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Ikeda K, Fukui S, Kobayashi M, Shimada Y, Nakazawa Y, Mizutani H, Nisiura Y, Suga D, Moritani I, Yamanaka Y, Inoue H, Fukutome K, Shiraki K. Clinicopathological characteristics of autoimmune‑like hepatitis after drug‑induced liver injury. Biomed Rep 2025; 22:75. [PMID: 40083601 PMCID: PMC11904752 DOI: 10.3892/br.2025.1953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 02/10/2025] [Indexed: 03/16/2025] Open
Abstract
Autoimmune hepatitis (AIH) can be induced by drugs, but the underlying mechanisms remain unclear. The present study attempted to elucidate the clinicopathological characteristics of autoimmune-like hepatitis following drug-induced liver injury (DILI-ALH). The medical records of 57 patients diagnosed with AIH at Mie General Medical Center (Yokkaichi, Japan) were retrospectively reviewed, paying particular attention to the history of drug administration. Patients were classified into three groups: De novo AIH, drug-induced ALH (DI-ALH) and DILI-ALH. DILI-ALH was newly defined as cases in which the patient had a history of DILI and where the liver injury initially improved after drug discontinuation, but later worsened and was diagnosed as AIH. Of the 57 patients diagnosed with AIH, 42 patients were included in this study. De novo AIH was diagnosed in 29 patients, DI-ALH in 10 patients and DILI-ALH in 3 patients. Suspected causative drugs for drug-related pathologies were variable, including statins, health foods and supplements. No significant differences in sex or mean age were observed for DI-ALH and DILI-ALH compared with those for AIH. Distinguishing DI-ALH or DILI-ALH from AIH serologically and pathologically is difficult. No significant differences in the number of steroids used or the recurrence rate were observed between any groups. These findings suggest that drugs may present a more diverse cause of ALH than generally predicted. In particular, some AIH cases clearly present with DILI-ALH. Clarifying the involvement of drugs in the pathogenesis of AIH and establishing guidelines for diagnosis and treatment represent important issues for the future.
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Affiliation(s)
- Kohei Ikeda
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Shunsuke Fukui
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Mayu Kobayashi
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Yasuaki Shimada
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Yuichi Nakazawa
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Hiroki Mizutani
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Yuki Nisiura
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Daisuke Suga
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Isao Moritani
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Yutaka Yamanaka
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Hidekazu Inoue
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Kazuo Fukutome
- Department of Pathology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
| | - Katsuya Shiraki
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan
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Das S, Sood V, Rastogi A, Agarwal N, Kaul S, Yadav D, Lal BB, Khanna R, Alam S. Clinico-Pathological Spectrum of Hepatitis A Virus-Induced Autoimmune-Like Hepatitis in Children. J Viral Hepat 2025; 32:e14028. [PMID: 39484867 DOI: 10.1111/jvh.14028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 10/07/2024] [Accepted: 10/08/2024] [Indexed: 11/03/2024]
Abstract
There is limited evidence that hepatitis A virus (HAV) infection can trigger hepatic autoimmunity, but this area remains largely unexplored. This study was thus planned with the aim to compare HAV-induced autoimmune-like hepatitis (HAV-ALH) with HAV-related liver dysfunction (HAV-acute viral hepatitis or HAV-AVH) and classical autoimmune hepatitis (AIH). This was a retrospective review of 46 patients with HAV infection who underwent liver biopsy (including 17 cases of HAV-ALH: diagnosis based on histopathology), and they were compared to 46 cases of age- and gender-matched classical AIH. Overall, HAV cohort (n = 46) had higher prevalence of pruritus, higher bilirubin levels, higher proportion of cholestasis, lower IgG levels, higher seronegativity and lack of disease recurrence, while the classical AIH group had higher proportion/severity of interface hepatitis, fibrosis, necrosis and pseudorosetting (p < 0.05). In comparison to the classical HAV-AVH group, HAV-ALH group had higher AST levels, higher presence of autoantibodies, and higher prevalence of severe zone 3 perivenulitis and marked pseudorosetting on histology (p < 0.05). Also, HAV-ALH group, in comparison to the AIH group, had more pruritus (OR 7.29, p < 0.004) and more seronegativity (41% vs. 13%, p < 0.031), while duration of illness (p < 0.003), IgG (p < 0.001) levels and liver stiffness measurement (p < 0.006) were significantly higher in AIH group (versus the HAV-ALH and HAV-AVH groups). Histologically, in comparison to AIH, HAV-ALH group had significantly less interface hepatitis (OR 0.03, p < 0.001) and fibrosis (OR 0.08, p < 0.001) and significantly more cholestasis (OR 4.5, p < 0.021). HAV infection can act as a potential trigger for immune-mediated hepatic damage, akin to drug-induced autoimmune-like hepatitis. Larger multicentric studies are needed to further explore this aspect.
