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Han P, Wang C, Qiu Y. Assessing the associations of inflammatory bowel disease and hepatitis B virus infections with two-sample bidirectional mendelian randomization. CRITICAL PUBLIC HEALTH 2024; 34:1-9. [DOI: 10.1080/09581596.2024.2404874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 09/10/2024] [Indexed: 01/05/2025]
Affiliation(s)
- Ping Han
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chaohui Wang
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yan Qiu
- Department of General Practice, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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2
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Markopoulos P, Karmiris K, Dimas I, Voudoukis E, Siakavellas S, Axiaris G, Zacharopoulou E, Zampeli E, Tsironi E, Tzouvala M, Papatheodoridis G, Bamias G. Efficacy of Vaccination and Revaccination Against Hepatitis B Virus Using 2 Different Strategies in Patients With Inflammatory Bowel Disease. Inflamm Bowel Dis 2024:izae173. [PMID: 39102755 DOI: 10.1093/ibd/izae173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Indexed: 08/07/2024]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) exhibit an increased risk for acquiring hepatitis B virus (HBV), thus they should be vaccinated preferably, if not already infected or immunized. We assessed the efficacy of HBV vaccination in IBD patients and impact of different factors on the immune response. We also evaluated the success rate of 2 different revaccination strategies in the nonresponders. METHODS This was a retrospective observational cohort study carried out in 5 tertiary centers. All patients were tested for hepatitis B surface antigen, antibodies against hepatitis B surface antigen (anti-HBs), and antibodies against hepatitis B core antigen. Patients tested negative and underwent the standard schedule with 20 µg at 0, 1, and 6 months. Nonresponders (anti-HBs <10 IU/L) were offered a revaccination scheme with either 3 doses of 40 µg at 0, 1, and 6 months or an accelerated scheme with 20 µg at 0, 1, and 2 months. RESULTS A total of 409 patients were included, and 273 (66.7%) of those (females: 49.5%; Crohn's disease [CD]: 56.7%) responded to baseline vaccination. A total of 189 (69.2%) of 273 (females: 48.1%; CD: 60.3%) developed anti-HBs >100 IU/L. Body mass index <30 kg/m2 (P = .017) was positively associated, while diagnosis of CD (P = .013), extensive UC (P <.0001), extraintestinal manifestations (P = .001), and treatment with immunomodulators/anti-tumor necrosis factor (P < .00) negatively affected the response. Revaccination was offered to 103 patients, and 58.3% of them achieved anti-HBs >10 IU/L. Both revaccination strategies were equally effective. CONCLUSIONS IBD patients demonstrate lower response to HBV vaccination compared with the general population. Age, body mass index, type, disease activity, and immunosuppression negatively affect the response. Half of nonresponders may benefit from an enhanced revaccination attempt.
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Affiliation(s)
| | | | - Ioannis Dimas
- Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Greece
| | - Evangelos Voudoukis
- Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Greece
| | - Spyridon Siakavellas
- Department of Gastroenterology, General Hospital of Athens LAIKO, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Axiaris
- Department of Gastroenterology, Alexandra General Hospital, Athens, Greece
| | - Eirini Zacharopoulou
- Department of Gastroenterology, Agios Panteleimon General Hospital, Nikaia, Piraeus - Agia Varvara General Hospital of Western Attica, Athens, Greece
| | - Evanthia Zampeli
- Department of Gastroenterology, Alexandra General Hospital, Athens, Greece
| | - Eftychia Tsironi
- Department of Gastroenterology, Metaxa Memorial Cancer Hospital, Piraeus, Greece
| | - Maria Tzouvala
- Department of Gastroenterology, Agios Panteleimon General Hospital, Nikaia, Piraeus - Agia Varvara General Hospital of Western Attica, Athens, Greece
| | - Georgios Papatheodoridis
- Department of Gastroenterology, General Hospital of Athens LAIKO, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Bamias
- Department of Gastroenterology, General Hospital of Athens LAIKO, Medical School of National and Kapodistrian University of Athens, Athens, Greece
- GI Unit, 3rd Department of Internal Medicine, Sotiria General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
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Giri S, Agrawal D, Afzalpurkar S, Kasturi S, Gopan A, Sundaram S, Kale A. Prevalence of hepatitis B virus and hepatitis C virus infection in patients with inflammatory bowel disease: a systematic review and meta-analysis. Intest Res 2023; 21:392-405. [PMID: 36453006 PMCID: PMC10397541 DOI: 10.5217/ir.2022.00094] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/24/2022] [Accepted: 08/30/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND/AIMS The data on the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with inflammatory bowel disease (IBD) are conflicting. The present systematic review was thus conducted to study the prevalence of HBV and HCV markers in patients with IBD. METHODS A comprehensive literature search of 3 databases was conducted from 2000 to April 2022 for studies evaluating the prevalence of HBV or HCV in patients with IBD. Pooled prevalence rates across studies were expressed with summative statistics. RESULTS A total of 34 studies were included in the final analysis. The pooled prevalence of hepatitis B surface antigen (HBsAg) and hepatitis B core antibodies were 3.3% and 14.2%, respectively. In HBsAg positive IBD patients, hepatitis B e antigen positivity and detectable HBV DNA were seen in 15.3% and 61.0% of patients, respectively. Only 35.6% of the IBD patients had effective HBV vaccination. The pooled prevalence of anti-HCV and detectable HCV RNA were 1.8% and 0.8%, respectively. The pooled prevalence of markers of HBV infection was higher in Asian studies, while the prevalence of markers of HCV infection was higher in European studies. The prevalence of viral hepatitis markers was similar between IBD patients and the general population and that between ulcerative colitis and Crohn's disease. CONCLUSIONS The prevalence of markers of viral hepatitis remains same as the general population with significant regional variations, although the quality of evidence remains low due to publication bias. Only a small proportion of IBD patients had an effective HBV vaccination, requiring improvement in screening and vaccination practices.
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Affiliation(s)
- Suprabhat Giri
- Department of Gastroenterology, Nizam’s Institute of Medical Sciences, Hyderabad, India
| | - Dhiraj Agrawal
- Department of Gastroenterology, PACE Hospital, Hyderabad, India
| | - Shivaraj Afzalpurkar
- Institute of Gastrosciences and Liver, Apollo Multispecialty Hospital, Kolkata, India
| | - Sunil Kasturi
- Department of Gastroenterology, Fortis Hospital, Bengaluru, India
| | - Amrit Gopan
- Department of Gastroenterology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India
| | - Sridhar Sundaram
- Department of Digestive Disease and Clinical Nutrition, Tata Memorial Hospital, Mumbai, India
| | - Aditya Kale
- Department of Gastroenterology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India
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Kuiper VP, van der Plas P, Hoogerwerf MA, Pieter R Koopman J, van der Meulen AE, Roukens AHE, Visser LG, Roestenberg M. A comparison of two Fendrix hepatitis B vaccination schedules in patients with inflammatory bowel disease. Vaccine 2022; 40:6201-6205. [PMID: 36154758 DOI: 10.1016/j.vaccine.2022.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 08/31/2022] [Accepted: 09/02/2022] [Indexed: 11/18/2022]
Abstract
Systemic immunosuppressive therapy (IS) renders patients with inflammatory bowel disease (IBD) vulnerable to fulminant hepatitis B virus (HBV) infection. Seroprotection against HBV through a full vaccination scheme is preferably obtained before IS is initiated, but often conflicts with the clinical need to initiate therapy rapidly. Consequently, the vast majority of patients will use IS during booster vaccinations. In this retrospective cohort study, we examined the serological response after a modified vaccination schedule which includes an initial double dose of Fendrix in patients with IBD and compared the results with the serological responses of patients with IBD who received the standard schedule. Seroprotection rates were 86.2 % and 88.9 % in the modified and standard schedule groups respectively. One-third of patients obtained seroprotection after only one double dose vaccine. A double dose may be considered in patients with IBD at high short-term risk of HBV infection when a rapid protective response is warranted.
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Affiliation(s)
- Vincent P Kuiper
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Pauline van der Plas
- Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
| | - Marie-Astrid Hoogerwerf
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Jan Pieter R Koopman
- Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
| | - Andrea E van der Meulen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Anna H E Roukens
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Leo G Visser
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Meta Roestenberg
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
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Shin SH, Park SH. [Viral Hepatitis in Patients with Inflammatory Bowel Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2022; 80:51-59. [PMID: 36004631 DOI: 10.4166/kjg.2022.096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 07/29/2022] [Accepted: 07/30/2022] [Indexed: 06/15/2023]
Abstract
There has been a rise in the incidence of inflammatory bowel disease (IBD) in developing countries, including South Korea. Consequently, the use of immunosuppressive agents such as immunomodulators or biologics has also increased. Due to immunosuppression, patients on these agents are at increased risk of various opportunistic infections during treatment, which may sometimes lead to serious adverse outcomes. Viral hepatitis, especially hepatitis B, is one of the infectious conditions that can be reactivated during immunosuppressive therapy, and adequate strategies for monitoring and prophylaxis are needed to prevent it. South Korea is one of the countries with intermediate endemicity for hepatitis A and B. Thus, taking adequate precautions against viral hepatitis could prevent new infections or reactivation of these conditions in patients with IBD on immunosuppressive therapy. In this review article, we have summarized the latest evidence on viral hepatitis in patients with IBD that would be of assistance in clinical practice.
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Affiliation(s)
- Seung Hwan Shin
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Gaspar R, Branco CC, Macedo G. Liver manifestations and complications in inflammatory bowel disease: A review. World J Hepatol 2021; 13:1956-1967. [PMID: 35070000 PMCID: PMC8727205 DOI: 10.4254/wjh.v13.i12.1956] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/27/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatobiliary manifestations are common in inflammatory bowel disease (IBD), with 30% of patients presenting abnormal liver tests and 5% developing chronic liver disease. They range from asymptomatic elevated liver tests to life-threatening disease and usually follow an independent course from IBD. The pathogenesis of liver manifestations or complications and IBD can be closely related by sharing a common auto-immune background (in primary sclerosing cholangitis, IgG4-related cholangitis, and autoimmune hepatitis), intestinal inflammation (in portal vein thrombosis and granulomatous hepatitis), metabolic impairment (in non-alcoholic fatty liver disease or cholelithiasis), or drug toxicity (in drug induced liver injury or hepatitis B virus infection reactivation). Their evaluation should prompt a full diagnostic workup to identify and readily treat all complications, improving management and outcome.
