|
1
|
Amirinia F, Jabrodini A, Morovati H, Ardi P, Motamedi M. Fungal β-Glucans: Biological Properties, Immunomodulatory Effects, Diagnostic and Therapeutic Applications. INFECTIOUS DISEASES & CLINICAL MICROBIOLOGY 2025; 7:1-16. [PMID: 40225707 PMCID: PMC11991713 DOI: 10.36519/idcm.2025.448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 12/11/2025] [Indexed: 04/15/2025]
Abstract
Research from the past to the present has shown that natural ingredients in the human daily diet play a crucial role in preventing various diseases. One well-known compound is β-glucan, a natural polysaccharide found in the cell walls of many fungi, yeasts, and some microorganisms, as well as in plants such as barley and wheat. β-glucans are widely recognized for their ability to lower cholesterol and blood glucose levels, thereby reducing the risk of cardiovascular disease and diabetes. In addition to their effects on lipid levels and glucose metabolism, these molecules exhibit antioxidant properties by eliminating reactive oxygen species. As a result, they help lower the risk of conditions such as atherosclerosis, cardiovascular disease, neurological disorders, diabetes, and cancer. Furthermore, β-glucans have been reported to possess immune-boosting and antitumor effects. By binding to specific receptors on the surface of immune cells, they stimulate immune activity. Additionally, β-glucans belong to a group of probiotics that promote the growth and activity of beneficial gut microbiota, preventing the proliferation of harmful pathogens. They play a vital role in maintaining gastrointestinal health, reducing inflammation, and lowering the risk of colon cancer. Further research on the health benefits of β-glucans may be key to improving overall well-being and preventing many chronic non-communicable diseases such as diabetes, high cholesterol, obesity, cardiovascular disease, and cancer.
Collapse
Affiliation(s)
- Fatemeh Amirinia
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Jabrodini
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Cellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash, Iran
| | - Hamid Morovati
- Department of Medical Parasitology and Mycology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Pegah Ardi
- Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Marjan Motamedi
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| |
Collapse
|
|
2
|
Patel P, Lodh A, Beasley TM, Gupta U, Forrister N, Hegazy Y, Evers C, Xie S, Shoreibah M. Optimizing treatment outcomes in acute-on-chronic liver failure: The role of T2 candida panel in detecting invasive candidiasis. Am J Med Sci 2025; 369:366-372. [PMID: 39510501 DOI: 10.1016/j.amjms.2024.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 10/22/2024] [Accepted: 10/25/2024] [Indexed: 11/15/2024]
Abstract
INTRODUCTION Acute-on-Chronic Liver Failure(ACLF) is a syndrome characterized by organ dysfunction and high mortality in cirrhotic patients. ACLF has multiple triggers but those precipitated by fungal infection have higher mortality. Early detection and treatment of candidemia have shown mortality benefits in ACLF. The sensitivity of blood cultures ranged from 21 % - 71 %. Given the increase in mortality, it is vital to have a quick yet reliable diagnostic test for the detection of candida. This study examines the risk of developing ACLF and its impact on survival in hospitalized cirrhotic patients with invasive fungal infection via a positive T2 Candida Panel. We also examine the effects of earlier treatment on mortality in those with a positive T2 Candida Panel. METHODS We performed a retrospective study and included cirrhotic patients admitted from 2017 to 2021. Data collected includes baseline characteristics, labs, progression to ACLF, and mortality outcomes. The stages of ACLF were determined through the use of the CLIF-Consortium ACLF score. RESULTS Of the 489 patients sampled, 95 patients developed ACLF during the time of the T2 panel collection, of which 60 (63.2 %) (p ≤ 0.001) patients had a positive T2 Candida Panel. The data also demonstrates that patients who had earlier antifungal initiation had a decrease in mortality (6.15 ± 5.23 versus 13.53 ± 11.42)(p ≤ 001). CONCLUSION Our study shows that a positive T2 Panel leads to more frequent progression of ACLF and worsening survival outcomes. This study shows that earlier treatment of candidiasis via the T2 Panel leads to mortality benefits.
Collapse
Affiliation(s)
- P Patel
- University of Alabama at Birmingham, Birmingham, AL, USA; Princeton Baptist Medical Center, Birmingham, AL, USA.
| | - A Lodh
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - T M Beasley
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - U Gupta
- University of New Mexico, Albuquerque, NM, USA
| | - N Forrister
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - Y Hegazy
- University of Mississippi, Jackson, MS, USA
| | - C Evers
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - S Xie
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - M Shoreibah
- University of Alabama at Birmingham, Birmingham, AL, USA
| |
Collapse
|
|
3
|
Liu Y, Zhang Z, Zhou L, Lin T, Zhang R, Li M, Chen S, Liu X, Liu X. Invasive aspergillosis in critically ill patients with diabetes mellitus: a systematic review and meta-analysis. BMC Infect Dis 2025; 25:141. [PMID: 39885384 PMCID: PMC11783785 DOI: 10.1186/s12879-025-10560-y] [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: 11/24/2023] [Accepted: 01/24/2025] [Indexed: 02/01/2025] Open
Abstract
BACKGROUND In the intensive care unit (ICU), invasive aspergillosis (IA) has a poor prognosis. Some studies report a positive association between diabetes mellitus (DM) and IA in critically ill patients, but the relationship between DM and IA in the ICU remains controversial. We aimed to clarify the relationship between DM and IA among patients in the ICU in a systematic review and meta-analysis. METHODS We retrieved all reports published in PubMed, EMBASE, and the Cochrane Library databases before July 12, 2023. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the relationship between DM and IA. Subgroup analyses were conducted to further analyze sources of heterogeneity. Heterogeneity was evaluated using the Cochran's Q test and I2 statistic. Additionally, we evaluated publication bias using funnel plots, Egger's test, and Begg's test. Finally, sensitivity analysis was conducted to evaluate the robustness of the results. RESULTS Twenty studies with 6155 participants were included in this meta-analysis. We found a positive association between DM and IA among patients in the ICU (OR = 1.18, 95% CI:1.01 to 1.39; p = 0.04). The heterogeneity was not significant (I² = 5%; p = 0.39) and publication bias was not significant (Egger's test: p = 0.654; Begg's test: p = 0.417). The results of sensitivity analysis supported a stable association between DM and IA. Subgroup analysis indicated that patients' comorbidities might be a potential source of heterogeneity. Additionally, patients with DM had a significantly higher risk of COVID-19-associated pulmonary aspergillosis (CAPA) than those without DM (OR = 1.40, 95% CI: 1.15 to 1.70; p < 0.001). The heterogeneity was not significant (I² = 0%; p = 0.91). In the subgroup with influenza, the OR of the relationship between DM and IA was 0.81 (95% CI: 0.54, 1.23; p = 0.32; heterogeneity: p = 0.36; I² = 8%). CONCLUSIONS Patients with DM in the ICU showed a higher risk of developing IA than patients in the ICU without DM. DM was a significant risk factor for IA, with the highest risk observed in critically ill patients diagnosed with CAPA.
