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Huang PH, Nowalk MP, Zimmerman RK, Olson SM, Talbot HK, Zhu Y, Gaglani M, Murthy K, Monto AS, Martin ET, Silveira FP, Balasubramani G. Vaccine effectiveness against influenza-associated hospitalizations in adults with liver disease, 2015-2020: US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). Hum Vaccin Immunother 2025; 21:2457205. [PMID: 39875316 PMCID: PMC11776484 DOI: 10.1080/21645515.2025.2457205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 01/07/2025] [Accepted: 01/20/2025] [Indexed: 01/30/2025] Open
Abstract
Influenza causes 100,000-710,000 hospitalizations annually in the U.S. Patients with liver disease are at higher risk of severe outcomes following influenza infection. This study evaluated influenza vaccine effectiveness (VE) against influenza-associated hospitalization among adults with liver disease. Data from the U.S. Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN), a test-negative case-control study, from 2015 to 2020 were used to estimate VE among adults ≥18 years admitted for acute respiratory illness. VE was calculated as (1-adjusted odds ratio)*100%, comparing the odds of vaccine receipt between laboratory-confirmed influenza cases and test-negative controls using multiple logistic regression with inverse probability of treatment weighting (IPTW). In total, 1,622 (12.8%) of 12,704 adults had ≥1 liver disease(s). Compared with those without liver disease, adults with liver disease were more likely to be admitted to the intensive care unit (15.7% vs 12.8%, p = .001) or to die in hospital (3.0% vs 1.4%, p < .001). The IPTW-adjusted VE against influenza-associated hospitalization was 27% (95% confidence interval [CI], 22-32%) among patients without liver disease, but the VE of 11% (95% CI, -8-26%) was not significant among those with liver disease. Significant effect modification of VE by the presence of liver disease was found (p < .05 for interaction term). While influenza vaccination significantly reduced the risk of influenza-associated hospitalization among adults without liver disease, the protective effect was not significant among those with liver disease. Further studies are warranted to evaluate influenza VE in patients with different types of liver disease and with specific vaccine formulations.
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Affiliation(s)
- Po-Han Huang
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | | | | | - Samantha M. Olson
- Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - H. Keipp Talbot
- Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Yuwei Zhu
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Manjusha Gaglani
- Department of Research Analytics and Development, Baylor Scott & White Health, Temple, TX, USA
- Department of Pediatrics, Baylor College of Medicine, Temple, TX, USA
| | - Kempapura Murthy
- Department of Research Analytics and Development, Baylor Scott & White Health, Temple, TX, USA
| | - Arnold S. Monto
- Center for Respiratory Virus Research and Response, School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | - Emily T. Martin
- Center for Respiratory Virus Research and Response, School of Public Health, University of Michigan, Ann Arbor, MI, USA
| | - Fernanda P. Silveira
- Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA
| | - G.K. Balasubramani
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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Hackstein CP. Liver damage and immune responses. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:56-64. [PMID: 39793602 DOI: 10.1055/a-2365-3796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2025]
Abstract
Chronic liver disease (CLD) has massive systemic repercussions including major impacts on the body's immune system. Abnormalities in phenotype, function and numbers of various immune cell subsets have been established by a large number of clinical and pre-clinical studies. The loss of essential immune functions renders CLD-patients exceptionally susceptible to bacterial and viral infections and also impairs the efficacy of vaccination. Consequently, infections represent a major clinical issue causing significant morbidity and mortality in these patients. Mechanistically, the immune dysfunction associated with CLD results from the increased translocation of bacteria and bacterial cues from the intestine. These trigger a signaling axis around the cytokines IFN I and IL-10 in hepatic myeloid cells, which aside from impairing the function of the myeloid cells themselves, also has notable negative impacts on the functionality of other immune cells. T cells in CLD-patients and -models are especially affected by this signaling axis and display a variety of quantitative and qualitative defects. Due to the high clinical relevance, understanding the mechanisms underlaying CED-associated immune dysfunction is of critical importance to discover and develop new therapeutic targets.
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Affiliation(s)
- Carl-Philipp Hackstein
- Institut für Molekulare Immunologie, Technische Universität München, München, Germany
- Zentrum für Infektionsprävention (ZIP), Technische Universität München, Freising, Germany
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3
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Piano S, Bunchorntavakul C, Marciano S, Rajender Reddy K. Infections in cirrhosis. Lancet Gastroenterol Hepatol 2024; 9:745-757. [PMID: 38754453 DOI: 10.1016/s2468-1253(24)00078-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 03/04/2024] [Accepted: 03/04/2024] [Indexed: 05/18/2024]
Abstract
Cirrhosis is an immune dysfunction state, and as such, patients with cirrhosis are susceptible to bacterial, fungal, and viral infections. Because of infection, these patients have a propensity to develop multiorgan failure, which is associated with high mortality. Bacterial infections are the most prevalent type of infection in patients with cirrhosis, with the prevalence of bacterial infections in patients admitted for an acute decompensating event ranging from 24% to 29%. Together with invasive fungal infections, bacterial infections are the most severe. Multidrug-resistant organisms have been evolving at a rapid and alarming rate around the world, which presents enormous challenges. The development of effective measures for the prevention, early detection, and treatment of infections in patients with cirrhosis is challenging, given the rising incidence of infections in this patient population.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
| | | | - Sebastian Marciano
- Department of Clinical Investigation, Italian Hospital, Buenos Aires, Argentina
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA.
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Stroffolini T, Stroffolini G. Vaccination in Patients with Liver Cirrhosis: A Neglected Topic. Vaccines (Basel) 2024; 12:715. [PMID: 39066353 PMCID: PMC11281357 DOI: 10.3390/vaccines12070715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 06/20/2024] [Accepted: 06/26/2024] [Indexed: 07/28/2024] Open
Abstract
Patients with liver cirrhosis, due to their weakened innate and adaptive immunity, are more prone to frequent and severe vaccine-preventable infections. Moreover, impaired adaptive immunity results in a limited antibody response to vaccines. Despite this suboptimal antibody response, vaccines have proven to be very effective in reducing severe outcomes and deaths in these patients. In the Western world, regulatory authorities and scientific liver societies (e.g., AASLD and EASL) have recommended vaccinations for cirrhotic patients. However, despite these strong recommendations, vaccine coverage remains suboptimal. Improving vaccine effectiveness and safety information, providing comprehensive counseling to patients, fact-checking to combat fake news and disinformation and removing barriers to vaccination for disadvantaged individuals may help overcome the low coverage rate. In view of this, vaccines should be administered early in the course of chronic liver diseases, as their efficacy declines with the increasing severity of the disease.
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Affiliation(s)
- Tommaso Stroffolini
- Department of Tropical and Infectious Diseases, Policlinico Umberto I, 00161 Rome, Italy;
| | - Giacomo Stroffolini
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 5, 37024 Verona, Italy
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5
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Olveira A, Jiménez V. Hemophilia and hepatology, back to the future. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:179-181. [PMID: 38450508 DOI: 10.17235/reed.2024.10105/2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/08/2024]
Abstract
Years ago, patients with hemophilia were often cared for because of liver issues. The use of hemoderivatives in the 1970s and 1980s, and the natural history of chronic hepatitis B and C, led to a surge of patients with cirrhosis and related complications after two or three decades. It was not until the approval of entecavir and tenofovir (2005-2008) against the B virus, and of direct-acting antiviral agents (2015) against the C virus, that a truly effective treatment became available for liver disease. Since then, patients with hemophilia disappeared from hepatology clinics and wards, apart from specific isolated problems.
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Airola C, Andaloro S, Gasbarrini A, Ponziani FR. Vaccine Responses in Patients with Liver Cirrhosis: From the Immune System to the Gut Microbiota. Vaccines (Basel) 2024; 12:349. [PMID: 38675732 PMCID: PMC11054513 DOI: 10.3390/vaccines12040349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 03/11/2024] [Accepted: 03/21/2024] [Indexed: 04/28/2024] Open
Abstract
Vaccines prevent a significant number of deaths annually. However, certain populations do not respond adequately to vaccination due to impaired immune systems. Cirrhosis, a condition marked by a profound disruption of immunity, impairs the normal immunization process. Critical vaccines for cirrhotic patients, such as the hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcal, and coronavirus disease 19 (COVID-19), often elicit suboptimal responses in these individuals. The humoral response, essential for immunization, is less effective in cirrhosis due to a decline in B memory cells and an increase in plasma blasts, which interfere with the creation of a long-lasting response to antigen vaccination. Additionally, some T cell subtypes exhibit reduced activation in cirrhosis. Nonetheless, the persistence of memory T cell activity, while not preventing infections, may help to attenuate the severity of diseases in these patients. Alongside that, the impairment of innate immunity, particularly in dendritic cells (DCs), prevents the normal priming of adaptive immunity, interrupting the immunization process at its onset. Furthermore, cirrhosis disrupts the gut-liver axis balance, causing dysbiosis, reduced production of short-chain fatty acids (SCFAs), increased intestinal permeability, and bacterial translocation. Undermining the physiological activity of the immune system, these alterations could impact the vaccine response. Enhancing the understanding of the molecular and cellular factors contributing to impaired vaccination responses in cirrhotic patients is crucial for improving vaccine efficacy in this population and developing better prevention strategies.
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Affiliation(s)
- Carlo Airola
- Liver Unit, CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (S.A.); (A.G.)
| | - Silvia Andaloro
- Liver Unit, CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (S.A.); (A.G.)
| | - Antonio Gasbarrini
- Liver Unit, CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (S.A.); (A.G.)
- Department of Translational Medicine and Surgery, Catholic University, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Liver Unit, CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (S.A.); (A.G.)