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Affiliation(s)
- Rui Gaspar
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
| | - Catarina Castelo Branco
- Internal Medicine Department, Centro Hospitalar e Universitário do Porto, Porto 4200, Portugal
| | - Guilherme Macedo
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
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Losurdo G, Brescia IV, Lillo C, Mezzapesa M, Barone M, Principi M, Ierardi E, Di Leo A, Rendina M. Liver involvement in inflammatory bowel disease: What should the clinician know? World J Hepatol 2021; 13:1534-1551. [PMID: 34904028 PMCID: PMC8637677 DOI: 10.4254/wjh.v13.i11.1534] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/06/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) may show a wide range of extraintestinal manifestations. In this context, liver involvement is a focal point for both an adequate management of the disease and its prognosis, due to possible serious comorbidity. The association between IBD and primary sclerosing cholangitis is the most known example. This association is relevant because it implies an increased risk of both colorectal cancer and cholangiocarcinoma. Additionally, drugs such as thiopurines or biologic agents can cause drug-induced liver damage; therefore, this event should be considered when planning IBD treatment. Additionally, particular consideration should be given to the evidence that IBD patients may have concomitant chronic viral hepatitis, such as hepatitis B and hepatitis C. Chronic immunosuppressive regimens may cause a hepatitis flare or reactivation of a healthy carrier state, therefore careful monitoring of these patients is necessary. Finally, the spread of obesity has involved even IBD patients, thus increasing the risk of non-alcoholic fatty liver disease, which has already proven to be more common in IBD patients than in the non-IBD population. This phenomenon is considered an emerging issue, as it will become the leading cause of liver cirrhosis.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Irene Vita Brescia
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Chiara Lillo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Martino Mezzapesa
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Michele Barone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Mariabeatrice Principi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Maria Rendina
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
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Cunha IDS, Silva TCD, Malluta ÉF, Scolaro BL, Velho PS, Stall J. SEROCONVERSION ANALYSIS AFTER HABITUAL HEPATITIS B VACCINATION SCHEME IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:69-73. [PMID: 32294738 DOI: 10.1590/s0004-2803.202000000-12] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 01/06/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) vaccinated for hepatitis B have a low success rate in achieving protective antibody levels. The main factors suggested for this are IBD itself and the use of immunosuppressive drugs. OBJECTIVE To evaluate the concentration of anti-HBs antibodies and to verify factors associated with the effectiveness of hepatitis B vaccination in patients with IBD. METHODS This is a prospective, consecutive, observational, descriptive and analytical, non-randomized, qualitative study that evaluated the levels of anti-HBs antibodies in IBD patients at the Interdisciplinary Inflammatory Bowel Disease Clinic of the Family and Community Health Unit of UNIVALI - Itajaí, Santa Catarina. RESULTS Thirty-six patients were vaccinated against hepatitis B virus (HBV), of which 29 were female. The average age was 46.2 years. Regarding the type of IBD, twenty-four patients had Crohn's disease and the duration of inflammatory bowel disease was 74 months. Fifteen patients were on concomitant immunosuppressive therapy. The effective response rate to HBV vaccine was 72.2%, verified by anti-HBs titration ≥10 UI/L. Statistical analysis revealed a negative response to vaccination in patients with Crohn's disease and immunosuppressive drugs. CONCLUSION The success rate of HBV immunization in IBD patients is low compared to the general population. Type of disease and use of immunosuppressive drugs appear to influence the vaccine response.
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Affiliation(s)
- Isabella de Souza Cunha
- UNIVALI, Unidade de Saúde da Família e Comunidade, Clínica Interdisciplinar de Doença Inflamatória Intestinal, Itajaí, SC, Brasil
| | - Tayná Cristina da Silva
- UNIVALI, Unidade de Saúde da Família e Comunidade, Clínica Interdisciplinar de Doença Inflamatória Intestinal, Itajaí, SC, Brasil
| | - Éverson Fernando Malluta
- UNIVALI, Unidade de Saúde da Família e Comunidade, Clínica Interdisciplinar de Doença Inflamatória Intestinal, Itajaí, SC, Brasil
| | - Bruno Lorenzo Scolaro
- UNIVALI, Unidade de Saúde da Família e Comunidade, Clínica Interdisciplinar de Doença Inflamatória Intestinal, Itajaí, SC, Brasil
| | - Pablo Sebastian Velho
- UNIVALI, Unidade de Saúde da Família e Comunidade, Clínica Interdisciplinar de Doença Inflamatória Intestinal, Itajaí, SC, Brasil
| | - Juliane Stall
- UNIVALI, Unidade de Saúde da Família e Comunidade, Clínica Interdisciplinar de Doença Inflamatória Intestinal, Itajaí, SC, Brasil
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Coukos J, Farraye FA. Update on Vaccinating the Patient With Inflammatory Bowel Disease. ACTA ACUST UNITED AC 2018; 16:548-560. [PMID: 30293209 DOI: 10.1007/s11938-018-0200-4] [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] [Indexed: 12/25/2022]
Abstract
PURPOSE OF REVIEW Patients with inflammatory bowel disease (IBD) are at increased risk of infectious diseases independent of their immunosuppression status, and yet, studies suggest that this population is not receiving standard vaccinations at the same rate as the general population. This review seeks to understand why IBD patients may not be receiving recommended immunizations and to provide guidelines on vaccinating this vulnerable population. RECENT FINDINGS Inactive vaccines are recommended for patients with IBD regardless of immunosuppression status due to the increased risk for many vaccine-preventable illnesses. Certain live vaccines can be administered to the immunocompromised patient with IBD. Additionally, many patients with IBD will be immunosuppressed some time in their disease course, further increasing their risk for infection. Despite this understanding, patients with IBD have poor vaccination rates. Inadequate knowledge, limited time with patients, and lack of consensus as to who is responsible for identifying and administering vaccinations are some of the most important barriers to vaccinating the patient with IBD. In this review, we discuss guidelines for vaccinating both the immunocompetent and immunosuppressed patient with IBD as well as provide vaccine-specific recommendations. The evidence suggests that patients with IBD are not receiving recommended vaccinations because of misconceptions on the part of patients as well as a paucity of knowledge by their health care team. Educational programs can be successfully implemented to increase knowledge about appropriate vaccinations and can ultimately increase vaccine uptake among patients with IBD. In the end, gastroenterologists and primary care physicians must work together with their patients with IBD to ensure that recommended vaccinations are administered.
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Affiliation(s)
- Jennifer Coukos
- Department of Internal Medicine, University of Massachusetts Medical School, Worcester, MA, USA
| | - Francis A Farraye
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, 85 East Concord Street, Boston, MA, 02118, USA.
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Evidence-based consensus on opportunistic infections in inflammatory bowel disease (republication). Intest Res 2018; 16:178-193. [PMID: 29743831 PMCID: PMC5934591 DOI: 10.5217/ir.2018.16.2.178] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 04/08/2018] [Accepted: 04/16/2018] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) patients are a high-risk population for opportunistic infections. The IBD group of the Chinese Society of Gastroenterology of the Chinese Medical Association organized an expert group to discuss and develop this consensus opinion. This consensus opinion referenced clinical study results from China and other countries to provide guidance for clinical practices. Eight major topics, including cytomegalovirus infection, Epstein-Barr virus infection, viral hepatitis, bacterial infection, Mycobacterium tuberculosis infection, fungal infection, parasitic infection, and vaccines were introduced in this article.
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11
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Evidence-based consensus on opportunistic infections in inflammatory bowel disease. J Dig Dis 2018; 19:54-65. [PMID: 29330905 DOI: 10.1111/1751-2980.12578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/12/2018] [Indexed: 01/30/2023]
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12
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Incidence of Low Seroimmunity to Hepatitis B Virus in Children With Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2017; 65:551-554. [PMID: 28333769 DOI: 10.1097/mpg.0000000000001580] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
OBJECTIVES Patients with inflammatory bowel disease (IBD) often receive immunosuppressive therapy, which may make them vulnerable to infections such as hepatitis B. We hypothesized that hepatitis B virus titers are low in the vaccinated pediatric population with IBD. The aims of our study were to identify the incidence of lower titers of hepatitis B surface antibody (HBsAb) and determine which patient factors may be associated with lower HBsAb titers. METHODS Patients with diagnosis of IBD, ages 5 to 18 years, were prospectively enrolled. Patients were confirmed to have had a full series of hepatitis B vaccination. Quantitative serum HBsAb titers were measured and logistic regression analysis with independent variables of age, sex, race, disease phenotype, surgery, medications and a dependent variable of adequate HBsAb titers (> 10 mIU/mL) was performed. RESULTS Of the 116 patients enrolled, 57 were boys and 59 were girls. 75 patients had a diagnosis of Crohn disease; 32 had a diagnosis of ulcerative colitis; and 9 patients had been diagnosed as having indeterminate colitis. At the time of the study, 15 patients were taking corticosteroid, 66 on an immunomodulator, and 53 on a biologic. Sixty percent of patients in the 5- to 10-year age group had protective titers versus 22% to 27% in the older groups, P = 0.04. Only 28% of the 116 patients had HBsAb titers of >10m IU/mL. Twenty percent of the patients taking corticosteroids, 27% taking immunomodulators, and 24% taking biologics were found to be seroimmune. CONCLUSIONS Nearly two-thirds of pediatric patients with IBD have low titers against hepatitis B virus. Titers were highest in the younger patients. No patient-specific variable, such as the use of immunosuppressants, appeared to influence these low titers.