Collapse
Affiliation(s)
- Yuhua Liu
- State Key Lab of Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, 510120, Guangdong, China
| | - Zhaopei Zhang
- State Key Lab of Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, 510120, Guangdong, China
| | - Liang Zhou
- State Key Lab of Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, 510120, Guangdong, China
| | - Tianlai Lin
- Department of Critical Care Medicine, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, China
| | - Rong Zhang
- State Key Lab of Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, 510120, Guangdong, China
| | - Manshu Li
- State Key Lab of Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, 510120, Guangdong, China
| | - Sihao Chen
- Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Xiaoqing Liu
- State Key Lab of Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, 510120, Guangdong, China.
| | - Xuesong Liu
- State Key Lab of Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, 510120, Guangdong, China.
| |
Collapse
|
|
4
|
Zhang X, Zheng C, Zhang L, Sun Y, Liang Y, Chen X, Pang L, Zhang Y. Safety and recommendation of voriconazole for invasive pulmonary aspergillosis in severe liver disease patients: a retrospective cohort study. BMC Infect Dis 2025; 25:70. [PMID: 39819426 PMCID: PMC11740529 DOI: 10.1186/s12879-025-10459-8] [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: 06/13/2024] [Accepted: 01/08/2025] [Indexed: 01/19/2025] Open
Abstract
BACKGROUND Invasive pulmonary aspergillosis (IPA) is a common opportunistic infection in patients with severe liver disease (SLD), which increases the mortality of patients. The aim of this study was to evaluate the efficacy and safety of voriconazole for IPA in patients with SLD and explore an optimal antifungal regimen. METHODS This was a retrospective cohort study of SLD patients diagnosed with proven or probable IPA at Beijing Youan Hospital, Capital Medical University between January 1, 2012 to January 31, 2023. Univariate and multivariate logistic regression analysis were performed to identify the impact of voriconazole on outcomes of SLD patients with IPA. RESULTS A total of 142 patients were enrolled and categorized into voriconazole group (n = 92), echinocandins group (n = 26) and a combination of voriconazole and echinocandins group (n = 24). The 28-day all-cause mortality was lower in voriconazole group compared to the other groups (p = 0.033). Voriconazole monotherapy was associated with lower short-term mortality (OR 0.223, 95%CI 0.070-0.650, p = 0.008) and did not seem to exacerbate hepatic function deterioration in SLD patients with IPA (OR 0.259, 95%CI 0.094-0.674, p = 0.007) when compared to echinocandins monotherapy. Among the three subgroups of voriconazole monotherapy, no-loading dose regime demonstrated a superior response to IPA therapy compared to the standard-dose regimen (OR 0.264, 95%CI 0.068-0.845, p = 0.035). CONCLUSION Voriconazole monotherapy demonstrated good tolerability with lower mortality in SLD patients with IPA. A no-loading dose voriconazole regimen is proposed for IPA treatment in SLD patients, yet pharmacokinetic studies combined with prospective studies are needed for further validation.
Collapse
Affiliation(s)
- Xin Zhang
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai, Fengtai District, Beijing, 100069, China
- Beijing Youan Hospital, Beijing Institute of Hepatology, Capital Medical University, Beijing, China
| | - Caopei Zheng
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai, Fengtai District, Beijing, 100069, China
- Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
| | - Ling Zhang
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai, Fengtai District, Beijing, 100069, China
- Beijing Youan Hospital, Beijing Institute of Hepatology, Capital Medical University, Beijing, China
| | - Yuqing Sun
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai, Fengtai District, Beijing, 100069, China
| | - Ying Liang
- Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Centre for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
| | - Xue Chen
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai, Fengtai District, Beijing, 100069, China
- Beijing Youan Hospital, Beijing Institute of Hepatology, Capital Medical University, Beijing, China
- Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Centre for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Lijun Pang
- Beijing Youan Hospital, Beijing Institute of Hepatology, Capital Medical University, Beijing, China
| | - Yulin Zhang
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai, Fengtai District, Beijing, 100069, China.
- Beijing Youan Hospital, Beijing Institute of Hepatology, Capital Medical University, Beijing, China.
- Beijing Research Center for Respiratory Infectious Diseases, Beijing, China.
| |
Collapse
|
|
5
|
Verma N, Piano S. Regional disparities of infections in cirrhosis: a call for action. Lancet Gastroenterol Hepatol 2024; 9:967-969. [PMID: 39243796 DOI: 10.1016/s2468-1253(24)00266-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 07/22/2024] [Accepted: 08/02/2024] [Indexed: 09/09/2024]
Affiliation(s)
- Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160047, India.
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
| |
Collapse
|
|
6
|
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.
Collapse
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.
| |
Collapse
|
|
7
|
Karvellas CJ, Bajaj JS, Kamath PS, Napolitano L, O'Leary JG, Solà E, Subramanian R, Wong F, Asrani SK. AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis. Hepatology 2024; 79:1463-1502. [PMID: 37939273 DOI: 10.1097/hep.0000000000000671] [Citation(s) in RCA: 32] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 11/01/2023] [Indexed: 11/10/2023]
Affiliation(s)
- Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, Edmonton, Canada
| | - Jasmohan S Bajaj
- Virginia Commonwealth University, Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | | | - Jacqueline G O'Leary
- Department of Medicine, Dallas Veterans Medical Center, University of Texas Southwestern Medical Center Dallas, Texas, USA
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA
| | | | | | | |
Collapse
|
|
8
|
Kosuta I, Premkumar M, Reddy KR. Review article: Evaluation and care of the critically ill patient with cirrhosis. Aliment Pharmacol Ther 2024; 59:1489-1509. [PMID: 38693712 DOI: 10.1111/apt.18016] [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: 01/15/2024] [Revised: 03/21/2024] [Accepted: 04/12/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND The increase in prevalence of liver disease globally will lead to a substantial incremental burden on intensive care requirements. While liver transplantation offers a potential life-saving intervention, not all patients are eligible due to limitations such as organ availability, resource constraints, ongoing sepsis or multiple organ failures. Consequently, the focus of critical care of patients with advanced and decompensated cirrhosis turns to liver-centric intensive care protocols, to mitigate the high mortality in such patients. AIM Provide an updated and comprehensive understanding of cirrhosis management in critical care, and which includes emergency care, secondary organ failure management (mechanical ventilation, renal replacement therapy, haemodynamic support and intensive care nutrition), use of innovative liver support systems, infection control, liver transplantation and palliative and end-of life care. METHODS We conducted a structured bibliographic search on PubMed, sourcing articles published up to 31 March 2024, to cover topics addressed. We considered data from observational studies, recommendations of society guidelines, systematic reviews, and meta-analyses, randomised controlled trials, and incorporated our clinical expertise in liver critical care. RESULTS Critical care management of the patient with cirrhosis has evolved over time while mortality remains high despite aggressive management with liver transplantation serving as a crucial but not universally available resource. CONCLUSIONS Implementation of organ support therapies, intensive care protocols, nutrition, palliative care and end-of-life discussions and decisions are an integral part of critical care of the patient with cirrhosis. A multi-disciplinary approach towards critical care management is likely to yield better outcomes.