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Affiliation(s)
- Samannay Das
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Neha Agarwal
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sanjeevani Kaul
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Deepika Yadav
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Malakar S, Shah N, Mishra A, Pandey V, Shirol VV, Wodeyar NK, Verma P, Prathap S, Balankhe K, Rao R, Ghoshal UC. Acute Hepatitis E Virus Infection Triggering Autoimmune Hepatitis in a Patient With Chronic Liver Disease: Case Report and the Review of the Literature. Cureus 2024; 16:e56344. [PMID: 38633970 PMCID: PMC11021215 DOI: 10.7759/cureus.56344] [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: 03/17/2024] [Indexed: 04/19/2024] Open
Abstract
Acute viral hepatitis E (HEV) is the most common form of acute viral hepatitis in India. It is associated with self-limiting disease in most cases. However, the chronic form of HEV is also being increasingly recognized. Other viral infections like the hepatitis A virus (HAV) have been implicated in inciting autoimmune hepatitis. HEV infection has been associated with the formation of circulating liver-directed autoantibodies, however autoimmune liver disease following acute HEV infection has been rarely reported. Here we present a case of a 72-year-old diabetic lady who presented to us with an asymptomatic rise of liver enzymes. Investigations suggested metabolic dysfunction associated with steatotic liver disease. After three months of the diagnosis, she developed acute-on-chronic liver failure and her anti-HEV came out positive. She was managed accordingly. Afterwards patient had persistent high liver enzymes, so she underwent a liver biopsy. Her liver biopsy was compatible with autoimmune hepatitis.
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Affiliation(s)
- Sayan Malakar
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Nishant Shah
- Gastroenterology and Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Ankit Mishra
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Vipin Pandey
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Vivek V Shirol
- Gastroenterology and Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Naganath K Wodeyar
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Prabhat Verma
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Sai Prathap
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Kartik Balankhe
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Ramnawal Rao
- Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Uday C Ghoshal
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
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Xu L, Xu Y, Zhang F, Xu P, Wang L. Immunological pathways in viral hepatitis-induced hepato-cellular carcinoma. Zhejiang Da Xue Xue Bao Yi Xue Ban 2024; 53:64-72. [PMID: 38426692 PMCID: PMC10945487 DOI: 10.3724/zdxbyxb-2023-0481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 12/25/2023] [Indexed: 03/02/2024]
Abstract
Hepatocellular carcinoma (HCC) is a serious neoplastic disease with increasing incidence and mortality, accounting for 90% of all liver cancers. Hepatitis viruses are the major causative agents in the development of HCC. Hepatitis A virus (HAV) primarily causes acute infections, which is associated with HCC to a certain extent, as shown by clinicopathological studies. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections lead to persistent liver inflammation and cirrhosis, disrupt multiple pathways associated with cellular apoptosis and proliferation, and are the most common viral precursors of HCC. Mutations in the HBV X protein (HBx) gene are closely associated with the incidence of HCC, while the expression of HCV core proteins contributes to hepatocellular lipid accumulation, thereby promoting tumorigenesis. In the clinical setting, hepatitis D virus (HDV) frequently co-infects with HBV, increasing the risk of chronic hepatitis. Hepatitis E virus (HEV) usually causes acute infections. However, chronic infections of HEV have been increasing recently, particularly in immuno-compromised patients and organ transplant recipients, which may increase the risk of progression to cirrhosis and the occurrence of HCC. Early detection, effective intervention and vaccination against these viruses may significantly reduce the incidence of liver cancer, while mechanistic insights into the interplay between hepatitis viruses and HCC may facilitate the development of more effective intervention strategies. This article provides a comprehensive overview of hepatitis viruses and reviews recent advances in research on aberrant hepatic immune responses and the pathogenesis of HCC due to viral infection.
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Affiliation(s)
- Lingdong Xu
- Laboratory Animal Center, Zhejiang University, Hangzhou 310058, China.
- Zhejiang University School of Medicine, Hangzhou 310058, China.
| | - Yifan Xu
- Life Sciences Institute, Zhejiang University, Hangzhou 310058, China
| | - Fei Zhang
- Life Sciences Institute, Zhejiang University, Hangzhou 310058, China
- Institute of Intelligent Medicine, Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311200, China
| | - Pinglong Xu
- Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
- Institute of Intelligent Medicine, Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311200, China.
- Key Laboratory of Biosystems Homeostasis and Protection, Ministry of Education, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Zhejiang University, Hangzhou 310058, China.
- Cancer Center, Zhejiang University, Hangzhou 310058, China.
| | - Lie Wang
- Laboratory Animal Center, Zhejiang University, Hangzhou 310058, China.