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13
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Chan HCH, Wong VWS, Wong GLH, Tang W, Wu JCY, Ng SC. Prevalence of hepatitis B and clinical outcomes in inflammatory bowel disease patients in a viral-endemic region. BMC Gastroenterol 2016; 16:100. [PMID: 27549153 PMCID: PMC4994386 DOI: 10.1186/s12876-016-0516-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 08/11/2016] [Indexed: 02/06/2023] Open
Abstract
Background Little is known of the prevalence of hepatitis B virus (HBV) infection and its effect on choice of therapy and disease course in patients with inflammatory bowel disease (IBD). We assessed the prevalence of HBV in Hong Kong as well as determinants of altered transaminases, effects of HBV infection on therapeutic strategy and clinical course in IBD. Methods In this retrospective cohort, hepatitis B surface antigen (HBsAg), liver function tests, and IBD disease characteristics were recorded. Logistic regression was used to identify factors associated with altered transaminases. Results Four hundred six IBD patients were recruited. HBV infection was found in 5.7 % patients in Hong Kong. The use of steroids (OR, 2.52; p = 0.010) and a previous history of surgery (OR 2.33; p = 0.026) were associated with altered transaminases in IBD. There was no significant difference in disease control and use of IBD medication between HBsAg-positive and HBsAg-negative IBD patients. Conclusion The prevalence of HBV among patients with IBD in Hong Kong (5.7 %) is similar to that of general population (~7 %). There was no difference in disease control and use of IBD medication between subjects with or without HBV.
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Affiliation(s)
- Heyson C H Chan
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, State Key Laboratory of Digestive Diseases, Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Vincent W S Wong
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, State Key Laboratory of Digestive Diseases, Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Grace L H Wong
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, State Key Laboratory of Digestive Diseases, Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Whitney Tang
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, State Key Laboratory of Digestive Diseases, Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Justin C Y Wu
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, State Key Laboratory of Digestive Diseases, Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, State Key Laboratory of Digestive Diseases, Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
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Andrisani G, Armuzzi A, Marzo M, Felice C, Pugliese D, Papa A, Guidi L. What is the best way to manage screening for infections and vaccination of inflammatory bowel disease patients? World J Gastrointest Pharmacol Ther 2016; 7:387-396. [PMID: 27602239 PMCID: PMC4986392 DOI: 10.4292/wjgpt.v7.i3.387] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Accepted: 06/16/2016] [Indexed: 02/07/2023] Open
Abstract
The use of biological agents and immunomodulators for inflammatory bowel disease (IBD) is associated with an increased risk of opportunistic infections, in particular of viral or bacterial etiology. Despite the existence of international guidelines, many gastroenterologists have not adopted routine screening and vaccination in those patients with IBD, which are candidate for biologic therapy. Available strategies to screen, diagnose and prevent bacterial and viral infections in patients with IBD prior to start biological therapy are discussed in this review.
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Andrade P, Santos-Antunes J, Rodrigues S, Lopes S, Macedo G. Treatment with infliximab or azathioprine negatively impact the efficacy of hepatitis B vaccine in inflammatory bowel disease patients. J Gastroenterol Hepatol 2015; 30:1591-5. [PMID: 25967740 DOI: 10.1111/jgh.13001] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/16/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Immunization against hepatitis B virus (HBV) infection is recommended in patients with inflammatory bowel disease (IBD), particularly in those under immunosuppressive therapy. Limited data are available about IBD patient's response to HBV vaccination. We assessed the response rate to HBV vaccination in IBD patients and evaluated the impact of different factors on the efficacy of HBV vaccination. METHODS Anti-HBs titers were measured in a cohort of IBD patients under treatment with infliximab and/or azathioprine. Vaccination was considered efficient when anti-HBs titers were higher than 10 IU/L. RESULTS We have identified 217 patients with IBD under infliximab who were vaccinated for hepatitis B, 172 (79%) with Crohn's Disease and the remaining with ulcerative colitis; 114 patients (53%) were male and mean age was 33 ± 11 years. Overall, HBV vaccine was successful in 164 (76%) patients. Only 14 patients were vaccinated after infliximab was initiated, and only two of them had antibody levels above 10 IU/L. Among the patients that received vaccination before the beginning of infliximab, 88% of those who were vaccinated before starting azathioprine developed antibodies in contrast to 55% who already were under azathioprine. In multivariable analysis, treatment with infliximab (adjusted OR [95% CI]: 17.642 [8.514-33.937]) and with azathioprine (adjusted OR [95% CI]: 3.344 [1.653-9.145]) were the only factors associated with weaker response to HBV vaccination. CONCLUSION The response rate to the standard HBV vaccination in IBD patients is low mainly in those treated with infliximab and/or azathioprine.
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Affiliation(s)
- Patrícia Andrade
- Gastroenterology Department, Faculty of Medicine, Hospital de São João, Porto, Portugal
| | - João Santos-Antunes
- Gastroenterology Department, Faculty of Medicine, Hospital de São João, Porto, Portugal.,Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Portugal
| | - Susana Rodrigues
- Gastroenterology Department, Faculty of Medicine, Hospital de São João, Porto, Portugal
| | - Susana Lopes
- Gastroenterology Department, Faculty of Medicine, Hospital de São João, Porto, Portugal
| | - Guilherme Macedo
- Gastroenterology Department, Faculty of Medicine, Hospital de São João, Porto, Portugal
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Impact of immunosuppressive therapy on hepatitis B vaccination in inflammatory bowel diseases. Eur J Gastroenterol Hepatol 2015; 27:877-81. [PMID: 26121376 DOI: 10.1097/meg.0000000000000370] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS The vaccination rate against hepatitis B virus (HBV) is low in inflammatory bowel disease (IBD) patients. The Consensus from the European Crohn's and Colitis Organisation on opportunistic infections recommends testing all IBD patients for HBV at diagnosis and vaccinating all HBV-negative patients. We compared the efficacy of HBV vaccine between IBD patients and healthy controls and investigated the impact of immunosuppressive therapy on vaccine response in IBD patients. MATERIALS AND METHODS IBD patients and healthy adult workers were vaccinated against HBV following a standard protocol (at 0, 1, and 6 months; Engerix B). The efficacy of vaccination was evaluated at 8 months by a titer of antibodies against hepatitis B surface antigen (anti-HBs). RESULTS Among 164 participants (96 with IBD and 68 healthy workers), the level of anti-HBs was greater than 10 IU/l in 80.2 and 94.1% (P=0.0115) of IBD patients and healthy controls, respectively, and anti-HBs levels greater than 100 IU/l were seen in 45.8 versus 77.9% (P<0.0001) of IBD patients and healthy controls, respectively. The median level of anti-HBs was significantly higher in healthy controls (497.0±386.2) than in IBD patients (253.9±34.5) (P<0.0001). None of the baseline characteristics of IBD patients, including immunomodulators and antitumor necrosis factor therapy, influenced the vaccine response. In the multivariate analysis, ileal disease was the only factor associated with a lower response to the vaccine (odds ratio=3.2; 95% confidence interval=1.0-9.7; P=0.049). CONCLUSION The response rate to HBV vaccination is significantly lower in IBD patients than in the general population. Immunosuppressive therapy for IBD did not influence the vaccine response.
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Cordero-Coma M, Salazar-Méndez R, Yilmaz T. Treatment of severe non-infectious uveitis in high-risk conditions (Part 2): systemic infections; management and safety issues. Expert Opin Drug Saf 2015; 14:1353-71. [PMID: 26118392 DOI: 10.1517/14740338.2015.1061992] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Management of patients with severe immune-mediated uveitis requires the use of immunosuppressive (IS) drugs in selected cases. This may be particularly challenging in certain patients with associated conditions, which may increase the risk of side effects or modify guidelines for the use of such drugs. Chronic viral and mycobacterial infections in the setting of non-infectious uveitis create a number of diagnostic but also therapeutic dilemmas to clinicians because they can be exacerbated by IS therapies with detrimental effects. AREAS COVERED In this review, we will focus on very specific chronic infections that can be affected by IS therapies: human immunodeficiency virus infection, chronic hepatitis virus infection and tuberculosis. The main aim of this review is to provide an updated and comprehensive practical guide for practitioners regarding the therapeutic decision-making and management of patients with non-infectious uveitis affected by the aforementioned infectious conditions. EXPERT OPINION Clinicians should be aware of the risk of viral and mycobacterial reactivation of an underlying infection during IS therapy. However, most of these conditions do not represent an absolute contraindication if one were able to apply an appropriate prior screening and close monitoring of such therapy.
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Affiliation(s)
- Miguel Cordero-Coma
- a 1 University of León, Instituto Biomedicina (IBIOMED), University Hospital of León , León, Spain +34 654403609 ; +34 987 233322 ;
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Kierkus J, Szymanska E, Oracz G, Wiernicka A, Dadalski M. Profile of infliximab in the treatment of pediatric Crohn's disease. PEDIATRIC HEALTH MEDICINE AND THERAPEUTICS 2015; 6:79-85. [PMID: 29388577 PMCID: PMC5683274 DOI: 10.2147/phmt.s64943] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
In recent years, a novel biologic therapy with monoclonal antibodies against tumor necrosis factor-alpha has revolutionized the treatment of Crohn’s disease. Infliximab, the first biologic agent, has been demonstrated to considerably improve both clinical and endoscopic outcomes. In view of the growing popularity of infliximab in the management of Crohn’s disease, we review the profile of the agent in the treatment of this disease in a pediatric setting.