Collapse
Affiliation(s)
- Iva Kosuta
- Department of Intensive Care Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
9
|
Yu W, Xiao Y, Luo Y, Hu Y, Ji R, Wang W, Wu Z, Qi Z, Guo T, Wang Y, Zhao C. Risk factors for short-term prognosis of end-stage liver disease complicated by invasive pulmonary aspergillosis. Eur J Clin Microbiol Infect Dis 2024; 43:713-721. [PMID: 38347245 DOI: 10.1007/s10096-024-04775-1] [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: 10/18/2023] [Accepted: 02/05/2024] [Indexed: 03/27/2024]
Abstract
BACKGROUND AND AIM Patients with end-stage liver disease (ESLD) are susceptible to invasive pulmonary aspergillosis (IPA). This study aimed to investigate the risk factors affecting the occurrence and short-term prognosis of ESLD complicated by IPA. METHODS This retrospective case-control study included 110 patients with ESLD. Of them, 27 ESLD-IPA received antifungal therapy with amphotericin B (AmB); 27 AmB-free-treated ESLD-IPA patients were enrolled through 1:1 propensity score matching. Fifty-six ESLD patients with other comorbid pulmonary infections were enrolled as controls. The basic features of groups were compared, while the possible risk factors affecting the occurrence and short-term outcomes of IPA were analyzed. RESULTS Data analysis revealed invasive procedures, glucocorticoid exposure, and broad-spectrum antibiotic use were independent risk factors for IPA. The 54 patients with ESLD-IPA exhibited an overall treatment effectiveness and 28-d mortality rate of 50.00% and 20.37%, respectively, in whom patients treated with AmB-containing showed higher treatment efficacy than patients treated with AmB-free antifungal regimens (66.7% vs. 33.3%, respectively, χ2 = 6.000, P = 0.014). Multivariate logistic regression analysis revealed that the treatment regimen was the only predictor affecting patient outcomes, with AmB-containing regimens were 4.893 times more effective than AmB-free regimens (95% CI, 1.367-17.515; P = 0.015). The only independent predictors affecting the 28-d mortality rate were neutrophil-to-lymphocyte ratio and IPA diagnosis (OR = 1.140 and 10.037, P = 0.046 and 0.025, respectively). CONCLUSIONS Glucocorticoid exposure, invasive procedures, and broad-spectrum antibiotic exposure increased the risk of IPA in ESLD patients. AmB alone or combined with other antifungals may serve as an economical, safe, and effective treatment option for ESLD-IPA.
Collapse
Affiliation(s)
- Weiyan Yu
- Department of Infectious Disease, the Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei, China
- Hebei Clinical Medical Research Center of Infectious Diseases, Shijiazhuang, 050051, China
| | - Ying Xiao
- Department of Infectious Disease, the Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei, China
| | - Yue Luo
- Department of Infectious Disease, the Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei, China
- Public Health Clinical Center of Chengdu, Chengdu, 610011, China
| | - Yangyang Hu
- Department of Infectious Disease, the Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei, China
| | - Ru Ji
- Department of Infectious Disease, the Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei, China
- Hebei Clinical Medical Research Center of Infectious Diseases, Shijiazhuang, 050051, China
| | - Wei Wang
- Department of Infectious Disease, the Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei, China
- Hebei Clinical Medical Research Center of Infectious Diseases, Shijiazhuang, 050051, China
| | - Zhinian Wu
- Department of Infectious Disease, the Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei, China
| | - Zeqiang Qi
- Department of Infectious Disease, the Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei, China
| | - Tingyu Guo
- Department of Infectious Disease, the Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei, China
| | - Yadong Wang
- Department of Infectious Disease, the Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei, China.
- Hebei Clinical Medical Research Center of Infectious Diseases, Shijiazhuang, 050051, China.
| | - Caiyan Zhao
- Department of Infectious Disease, the Hebei Medical University Third Hospital, No. 139, Ziqiang Road, Shijiazhuang, 050051, Hebei, China.
- Hebei Clinical Medical Research Center of Infectious Diseases, Shijiazhuang, 050051, China.
| |
Collapse
|
|
10
|
Wu YP, Li FC, Ma HY, Yang XY, Zuo J, Tian YX, Lv L, Wang K, Fan YC. Characteristics and risk factors for invasive fungal infection in hospitalized patients with acute-on-chronic hepatitis B liver failure: a retrospective cohort study from 2010 to 2023. Front Microbiol 2024; 15:1391814. [PMID: 38601929 PMCID: PMC11004317 DOI: 10.3389/fmicb.2024.1391814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 03/12/2024] [Indexed: 04/12/2024] Open
Abstract
BACKGROUND AND AIM The global burden of invasive fungal infections (IFIs) is emerging in immunologic deficiency status from various disease. Patients with acute-on-chronic hepatitis B liver failure (ACHBLF) are prone to IFI and their conditions are commonly exacerbated by IFI. However, little is known about the characteristics and risk factors for IFI in hospitalized ACHBLF patients. METHODS A total of 243 hospitalized ACHBLF patients were retrospectively enrolled from January 2010 to July 2023. We performed restricted cubic spline analysis to determine the non-linear associations between independent variables and IFI. The risk factors for IFI were identified using logistic regression and the extreme gradient boosting (XGBoost) algorithm. The effect values of the risk factors were determined by the SHapley Additive exPlanations (SHAP) method. RESULTS There were 24 ACHBLF patients (9.84%) who developed IFI on average 17.5 (13.50, 23.00) days after admission. The serum creatinine level showed a non-linear association with the possibility of IFI. Multiple logistic regression revealed that length of hospitalization (OR = 1.05, 95% CI: 1.02-1.08, P = 0.002) and neutrophilic granulocyte percentage (OR = 1.04, 95% CI: 1.00-1.09, P = 0.042) were independent risk factors for IFI. The XGBoost algorithm showed that the use of antibiotics (SHAP value = 0.446), length of hospitalization (SHAP value = 0.406) and log (qHBV DNA) (SHAP value = 0.206) were the top three independent risk factors for IFI. Furthermore, interaction analysis revealed no multiplicative effects between the use of antibiotics and the use of glucocorticoids (P = 0.990). CONCLUSION IFI is a rare complication that leads to high mortality in hospitalized ACHBLF patients, and a high neutrophilic granulocyte percentage and length of hospitalization are independent risk factors for the occurrence of IFI.
