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Zhang J, Ji X, Liu S, Sun Z, Cao X, Liu B, Li Y, Zhao H. Helicobacter pylori infection promotes liver injury through an exosome-mediated mechanism. Microb Pathog 2024; 195:106898. [PMID: 39208956 DOI: 10.1016/j.micpath.2024.106898] [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: 05/02/2024] [Revised: 08/12/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
Helicobacter pylori infection has been thought to be associated with liver diseases, although the exact mechanisms remain elusive. This study identified H. pylori-induced liver inflammation and tissue damage in infected mice and examined the exosome-mediated mechanism underlying H. pylori infection's impact on liver injury. Exosomes were isolated from H. pylori-infected gastric epithelial GES-1 cells (Hp-GES-EVs), and the crucial virulence factor CagA was identified within these exosomes. Fluorescent labeling demonstrated that Hp-GES-EVs can be absorbed by liver cells. Treatment with Hp-GES-EVs enhanced the proliferation, migration, and invasion of Hep G2 and Hep 3B cells. Additionally, exposure to Hp-GES-EVs activated NF-κB and PI3K/AKT signaling pathways, which provides a reasonable explanation for the liver inflammation and neoplastic traits. Using a mouse model established via tail vein injection of Hp-GES-EVs, exosome-driven liver injury was evidenced by slight hepatocellular erosion around the central hepatic vein and elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and IL-6. Administering the exosome inhibitor GW4869 via intraperitoneal injection in mice resulted in a reduction of liver damage caused by H. pylori infection. These findings illuminate the exosome-mediated pathogenesis of H. pylori-induced liver injury and offer valuable insights into the extra-gastrointestinal manifestations of H. pylori infection.
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Affiliation(s)
| | - Xiaofei Ji
- Binzhou Medical University, Yantai, China
| | | | - Zekun Sun
- Binzhou Medical University, Yantai, China
| | | | | | - Yizheng Li
- Binzhou Medical University, Yantai, China
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Chen T, Han B, Cochran E, Chen G. Helicobacter pylori infection is associated with the development of sporadic colorectal carcinoma and colorectal adenomatous polyps. Pathol Res Pract 2024; 260:155368. [PMID: 38850877 DOI: 10.1016/j.prp.2024.155368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 05/07/2024] [Accepted: 05/23/2024] [Indexed: 06/10/2024]
Abstract
Helicobacter pylori (H. pylori) infection is a well-established carcinogen that has been extensively studied in the context of gastric diseases. Recent studies suggested a potential association between H. pylori and the risk of colorectal carcinoma (CRC). However, available data remains insufficient to definitively establish a causal relationship between H. pylori infection and the development of CRC and its precursor lesions. In our study, we reviewed all patients diagnosed with CRC in 2020 at our institution. H. pylori assessment was performed in all 92 CRC specimens by immunohistochemistry. Notably, two of the three patients detected with H. pylori infection are under the age of 50. Subsequently, we reviewed a total of 52 patients under the age of 50 diagnosed with CRC at our institution from 2015 to 2022. Among these patients, H. pylori infection was detected in 7 CRC specimens (13.46 %). All seven patients had adenocarcinoma on the left side of the colon. In exploring the link between H. pylori infection and the risk of developing CRC precursor lesions, we analyzed 242 patients who underwent colonoscopy guided polypectomy and also had stomach biopsies from 2015 to 2022. Of these patients, 21 were proved to be positive for H. pylori infection in the stomach, while the remaining 221 were negative. Among the H. pylori-positive group, 76.19 % (16 patients) exhibited adenomatous polyps, compared to 33.48 % (74 patients) in the H. pylori-negative patients (p=0.0001). However, no H. pylori was detected in any colonic adenomatous polyps. Our findings contribute additional evidence supporting the association between H. pylori infection and the development of sporadic CRC, probably a particular association with early-onset ones. Furthermore, gastric H. pylori infection appears to be linked to the higher prevalence of colonic adenomatous polyps, suggesting that individuals with gastric H. pylori infection may benefit from closer and earlier monitoring through colonoscopy.
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Affiliation(s)
- Tiane Chen
- Department of Pathology and Laboratory Medicine, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA 17033, United States
| | - Bing Han
- Department of Pathology and Laboratory Medicine, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA 17033, United States
| | - Eric Cochran
- Department of Pathology and Laboratory Medicine, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA 17033, United States
| | - Guoli Chen
- Department of Pathology and Laboratory Medicine, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA 17033, United States.
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Moreno Trigos Y, Tortajada-Girbés M, Simó-Jordá R, Hernández Pérez M, Hortelano I, García-Ferrús M, Ferrús Pérez MA. Use of Deep-Amplicon Sequencing (DAS), Real-Time PCR and In Situ Hybridization to Detect H. pylori and Other Pathogenic Helicobacter Species in Feces from Children. Diagnostics (Basel) 2024; 14:1216. [PMID: 38928632 PMCID: PMC11203337 DOI: 10.3390/diagnostics14121216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 05/30/2024] [Accepted: 06/04/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND Detecting Helicobacter pylori in fecal samples is easier and more comfortable than invasive techniques, especially in children. Thus, the objective of the present work was to detect H. pylori in feces from children by molecular methods as an alternative for diagnostic and epidemiological studies. METHODS Forty-five fecal samples were taken from pediatric patients who presented symptoms compatible with H. pylori infection. HpSA test, culture, real-time quantitative PCR (qPCR), fluorescence in situ hybridization (FISH), direct viable count associated with FISH (DVC-FISH), and Illumina-based deep-amplicon sequencing (DAS) were applied. RESULTS No H. pylori colonies were isolated from the samples. qPCR analysis detected H. pylori in the feces of 24.4% of the patients. In comparison, DVC-FISH analysis showed the presence of viable H. pylori cells in 53.3% of the samples, 37% of which carried 23S rRNA mutations that confer resistance to clarithromycin. After DAS, H. pylori-specific 16S rDNA sequences were detected in 26 samples. In addition, DNA from H. hepaticus was identified in 10 samples, and H. pullorum DNA was detected in one sample. CONCLUSION The results of this study show the presence of H. pylori, H. hepaticus, and H. pullorum in children's stools, demonstrating the coexistence of more than one Helicobacter species in the same patient. The DVC-FISH method showed the presence of viable, potentially infective H. pylori cells in a high percentage of the children's stools. These results support the idea that fecal-oral transmission is probably a common route for H. pylori and suggest possible fecal-oral transmission of other pathogenic Helicobacter species.
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Affiliation(s)
- Yolanda Moreno Trigos
- Research Institute of Water and Environmental Engineering (IIAMA), Universitat Politècnica de València, 46022 Valencia, Spain; (Y.M.T.); (I.H.)
| | - Miguel Tortajada-Girbés
- Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, 46010 Valencia, Spain;
- Department of Pediatrics, La Fe Polytechnique and University Hospital, 46026 Valencia, Spain
- Foundation for Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46020 Valencia, Spain
| | - Raquel Simó-Jordá
- Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, 46010 Valencia, Spain;
- Foundation for Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46020 Valencia, Spain
- Department of Pediatrics, University Hospital Doctor Peset, 46017 Valencia, Spain
| | - Manuel Hernández Pérez
- Biotechnology Department, Universitat Politècnica de València, 46022 Valencia, Spain; (M.H.P.); (M.A.F.P.)
| | - Irene Hortelano
- Research Institute of Water and Environmental Engineering (IIAMA), Universitat Politècnica de València, 46022 Valencia, Spain; (Y.M.T.); (I.H.)
| | - Miguel García-Ferrús
- Biotechnology Department, Universitat Politècnica de València, 46022 Valencia, Spain; (M.H.P.); (M.A.F.P.)
| | - María Antonia Ferrús Pérez
- Biotechnology Department, Universitat Politècnica de València, 46022 Valencia, Spain; (M.H.P.); (M.A.F.P.)
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Xuan M, Gu X, Liu Y, Yang L, Li Y, Huang D, Li J, Xue C. Intratumoral microorganisms in tumors of the digestive system. Cell Commun Signal 2024; 22:69. [PMID: 38273292 PMCID: PMC10811838 DOI: 10.1186/s12964-023-01425-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 12/06/2023] [Indexed: 01/27/2024] Open
Abstract
Tumors of the digestive system pose a significant threat to human health and longevity. These tumors are associated with high morbidity and mortality rates, leading to a heavy economic burden on healthcare systems. Several intratumoral microorganisms are present in digestive system tumors, and their sources and abundance display significant heterogeneity depending on the specific tumor subtype. These microbes have a complex and precise function in the neoplasm. They can facilitate tumor growth through various mechanisms, such as inducing DNA damage, influencing the antitumor immune response, and promoting the degradation of chemotherapy drugs. Therefore, these microorganisms can be targeted to inhibit tumor progression for improving overall patient prognosis. This review focuses on the current research progress on microorganisms present in the digestive system tumors and how they influence the initiation, progression, and prognosis of tumors. Furthermore, the primary sources and constituents of tumor microbiome are delineated. Finally, we summarize the application potential of intratumoral microbes in the diagnosis, treatment, and prognosis prediction of digestive system tumors. Video Abstract.
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Affiliation(s)
- Mengjuan Xuan
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China
| | - Xinyu Gu
- Department of Oncology, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471000, Henan, China
| | - Yingru Liu
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China
| | - Li Yang
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China
| | - Yi Li
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China
| | - Di Huang
- Department of Child Health Care, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Juan Li
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China.
| | - Chen Xue
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China.