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Affiliation(s)
- Jaroslaw Kierkus
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics
| | - Edyta Szymanska
- Department of Pediatrics, Nutrition and Metabolic Disorders, The Children's Memorial Health Institute, Warsaw, Poland
| | - Grzegorz Oracz
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics
| | - Anna Wiernicka
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics
| | - Maciej Dadalski
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics
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Cekic C, Aslan F, Kirci A, Gümüs ZZ, Arabul M, Yüksel ES, Vatansever S, Yurtsever SG, Alper E, Ünsal B. Evaluation of factors associated with response to hepatitis B vaccination in patients with inflammatory bowel disease. Medicine (Baltimore) 2015; 94:e940. [PMID: 26039133 PMCID: PMC4616368 DOI: 10.1097/md.0000000000000940] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
It is recommended to investigate the serology of hepatitis B virus (HBV) and vaccinate seronegative patients at the time of diagnosis in inflammatory bowel diseases (IBD). This study aimed to investigate the efficacy of HBV vaccine and factors affecting the response.In this retrospective, observational study, HBV-seronegative IBD patients were administered 3 doses (at months 0, 1, and 6) recombinant 20 μg HbsAg. Patients' demographics, IBD attributes, and treatment methods were investigated as the factors with potential impacts on vaccination outcomes.One hundred twenty-five patients with IBD were evaluated. The number of patients with Anti-HBs >10 IU/L was 71 (56.8%), and the number of patients with anti-HBs >100 IU/L was 50 (40%). Age, disease activity, Crohn disease subtype, and immunosuppressive treatment (IST) were found to have significant effects on immune response (P = 0.011, P < 0.001, P = 0.003, and P < 0.001, respectively). With multivariate analysis, age < 45 years (OR 3.1, 95% CI 1.2-8.3, P = 0.020), vaccination during remission (OR 5.6, 95% CI 2.3-14, P < 0.001), and non-IST (OR 11.1, 95% CI 2.9-43.2, P = 0.001) had favorable effects on the occurrence of adequate vaccine response.The likelihood of achieving adequate immune response with standard HBV vaccination protocol in IBD is low. Selecting vaccination protocols with more potent immunogenicity is a better approach to achieve effective vaccine response in patients with multiple unfavorable factors.
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Affiliation(s)
- Cem Cekic
- From the Department of Gastroenterology, Katip Celebi University, Atatürk Training and Research Hospital (CC, FA, MA, ESY, SV, SG, EA, BÜ); Department of Gastroenterology, Şifa University, Faculty of Medicine (AK); Department of Internal Medicine (ZZG); and Department of Medical Microbiology, Katip Celebi University, Atatürk Training and Research Hospital, İzmir, Turkey (SGY)
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Cao Y, Zhao D, Xu AT, Shen J, Ran ZH. Effects of immunosuppressants on immune response to vaccine in inflammatory bowel disease. Chin Med J (Engl) 2015; 128:835-8. [PMID: 25758282 PMCID: PMC4833992 DOI: 10.4103/0366-6999.152683] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVE To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants). DATA SOURCES We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators). The following terms were used: "inflammatory bowel disease (IBD)" OR "Crohn's disease" OR "ulcerative colitis" AND ("vaccination" OR "vaccine") AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]") AND "immunomodulators." STUDY SELECTION The inclusion criteria of articles were that the studies: (1) Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical, radiographic, endoscopic, and histologic criteria); (2) exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping, 15 mg or more MTX per week or within 3 months of stopping; (3) exposed patients received nonimmunomodulators (no therapy, antibiotics only, mesalazine only, biological agent only such as infliximab, adalimumab, certolizumab or natalizumab or within 3 months of stopping one of these agents). The exclusion criteria of articles were that the studies: (1) History of hepatitis B virus (HBV), influenza or streptococcus pneumoniae infection; (2) patients who had previously been vaccinated against HBV, influenza or streptococcus pneumoniae; (3) any medical condition known to cause immunosuppression (e.g. chronic renal failure and human immunodeficiency virus infection); (4) individuals with positive hepatitis markers or liver cirrhosis; (5) patients with a known allergy to eggs or other components of the vaccines and (6) pregnancy. RESULTS Patients treated with immunomodulators were associated with lower response rates to vaccination. CONCLUSIONS Immunomodulators may impair the immune response to vaccination in patients with IBD. Vaccination should be made at the time of diagnosis or before starting immunosuppressed therapy.
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Affiliation(s)
- Yuan Cao
- Division of Gastroenterology and Hepatology, School of Medicine, Shanghai Jiaotong University, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai 200001, China
| | - Di Zhao
- Division of Gastroenterology and Hepatology, School of Medicine, Shanghai Jiaotong University, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai 200001, China
| | - An-Tao Xu
- Division of Gastroenterology and Hepatology, School of Medicine, Shanghai Jiaotong University, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai 200001, China
| | - Jun Shen
- Division of Gastroenterology and Hepatology, School of Medicine, Shanghai Jiaotong University, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai 200001, China
| | - Zhi-Hua Ran
- Division of Gastroenterology and Hepatology, School of Medicine, Shanghai Jiaotong University, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai 200001, China
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Cossio-Gil Y, Martínez-Gómez X, Campins-Martí M, Rodrigo-Pendás JÁ, Borruel-Sainz N, Rodríguez-Frías F, Casellas-Jordà F. Immunogenicity of hepatitis B vaccine in patients with inflammatory bowel disease and the benefits of revaccination. J Gastroenterol Hepatol 2015; 30:92-8. [PMID: 25160690 DOI: 10.1111/jgh.12712] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/12/2014] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM The vaccination against hepatitis B virus (HBV) is recommended in patients with inflammatory bowel disease (IBD). However, the response to this vaccine seems to be lower in IBD patients than in the general population. This study aims to evaluate the immunogenicity of the HBV vaccine in a cohort of patients with IBD, to associate factors with the response and to analyze the effects of a second schedule vaccination. METHODS We conducted a retrospective cohort study of adults with IBD, susceptible to HBV infection. All patients received a three-dose standard schedule of HBV vaccine. Non-responders were revaccinated with a second three-dose standard schedule. Adequate immunity to HBV was defined as antibodies against hepatitis B surface antigen (anti-HBs) ≥ 10 mIU/mL. Age, comorbidities, treatment, and other variables were collected. RESULTS One hundred seventy-two patients were included and received the first HBV vaccine schedule. Eighty-seven developed anti-HBs ≥ 10 mIU/mL (50.6%; 95% confidence interval [CI]: 42.9-58.3). From the non-responders, 53 were revaccinated and 28 showed an adequate serological response (52.8%; 95% CI: 38.6-66.7). Age older than 55 years (OR: 3.6; 95% CI: 1.3-10.2) and comorbidities (OR: 2.8; 95% CI: 1.1-7.1) were associated with suboptimal response. In the multivariate analysis, only age was a predictor of non-response (age higher than 55 years; OR: 3.9; 95% CI: 1.3-11.9) CONCLUSION: The response rate to the HBV vaccine is lower in patients with IBD compared with the general population, especially in those older than 55 years. Revaccination improved response rate by 50%.
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Affiliation(s)
- Yolima Cossio-Gil
- Department of Preventive Medicine and Epidemiology, Hospital Universitari Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain
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Ben Musa R, Gampa A, Basu S, Keshavarzian A, Swanson G, Brown M, Abraham R, Bruninga K, Losurdo J, DeMeo M, Mobarhan S, Shapiro D, Mutlu E. Hepatitis B vaccination in patients with inflammatory bowel disease. World J Gastroenterol 2014; 20:15358-15366. [PMID: 25386085 PMCID: PMC4223270 DOI: 10.3748/wjg.v20.i41.15358] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2013] [Revised: 05/31/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the prevalence for hepatitis B virus (HBV) and HBV screening and vaccination practices for inflammatory bowel disease (IBD).
METHODS: This study is a retrospective, cross-sectional observational study. A retrospective chart review was performed in 500 patients who have been consecutively treated for IBD between September 2008 and January 2013 at the Rush University Medical Center Gastroenterology section. The patients were identified through the electronic medical record with the criteria that they attended the gastroenterology clinic, and that they had a diagnosis of IBD at the time of visit discharge. Once identified, each record was analyzed to determine whether the subject had been infected with HBV in the past, already been vaccinated against HBV, or advised to get vaccinated and followed through with the recommended vaccination.
RESULTS: About 254 out of 500 patients (51%) had HBV screening ordered. Among those ordered to have screening tests, 86% followed through with HBV serology. Gastroenterology physicians had significantly different screening ratios from each other (P < 0.001). There were no significant differences in the ratios of HBV screening when IBD specialists were compared to other gastroenterology physicians (0.505 ± 0.023 vs 0.536 ± 0.066, P = 0.66). Of those 220 patients screened, 51% of IBD patients were found not to be immune against HBV. Approximately 50% of gastroenterology physicians recommended HBV vaccinations to their patients in whom serology was negative for antibodies against HBV. IBD specialists recommended vaccinations to a higher percentage of their patients compared to other gastroenterology physicians (0.168 ± 0.019 vs 0.038 ± 0.026, P = 0.015). Present and/or past HBV infection was found in 3.6% of the patients who had serology checked. There was no statistically significant difference in the prevalence of hepatitis B surface antigen (HBsAg) between our study and that reported in previous studies done in Spain (4/220 vs 14/2076 respectively, P = 0.070); and in France (4/220 vs 3/315 respectively, P = 0.159). But, the prevalence of anti-HBcAb in this study was less than that reported in the study in Spain (7/220 vs 155/2076 respectively, P = 0.006); and was not significantly different from that reported in the study in France (7/220 vs 8/315 respectively, P = 0.313).
CONCLUSION: The prevalence of HBsAg in our IBD patients was not higher than previously reported European studies. Most IBD patients are not routinely screened or vaccinated against HBV at a tertiary referral center in the United States.
