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Kugler TE, Taradin GG, Rakitskaya IV, Khristulenko AL, Gnilitskaya VB. Helicobacter infection and hepatobiliary cancer: epidemiology and pathogenesis. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2023:36-46. [DOI: 10.31146/1682-8658-ecg-220-12-36-46] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Hepatobiliary cancer is one of the leading causes of cancer death and a major public health problem in both developed and developing countries. Chronic infections are common risk factors for cancer. Animal studies have shown that Helicobacter pylori (H. pylori) infection can cause hepatitis, colitis, and liver cancer in susceptible individuals. Data from clinical and experimental studies point to the involvement of the gastrointestinal microbiota in the pathogenesis of the non-alcoholic fatty liver disease, including H. pylori infection. The researchers included H. pylori infection in the list of etiopathogenetic factors of primary biliary cholangitis due to the detection of its DNA in the liver tissue and antibodies to H. pylori in the bile and serum of patients with primary biliary cholangitis. A growing body of evidence suggests that H. pylori may be a risk factor for the development of liver cirrhosis and hepatocellular carcinoma in patients with viral hepatitis B and C. The contribution of H. pylori infection to the development of hepatic encephalopathy and hyperammonemia has been identified. H. pylori infection is associated with liver inflammation, fibrosis, and necrosis by inducing the synthesis of systemic inflammatory mediators and increasing intestinal permeability. Along with these consequences, bacterial translocation through the biliary tract can also lead to direct liver damage, predisposing or even triggering the carcinogenic process. The study of subspecies of Helicobacter shows that they can lead to the development of not only hepatocellular carcinoma but also other malignant neoplasms of the hepatobiliary system. This review presents current data on the epidemiology and mechanisms of the influence of H. pylori infection on malignant neoplasms of the hepatobiliary tract, with an emphasis on possible prevention strategies.
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Kugler T, Taradin G. HELICOBACTER AND HEPATOBILIARY DISEASES: UPDATE 2023. ARQUIVOS DE GASTROENTEROLOGIA 2023; 60:271-281. [PMID: 37556754 DOI: 10.1590/s0004-2803.202302023-15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 04/28/2023] [Indexed: 08/11/2023]
Abstract
•Clinical studies have shown that hepatobiliary diseases of inflammatory and neoplastic origin are associated with Helicobacter infection. •Translocation and the ascending pathway are putative mechanisms for Helicobacter spp to enter the hepatobiliary system. •H. pylori infection has a systemic effect through the activity of pro-inflammatory cytokines, TNF-α, leukotrienes, interferon-β, interferon-γ, and acute phase proteins. •Histopathological confirmation is needed to present that H. pylori eradication prevents or improves hepatobiliary disease progression. Helicobacter Pylori (H. pylori) is one of the main infectious causes of gastroduodenal diseases, however, its role in developing different extragastric diseases has been proven. The possible involvement of H. pylori in the pathogenesis of cardiovascular, metabolic, neurodegenerative, skin, and hepatobiliary diseases is suggested. The bacterium has been found in tissue samples from the liver, biliary tract, and gallstones of animals and humans. However, the role of H. pylori infection in the pathogenesis of liver and biliary diseases has not been finally established. The histopathological confirmation of the positive effect of H. pylori eradication is needed. In addition, there are discussions on the clinical significance of other Helicobacter species. The review presents the data available for and against the involvement of H. pylori in hepatobi-liary disease development and progression.
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Affiliation(s)
- Tatyana Kugler
- Donetsk National Medical University, Faculty of postgraduate education, Department of Therapy, Donetsk Oblast, Ucrânia
| | - Gennady Taradin
- Donetsk National Medical University, Faculty of postgraduate education, Department of Therapy, Donetsk Oblast, Ucrânia
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Cui MY, Cui ZY, Zhao MQ, Zhang MJ, Jiang QL, Wang JJ, Lu LG, Lu YY. The impact of Helicobacter pylori infection and eradication therapy containing minocycline and metronidazole on intestinal microbiota. BMC Microbiol 2022; 22:321. [PMID: 36581836 PMCID: PMC9798553 DOI: 10.1186/s12866-022-02732-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 12/12/2022] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter the gut microbiota. However, few studies explored the impact of eradication therapy containing minocycline and metronidazole on gut microbiota. AIM The objective of the present study was to explore the changes of gut microbiota after H. pylori infection. Besides, learn more about the dynamic changes of gut microbiota during different stages of eradication treatment containing minocycline, metronidazole, bismuth agents and proton pump inhibitors. METHODS Sixty stool samples from the patients with H. pylori infection before eradication, 14 and 42 days after eradication, and ten stool samples from non-infected individuals were collected. Subsequently, we performed 16S rRNA gene amplicon sequencing to analyze these samples, and the results were evaluated by using alpha diversity, beta diversity and microbial composition analyses. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was also used to predict the metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes database. RESULTS The alpha and beta diversity of the microbiota changed significantly in H. pylori infected individuals, but returned to baseline 42 days after eradication therapy. At the genus level, the abundances of Bacteroidetes, [Ruminococcus]_gnavus_group, Ruminococcaceae_Incertae_Sedis, Tuzzrealla, Butyricicoccus were significantly lower in the H. pylori infected group. Bacterial abundance was also dynamically changing during eradication treatment. In addition, PICRUST analysis found the levels of uronic acid metabolism, uncharacterized transport system, and biosynthesis of unsaturated fatty acids were higher in H. pylori infected individuals than in the non-infected group. CONCLUSIONS Intestinal microbiota diversity, composition, functional predictions altered significantly after H. pylori infection, and gradually returned to healthy control levels after the application of eradication therapy containing minocycline and metronidazole in one month and a half.