- Zhejiang University School of Medicine, Hangzhou 310058, China.
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Doulberis M, Papaefthymiou A, Polyzos SA, Vardaka E, Tzitiridou-Chatzopoulou M, Chatzopoulos D, Koffas A, Papadopoulos V, Kyrailidi F, Kountouras J. Local and systemic autoimmune manifestations linked to hepatitis A infection. Acta Gastroenterol Belg 2023; 86:429-436. [PMID: 37814559 DOI: 10.51821/86.3.11299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
Hepatitis A virus (HAV) represents a global burdening infectious agent causing in the majority of cases a self-limiting acute icteric syndrome, the outcome is related to the hepatic substrate and the potential pre-existing damage, whereas a plethora of extra-hepatic manifestations has also been reported. Despite the absence of post- HAV chronicity it has been associated with an additional burden on existing chronic liver diseases. Moreover, the induced immune response and the antigenic molecular mimicry are considered as triggering factors of autoimmunity with regional and distal impact. Diseases such as autoimmune hepatitis, Guillain-Barré syndrome, rheumatoid arthritis, Still's syndrome, Henoch-Schönlein purpura, autoimmune hemolytic anemia, antiphospholipid syndrome, systematic lupus erythematosus or cryoglobulinemic vasculitis have been described in patients with HAV infection. Although the exact mechanisms remain unclear, this review aims to accumulate and clarify the pathways related to this linkage.
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Affiliation(s)
- M Doulberis
- Department of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, Switzerland
- Department of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - A Papaefthymiou
- Pancreaticobiliary Medicine Unit, University College London Hospitals (UCLH), London, UK
- First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - S A Polyzos
- First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - E Vardaka
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Department of Nutritional Sciences and Dietetics, School of Health Sciences, International Hellenic University, Thessaloniki, Macedonia, Greece
| | - M Tzitiridou-Chatzopoulou
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Department of Midwifery, University of Western Macedonia, Macedonia, Greece
| | - D Chatzopoulos
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - A Koffas
- Barts Liver Centre, Centre for Immunobiology, Blizzard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London, UK
| | - V Papadopoulos
- Department of Gastroenterology, University Hospital of Larissa, Larissa, Greece
| | - F Kyrailidi
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - J Kountouras
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Sbikina ES, Vinnitskaya EV, Batskikh SN, Sandler YG, Saliev KG, Khaimenova TY, Bordin DS. [Assessment of the possible impact of hepatitis viruses on the development and course of autoimmune liver diseases]. TERAPEVT ARKH 2023; 95:173-178. [PMID: 37167134 DOI: 10.26442/00403660.2023.02.202113] [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: 03/29/2023] [Accepted: 03/29/2023] [Indexed: 04/01/2023]
Abstract
BACKGROUND Despite the well-studied pathogenesis, the etiology of autoimmune liver disease (AILD) remains unknown. AIM To determine the significance of hepatitis A, B, C and E viruses in the development and progression of AILD. MATERIALS AND METHODS A single-center case-control study included 139 patients with AILD: autoimmune hepatitis - AIH (n=46), primary biliary cholangitis - PBS (n=74), primary sclerosing cholangitis - PSC (n=19). Median age 56 years, IQR 48-65 years. 125 patients - without liver disease - control group (median age 55 years, IQR 46-65 years). Testing of blood serum samples for anti-HAV IgG, anti-HEV IgG, HBsAg, anti-HBc IgG, anti-HCV was carried out by solid-phase ELISA. All patients underwent fibroelastography. Needle liver biopsy - 70 patients: AIH (n=37), PBC (n=28) and PSC (n=5). RESULTS Ab(IgG) to HAV and HBV were detected in patients with AILD significantly more often than in the control group (74.8% vs 54.4%; p<0.001). An increased risk of developing AILD was established in patients with the presence of antibodies to HAV, HBV and HEV (OR 2.491, CI 95% [1.481-4.190]). The highest risk of developing PBC was found in patients with antibodies to HAV and HBV (OR 3.008, 95% CI [1.633-5.542] and OR 2.515, 95% CI [1.242-5.093]). In patients with severe liver fibrosis (F3-F4 according to METAVIR), antibodies to HAV and HBV were detected significantly more often than in patients with F0-F2 [85% vs 65%; p=0.008]. CONCLUSION In our work, we have demonstrated the relationship of past hepatitis A, B, E and AILD, as well as the high risk of developing severe fibrosis in patients with AILD and markers of hepatitis A and B viruses indicates the possible involvement of these viruses in the pathogenesis of AILD.