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Approach and management of patients with chronic hepatitis B and C during the course of inflammatory bowel disease. Inflamm Bowel Dis 2014; 20:2142-50. [PMID: 25072501 DOI: 10.1097/mib.0000000000000126] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease and chronic viral hepatitis are 2 distinct but common conditions throughout the world. Mostly, both need life-long follow-up. Since immunosuppressive drugs remain corner stones of inflammatory bowel disease management, one should be aware of the concomitant presence of chronic viral hepatitis in such patients to prevent serious (even fatal) outcomes. Recently, new treatment options have become available in the treatment of both inflammatory bowel disease and chronic viral hepatitis. In this review, we have discussed and summarized current treatment and follow-up strategies for those 2 important public health issues in light of available literature.
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Abstract
Patients with inflammatory bowel diseases (IBDs) may present with several hepatic abnormalities. Some of these liver diseases are benign and only require observation, whereas others may cause liver failure and require liver transplantation. The aim of this review was to present and summarize the latest evidence on the most common liver diseases seen in patients with IBD. These manifestations can be divided in to 3 groups: those that are seen in association with IBD, those that are due to metabolic and physiologic changes induced by the IBD and those that are secondary to the drugs used in the treatment of IBD. Primary sclerosing cholangitis is one of the most common hepatobiliary manifestations of IBD that is more prevalent in patients with ulcerative colitis. There is no approved medical treatment for primary sclerosing cholangitis and about 50% of patients will require liver transplantation within 10 to 15 years from the time of diagnosis. Among the drugs that are commonly used in the treatment of IBD, thiopurines and methotrexate impose the higher risk of hepatotoxicity. In most cases, dose adjustment and avoidance of hepatotoxins will normalize the liver tests and discontinuation of the drug is required in a minority of cases. Reactivation of hepatitis B virus during immunosuppressive therapy is a major concern and adequate screening and vaccination is warranted. The approach to a patient with IBD who presents with abnormal liver chemistries can be challenging not only because 2 or more conditions can co-exist but also because management must be individualized.
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25
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Mill J, Lawrance IC. Preventing infective complications in inflammatory bowel disease. World J Gastroenterol 2014; 20:9691-9698. [PMID: 25110408 PMCID: PMC4123359 DOI: 10.3748/wjg.v20.i29.9691] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Accepted: 04/23/2014] [Indexed: 02/06/2023] Open
Abstract
Over the past decade there has been a dramatic change in the treatment of patients with Crohn’s disease and ulcerative colitis, which comprise the inflammatory bowel diseases (IBD). This is due to the increasing use of immunosuppressives and in particular the biological agents, which are being used earlier in the course of disease, and for longer durations, as these therapies result in better clinical outcomes for patients. This, however, has the potential to increase the risk of opportunistic and serious infections in these patients, most of which are preventable. Much like the risk for potential malignancy resulting from the use of these therapies long-term, a balance needs to be struck between medication use to control the disease with minimization of the risk of an opportunistic infection. This outcome is achieved by the physician’s tailored use of justified therapies, and the patients’ education and actions to minimize infection risk. The purpose of this review is to explore the evidence and guidelines available to all physicians managing patients with IBD using immunomodulating agents and to aid in the prevention of opportunistic infections.
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Mukhopadhyay A, Maulik U. Network-based study reveals potential infection pathways of hepatitis-C leading to various diseases. PLoS One 2014; 9:e94029. [PMID: 24743187 PMCID: PMC3990553 DOI: 10.1371/journal.pone.0094029] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Accepted: 03/11/2014] [Indexed: 12/17/2022] Open
Abstract
Protein-protein interaction network-based study of viral pathogenesis has been gaining popularity among computational biologists in recent days. In the present study we attempt to investigate the possible pathways of hepatitis-C virus (HCV) infection by integrating the HCV-human interaction network, human protein interactome and human genetic disease association network. We have proposed quasi-biclique and quasi-clique mining algorithms to integrate these three networks to identify infection gateway host proteins and possible pathways of HCV pathogenesis leading to various diseases. Integrated study of three networks, namely HCV-human interaction network, human protein interaction network, and human proteins-disease association network reveals potential pathways of infection by the HCV that lead to various diseases including cancers. The gateway proteins have been found to be biologically coherent and have high degrees in human interactome compared to the other virus-targeted proteins. The analyses done in this study provide possible targets for more effective anti-hepatitis-C therapeutic involvement.
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Affiliation(s)
- Anirban Mukhopadhyay
- Department of Computer Science and Engineering, University of Kalyani, Kalyani, West Bengal, India
- * E-mail:
| | - Ujjwal Maulik
- Department of Computer Science and Engineering, Jadavpur University, Kolkata, West Bengal, India
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Sansone S, Guarino M, Castiglione F, Rispo A, Auriemma F, Loperto I, Rea M, Caporaso N, Morisco F. Hepatitis B and C virus reactivation in immunosuppressed patients with inflammatory bowel disease. World J Gastroenterol 2014; 20:3516-3524. [PMID: 24707134 PMCID: PMC3974518 DOI: 10.3748/wjg.v20.i13.3516] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 12/13/2013] [Accepted: 03/06/2014] [Indexed: 02/06/2023] Open
Abstract
In recent years, a number of case reports and clinical studies have highlighted the risk of hepatitis B and C virus reactivation in patients with inflammatory bowel disease who are treated with immunosuppressive drugs. The cases of viral hepatitis reactivation that have been reported are characterized by a wide range of clinical manifestations, from viremia without clinically relevant manifestations to fulminant life-threatening hepatitis. The development and dissemination of biological immunosuppressive drugs have led to a significant increase in the number of reports of interest to physicians in a variety of clinical settings. On this topic, there have been a number of published guidelines and reviews that have collected the available evidence, providing recommendations on prophylactic and therapeutic strategies and methods for monitoring patients at risk. However, it should be noted that, to date, very few clinical studies have been published, and most of the recommendations have been borrowed from other clinical settings. The published studies are mostly retrospective and are based on very heterogeneous populations, using different therapeutic and prophylactic regimens and obtaining conflicting results. Thus, it seems clear that it is desirable to concentrate our efforts on prospective studies, not conducting further reviews of the literature in the continued absence of new evidence.
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Yokoyama Y, Fukunaga K, Kamikozuru K, Sato T, Kawai M, Nogami K, Nagase K, Nakamura M, Immured M, Hida N, Nakamura S. Crohn's disease complicated by hepatitis B virus successfully treated with the use of adsorptive depletion of myeloid lineage leucocytes to suppress inflammatory cytokine profile. Cytotherapy 2014; 16:821-5. [PMID: 24713332 DOI: 10.1016/j.jcyt.2014.01.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 01/10/2014] [Accepted: 01/13/2014] [Indexed: 01/26/2023]
Abstract
BACKGROUND AIMS In patients with inflammatory bowel disease infected with hepatitis B virus (HBV), immunosuppressive therapy required to suppress active inflammatory bowel disease may promote HBV reactivation. METHODS A 27-year-old corticosteroid-naive woman with Crohn's disease (CD) activity index of 249.8 complicated by HBV infection was offered Entecavir to control HBV reactivation during immunosuppressive therapy for CD. The patient refused Entecavir, fearing that it might adversely affect her pregnancy outcome. Instead, we applied intensive granulocyte/monocyte adsorptive apheresis (GMA) at two sessions per week to deplete inflammatory cytokine-producing leucocytes as an immunosuppressive therapy in this case. RESULTS GMA induced stable remission (CD activity index, I 105) and endoscopic improvement without HBV reactivation or safety concern. Furthermore, CD remission was paralleled by suppression of tumor necrosis factor and interleukin as measured in serum samples. CONCLUSIONS Immunosuppressive therapy required to treat an active CD potentially can promote HBV reactivation and worsen liver function. In this study involving a CD case complicated by chronic HBV infection, intensive GMA as a non-pharmacologic treatment intervention was associated with clinical remission and endoscopic improvement without HBV reactivation. Furthermore, GMA was well-tolerated and was without any safety concern. However, suppression of tumor necrosis and interleukin-6by GMA in this clinical setting is potentially very interesting.
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Affiliation(s)
- Yoko Yokoyama
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
| | - Ken Fukunaga
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Koji Kamikozuru
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Toshiyuki Sato
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Mikio Kawai
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Koji Nogami
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Kazuko Nagase
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Misaki Nakamura
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Masaki Immured
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Nobuyuki Hida
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Shiro Nakamura
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
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Abstract
Crohn's disease and ulcerative colitis affect an increasing number of patients. A variety of medical options exist for the treatment of these diseases including immune suppressants and biologic therapies. Unfortunately, these agents are associated with adverse events ranging from mild nuisance symptoms to potentially life-threatening complications including infections and malignancies. This review discusses adverse events associated with azathioprine, mercaptopurine, and methotrexate as well as anti-TNF-α and anti-integrin antibodies. In addition, adverse events associated with combination therapy are discussed as are clinical scenarios in which it may be reasonable to discontinue or de-escalate drug therapy. It is the responsibility of the treating gastroenterologist to effectively communicate the benefits and risks of therapy with patients; this review offers strategies that may assist providers in communicating risk with patients in addition to offering our perspective on whether modification or cessation of therapy can be considered.