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Lupu A, Miron IC, Cianga AL, Cernomaz AT, Lupu VV, Gavrilovici C, Stârcea IM, Tarca E, Ghica DC, Fotea S. The Prevalence of Liver Cytolysis in Children with Helicobacter pylori Infection. CHILDREN (BASEL, SWITZERLAND) 2022; 9:children9101498. [PMID: 36291434 PMCID: PMC9600054 DOI: 10.3390/children9101498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/22/2022] [Accepted: 09/26/2022] [Indexed: 11/06/2022]
Abstract
(1) Background: The relationship between Helicobacter pylori (H. pylori) infection and liver disease has been discussed for many years, but the association between the infection and liver cytolysis in children has been insufficiently explored. In our study, we evaluate this relationship in a pediatric population from the northeast of Romania. (2) Methods: A retrospective study of children with H. pylori infection and liver cytolysis was conducted on a group of 1757 children, admitted to a pediatric gastroenterology regional center in northeast Romania over 3 years. (3) Results: Liver cytolysis syndrome was present in 112 children of both sexes. Of the 112 children, 20 children (17.9%) also had H. pylori infection. In the statistical analysis, we noted a significant association between liver cytolysis syndrome and H. pylori infection (χ2; p < 0.001). (4) Conclusions: This relationship requires further in-depth studies that also consider certain parameters that may influence the results of these correlations. In addition, we point out the need for further analyses evaluating, in terms of the histopathological changes in each liver disease, the efficacy of H. pylori eradication.
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Affiliation(s)
- Ancuta Lupu
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Ingrith Crenguta Miron
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Anca Lavinia Cianga
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Andrei Tudor Cernomaz
- III-rd Medical Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Vasile Valeriu Lupu
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Correspondence:
| | - Cristina Gavrilovici
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | | | - Elena Tarca
- Department of Pediatric Surgery, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Dragos Catalin Ghica
- Preventive Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Silvia Fotea
- Pediatrics Department, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800008 Galati, Romania
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Basu A, Singh R, Gupta S. Bacterial infections in cancer: A bilateral relationship. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2022; 14:e1771. [PMID: 34994112 DOI: 10.1002/wnan.1771] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 10/09/2021] [Accepted: 11/12/2021] [Indexed: 12/15/2022]
Abstract
Bacteria share a long commensal relationship with the human body. New findings, however, continue to unravel many complexities associated with this old alliance. In the past decades, the dysbiosis of human microbiome has been linked to tumorigenesis, and more recently to spontaneous colonization of existing tumors. The topic, however, remains open for debate as the claims for causative-prevailing dual characteristics of bacteria are mostly based on epidemiological evidence rather than robust mechanistic models. There are also no reviews linking the collective impact of bacteria in tumor microenvironments to the efficacy of cancer drugs, mechanisms of pathogen-initiated cancer and bacterial colonization, personalized nanomedicine, nanotechnology, and antimicrobial resistance. In this review, we provide a holistic overview of the bilateral relationship between cancer and bacteria covering all these aspects. Our collated evidence from the literature does not merely categorize bacteria as cancer causative or prevailing agents, but also critically highlights the gaps in the literature where more detailed studies may be required to reach such a conclusion. Arguments are made in favor of dual drug therapies that can simultaneously co-target bacteria and cancer cells to overcome drug resistance. Also discussed are the opportunities for leveraging the natural colonization and remission power of bacteria for cancer treatment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.
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Affiliation(s)
- Abhirup Basu
- Department of Chemical Engineering, Indian Institute of Technology, Delhi, India
| | - Rohini Singh
- Department of Chemical Engineering, Indian Institute of Technology, Delhi, India
| | - Shalini Gupta
- Department of Chemical Engineering, Indian Institute of Technology, Delhi, India
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Liu B, Zhou Z, Jin Y, Lu J, Feng D, Peng R, Sun H, Mu X, Li C, Chen Y. Hepatic stellate cell activation and senescence induced by intrahepatic microbiota disturbances drive progression of liver cirrhosis toward hepatocellular carcinoma. J Immunother Cancer 2022; 10:jitc-2021-003069. [PMID: 34996812 PMCID: PMC8744134 DOI: 10.1136/jitc-2021-003069] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/04/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The significance of the relationship between the microbiota and diseases is increasingly being recognized. However, the characterization of tumor microbiome and their precise molecular mechanisms through which microbiota promotes hepatocellular carcinoma (HCC) development are still unclear. METHODS The intrahepatic microbiota was investigated from tumor, normal adjacent tissues in 46 patients with HCC and normal hepatic tissues in 33 patients with hemangioma by 16S rRNA gene sequencing. Taxonomic composition differences in patients were evaluated using Linear discriminant analysis Effect Size (LefSe) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional pathways. Associations between the most relevant taxa and clinical characteristics of HCC patients were analyzed by Spearman rank correlations. The effects of microbe on hepatic stellate cells (HSCs) activation and HCC progression were examined. RESULTS We observed intrahepatic microbiota disturbances by reduced microbial diversity in HCC. The tumor microbiota of the HCC patients with cirrhosis showed higher abundance of Stenotrophomonas maltophilia (S. maltophilia). S. maltophilia provoked senescence-associated secretory phenotype (SASP) in HSCs by activating TLR-4-mediated NF-κB signaling pathway, which in turn induced NLRP3 inflammasome complex formation and secreted various inflammatory factors in the liver, thus facilitating HCC progression in mice. Moreover, signs of SASP were also observed in the HSCs in the area of HCC with higher S. maltophilia enrichment arising in patients with cirrhosis. CONCLUSIONS Our analysis of the hepatic microbiota revealed for the first time that patients with HCC exhibited a dysbiotic microbial community with higher S. maltophilia abundance, which induced the expression SASP factors of HSCs and cirrhosis in the liver, concurring in the process of hepatocarcinogenesis.
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Affiliation(s)
- Boyuan Liu
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Zewei Zhou
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China
| | - Yu Jin
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Jinying Lu
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Dongju Feng
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China
| | - Rui Peng
- Department of General Surgery, Research Center for Clinical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China
| | - Hua Sun
- Department of Immunology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Xiaoxin Mu
- Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Changxian Li
- Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yun Chen
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China .,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of General Surgery, Research Center for Clinical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China
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Madala S, MacDougall K, Surapaneni BK, Park R, Girotra M, Kasi A. Coinfection of Helicobacter pylori and Hepatitis C Virus in the Development of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. J Clin Med Res 2021; 13:530-540. [PMID: 35059071 PMCID: PMC8734513 DOI: 10.14740/jocmr4637] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 11/29/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The relationship between Helicobacter pylori (H. pylori) and hepatocellular carcinoma (HCC) was firstly proposed in 1994 after Ward et al demonstrated the role of Helicobacter hepaticus in the development of HCC in mice. Studies also investigated the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) coexisting with H. pylori in causing HCC. A causal relationship was never confirmed, and the relationship remains controversial. This meta-analysis aimed to summarize the research on this topic and investigate if a relationship exists between H. pylori infection and the development of HCC and if the presence of HCV and HBV along with H. pylori plays a role in liver carcinogenesis. METHODS Following PRISMA guidelines, we performed a systematic review of all relevant studies published in the literature using the keywords "Helicobacter pylori" and "hepatocellular carcinoma" on major literature databases, including PubMed, EMBASE, Web of Science, and Cochrane controlled trials register. A total of 656 research studies were identified between 1994 and 2020. Of those, 26 qualified under our selection criteria. Patients who were positive for HCC were classified as cases and those who did not have HCC were classified as controls. The H. pylori status and HCV status, if available, were identified for both groups. Statistical analysis was carried out by a biostatistician according to the Cochrane reviewer's handbook. RESULTS Out of the 26 studies included in the final analysis, 13 were retrospective case-control studies, 11 were cross-sectional studies, and two were prospective case-control and cohort studies. Overall, the prevalence of H. pylori infection was 64.78% (561 of 866) amongst HCC cases and 47.92% (1,718 of 3,585) in the non-HCC control group. The summary odds ratio (OR) for the association of H. pylori infection with the risk for HCC (using the random-effects model, which accounted for the heterogeneity across the 26 studies) was determined to be 4.75 (95% confidence interval (CI): 3.06 - 7.37, I2 = 63%). We also performed a subgroup analysis to determine the odds of developing HCC in the presence of H. pylori and HCV coinfection. The summary OR of it was 12.76 (95% CI: 4.13 - 39.41, I2 = 78%). The summary OR for the risk of developing HCC in the presence of HCV infection without H. pylori infection was 2.21 (95% CI: 0.70 - 6.94, I2 = 79%). Whereas, the odds of developing HCC in the presence of only H. pylori infection without HCV was found to be 0.54 (95% CI: 0.11 - 2.63, I2 = 80%). There was inconsistency in the data presented in some studies regarding HCV infection status. Since data were extracted from different study designs, subgroup analysis by study design was performed which showed no significant difference between the study groups (P = 0.5705). CONCLUSION This meta-analysis demonstrates a positive association between H. pylori infection and the development of HCC. There is a significantly higher risk of developing HCC in the presence of HCV infection along with H. pylori. Further prospective cohort studies are needed to prove the causal relationship, especially in cases of HBV and HCV coinfection, and cirrhotic patients.
