2. [PMID: 18835807 DOI: 10.1093/jac/dkn416] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
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