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Affiliation(s)
- Leon P McLean
- Department of Medicine, Division of Gastroenterology and Hepatology University of Maryland, 100 North Greene Street, Lower Level, Baltimore, MD 21201, USA
| | - Raymond K Cross
- Department of Medicine, Division of Gastroenterology and Hepatology University of Maryland, 100 North Greene Street, Lower Level, Baltimore, MD 21201, USA
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González-Artacho C, Rodríguez Sicilia MJ, Alegría-Motte C, Gómez García M. [Outcome of chronic hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive drugs and anti-TNF agents]. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 37:23-24. [PMID: 24094622 DOI: 10.1016/j.gastrohep.2013.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Revised: 07/17/2013] [Accepted: 07/19/2013] [Indexed: 06/02/2023]
Affiliation(s)
| | | | - Carlos Alegría-Motte
- Servicio de Aparato Digestivo, Hospital Universitario Virgen de las Nieves, Granada
| | - María Gómez García
- Servicio de Aparato Digestivo, Hospital Universitario Virgen de las Nieves, Granada
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Role of the Nrf2-ARE pathway in liver diseases. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2013; 2013:763257. [PMID: 23766860 PMCID: PMC3665261 DOI: 10.1155/2013/763257] [Citation(s) in RCA: 138] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2012] [Accepted: 04/12/2013] [Indexed: 12/14/2022]
Abstract
The liver is a central organ that performs a wide range of functions such as detoxification and metabolic homeostasis. Since it is a metabolically active organ, liver is particularly susceptible to oxidative stress. It is well documented that liver diseases including hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma are highly associated with antioxidant capacity. NF-E2-related factor-2 (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. It is activated in response to electrophiles and induces its target genes by binding to the antioxidant response element (ARE). Therefore, the roles of the Nrf2-ARE pathway in liver diseases have been extensively investigated. Studies from several animal models suggest that the Nrf2-ARE pathway collectively exhibits diverse biological functions against viral hepatitis, alcoholic and nonalcoholic liver disease, fibrosis, and cancer via target gene expression. In this review, we will discuss the role of the Nrf2-ARE pathway in liver pathophysiology and the potential application of Nrf2 as a therapeutic target to prevent and treat liver diseases.
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Abstract
Patients with IBD are at increased risk of infection, in part owing to the disease itself, but mostly because of treatment with immunosuppressive drugs. Although many of these infections are vaccine-preventable, vaccination coverage in patients with IBD is extremely low. The vaccine strategies examined in this Review are based on data that enable us to provide practical advice for clinicians. Clinical evidence indicates that vaccines do not increase the risk of relapse in patients with IBD. Live vaccines are contraindicated in immunocompromised individuals, but inactivated vaccines can be safely administered. Most patients receiving immunosuppressive therapy develop an immune response after vaccination, but response rates might differ from those of nonimmunosuppressed individuals. Therefore, vaccination status should be checked and updated upon diagnosis of IBD.
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Immunogenecity of hepatitis A and B vaccination in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2013; 56:412-15. [PMID: 23841120 DOI: 10.1097/mpg.0b013e31827dd87d] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Aim of the study was to evaluate the response to hepatitis A and B vaccination in pediatric patients with inflammatory bowel disease (IBD). METHODS A total of 47 patients with IBD (25 ulcerative colitis, 14 Crohn's disease, and 8 indeterminate colitis) ages 3 to 17 years were compared with 50 healthy age- and sex-matched controls. Screening for hepatitis A and B serology was carried out before vaccination. Susceptible cases received 20 mg of recombinant DNA vaccine for hepatitis B (0, 1, and 6 months)and 720 milliELISA units of inactivated hepatitis A virus vaccine (HAV) (0 and 6 months). Postvaccination serologic evaluation was performed 1 month after the last dose of primary vaccination, 1 month after the booster dose, and once every year during follow-up. RESULTS A total of 23 patients and 35 controls received HAV and protective anti-HAV antibodies were developed in all of the patients and controls (P =1.00). Forty-seven patients and 50 controls received hepatitis B vaccine and 70.2% of the patients versus 90% of the controls achieved seroprotection(anti-HBs titers 10 mIU/mL) 1 month after primary vaccination (95% confidence interval 0.71–0.87, P = 0.02). The overall seroprotection rates were 96% in controls and 85.1% in patients after the whole hepatitis B vaccination series (95% confidence interval 0.83–0.95, P = 0.08). No significant reduction was observed in antibody response among patients and controls during the follow-up period. CONCLUSIONS The rate of seroconversion to the hepatitis B vaccine was lower in pediatric patients with IBD than in healthy controls and hepatitis A vaccine was highly immunogenic among patients with IBD.
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López-Serrano P, Pérez-Calle JL, Sánchez-Tembleque MD. Hepatitis B and inflammatory bowel disease: Role of antiviral prophylaxis. World J Gastroenterol 2013; 19:1342-8. [PMID: 23538480 PMCID: PMC3602492 DOI: 10.3748/wjg.v19.i9.1342] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2012] [Revised: 08/22/2012] [Accepted: 08/25/2012] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is a very common infection worldwide. Its reactivation in patients receiving immunosuppression has been widely described as being associated with significant morbidity and mortality unless anti-viral prophylaxis is administered. Treatment in inflammatory bowel disease (IBD) patients has changed in recent years and immunosuppression and biological therapies are now used more frequently than before. Although current studies have reported an incidence of hepatitis B in inflammatory bowel disease patients similar to that in the general population, associated liver damage remains an important concern in this setting. Liver dysfunction may manifest in several ways, from a subtle change in serum aminotransferase levels to fulminant liver failure and death. Patients undergoing double immunosuppression are at a higher risk, and reactivation usually occurs after more than one year of treatment. As preventive measures, all IBD patients should be screened for HBV markers at diagnosis and those who are positive for the hepatitis B surface antigen should receive antiviral prophylaxis before undergoing immunosuppression in order to avoid HBV reactivation. Tenofovir/entecavir are preferred to lamivudine as nucleos(t)ide analogues due to their better resistance profile. In patients with occult or resolved HBV, viral reactivation does not appear to be a relevant issue and regular DNA determination is recommended during immunosuppression therapy. Consensus guidelines on this topic have been published in recent years. The prevention and management of HBV infection in IBD patients is addressed in this review in order to address practical recommendations
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Sánchez-Tembleque MD, Corella C, Pérez-Calle JL. Vaccines and recommendations for their use in inflammatory bowel disease. World J Gastroenterol 2013; 19:1354-8. [PMID: 23538680 PMCID: PMC3602494 DOI: 10.3748/wjg.v19.i9.1354] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2012] [Revised: 08/21/2012] [Accepted: 09/19/2012] [Indexed: 02/06/2023] Open
Abstract
The patient with inflammatory bowel disease will be predisposed to numerous infections due their immune status. It is therefore important to understand the immune and serologic status at diagnosis and to put the patient into an adapted vaccination program. This program would be applied differently according to two patient groups: the immunocompromised and the non-immunocompromised. In general, the first group would avoid the use of live-virus vaccines, and in all cases, inflammatory bowel disease treatment would take precedence over vaccine risk. It is important to individualize vaccination schedules according to the type of patient, the treatment used and the disease pattern.In addition, patient with inflammatory bowel disease should be considered for the following vaccines: varicella vaccine, human papilloma virus, influenza, pneumococcal polysaccharide vaccine and hepatitis B vaccine.
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36
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Kinetics of anti-hepatitis B surface antigen titers after hepatitis B vaccination in patients with inflammatory bowel disease. Inflamm Bowel Dis 2013; 19:554-8. [PMID: 23380936 DOI: 10.1097/mib.0b013e31827febe9] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Clinically significant hepatitis B (HB) virus infection has been documented among immunocompromised patients who do not maintain anti-hepatitis surface antigen (anti-HBs) concentrations ≥ 10 IU/L after an adequate response to the vaccine. The aims of the study were to understand the kinetics of anti-HBs titers over time in patients with inflammatory bowel disease (IBD) who initially responded to vaccination and to identify factors predictive of losing protective anti-HBs titers. METHODS Patients with IBD with a response (anti-HBs > 10 IU/L at 1-3 months) to HB virus vaccination were prospectively included. Anti-HBs titers were measured at 6 and 12 months. Anti-HBs titers were considered negative if they were <10 IU/L at any time during the follow-up. The kinetics of anti-HBs titers in the long term was estimated using Kaplan-Meier curves. Cox regression analysis was performed to identify the factors predictive of losing protective anti-HBs titers. RESULTS The sample comprised 100 patients (mean age, 42 years; 68% Crohn's disease; 49% on thiopurines; and 14% on anti-tumor necrosis factors during follow-up). The cumulative incidence of loss of anti-HBs titers was 2% after 6 months and 15% after 12 months. The incidence rate of loss of protective anti-HBs titers was 18% per patient-year. Baseline (after vaccination) anti-HBs titers were lower among patients whose titers became negative during the follow-up than among those who maintained them >10 IU/L (191 versus 515 IU/L; P < 0.001). Treatment with anti-TNFs was the only factor associated with a higher risk of loss of anti-HBs (hazard ratio = 3.1; 95% confidence interval = 1.1-8.8; P = 0.03). CONCLUSIONS A high proportion of patients with IBD with protective anti-HBs titers after vaccination lose them over time (18% per patient-year of follow-up). The risk of losing protective anti-HBs titers is 3-fold higher among patients on anti- tumor necrosis factors therapy.
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37
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38
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Papa A, Felice C, Marzo M, Andrisani G, Armuzzi A, Covino M, Mocci G, Pugliese D, De Vitis I, Gasbarrini A, Rapaccini GL, Guidi L. Prevalence and natural history of hepatitis B and C infections in a large population of IBD patients treated with anti-tumor necrosis factor-α agents. J Crohns Colitis 2013; 7:113-9. [PMID: 22464811 DOI: 10.1016/j.crohns.2012.03.001] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Revised: 03/02/2012] [Accepted: 03/04/2012] [Indexed: 12/22/2022]
Abstract
BACKGROUND The prevalence rates of hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients with inflammatory bowel disease (IBD) have been reported to be higher than rates of infection among the general population. Although several cases of HBV infection reactivation in IBD patients treated with anti-TNF-α agents have been described, no evidence exists that anti-TNF-α therapy exacerbates the course of HCV. The aims of this study were to assess the prevalence of HBV and HCV and the rate of HBV vaccination in a population of IBD patients; and to investigate the long-term effects of anti-TNF-α therapy in the subgroup with HBV or HCV infections. METHODS 301 patients were studied. Prior to the initiation of anti-TNF-α therapy, serum samples were tested for HBsAg and anti-HBc, anti-HBs and anti-HCV antibodies. During the follow-up, HBsAg and anti-HBc positive patients underwent periodic blood testing for viral markers, HBV-DNA and liver function; anti-HCV positive patients were assessed for liver function and HCV-RNA. RESULTS One patient was HBsAg positive (0.3%), and 22 (7.3%) tested positive for anti-HBc. Seventy-two patients (23.9%) had been vaccinated for HBV. Four patients tested positive for anti-HCV (1.3%). During anti-TNF-α therapy, none of the patients experienced HBV or HCV reactivation. CONCLUSIONS HBV and HCV infection rates were similar to infection rates among the general population. Less than one quarter of the patients had been vaccinated against HBV. Anti-TNF-α agents appear to be safe for patients with HBV infection; more data are needed for patients with HCV infection.