Collapse
Affiliation(s)
- Yin-Ping Wu
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Feng-Cai Li
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Hang-Yu Ma
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Xue-Yan Yang
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Jing Zuo
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Yu-Xin Tian
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Li Lv
- Clinical Follow-up Center, Qilu Hospital of Shandong University, Jinan, China
| | - Kai Wang
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
- Hepatology Institute of Shandong University, Jinan, China
| | - Yu-Chen Fan
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
- Hepatology Institute of Shandong University, Jinan, China
| |
Collapse
|
|
11
|
Wang Y, Li C, Su H, Hu J. Invasive Fungal Infections in Acute Decompensation of Cirrhosis: Epidemiology, Predictors of 28-Day Mortality, and Outcomes. Indian J Microbiol 2024. [DOI: 10.1007/s12088-024-01243-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 02/28/2024] [Indexed: 04/16/2025] Open
|
|
12
|
Chen WC, Chen IC, Chen JP, Liao TL, Chen YM. Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study. PeerJ 2024; 12:e17066. [PMID: 38436032 PMCID: PMC10908254 DOI: 10.7717/peerj.17066] [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: 10/18/2023] [Accepted: 02/16/2024] [Indexed: 03/05/2024] Open
Abstract
Objective Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Methods Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. Results We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Conclusion Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.
Collapse
Affiliation(s)
- Wei-Che Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan
| | - I-Chieh Chen
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jun-Peng Chen
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Tsai-Ling Liao
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
- Institute of Biomedical Science and Rong-Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taichung, Taiwan
| | - Yi-Ming Chen
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
- Institute of Biomedical Science and Rong-Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taichung, Taiwan
- Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, National Chung Hsing University, Taichung, Taichung, Taiwan
- Precision Medicine Research Center, National Chung Hsing University, Taichung, Taichung, Taiwan
- School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| |
Collapse
|
|
13
|
Heylen J, Vanbiervliet Y, Maertens J, Rijnders B, Wauters J. Acute Invasive Pulmonary Aspergillosis: Clinical Presentation and Treatment. Semin Respir Crit Care Med 2024; 45:69-87. [PMID: 38211628 DOI: 10.1055/s-0043-1777769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
Among all clinical manifestations of pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA) is the most acute presentation. IPA is caused by Aspergillus hyphae invading the pulmonary tissue, causing either tracheobronchitis and/or bronchopneumonia. The degree of fungal invasion into the respiratory tissue can be seen as a spectrum, going from colonization to deep tissue penetration with angio-invasion, and largely depends on the host's immune status. Patients with prolonged, severe neutropenia and patients with graft-versus-host disease are at particularly high risk. However, IPA also occurs in other groups of immunocompromised and nonimmunocompromised patients, like solid organ transplant recipients or critically ill patients with severe viral disease. While a diagnosis of proven IPA is challenging and often warranted by safety and feasibility, physicians must rely on a combination of clinical, radiological, and mycological features to assess the likelihood for the presence of IPA. Triazoles are the first-choice regimen, and the choice of the drug should be made on an individual basis. Adjunctive therapy such as immunomodulatory treatment should also be taken into account. Despite an improving and evolving diagnostic and therapeutic armamentarium, the burden and mortality of IPA still remains high. This review aims to give a comprehensive and didactic overview of the current knowledge and best practices regarding the epidemiology, clinical presentation, diagnosis, and treatment of acute IPA.
Collapse
Affiliation(s)
- Jannes Heylen
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Yuri Vanbiervliet
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Haematology, University Hospitals Leuven, Leuven, Belgium
| | - Johan Maertens
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Haematology, University Hospitals Leuven, Leuven, Belgium
| | - Bart Rijnders
- Department of Internal Medicine and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Joost Wauters
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| |
Collapse
|
|
14
|
Zhao Y, Liu H, Xiao C, Hou J, Zhang B, Li J, Zhang M, Jiang Y, Sandaradura I, Ding X, Yan M. Enhancing voriconazole therapy in liver dysfunction: exploring administration schemes and predictive factors for trough concentration and efficacy. Front Pharmacol 2024; 14:1323755. [PMID: 38239188 PMCID: PMC10794455 DOI: 10.3389/fphar.2023.1323755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 12/14/2023] [Indexed: 01/22/2024] Open
Abstract
Introduction: The application of voriconazole in patients with liver dysfunction lacks pharmacokinetic data. In previous study, we proposed to develop voriconazole dosing regimens for these patients according to their total bilirubin, but the regimens are based on Monte Carlo simulation and has not been further verified in clinical practice. Besides, there are few reported factors that significantly affect the efficacy of voriconazole. Methods: We collected the information of patients with liver dysfunction hospitalized in our hospital from January 2018 to May 2022 retrospectively, including their baseline information and laboratory data. We mainly evaluated the efficacy of voriconazole and the target attainment of voriconazole trough concentration. Results: A total of 157 patients with liver dysfunction were included, from whom 145 initial and 139 final voriconazole trough concentrations were measured. 60.5% (95/157) of patients experienced the adjustment of dose or frequency. The initial voriconazole trough concentrations were significantly higher than the final (mean, 4.47 versus 3.90 μg/mL, p = 0.0297). Furthermore, daily dose, direct bilirubin, lymphocyte counts and percentage, platelet, blood urea nitrogen and creatinine seven covariates were identified as the factors significantly affect the voriconazole trough concentration. Binary logistic regression analysis revealed that the lymphocyte percentage significantly affected the efficacy of voriconazole (OR 1.138, 95% CI 1.016-1.273), which was further validated by the receiver operating characteristic curve. Conclusion: The significant variation in voriconazole trough concentrations observed in patients with liver dysfunction necessitates caution when prescribing this drug. Clinicians should consider the identified factors, particularly lymphocyte percentage, when dosing voriconazole in this population.
Collapse
Affiliation(s)
- Yichang Zhao
- Department of Clinical Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Huaiyuan Liu
- Department of Clinical Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Chenlin Xiao
- Department of Clinical Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Jingjing Hou
- Department of Clinical Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Bikui Zhang
- Department of Clinical Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Jiakai Li
- Department of Clinical Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Min Zhang
- Department of Infectious Disease, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yongfang Jiang
- Department of Infectious Disease, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Indy Sandaradura
- School of Medicine, University of Sydney, Sydney, NSW, Australia
- Centre for Infectious Diseases and Microbiology, Westmead Hospital, Sydney, NSW, Australia
| | - Xuansheng Ding
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Miao Yan
- Department of Clinical Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
| |
Collapse
|
|
15
|
Kaur P, Verma N, Valsan A, Garg P, Rathi S, De A, Premkumar M, Taneja S, Duseja A, Singh V, Dhiman RK. Prevalence, Risk Factors, and Impact of Bacterial or Fungal Infections in Acute Liver Failure Patients from India. Dig Dis Sci 2023; 68:4022-4038. [PMID: 37578566 DOI: 10.1007/s10620-023-07971-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 05/10/2023] [Indexed: 08/15/2023]
Abstract
BACKGROUND We evaluated the prevalence, risk factors, and impact of bacterial/fungal infections in acute liver failure (ALF) patients. METHODS We analyzed clinical, biochemical, and microbiological data of ALF patients with and without bacterial/fungal infections admitted at an institute over the last 5 years. RESULTS We enrolled 143 patients, 50% males, median age 25 years, with acute viral hepatitis (32.2%), drug-induced injury (18.2%), and tropical illness (14%) as aetiologies of ALF. 110 patients (76.9%) developed bacterial/fungal infections [Bacterial infection: MDR: 70%, PDR: 7%, ESBL: 40%, CRE: 30%, CRAB: 26.6%, MDR-EF: 13.3% and fungal infection: 19 (17.3%)]. On univariable analysis, SIRS (33.6% vs.3%), ICU admission (78.2% vs. 45.5%), mechanical ventilation (88.2% vs. 51.5%), inotropes (39.1% vs. 6.1%), invasive catheters (91.8% vs. 39.4%), and prolonged catheterization (6 days vs. 0 days) were significant risk factors for infections (p < 0.05, each). In contrast, SIRS and catheterization independently predicted infection on multivariable regression. Organ failures [3 (2-4) vs. 1 (0-2)], grade-III-IV HE (67.3% vs. 33.3%), circulatory failure (39.1% vs. 6.1%), coagulopathy (INR > 2.5: 58.2% vs. 33.3%), renal injury (28.2% vs. 6.1%) (p < 0.05), MELD (32.9 ± 8.2 vs. 26.7 ± 8.3) and CPIS [3(2-4) vs. 2(0-2)] were higher in infected vs. non-infected patients (p < 0.001). 30-day survival was significantly lower in infected vs. non-infected patients (17.3% vs. 75.8%, p < 0.001), while no patient survived with fungal infections. Refractory septic shock was the commonest cause of mortality in patients. CONCLUSIONS Infections due to MDR organisms are high, fungal infections are fatal, and refractory septic shock is the dominant reason for mortality, implying bacterial and fungal infections as the major killer in ALF patients.