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Affiliation(s)
| | | | | | | | - K G Saliev
- Loginov Moscow Clinical Scientific Center
| | | | - D S Bordin
- Loginov Moscow Clinical Scientific Center
- Yevdokimov Moscow State University of Medicine and Dentistry
- Tver State Medical University
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Durazzo M, Ferro A. SARS-CoV-2 and autoimmune hepatitis onset: a new association. Minerva Gastroenterol (Torino) 2022; 68:259-260. [PMID: 36083103 DOI: 10.23736/s2724-5985.22.03167-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Marilena Durazzo
- Department of Medical Sciences, University of Turin, Turin, Italy -
| | - Arianna Ferro
- Department of Medical Sciences, University of Turin, Turin, Italy
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8
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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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9
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Datfar T, Doulberis M, Papaefthymiou A, Hines IN, Manzini G. Viral Hepatitis and Hepatocellular Carcinoma: State of the Art. Pathogens 2021; 10:pathogens10111366. [PMID: 34832522 PMCID: PMC8619105 DOI: 10.3390/pathogens10111366] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 09/26/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore, hepatitis B excretory antigen (HBeAg) seems to be a more sensitive predictive tumor marker exhibiting a six-fold higher relative risk in patients with positive HBsAg and HBeAg than those with HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core protein in HCV leads to hepatocellular lipid accumulation associated with oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in tumor and viral cells resulting in HCC. Furthermore, high T-cell immunoglobulin and mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation. Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of reactive oxygen species with the LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV infection represent the most associated forms of viral hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted therapeutics preventing the transition from hepatic inflammation–fibrosis to cancer.
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Affiliation(s)
- Toofan Datfar
- Department of General and Visceral Surgery, Hospital of Aarau, 5001 Aarau, Switzerland;
- Correspondence: ; Tel.: +41-76-4930834
| | - Michael Doulberis
- Department of Gastroenterology and Hepatology, Hospital of Aarau, 5001 Aarau, Switzerland;
| | | | - Ian N. Hines
- Department of Nutrition Science, East Carolina University, Greenville, NC 27858, USA;
| | - Giulia Manzini
- Department of General and Visceral Surgery, Hospital of Aarau, 5001 Aarau, Switzerland;
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10
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S-Are V, Yoder L, Samala N, Nephew L, Lammert C, Vuppalanchi R. An Outbreak Presents An Opportunity to Learn About A Rare Phenotype: Autoimmune Hepatitis After Acute Hepatitis A. Ann Hepatol 2021; 19:694-696. [PMID: 32927125 DOI: 10.1016/j.aohep.2020.08.069] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 08/18/2020] [Accepted: 08/21/2020] [Indexed: 02/04/2023]
Abstract
There are rare instances where patients with acute hepatitis A virus infection subsequently developed autoimmune hepatitis. The diagnosis of autoimmune hepatitis in this setting is challenging. Furthermore, information on treatment with steroids or other immune suppressants, duration of therapy and possibility of treatment discontinuation is currently unclear. Here we report a case series of four patients with histology proven autoimmune hepatitis after hepatitis A virus infection. We describe the presenting features, diagnosis, treatment and long-term outcomes of these cases. This case series provides a insight into the clinical presentation and treatment of autoimmune hepatitis after hepatitis A infection with interesting take home points for clinical hepatologists.
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Affiliation(s)
- Vijay S-Are
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis IN, USA
| | - Lindsay Yoder
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis IN, USA
| | - Niharika Samala
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis IN, USA
| | - Lauren Nephew
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis IN, USA
| | - Craig Lammert
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis IN, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis IN, USA.
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11
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Zachou K, Arvaniti P, Lyberopoulou A, Dalekos GN. Impact of genetic and environmental factors on autoimmune hepatitis. J Transl Autoimmun 2021; 4:100125. [PMID: 34622188 PMCID: PMC8479787 DOI: 10.1016/j.jtauto.2021.100125] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 09/20/2021] [Indexed: 02/07/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic non-resolving liver disease characterized by diffuse hypergammaglobulinemia, the presence of autoantibodies and characteristic histological findings. The disease can have catastrophic outcome with the development of end-stage liver disease if misdiagnosed/undiagnosed and left untreated. AIH pathogenesis remains obscure and the main hypothesis supports its development in genetically predisposed individuals after being exposed to certain environmental triggers. Genetic predisposition is linked to the presence of certain HLA alleles, mainly HLA-DR3 and HLA-DR4. However, a wide number of non-HLA epitopes have also been associated with the disease although data vary significantly among different ethnic groups. Therefore, it is likely that epigenetic alterations may also play a crucial role in disease's pathogenesis, although not yet extensively studied. The aim of this review was to summarize the genetic and environmental factors that have been associated with AIH, but also to open new insights towards the role of epigenetic modifications in the etiology of the disease.