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Affiliation(s)
- Samragnyi Madala
- Department of Geriatric Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Kira MacDougall
- Division of Medical Oncology, University of Oklahoma, Norman, OK, USA
| | | | - Robin Park
- Department of Internal Medicine, MetroWest Medical Center, Framingham, MA, USA
| | - Mohit Girotra
- Division of Gastroenterology and Therapeutic Endoscopy, Swedish Medical Center, Seattle, WA, USA
| | - Anup Kasi
- Division of Medical Oncology, University of Kansas Medical Center, Westwood, KS, USA
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Varon C, Azzi-Martin L, Khalid S, Seeneevassen L, Ménard A, Spuul P. Helicobacters and cancer, not only gastric cancer? Semin Cancer Biol 2021; 86:1138-1154. [PMID: 34425210 DOI: 10.1016/j.semcancer.2021.08.007] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 08/11/2021] [Accepted: 08/16/2021] [Indexed: 12/11/2022]
Abstract
The Helicobacter genus actually comprises 46 validly published species divided into two main clades: gastric and enterohepatic Helicobacters. These bacteria colonize alternative sites of the digestive system in animals and humans, and contribute to inflammation and cancers. In humans, Helicobacter infection is mainly related to H. pylori, a gastric pathogen infecting more than half of the world's population, leading to chronic inflammation of the gastric mucosa that can evolve into two types of gastric cancers: gastric adenocarcinomas and gastric MALT lymphoma. In addition, H. pylori but also non-H. pylori Helicobacter infection has been associated with many extra-gastric malignancies. This review focuses on H. pylori and its role in gastric cancers and extra-gastric diseases, as well as malignancies induced by non-H. pylori Helicobacters. Their different virulence factors and their involvement in carcinogenesis is discussed. This review highlights the importance of both gastric and enterohepatic Helicobacters in gastrointestinal and liver cancers.
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Affiliation(s)
- Christine Varon
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France
| | - Lamia Azzi-Martin
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France; Univ. Bordeaux, UFR des Sciences Médicales, Bordeaux, France
| | - Sadia Khalid
- Tallinn University of Technology, Department of Chemistry and Biotechnology, Akadeemia RD 15, 12618, Tallinn, Estonia
| | - Lornella Seeneevassen
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France
| | - Armelle Ménard
- Univ. Bordeaux, INSERM, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, Bordeaux, France
| | - Pirjo Spuul
- Tallinn University of Technology, Department of Chemistry and Biotechnology, Akadeemia RD 15, 12618, Tallinn, Estonia.
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Mirzaei R, Afaghi A, Babakhani S, Sohrabi MR, Hosseini-Fard SR, Babolhavaeji K, Khani Ali Akbari S, Yousefimashouf R, Karampoor S. Role of microbiota-derived short-chain fatty acids in cancer development and prevention. Biomed Pharmacother 2021; 139:111619. [PMID: 33906079 DOI: 10.1016/j.biopha.2021.111619] [Citation(s) in RCA: 185] [Impact Index Per Article: 46.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 04/01/2021] [Accepted: 04/12/2021] [Indexed: 02/07/2023] Open
Abstract
Following cancer, cells in a particular tissue can no longer respond to the factors involved in controlling cell survival, differentiation, proliferation, and death. In recent years, it has been indicated that alterations in the gut microbiota components, intestinal epithelium, and host immune system are associated with cancer incidence. Also, it has been demonstrated that the short-chain fatty acids (SCFAs) generated by gut microbiota are vitally crucial in cell homeostasis as they contribute to the modulation of histone deacetylases (HDACs), resulting effected cell attachment, immune cell immigration, cytokine production, chemotaxis, and the programmed cell death. Therefore, the manipulation of SCFA levels in the intestinal tract by alterations in the microbiota structure can be potentially taken into consideration for cancer treatment/prevention. In the current study, we will explain the most recent findings on the detrimental or protective roles of SFCA (particularly butyrate, propionate, and acetate) in several cancers, including bladder, colon, breast, stomach, liver, lung, pancreas, and prostate cancers.
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Affiliation(s)
- Rasoul Mirzaei
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
| | - Azam Afaghi
- Department of Biology, Sofian Branch, Islamic Azad University, Sofian, Iran
| | - Sajad Babakhani
- Department of Microbiology, North Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Masoud Reza Sohrabi
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Seyed Reza Hosseini-Fard
- Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Kiandokht Babolhavaeji
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Shabnam Khani Ali Akbari
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Rasoul Yousefimashouf
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Sajad Karampoor
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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Doulberis M, Papaefthymiou A, Srivastava DS, Exadaktylos AK, Katsinelos P, Kountouras J, Polyzos SA. Update on the association between non-alcoholic fatty liver disease and Helicobacter pylori infection. Int J Clin Pract 2021; 75:e13737. [PMID: 32991019 DOI: 10.1111/ijcp.13737] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Michael Doulberis
- Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, Aarau, Switzerland
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
- First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
- Emergency Department, University Hospital Inselspital, Bern, Switzerland
| | - Apostolis Papaefthymiou
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
- First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
- Department of Gastroenterology, University Hospital of Larisa, Larisa, Greece
| | - David S Srivastava
- Emergency Department, University Hospital Inselspital, Bern, Switzerland
| | | | - Panagiotis Katsinelos
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Jannis Kountouras
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Stergios A Polyzos
- Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
- First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
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12
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Lin HC, Hsu HY, Lin HL, Uang YS, Ho Y, Wang LH. Association Between Acid-Suppressive Agents’ Use and Risk of Hepatocellular Carcinoma. Dose Response 2020; 18:1559325820907530. [PMID: 35185412 PMCID: PMC8851131 DOI: 10.1177/1559325820907530] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 01/01/2020] [Accepted: 01/16/2020] [Indexed: 01/02/2023] Open
Abstract
Background: Acid-suppressive agents (ASAs), which are mostly used in patients with upper gastrointestinal diseases (UGIDs), may influence the risk of hepatocellular carcinoma (HCC). Methods: A population-based retrospective cohort study was conducted. Patients with UGID who used ASAs and those who did not receive ASAs were identified. Patients without UGIDs were randomly selected and matched (comparison group). All groups were followed up for 6 years. A Cox proportional hazard model was used to estimate the risk of HCC among the different groups. Results: Patients with UGID who used ASAs had a significantly elevated HCC risk (adjusted hazard ratio [HR] 1.53; 95% confidence interval [CI], 1.32-1.76] compared to those who did not use ASAs. Patients with UGID who used more than 540 defined daily doses of ASAs had a significantly higher risk of HCC (adjusted HR 2.04; 95% CI, 1.62-2.58). Moreover, the dose effect on HCC risk exhibited a significant increasing trend ( P < .01). Furthermore, patients with UGID who did not use ASAs had a significantly elevated HCC risk (adjusted HR 1.94; 95% CI, 1.59-2.36) compared to the comparison group. Conclusion: The use of ASAs increased the risk of HCC in patients with UGIDs, and the effect of ASAs was dose dependent. In addition, UGIDs alone increased the risk of HCC.
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Affiliation(s)
- Hsiu C. Lin
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei
- Department of Clinical Pathology, Taipei Medical University Hospital, Taipei
| | - Huan Y. Hsu
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei
| | - Hsiu L. Lin
- Department of Neurology, General Cathay Hospital, Sijhih Branch, New Taipei City
| | - Yow S. Uang
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei
| | - Yi Ho
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei
| | - Li H. Wang
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei
- Department of Pharmacy, Taipei Medical University Hospital, Taipei
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13
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Abdel-Razik A, Mousa N, Elhelaly R, Elzehery R, Hasan AS, Abdelsalam M, Seif AS, Tawfik AM, El-Wakeel N, Eldars W. Helicobacter pylori as an Initiating Factor of Complications in Patients With Cirrhosis: A Single-Center Observational Study. Front Med (Lausanne) 2020; 7:96. [PMID: 32266280 PMCID: PMC7105722 DOI: 10.3389/fmed.2020.00096] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 03/04/2020] [Indexed: 12/11/2022] Open
Abstract
Background and Aim: The relationship between liver cirrhosis and Helicobacter pylori (H. pylori) is a debatable matter. The aim of this study is to evaluate the possible association between H. pylori infection and liver cirrhosis. Methods: A single-center prospective cohort pilot study of 558 patients with cirrhosis was followed up for 1 year. Serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), vascular endothelial growth factor (VEGF) levels and Fecal H. pylori antigen were evaluated by enzyme-linked immunosorbent assay (ELISA). All patients with positive H. pylori were treated and then followed up for 3 months. Participants with eradicated H. pylori were followed up for one further year. Results: H. pylori-positive patients (48.4%) were associated with increased levels of serum CRP, TNF-α, IL-6, NO, and VEGF, as well as increased incidence of varices, portal hypertensive gastropathy, gastric antral vascular ectasia, hepatocellular carcinoma (HCC), spontaneous bacterial peritonitis, hepatic encephalopathy, portal vein thrombosis (PVT), and hepatorenal syndrome (all P < 0.05). Multivariate analysis models revealed that the presence of H. pylori was an independent risk variable for the development of portal vein thrombosis and hepatocellular carcinoma (P = 0.043, P = 0.037) respectively. After treatment of H. pylori infection, there was a significant reduction in all measured biochemical parameters and reported cirrhotic complications (all P < 0.05). Conclusion: Incidence of PVT and HCC development increased with H. pylori infection through increased inflammatory markers and vascular mediators. Moreover, its eradication may reduce the incidence of these complications.