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Affiliation(s)
- Meng-Yan Cui
- grid.412478.c0000 0004 1760 4628Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620 China
| | - Zhen-Yu Cui
- grid.16821.3c0000 0004 0368 8293Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201800 China
| | - Meng-Qi Zhao
- grid.412478.c0000 0004 1760 4628Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620 China
| | - Meng-Jie Zhang
- grid.16821.3c0000 0004 0368 8293Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201800 China
| | - Qiao-Li Jiang
- grid.16821.3c0000 0004 0368 8293Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201800 China
| | - Jing-Jing Wang
- grid.412478.c0000 0004 1760 4628Shanghai Key Laboratory of Pancreatic Diseases, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620 China
| | - Lun-Gen Lu
- grid.412478.c0000 0004 1760 4628Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620 China
| | - Ying-Ying Lu
- grid.412478.c0000 0004 1760 4628Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620 China ,grid.16821.3c0000 0004 0368 8293Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201800 China
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Wang L, Cao ZM, Zhang LL, Dai XC, Liu ZJ, Zeng YX, Li XY, Wu QJ, Lv WL. Helicobacter Pylori and Autoimmune Diseases: Involving Multiple Systems. Front Immunol 2022; 13:833424. [PMID: 35222423 PMCID: PMC8866759 DOI: 10.3389/fimmu.2022.833424] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 01/24/2022] [Indexed: 12/12/2022] Open
Abstract
The modern Gastroenterology have witnessed an essential stride since Helicobacter pylori was first found in the stomach and then its pathogenic effect was discovered. According to the researches conducted during the nearly 40 years, it has been found that this bacterium is associated with a natural history of many upper gastrointestinal diseases. Epidemiological data show an increased incidence of autoimmune disorders with or after infection with specific microorganisms. The researches have revealed that H. pylori is a potential trigger of gastric autoimmunity, and it may be associated with other autoimmune diseases, both innate and acquired. This paper reviews the current support or opposition about H. pylori as the role of potential triggers of autoimmune diseases, including inflammatory bowel disease, autoimmune thyroiditis, type 1 diabetes mellitus, autoimmune liver diseases, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, as well as Sjogren’s syndrome, chronic urticaria and psoriasis, and tried to explain the possible mechanisms.
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Affiliation(s)
- Li Wang
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zheng-Min Cao
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Li-Li Zhang
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xin-Can Dai
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhen-Ju Liu
- Department of Proctology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yi-Xian Zeng
- Department of Proctology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xin-Ye Li
- Department of Cardiovascular, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qing-Juan Wu
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wen-Liang Lv
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Zheng Y, Ran Y, Zhang H, Wang B, Zhou L. The Microbiome in Autoimmune Liver Diseases: Metagenomic and Metabolomic Changes. Front Physiol 2021; 12:715852. [PMID: 34690796 PMCID: PMC8531204 DOI: 10.3389/fphys.2021.715852] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 08/24/2021] [Indexed: 12/12/2022] Open
Abstract
Recent studies have identified the critical role of microbiota in the pathophysiology of autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Metagenomic studies reveal significant decrease of gut bacterial diversity in AILDs. Although profiles of metagenomic vary widely, Veillonella is commonly enriched in AIH, PBC, and PSC. Apart from gut microbiome, the oral and bile microbiome seem to be associated with these diseases as well. The functional analysis of metagenomics suggests that metabolic pathways changed in the gut microbiome of the patients. Microbial metabolites, including short-chain fatty acids (SCFAs) and microbial bile acid metabolites, have been shown to modulate innate immunity, adaptive immunity, and inflammation. Taken together, the evidence of host–microbiome interactions and in-depth mechanistic studies needs further accumulation, which will offer more possibilities to clarify the mechanisms of AILDs and provide potential molecular targets for the prevention and treatment in the future.