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Affiliation(s)
- Alfredo Papa
- Internal Medicine and Gastroenterology, Catholic University of Rome, Italy.
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Abreu NA, Nagalingam NA, Song Y, Roediger FC, Pletcher SD, Goldberg AN, Lynch SV. Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. Sci Transl Med 2013; 4:151ra124. [PMID: 22972842 DOI: 10.1126/scitranslmed.3003783] [Citation(s) in RCA: 311] [Impact Index Per Article: 25.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Persistent mucosal inflammation and microbial infection are characteristics of chronic rhinosinusitis (CRS). Mucosal microbiota dysbiosis is found in other chronic inflammatory diseases; however, the relationship between sinus microbiota composition and CRS is unknown. Using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, we demonstrate that the sinus microbiota of CRS patients exhibits significantly reduced bacterial diversity compared with that of healthy controls. In our cohort of CRS patients, multiple, phylogenetically distinct lactic acid bacteria were depleted concomitant with an increase in the relative abundance of a single species, Corynebacterium tuberculostearicum. We recapitulated the conditions observed in our human cohort in a murine model and confirmed the pathogenic potential of C. tuberculostearicum and the critical necessity for a replete mucosal microbiota to protect against this species. Moreover, Lactobacillus sakei, which was identified from our comparative microbiome analyses as a potentially protective species, defended against C. tuberculostearicum sinus infection, even in the context of a depleted sinus bacterial community. These studies demonstrate that sinus mucosal health is highly dependent on the composition of the resident microbiota as well as identify both a new sino-pathogen and a strong bacterial candidate for therapeutic intervention.
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Affiliation(s)
- Nicole A Abreu
- Department of Biology, San Francisco State University, Hensill 534, 1600 Holloway Avenue, San Francisco, CA 94132, USA.,Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Nabeetha A Nagalingam
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Yuanlin Song
- Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Frederick C Roediger
- Department of Otolaryngology - Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Steven D Pletcher
- Department of Otolaryngology - Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Andrew N Goldberg
- Department of Otolaryngology - Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Susan V Lynch
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
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Shakya N, Vedi S, Liang C, Agrawal B, Tyrrell DL, Kumar R. A new class of pyrimidine nucleosides: inhibitors of hepatitis B and C viruses. Bioorg Med Chem Lett 2012; 22:6475-80. [PMID: 22985854 DOI: 10.1016/j.bmcl.2012.08.042] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2012] [Revised: 08/03/2012] [Accepted: 08/13/2012] [Indexed: 01/09/2023]
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health threats worldwide leading to liver cirrhosis, liver cancer and mortality. Herein, we report a new category of dideoxy pyrimidine nucleosides possessing a 4'-carboxyl (or carboxymethyl) function (7-9, 13, 16, 17), which are discovered as potential antiviral agents. For the first time, these nucleosides are recognized to be inhibitors of HBV and/or HCV replication. Among 4'-carboxy compounds, 3',4'-didehydrothymidine (16) was most effective against DHBV, HBV and HCV. Modification of the 4'-position in compound 7 from a carboxyl to carboxymethyl group (17) did not affect the anti-HBV activity but greatly increased the anti-HCV activity. Importantly, 17 yielded synergistic antiviral effect when combined with ribavirin without toxicity. The activity exhibited by a single agent towards both hepatitis viruses and no detectable in vitro cytotoxicity make this new class of compounds of interest.
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Affiliation(s)
- Neeraj Shakya
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
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Gisbert JP, Villagrasa JR, Rodríguez-Nogueiras A, Chaparro M. Efficacy of hepatitis B vaccination and revaccination and factors impacting on response in patients with inflammatory bowel disease. Am J Gastroenterol 2012; 107:1460-6. [PMID: 23034605 DOI: 10.1038/ajg.2012.79] [Citation(s) in RCA: 107] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES We assessed the effectiveness of hepatitis B virus (HBV) vaccine in inflammatory bowel disease (IBD) patients, evaluated the impact of immunosuppressors and anti-tumor necrosis factor (anti-TNF) agents, and assessed the effectiveness of revaccination. METHODS IBD patients were vaccinated against HBV with a quick (0, 1, and 2 months) and double-dose schedule (Engerix B). A second vaccination was administered to nonresponders. RESULTS Of 241 vaccinated patients, anti-HBs was >10 IU/l in 59% and >100 IU/l in 39%. The response rate (anti-HBs >10 IU/l) was lower among patients under anti-TNF therapy: 46% vs. 62%. In the multivariate analysis, a lower response rate was demonstrated in older patients and those receiving anti-TNFs. The response rate (anti-HBs >100 IU/l) after revaccination was 42%. CONCLUSIONS The response rate to the HBV vaccination--even with a double-dose schedule--is very low in IBD patients, mainly in those receiving anti-TNFs. However, treatment with immunosuppressors did not affect the efficacy of the vaccine. A considerable--albeit insufficient--success rate may be obtained when two consecutive vaccination courses, each with a three-dose vaccine series, are administered.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
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Gisbert JP, Menchén L, García-Sánchez V, Marín I, Villagrasa JR, Chaparro M. Comparison of the effectiveness of two protocols for vaccination (standard and double dosage) against hepatitis B virus in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2012; 35:1379-85. [PMID: 22530631 DOI: 10.1111/j.1365-2036.2012.05110.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2012] [Revised: 03/24/2012] [Accepted: 04/04/2012] [Indexed: 12/15/2022]
Abstract
BACKGROUND The response rate to hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) is low. AIM To compare two vaccination protocols-the standard dose and the double dose-in IBD patients. METHODS Patients diagnosed with IBD from three tertiary hospitals were vaccinated against HBV with two different protocols: the standard protocol (Engerix-B single dose at 0, 1 and 6 months) and the new faster protocol based on a double dose (Engerix B double dose at 0, 1 and 2 months). Anti-HBs titres were measured 1-3 months after the last dose. A multivariate analysis was performed to identify factors that were predictive of response to the vaccine. RESULTS The study sample comprised 148 patients (mean age 40 years, 69% Crohn's disease), 70% of whom were receiving immunosuppressive therapy (22% thiopurines, 23% anti-TNF and 25% both). The standard protocol was followed in 46% of patients and the double dose protocol in 54%. Considering anti-HBs >10 IU/L as a successful response to vaccination, the seroconversion rate was higher among patients vaccinated with the double dose than with the standard dose: 75% (95% CI, 65-85%) vs. 41% (95% CI, 29-54%) (P < 0.001). In the multivariate analysis, vaccination with the double dose was the only factor associated with a better response to the vaccine (OR, 4; 95% CI, 2-8; P < 0.001). CONCLUSIONS The response rate to the HBV vaccination in IBD patients is low. Administration of a double dose was associated with a higher response rate. Therefore, the double dose protocol could be a suitable option in patients with IBD.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
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Abstract
The management of chronic hepatitis B virus (HBV) infection requires understanding the natural history of the disease as well as the risks, benefits, and limitations of the therapeutic options. This article covers the principles governing when to start antiviral therapy, discusses recent advances using hepatitis B surface antigen quantification to better define various phases of infection, describes the use of HBV core, precore, and viral genotyping as well as host IL28B genotyping to predict response to interferon therapy, and reports on the management of HBV in 3 special populations (pregnancy, postliver transplantation, and in the setting of chemotherapy or immunosuppression).
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Affiliation(s)
- Alexander Kuo
- Division of Gastroenterology, University of California, San Diego, 92103, USA.
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Abstract
Inflammatory bowel disease affects an increasing number of patients worldwide and is associated with significant morbidity. The dysregulation of the immune system with increased expression of proinflammatory cytokines and increased mucosal expression of vascular adhesion molecules play an important role in its pathogenesis. Strategies targeting TNF-alpha and alpha4-integrin have led to the development of novel therapies for treatment of patients with IBD. This article discusses the efficacy of immunologic agents currently approved for treating Crohn disease and ulcerative colitis and reviews the risks and challenges associated with their use.
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Affiliation(s)
- Jatinder P Ahluwalia
- Gastroenterology Clinic of Acadiana and Lafayette General Medical Center, Lafayette, LA, USA.
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Louis E, Baumgart DC, Ghosh S, Gomollón F, Hanauer S, Hart A, Irving P. What changes in inflammatory bowel disease management can be implemented today? J Crohns Colitis 2012; 6 Suppl 2:S260-7. [PMID: 22463933 DOI: 10.1016/s1873-9946(12)60506-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Innovative ideas are required to improve the management of inflammatory bowel disease and to share best practice that can be implemented into clinical practice today. The use of biomarkers such as calprotectin to monitor disease progression and treatment response could help to improve management of inflammatory bowel disease, but several strategies need to be implemented to make this a reality in clinical practice. The use of calprotectin as a biomarker and the manipulation of the thiopurine pathway to extend the use of current therapies are examples of how basic research can translate into patient benefit. Translational research into the use of microbiota and predictive factors for response and toxicity to drugs, may provide future clinical applications. Global improvement in care in inflammatory bowel disease could also be advanced by improving service provision. For example, the establishment of 'Centres of Excellence', a global interactive inflammatory disease map, and the alignment of processes and standards of care within treatment centres may help to achieve better outcomes for patients with inflammatory bowel disease. Realization of this goal, as well as a better understanding of the aetiology of the disease, may be furthered by collaborative efforts between organizations involved in inflammatory bowel disease as well as wider collaboration across countries and globally.