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Affiliation(s)
- Ahmed Abdel-Razik
- Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Nasser Mousa
- Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Rania Elhelaly
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Rasha Elzehery
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmad S. Hasan
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mostafa Abdelsalam
- Nephrology and Dialysis Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Salah Seif
- Scientific Fellow of Tropical Medicine, Hepatology and Gastroenterology Department, Shebin Elkom Teaching Hospital, Menoufia, Egypt
| | - Ahmed M. Tawfik
- Diagnostic & Interventional Radiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Niveen El-Wakeel
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Waleed Eldars
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Medical Microbiology and Immunology Department, Faculty of Medicine, Delta University for Science and Technology, Talkha, Egypt
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14
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Xia CX, Kao YW, Qin L, Chen MC, Shia BC, Wu SY. Cancer risk in chronic rhinosinusitis: a propensity score matched case-control cohort study. Am J Transl Res 2019; 11:7146-7156. [PMID: 31814917 PMCID: PMC6895518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 11/04/2019] [Indexed: 06/10/2023]
Abstract
BACKGROUND Chronic rhinosinusitis (CRS) have infection, innate immune disorder and chronic inflammation problems which are considered as potential mechanism of tumorigenesis. To estimate cancer risk in CRS using propensity scores matching (PSM) case-control cohort study. METHODS A nationwide retrospective case-control cohort study is conducted on claim data from National Health Insurance Research Database in Taiwan. From January 2000 to December 2005, case group included 32677 CRS patients (including 544 with surgery in case 1 group and 32133 without surgery in case 2 group), and control group included 98031 subjects without CRS which were matching by PSM method on all baseline characteristics. All subjects were followed up from January 2006 till December 2013, the risk of cancers were calculated during the period. Conditional logistic regression Analysis of Cancer Risk is used to calculate the odds ratio (OR) and 95% confidence interval (CI) for case, case 1 and case 2 compared with control group. The difference in cancer risk among case, case 1 and case 2 drew the conclusions of this paper. RESULTS The risk of cancers in head and neck (adjusted OR: 1.53, 95% CI: 1.33-1.75), colon (adjusted OR: 1.23, 95% CI: 1.09-1.39), liver (adjusted OR: 1.24, 95% CI: 1.09-1.41), lung (adjusted OR: 1.14, 95% CI: 1-1.3), skin (adjusted OR: 1.37, 95% CI: 1.05-1.79), breast (adjusted OR: 1.17, 95% CI: 1.01-1.36), prostate (adjusted OR: 1.85, 95% CI: 1.54-2.22) and bladder (adjusted OR: 1.48, 95% CI: 1.17-1.48) were statistical significantly higher in CRS patients than non-CRS group. Compared with CRS patients without surgery, risk of cancers in head and neck, colon, liver, lung, skin, breast, and prostate were higher in CRS patients receiving surgery. CONCLUSION Cancer risk in CRS patients is significant high than non-CRS patients, especially in head and neck, breast, lung, bladder, colorectal, liver, prostate, and skin cancers. Surgical interventions in CRS patients could not decrease cancer risk in CRS patients.
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Affiliation(s)
- Chuan-Xin Xia
- Guanghua School of Management, Peking UniversityBeijing, China
| | - Yi-Wei Kao
- Graduate Institute of Business Administration, Fu Jen Catholic UniversityTaipei, Taiwan
- Research Center of Big Data, College of Management, Taipei Medical UniversityTaipei, Taiwan
| | - Lei Qin
- School of Statistics, University of International Business and EconomicsBeijing, China
| | - Ming-Chih Chen
- Graduate Institute of Business Administration, Fu Jen Catholic UniversityTaipei, Taiwan
| | - Ben-Chang Shia
- Research Center of Big Data, College of Management, Taipei Medical UniversityTaipei, Taiwan
- Executive Master Program of Business Administration in Biotechnology, College of Management, Taipei Medical UniversityTaipei, Taiwan
- College of Management, Taipei Medical UniversityTaipei, Taiwan
| | - Szu-Yuan Wu
- Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia UniversityTaichung, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia UniversityTaichung, Taiwan
- Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai HospitalYilan, Taiwan
- Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai HospitalYilan, Taiwan
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical UniversityTaipei, Taiwan
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15
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Bhattacharjee S, Mejías-Luque R, Loffredo-Verde E, Toska A, Flossdorf M, Gerhard M, Prazeres da Costa C. Concomitant Infection of S. mansoni and H. pylori Promotes Promiscuity of Antigen-Experienced Cells and Primes the Liver for a Lower Fibrotic Response. Cell Rep 2019; 28:231-244.e5. [DOI: 10.1016/j.celrep.2019.05.108] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 01/29/2019] [Accepted: 05/29/2019] [Indexed: 12/12/2022] Open
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Panebianco C, Potenza A, Andriulli A, Pazienza V. Exploring the microbiota to better understand gastrointestinal cancers physiology. Clin Chem Lab Med 2019; 56:1400-1412. [PMID: 29630505 DOI: 10.1515/cclm-2017-1163] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 02/26/2018] [Indexed: 02/07/2023]
Abstract
Gastrointestinal cancers account for around 40% of cancer-related deaths worldwide, representing a global health burden. There is a growing body of evidence highlighting the link between microbiota and gastrointestinal tumorigenesis and/or resistance to therapy. In the present manuscript, we reviewed the published studies on the relationship between the microbiota and the different gastrointestinal tumors, namely, gastric, colorectal and esophageal, including also the cancer of accessory organs such as liver and pancreas. There is an emergent interest in the manipulation of gastrointestinal microflora in order to understand the gastrointestinal tumorigenesis' processes and the establishment of chemoresistance mechanisms.
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Affiliation(s)
- Concetta Panebianco
- Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy
| | - Adele Potenza
- Dietetic and Clinical Nutrition Unit IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy
| | - Angelo Andriulli
- Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy
| | - Valerio Pazienza
- Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, Viale dei Cappuccini, 1, 71013 San Giovanni Rotondo (FG), Italy, Phone: +39-0882.416281, Fax: +39-0882.410271
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17
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Takemura LS, Marcasso RA, Lorenzetti E, Alfieri AA, Bracarense APL. Helicobacter infection in the hepatobiliary system and hepatic lesions: a possible association in dogs. Braz J Microbiol 2018; 50:297-305. [PMID: 30637645 DOI: 10.1007/s42770-018-0003-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Accepted: 07/11/2018] [Indexed: 12/25/2022] Open
Abstract
Helicobacter infection has been associated with hepatobiliary diseases in humans and animals. The aims of this study were to identify Helicobacter species in the hepatobiliary tract of dogs and to elucidate the possible association of these bacteria in liver diseases. Twenty-seven gastric and hepatobiliary samples were collected from 33 dogs with hepatic lesions and 17 dogs with no liver histological changes. Warthin-Starry staining, immunohistochemical assay, and PCR were performed to detect the presence of Helicobacter. Helicobacter genus was detected in 21.2% of the samples with hepatic lesions. The main lesion was chronic hepatitis. Immunohistochemistry revealed infection in liver (1/5) and gallbladder (1/3) 32 samples. The sequence analysis of seven amplicons of the 16S rRNA gene of Helicobacter genus from hepatobiliary samples showed 97.8 to 100% of nucleotide identity with gastric helicobacter. One amplicon of the ureA and ureB gene of Helicobacter genus from the stomach showed 89.1 to 90.7% nucleotide identity with H. heilmannii. The presence of Helicobacter genus in liver samples showing hepatic lesions suggests the involvement of these bacteria in the etiology of hepatobiliary disease in dogs. DNA sequences were similar to gastric Helicobacter species, reinforcing the hypothesis of bacterial translocation from the stomach to liver by the biliary pathway.
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Affiliation(s)
- L S Takemura
- Laboratory of Animal Pathology, School of Veterinary Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, Km 380, Londrina, Parana, 86057-970, Brazil
| | - R A Marcasso
- Laboratory of Animal Pathology, School of Veterinary Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, Km 380, Londrina, Parana, 86057-970, Brazil
| | - E Lorenzetti
- Laboratory of Animal Virology, School of Veterinary Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, Km 380, Londrina, Parana, 86057-970, Brazil
| | - A A Alfieri
- Laboratory of Animal Virology, School of Veterinary Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, Km 380, Londrina, Parana, 86057-970, Brazil
| | - A P L Bracarense
- Laboratory of Animal Pathology, School of Veterinary Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, Km 380, Londrina, Parana, 86057-970, Brazil.
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18
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Helicobacter pylori Infection as a Risk Factor for Hepatocellular Carcinoma: A Case-Control Study in Ethiopia. Int J Hepatol 2018; 2018:1941728. [PMID: 30631602 PMCID: PMC6304578 DOI: 10.1155/2018/1941728] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 11/14/2018] [Indexed: 12/31/2022] Open
Abstract
Background and Aims. Hepatocellular carcinoma is a major cause of cancer death worldwide, accounting for over half a million deaths per year. Its incidence varies with geographic locations and the type of etiologic factors. In Ethiopia, unidentified causes of liver disease are of sizeable proportion. Recent studies have shown an association of H. pylori infection with different spectrums of chronic liver disease. This study was conducted at St. Paul's Hospital Millennium Medical College in Ethiopia and assesses liver cancer and the association with H. pylori infection. Method. A prospective case-control study conducted on patients with chronic liver disease presenting with a suspicious liver lesion and diagnosed to have HCC in the Gastrointestinal (GI) Clinic of St. Paul's Hospital MMC from Dec 30, 2016, to Nov 1, 2017 G.C. Descriptive surveys on clinical history and physical examination and laboratory profiles were obtained, and the clinical course of the patients including the type of treatment was followed prospectively. Control cases were taken from adult patients without evidence of liver disease in the internal medicine clinic coming for routine evaluation. After collection data were analyzed using SPSS version 23 and associations were assessed using chi-square test. Binary logistic regression was used to assess the association of HCC with different variables and H. pylori infection. All variables with p-value <0.05 were considered as statistically significant. Results. One hundred twenty patients were analyzed with equal representation of cases and controls. The majority of patients with HCC were male with a mean age of 36 years. Older age adjusted Odds Ratio (AOR) (95%CI, p-value) 1.07(1.03-1.09, <0.001), viral hepatitis B (AOR) (95%CI, p-value) 6.19 (1.92-19.93, 0.002), and H. pylori infection (AOR) (95%CI, p-value) 5.22 (2.04-13.31, <0.001) were statistically significantly associated with HCC. Conclusion. H. pylori infection is associated with HCC in this case-control study. This study supports the emerging evidence of H. pylori association with other extra-gastric manifestations.