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Affiliation(s)
- Kalliopi Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center in Autoimmune Liver Diseases, University Hospital of Larissa, Larissa, Greece
| | - Pinelopi Arvaniti
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center in Autoimmune Liver Diseases, University Hospital of Larissa, Larissa, Greece
| | - Aggeliki Lyberopoulou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center in Autoimmune Liver Diseases, University Hospital of Larissa, Larissa, Greece
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center in Autoimmune Liver Diseases, University Hospital of Larissa, Larissa, Greece
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Yan J, He YS, Song Y, Chen XY, Liu HB, Rao CY. False positive anti-hepatitis A virus immunoglobulin M in autoimmune hepatitis/primary biliary cholangitis overlap syndrome: A case report. World J Clin Cases 2021; 9:6464-6468. [PMID: 34435013 PMCID: PMC8362578 DOI: 10.12998/wjcc.v9.i22.6464] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 04/30/2021] [Accepted: 05/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is an immune-mediated liver disease affecting all age groups. Associations between hepatitis A virus (HAV) and AIH have been described for many years. Herein, we report a case of an AIH/primary biliary cholangitis (PBC) overlap syndrome with anti-HAV immunoglobulin M (IgM) false positivity.
CASE SUMMARY A 55-year-old man was admitted with manifestations of anorexia and jaundice along with weakness. He had marked transaminitis and hyperbilirubinemia. Viral serology was positive for HAV IgM and negative for others. Autoantibody screening was positive for anti-mitochondria antibody but negative for others. Abdominal ultrasound imaging was normal. He was diagnosed with acute hepatitis A. After symptomatic treatment, liver function tests gradually recovered. Several months later, his anti-HAV IgM positivity persisted and transaminase and bilirubin levels were also more than 10 times above of the upper limit of normal. Liver histology was prominent, and HAV RNA was negative. Therefore, AIH/primary biliary cholangitis (PBC) overlap syndrome diagnosis was made based on the “Paris Criteria”. The patient was successfully treated by immunosuppression.
CONCLUSION This case highlights that autoimmune diseases or chronic or acute infections, may cause a false-positive anti-HAV IgM result because of cross-reacting antibodies. Therefore, the detection of IgM should not be the only method for the diagnosis of acute HAV infection. HAV nucleic acid amplification tests should be employed to confirm the diagnosis.
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Affiliation(s)
- Jun Yan
- Department of Hepatology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China
| | - Yan-Sha He
- Department of Hepatology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China
| | - Yi Song
- Department of Hepatology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China
| | - Xin-Yu Chen
- Department of Hepatology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China
| | - Hua-Bao Liu
- Department of Hepatology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China
| | - Chun-Yan Rao
- Department of Hepatology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China
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Maslennikov R, Ivashkin V, Efremova I, Shirokova E. Immune disorders and rheumatologic manifestations of viral hepatitis. World J Gastroenterol 2021; 27:2073-2089. [PMID: 34025065 PMCID: PMC8117740 DOI: 10.3748/wjg.v27.i18.2073] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 02/28/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
Abstract
Infection with hepatotropic viruses is not limited to the liver and can lead to the development of various immunological disorders (the formation of cryoglobulins, rheumatoid factor, antinuclear antibodies, autoantibodies specific for autoimmune hepatitis and primary biliary cholangitis, and others), which can manifest as glomerulonephritis, arthritis, uveitis, vasculitis (cryoglobulinemic vasculitis, polyarteritis nodosa, Henoch-Schonlein purpura, isolated cutaneous necrotizing vasculitis), and other rheumatologic disorders, and be a trigger for the subsequent development of autoimmune hepatitis and primary biliary cholangitis. A further study of the association between autoimmune liver diseases and hepatotropic virus infection would be useful to assess the results of treatment of these associated diseases with antiviral drugs. The relationship of these immune disorders and their manifestations with hepatotropic viruses is best studied for chronic hepatitis B and C. Only isolated cases of these associations are described for hepatitis A. These links are least studied, and are often controversial for hepatitis E, possibly due to their relatively rare diagnoses. Patients with uveitis, glomerulonephritis, arthritis, vasculitis, autoimmune liver diseases should be tested for biomarkers of viral hepatitis, and if present, these patients should be treated with antiviral drugs.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119435, Russia
- Department of Internal Medicine 1, Сonsultative and Diagnostic Center 2 of the Moscow City Health Department, Moscow 107564, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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Yeend-Curd-Trimble H, Kelly K, Ghosh I, MacDonald D. Autoimmune liver disease following acute hepatitis A infection. BMJ Case Rep 2019; 12:12/5/e228433. [PMID: 31151971 DOI: 10.1136/bcr-2018-228433] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
A male patient in his late 30s presented to our outpatient clinic at Mortimer Market Centre with worsening liver transaminases tests 2 months after a resolved acute hepatitis A infection. A diagnosis of parainfectious autoimmune-like hepatitis phenomena was made based on the history, laboratory and histological features.