Collapse
Affiliation(s)
- Parminder Kaur
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Arun Valsan
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pratibha Garg
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sahaj Rathi
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Arka De
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Virendra Singh
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Radha Krishan Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| |
Collapse
|
|
16
|
Abstract
In recent years there has been a significant increase in the incidence of acute-on-chronic liver failure (ACLF). This syndrome is characterized by infections, organ failures, and high short-term mortality. Although progress in the management of these sick patients has been evident, liver transplantation (LT) remains the best treatment modality to date. Several studies have reported LT as a feasible option, despite organ failures. The outcomes following LT are inversely related to the grade of ACLF. This review discusses the current literature on the feasibility, futility, timing, and outcomes of LT in patients with ACLF.
Collapse
Affiliation(s)
- Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad-500032, India
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, 2 Dulles, Liver Transplant Office 3400 Spruce Street, Philadelphia, PA 19104, USA.
| |
Collapse
|
|
17
|
Factors Influencing Blood Concentration of Voriconazole and Therapeutic Drug Monitoring in Patients with Child–Pugh Class C Cirrhosis. J Clin Pharm Ther 2023. [DOI: 10.1155/2023/4240869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2023]
Abstract
What Is Known and Objective. CYP2C19 is an important influencing factor for voriconazole trough plasma concentration (Cmin); however, it is not verified in Child–Pugh C (CP-C) cirrhosis patients, and no voriconazole dosage regimen is recommended for these patients in the package insert. This retrospective study identified CYP2C19 and other factors influencing voriconazole Cmin for CP-C cirrhosis, and obtained an appropriate method of application of voriconazole for them. Methods. A total of 66 patients with CP-C cirrhosis who accepted voriconazole therapy were involved. The voriconazole Cmin, clinical characteristics, CYP2C19 genotype, and adverse effects (AEs) were recorded and analyzed. Results. Unlike other research studies, voriconazole Cmin was not different among normal metabolizers (NMs), intermediate metabolizers (IMs), and poor metabolizers (PMs) of the CYP2C19 enzyme in CP-C cirrhosis (
> 0.05). The maintenance dose regimen for voriconazole was the only independent influencing factor for Cmin (
= 0.045; OR = 3.753; 95% CI, 1.029–13.694). At about 1/3 of the recommended maintenance dose, only 16.7% (8/48) had Cmin >5.5 μg/mL, 4.5% (3/48) had Cmin <1 μg/mL, and only one AE happened. There were four voriconazole-related AEs that happened in this study, and three AEs occurred (3/4, 75%) when the maintenance dose was not adjusted with therapeutic drug monitoring (TDM). What Is New and Conclusion. Voriconazole Cmin did not significantly vary according to CYP2C19 enzyme metabolization status (being an NM, IM, or PM) in CP-C cirrhosis. Reducing the maintenance dose of voriconazole to approximately 1/3 the standard maintenance dose and administering in combination with TDM in patients with CP-C cirrhosis are recommended.
Collapse
|
|
18
|
The Mechanisms of Systemic Inflammatory and Immunosuppressive Acute-on-Chronic Liver Failure and Application Prospect of Single-Cell Sequencing. J Immunol Res 2022; 2022:5091275. [PMID: 36387424 PMCID: PMC9646330 DOI: 10.1155/2022/5091275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 09/14/2022] [Accepted: 10/11/2022] [Indexed: 01/24/2023] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a complex clinical syndrome, and patients often have high short-term mortality. It occurs with intense systemic inflammation, often accompanied by a proinflammatory event (such as infection or alcoholic hepatitis), and is closely related to single or multiple organ failure. Liver inflammation begins when innate immune cells (such as Kupffer cells (KCs)) are activated by binding of pathogen-associated molecular patterns (PAMPs) from pathogenic microorganisms or damage-associated molecular patterns (DAMPs) of host origin to their pattern recognition receptors (PRRs). Activated KCs can secrete inflammatory factors as well as chemokines and recruit bone marrow-derived cells such as neutrophils and monocytes to the liver to enhance the inflammatory process. Bacterial translocation may contribute to ACLF when there are no obvious precipitating events. Immunometabolism plays an important role in the process (including mitochondrial dysfunction, amino acid metabolism, and lipid metabolism). The late stage of ACLF is mainly characterized by immunosuppression. In this process, the dysfunction of monocyte and macrophage is reflected in the downregulation of HLA-DR and upregulation of MER tyrosine kinase (MERTK), which weakens the antigen presentation function and reduces the secretion of inflammatory cytokines. We also describe the specific function of bacterial translocation and the gut-liver axis in the process of ACLF. Finally, we also describe the transcriptomics in HBV-ACLF and the recent progress of single-cell RNA sequencing as well as its potential application in the study of ACLF in the future, in order to gain a deeper understanding of ACLF in terms of single-cell gene expression.
Collapse
|
|
19
|
Chen YC, Chayakulkeeree M, Chakrabarti A, Gan GG, Kwong YL, Liu WL, Tan BH, Todi S. Unmet needs and practical solutions in the management of invasive mould infections in Asia. J Antimicrob Chemother 2022; 77:2579-2585. [PMID: 35904002 DOI: 10.1093/jac/dkac251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Management of invasive mould infections (IMIs) is challenging in Asia, as awareness among medical practitioners can be low and resources are limited. Timely diagnosis and appropriate treatment of IMIs can mitigate the impact on morbidity and mortality, but diagnostic methods, as well as access to preferred antifungal medications, may vary throughout the region. Knowledge of local epidemiology and accurate diagnosis and identification of causal pathogens would facilitate optimal treatment but data in Asia are lacking. To address these unmet needs in the management of IMIs, this paper is a call for urgent action in the following areas: improving awareness of the threat of IMIs; providing education to frontline clinicians across a broad range of specialties on 'red flags' for suspicion of IMIs; prioritizing cost-effective rapid diagnostic testing; improving access to preferred antifungal medications; and closing the gaps in local epidemiological data on IMIs to inform local treatment guidelines.