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19
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Okushin K, Tsutsumi T, Ikeuchi K, Kado A, Enooku K, Fujinaga H, Moriya K, Yotsuyanagi H, Koike K. Helicobacter pylori infection and liver diseases: Epidemiology and insights into pathogenesis. World J Gastroenterol 2018; 24:3617-3625. [PMID: 30166857 PMCID: PMC6113725 DOI: 10.3748/wjg.v24.i32.3617] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 05/30/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Both Helicobacter pylori (H. pylori) infection and liver diseases, including nonalcoholic fatty liver disease (NAFLD), viral hepatitis, and hepatocellular carcinoma (HCC), have high prevalences worldwide, and the relationship between H. pylori infection and liver disease has been discussed for many years. Although positive correlations between H. pylori and NAFLD have been identified in some clinical and experimental studies, negative correlations have also been obtained in high-quality clinical studies. Associations between H. pylori and the pathogenesis of chronic viral hepatitis, mainly disease progression with fibrosis, have also been suggested in some clinical studies. Concerning HCC, a possible role for H. pylori in hepatocarcinogenesis has been identified since H. pylori genes have frequently been detected in resected HCC specimens. However, no study has revealed the direct involvement of H. pylori in promoting the development of HCC. Although findings regarding the correlations between H. pylori and liver disease pathogenesis have been accumulating, the existing data do not completely lead to an unequivocal conclusion. Further high-quality clinical and experimental analyses are necessary to evaluate the efficacy of H. pylori eradication in ameliorating the histopathological changes observed in each liver disease.
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Affiliation(s)
- Kazuya Okushin
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Takeya Tsutsumi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Kazuhiko Ikeuchi
- Department of Infectious Diseases, The University of Tokyo, Tokyo 113-8655, Japan
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Akira Kado
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Hidetaka Fujinaga
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Kyoji Moriya
- Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
- Department of Infectious Diseases, The University of Tokyo, Tokyo 113-8655, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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20
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Caviglia GP, Olivero A, Rosso C, Bosco C, Ribaldone DG, Fagoonee S. Laboratory evidence of Helicobacter species infection in hepatocellular carcinoma. MINERVA BIOTECNOL 2018; 30. [DOI: 10.23736/s1120-4826.18.02428-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/10/2025]
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21
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Edwards SW, Spofford EM, Price C, Wright HL, Salao K, Suttiprapa S, Sripa B. Opisthorchiasis-Induced Cholangiocarcinoma: How Innate Immunity May Cause Cancer. ADVANCES IN PARASITOLOGY 2018; 101:149-176. [PMID: 29907253 DOI: 10.1016/bs.apar.2018.05.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Innate, inflammatory responses towards persistent Opisthorchis viverrini (OV) infection are likely to contribute to the development of cholangiocarcinoma (CCA), a liver cancer that is rare in the West but prevalent in Greater Mekong Subregion countries in Southeast Asia. Infection results in the infiltration of innate immune cells into the bile ducts and subsequent activation of inflammatory immune responses that fail to clear OV but instead may damage local tissues within the bile ducts. Not all patients infected with OV develop CCA, and so tumourigenesis may be dependent on multiple factors including the magnitude of the inflammatory response that is activated in infected individuals. The purpose of this review is to summarize how innate immune responses may promote tumourigenesis following OV infection and if such responses can be used to predict CCA onset in OV-infected individuals. It also hypothesizes on the role that Helicobacterspp., which are associated with liver fluke infections, may play in activation of the innate the immune system to promote tissue damage and persistent inflammation leading to CCA.
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Affiliation(s)
- Steven W Edwards
- Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom
| | - Edward M Spofford
- Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom
| | - Charlotte Price
- Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom
| | - Helen L Wright
- Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom
| | - Kanin Salao
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Sutas Suttiprapa
- Tropical Medicine Graduate Program, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Banchob Sripa
- Tropical Medicine Graduate Program, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
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22
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Søgaard KK, Farkas DK, Pedersen L, Lund JL, Thomsen RW, Sørensen HT. Long-term risk of gastrointestinal cancers in persons with gastric or duodenal ulcers. Cancer Med 2016; 5:1341-51. [PMID: 26923747 PMCID: PMC4924392 DOI: 10.1002/cam4.680] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Revised: 01/11/2016] [Accepted: 02/01/2016] [Indexed: 12/31/2022] Open
Abstract
Peptic ulcer predicts gastric cancer. It is controversial if peptic ulcers predict other gastrointestinal cancers, potentially related to Helicobacter pylori or shared lifestyle factors. We hypothesized that gastric and duodenal ulcers may have different impact on the risk of gastrointestinal cancers. In a nationwide cohort study using Danish medical databases 1994-2013, we quantified the risk of gastric and other gastrointestinal cancers among patients with duodenal ulcers (dominantly H. pylori-related) and gastric ulcers (dominantly lifestyle-related) compared with the general population. We started follow-up 1-year after ulcer diagnosis to avoid detection bias and calculated absolute risks of cancer and standardized incidence ratios (SIRs). We identified 54,565 patients with gastric ulcers and 38,576 patients with duodenal ulcers. Patient characteristics were similar in the two cohorts. The 1-5-year risk of any gastrointestinal cancer was slightly higher for gastric ulcers patients (2.1%) than for duodenal ulcers patients (2.0%), and SIRs were 1.38 (95% CI: 1.31-1.44) and 1.30 (95% CI: 1.23-1.37), respectively. The SIR of gastric cancer was higher among patients with gastric ulcer than duodenal ulcer (1.92 vs. 1.38), while the SIRs for other gastrointestinal cancers were similar (1.33 vs. 1.29). Compared with gastric ulcer patients, duodenal ulcer patients were at lower risk of smoking- and alcohol-related gastrointestinal cancers. The risk of nongastric gastrointestinal cancers is increased both for patients with gastric ulcers and with duodenal ulcers, but absolute risks are low. H. pylori may be less important for the development of nongastric gastrointestinal cancer than hypothesized.
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Affiliation(s)
- Kirstine K Søgaard
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Dóra K Farkas
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Lars Pedersen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Jennifer L Lund
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.,Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina
| | - Reimar W Thomsen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Henrik T Sørensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
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Wang J, Wang X, Tang N, Chen Y, She F. Impact of Helicobacter pylori on the growth of hepatic orthotopic graft tumors in mice. Int J Oncol 2015; 47:1416-28. [PMID: 26238296 DOI: 10.3892/ijo.2015.3107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 05/25/2015] [Indexed: 11/05/2022] Open
Abstract
Helicobacter pylori is a well-known causative organism of chronic gastric diseases and has been found in many hepatic carcinoma samples. To explore the expression of apoptosis-related proteins and carcinoma development in H. pylori-infected livers, we utilized BALB/cAnSlac mice to establish an H. pylori-infected model by oral inoculation and orthotopic grafts of hepatic tumors by H22 cells, respectively. We found that H. pylori colonies could not be cultured from all liver and tumor samples. However, its 16S rRNA was detectable in 85.3% of livers and 66.7% of tumors in the infected mice. Inflammatory cells were observed and thinly distributed in the lobule portions of the liver, and H. pylori mainly existed in the infected hepatic sinusoids and the necrotic areas of the infected tumors. No significant difference was found in liver to body weight ratio between the infected and uninfected. Moreover, the pathological tumor difference was unremarkable between the two. The proliferating cell nuclear antigen (PCNA) and Bcl-2-associated X protein (Bax) expression in the infected tumors was significantly higher and lower, respectively, than those of the uninfected tumors. However, no significant difference in Bcl-2 (B-cell lymphoma 2) expression existed. The results indicate that H. pylori found in the livers which were infected by H. pylori oral inoculation could contribute to the infiltration of inflammatory cells in livers. Although H. pylori has no significant impact on the liver to body weight ratio or tumor Bcl-2 expression, it may upregulate PCNA expression and downregulate Bax expression, respectively. All our findings show that H. pylori may promote proliferation and inhibit apoptosis of tumor cells.
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Affiliation(s)
- Junwei Wang
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
| | - Xiaoqian Wang
- Department of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Nanhong Tang
- Department of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Yanling Chen
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
| | - Feifei She
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
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24
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Loayza MF, Villavicencio FX, Santander SC, Baldeón M, Ponce LK, Salvador I, Vivar Díaz N. Improved method for extraction and detection of Helicobacter pylori DNA in formalin-fixed paraffin embedded gastric biopsies using laser micro-dissection. MethodsX 2014; 2:1-7. [PMID: 26150965 PMCID: PMC4487329 DOI: 10.1016/j.mex.2014.11.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 11/26/2014] [Indexed: 01/24/2023] Open
Abstract
To assess the molecular events exerted by Helicobacter pylori interacting directly with gastric epithelial cells, an improved procedure for microbial DNA isolation from stained hematoxilin-eosin gastric biopsies was developed based on laser micro-dissection (LM) [1]. Few articles have described the use of LM to select and detect H. pylori genome from formalin-fixed paraffin embedded gastric tissue [2]. To improve the yield and quality of DNA isolated from H. pylori contacting intestinal epithelial cells, the following conditions were established after modification of the QIAamp DNA Micro kit.
Use of at least 25 cut sections of 10–20 μm of diameter and 3 μm thick with more than 10 bacteria in each cut. Lysis with 30 μL of tissue lysis buffer and 20 μL of proteinase K (PK) with the tube in an upside-down position. The use of thin purification columns with 35 μL of elution buffer. The mean of DNA concentration obtained from 25 LM cut sections was 1.94± 0 .16 ng/μL, and it was efficiently amplified with qPCR in a Bio Rad iCycler instrument. The LM can improve the sample selection and DNA extraction for molecular analysis of H. pylori associated with human gastric epithelium.