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Affiliation(s)
| | - Kate Kelly
- HIV and Sexual Health, Central and North West London NHS Foundation Trust, London, UK
| | - Indrajit Ghosh
- HIV and Sexual Health, Central and North West London NHS Foundation Trust, London, UK
| | - Douglas MacDonald
- Gastroenterology and Hepatology, Royal Free London NHS Foundation Trust, London, UK
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15
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Taubert R, Diestelhorst J, Junge N, Kirstein MM, Pischke S, Vogel A, Bantel H, Baumann U, Manns MP, Wedemeyer H, Jaeckel E. Increased seroprevalence of HAV and parvovirus B19 in children and of HEV in adults at diagnosis of autoimmune hepatitis. Sci Rep 2018; 8:17452. [PMID: 30487523 PMCID: PMC6261942 DOI: 10.1038/s41598-018-35882-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 11/13/2018] [Indexed: 12/13/2022] Open
Abstract
Preceding viral infections have mostly been described in autoimmune hepatitis (AIH) in single cases. We aimed to identify viral infections that potentially trigger AIH, as suggested for hepatitis E virus (HEV) infections. Therefore, antibodies against hepatitis A (HAV), B, C and E viruses; hepatotropic herpesviruses; and parvovirus B19 (PVB19) were analyzed retrospectively in 219 AIH patients at diagnosis, 356 patients with other liver diseases and 89 children from our center. Untreated adult AIH (aAIH) patients showed higher anti-HEV seroprevalences at diagnosis than patients with other liver diseases. Untreated aAIH patients had no increased incidence of previous hepatitis A, B or C. Antibodies against hepatotropic herpesviruses in untreated AIH were in the range published for the normal population. Untreated pediatric AIH (pAIH) patients had evidence of more previous HAV and PVB19 infections than local age-matched controls. The genetic AIH risk factor HLA DRB1*03:01 was more frequent in younger patients, and DRB1*04:01 was more frequent in middle-aged patients without an obvious link to virus seropositivities. Pediatric and adult AIH seem to be distinct in terms of genetic risk factors and preceding viral infections. While associations cannot prove causal relations, the results suggest that hepatotropic virus infections could be involved in AIH pathogenesis.
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Affiliation(s)
- Richard Taubert
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
| | - Jana Diestelhorst
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - Norman Junge
- Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - Martha M Kirstein
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Sven Pischke
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Department of Internal Medicine, Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heike Bantel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Ulrich Baumann
- Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany.,Department of Gastroenterology and Hepatology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany
| | - Elmar Jaeckel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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van Gemeren MAJ, van Wijngaarden P, Doukas M, de Man RA. Vaccine-related autoimmune hepatitis: the same disease as idiopathic autoimmune hepatitis? Two clinical reports and review. Scand J Gastroenterol 2017; 52:18-22. [PMID: 27565372 DOI: 10.1080/00365521.2016.1224379] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Autoimmune hepatitis (AIH) develops in genetically predisposed individuals after an inciting or environmental trigger. These factors are unknown but may include viral infections, environmental toxins, drugs and vaccinations. Few reports are written about vaccination as potential trigger of autoimmune hepatitis. In this article, we additionally describe two vaccine-related cases of AIH. In both cases, long-term immune-suppressive therapy is demanded. Moreover, we present the cases of vaccine-related AIH from literature and compare these with idiopathic AIH and our own cases.