- Department of Translational Medicine and Surgery, Catholic University, 00168 Rome, Italy
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Bianchi FP, Losito F, Labarile N, Shahini E, Cozzolongo R. Prevention of influenza complications in patients with liver disease: a retrospective cohort study. Front Public Health 2023; 11:1288126. [PMID: 38186701 PMCID: PMC10771385 DOI: 10.3389/fpubh.2023.1288126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 12/06/2023] [Indexed: 01/09/2024] Open
Abstract
Introduction Patients with chronic liver disease are highly prone to acquiring influenza infection diseases and experiencing associated complications. National and international guidelines recommend the influenza vaccine for patients with liver disorders to reduce the risk of influenza complications. Our study aims to evaluate the risk of flu complications faced by patients with liver disease and assess influenza vaccination coverage. Methods The archive of hospital discharge forms was used to define the list of Apulian patients with liver disease, considering data from 2017 through 2022. The vaccination status of these patients was assessed via data collected from the Regional Immunization Database. We focused on influenza vaccine shots administered during the 2020/21, 2021/22, and 2022/23 flu seasons. Results A declining trend across the flu seasons was observed, with a VC of 49.5% in the 2020/21 flu season, 48.1% in the 2021/22 season, and 45.0% in the 2022/23 season. Subjects with multiple comorbidities have higher vaccination rates. Additionally, the multivariate models demonstrate that vaccination compliance increases with age and is strongly associated with having received a previous influenza vaccine shot. Conclusion The VC rates reported in our study are unsatisfactory and did not reach the minimum achievable goal (75%) the Italian Ministry of Health set. A multifactorial approach is required to raise the immunization rates and therefore protect the patients from the influenza-associated risk of collateral liver damage; the role of gastroenterologists and hepatologists is crucial, as their responsibilities should extend beyond patient care to the prevention of complications after infectious diseases.
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Affiliation(s)
| | - Francesco Losito
- Gastroenterology Unit, National Institute of Gastroenterology, IRCCS S. De Bellis, Research Hospital, Castellana Grotte, Italy
| | - Nunzia Labarile
- Gastroenterology Unit, National Institute of Gastroenterology, IRCCS S. De Bellis, Research Hospital, Castellana Grotte, Italy
| | - Endrit Shahini
- Gastroenterology Unit, National Institute of Gastroenterology, IRCCS S. De Bellis, Research Hospital, Castellana Grotte, Italy
| | - Raffaele Cozzolongo
- Gastroenterology Unit, National Institute of Gastroenterology, IRCCS S. De Bellis, Research Hospital, Castellana Grotte, Italy
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8
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Ballester MP, Jalan R, Mehta G. Vaccination in liver diseases and liver Transplantation: Recommendations, implications and opportunities in the post-covid era. JHEP Rep 2023:100776. [PMID: 37360567 PMCID: PMC10241163 DOI: 10.1016/j.jhepr.2023.100776] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 03/07/2023] [Accepted: 04/11/2023] [Indexed: 06/28/2023] Open
Abstract
The interest in vaccination efficacy and toxicity has surged following the Covid-19 pandemic. Immune responses to several vaccines have been shown to be suboptimal in patients with chronic liver disease (CLD) or post-liver transplant (LT), as a consequence of cirrhosis-associated immune dysfunction (CAID) or post-LT immunosuppression respectively. Accordingly, vaccine-preventable infections may be more common or severe than in the general population. The Covid-19 pandemic has greatly accelerated research and development into vaccination technology and platforms, which will have spillover benefits for liver patients. The aims of this review are: (i) to discuss the impact of vaccine-preventable infections on CLD and post-LT patients, (ii) to appraise current evidence supporting vaccination strategies, and (iii) to provide some insight into recent developments relevant for liver patients.
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Affiliation(s)
- Maria Pilar Ballester
- Digestive Disease Department, Clinic University Hospital of Valencia, Spain
- Incliva Biomedical Research Institute, Valencia, Spain
| | - Rajiv Jalan
- Institute for Liver and Digestive Health, University College London, London, UK
| | - Gautam Mehta
- Institute for Liver and Digestive Health, University College London, London, UK
- Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK
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9
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Approaches for Selective Vaccinations in Cirrhotic Patients. Vaccines (Basel) 2023; 11:vaccines11020460. [PMID: 36851337 PMCID: PMC9967540 DOI: 10.3390/vaccines11020460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 02/11/2023] [Accepted: 02/13/2023] [Indexed: 02/19/2023] Open
Abstract
Bacterial and viral infections are common in cirrhotic patients, and their occurrence is associated with the severity of liver disease. Bacterial infection may increase the probability of death by 3.75 times in patients with decompensated cirrhosis, with ranges of 30% at 1 month and 63% at 1 year after infection. We illustrate the indications and the modalities for vaccinating cirrhotic patients. This topic is important for general practitioners and specialists.
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10
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Luo M, Ballester MP, Soffientini U, Jalan R, Mehta G. SARS-CoV-2 infection and liver involvement. Hepatol Int 2022; 16:755-774. [PMID: 35767172 PMCID: PMC9243815 DOI: 10.1007/s12072-022-10364-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 05/07/2022] [Indexed: 02/06/2023]
Abstract
The COVID-19 pandemic is the largest public health challenge in living memory. Patients with underlying liver disease have been disproportionately affected, experiencing high morbidity and mortality. In addition, elevated liver enzymes appear to be a risk factor for disease progression, even in the absence of underlying liver disease. Nevertheless, the mechanism of liver injury in SARS-CoV-2 infection remains largely unknown. This review aims to provide an overview of the mechanisms by which SARS-CoV-2 induces liver injury, and the impact of COVID-19 on cirrhosis, alcohol-related liver disease, autoimmune liver disease, non-alcoholic fatty liver disease, hepatitis B and C virus infection, liver-transplant recipients and patients with hepatocellular carcinoma. Finally, emerging data on vaccination in liver diseases is discussed, to help inform public health policy.
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Affiliation(s)
- Mingjia Luo
- Division of Medicine, University College London, London, UK
| | - Maria Pilar Ballester
- Digestive Disease Department, Hospital Clínic, Universitario de Valencia, Valencia, Spain.,INCLIVA-Biomedical Research Institute, Valencia, Spain
| | - Ugo Soffientini
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.,Liver Failure Group, UCL Medical School, Institute for Liver and Disease Health, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK
| | - Rajiv Jalan
- Liver Failure Group, UCL Medical School, Institute for Liver and Disease Health, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK
| | - Gautam Mehta
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK. .,Liver Failure Group, UCL Medical School, Institute for Liver and Disease Health, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK.
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11
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Alukal JJ, Naqvi HA, Thuluvath PJ. Vaccination in Chronic Liver Disease: An Update. J Clin Exp Hepatol 2022; 12:937-947. [PMID: 34975241 PMCID: PMC8710401 DOI: 10.1016/j.jceh.2021.12.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 12/04/2021] [Indexed: 12/12/2022] Open
Abstract
Patients with chronic liver disease (CLD) with or without cirrhosis remain at risk of developing hepatic decompensation when infected with viral or bacterial pathogens. The Advisory Committee on Immunization Practices (ACIP) currently recommends vaccination in CLD against hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcus, herpes zoster, tetanus, diphtheria, pertussis, and SARS-CoV-2. Inactivated vaccines are preferred over live attenuated ones, especially in transplant recipients where live vaccines are contraindicated. As the severity of the liver disease progresses, vaccine efficacy declines, and therefore, vaccines should be ideally administered early in the disease course for optimal immune response. Despite the strong recommendations, overall vaccination coverage in CLD remains poor; however, it is encouraging to note that in recent years coverage against influenza and pneumococcus has shown some improvement. Inadequate access to healthcare, lack of information on vaccine safety, poor financial reimbursement for healthcare providers, and vaccine misinformation are often responsible for low immunization rates. This review summarizes the impact of vaccine-preventable illness in those with CLD, updated vaccine guidelines, seroconversion rates in the vaccinated, and barriers faced by healthcare professionals in immunizing those with liver disease.
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Key Words
- ACIP, Advisory Committee on Immunization Practices
- ACLF, acute on chronic liver failure
- ALD, alcohol-related liver disease
- CLD, Chronic liver disease
- CLIF-C, Chronic Liver Failure Consortium
- DAA, direct-acting antiviral drugs
- HAV, hepatitis A virus
- HBV, hepatitis B virus
- HCV, hepatitis C virus
- LT, liver transplant
- NAFLD, nonalcoholic fatty liver disease
- SARS-CoV-2
- SOFA, sequential organ failure assessment
- chronic liver disease
- immunization
- vaccines
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Affiliation(s)
- Joseph J. Alukal
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore MD, USA
| | | | - Paul J. Thuluvath
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore MD, USA
- Department of Medicine, University of Maryland School of Medicine, Baltimore MD, USA
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12
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Sobotka LA, Mumtaz K, Hinton A, Conteh LF. The time to advocate for influenza vaccines in patients with cirrhosis is now. Clin Res Hepatol Gastroenterol 2022; 46:101838. [PMID: 34813944 DOI: 10.1016/j.clinre.2021.101838] [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: 04/21/2021] [Revised: 10/11/2021] [Accepted: 11/08/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM The effect of an influenza infection on patients with cirrhosis remains unclear. This study aimed to compare the rate of influenza hospitalizations, influenza associated complications, and healthcare outcomes in patients with and without cirrhosis. METHODS Utilizing the Nationwide Inpatient Sample between 2005 and 2013, hospitalized patients with a diagnosis of influenza were identified. Patients with cirrhosis were classified as compensated or decompensated based on the Baveno criteria. Multivariable analyses were performed to evaluate complications of influenza, inpatient mortality and healthcare utilization including length of stay and cost of admission. RESULTS In total, 236,513 patients with a diagnosis of influenza were admitted during the study period, including 1,553 (0.66%) with cirrhosis. Of those with cirrhosis, 1,176 (75.7%) were compensated and 377 (24.3%) were decompensated. On multivariable analysis, influenza patients with cirrhosis had a higher total cost of admission [$1,030; CI: $710-$1,351] compared to the general population. Influenza patients with decompensated cirrhosis had a longer length of stay [1.92 days; CI:1.63-2.21], higher total cost of admission [$5,005; CI: $4,459-$5,551] and increased rates of influenza complications [OR: 2.56; CI:1.32-4.93] compared to patients with compensated cirrhosis. CONCLUSIONS Patients with cirrhosis have increased healthcare utilization when admitted with influenza compared to the general population. Providers must advocate for patients with cirrhosis to obtain the influenza vaccine.
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Affiliation(s)
- Lindsay A Sobotka
- Gastroenterology, Hepatology and Nutrition, The Ohio State Wexner Medical Center, Columbus Ohio, United States of America 43210
| | - Khalid Mumtaz
- Gastroenterology, Hepatology and Nutrition, The Ohio State Wexner Medical Center, Columbus Ohio, United States of America 43210
| | - Alice Hinton
- Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio, United States of America 43210
| | - Lanla F Conteh
- Gastroenterology, Hepatology and Nutrition, The Ohio State Wexner Medical Center, Columbus Ohio, United States of America 43210.