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Affiliation(s)
- Edouard Louis
- Department of Gastroenterology, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
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Hepatitis B immunity and response to booster vaccination in children with inflammatory bowel disease treated with infliximab. Am J Gastroenterol 2012; 107:133-8. [PMID: 21876562 DOI: 10.1038/ajg.2011.295] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Hepatitis B virus (HBV) reactivation has been described in patients treated with infliximab for inflammatory bowel disease (IBD). This has resulted in a "black box" warning. Although universal vaccination against hepatitis B was implemented in the United States in 1991, up to 10% of vaccine recipients fail to respond with adequate anti-hepatitis B surface antibodies (anti-HBs) levels after a primary series of vaccinations. In addition, anti-HBs levels are expected to decline with time. The objectives of this study were to determine HBV immunity in children with IBD on infliximab therapy and to determine response to a booster dose of the HBV vaccine in patients who were found to be non-immune. METHODS This was a prospective cross-sectional, single-center study that included 100 pediatric IBD patients on infliximab. Serologic specimens were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and anti-HBs. Patients with an anti-HBs level ≥10 mIU/ml were considered to be immune. One booster dose was given to non-immune patients and a serum sample was collected after 4 weeks to assess the presence of anamnestic response (anti-HBs level ≥10 mIU/ml after booster). RESULTS The mean age of the patients was 17.9 (±4.0) years. None of the patients were positive for HBsAg or anti-HBc. In all, 87 patients were vaccinated against HBV and 49/87 (56%) had immunity to HBV as defined by anti-HBs level ≥10 mIU/ml. The mean concentration of anti-HBs levels in immune patients was 295.6 (±350.6) mIU/ml. Older age, lower albumin levels, and the presence of pancolitis were associated with the absence of protective antibodies; however, infliximab dose, frequency, duration, and the concurrent use of immunomodulators were not significantly different between immune and non-immune patients. Thirty-four patients received booster immunization and 26/34 (76%) had an anamnestic response. Interestingly, non-responders were given infliximab with higher frequency (every 5.9 ± 1.2 weeks vs. every 7.1 ± 1.8 weeks, P=0.01). Overall, 75/87 (86%) of previously immunized patients were considered immune against HBV infection. CONCLUSIONS In pediatric IBD patients seen at a large, urban tertiary care facility in the United States, a significant minority (13%) have not been vaccinated against HBV. Nearly one-half of all patients (and 44% of previously vaccinated patients) did not have protective anti-HBs levels. Moreover, of those previously vaccinated, a significant minority (14%) appear at risk for HBV because protective anti-HBs levels were absent and could not be elicited through booster immunization. Given the high risk for severe HBV infection in this group, efforts should be made to screen for HBV immunity at the time of IBD diagnosis. Booster immunization should be considered in patients without protective antibodies.
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Crawford NW, Catto-Smith AG, Oliver MR, Cameron DJS, Buttery JP. An Australian audit of vaccination status in children and adolescents with inflammatory bowel disease. BMC Gastroenterol 2011; 11:87. [PMID: 21798078 PMCID: PMC3160403 DOI: 10.1186/1471-230x-11-87] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2011] [Accepted: 07/29/2011] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Children and adolescents with inflammatory bowel disease (IBD) are at increased risk of vaccine preventable diseases (VPD). This includes invasive pneumococcal disease and influenza. The primary aim of this study was to describe compliance with current Australian guidelines for vaccination of children and adolescents diagnosed with IBD. A secondary aim was to review the serological screening for VPD. METHODS A random sample of patients (0-18 years at diagnosis), were selected from the Victoria Australia state based Pediatric Inflammatory Bowel Disease Register. A multi-faceted retrospective review of immunization status was undertaken, with hospital records audited, a telephone interview survey conducted with consenting parents and the vaccination history was checked against the primary care physician and Australian Childhood Immunization Register (ACIR) records. The routine primary childhood vaccinations and administration of the recommended additional influenza and pneumococcal vaccines was clarified. RESULTS This 2007 audit reviewed the immunization status of 101 individuals on the Victorian Pediatric IBD database. Median age at diagnosis was 12.1 years, 50% were on active immunosuppressive therapy. 90% (38/42) [95% confidence intervals (CI) 77%; 97%] with complete immunization information were up-to-date with routine primary immunizations. Only 5% (5/101) [95% CI 2%; 11%] received a recommended pneumococcal vaccine booster and 10% (10/101) [95% CI 5%; 17%] had evidence of having ever received a seasonal influenza vaccine. Those living in rural Victoria (p = 0.005) and younger at the age of diagnosis (p = 0.002) were more likely to have ever received an influenza vaccine Serological testing, reviewing historical protection from VPD, identified 18% (17/94) with evidence of at least one serology sample. CONCLUSION This study highlights poor compliance in IBD patients for additional recommended vaccines. A multi-faceted approach is required to maximize protection from VPD in this vulnerable special risk population.
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Affiliation(s)
- Nigel W Crawford
- SAEFVIC, Department of General Medicine, Royal Children's Hospital (RCH), Melbourne, Victoria 3011, Australia.
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King LK, Lee A, Anandacoomarasamy A. Use of biological disease-modifying anti-rheumatic drugs in patients with concurrent rheumatic disease and hepatitis B. Intern Med J 2011; 42:523-31. [PMID: 21790927 DOI: 10.1111/j.1445-5994.2011.02569.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Biological disease-modifying anti-rheumatic drugs (bDMARDs) are effective in the management of inflammatory arthritides. Reactivation of hepatitis B virus (HBV) is a potential adverse outcome in patients treated with bDMARDs. There is currently no consensus on the approach to identifying and treating these patients with underlying HBV infection. AIM The aims of this study were to assess the risk of HBV reactivation in patients treated with bDMARDs, and to determine whether HBV screening should be carried out in all patients prior to commencing bDMARDs. METHODS A literature search was undertaken to identify all reports of patients with inflammatory arthritides and concurrent HBV infection being treated with bDMARDs. RESULTS Forty-three patients with HBV infection were identified, of whom eight patients developed HBV reactivation after exposure to bDMARDs. Of the patients who experienced reactivation, two had unknown infection that surfaced during bDMARD therapy. Patients who experienced reactivation were promptly treated with antiviral therapy and saw clinical improvement. There are no long-term data on these patients. CONCLUSIONS HBV reactivation may result in serious consequences, including death. Tuberculosis screening prior to bDMARD treatment is already standard practice, as is HBV screening for patients undergoing cancer chemotherapy. Implementing HBV screening for all patients prior to bDMARD treatment can identify patients with chronic HBV who may require antiviral therapy.
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Affiliation(s)
- L K King
- Concord Clinical School, Sydney Medical School, Sydney, New South Wales, Australia
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Wilckens V, Kannengiesser K, Hoxhold K, Frenkel C, Kucharzik T, Maaser C. The immunization status of patients with IBD is alarmingly poor before the introduction of specific guidelines. Scand J Gastroenterol 2011; 46:855-61. [PMID: 21506630 DOI: 10.3109/00365521.2011.574734] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION With immunosuppressive therapy of inflammatory bowel diseases (IBDs) becoming more aggressive, the risk of serious infections is increasing. Guidelines are currently being modified in respect to advisable immunizations. The aim of this study was to evaluate the immunization habits of IBD patients in daily practice before the implementation of specific guidelines. METHODS Hundred and two consecutive patients attending the outpatients IBD clinic at our hospital were interviewed regarding their immunization record. In addition, hepatitis B and C, HIV, and cytomegalovirus (CMV) serostatus were measured following a European Crohn's and Colitis Organization (ECCO) consensus. RESULTS Hundred and two patients with IBD have been included; of these 72% were taking steroids, 46% azathioprine, and 23% anti-TNF medication. Nineteen percent of the study population had been vaccinated against influenza, 3% against pneumoccous pneumonia, 22% against hepatitis B, 5% against varizella, 55% against rubella/mumps/measles, and 63% against tetanus. Of those who had traveled, 9% had been vaccinated for hepatitis A and 1% for yellow fever. Reasons given for not being vaccinated were not being aware of the necessity in 45% of those questioned and being afraid in 17%. While no patient was tested positive for hepatitis B, HIV, and CMV-IgM, one female patient was tested positive for hepatitis C (antibody and PCR positive, genotype I), which was unknown at that point. CONCLUSION Considering the high number of our patients receiving immunosuppressive therapy, the immunization record is alarmingly poor supporting the need for optimized IBD guidelines, better awareness, and patient education. In addition, the screening for chronic infections appears to be useful as suggested by the positive finding of a previously unknown hepatitis C.
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Affiliation(s)
- Volker Wilckens
- Department of Anaesthesiology, University Teaching Hospital Lueneburg, Lueneburg, Germany
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Selmi C, De Santis M, Gershwin ME. Liver involvement in subjects with rheumatic disease. Arthritis Res Ther 2011; 13:226. [PMID: 21722332 PMCID: PMC3218873 DOI: 10.1186/ar3319] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The liver is often overlooked as a target organ, with pathology either secondary to an underlying disease or due to the toxicity of therapies and the medical complications of extrahepatic diseases. It is thus important for the clinical rheumatologist to be aware of the diagnostic procedure to monitor liver injury. Indeed, systemic rheumatologic diseases may be associated with liver abnormalities secondary to the presence of a coexisting autoimmune liver disease (particularly primary biliary cirrhosis or autoimmune hepatitis), the direct involvement of the liver parenchyma, or the impact of medical treatments (particularly methotrexate) on the liver. In addition, the rheumatologist should be aware of the impact of immunosuppressive agents on underlying viral infections, particularly viral hepatitis. We review herein the data on the role of the liver in the clinical management of systemic rheumatic diseases.
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Affiliation(s)
- Carlo Selmi
- Department of Medicine and Autoimmunity and Metabolism Unit, IRCCS-Istituto Clinico Humanitas, University of Milan, via. A. Manzoni 56, 20089 Rozzano (MI), Italy
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