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Affiliation(s)
- Yanping Zheng
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Ying Ran
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Hongxia Zhang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Lu Zhou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Department of Gastroenterology and Hepatology, Hotan People's Hospital, Xinjiang, China
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Li N, Li J, Zhang Q, Gao S, Quan X, Liu P, Xu C. Effects of endocrine disrupting chemicals in host health: Three-way interactions between environmental exposure, host phenotypic responses, and gut microbiota. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2021; 271:116387. [PMID: 33401209 DOI: 10.1016/j.envpol.2020.116387] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 12/20/2020] [Accepted: 12/23/2020] [Indexed: 06/12/2023]
Abstract
Endocrine disrupting chemicals (EDCs) have gradually become a global health hazard in recent decades. Gut microbiota (GM) provides a crucial interface between the environment and the human body. A triad relationship may exist between EDCs exposure, host phenotypic background, and GM effects. In this review, we attempted to parse out the contribution of GM on the alteration of host phenotypic responses induced by EDCs, suggesting that GM intervention may be used as a therapeutic strategy to limit the expansion of pathogen. These studies can increase the understanding of pathogenic mechanisms, and help to identify the modifiable environmental factors and microbiota characteristics in people with underlying disease susceptibility for prevention and remediation.
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Affiliation(s)
- Na Li
- Pediatric Department, Ruijin Hospital, Shanghai Jiaotong University. School of Medicine, Shanghai, China; Institute of Tropical Medicine, Hainan Medical University, HaiKou, China
| | - Jinhua Li
- School of Public Health, Jilin University, Changchun, China
| | - Qingqing Zhang
- Pediatric Department, Ruijin Hospital, Shanghai Jiaotong University. School of Medicine, Shanghai, China
| | - Shenshen Gao
- Pediatric Department, Ruijin Hospital, Shanghai Jiaotong University. School of Medicine, Shanghai, China
| | - Xu Quan
- Pediatric Department, Ruijin Hospital, Shanghai Jiaotong University. School of Medicine, Shanghai, China
| | - Ping Liu
- Pediatric Department, Ruijin Hospital, Shanghai Jiaotong University. School of Medicine, Shanghai, China
| | - Chundi Xu
- Pediatric Department, Ruijin Hospital, Shanghai Jiaotong University. School of Medicine, Shanghai, China.
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Baker SS, Baker RD. Gut Microbiota and Liver Injury (II): Chronic Liver Injury. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1238:39-54. [PMID: 32323179 DOI: 10.1007/978-981-15-2385-4_4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Chronic liver injury mainly comprises viral hepatitis, fatty liver disease, autoimmune hepatitis, cirrhosis and liver cancer. It is well established that gut microbiota serves as the key upstream modulator for chronic liver injury progression. Indeed, the term "gut-liver axis" was mostly applied for chronic liver injury. In the current chapter, we will summarize the relationship between gut microbiota and chronic liver injury, including the interaction between them based on latest clinic and basic research.
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Affiliation(s)
- Susan S Baker
- Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, USA. .,39 Irving Place, Buffalo, NY, 14201, USA.
| | - Robert D Baker
- Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, USA
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Gravina AG, Zagari RM, De Musis C, Romano L, Loguercio C, Romano M. Helicobacter pylori and extragastric diseases: A review. World J Gastroenterol 2018; 24:3204-3221. [PMID: 30090002 PMCID: PMC6079286 DOI: 10.3748/wjg.v24.i29.3204] [Citation(s) in RCA: 192] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 05/19/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is very common and affects approximately half of the world population. It causes gastric diseases, but some authors have reported an association of H. pylori infection with other systemic manifestations beginning in 1994. The list of potential effects of H. pylori outside the stomach includes a number of extragastric manifestations and we focused on neurological, dermatological, hematologic, ocular, cardiovascular, metabolic, allergic, and hepatobiliary diseases. This review discusses these important reported manifestations that are not related to the gastrointestinal tract.
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Affiliation(s)
- Antonietta Gerarda Gravina
- Dipartimento di “Medicina di Precisione”, UOC Epatogastroenterologia, Università della Campania “Luigi Vanvitelli”, Napoli 80131, Italy
| | - Rocco Maurizio Zagari
- Dipertimento Di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna 40138, Italy
| | - Cristiana De Musis
- Dipartimento di “Medicina di Precisione”, UOC Epatogastroenterologia, Università della Campania “Luigi Vanvitelli”, Napoli 80131, Italy
| | - Lorenzo Romano
- Dipartimento di “Medicina di Precisione”, UOC Epatogastroenterologia, Università della Campania “Luigi Vanvitelli”, Napoli 80131, Italy
| | - Carmelina Loguercio
- Dipartimento di “Medicina di Precisione”, UOC Epatogastroenterologia, Università della Campania “Luigi Vanvitelli”, Napoli 80131, Italy
| | - Marco Romano
- Dipartimento di “Medicina di Precisione”, UOC Epatogastroenterologia, Università della Campania “Luigi Vanvitelli”, Napoli 80131, Italy
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9