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13
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Mastroianni A, Vangeli V, Greco S, Urso F, Greco F, Chidichimo L, Mauro MV. Oseltamivir and acute hepatitis, reality association or coincidence? Antivir Ther 2021; 26:87-92. [DOI: 10.1177/13596535211041494] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Oseltamivir is an orally administered antiviral medication that selectively inhibits the influenza neuraminidase enzymes that are essential for viral replication and it is active against both influenza A and B viruses. Oseltamivir is indicated for therapy or post-exposure prevention of influenza A and B. Side effects are uncommon and include mild nausea, gastrointestinal upset, dizziness, and headache. Despite widespread use, oseltamivir has not been associated with clinically apparent liver injury; however, there is growing evidence of possible toxic liver involvement during oseltamivir therapy. To the best of our knowledge, this is the first reported case in Italy linking the development of acute hepatitis and oseltamivir therapy, in a patient suffering from influenza H1N1 infection. We also present a review of the literature on cases of oseltamivir hepatotoxicity, through the consultation of PubMed database, the bibliographical references of various articles and an extensive search using Google. In view of the analyzed results, we suggest that experts should carefully consider the need for inclusion of potential serious liver reactions be added to the oseltamivir product label.
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Affiliation(s)
- Antonio Mastroianni
- UOC Malattie Infettive e Tropicali, Azienda Ospedaliera di Cosenza, Cosenza, Italy
| | - Valeria Vangeli
- UOC Malattie Infettive e Tropicali, Azienda Ospedaliera di Cosenza, Cosenza, Italy
| | - Sonia Greco
- UOC Malattie Infettive e Tropicali, Azienda Ospedaliera di Cosenza, Cosenza, Italy
| | - Filippo Urso
- UOC Farmacia Ospedaliera, Azienda Ospedaliera di Cosenza, Cosenza, Italy
| | - Francesca Greco
- UOC Microbiologia e Virologia, Azienda Ospedaliera di Cosenza, Cosenza, Italy
| | - Luciana Chidichimo
- UOC Malattie Infettive e Tropicali, Azienda Ospedaliera di Cosenza, Cosenza, Italy
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14
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Kim D, Adeniji N, Latt N, Kumar S, Bloom PP, Aby ES, Perumalswami P, Roytman M, Li M, Vogel AS, Catana AM, Wegermann K, Carr RM, Aloman C, Chen VL, Rabiee A, Sadowski B, Nguyen V, Dunn W, Chavin KD, Zhou K, Lizaola-Mayo B, Moghe A, Debes J, Lee TH, Branch AD, Viveiros K, Chan W, Chascsa DM, Kwo P, Dhanasekaran R. Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center Study. Clin Gastroenterol Hepatol 2021; 19:1469-1479.e19. [PMID: 32950749 PMCID: PMC7497795 DOI: 10.1016/j.cgh.2020.09.027] [Citation(s) in RCA: 174] [Impact Index Per Article: 43.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/14/2020] [Accepted: 09/15/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19). METHODS We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD. RESULTS Of the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19. CONCLUSIONS The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. Clinicaltrials.gov number NCT04439084.
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Affiliation(s)
| | | | - Nyann Latt
- Ochsner Medical Center, New Orleans, Louisiana
| | | | | | - Elizabeth S. Aby
- Hennepin County Medical Center, Minneapolis, Minnesota,University of Minnesota, Minneapolis, Minnesota
| | | | - Marina Roytman
- University of California San Francisco, Fresno, California
| | - Michael Li
- Brigham and Women’s Hospital, Boston, Massachusetts
| | | | | | | | | | | | | | | | | | | | - Winston Dunn
- University of Kansas Medical Center, Kansas City, Kansas
| | | | - Kali Zhou
- University of Southern California, Los Angeles, California
| | | | - Akshata Moghe
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - José Debes
- Hennepin County Medical Center, Minneapolis, Minnesota,University of Minnesota, Minneapolis, Minnesota
| | | | | | | | - Walter Chan
- Brigham and Women’s Hospital, Boston, Massachusetts
| | | | - Paul Kwo
- Stanford University, Stanford, California
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15
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Stroffolini T, Lombardi A, Ciancio A, Niro GA, Colloredo G, Marignani M, Vinci M, Morisco F, Babudieri S, Ferrigno L, Sagnelli E. Low influenza vaccination coverage in subjects with liver cirrhosis. An alert waiting for winter season 2020–2021 during the COVID‐19 pandemic. J Med Virol 2021; 93:2446-2452. [DOI: 10.1002/jmv.26763] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 12/07/2020] [Accepted: 12/23/2020] [Indexed: 12/31/2022]
Affiliation(s)
- Tommaso Stroffolini
- Department of Tropical and Infectious Diseases Policlinico Umberto I Roma Italy
| | | | - Alessia Ciancio
- Department of Gastroenterology Ospedale Molinette Torino Italy
| | - Grazia A. Niro
- Gastroenterology Unit Fondazione Casa Sollievo della Sofferenza IRCCS San Giovanni Rotondo Italy
| | | | - Massimo Marignani
- Department of Digestive and Liver Diseases S. Andrea Hospital and School of Medicine Rome Italy
| | - Maria Vinci
- Department of Gastroenterology Ospedale Niguarda Milano Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Gastroenterology and Hepatology Unit University of Naples Federico II Naples Italy
| | - Sergio Babudieri
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, Clinic of Infectious Diseases University of Sassari Sassari Italy
| | - Luigina Ferrigno
- National Health Institute National Center for Global Health Rome Italy
| | - Evangelista Sagnelli
- Dipartimento di Salute Mentale e Fisica e Medicina Preventiva, Clinic of Infectious Diseases University of Naples Naples Italy
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16
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Ahmmad EM, Roberts LR. Quality of Care in Patients With Cirrhosis: Trends in Recommended Adult Vaccination Coverage. Mayo Clin Proc Innov Qual Outcomes 2020; 4:667-682. [PMID: 33367212 PMCID: PMC7749261 DOI: 10.1016/j.mayocpiqo.2020.06.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objective To assess the proportion of patients with cirrhosis up to date with vaccinations and associations of vaccination with age, sex, race, ethnicity, marital status, and type of provider follow-up. Patients and Methods Patients with cirrhosis diagnosed at Mayo Clinic in Rochester and Mayo Clinic Health System in Minnesota from January 1, 2007, to December 31, 2009, were followed up from diagnosis until May 31, 2015. Data were abstracted from Mayo Clinic and Minnesota State records. Factors determining vaccination coverage were assessed. Results At the end of the study period (8 years follow-up), 26.4% (95 of 360), 24.7% (82 of 332), 63.2% (180 of 285), and 25.5% (54 of 212) of patients with cirrhosis were up to date with hepatitis A virus (HAV), hepatitis B virus, pneumococcal pneumonia (PN), and herpes zoster vaccinations, respectively. Influenza (FLU) vaccine coverage increased from 36.1% (57 of 158) in 2007 to 2008 to 65.8% (106 of 161) in 2014 to 2015. Of those unvaccinated for HAV and hepatitis B virus before cirrhosis diagnosis, 18.6% (59 of 318) and 23.4% (71 of 304) completed vaccination. For HAV, more whites than nonwhites (28.3% [91 of 322] vs 10.5% [4 of 38]; odds ratio [OR], 3.35; 95% CI, 1.29 to 11.45; P=.02) and more non-Hispanics than Hispanics (27.4% [95 of 347] vs 0% [0 of 13]; OR, 0.00; 95% CI, 0.00 to 0.43; P=.03) were vaccinated. For PN, more younger than elderly people (66.8% [135 of 202] vs 54.2% [45 of 83]; OR, 1.70; 95% CI, 1.01 to 2.87; P=.04) and married vs single people (56.8% [100 of 176] vs 73.4% [80 of 109]; OR, 2.10; 95% CI, 1.26 to 3.56; P=.005) were vaccinated. For FLU, in 2013 to 2014, more elderly (72.0% [54 of 75] vs 58.0% [69 of 119]; OR, 0.54; 95% CI, 0.28 to 0.99; P=.05); in 2008 to 2009, more Hispanics (100% [4 of 4] vs 41.6% [116 of 279]; OR, ∞; 95% CI, 2.25 to ∞; P=.02); and in 2011 to 2012, more married people (62.4% [101 of 162] vs 50.5% [56 of 111]; OR, 1.63; 95% CI, 0.1.0 to 2.66; P=.05) were vaccinated. For FLU in 2008 to 2009, coverage was higher in the primary care than the specialist setting (55.8% [48 of 86] vs 36.6% [72 of 197]; P=.003). Conclusion Except for PN and FLU, vaccination coverage in patients with cirrhosis falls short of Healthy People 2020 target. Specific interventions are needed to improve vaccination coverage in patients with cirrhosis.
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Key Words
- ACIP, Advisory Committee on Immunization Practices
- CLD, chronic liver disease
- EMR, electronic medical record
- FLU, influenza
- GIH, gastroenterologist and/or hepatologist
- HAV, hepatitis A virus
- HBV, hepatitis B virus
- HR, high-risk people
- HZ, herpes zoster
- LT, liver transplant specialist
- OR, odds ratio
- PCP, primary care provider
- PN, pneumococcal pneumonia
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Affiliation(s)
- Eimad M Ahmmad
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN
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17
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Nasir M, Vinsard DG, Wakefield D, Karagozian R. The important role of immunization in alcoholic and non-alcoholic chronic liver disease: A population-based study. J Dig Dis 2020; 21:583-592. [PMID: 32729256 DOI: 10.1111/1751-2980.12926] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 07/22/2020] [Accepted: 07/26/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To determine differences in frequencies of vaccine-preventable diseases between alcoholic liver disease (ALD) and non-alcoholic liver disease (NALD) patients. METHODS This population-based cohort study used USA national inpatient sample ICD-9 codes from January 2012 to September 2015. Frequencies of admissions for ALD and NALD in patients with pneumococcal pneumonia, influenza, herpes zoster virus, varicella zoster virus, hepatitis A, hepatitis B, human papilloma virus, meningococcal meningitis, diphtheria, pertussis and tetanus were measured. Frequencies and patients' characteristics were compared for ALD and NALD using χ2 test and multivariate logistic regression analysis. RESULTS There was no difference in admissions for hepatitis A and pneumococcal pneumonia between the ALD and NALD groups. There were fewer admissions for hepatitis B (1.17% vs 1.80%, odds ratio [OR] 0.64, P < 0.01), herpes zoster (0.12% vs 0.17%, OR 0.69, P < 0.01), influenza (0.16% vs 0.26%, OR 0.59, P < 0.01) and all others (0.005% vs 0.015%, OR 0.36, P = 0.01) in the ALD group than the NALD group. The extreme all patient refined-diagnosis related groups mortality risk was 15.24% in ALD and 7.77% in NALD admissions (P < 0.0001). CONCLUSIONS The most frequent vaccine-preventable disease in both groups was hepatitis B. Patients with NALD had higher odds of admissions for hepatitis B, herpes zoster virus, influenza and other vaccine-preventable disease than ALD patients. However, the ALD group had a higher risk of mortality when admitted to hospital with a vaccine-preventable disease than the NALD group.