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Affiliation(s)
- María Fernanda Loayza
- Universidad de las Fuerzas Armadas ESPE, P.O. Box 171-5-231B, Av. General Rumiñahui s/n, Sangolquí, Ecuador ; Hospital Carlos Andrade Marín, P.O. Box 170411, Av. 18 de Septiembre s/n y Ayacucho, Quito, Ecuador
| | | | | | - Manuel Baldeón
- Centro de Investigación Traslacional, Universidad de las Américas, Calle José Queri. Quito, Ecuador
| | - Lourdes Karina Ponce
- Universidad de las Fuerzas Armadas ESPE, P.O. Box 171-5-231B, Av. General Rumiñahui s/n, Sangolquí, Ecuador
| | - Iván Salvador
- Hospital Carlos Andrade Marín, P.O. Box 170411, Av. 18 de Septiembre s/n y Ayacucho, Quito, Ecuador
| | - Nicolás Vivar Díaz
- Hospital Carlos Andrade Marín, P.O. Box 170411, Av. 18 de Septiembre s/n y Ayacucho, Quito, Ecuador ; NETLAB S.A., Calle "A" (Oe7A) N31-145 y Av. Mariana de Jesús, Quito, Ecuador
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25
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Tu T, Budzinska MA, Maczurek AE, Cheng R, Di Bartolomeo A, Warner FJ, McCaughan GW, McLennan SV, Shackel NA. Novel aspects of the liver microenvironment in hepatocellular carcinoma pathogenesis and development. Int J Mol Sci 2014; 15:9422-58. [PMID: 24871369 PMCID: PMC4100103 DOI: 10.3390/ijms15069422] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2014] [Revised: 05/13/2014] [Accepted: 05/14/2014] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer that is derived from hepatocytes and is characterised by high mortality rate and poor prognosis. While HCC is driven by cumulative changes in the hepatocyte genome, it is increasingly recognised that the liver microenvironment plays a pivotal role in HCC propensity, progression and treatment response. The microenvironmental stimuli that have been recognised as being involved in HCC pathogenesis are diverse and include intrahepatic cell subpopulations, such as immune and stellate cells, pathogens, such as hepatitis viruses, and non-cellular factors, such as abnormal extracellular matrix (ECM) and tissue hypoxia. Recently, a number of novel environmental influences have been shown to have an equally dramatic, but previously unrecognized, role in HCC progression. Novel aspects, including diet, gastrointestinal tract (GIT) microflora and circulating microvesicles, are now being recognized as increasingly important in HCC pathogenesis. This review will outline aspects of the HCC microenvironment, including the potential role of GIT microflora and microvesicles, in providing new insights into tumourigenesis and identifying potential novel targets in the treatment of HCC.
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Affiliation(s)
- Thomas Tu
- Liver Cell Biology, Centenary Institute, Sydney, NSW 2050, Australia.
| | | | | | - Robert Cheng
- Liver Cell Biology, Centenary Institute, Sydney, NSW 2050, Australia.
| | - Anna Di Bartolomeo
- School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia.
| | - Fiona J Warner
- Liver Cell Biology, Centenary Institute, Sydney, NSW 2050, Australia.
| | | | - Susan V McLennan
- Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.
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26
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Mitchell HM, Rocha GA, Kaakoush NO, O’Rourke JL, Queiroz DMM. The Family Helicobacteraceae. THE PROKARYOTES 2014:337-392. [DOI: 10.1007/978-3-642-39044-9_275] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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27
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Rabelo-Gonçalves EMA, Sgardioli IC, Lopes-Cendes I, Escanhoela CAF, Almeida JRDS, Zeitune JMR. Improved detection of Helicobacter pylori DNA in formalin-fixed paraffin-embedded (FFPE) tissue of patients with hepatocellular carcinoma using laser capture microdissection (LCM). Helicobacter 2013; 18:244-5. [PMID: 23350684 DOI: 10.1111/hel.12040] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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28
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Association between Helicobacter pylori infection and liver cancer mortality in 67 rural Chinese counties. Cancer Causes Control 2013; 24:1331-7. [DOI: 10.1007/s10552-013-0211-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2012] [Accepted: 04/01/2013] [Indexed: 01/22/2023]
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29
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Effects of Helicobacter pylori γ-glutamyltranspeptidase on apoptosis and inflammation in human biliary cells. Dig Dis Sci 2012; 57:2615-24. [PMID: 22581342 DOI: 10.1007/s10620-012-2216-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2011] [Accepted: 04/25/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND Several studies have reported the presence of H. pylori in individuals with hepatobiliary diseases, but in vitro and in vivo studies are still needed. Here, we determined the effects of H. pylori γ-glutamyltranspeptidase (GGT) on the induction of apoptosis and IL-8 production in a human cholangiocarcinoma cell line (KKU-100 cells). METHODS Cell viability and DNA synthesis were examined by MTT and BrdU assays, respectively. RT-PCR and western blot analysis were performed to assess gene and protein expression, respectively. IL-8 secretion in KKU-100 cells was measured by ELISA. RESULTS Exposure to the H. pylori ggt (+) strain decreased KKU-100 cell survival and DNA synthesis when compared with cells exposed to the H. pylori ggt mutant strain. Treatment with recombinant H. pylori GGT (rHP-GGT) dramatically decreased cell survival and DNA synthesis, and stimulated apoptosis; these features corresponded to an increased level of iNOS gene expression in KKU-100 cells treated with rHP-GGT. RT-PCR and western blot analyses revealed that rHP-GGT treatment enhanced the expression of pro-apoptotic molecules (Bax, Caspase-9, and Caspase-3) and down-regulated the expression of anti-apoptotic molecules (Bcl-2 and Bcl-xL). The extrinsic-mediated apoptosis molecules, including Fas and activated Caspase-8, were not expressed after treatment with rHP-GGT. Furthermore, rHP-GGT significantly stimulated IL-8 secretion in KKU-100 cells. CONCLUSION Our data indicate that H. pylori GGT might be involved in the development of cancer in hepatobiliary cells by altering cell kinetics and promoting inflammation.
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30
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Le Roux-Goglin E, Varon C, Spuul P, Asencio C, Mégraud F, Génot E. Helicobacter infection induces podosome assembly in primary hepatocytes in vitro. Eur J Cell Biol 2012; 91:161-70. [DOI: 10.1016/j.ejcb.2011.11.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2011] [Revised: 10/21/2011] [Accepted: 11/14/2011] [Indexed: 12/29/2022] Open
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31
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Boonyanugomol W, Chomvarin C, Sripa B, Bhudhisawasdi V, Khuntikeo N, Hahnvajanawong C, Chamsuwan A. Helicobacter pylori in Thai patients with cholangiocarcinoma and its association with biliary inflammation and proliferation. HPB (Oxford) 2012; 14:177-84. [PMID: 22321036 PMCID: PMC3371200 DOI: 10.1111/j.1477-2574.2011.00423.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To investigate whether Helicobacter spp. infection and the cagA of H. pylori are associated with hepatobiliary pathology, specifically biliary inflammation, cell proliferation and cholangiocarcinoma (CCA). METHODS Helicobacter species including H. pylori, H. bilis and H. hepaticus were detected in the specimens using the polymerase chain reaction (PCR). Biliary inflammation of the liver and gallbladders was semi-quantitatively graded on hematoxylin and eosin (H&E)-stained slides. Biliary proliferation was evaluated by immunohistochemistry using the Ki-67-labelling index. RESULTS Helicobacter pylori was found in 66.7%, 41.5% and 25.0% of the patients in the CCA, cholelithiasis and control groups (P < 0.05), respectively. By comparison, H. bilis was found in 14.9% and 9.4% of the patients with CCA and cholelithiasis, respectively (P > 0.05), and was absent in the control group. The cagA gene of H. pylori was detected in 36.2% and 9.1% of the patients with CCA and cholelithiasis, respectively (P < 0.05). Among patients with CCA, cell inflammation and proliferation in the liver and gallbladder were significantly higher among those DNA H. pylori positive than negative. CONCLUSIONS The present findings suggest that H. pylori, especially the cagA-positive strains, may be involved in the pathogenesis of hepatobiliary diseases, especially CCA through enhanced biliary cell inflammation and proliferation.
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Affiliation(s)
- Wongwarut Boonyanugomol
- Department of Microbiology, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand,Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand
| | - Chariya Chomvarin
- Department of Microbiology, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand,Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand
| | - Banchob Sripa
- Department of Pathology, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand,Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand
| | - Vajarabhongsa Bhudhisawasdi
- Department of Surgery, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand,Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand
| | - Narong Khuntikeo
- Department of Surgery, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand,Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand
| | - Chariya Hahnvajanawong
- Department of Microbiology, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand,Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand
| | - Amporn Chamsuwan
- Department of Forensic Medicine, Faculty of Medicine, Khon Kaen UniversityKhon Kaen, Thailand
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32
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Boonyanugomol W, Chomvarin C, Sripa B, Bhudhisawasdi V, Khuntikeo N, Hahnvajanawong C, Chamsuwan A. Helicobacter pylori in Thai patients with cholangiocarcinoma and its association with biliary inflammation and proliferation. HPB (Oxford) 2012. [PMID: 22321036 DOI: 10.1111/j.1477-574.2011.00423.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To investigate whether Helicobacter spp. infection and the cagA of H. pylori are associated with hepatobiliary pathology, specifically biliary inflammation, cell proliferation and cholangiocarcinoma (CCA). METHODS Helicobacter species including H. pylori, H. bilis and H. hepaticus were detected in the specimens using the polymerase chain reaction (PCR). Biliary inflammation of the liver and gallbladders was semi-quantitatively graded on hematoxylin and eosin (H&E)-stained slides. Biliary proliferation was evaluated by immunohistochemistry using the Ki-67-labelling index. RESULTS Helicobacter pylori was found in 66.7%, 41.5% and 25.0% of the patients in the CCA, cholelithiasis and control groups (P < 0.05), respectively. By comparison, H. bilis was found in 14.9% and 9.4% of the patients with CCA and cholelithiasis, respectively (P > 0.05), and was absent in the control group. The cagA gene of H. pylori was detected in 36.2% and 9.1% of the patients with CCA and cholelithiasis, respectively (P < 0.05). Among patients with CCA, cell inflammation and proliferation in the liver and gallbladder were significantly higher among those DNA H. pylori positive than negative. CONCLUSIONS The present findings suggest that H. pylori, especially the cagA-positive strains, may be involved in the pathogenesis of hepatobiliary diseases, especially CCA through enhanced biliary cell inflammation and proliferation.