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Berntsen NL, Fosby B, Valestrand L, Tan C, Reims HM, Schrumpf E, Karlsen TH, Line PD, Melum E. Establishment of a surgical bile duct injection technique giving direct access to the bile ducts for studies of the murine biliary tree. Am J Physiol Gastrointest Liver Physiol 2018; 314:G349-G359. [PMID: 29212771 DOI: 10.1152/ajpgi.00124.2017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Cholangiopathies are progressive disorders with largely unknown pathoetiology and limited treatment options. We aimed to develop a novel surgical technique with direct access to the bile ducts that would complement existing mouse models of cholestasis, biliary inflammation, and fibrosis and present a new route of administration for testing of potential treatment strategies. We developed a surgical technique to access the murine biliary tree by injection of different solvents through catheterization of the gall bladder with simultaneous clamping of the common bile duct. To demonstrate the applicability of the technique, we injected either phosphate-buffered saline or dimethyl sulfoxide in concentrations of 50 or 65% and compared these groups with sham-operated mice. The surgery was optimized to achieve a mortality rate close to 0. There were no significant changes in pain, activity level, or mortality from the day of the surgery until euthanization for any groups. Injection of phosphate-buffered saline or 50% dimethyl sulfoxide was generally well-tolerated, whereas 65% dimethyl sulfoxide led to higher weight loss, an increase of serum alanine transaminase, and histological portal inflammation. There were no signs of inflammation in the gut. We have developed a bile duct injection technique that is well-tolerated, easily reproducible, and that may complement existing models of cholangiopathies. Direct access to the bile ducts without causing harm to the hepatobiliary or intestinal tissue may be valuable in future studies of normal biliary physiology and different pathophysiological mechanisms of disease and to test novel therapeutic strategies. NEW & NOTEWORTHY To evaluate tolerability of the bile duct to injection of both polar and nonpolar compounds, we established a novel biliary injection technique. This technique is well-tolerated, easily reproducible, and with direct access to the bile ducts for studies of the murine biliary tree. The bile duct injection technique may complement existing animal models and be a valuable tool in future studies of normal biliary physiology or pathophysiology and to test novel therapeutic strategies.
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Affiliation(s)
- Natalie Lie Berntsen
- Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
- Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital , Oslo , Norway
- K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo , Norway
| | - Bjarte Fosby
- Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
- Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
| | - Laura Valestrand
- Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
- Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital , Oslo , Norway
- K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo , Norway
| | - Corey Tan
- Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
| | - Henrik M Reims
- Department of Pathology, Oslo University Hospital Rikshospitalet , Oslo , Norway
| | - Elisabeth Schrumpf
- Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
- Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital , Oslo , Norway
- K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo , Norway
| | - Tom Hemming Karlsen
- Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
- Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital , Oslo , Norway
- K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo , Norway
- Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo , Norway
| | - Pål-Dag Line
- Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo , Norway
| | - Espen Melum
- Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
- Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital , Oslo , Norway
- K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo , Norway
- Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
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Castaño-Rodríguez N, Mitchell HM, Kaakoush NO. NAFLD, Helicobacter species and the intestinal microbiome. Best Pract Res Clin Gastroenterol 2017; 31:657-668. [PMID: 29566909 DOI: 10.1016/j.bpg.2017.09.008] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 09/03/2017] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. It is well-accepted that gut dysbiosis is associated with NAFLD, however, there is some conflicting evidence regarding the nature of these alterations. Infection with Helicobacter species, mainly H. pylori, has also been associated with increased NAFLD risk, however, some studies have failed to reproduce this finding. Further studies including large study samples and standardised procedures for microbiota analyses, H. pylori detection and NAFLD diagnostic criteria, are required. The mechanisms involving Helicobacter species and the intestinal microbiome in NAFLD pathogenesis appear to be part of the multiple-hit theory, in which increased intestinal permeability, inflammatory responses, altered choline, bile acids and carbohydrate metabolism, production of short-chain fatty acids, urea cycle and urea transport systems, altered maintenance of hepatic γδT-17 cells, insulin resistance, hormones secreted by the adipose tissue, metabolic hormones, bacterial metabolites and Helicobacter toxins, are all implicated.
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Affiliation(s)
| | - Hazel M Mitchell
- School of Biotechnology and Biomolecular Sciences, UNSW Sydney, Sydney, NSW, 2052, Australia
| | - Nadeem O Kaakoush
- School of Medical Sciences, UNSW Sydney, Sydney, NSW, 2052, Australia
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11
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Abstract
PURPOSE OF REVIEW The only currently approved treatment for primary sclerosing cholangitis (PSC) is liver transplantation, with a median time to transplant of 12-18 years after diagnosis. There are a number of emerging drugs that have the potential to meet this critically unmet need that will be summarized and discussed herein. RECENT FINDINGS Although the cause of PSC is unknown, there are a number of novel therapeutics under development. These drugs target presumed pathogenic mechanisms largely extrapolated from ex-vivo and in-vivo preclinical models, as well as translational observations. SUMMARY Future therapeutic strategies for PSC may include a multitude of complex pathogenic mechanisms encompassing pathways of immunomodulation, the microbiome and inflammation-related fibrosis.
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Affiliation(s)
- Angela C Cheung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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Smyk DS, Koutsoumpas AL, Mytilinaiou MG, Rigopoulou EI, Sakkas LI, Bogdanos DP. Helicobacter pylori and autoimmune disease: Cause or bystander. World J Gastroenterol 2014; 20:613-629. [PMID: 24574735 PMCID: PMC3921471 DOI: 10.3748/wjg.v20.i3.613] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 11/26/2013] [Accepted: 12/06/2013] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research.