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Affiliation(s)
- Myra Nasir
- Division of Internal Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA
| | - Daniela Guerrero Vinsard
- Division of Internal Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA
| | - Dorothy Wakefield
- Center of Aging, University of Connecticut Health Center, Farmington, Connecticut, USA
| | - Raffi Karagozian
- Division of Gastroenterology and Hepatology, Tufts University School of Medicine, Boston, Massachusetts, USA
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18
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Alqahtani SA, Aljumah AA, Hashim A, Alenazi TH, AlJawad M, Al Hamoudi WK, Alghamdi MY. Principles of Care for Patients with Liver Disease During the Coronavirus Disease 2019 (COVID-19) Pandemic: Position Statement of the Saudi Association for the Study of Liver Disease and Transplantation. Ann Saudi Med 2020; 40:273-280. [PMID: 32564624 PMCID: PMC7316371 DOI: 10.5144/0256-4947.2020.273] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 05/22/2020] [Indexed: 12/15/2022] Open
Abstract
In December 2019, a novel coronavirus was identified in patients in Wuhan, China. The virus, subsequently named severe acute respiratory syndrome coronavirus-2, spread worldwide and the disease (coronavirus disease 2019 or COVID-19) was declared a global pandemic by the World Health Organization in March 2020. Older adults and individuals with comorbidities have been reported as being more vulnerable to COVID-19. Patients with chronic liver disease (CLD) have compromised immune function due to cirrhosis and are more susceptible to infection. However, it is unclear if patients with CLD are more vulnerable to COVID-19 and its complications than other populations. The high number of severe cases of COVID-19 has placed an unusual burden on health systems, compromising their capacity to provide the regular care that patients with CLD require. Hence, it is incredibly crucial at this juncture to provide a set of interim recommendations on the management of patients with CLD during the current COVID-19 outbreak.
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MESH Headings
- Adenosine Monophosphate/adverse effects
- Adenosine Monophosphate/analogs & derivatives
- Adrenal Cortex Hormones/adverse effects
- Alanine/adverse effects
- Alanine/analogs & derivatives
- Amides/adverse effects
- Antiviral Agents/therapeutic use
- Azetidines/adverse effects
- Betacoronavirus
- Biopsy/methods
- COVID-19
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/therapy
- Comorbidity
- Coronavirus Infections/drug therapy
- Coronavirus Infections/epidemiology
- Coronavirus Infections/prevention & control
- Drug Combinations
- Drug Interactions
- Enzyme Inhibitors/adverse effects
- Hepatitis, Autoimmune/epidemiology
- Hepatitis, Autoimmune/therapy
- Hepatitis, Viral, Human/epidemiology
- Hepatitis, Viral, Human/therapy
- Humans
- Hydroxychloroquine/adverse effects
- Immunosuppressive Agents/therapeutic use
- Janus Kinase Inhibitors/adverse effects
- Liver Cirrhosis/epidemiology
- Liver Cirrhosis/therapy
- Liver Diseases/epidemiology
- Liver Diseases/therapy
- Liver Neoplasms/epidemiology
- Liver Neoplasms/therapy
- Liver Transplantation
- Lopinavir/adverse effects
- Non-alcoholic Fatty Liver Disease/epidemiology
- Non-alcoholic Fatty Liver Disease/therapy
- Pandemics/prevention & control
- Pneumonia, Viral/drug therapy
- Pneumonia, Viral/epidemiology
- Pneumonia, Viral/prevention & control
- Purines
- Pyrazines/adverse effects
- Pyrazoles
- Ritonavir/adverse effects
- SARS-CoV-2
- Saudi Arabia/epidemiology
- Sulfonamides/adverse effects
- Ultrasonography/methods
- COVID-19 Drug Treatment
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Affiliation(s)
- Saleh A. Alqahtani
- From the Liver Transplant Unit, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- From the Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, United States
| | | | - Almoutaz Hashim
- From the Department of Medicine, University of Jeddah, Jeddah, Saudi Arabia
| | - Thamer H. Alenazi
- From the College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- From the Infectious Disease Division, King Abdulaziz Medical City, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Mohammed AlJawad
- From the Multi-organ Transplant Center, King Fahad Specialist Hospital, Dammam. Saudi Arabia
| | | | - Mohammed Y. Alghamdi
- From the Department of Medicine, King Fahd Military Medical Complex, Dhahran, Saudi Arabia
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19
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Valour F, Conrad A, Ader F, Launay O. Vaccination in adult liver transplantation candidates and recipients. Clin Res Hepatol Gastroenterol 2020; 44:126-134. [PMID: 31607643 DOI: 10.1016/j.clinre.2019.08.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 08/26/2019] [Indexed: 02/07/2023]
Abstract
In patients with chronic liver disease and liver transplant recipients, cirrhosis-associated immune dysfunction syndrome and immunosuppressant drug regimens required to prevent graft rejection lead to a high risk of severe infections, associated with acute liver decompensation, graft loss and increased mortality. In addition to maintain their global health status, vaccination represents a major preventive measure against specific infectious risks of particular concern in this population, such as invasive pneumococcal diseases, influenza or viral hepatitis A and B. However, immunization in this setting raises several issues: i) recommended vaccination schedules rely on sparse immunogenicity data without clinical efficacy and effectiveness trials designed for this specific population; ii) dynamics of immunosuppression makes timing of immunization challenging; iii) live attenuated vaccines are contraindicated after transplantation; and iv) vaccines tolerance is poorly known in cirrhotic patients. This review outlines the rational for vaccination in adult liver transplant candidates and recipients and available data regarding immunization in this specific population.
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Affiliation(s)
- Florent Valour
- Service des maladies infectieuses et tropicales, Hospices Civils de Lyon, 69004 Lyon, France; Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude-Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Univ Lyon, 69007, Lyon, France; Université Claude-Bernard Lyon 1, 69008 Lyon, France
| | - Anne Conrad
- Service des maladies infectieuses et tropicales, Hospices Civils de Lyon, 69004 Lyon, France; Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude-Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Univ Lyon, 69007, Lyon, France; Université Claude-Bernard Lyon 1, 69008 Lyon, France
| | - Florence Ader
- Service des maladies infectieuses et tropicales, Hospices Civils de Lyon, 69004 Lyon, France; Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude-Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Univ Lyon, 69007, Lyon, France; Université Claude-Bernard Lyon 1, 69008 Lyon, France
| | - Odile Launay
- Inserm, CIC 1417, F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), 75014 Paris, France; Université de Paris, 75014 Paris, France; Assistance Publique-Hôpitaux de Paris, CIC Cochin Pasteur, Hôpital Cochin Paris, 75014 Paris, France.
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20
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Härmälä S, Parisinos CA, Shallcross L, O'Brien A, Hayward A. Effectiveness of influenza vaccines in adults with chronic liver disease: a systematic review and meta-analysis. BMJ Open 2019; 9:e031070. [PMID: 31494620 PMCID: PMC6731888 DOI: 10.1136/bmjopen-2019-031070] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 08/13/2019] [Accepted: 08/19/2019] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES Patients with liver disease frequently require hospitalisation with infection often the trigger. Influenza vaccination is an effective infection prevention strategy in healthy and elderly but is often perceived less beneficial in patients with liver disease. We investigated whether influenza vaccination triggered serological response and prevented hospitalisation and death in liver disease. DESIGN Systematic review and meta-analysis. DATA SOURCES MEDLINE, EMBASE, PubMed and CENTRAL up to January 2019. ELIGIBILITY CRITERIA Randomised or observational studies of the effects of influenza vaccine in adults with liver disease. DATA EXTRACTION AND SYNTHESIS Two reviewers screened studies, extracted data and assessed risk of bias and quality of evidence. Primary outcomes were all-cause hospitalisation and mortality. Secondary outcomes were cause-specific hospitalisation and mortality, and serological vaccine response. Random-effects meta-analysis was used to estimate pooled effects of vaccination. RESULTS We found 10 041 unique records, 286 were eligible for full-text review and 12 were included. Most patients had viral liver disease. All studies were of very low quality. Liver patients both with and without cirrhosis mounted an antibody response to influenza vaccination, and vaccination was associated with a reduction in risk of hospital admission from 205/1000 to 149/1000 (risk difference -0.06, 95% CI -0.07 to 0.04) in patients with viral liver disease. Vaccinated patients were 27% less likely to be admitted to hospital compared with unvaccinated patients (risk ratio 0.73, 95% CI 0.66 to 0.80). No effect against all-cause or cause-specific mortality or cause-specific hospitalisation was found. CONCLUSIONS The low quantity and quality of the evidence means that the protective vaccine effect may be uncertain. Considering the high risk of serious health outcomes from influenza infection in patients with liver disease and the safety and low cost of vaccination, overall, the potential benefits of seasonal vaccination both to patients and the healthcare systems are likely to outweigh the costs and risks associated with vaccination. PROSPERO REGISTRATION NUMBER CRD42017067277.