Collapse
Affiliation(s)
- Yee-Chun Chen
- Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Methee Chayakulkeeree
- Division of Infectious Diseases and Tropical Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Arunaloke Chakrabarti
- Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.,Doodhadhari Burfani Hospital and Research Institute, Haridwar, India
| | - Gin Gin Gan
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Yok Lam Kwong
- Division of Haematology, Oncology and Bone Marrow Transplantation, University of Hong Kong, Pokfulam, Hong Kong
| | - Wei-Lun Liu
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan.,Division of Critical Care Medicine, Department of Emergency and Critical Care Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei, Taiwan
| | - Ban Hock Tan
- Department of Infectious Diseases, Singapore General Hospital Singapore 169608, Singapore
| | - Subhash Todi
- Critical Care and Emergency Medicine, AMRI Hospitals, Kolkata, India
| |
Collapse
|
|
20
|
Verma N, Singh S, Roy A, Valsan A, Garg P, Pradhan P, Chakrabarti A, Singh M. Cirrhosis and fungal infections-a cocktail for catastrophe: A systematic review and meta-analysis with machine learning. Mycoses 2022; 65:844-858. [PMID: 35713607 DOI: 10.1111/myc.13482] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 06/08/2022] [Accepted: 06/13/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVES We evaluated the magnitude and factors contributing to poor outcomes among cirrhosis patients with fungal infections (FIs). METHODS We searched PubMed, Embase, Ovid and WOS and included articles reporting mortality in cirrhosis with FIs. We pooled the point and relative-risk (RR) estimates of mortality on random-effects meta-analysis and explored their heterogeneity (I2 ) on subgroups, meta-regression and machine learning (ML). We assessed the study quality through New-Castle-Ottawa Scale and estimate-asymmetry through Eggers regression. (CRD42019142782). RESULTS Of 4345, 34 studies (2134 patients) were included (good/fair/poor quality: 12/21/1). Pooled mortality of FIs was 64.1% (95% CI: 55.4-72.0, I2 : 87%, p < .01), which was 2.1 times higher than controls (95% CI: 1.8-2.5, I2 :89%, p < .01). Higher CTP (MD: +0.52, 95% CI: 0.27-0.77), MELD (MD: +2.75, 95% CI: 1.21-4.28), organ failures and increased hospital stay (30 vs. 19 days) were reported among cases with FIs. Patients with ACLF (76.6%, RR: 2.3) and ICU-admission (70.4%, RR: 1.6) had the highest mortality. The risk was maximum for pulmonary FIs (79.4%, RR: 1.8), followed by peritoneal FIs (68.3%, RR: 1.7) and fungemia (55%, RR: 1.7). The mortality was higher in FIs than in bacterial (RR: 1.7) or no infections (RR: 2.9). Estimate asymmetry was evident (p < 0.05). Up to 8 clusters and 5 outlier studies were identified on ML, and the estimate-heterogeneity was eliminated by excluding such studies. CONCLUSIONS A substantially worse prognosis, poorer than bacterial infections in cirrhosis patients with FIs, indicates an unmet need for improving fungal diagnostics and therapeutics in this population. ACLF and ICU admission should be included in the host criteria for defining IFIs.
Collapse
Affiliation(s)
- Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shreya Singh
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Akash Roy
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Arun Valsan
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pratibha Garg
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pranita Pradhan
- Indian Council of Medical Research Center for evidence based child health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Arunaloke Chakrabarti
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Meenu Singh
- Indian Council of Medical Research Center for evidence based child health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| |
Collapse
|
|
21
|
Saffo S, Jain D, Sanchez H, Garcia-Tsao G. Invasive Fungal Infections Are Underdiagnosed in Hospitalized Patients With Decompensated Cirrhosis: An Autopsy Study. GASTRO HEP ADVANCES 2022; 1:803-806. [PMID: 36160304 PMCID: PMC9497452 DOI: 10.1016/j.gastha.2022.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 05/20/2022] [Indexed: 11/23/2022]
Affiliation(s)
- S. Saffo
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut
| | - D. Jain
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut
| | - H. Sanchez
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut
| | - G. Garcia-Tsao
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut
- Section of Digestive Diseases, VA Connecticut Healthcare System, West Haven, Connecticut
| |
Collapse
|
|
22
|
Su Q, Pan J, Zhang L, Xia L, Gao Y, Li J. Observation of Voriconazole in the Treatment of Liver Failure Complicated With Invasive Pulmonary Fungal Infection Induced by Chinese Patent Medicine in Teenagers: 2 Case Reports. Front Pharmacol 2022; 13:862222. [PMID: 35517824 PMCID: PMC9065283 DOI: 10.3389/fphar.2022.862222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 03/16/2022] [Indexed: 12/05/2022] Open
Abstract
Background: Drug-induced liver injury (DILI) caused by Chinese patent medicines is increasing in China. The incidence of invasive fungal infections (IFIs) is increasing due to the suppression of the immune function in greater numbers of patients. Invasive procedures such as deep vein catheterization and the use of glucocorticoids are also predisposing factors to IFIs. The clinical presentation of IFI in teenagers is often atypical, challenging to diagnose, difficult to treat, and associated with a high fatality rate. Case presentation: Herein, we report 2 teenagers with liver failure after receiving oral Chinese patent medicines. Case 1 was a 14-year-old boy who presented with subacute liver failure who had been administered a Chinese patent medicine that included acetaminophen. Administration of glucocorticoids and non-bioartificial liver treatment improved his condition. Subsequently, invasive pulmonary Aspergillus (IPA) was diagnosed and was successfully treated with voriconazole for 85 days. Case 2 was a 17-year-old girl who presented with acute liver failure after taking the Chinese patent medicine QubaiBabuqi tablets for vitiligo. Chest computed tomography (CT) revealed multiple pulmonary nodules with an intermittent low-grade fever, and she was diagnosed with IPA. She was initially treated with caspofungin (23 days) and then voriconazole (406 days) for 429 days. Her liver function returned to normal, and lung lesions were absorbed in 2 patients. At the same time, two to three histopathological examinations of the liver biopsy showed that the drug-induced autoimmune-like phenomena could be improved by glucocorticoid therapy. Conclusion: To the best of our knowledge, this is the first report of the successful treatment of 2 cases of liver failure (Child-Pugh class C) caused by Chinese patent medicines complicated with IPA in teenagers. Drug-induced autoimmune-like phenomena could be improved by glucocorticoid therapy.