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Sakr SA, Badrah GA, Sheir RA. Histological and histochemical alterations in liver of chronic hepatitis C patients with Helicobacter pylori infection. Biomed Pharmacother 2013; 67:367-74. [PMID: 23659901 DOI: 10.1016/j.biopha.2013.03.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2012] [Accepted: 03/03/2013] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C is an infectious disease affecting the liver. Chronic infection can progress fibrosis and cirrhosis, liver failure or liver cancer. Helicobacter pylori (H. pylori) is a spiral bacterium infects the stomach of more than 50% of the human population worldwide. H. pylori DNA has been identified in human livers and has been implicated in chronic liver disease and liver cancer. The present work was aimed to study the histological and histochemical alterations in liver of HCV patients with or without H. pylori infection. Immunohistochemical detection of H. pylori showed positive reactivity in 62 biopsies out of 100 biopsies (38% HCV patients and 62% HCV patients coinfected with H. pylori). Histological examination of liver of HCV patients showed microvesicular and macrovesicular steatosis, lymphocytic infiltrations, fibrosis and cirrhosis. Cirrhotic nodules and impairment of hepatic parenchyma were common in HCV patients coinfected with H. pylori. HCV patients coinfected with H. pylori recorded higher NIC score and pronounced fibrosis stages than HCV patients. Glycogen and total proteins decreased in hepatocytes and cirrhotic nodules in HCV patients. Such decrease was marked in liver of HCV patients coinfected with H. pylori. So it is recommended to perform a complete analysis for H. pylori in HCV patients suggesting that it will help in therapy of this disease.
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Affiliation(s)
- Saber A Sakr
- Zoology Department, Faculty of Science, Menoufia University, Menoufia, Egypt.
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14
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Liang S, Webb T, Li Z. Role of gut microbiota in liver diseases. Hepatol Res 2013; 43:139-46. [PMID: 22970713 PMCID: PMC3894231 DOI: 10.1111/j.1872-034x.2012.01088.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2012] [Revised: 07/24/2012] [Accepted: 08/15/2012] [Indexed: 12/19/2022]
Abstract
The liver constantly encounters food-derived antigens and bacterial components such as lipopolysaccharide translocated from the gut into the portal vein. Bacterial components stimulate Toll-like receptors (TLR), which are expressed on Kupffer cells, biliary epithelial cells, hepatocytes, hepatic stellate cells, endothelial cells and dendritic cells and recognize specific pathogen-associated molecular patterns. The signaling of TLR to its main ligand triggers inflammation. Usually, in order to protect against hyperactivation of the immune system and to prevent organ failure by persistent inflammation, TLR tolerance to repeated stimuli is induced. In chronic liver diseases, a breakdown in TLR tolerance occurs. Furthermore, Kupffer cells, hepatic stellate cells and natural killer T cells are key components of innate immunity. Decreased numbers and impaired ability of these cells lead to failures in immune tolerance, resulting in persistent inflammation. Recently, the activation of inflammasome was revealed to control the secretion of pro-inflammatory cytokines such as interleukin-1β in response to bacterial pathogens. Innate immunity seems to be an important contributor to the pathogenesis of fatty liver disease and autoimmune liver disease. Recently, probiotics were reported to affect various liver diseases via shifts in gut microbiota and the stability of intestinal permeability. However, many unresolved questions remain. Further analysis will be needed to gain a more comprehensive understanding of the association of innate immunity with the pathogenesis of various liver diseases.
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Affiliation(s)
- Shuwen Liang
- Department of Medicine, Johns Hopkins University, Baltimore, MD 21205
| | - Tonya Webb
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201
| | - Zhiping Li
- Department of Medicine, Johns Hopkins University, Baltimore, MD 21205
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15
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Abstract
Cholestasis develops either from a defect in bile synthesis, impairment in bile secretion, or obstruction to bile flow, and is characterized by an elevated serum alkaline phosphatase and gamma-glutamyltransferase disproportionate to elevation of aminotransferase enzymes. Key elements to the diagnostic workup include visualization of the biliary tree by cholangiography and evaluation of liver histology. The hope is that recent advances in understanding the genetic factors and immune mechanisms involved in the pathogenesis of cholestasis will lead to newer therapeutic interventions in the treatment of these diseases.
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Affiliation(s)
- Asma Siddique
- Department of Gastroenterology, Center for Liver Disease, Digestive Disease Institute, Seattle, WA 98111, USA
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16
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease characterized by the destruction of medium- to large-sized bile ducts and intense concentric fibrosis. Complications from PSC include bacterial cholangitis, cirrhosis, and cholangiocarcinoma and a therapy that might alter the natural history of the disease remains lacking. Our understanding of the pathogenesis of PSC also remains rudimentary but the strong association between PSC and inflammatory bowel disease suggest causal links between the diseases. The male predominance in PSC, lack of a defined, pathogenic auto-antigen, and the potential role of the innate immune system suggest that PSC may be due to dysregulation of immunity rather than a classic autoimmune disease. However, PSC shares several genetic susceptibility loci with other autoimmune diseases including the human leukocyte antigen DRB01*03 haplotype. The precise immune response of PSC is largely unknown but likely involves activation of the innate immune system by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis. Progress in our basic understanding of PSC is desperately needed in order to rationally design new therapeutic approaches to this disease.