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Affiliation(s)
- Suvi Härmälä
- Institute of Health Informatics, University College London, London, UK
| | | | - Laura Shallcross
- Institute of Health Informatics, University College London, London, UK
| | | | - Andrew Hayward
- Institute of Epidemiology and Health Care, University College London, London, UK
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21
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Nakanishi K, Kaito H, Ogi M, Takai D, Fujimura J, Horinouchi T, Yamamura T, Minamikawa S, Ninchoji T, Nozu K, Imadome KI, Iijima K. Three Severe Cases of Viral Infections with Post-Kidney Transplantation Successfully Confirmed by Polymerase Chain Reaction and Flow Cytometry. Case Rep Nephrol Dial 2018; 8:198-206. [PMID: 30397600 PMCID: PMC6206958 DOI: 10.1159/000493092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Accepted: 08/20/2018] [Indexed: 11/19/2022] Open
Abstract
Viral infections in patients with post-kidney transplantation are often difficult to diagnose as well as treat. We herein report three cases with severe viral infections after kidney transplantation. All their causative pathogens could be detected promptly by polymerase chain reaction and flow cytometry during the early stages of infection. These examinations would also be of great use to monitor therapeutic responses and disease activity. It is indeed true that no specific treatment is available for most of the viral infections, but we should be aware that some infections, such as Epstein-Barr virus infection, can be treatable with prompt and specific treatment, such as rituximab.
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Affiliation(s)
- Keita Nakanishi
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hiroshi Kaito
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Miki Ogi
- Hyogo Prefectural Institute of Public Health and Consumer Sciences Public Health Science Research Center, Kobe, Japan
| | - Denshi Takai
- Hyogo Prefectural Institute of Public Health and Consumer Sciences Public Health Science Research Center, Kobe, Japan
| | - Junya Fujimura
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoko Horinouchi
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomohiko Yamamura
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shogo Minamikawa
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takeshi Ninchoji
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kandai Nozu
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ken-Ichi Imadome
- Division of Advanced Medicine for Virus Infections, National Center for Child Health and Development, Tokyo, Japan
| | - Kazumoto Iijima
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
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22
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Sellers SA, Hagan RS, Hayden FG, Fischer WA. The hidden burden of influenza: A review of the extra-pulmonary complications of influenza infection. Influenza Other Respir Viruses 2018; 11:372-393. [PMID: 28745014 PMCID: PMC5596521 DOI: 10.1111/irv.12470] [Citation(s) in RCA: 272] [Impact Index Per Article: 38.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/11/2017] [Indexed: 12/13/2022] Open
Abstract
Severe influenza infection represents a leading cause of global morbidity and mortality. Although influenza is primarily considered a viral infection that results in pathology limited to the respiratory system, clinical reports suggest that influenza infection is frequently associated with a number of clinical syndromes that involve organ systems outside the respiratory tract. A comprehensive MEDLINE literature review of articles pertaining to extra‐pulmonary complications of influenza infection, using organ‐specific search terms, yielded 218 articles including case reports, epidemiologic investigations, and autopsy studies that were reviewed to determine the clinical involvement of other organs. The most frequently described clinical entities were viral myocarditis and viral encephalitis. Recognition of these extra‐pulmonary complications is critical to determining the true burden of influenza infection and initiating organ‐specific supportive care.
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Affiliation(s)
- Subhashini A Sellers
- Division of Pulmonary and Critical Care Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Robert S Hagan
- Division of Pulmonary and Critical Care Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Frederick G Hayden
- Division of Infectious Diseases, The University of Virginia, Charlottesville, VA, USA
| | - William A Fischer
- Division of Pulmonary and Critical Care Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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23
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Härmälä S, Parisinos C, Shallcross L, O'Brien A, Hayward A. Effectiveness of pneumococcal and influenza vaccines to prevent serious health complications in adults with chronic liver disease: a protocol for a systematic review. BMJ Open 2018; 8:e018223. [PMID: 29549199 PMCID: PMC5857657 DOI: 10.1136/bmjopen-2017-018223] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Revised: 01/31/2018] [Accepted: 02/08/2018] [Indexed: 01/28/2023] Open
Abstract
INTRODUCTION In advanced chronic liver disease, diseases caused by common bacteria Streptococcus pneumoniae or influenza virus put people at an increased risk of serious health complications and death. The effectiveness of the available vaccines in reducing the risk of poor health outcomes, however, is less clear. METHODS AND ANALYSIS We will search Medline (Ovid), Embase (Ovid), PubMed and Cochrane Central Register of Controlled Trials for published reports on randomised controlled trials and observational studies on the effectiveness of pneumococcal and influenza vaccines in people with chronic liver disease. Two independent reviewers will screen the studies for eligibility, extract data and assess study quality and risk of bias. Random effects meta-analyses will be performed as appropriate. ETHICS AND DISSEMINATION Formal ethical approval is not required, as no primary data will be collected for this study. We will publish results of this study in relevant peer-reviewed medical journal or journals. Where possible, the study results will also be presented as posters or talks at relevant medical conferences and meetings. PROSPERO REGISTRATION NUMBER CRD42017067277.
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Affiliation(s)
- Suvi Härmälä
- Institute of Health Informatics, University College London, London, UK
| | | | - Laura Shallcross
- Institute of Health Informatics, University College London, London, UK
| | | | - Andrew Hayward
- Institute of Epidemiology and Health Care, University College London, London, UK
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24
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Yükselmiş U, Girit S, Çağ Y, Özçetin M. A child with acute liver failure associated with influenza A and resolved with plasma exchange treatment. HONG KONG J EMERG ME 2018. [DOI: 10.1177/1024907918754441] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Introduction: Although liver support systems play a major role as a bridge to transplantation, they may sometimes serve as a lifesaving treatment eliminating this need. Case presentation: We report on a 4-year-old boy who developed acute liver failure due to an influenza A (H3N2) infection as confirmed by clinical and laboratory data (molecular typing, stage 3 encephalopathy, brain edema, increased levels of ammonia, bilirubin, and international normalized ratio 5.2). Testing for any possible underlying liver disease showed no congenital or acquired liver pathology. Oral oseltamivir treatment was initiated and liver support therapy with plasma exchange was performed as a bridge to transplantation. A total of three plasma exchange sessions every other day, with fresh frozen plasma 1.5 times the total blood volume for the first course and 1 times for the subsequent courses, were performed. After the first plasma exchange, encephalopathy improved to stage 2, accompanied by substantial decreases in the elevated liver function tests. At the end of three plasma exchange sessions, the patient’s clinical condition improved significantly. At 14 days after admission, deep tendon reflexes of the patient were normal and levels of alanine transaminase, aspartate transaminase, bilirubin, ammonia, and international normalized ratio returned to normal. Liver support treatment with plasma exchange resulted in complete recovery and the patient was discharged on the 17th day of admission. Conclusion: Acute supportive treatment with plasma exchange proved to be life-saving in our case.
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Affiliation(s)
- Ufuk Yükselmiş
- Division of Pediatric Intensive Care Unit, Department of Pediatrics, Dr. Lutfi Kırdar Kartal Educational and Research Hospital, Istanbul, Turkey
| | - Saniye Girit
- Division of Pediatric Pulmonology, Department of Pediatrics, Dr. Lutfi Kırdar Kartal Education and Research Hospital, Istanbul, Turkey
| | - Yakup Çağ
- Department of Pediatrics, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey
| | - Mustafa Özçetin
- Department of Pediatrics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Ison MG, Heldman M. Bacterial Infections. HEPATIC CRITICAL CARE 2018. [PMCID: PMC7120903 DOI: 10.1007/978-3-319-66432-3_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Bacterial infections are the most significant infectious source of morbidity and mortality in cirrhotic patients. Bacteria infections result is both acute decompensation in chronic liver disease and mortality in patients with decompensated cirrhosis. Spontaneous bacterial peritonitis (SBP), bacteremia, pneumonia, urinary tract infections (UTI) and skin and soft tissue infection (SSTI) are the most significant sources of infection in cirrhosis. Bacterial infections can precipitate renal failure and worsening hepatic encephalopathy, and patients with sepsis and liver disease have higher rates of acute respiratory distress syndrome (ARDS) and coagulopathy.
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Loubet P, Loulergue P, Galtier F, Launay O. Seasonal influenza vaccination of high-risk adults. Expert Rev Vaccines 2016; 15:1507-1518. [PMID: 27169689 DOI: 10.1080/14760584.2016.1188696] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
INTRODUCTION Adults at a high risk of severe influenza, because of their age and/or underlying health disorders, should receive seasonal influenza vaccination in order to reduce the incidence of severe illness and premature death. However, because current influenza vaccines are perceived to have suboptimal efficacy, vaccine coverage is below the recommended level in this population. Areas covered: This review examines, for each high-risk group, available data on influenza infection, vaccine efficacy and safety, and vaccine coverage. We conducted a literature search in the PubMed database to identify randomized controlled trials, observational studies and reviews published from 2000 through 2015 on both seasonal and pandemic influenza. Only studies published in English were considered. While the topic of this review is seasonal influenza, data on pandemics are included when relevant. Expert Commentary: Current seasonal influenza vaccines are only moderately protective, and vaccines eliciting broader and more durable immunity are therefore needed. Research on the use of higher doses, adjuvants, and a universal influenza vaccine is ongoing. Influenza vaccine coverage needs to be increased. Vaccination of contacts of high-risk individuals, including healthcare workers, should be encouraged.
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Affiliation(s)
- Paul Loubet
- a Inserm, CIC 1417 , Paris , France.,b Department of Infectious Diseases , Assistance Publique-Hôpitaux de Paris (AP-HP), Cochin Broca Hôtel-Dieu hospital, CIC Cochin Pasteur , Paris , France
| | - Pierre Loulergue
- a Inserm, CIC 1417 , Paris , France.,b Department of Infectious Diseases , Assistance Publique-Hôpitaux de Paris (AP-HP), Cochin Broca Hôtel-Dieu hospital, CIC Cochin Pasteur , Paris , France.,c Inserm, F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC) , Paris , France
| | - Florence Galtier
- c Inserm, F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC) , Paris , France.,d CHRU de Montpellier, CIC 1411, Hôpital Saint-Eloi , Montpellier , France
| | - Odile Launay
- a Inserm, CIC 1417 , Paris , France.,b Department of Infectious Diseases , Assistance Publique-Hôpitaux de Paris (AP-HP), Cochin Broca Hôtel-Dieu hospital, CIC Cochin Pasteur , Paris , France.,c Inserm, F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC) , Paris , France.,e Université Paris Descartes, Sorbonne Paris Cité , Paris , France
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Ortega-Alonso A, García-Cortés M, Fernández-Castañer A, Ruiz J, González-Amores Y, Andrade RJ. [Acute hepatitis in a woman with influenza A virus: Cause or coincidence?]. GASTROENTEROLOGIA Y HEPATOLOGIA 2016; 39:20-21. [PMID: 26072137 DOI: 10.1016/j.gastrohep.2015.04.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2015] [Revised: 04/22/2015] [Accepted: 04/23/2015] [Indexed: 06/04/2023]
Affiliation(s)
- Aida Ortega-Alonso
- Unidad de Gestión Clínica de Digestivo, Instituto de Biomedicina de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, España.