Collapse
Affiliation(s)
| | | | | | | | | | - Jiabin Li
- Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| |
Collapse
|
|
23
|
Ye C, Li W, Li L, Zhang K. Glucocorticoid Treatment Strategies in Liver Failure. Front Immunol 2022; 13:846091. [PMID: 35371046 PMCID: PMC8965693 DOI: 10.3389/fimmu.2022.846091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 02/23/2022] [Indexed: 11/13/2022] Open
Abstract
Liver failure is characterized by serious liver decompensation and high mortality. The activation of systemic immune responses and systemic inflammation are widely accepted as the core pathogenesis of liver failure. Glucocorticoids (GCs) are most regularly utilized to suppress excessive inflammatory reactions and immunological responses. GCs have been used in the clinical treatment of liver failure for nearly 60 years. While there has been no unanimity on the feasibility and application of GC treatment in liver failure until recently. The most recent trials have produced conflicting results when it comes to the dose and time for GC therapy of different etiology of liver failure. Our review outlines the issues and options in managing GC treatment in liver failure based on an investigation of the molecular mechanism that GC may give in the treatment.
Collapse
Affiliation(s)
- Chao Ye
- Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Wenyuan Li
- Department of Infectious Diseases, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Lei Li
- Department of Infectious Diseases, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Kaiguang Zhang
- Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| |
Collapse
|
|
24
|
Primary Norfloxacin Prophylaxis for APASL-Defined Acute-on-Chronic Liver Failure: A Placebo-Controlled Double-Blind Randomized Trial. Am J Gastroenterol 2022; 117:607-616. [PMID: 35041634 DOI: 10.14309/ajg.0000000000001611] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 12/14/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION This study aimed to evaluate the role of prophylactic norfloxacin in preventing bacterial infections and its effect on transplant-free survival (TFS) in patients with acute-on-chronic liver failure (ACLF) identified by the Asian Pacific Association for the Study of the Liver criteria. METHODS Patients with ACLF included in the study were randomly assigned to receive oral norfloxacin 400 mg or matched placebo once daily for 30 days. The incidence of bacterial infections at days 30 and 90 was the primary outcome, whereas TFS at days 30 and 90 was the secondary outcome. RESULTS A total of 143 patients were included (72 in the norfloxacin and 71 in the placebo groups). Baseline demographics, biochemical variables, and severity scores were similar between the 2 groups. On Kaplan-Meier analysis, the incidence of bacterial infections at day 30 was 18.1% (95% confidence interval [CI], 10-28.9) and 33.8% (95% CI, 23-46) (P = 0.03); and the incidence of bacterial infections at day 90 was 46% (95% CI, 34-58) and 62% (95% CI, 49.67-73.23) in the norfloxacin and placebo groups, respectively (P = 0.02). On Kaplan-Meier analysis, TFS at day 30 was 77.8% (95% CI, 66.43-86.73) and 64.8% (95% CI, 52.54-75.75) in the norfloxacin and placebo groups, respectively (P = 0.084). Similarly, TFS at day 90 was 58.3% (95% CI, 46.11-69.84) and 43.7% (95% CI, 31.91-55.95), respectively (P = 0.058). Thirty percent of infections were caused by multidrug-resistant organisms. More patients developed concomitant candiduria in the norfloxacin group (25%) than in the placebo group (2.63%). DISCUSSION Primary norfloxacin prophylaxis effectively prevents bacterial infections in patients with ACLF.
Collapse
|
|
25
|
Passi NN, McPhail MJW. The patient with cirrhosis in the intensive care unit and the management of acute-on-chronic liver failure. J Intensive Care Soc 2022; 23:78-86. [PMID: 37593538 PMCID: PMC10427846 DOI: 10.1177/1751143720978849] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/19/2023] Open
Abstract
Acute on chronic liver failure (ACLF) is a clinical syndrome characterised by acute hepatic decompensation, multi-organ failure and high mortality, in patients with cirrhosis. Organ dysfunction in ACLF is often reversible and when necessary these patients should be considered appropriate candidates for admission to an intensive care unit (ICU). The yearly increase in numbers of patients with ACLF admitted to ICU has been matched with an improvement in survival. ACLF has only been recently defined. In the absence of evidence-based guidelines we outline a systems-based approach to care which encompasses accepted ICU practice and evidence from trials in this cohort. We advocate for timely referral to specialist liver centres and consider the complexities of proceeding with liver transplantation. Equally, in a proportion of patients who continue to deteriorate, appropriate ceilings of care should be established. Future clinical trials may change treatment paradigms but care of patients with ACLF is undoubtedly becoming an integral part of an intensivist's practice. We hope that this review is a welcome starting point when managing this complex clinical syndrome.
Collapse
Affiliation(s)
- Neha N Passi
- Institute of Liver Studies, Kings College Hospital, London, UK
| | - Mark JW McPhail
- Institute of Liver Studies, Kings College Hospital, London, UK
| |
Collapse
|
|
26
|
Abstract
In patients with cirrhosis and chronic liver disease, acute-on-chronic liver failure is emerging as a major cause of mortality. These guidelines indicate the preferred approach to the management of patients with acute-on-chronic liver failure and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.
Collapse
|
|
27
|
Prevalence, Predictors, and Outcomes of Esophageal Candidiasis in Cirrhosis: An Observational Study With Systematic Re view and Meta-Analysis (CANDID-VIEW). J Clin Exp Hepatol 2022; 12:118-128. [PMID: 35068792 PMCID: PMC8766531 DOI: 10.1016/j.jceh.2021.03.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Accepted: 03/12/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Gastrointestinal candidiasis is often neglected and potentially serious infection in cirrhosis patients. Therefore, we evaluated the prevalence, risk factors, and outcomes of esophageal candidiasis (EC) in cirrhotics and did a systematic review to summarize EC's available evidence in cirrhosis. METHODS Consecutive patients with cirrhosis posted for esophagogastroduodenoscopy (EGD) at a tertiary care institute were screened for EC (cases) between January 2019 and March 2020. EC was diagnosed on EGD findings and/or brush cytology. Controls (without EC) were recruited randomly, and EC's risk factors and outcomes were compared between cases and controls.Four electronic databases were searched for studies describing EC in cirrhosis. Prevalence estimates of EC were pooled on random-effects meta-analysis, and heterogeneity was assessed by I2. A checklist for prevalence studies was used to evaluate the risk of bias in studies. RESULTS EC was diagnosed in 100 of 2762 patients with cirrhosis (3.6%). Patients with EC had a higher model for end-stage liver disease (MELD) (12.4 vs. 11.2; P = 0.007), acute-on-chronic liver failure (ACLF) (26% vs. 10%; P = 0.003) and concomitant bacterial infections (24% vs. 7%; P = 0.001), as compared with controls. A multivariable model, including recent alcohol binge, hepatocellular carcinoma (HCC), upper gastrointestinal (UGI) bleed, ACLF, diabetes, and MELD, predicted EC's development in cirrhosis with excellent discrimination (C-index: 0.918). Six percent of cases developed the invasive disease and worsened with multiorgan failures, and four patients with EC died on follow-up.Of 236 articles identified, EC's pooled prevalence from 8 studies (all with low-risk of bias) was 2.1% (95% CI: 0.8-5.8). Risk factors and outcomes of EC in cirrhosis were not reported in the literature. CONCLUSIONS EC is not a rare infection in cirrhosis patients, and it may predispose to invasive candidiasis and untimely deaths. Alcohol binge, HCC, UGI bleed, ACLF, diabetes, and higher MELD are the independent predictors of EC in cirrhosis. At-risk patients with cirrhosis or those with deglutition symptoms should be rapidly screened and treated for EC.