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Affiliation(s)
- Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis Medical Center, Sacramento, USA.
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17
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that is associated with considerable morbidity and mortality. The disease etiopathogenesis has not been well defined. Several observations suggest that portal bacteremia or chronic bile duct infection may be factors that could play a role in the pathogenesis of the disease. Clinical trials have tested different treatments for PSC but without convincing evidence of benefit. Liver transplantation is the only available therapeutic option that is thought to be beneficial for PSC. Antibiotics have been used in several case series over the years to treat PSC and have had, in some cases, impressive benefits when compared with other drugs used for treating the disease. We gathered the available data for different antibiotics used in PSC in this review. Further studies are needed to support the efficacy of using antibiotics for PSC patients.
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Affiliation(s)
- Diaa Aldin H Elfaki
- Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, MN 55901, USA
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18
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Fosby B, Karlsen TH, Melum E. Recurrence and rejection in liver transplantation for primary sclerosing cholangitis. World J Gastroenterol 2012; 18:1-15. [PMID: 22228965 PMCID: PMC3251800 DOI: 10.3748/wjg.v18.i1.1] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2011] [Revised: 06/15/2011] [Accepted: 06/22/2011] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to fibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can influence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible influence of rejection on the risk of recurrent disease in the allograft.
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Hirschfield GM, Heathcote EJ, Gershwin ME. Pathogenesis of cholestatic liver disease and therapeutic approaches. Gastroenterology 2010; 139:1481-96. [PMID: 20849855 DOI: 10.1053/j.gastro.2010.09.004] [Citation(s) in RCA: 208] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2010] [Revised: 09/01/2010] [Accepted: 09/07/2010] [Indexed: 12/11/2022]
Abstract
Cholestatic liver disorders are caused by genetic defects, mechanical aberrations, toxins, or dysregulations in the immune system that damage the bile ducts and cause accumulation of bile and liver tissue damage. They have common clinical manifestations and pathogenic features that include the responses of cholangiocytes and hepatocytes to injury. We review the features of bile acid transport, tissue repair and regulation, apoptosis, vascular supply, immune regulation, and cholangiocytes that are associated with cholestatic liver disorders. We now have a greater understanding of the physiology of cholangiocytes at the cellular and molecular levels, as well as genetic factors, repair pathways, and autoimmunity mechanisms involved in the pathogenesis of disease. These discoveries will hopefully lead to new therapeutic approaches for patients with cholestatic liver disease.
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20
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Ma YJ, Duan GC, Zhang RG, Fan QT, Zhang WD. Mutation of iceA in Helicobacter pylori compromised IL-8 induction from human gastric epithelial cells. J Basic Microbiol 2010; 50 Suppl 1:S83-8. [DOI: 10.1002/jobm.200900410] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2009] [Accepted: 04/19/2010] [Indexed: 01/30/2023]
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21
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Knight C, Murray KF. Hepatobiliary associations with inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2009; 3:681-91. [PMID: 19929587 DOI: 10.1586/egh.09.53] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatobiliary disease is not uncommon in patients with inflammatory bowel disease (IBD). The most common autoimmune hepatic associations are primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). The immunosuppressant medications used in the treatment of IBD also have potential hepatotoxicity. PSC is most commonly associated with IBD, specifically ulcerative colitis. AIH, a more classic autoimmune disease diagnosed commonly in isolation of other conditions in the same individual, is less commonly associated with IBD. Additionally, a subgroup of patients have features of both PSC and AIH, termed overlap syndrome, that is also sometimes seen in IBD patients. This review will discuss the most common liver disease associations seen in patients with IBD: PSC, AIH and overlap syndrome. Additionally, the most common drug-related hepatotoxicities encountered when treating IBD will be reviewed.
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Affiliation(s)
- Crystal Knight
- Seattle Children's and University of Washington School of Medicine, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, 4800 Sand Point Way, NE, PO Box 5371/W-7830, Seattle, WA 98105, USA.
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22
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Detection of Helicobacter pylori in paraffin-embedded specimens from patients with chronic liver diseases, using the amplification method. Dig Dis Sci 2009; 54:1456-9. [PMID: 18975076 DOI: 10.1007/s10620-008-0522-5] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2008] [Accepted: 08/28/2008] [Indexed: 12/12/2022]
Abstract
Helicobacter DNA has been detected in the liver specimens of patients with various hepato-biliary diseases. The aim of this study was to investigate the presence of H. pylori DNA in the liver tissue of Iranian patients with chronic liver diseases (CLD). Genomic DNA was extracted from the paraffin sections of 46 liver biopsies of patients with CLD and 13 from patients with metastatic adenocarcinoma as a control group. Polymerase chain reaction (PCR) analysis was carried out using primers for H. pylori 16S rRNA and cagA genes. On analysis, 17 of the 46 patient samples were positive in H. pylori 16S rRNA PCR and 2 of the 13 were positive from the control group. None of the samples were positive for the cagA gene. This study showed the greater presence of H. pylori-like DNA in the liver samples from patients with CLD than in controls.