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33
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Bulajic M, Panic N, Stimec B, Isaksson B, Jesenofsky R, Schneider-Brachert W, Löhr JM. PCR in Helicobacter spp. diagnostic in extragastric malignancies of digestive system. Eur J Gastroenterol Hepatol 2012; 24:117-125. [PMID: 22081011 DOI: 10.1097/meg.0b013e32834dfde1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Recognition of Helicobacter pylori as an important factor in genesis of gastric adenocarcinoma lead to a large number of studies concerning potential role of Helicobacter spp. in the development of extragastric digestive malignancies. The serological studies indicated possible localizations in the digestive system being from interest in enlightening Helicobacter spp. carcinogenic potential. The PCR obtruded itself as a gold standard in proving existence of actual correlation. In this review, the authors have examined studies conducted in the last 10 years examining Helicobacter spp. correlation with extragastric digestive carcinogenesis. Studies have been observed in four groups referring to hepatic carcinoma, bile duct cancer, pancreatic cancer, and colon cancer. The results of these researches have shown that there is a strong correlation between Helicobacter spp. colonization and primary liver tumors as well as bile duct tumors, whereas conclusions made by authors examining pancreatic cancer are contradictory and demands further investigation. No correlation between Helicobacter spp. and colon cancer have been proven. The PCR subtype most widely used in studies included in this review was nested PCR, whereas genes targeted most frequently for amplification are 16S rDNA of Helicobacter spp. and UreA gene or cagA gene of H. pylori. During the last 10 years PCR has proven itself as a sovereign method for Helicobacter spp. diagnostic in extragastric organs in the digestive system. Knowledge and experiences obtained in this domain could be encouraging for researchers in analogous fields of interest.
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Affiliation(s)
- Milutin Bulajic
- Medical Faculty of Belgrade, University Clinic Dr D. Misovic-Dedinje, Belgrade, Serbia
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34
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Mahmoud MA, Elden LAT, Awad MM, Haile HA. Helicobacter Pylori DNA in Liver Tissues From Chronic Hepatitis C Egyptian Patients. Gastroenterology Res 2011; 4:262-267. [PMID: 27957026 PMCID: PMC5139864 DOI: 10.4021/gr356w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/26/2011] [Indexed: 02/06/2023] Open
Abstract
Background Hepatitis C virus (HCV) is considered the most common etiology of chronic liver disease in Egypt, which may progress to cirrhosis and hepatocellular carcinoma (HCC). Previous studies have documented an association between Helicobacter pylori (H. pylori) infection and liver cirrhosis with or without HCC. This study aimed to investigate the presence of H. pylori DNA in the liver tissue of Egyptian patients with chronic hepatitis C (CHC). Methods Fifty-two CHC Egyptian patients were enrolled in this study. Plasma anti-H. pylori IgG was assessed with ELISA. Liver biopsies were tested for presence of Helicobacter DNA using genus specific nested polymerase chain reaction (PCR) and species was identified by sequencing. Results Anti-H. pylori IgG was detected in 31/52 (59.6%) CHC patients while Helicobacter DNA was detected in 6 (11.5%) patients, all were H. Pylori by sequencing. Helicobacter DNA was more frequent in patients with high stage liver fibrosis (33.3%) than in those with low stage fibrosis (2.7%) (P = 0.006). There was no association between the presence of H. pylori DNA in the liver and age, gender of patients, liver function tests, AFP levels or viral load. Conclusions These data confirm the presence of H. pylori DNA in liver of some CHC Egyptian patients and suggest an association of this bacterium with progression of liver fibrosis.
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Affiliation(s)
- Moushira A Mahmoud
- Department of Medical Biochemistry, Suez Canal Faculty of medicine, Ismailia, Egypt
| | - Loaa A Tag Elden
- Department of Medical Biochemistry, Suez Canal Faculty of medicine, Ismailia, Egypt
| | - Mohamed M Awad
- Department of Internal Medicine, Suez Canal Faculty of medicine, Ismailia, Egypt
| | - Henock A Haile
- Department of Medical Biochemistry, Suez Canal Faculty of medicine, Ismailia, Egypt
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Abstract
Emerging evidence suggests a strong interaction between the gut microbiota and health and disease. The interactions of the gut microbiota and the liver have only recently been investigated in detail. Receiving approximately 70% of its blood supply from the intestinal venous outflow, the liver represents the first line of defense against gut-derived antigens and is equipped with a broad array of immune cells (i.e., macrophages, lymphocytes, natural killer cells, and dendritic cells) to accomplish this function. In the setting of tissue injury, whereby the liver is otherwise damaged (e.g., viral infection, toxin exposure, ischemic tissue damage, etc.), these same immune cell populations and their interactions with the infiltrating gut bacteria likely contribute to and promote these pathologies. The following paper will highlight recent studies investigating the relationship between the gut microbiota, liver biology, and pathobiology. Defining these connections will likely provide new targets for therapy or prevention of a wide variety of acute and chronic liver pathologies.
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Tu QV, Okoli AS, Kovach Z, Mendz GL. Hepatocellular carcinoma: prevalence and molecular pathogenesis of Helicobacter spp. Future Microbiol 2009; 4:1283-301. [PMID: 19995189 DOI: 10.2217/fmb.09.90] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori infection is one of the most common chronic bacterial infections in humans. The association of other Helicobacter spp. with extragastric diseases in animals is well established, and a role of these bacteria in human liver disease is becoming clearer. Several case-control studies have reported possible associations of Helicobacter spp. with various liver diseases, including hepatocellular carcinoma, which is the fifth most common type of carcinoma among men worldwide, and the eighth most common among women. Thus, it is important to understand molecular mechanisms that may lead to hepatotoxicity or hepatocellular dysfunction in which Helicobacter spp. may play a role in inducing malignant transformation of liver cells.
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Affiliation(s)
- Quoc V Tu
- School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
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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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Ito K, Yamaoka Y, Ota H, El-Zimaity H, Graham DY. Adherence, internalization, and persistence of Helicobacter pylori in hepatocytes. Dig Dis Sci 2008; 53:2541-9. [PMID: 18320323 PMCID: PMC3128246 DOI: 10.1007/s10620-007-0164-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2007] [Accepted: 11/26/2007] [Indexed: 12/11/2022]
Abstract
Although Helicobacter pylori have been identified in the liver, the role of Helicobacter sp. in human liver diseases remains unclear. This study explored whether H. pylori were internalized and could persist in hepatocytes. The majority of an inoculum of H. pylori (1 x 10(7) colony forming units) adhered to hepatocytes. Using the gentamicin invasion assay we found that approximately 2% were internalized and persisted following passage for more than 2 months. Electron microscopy confirmed the presence of intracellular Helicobacter. The number of adherent or internalized H. pylori was significantly greater with hepatocytes than with gastric epithelial cells (P < 0.05) and was also dependent on cag pathogenicity island (PAI), VacA, OipA, or BabA status. Transmission electron microscopy was used to confirm adherence and invasion of H. pylori into hepatocytes. Internalization of H. pylori was inhibited by antibodies to beta1-integrin receptors, genistein, and cytochalasin D (P < 0.05) consistent with beta1-integrin acting as a surface receptor with additional requirements for tyrosine kinase phosphorylation and actin polymerization. In summary, H. pylori both adhered to and invaded into hepatocytes in vitro, depending on the virulent factors, and persisted within hepatocytes during subcultures. beta1-integrin is likely a receptor involved in internalization of H. pylori into hepatocytes.
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Affiliation(s)
- Kyoko Ito
- Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd. 3A-320, Houston, TX 77030, USA, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei School of Medicine, Tokyo, Japan
| | - Yoshio Yamaoka
- Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd. 3A-320, Houston, TX 77030, USA
| | - Hiroyoshi Ota
- Department of Biomedical Laboratory Sciences, School of Health Sciences, Shinshu University, School of Medicine, Nagano, Japan
| | - Hala El-Zimaity
- Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd. 3A-320, Houston, TX 77030, USA
| | - David Y. Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd. 3A-320, Houston, TX 77030, USA
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Ji SW, Zhang YG, Wang JB. Helicobacter pylori infection in patients with chronic hepatitis C and its related factors. Shijie Huaren Xiaohua Zazhi 2008; 16:535-539. [DOI: 10.11569/wcjd.v16.i5.535] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the role of H. pylori in chronic hepatitis C.
METHODS: Serum anti-H. pylori-IgG was detected by ELISA to determine whether there is H. pylori infection according to the diagnostic criteria of H. pylori epidemiology. Serum HCV RNA level was detected by real time fluorescence quantitative polymerase chain reaction (FQ-PCR). HCV genotypes were identified by polymerase chain reaction-microplate hybridization-enzyme linked immunosorbent assay (PCR-MPH-ELISA).
RESULTS: H. pylori infection was more prevalent in patients with chronic hepatitis C, cirrhosis due to chronic hepatitis C and HCC than in healthy controls (55.5%, 76.5%, 78.6% vs 43.4%, P < 0.05). H. pylori infection aggravated with the extent of hepatic lesions and the load of hepatitis C virus. H. pylori infection was 59.5%, 66.7%, 65.0% and 59.2% in patients with genotypes 1a, 1b, 2a and 2b, respectively. However, there was no significant difference in these genotypes.
CONCLUSION: H. pylori infection is higher in patients with chronic hepatitis C than in healthy controls. H. pylori might play a role in the progress from chronic hepatitis C to cirrhosis and hepatocellular carcinoma.