| | - Miren García-Cortés
- Unidad de Gestión Clínica de Digestivo, Instituto de Biomedicina de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), España
| | - Alejandra Fernández-Castañer
- Unidad de Gestión Clínica de Digestivo, Instituto de Biomedicina de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), España
| | - Josefa Ruiz
- Unidad de Gestión Clínica de Medicina Interna, Unidad de Infecciosos, Hospital Universitario Virgen de la Victoria, Málaga, España
| | - Yolanda González-Amores
- Unidad de Gestión Clínica de Digestivo, Instituto de Biomedicina de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), España
| | - Raúl J Andrade
- Unidad de Gestión Clínica de Digestivo, Instituto de Biomedicina de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), España
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Annual influenza vaccination reduces total hospitalization in patients with chronic hepatitis B virus infection: A population-based analysis. Vaccine 2015; 34:120-7. [PMID: 26614589 DOI: 10.1016/j.vaccine.2015.10.129] [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] [Received: 02/04/2015] [Revised: 09/03/2015] [Accepted: 10/28/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND This study evaluated hospitalization and mortality in patients with chronic hepatitis B virus infection (HBV (+)) and matched comparison patients after stratifying the patients according to annual influenza vaccination (Vaccine (+)). METHODS Data from Taiwan's National Health Insurance program from 2000 to 2009 were used to identify HBV(+)/vaccine(+) (n=4434), HBV(+)/Vaccine(-) (n=3646), HBV(-)/Vaccine(+) (n=8868), and HBV(-)/Vaccine(-) (n=8868) cohorts. The risk of pneumonia/influenza, respiratory failure, intensive care, hospitalization, and mortality in the four cohorts was evaluated. RESULTS The total hospitalization rate was significantly lower in patients with chronic HBV infection who received an annual influenza vaccination than in chronic HBV-infected patients who did not receive an influenza vaccination (16.29 vs. 24.02 per 100 person-years), contributing to an adjusted hazard ratio (HR) of 0.56 (95% confidence interval (CI)=0.50-0.62). The HBV(+)/Vaccine(+) cohort also had lower risks than the HBV(+)/Vaccine(-) cohort for pneumonia and influenza (adjusted HR=0.79, 95% CI=0.67-0.92), intensive care unit admission (adjusted HR=0.33, 95% CI=0.25-0.43), and mortality (adjusted HR=0.19, 95% CI=0.15-0.24). CONCLUSIONS Our results suggest that annual influenza vaccination can reduce the risk of hospitalization and mortality in patients with chronic HBV infection.
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Mok MMY, Cheng VCC, Lui SL, Kwan LPY, Chan GCW, Yap DYH, Chan TM, Lo WK. Severe liver failure due to influenza A infection in a hemodialysis patient. Hemodial Int 2015. [DOI: 10.1111/hdi.12335] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Maggie Ming Yee Mok
- Division of Nephrology; Department of Medicine; Queen Mary Hospital; University of Hong Kong; Hong Kong
| | | | - Sing Leung Lui
- Division of Nephrology; Department of Medicine; Tung Wah Hospital; Hong Kong
| | - Lorraine Pui Yuen Kwan
- Division of Nephrology; Department of Medicine; Queen Mary Hospital; University of Hong Kong; Hong Kong
| | - Gary Chi Wang Chan
- Division of Nephrology; Department of Medicine; Tung Wah Hospital; Hong Kong
| | - Desmond Yat Hin Yap
- Division of Nephrology; Department of Medicine; Queen Mary Hospital; University of Hong Kong; Hong Kong
| | - Tak Mao Chan
- Division of Nephrology; Department of Medicine; Queen Mary Hospital; University of Hong Kong; Hong Kong
| | - Wai Kei Lo
- Division of Nephrology; Department of Medicine; Tung Wah Hospital; Hong Kong
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Abstract
Vaccines play a key role in the prevention of illness in the elderly, are cost effective, and generally safe. Hepatitis C, cirrhosis, autoimmune hepatitis, and inflammatory bowel disease are more prevalent than ever among older adults. Along with an age-related decline in immune system function (immunosenescence), these diseases make elderly individuals more susceptible to infections and more likely to experience a poor outcome relative to their younger counterparts. Vaccinations also appear to be less effective in the elderly, warranting research into different vaccination strategies such as booster vaccines, higher doses of vaccine, and measurement of antibody titers to guide vaccination.
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Affiliation(s)
- Henry A Horton
- Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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31
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Squires RH, Ng V, Romero R, Ekong U, Hardikar W, Emre S, Mazariegos GV. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Hepatology 2014; 60:362-98. [PMID: 24782219 DOI: 10.1002/hep.27191] [Citation(s) in RCA: 141] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Accepted: 04/22/2014] [Indexed: 12/16/2022]
Affiliation(s)
- Robert H Squires
- Department of Pediatrics, University of Pittsburgh School of Medicine; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA
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Ohfuji S, Fukushima W, Sasaki Y, Tamori A, Kurai O, Kioka K, Maeda K, Maeda A, Hirota Y. Influenza A(H1N1)pdm09 vaccine effectiveness and other characteristics associated with hospitalization in chronic liver disease patients. Liver Int 2014; 34:700-6. [PMID: 23981146 PMCID: PMC4265193 DOI: 10.1111/liv.12295] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2013] [Accepted: 07/24/2013] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS To date, few studies have investigated the clinical effectiveness of influenza vaccine in chronic liver disease patients. The aim of this study was to examine the effectiveness of monovalent inactivated influenza A(H1N1)pdm09 vaccine and other characteristics associated with hospitalization in patients with chronic hepatitis C. METHODS We conducted a hospital-based cohort study during influenza A(H1N1)pdm09 pandemic. A total of 408 patients (132 vaccinated, 276 unvaccinated) with detectable HCV-RNA were followed up with respect to any hospitalization using a weekly postal questionnaire. Reported hospitalizations were verified by medical records. RESULTS During the epidemic period, 28 hospitalizations (6 vaccinated, 22 unvaccinated) were observed. After adjustment for potential confounders, vaccination decreased the odds ratio (OR) for hospitalization with marginal significance (OR = 0.43, 95%CI = 0.16-1.17). Besides, positive association with hospitalization was observed in patients with albumin levels <3.5 g/dl (OR = 8.40, 3.66-19.3) and steroid users (OR = 5.58, 0.98-31.7). CONCLUSIONS Among patients with chronic hepatitis C, A(H1N1)pdm09 vaccine appeared to have a protective effect against hospitalization. Those patients with a higher risk for hospitalization should be carefully followed during the influenza season, even when vaccinated.
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Affiliation(s)
- Satoko Ohfuji
- Department of Public Health, Osaka City University Faculty of MedicineOsaka, Japan
| | - Wakaba Fukushima
- Department of Public Health, Osaka City University Faculty of MedicineOsaka, Japan
| | - Yachiyo Sasaki
- Department of Public Health, Osaka City University Faculty of MedicineOsaka, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka City University Faculty of MedicineOsaka, Japan
| | - Osamu Kurai
- Department of Gastroenterology and Hepatology, Osaka City Juso HospitalOsaka, Japan
| | - Kiyohide Kioka
- Department of Hepatology, Osaka City General HospitalOsaka, Japan
| | - Kazuhiro Maeda
- The Research Foundation for Microbial Diseases of Osaka UniversityOsaka, Japan
| | - Akiko Maeda
- Department of Public Health, Osaka City University Faculty of MedicineOsaka, Japan
| | - Yoshio Hirota
- Department of Public Health, Osaka City University Faculty of MedicineOsaka, Japan
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Bal CK, Bhatia V, Kumar S, Saini D, Khillan V, Gupta E, Rathor N, Choudhury A, Kumar N, Daman R, Sarin SK. Influenza A/H1/N1/09 infection in patients with cirrhosis has a poor outcome: a case series. Indian J Gastroenterol 2014; 33:178-82. [PMID: 24470044 DOI: 10.1007/s12664-014-0443-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2013] [Accepted: 01/05/2014] [Indexed: 02/04/2023]
Abstract
Seasonal influenza is often unsuspected in cirrhotic patients admitted with pneumonia and acute hepatic decompensation. We report five consecutive patients with influenza A subtype H1N1 2009 strain (influenza A/H1N1/09) admitted to our intensive care unit. All had a short history of rapidly worsening respiratory symptoms, but there were no characteristic clinical or radiographic features. Secondary pulmonary infection was universal. All five patients died, despite prompt institution of oseltamivir and intensive supportive care. A high index of suspicion is needed for influenza infection among patients with decompensated cirrhosis.
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Affiliation(s)
- Chinmaya Kumar Bal
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110 070, India
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Mawson AR. Role of Fat-Soluble Vitamins A and D in the Pathogenesis of Influenza: A New Perspective. ACTA ACUST UNITED AC 2013. [DOI: 10.5402/2013/246737] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Reduced exposure to solar radiation, leading to a deficiency of vitamin D and hence impaired innate immunity, has been suggested as a trigger for influenza viral replication and as an explanation of seasonal influenza. Although this hypothesis accounts for many unexplained facts about the epidemiology of influenza, gaps remain in understanding the pathogenesis and manifestations of the disease. Several observations suggest a role for vitamin A compounds (retinoids) in the disease. This paper presents a new model of the etiopathogenesis of influenza, suggesting that host resistance and susceptibility depend importantly on the ratio of vitamin D to vitamin A activity. Retinoid concentrations within normal physiological limits appear to inhibit influenza pathogenesis whereas higher background concentrations (i.e., very low vitamin D : A ratios) increase the risk of severe complications of the disease. There is also evidence that influenza-induced or preexisting liver disease, diabetes, and obesity worsen the severity of infection, possibly via liver dysfunction and alterations in retinoid metabolism. The model could be tested by determining the presence of retinoids in the secretions of patients with influenza and by studies of retinoid profiles in patients and controls. Potential strategies for prevention and treatment are discussed.