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23
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Aron JH, Bowlus CL. The immunobiology of primary sclerosing cholangitis. Semin Immunopathol 2009; 31:383-97. [PMID: 19468733 PMCID: PMC2758173 DOI: 10.1007/s00281-009-0154-7] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2009] [Accepted: 05/06/2009] [Indexed: 12/15/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease histologically characterized by the presence of intrahepatic and/or extrahepatic biliary duct concentric, obliterative fibrosis, eventually leading to cirrhosis. Approximately 75% of patients with PSC have inflammatory bowel disease. The male predominance of PSC, the lack of a defined, pathogenic autoantigen, and the potential role of the innate immune system suggest that it may be due to dysregulation of immunity rather than a classic autoimmune disease. However, PSC is associated with several classic autoimmune diseases, and the strongest genetic link to PSC identified to date is with the human leukocyte antigen DRB01*03 haplotype. The precise immunopathogenesis of PSC is largely unknown but likely involves activation of the innate immune system by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis. Currently, there is no effective therapy for PSC and developing a rational therapeutic strategy demands a better understanding of the disease.
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Affiliation(s)
- Jonathan H Aron
- Department of Internal Medicine, University of California Davis Medical Center, 4150 V Street, PSSB 3100, Sacramento, CA 95817, USA
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24
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Terjung B, Spengler U. Atypical p-ANCA in PSC and AIH: a hint toward a "leaky gut"? Clin Rev Allergy Immunol 2009; 36:40-51. [PMID: 18626795 DOI: 10.1007/s12016-008-8088-8] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) are enigmatic chronic inflammatory diseases of the liver, which are frequently associated with chronic inflammatory bowel diseases. Both types of liver disease share various distinct autoantibodies such as atypical perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), and thus are considered autoimmune disorders with atypical features. The discovery that atypical p-ANCA recognize both tubulin beta isoform 5 in human neutrophils and the bacterial cell division protein FtsZ has renewed the discussion on the potential role of microorganisms in the pathogenesis of both diseases. In this paper, we review the evidence for microbial infection in PSC and AIH and discuss new concepts how cross-recognition between microbial antigens in the gut and host components by the immune system along with stimulation of pattern recognition receptors might give rise to chronic hepatic inflammatory disorders with features of autoimmunity.
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Affiliation(s)
- Birgit Terjung
- Department of Internal Medicine, University of Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany.
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25
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Abstract
Infections account for significant GI morbidity and mortality worldwide. New organisms are being identified, associated with diarrhoeal illness and some with other gastrointestinal illness as well. Among GI viruses, Sapovirus is now recognised to cause diarrhoea, especially in children. A hypervirulent strain of Clostridium difficile has caused epidemics in many countries. Newly identified bacterial species that may cause diarrhoea include Campylobacter concisus, Arcobacteria, Edwardsiella tarda, Aeromonas, Plesiomonas and Laribacter. Helicobacteria are reviewed, as well as the role of gastric acid suppression in predisposing to enteric infections.
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Affiliation(s)
- Christine Schlenker
- Division of Gastroenterology, Department of Medicine, University of Washington, School of Medicine, Seattle, WA 98104, USA
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26
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Moyaert H, Franceschi F, Roccarina D, Ducatelle R, Haesebrouck F, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection: other Helicobacters. Helicobacter 2008; 13 Suppl 1:47-57. [PMID: 18783522 DOI: 10.1111/j.1523-5378.2008.00634.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The finding that Helicobacter pylori is the main cause of gastritis and peptic ulcer disease has opened a new era in the gastrointestinal world. Today there is evidence that H. pylori may also play a role in different nongastric diseases, opening the new "extragastric manifestations of H. pylori infection" field. Concerning this, several studies have been published in the last year. The most convincing data arise from those investigating idiopathic thrombocytopenic purpura and sideropenic anemia, while there is also an increasing evidence for a possible association with atherosclerotic disease. Furthermore, the discovery of a number of other novel Helicobacter species has stimulated the research in different extragastric diseases, in which an infectious hypothesis is plausible. In particular, several species have been studied for a potential role in different liver and intestinal diseases with interesting findings.