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Affiliation(s)
- Marline A J van Gemeren
- a Department of Internal Medicine and Gastroenterology , Amphia Ziekenhuis Locatie Molengracht , Breda , the Netherlands
| | - Peter van Wijngaarden
- a Department of Internal Medicine and Gastroenterology , Amphia Ziekenhuis Locatie Molengracht , Breda , the Netherlands
| | - Michael Doukas
- b Department of Pathology , Erasmus University Medical Centre Rotterdam , Rotterdam , the Netherlands
| | - Robert A de Man
- c Department of Gastroenterology and Hepatology , Erasmus University Medical Centre, Rotterdam , Rotterdam , the Netherlands
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17
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Affiliation(s)
- Resat Ozaras
- aDepartment of Infection, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey bDepartment of Gastroenterology, Missouri University, Columbia, Missouri, USA
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Abdel-Ghaffar TY, Sira MM, Sira AM, Salem TA, El-Sharawy AA, El Naghi S. Serological markers of autoimmunity in children with hepatitis A: relation to acute and fulminant presentation. Eur J Gastroenterol Hepatol 2015; 27:1161-1169. [PMID: 26062080 DOI: 10.1097/meg.0000000000000413] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Hepatitis A virus (HAV) infection tends to be a self-limiting disease without serious sequelae, but fulminant hepatitis, with a high mortality, develops in 0.1-0.2% of the cases. Sometimes, HAV infection precipitates autoimmune hepatitis (AIH). We aimed to assess the frequency and clinical significance of serologic markers of autoimmunity during hepatitis A infection with an acute or fulminant presentation compared with those in AIH. METHODS The study included 126 children: 46 with HAV infection (33 with acute and 13 with fulminant presentation), 53 with AIH, and 27 healthy controls. In all, we measured autoantibodies titer (antinuclear antibody, antismooth muscle antibody, and liver kidney microsomal antibody-1) and serum gammaglobulins. RESULTS Autoantibodies were detected in the majority of HAV (63.1%) and AIH (79.2%) groups, but in none of the controls. Gammaglobulins were significantly higher in the HAV group (1.93±0.57 g/dl) than in the controls (1.32±0.29 g/dl), but lower than that in the AIH group (2.93±1.2 g/dl) (P<0.0001 for all). In the HAV group, gammaglobulins were significantly higher in those with fulminant (2.21±0.46 g/dl) than in those with acute presentation (1.82±0.57 g/dl) (P=0.019), but comparable with that in AIH (P=0.095). Gammaglobulins correlated significantly with disease severity in both HAV and AIH groups. CONCLUSION Hypergammaglobulinemia and a high occurrence of autoantibodies are encountered in HAV infection. This may support the immunological basis of its pathogenesis. Moreover, the higher gammaglobulins in fulminant HAV, with an insignificant difference from that in AIH, suggest that a more aggressive immunological reaction is related to this presentation.
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Affiliation(s)
- Tawhida Y Abdel-Ghaffar
- aYassin Abdel-Ghaffar Charity Center for Liver Disease and Research bDepartment of Pediatrics, Faculty of Medicine, Ain Shams University cPediatric Department, National Hepatology and Tropical Medicine Research Institute, Cairo Departments of dPediatric Hepatology eClinical Pathology, National Liver Institute, Menofiya University, Menofiya, Egypt
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Saadah OI, Bokhary RY. Anti-mitochondrial antibody positive autoimmune hepatitis triggered by EBV infection in a young girl. Arab J Gastroenterol 2013; 14:130-2. [DOI: 10.1016/j.ajg.2013.05.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2012] [Revised: 10/30/2012] [Accepted: 05/30/2013] [Indexed: 01/30/2023]
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20
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Trivedi PJ, Hirschfield GM. Review article: overlap syndromes and autoimmune liver disease. Aliment Pharmacol Ther 2012; 36:517-33. [PMID: 22817525 DOI: 10.1111/j.1365-2036.2012.05223.x] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2012] [Revised: 03/30/2012] [Accepted: 07/01/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) all nestle within the family of autoimmune liver diseases, whereby the result of immune-mediated liver injury gives rise to varied clinical presentations. Some patients demonstrate a phenotype whereby there is evidence of either PBC or PSC together with overlapping features of AIH. Due to an absence of well-validated diagnostic criteria and a lack of large therapeutic trials, treatment of overlap conditions is empiric and extrapolated from data derived from the primary autoimmune liver diseases. AIMS To review overlaps in the context of autoimmune liver diseases. METHODS General and specific review of published articles using PubMed, Medline and Ovid search engines, alongside pre-existing clinical management protocols, guidelines, and the authors' own knowledge of the published literature. RESULTS The challenges in diagnosis, clinical presentation, determining natural history and outcome of overlaps are presented, as well as present-day management suggestions, some based on evidence, others on consensus and opinion. CONCLUSIONS Overlapping autoimmune features, be they clinical, serological, histological or radiological are not infrequent, but appropriate diagnosis remains hindered by a lack of standardised diagnostic criteria. Optimum care for those with suspected overlap should thus focus on attention to detail over the fundamental aspects of timely secure diagnosis of the dominant disease entity. Clinicians should counsel patients carefully with regard to the risks and benefits of treatment, bearing in mind the paucity of randomised and controlled outcome data for medical interventions.