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Affiliation(s)
- Anthony R. Mawson
- Department of Health Policy and Management, School of Health Sciences, College of Public Service, Jackson State University,
350 West Woodrow Wilson Avenue, Room 229, Jackson, MS 39213, USA
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Immunizations in chronic liver disease: what should be done and what is the evidence. Curr Gastroenterol Rep 2013; 15:300. [PMID: 23250700 DOI: 10.1007/s11894-012-0300-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Infections are common in patients with chronic liver disease, especially those with cirrhosis. Patients with advanced liver disease, who develop bacterial infections, are at a substantially higher risk of death. As liver disease progresses, most immunizations lose their effectiveness. Overall, it is important to address immunization needs in patients with chronic liver disease early on, when immunizations are most effective. Inactivated or killed-type vaccinations rather than live, attenuated vaccinations are always preferable in patients with cirrhosis. The influenza vaccination is less effective in patients with cirrhosis and in the early post-liver transplant setting as compared to healthy individuals. The influenza vaccination may prevent hepatic decompensation, but further data are needed to confirm this. Yearly inactivated influenza vaccinations should be provided to those with chronic liver disease. The pneumonia vaccination is less effective in patients with cirrhosis, with a further decline in protective serologies after liver transplantation. Standard guidelines for the administration of Pneumovax23 for immunocompromised hosts apply to patients with chronic liver disease. Chronic liver disease also leads to higher non-response rates to the hepatitis B vaccination. Early-stage chronic liver disease patients should receive conventional hepatitis B series. Cirrhotics benefit from a double-dose hepatitis B vaccination at standard intervals. Hepatitis A superimposed on chronic viral hepatitis or chronic liver disease increases risk of mortality. Hepatitis A vaccination effectiveness wanes in cirrhosis, and should if possible be given before the development of cirrhosis. More data are needed for routine use of herpes zoster and human papillomavirus in chronic liver disease.
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Attenuated antigen-specific T cell responses in cirrhosis are accompanied by elevated serum interleukin-10 levels and down-regulation of HLA-DR on monocytes. BMC Gastroenterol 2013; 13:37. [PMID: 23446058 PMCID: PMC3598528 DOI: 10.1186/1471-230x-13-37] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2012] [Accepted: 02/21/2013] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Advanced liver disease predisposes to bacterial translocation and endotoxaemia which can contribute to elevated circulating levels of IL-10 and down-regulation of MHC class II on antigen-presenting cells. We sought to evaluate antigen-specific T-cell responses toward common viral antigens in order to investigate defects in cellular immunity in cirrhosis. METHODS Peripheral blood was obtained from 22 cirrhotic patients with systemic inflammation, 13 cirrhotic patients without systemic inflammation and 14 healthy controls. C-reactive protein was used as an indicator for systemic inflammation using a cut-off of 10 mg/l. Intracellular Th1 cytokines were quantified after T cell-stimulation with the viral peptides EBNA1 and BZLF1 or the bacterial superantigen SEB by flow cytometry. Serum levels of lipopolysaccharide-binding protein (LBP) and IL-10 were quantified by ELISA. RESULTS Compared to healthy controls, patients with cirrhosis had higher circulating levels of LBP and IL-10, an expansion of peripheral blood CD14+ monocytes with low HLA-DR expression and an increased fraction of CD25-positive CD4+ and CD8+ T cells. These findings were most pronounced in cirrhotic patients with systemic inflammation but fell short of reaching statistical significance when comparing against cirrhotic patients without systemic inflammation. In the former group TNF-α production in CD4+ and CD8+ T cells was reduced after stimulation with SEB, whereas there was no significant difference between the total cohort of cirrhotic patients and controls. After stimulation with the overlapping peptide pools for viral antigens EBNA1 and BZLF1, the number of responding T cells and the amount of TNF-α or IFN-γ production did not differ between the three pre-defined groups. However, cirrhotic patients with null-responses to EBV peptides had significantly higher serum IL-10 levels than responders to EBV peptides. Furthermore, TNF-α production in responding T cells was attenuated in patients with a high frequency of CD14+ HLA-DR- monocytes. CONCLUSION Our data suggest that bacterial translocation, endotoxaemia, inflammation and T cell activation in cirrhosis are accompanied by an increase in circulating anti-inflammatory cytokines, reduced monocytic MHC class II expression and attenuated cytokine production in T cells. These changes are likely to contribute to altered adaptive immune responses during infection or after vaccination.
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Hung TH, Tseng CW, Hsieh YH, Tseng KC, Tsai CC, Tsai CC. High mortality of pneumonia in cirrhotic patients with ascites. BMC Gastroenterol 2013; 13:25. [PMID: 23390924 PMCID: PMC3599048 DOI: 10.1186/1471-230x-13-25] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2012] [Accepted: 01/28/2013] [Indexed: 12/18/2022] Open
Abstract
Background Cirrhotic patients with ascites are prone to develop various infectious diseases. This study aimed to evaluate the occurrence and effect of major infectious diseases on the mortality of cirrhotic patients with ascites. Methods We reviewed de-identified patient data from the National Health Insurance Database, derived from the Taiwan National Health Insurance Program, to enroll 4,576 cirrhotic patients with ascites, who were discharged from Taiwan hospitals between January 1, 2004 and June 30, 2004. We collected patients’ demographic and clinical data, and reviewed diagnostic codes to determine infectious diseases and comorbid disorders of their hospitalizations. Patients were divided into an infection group and non-infection group and hazard ratios (HR) were determined for specific infectious diseases. Results Of the total 4,576 cirrhotic patients with ascites, 1,294 (28.2%) were diagnosed with infectious diseases during hospitalization. The major infectious diseases were spontaneous bacterial peritonitis (SBP) (645, 49.8%), urinary tract infection (151, 11.7%), and pneumonia (100, 7.7%). After adjusting for patients’ age, gender, and other comorbid disorders, the HRs of infectious diseases for 30-day and 90-day mortality of cirrhotic patients with ascites were 1.81 (1.54-2.11) and 1.60 (1.43-1.80) respectively, compared to those in the non-infection group. The adjusted HRs of pneumonia, urinary tract infection (UTI), spontaneous bacterial peritonitis (SBP), and sepsis without specific focus (SWSF) were 2.95 (2.05-4.25), 1.32 (0.86-2.05), 1.77 (1.45-2.17), and 2.19 (1.62-2.96) for 30-day mortality, and 2.57 (1.93-3.42), 1.36 (1.01-1.82), 1.51 (1.29-1.75), and 2.13 (1.70-2.66) for 90-day mortality, compared to those in the non-infection group. Conclusion Infectious diseases increased 30-day and 90-day mortality of cirrhotic patients with ascites. Among all infectious diseases identified, pneumonia carried the highest risk for mortality.
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Affiliation(s)
- Tsung-Hsing Hung
- Division of Gastroenterology, Department of Medicine, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan
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Ohfuji S, Fukushima W, Tamori A, Maeda K, Maeda A, Hirota Y. Immunogenicity of influenza A(H1N1)pdm09 vaccine and the associated factors on lowered immune response in patients with hepatitis C. Influenza Other Respir Viruses 2012; 7:456-65. [PMID: 22897938 PMCID: PMC5779820 DOI: 10.1111/j.1750-2659.2012.00424.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Background Patients with underlying disease represent a high‐risk group for influenza‐associated complications and hospitalization. However, few studies investigated the immunogenicity of influenza vaccine in patients with liver disease. Objective To examine immunogenicity of influenza A(H1N1)pdm09 vaccine in patients with liver disease and to explore the associated factors on lowered immune response. Patients/Methods A single subcutaneous dose of monovalent inactivated unadjuvanted split‐virus influenza A(H1N1)pdm09 vaccination was performed in 80 patients with chronic hepatitis C virus infection at Osaka City University Hospital in Japan. To measure the hemagglutination inhibition antibody titer, serum samples were collected before and 3 weeks after vaccination. Results No serious adverse events were observed. After vaccination, antibody titers ≥1:40 were observed in 56 patients (71%). The corresponding seroconversion proportion was 72%, and the mean fold rise was 10·3. Immune responses were robust regardless of severity of liver disease or existence of probable cirrhosis. However, patients with older age, lower body mass index, or receiving Stronger Neo‐Minophagen C tended to show lower antibody responses to A(H1N1)pdm09 vaccine. In addition, reduced immune responses were observed in patients who had received the 2009/10 seasonal vaccination prior to A(H1N1)pdm09 vaccination. Conclusions Single dose of A(H1N1)pdm09 vaccine achieved a sufficient level of immunity among patients with chronic hepatitis C. Antibody response may be affected by age, body mass index, Stronger Neo‐Minophagen C administration, and recent seasonal influenza vaccination.
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Affiliation(s)
- Satoko Ohfuji
- Department of Public Health, Osaka City University Faculty of Medicine, Osaka, Japan.
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Bunchorntavakul C, Chavalitdhamrong D. Bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. World J Hepatol 2012; 4:158-68. [PMID: 22662285 PMCID: PMC3365435 DOI: 10.4254/wjh.v4.i5.158] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2011] [Revised: 09/08/2011] [Accepted: 04/25/2012] [Indexed: 02/06/2023] Open
Abstract
Cirrhotic patients are immunocompromised with a high risk of infection. Proinflammatory cytokines and hemodynamic circulation derangement further facilitate the development of serious consequences of infections. Other than spontaneous bacterial peritonitis, bacteremia and bacterial infections of other organ systems are frequently observed. Gram-negative enteric bacteria are the most common causative organism. Other bacterial infections, such as enterococci, Vibrio spp., Aeromonas spp., Clostridium spp., Listeria monocytogenes, Plesiomonas shigelloides and Mycobacterium tuberculosis are more prevalent and more virulent. Generally, intravenous third generation cephalosporins are recommended as empirical antibiotic therapy. Increased incidences of gram-positive and drug-resistant organisms have been reported, particularly in hospital-acquired infections and in patients receiving quinolones prophylaxis. This review focuses upon epidemiology, microbiology, clinical features and treatment of infections in cirrhosis other than spontaneous bacterial peritonitis, including pathogen-specific and liver disease-specific issues.