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Affiliation(s)
- Hilde Moyaert
- Department of Pathology, Bacteriology, and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
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27
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Hirano K, Tada M, Isayama H, Yashima Y, Yagioka H, Sasaki T, Kogure H, Togawa O, Arizumi T, Matsubara S, Nakai Y, Sasahira N, Tsujino T, Kawabe T, Omata M. Clinical features of primary sclerosing cholangitis with onset age above 50 years. J Gastroenterol 2008; 43:729-733. [PMID: 18807135 DOI: 10.1007/s00535-008-2216-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2008] [Accepted: 05/09/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND Although there are two peaks in the age distribution of primary sclerosing cholangitis (PSC) in Japan, the clinical differences between the patients with an older or younger onset age have not been reported. METHODS We compared clinical features of 18 patients with onset age less than 50 years (younger group) and ten PSC patients with onset age above 50 years (older group). RESULTS An association with ulcerative colitis (UC) was recognized in six patients in the younger group and in one in the older group. High serum IgE (>170 IU/ml) was observed more frequently in the older than in the younger group (1/10 vs. 7/8, P = 0.0029). Mean serum IgM tended to be higher in the younger group (198 vs. 119 mg/dl, P = 0.083). More patients received liver transplantation or continuous bile drainage, or developed liver failure or cholangiocellular carcinoma in the younger than in the older group (11/18 vs. 1/10, P = 0.016). CONCLUSIONS Older PSC patients have higher IgE, possibly less association with UC, lower IgM, and a better prognosis. The pathogenesis of PSC may be different between older and younger patients.
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Affiliation(s)
- Kenji Hirano
- Department of Gastroenterology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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28
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The challenges in primary sclerosing cholangitis--aetiopathogenesis, autoimmunity, management and malignancy. J Hepatol 2008; 48 Suppl 1:S38-57. [PMID: 18304683 DOI: 10.1016/j.jhep.2008.01.020] [Citation(s) in RCA: 118] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, characterized by progressive inflammation and fibrosis of the bile ducts, resulting in biliary cirrhosis and is associated with a high risk of cholangiocarcinoma. The majority of patients are young, male and have coexisting inflammatory bowel disease. PSC is found with a prevalence of 10/100,000 in Northern European populations. The pathophysiology of PSC is a complex multistep process including immunological mechanisms, immunogenetic susceptibility and disorders of the biliary epithelia. The diagnosis is primarily based on endoscopic cholangiography although magnetic resonance imaging is increasingly used; biochemistry and immunoserology as well as histology play only a minor role. Due to the high risk of developing cholangiocarcinoma and also other tumours of the GI tract, surveillance strategies are essential, however they have yet to be established and evaluated. Biochemical parameters, clinical risk factors, endoscopic procedures and imaging techniques contribute to the early identification of patients at risk. Since medical therapy of PSC with ursodeoxycholic acid does not improve survival, to date, liver transplantation is the only option with a cure potential; if transplantation is accurately timed, transplanted PSC patients have an excellent rate of survival. However if cholangiocarcinoma is detected, a curative treatment is not possible in the majority of cases. The present review critically summarizes the current knowledge on the aetiopathogenesis of PSC and gives an overview of the diagnostic approaches, surveillance strategies and therapeutic options. Primary sclerosing cholangitis is a disease of unknown aetiology and without any further curative treatment options apart from liver transplantation. Therefore it may be regarded as the greatest challenge in hepatology today.
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Abstract
PURPOSE OF REVIEW Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by strictures of the biliary tree complicated by cirrhosis and cholangiocarcinoma. It is immune mediated, although the precise aetiology remains unknown. RECENT FINDINGS The research into aetiology, genetic associations, pathogenesis, epidemiology, diagnosis of cholangiocarcinoma and medical treatments are discussed. SUMMARY Multiple gene polymorphisms and human leucocyte antigen haplotype associations with primary sclerosing cholangitis have been investigated. Common inflammatory bowel disease associated polymorphisms and ulcerative colitis associated human leucocyte antigen haplotypes are not associated with primary sclerosing cholangitis. Biliary epithelial cells may mediate their own destruction by exaggerating innate and adaptive immune responses to bacterial products in the liver. The natural history of large and small duct primary sclerosing cholangitis has been reviewed. Positron emission tomography may be a useful adjunct to current imaging modalities in the pretransplant assessment of patients to exclude cholangiocarcinoma. Ursodeoxycholic acid remains the most studied medical treatment for primary sclerosing cholangitis; pilot studies suggest a possible role for tacrolimus and silymarin, however further studies are required.
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30
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Bohr URM, Annibale B, Franceschi F, Roccarina D, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection -- other Helicobacters. Helicobacter 2007; 12 Suppl 1:45-53. [PMID: 17727460 DOI: 10.1111/j.1523-5378.2007.00533.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Today there is evidence that Helicobacter pylori has a critical role in different extragastric diseases. The discovery of a number of other novel Helicobacter species has stimulated the research in different extragastric diseases, in which an infectious hypothesis is plausible. Enterohepatic Helicobacter species have been hypothesized to play a role in different disorders, including hepatocellular carcinoma, gallstones formation and cholangiocellular carcinoma, as well as enteric diseases and inflammatory bowel diseases. Concerning the extragastric manifestations of H. pylori infection, idiopathic thrombocytopenic purpura, and sideropenic anemia represent, based on the current data, the diseases in which the pathogenic link appears to be strongest. There is also an increasing evidence for a possible association of H. pylori with cardiovascular disease.
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Affiliation(s)
- Ulrich R M Bohr
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
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