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Suksumek N, Leelawat K, Leelawat S, Russell B, Lek-Uthai U. TaqMan real-time PCR assay for specific detection of Opisthorchis viverrini DNA in Thai patients with hepatocellular carcinoma and cholangiocarcinoma. Exp Parasitol 2008; 119:217-24. [PMID: 18329641 DOI: 10.1016/j.exppara.2008.01.018] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2007] [Revised: 11/21/2007] [Accepted: 01/28/2008] [Indexed: 01/28/2023]
Abstract
The aim of this study was to develop TaqMan real-time PCR assay that detected Opisthorchis viverrini DNA from 18 normal and 18 tumor tissue specimens from Thai patients with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), who underwent liver resection from October 2005 to May 2006. Control liver specimens were seven non-primary liver cancers. A conserved probe representing 100% sequence homology was used as a reference for O. viverrini-specific probe. Five of six tumors (83%) and all six normal tissues from CCA group; and seven of twelve tumors (58%) and ten of twelve normal tissues (83%) from HCC group were found to have O. viverrini DNA. The O. viverrini DNA detection among HCC and CCA patients were not associated (p=0.193; 90%CI). This RT-PCR will be a useful tool for investigating the relationship between cancer type and presence of the parasite and also for conducting epidemiological surveys.
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Affiliation(s)
- Nithikoon Suksumek
- Division of Molecular Laboratory, Vachira Hospital, Bangkok 10400, Thailand
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DNA of Helicobacter spp. and common gut bacteria in primary liver carcinoma. Dig Liver Dis 2008; 40:126-31. [PMID: 18083084 DOI: 10.1016/j.dld.2007.09.011] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2007] [Revised: 08/07/2007] [Accepted: 09/19/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Gastric and enteric Helicobacter species have been associated with the pathogenesis of some extragastric diseases. METHODS We retrospectively investigated the presence of DNA of Helicobacter species in samples of the cancer and the surrounding tumour-free liver tissues of patients with hepatocellular carcinoma (HCC, n=12) and cholangiocarcinoma (CC, n=13). The patients were from an area with low liver cancer incidence and with low hepatitis B and C prevalence. Patients with a benign liver disease (n=24) were included as controls. Paraffin-embedded liver samples were examined by a Helicobacter genus-specific PCR assay as well as group-specific PCR assays for Enterobacteriaceae, Bacteroides, Lactobacillus and Enterococcus. PCR products of positive samples were characterised by denaturing gradient gel electrophoresis (DGGE) and DNA sequencing. RESULTS PCR assay detected Helicobacter DNA in seven of 12 (58%) and eight of 13 (62%) normal liver tissue specimens from HCC and CC patients, respectively. Two cancer samples from HCC patients were Helicobacter-positive but none of the CC cancers. In the control group, three of 24 (12.5%) patients with a benign liver condition were positive for Helicobacter species (p<0.01 compared to results of tumour-free liver tissue from the cancer patients). DGGE and DNA sequence analysis showed that 90% of the detected PCR products were "H. pylori-like". DNA of some other enteric bacteria was detected in the liver of one cancer patient and one control (4% of all patients). CONCLUSION The presence of DNA of Helicobacter species in liver specimens, but not of other common gut bacteria, was associated with human hepatic carcinogenesis.
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Identification of Helicobacter species by 16S rDNA PCR and sequence analysis in human liver samples from patients with various etiologies of benign liver diseases. Eur J Gastroenterol Hepatol 2008; 20:33-6. [PMID: 18090988 DOI: 10.1097/meg.0b013e3282efa4f2] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIMS Several reports indicated an increased prevalence of the Helicobacter species in hepatocellular cancer tissue and in liver samples infected with hepatitis viruses. The frequency of Helicobacter spp. in benign liver diseases was, however, not thoroughly investigated. METHODS Seventy-five consecutive patients with suspected liver disease were enrolled. The indications were hepatitis B virus (n=30), C virus (n=8), B and C dual infection (n=1), nonalcoholic steatohepatitis (n=27), autoimmune hepatitis (n=3), primary biliary cirrhosis (n=1) and idiopathic elevation of liver enzymes (n=5). PCR detection of 16S recombinant RNA gene of Helicobacter spp. was performed on liver samples. PCR products of positive samples were further identified by DNA sequencing. The patients also had upper gastrointestinal endoscopy and gastric biopsy for the detection of H. pylori using histopathology and PCR. RESULTS Helicobacter spp. DNA was detected in two out of 75 liver biopsy samples (2.6%), which were typed as H. pylori by DNA sequencing. One of these patients had chronic hepatitis C infection (man, 51 years old) and the other had nonalcoholic steatohepatitis (woman, 44 years old). Fifty-two out of 75 of the patients (69.3%) had H. pylori infection in their stomachs. CONCLUSION We have found that H. pylori infection is much less prevalent in benign liver diseases. The presence of H. pylori in nonalcoholic steatohepatitis (NASH) patients is a novel finding and this finding should be confirmed in a larger series.
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Xuan SY, Xin YN, Chen H, Shi GJ, Guan HS, Li Y. Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues. World J Gastroenterol 2007; 13:1870-4. [PMID: 17465484 PMCID: PMC4149970 DOI: 10.3748/wjg.v13.i12.1870] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the correlation between hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) expression in hepatocellular carcinoma (HCC), the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein (AFP) level.
METHODS: The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immuno-histochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index (HAI) score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups: patients positive for HBsAg (HBsAg group), patients positive for HCV (HCV group), patients negative for both HCV and HBsAg (NBNC group) and patients positive for both HBsAg and HCV (BC group).
RESULTS: The BC group had significantly higher HAI scores than the other three groups. (BC > HCV > HBsAg > NBNC). HBV and HCV virus infection was positively correlated with HAI (rs = 0.39, P = 0.0001). The positive rate of AFP (85.7%) and the value of AFP (541.2 ng/mL) in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate (53.3%) of AFP and the value of AFP ( 53.3 ng/mL) in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP(rs = 0.38, P = 0.0001).
CONCLUSION: The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman’s rank correlation analysis, we can conclude that the severity of virally induced inflammation is correlated with HBsAg and HCV expression in HCC tissues and noncancerous tissues. Prior co-infection of HBV in HCV patients may be an adverse risk factor for intrahepatic inflammation.
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Affiliation(s)
- Shi-Ying Xuan
- College of Medicine and Pharmaceutics, Ocean University of China, 5 Yushan Road, Qingdao 266003, Shandong Province, China
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Veijola L, Nilsson I, Halme L, Al-Soud WA, Mäkinen J, Ljungh A, Rautelin H. Detection of Helicobacter species in chronic liver disease and chronic inflammatory bowel disease. Ann Med 2007; 39:554-60. [PMID: 17852032 DOI: 10.1080/07853890701545714] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To study the association between helicobacters and chronic liver diseases and chronic inflammatory bowel diseases. PATIENTS AND METHODS Thirty-two patients with various chronic liver diseases and 137 patients with inflammatory bowel disease were enrolled. Antibodies to H. pylori, H. hepaticus, H. bilis, and H. pullorum were measured by enzyme immunoassay (EIA), and sera positive in a non-pylori helicobacter EIA were further examined by immunoblot assay. Detection of Helicobacter DNA in liver biopsies was done by denaturating gradient gel electrophoresis of PCR products (PCR-DGGE) and DNA sequence analysis. RESULTS Six inflammatory bowel disease patients, four with ulcerative colitis and two with Crohn's disease, and one liver disease patient with autoimmune cholangitis had antibodies to non-pylori helicobacters by an immunoblot assay. Four immunoblot assay-negative patients, three with autoimmune and one with non-autoimmune liver disease, had Helicobacter DNA in liver biopsies; three of the polymerase chain reaction (PCR) products were closely related to non-pylori helicobacters. CONCLUSION Evidence for non-pylori helicobacters was scant in Finnish patients with inflammatory bowel disease or chronic but not end stage liver disease. We cannot, however, rule out their role in these diseases.
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Affiliation(s)
- Lea Veijola
- Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.
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Kast RE. Some fibrocystic breast change may be caused by sexually transmitted H. pylori during oral nipple contact: supporting literature and case report of resolution after gut H. pylori eradication treatment. Med Hypotheses 2006; 68:1041-6. [PMID: 17113238 DOI: 10.1016/j.mehy.2006.09.050] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2006] [Accepted: 09/25/2006] [Indexed: 12/24/2022]
Abstract
OBJECTIVES To briefly review previously published evidence for Helicobacter pylori (Hp), colonization of extra-intestinal sites and suggest an hypothesis that breast acini and ducts be added to this list, concluding such breast colonization is not rare and is a sexually transmitted infection. METHODS PubMed literature search and review with a case report. CONCLUSIONS (1) Evidence indicates oral Hp is common and can remain in the mouth after successful eradication in stomach and duodenum. (2) Evidence indicates that the breast is also occasionally colonized by Hp. (3) Hp may be injected retrograde up into ducts of the breast during oral nipple stimulation during sexual activity and this Hp may give rise to some cases of fibrocystic breast change. (4) A case of painful fibrocystic change that had been present for two years in a 27 year old female, resolved after gastrointestinal Hp treatment.
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Affiliation(s)
- R E Kast
- Department of Psychiatry, University of Vermont, 2 Church Street, Burlington, VT 05401, USA.
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Abstract
A growing interest in non-invasive tests for the detection of Helicobacter pylori has been observed recently, reflecting a large number of studies published this year. New tests have been validated, and the old ones have been used in different clinical situations or for different purposes. Stool antigen tests have been extensively evaluated in pre- and post-treatment settings both in adults and children, and the urea breath test has been studied as a predictor of bacterial load, severity of gastric inflammation, and response to eradication treatment. Several studies have also explored the usefulness of some serologic markers as indicators of the gastric mucosa status. With regard to invasive tests, molecular methods are being used more and more, but the breakthrough this year was the direct in vivo observation of H. pylori during endoscopy.
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