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Affiliation(s)
- Chalermrat Bunchorntavakul
- Chalermrat Bunchorntavakul, Division of Gastroenterology and Hepatology, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok 12000, Thailand
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Singal AK, Duchini A. Liver transplantation in acute alcoholic hepatitis: Current status and future development. World J Hepatol 2011; 3:215-8. [PMID: 21954410 PMCID: PMC3180607 DOI: 10.4254/wjh.v3.i8.215] [Citation(s) in RCA: 21] [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: 11/26/2011] [Revised: 06/13/2011] [Accepted: 07/15/2011] [Indexed: 02/06/2023] Open
Abstract
Acute alcoholic hepatitis (AH) is a distinct clinical entity amongst patients with chronic alcohol abuse. Patients with severe AH are at risk of dying in about 20%-25% cases despite specific treatment with corticosteroids and/or pentoxifylline. Clearly, a need for an additional more effective treatment option is unmet currently. Liver transplantation (LT), a definitive treatment option for alcoholic cirrhosis requires 6 mo abstinence. However, this rule cannot be applied to patients with AH as these patients are actively drinking prior to their presentation. Shortage of donors, ethical issues, and fear of recidivism after transplantation with less than 6 mo pre-transplant abstinence are some of the reasons behind this rule of 6 mo of abstinence and hesitancy of transplanting patients with AH. These issues are debated at length in this manuscript. Further, retrospective studies have shown that patients undergoing transplantation for alcoholic cirrhosis and having histological changes of AH have been shown to fare as well when compared to patients without these histological changes. Recently, French workers have reported a case matched prospective study showing encouraging data on the usefulness of LT for patients who are non-responders to corticosteroid and/or pentoxifylline therapy. Future studies are needed to identify patients with severe AH who are going to benefit most with LT. In the light of emerging data on the efficacy of LT in improving survival of patients with severe acute AH who do not respond to corticosteroids, the time is ripe to re-evaluate our policy of LT in patients with AH.
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Affiliation(s)
- Ashwani K Singal
- Ashwani K Singal, Andrea Duchini, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905-0001, United States
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Abstract
OBJECTIVES To review the management of complications related to end-stage liver disease in the intensive care unit. The goal of this review is to address topics important to the practicing physician. DATA SOURCES We performed an organ system-based PubMed literature review focusing on the diagnosis and treatment of critical complications of end-stage liver disease. DATA SYNTHESIS AND FINDINGS: When available, preferential consideration was given to randomized controlled trials. In the absence of trials, observational and retrospective studies and consensus opinions were included. We present our recommendations for the neurologic, cardiovascular, pulmonary, gastrointestinal, renal, and infectious complications of end-stage liver disease. CONCLUSIONS Complications related to end-stage liver disease have significant morbidity and mortality. Management of these complications in the intensive care unit requires awareness and expertise among physicians from a wide variety of fields.
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Abstract
BACKGROUND Data on the immunogenicity of the influenza vaccine in children after liver transplantation are sparse. Our study aims to evaluate the response of such patients to the trivalent influenza vaccine, administered by different protocols in 2 influenza seasons. METHODS Children attending the Liver Transplantation Unit of a tertiary care medical center were prospectively recruited and immunized with the inactivated subvirion influenza vaccine during the influenza seasons of 2004/2005 (1 dose, n = 18) and 2005/2006 (2 doses 4-6 weeks apart, n = 32). Antibodies were measured by hemagglutination inhibition assay. Immunity was defined as a titer of ≥1:40, and response was defined as a ≥4-fold increase in antibody titer from baseline. RESULTS In 2004/2005, the proportions of patients with protective antibodies were similar before and after 1 dose of vaccine. We found significant difference after the first dose for the A/H3N2 Wisconsin strain (43.2% vs. 70.3%, P = 0.003) and B/Malaysia strains (8.1% vs. 35.1%, P = 0.003) and for A/H1N1 New Caledonia strain (48.6% vs. 64.9% vs. 75%, P = 0.08, 0.005, respectively) after the second dose in 2005/2006 season. In 2004/2005, geometric mean titers rose significantly (P = 0.03) for the A/H3N2 New York strain; in 2005/2006, geometric mean titers for A/H3N2 New York and B/Malaysia increased after the first dose and for A/H1N1 New Caledonia after the second dose. Antibody titers were unrelated to age at transplantation, time from transplantation, and number of immunosuppressive drugs used. No serious vaccine-related events were documented. CONCLUSIONS Liver-transplanted children respond to influenza vaccination. For some strains, the response is similar to that reported for healthy children. A second vaccine dose yielded no statistically significant benefit.
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Heffelfinger JD, Patel P, Brooks JT, Calvet H, Daley CL, Dean HD, Edlin BR, Gensheimer KF, Jereb J, Kent CK, Lennox JL, Louie JK, Lynfield R, Peters PJ, Pinckney L, Spradling P, Voetsch AC, Fiore A. Pandemic influenza: implications for programs controlling for HIV infection, tuberculosis, and chronic viral hepatitis. Am J Public Health 2009; 99 Suppl 2:S333-9. [PMID: 19797745 PMCID: PMC4504393 DOI: 10.2105/ajph.2008.158170] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/15/2009] [Indexed: 01/21/2023]
Abstract
Among vulnerable populations during an influenza pandemic are persons with or at risk for HIV infection, tuberculosis, or chronic viral hepatitis. HIV-infected persons have higher rates of hospitalization, prolonged illness, and increased mortality from influenza compared with the general population. Persons with tuberculosis and chronic viral hepatitis may also be at increased risk of morbidity and mortality from influenza because of altered immunity and chronic illness. These populations also face social and structural barriers that will be exacerbated by a pandemic. Existing infrastructure should be expanded and pandemic planning should include preparations to reduce the risks for these populations.
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Affiliation(s)
- James D Heffelfinger
- Centers for Disease Control and Prevention, Mail Stop: E-46, Atlanta, GA 30333, USA.
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Loulergue P, Launay O. Vaccinations chez les patients ayant une cirrhose. Presse Med 2009; 38:1134-40. [DOI: 10.1016/j.lpm.2008.11.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2008] [Revised: 11/07/2008] [Accepted: 11/19/2008] [Indexed: 01/07/2023] Open
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Loulergue P, Pol S, Mallet V, Sogni P, Launay O. Why actively promote vaccination in patients with cirrhosis? J Clin Virol 2009; 46:206-9. [PMID: 19501019 DOI: 10.1016/j.jcv.2009.05.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2009] [Accepted: 05/01/2009] [Indexed: 02/07/2023]
Abstract
Patients with cirrhosis are immunocompromised and have an increased risk of infection, with a worse outcome. Some of those infections may be prevented by vaccination. Immunization can reduce the morbidity and mortality associated with cirrhosis. Immunizations against hepatitis A and B viruses, influenza and pneumococcus are recommended by the French Haute Autorité de Santé since 2007. Vaccination against hepatitis A is recommended in non-immunized cirrhotic patients. Vaccination against hepatitis B is recommended in every cirrhotic patient with no serological markers, and post-vaccinal antibodies titer should be checked. Annual influenza immunization can be done in cirrhotic patients, and pneumococcal polysaccharide vaccine should be repeated after 3-5 years. Few data regarding vaccination coverage are available, but studies suggest that immunization rates are too low in this population.
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Abstract
Timely surveillance for varices and hepatocellular carcinoma, prophylaxis against spontaneous bacterial peritonitis (SBP) improve survival in patients awaiting transplantation. Early diagnosis of minimal or overt hepatic encephalopathy can delay life threatening complications, reduce need for hospitalization, and potentially improve survival pending liver transplantation.
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Affiliation(s)
- Priya Grewal
- Division of Liver Diseases, Recanati/Miller Transplantation Institute, The Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1104, New York, NY 10029, USA.
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Guardia J. Hepatitis sobre hepatitis. La hora de la prevención. Med Clin (Barc) 2008; 131:536-7. [DOI: 10.1157/13127580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Dimmock DP, Dunn JK, Feigenbaum A, Rupar A, Horvath R, Freisinger P, Mousson de Camaret B, Wong LJ, Scaglia F. Abnormal neurological features predict poor survival and should preclude liver transplantation in patients with deoxyguanosine kinase deficiency. Liver Transpl 2008; 14:1480-5. [PMID: 18825706 DOI: 10.1002/lt.21556] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Deoxyguanosine kinase (DGUOK) deficiency is the commonest type of mitochondrial DNA depletion associated with a hepatocerebral phenotype. In this article, we evaluate predictors of survival and therapeutic options in patients with DGUOK deficiency. A systematic search of MEDLINE, LILAC, and SCIELO was carried out to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other studies with clinical pertinence. DGUOK deficiency was searched with the terms dGK, DGUOK, mitochondrial DNA depletion, mtDNA, and hepatocerebral. Bibliographies of identified articles were reviewed for additional references. Thirteen identified studies met the inclusion criteria and were used in this study. The analysis revealed that DGUOK deficiency is associated with a variable clinical phenotype. Long-term survival is best predicted by the absence of profound hypotonia, significant psychomotor retardation, or nystagmus. In the presence of these features, there is increased mortality, and liver transplantation does not confer increased survival. In summary, liver transplantation appears to be futile in the presence of specific neurological signs or symptoms in patients affected with DGUOK deficiency. Conversely, in the absence of these neurological features, liver transplantation may be considered a potential treatment.
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Affiliation(s)
- David P Dimmock
- Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
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Isaguliants MG. Functionality of the immune system in patients with chronic hepatitis C: trial by superinfections and vaccinations. Expert Rev Vaccines 2007; 6:527-37. [PMID: 17669007 DOI: 10.1586/14760584.6.4.527] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Viral infections, specifically chronic, markedly influence the host response to subsequent infections and vaccinations. Does this apply to chronic hepatitis C (CHC)? The review considers this question with implications for the immune status and functionality of the immune system of a chronically HCV-infected host. The data collected here indicate that CHC may increase the risk of viral superinfections and modify their course by immunocompromising the host. Patients with CHC do not lose the 'memory' of previous infections and vaccinations but, apparently, have problems with building such immunity anew, as illustrated by their impaired response to hepatitis A and B vaccinations. This underlines the necessity of extra protection of CHC patients against blood-borne diseases, hepatitis A, possibly also varicella, influenza, tetanus, and diphtheria - immunity to which, in the Western population, appears to falter. Such immune protection has to be adapted to selective impairments of immune response characteristic to CHC. Some approaches to this are reviewed here and more need to be elaborated. Special attention has to be given to CHC patients who do not respond to common vaccines; further studies in this field are of great interest.
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Affiliation(s)
- Maria G Isaguliants
- Swedish Institute for Infectious Disease Control, Department of Virology, Stockholm, SE 17182, Sweden; and, Ivanovsky Institute of Virology, Moscow, 123098, Russia.
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