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Affiliation(s)
- P J Trivedi
- Centre for Liver Research and NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK
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HLA-DRB1 as a risk factor in children with autoimmune hepatitis and its relation to hepatitis A infection. Ital J Pediatr 2010; 36:73. [PMID: 21067577 PMCID: PMC2992538 DOI: 10.1186/1824-7288-36-73] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2010] [Accepted: 11/10/2010] [Indexed: 02/06/2023] Open
Abstract
Background The human leukocyte antigens (HLAs) are proteins found in the membranes of nearly all nucleated cells. People with certain HLA antigens are more likely to develop certain autoimmune diseases. The aim of this study was to determine the frequency of HLA-DRB1 in children with autoimmune hepatitis (AIH) as a risk factor for occurrence, its relation to preceding hepatitis A infection and treatment outcome. Subjects and methods 25 children with AIH were subjected to HLA-DRB 1 typing performed by sequence specific oligonucleotide probe technique and compared to HLA-DRB1 found in 548 normal populations. Results The most frequent alleles found in our children with AIH were HLA-DRB1*13 (36%), HLA-DRB1*04 (18%) and HLA-DRB1*03 (14%). HLA-DRB1*13 was significantly more frequent in AIH patients compared to controls. In type I AIH patients HLA-DRB1*13 was the most frequent allele (32.4%), followed by HLA-DRB1*04 in (20.6%) and HLA-DRB1*03 in (14.7%), While in type II, the most frequent alleles were HLA-DRB1*13 in (40%), HLA-DRB1*07 (20%) and HLA-DRB1*15 in (20%). HLA-DRB1*12 was significantly more frequent in AIH patients with positive Hepatitis A IgM than in patients with negative hepatitis A IgM. No statistically significant difference between partial responders and complete responders to treatment as regards HLA-DRB1 subtypes. Conclusion It is concluded from the previous study that HLA-DRB1*13 may be a susceptibility allele for the occurrence of autoimmune hepatitis in our population. HLA-DRB1*07 and HLA-DRB1*15 may be susceptibility alleles for occurrence of autoimmune hepatitis type 2. HLA-DRB1*12 association with AIH in patients triggered by hepatitis A needs further studies.
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Abstract
We report the case of a 24-year-old woman with an autoimmune hepatitis/primary biliary cirrhosis overlap syndrome triggered by an acute hepatitis A. A number of viruses have been proposed as potential triggers of autoimmune hepatitis in patients with genetic predisposition. To date, approximately 10 cases of type 1 autoimmune hepatitis following hepatitis A virus infection have been published in the medical literature. To our knowledge, this is the first case of overlap syndrome triggered by an acute hepatitis A.
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Tabak F, Ozdemir F, Tabak O, Erer B, Tahan V, Ozaras R. Autoimmune hepatitis induced by the prolonged hepatitis A virus infection. Ann Hepatol 2008; 7:177-179. [PMID: 18626439 DOI: 10.1016/s1665-2681(19)31878-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis in the world. Rarely, acute infection may persist for a long time. Autoimmune hepatitis (AIH) may provide anti-HAV IgM positivity detection for a prolonged time. On the other hand, HAV as an infectious agent may also trigger AIH. Here we presented a case which seemed like a simple acute viral hepatitis A infection at the beginning but turned out to be an AIH according to the International Autoimmune Hepatitis Group's system. A 21-year-old female was diagnosed as symptomatic acute HAV infection with anti-HAV IgM positivity and elevated aminotransferase levels. The other viral serological tests were negative. On the 6th, 12th and 18th months of the follow up, her anti-HAV IgM positivity still continued and transaminase levels were also 3 to 7 times high of the upper limit of normal. In addition, antinuclear antibody was positive. However, on the 19th month anti-HAV IgM could be detected as negative. Liver histology was prominent. The patient had a score of 16 according to the International Autoimmune Hepatitis Group's system. She was given prednisolone (10 mg/day) and azathioprine (100 mg/day). The aminotransferase levels were detected within normal ranges at the end of the first month of therapy. She was in remission during follow up for 6 years. In conclusion, prolonged HAV infection and AIH may not only trigger each other but also deteriorate the liver histology. AIH should be investigated in cases of long-lasting HAV infection in order to begin the treatment earlier. On the other hand, AIH patients should also be vaccinated for both HBV and HAV to avoid more severe diseases.
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Affiliation(s)
- Fehmi Tabak
- Istanbul University, Cerrahpasa Medical Faculty, Department of Infectious Diseases
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Abstract
To describe a case of probable relapsing autoimmune hepatitis associated with vaccination against hepatitis A virus (HAV). A case report and review of literature were written concerning autoimmune hepatitis in association with hepatitis A and other hepatotropic viruses. Soon after the administration of formalin-inactivated hepatitis A vaccine, a man who had recently recovered from an uncharacterized but self-limiting hepatitic illness, experienced a severe deterioration (AST 1687 U/L, INR 1.4). Anti-nuclear antibodies were detectable, and liver biopsy was compatible with autoimmune hepatitis. The observation supports the role of HAV as a trigger of autoimmune hepatitis. Studies in helper T-cell activity and antibody expression against hepatic proteins in the context of hepatitis A infection are summarized, and the concept of molecular mimicry with regard to other forms of viral hepatitis and autoimmunity is briefly explored.
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Affiliation(s)
- P-A Berry
- Medway Maritime Hospital, 31 Pentlow Street, Putney, London, SW15 1LX, United Kingdom.
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