Collapse
Key Words
- ACLF
- ACLF, Acute-on-chronic liver failure
- AIC, Akaike's Information Criteria
- AIDS, Acquired Immunodeficiency Syndrome
- BIC, Bayesian Information Criteria
- Candida
- DM, Diabetes Mellitus
- EC, Esophageal Candidiasis
- EGD, Esophagogastroduodenoscopy
- EVL, Endoscopic Variceal Ligation
- HAART, Highly Active Anti-Retroviral Therapy
- HCC, Hepatocellular Carcinoma
- HIV, Human Immunodeficiency Virus
- IC, Invasive Candidiasis
- MELD, Model for End-stage Liver Disease
- MELD-Na, Model for End-stage Liver Disease-Sodium
- RRT, Renal Replacement Therapy
- SBP, Spontaneous Bacterial Peritonitis
- SIRS, Systemic Inflammatory Response Syndrome
- UGI, Upper Gastrointestinal
- cirrhosis
- esophagitis
- invasive fungal infections
Collapse
|
|
28
|
Chen D, Qian Z, Su H, Meng Z, Lv J, Huang Y, Gao Y, Liu J, Zhao C, Gao H, Chen Y, Xia J, Peng L, Han T, Li H, Zheng X, Wang X, Lu X, Shi Y, Hu J, Chen J. Invasive Pulmonary Aspergillosis in Acute-on-Chronic Liver Failure Patients: Short-Term Outcomes and Antifungal Options. Infect Dis Ther 2021; 10:2525-2538. [PMID: 34468963 PMCID: PMC8572893 DOI: 10.1007/s40121-021-00524-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 08/10/2021] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Acute-on-chronic liver failure (ACLF) patients are susceptible to invasive fungal infections. We evaluated the prognosis and antifungal options in ACLF patients with invasive pulmonary aspergillosis (IPA). METHODS ACLF patients with IPA from 15 hospitals were retrospectively screened from 2011 to 2018, and 383 ACLF patients without lung infections were included from a prospective cohort (NCT02457637). Demographic, laboratory, clinical data, and 28-day outcomes were documented in the two cohorts. RESULTS ACLF patients with probable IPA (n = 145) had greater 28-day mortality (33.6% vs. 15.7%, p < 0.001) than those without (n = 383). The respiratory failure-associated 28-day mortality was greater in ACLF patients with IPA than in those without before (17.1% vs. 0.3%, p < 0.001) and after (16.0% vs. 0.0%, p < 0.001) propensity score matching in 116 pairs. IPA patients with lung injury had greater 28-day all-cause mortality (66.5% vs. 24.2%, p < 0.001) and IPA-associated mortality (45.8% vs. 8.1%, p < 0.001) than patients without lung injury (PaO2/FiO2 ≥ 400 mmHg). Antifungal therapy was prescribed to 139 of 145 patients, and 102 patients were treated with voriconazole alone (n = 59) or sequential/combined therapy (n = 43) with varying loading doses (100-800 mg) and daily maintenance doses (0-800 mg). A proposed optimal voriconazole regimen (loading dose, 200 mg twice daily; daily maintenance dose, 100 mg) achieved comparable short-term survival and optimal trough drug concentrations (1-5 μg/mL) on therapeutic drug monitoring in 26 patients. CONCLUSION Presence of IPA increases the short-term mortality of ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients.
Collapse
Affiliation(s)
- Danli Chen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No 1838, Guangzhou Dadao Bei, Guangzhou, 510515 People’s Republic of China
| | - Zhiping Qian
- Department of Infectious Disease, Shanghai Public Health Clinical Center Affiliated to Fudan University, Shanghai, People’s Republic of China
| | - Haibin Su
- Liver Failure Treatment and Research Center, The Fifth Medical Center of PLA General Hospital, No 100, Xisihuanzhonglu Road, Beijing, 100039 People’s Republic of China
| | - Zhongji Meng
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China
| | - Jun Lv
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China
| | - Yan Huang
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Yanhang Gao
- Hepatology Department, First Hospital of Jilin University, Changchun, Jilin People’s Republic of China
| | - Jingyuan Liu
- Department of Intensive Care Unit, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Caiyan Zhao
- Department of Infectious Disease, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
| | - Hongbo Gao
- Department of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangdong, People’s Republic of China
| | - Yu Chen
- Difficult and Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Jie Xia
- Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China
| | - Liang Peng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun-Yat-Sen University, Guangzhou, People’s Republic of China
| | - Tao Han
- Department of Hepatology and Gastroenterology, Tianjin Third Central Hospital, Tianjin, China
| | - Hai Li
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), Shanghai, People’s Republic of China
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
| | - Xin Zheng
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People’s Republic of China
| | - Xianbo Wang
- Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Xiaobo Lu
- The First Affiliated Hospital of Xinjiang Medical University (XMU), Xinjiang, People’s Republic of China
| | - Yu Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
| | - Jinhua Hu
- Liver Failure Treatment and Research Center, The Fifth Medical Center of PLA General Hospital, No 100, Xisihuanzhonglu Road, Beijing, 100039 People’s Republic of China
| | - Jinjun Chen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No 1838, Guangzhou Dadao Bei, Guangzhou, 510515 People’s Republic of China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), Shanghai, People’s Republic of China
| |
Collapse
|
|
29
|
Khalid M, Neupane R, Anjum H, Surani S. Fungal infections following liver transplantation. World J Hepatol 2021; 13:1653-1662. [PMID: 34904035 PMCID: PMC8637669 DOI: 10.4254/wjh.v13.i11.1653] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 06/24/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
With increasing morbidity and mortality from chronic liver disease and acute liver failure, the need for liver transplantation is on the rise. Most of these patients are extremely vulnerable to infections as they are immune-compromised and have other chronic co-morbid conditions. Despite the recent advances in practice and improvement in diagnostic surveillance and treatment modalities, a major portion of these patients continue to be affected by post-transplant infections. Of these, fungal infections are particularly notorious given their vague and insidious onset and are very challenging to diagnose. This mini-review aims to discuss the incidence of fungal infections following liver transplantation, the different fungi involved, the risk factors, which predispose these patients to such infections, associated diagnostic challenges, and the role of prophylaxis. The population at risk is increasingly old and frail, suffering from various other co-morbid conditions, and needs special attention. To improve care and to decrease the burden of such infections, we need to identify the at-risk population with more robust clinical and diagnostic parameters. A more robust global consensus and stringent guidelines are needed to fight against resistant microbes and maintain the longevity of current antimicrobial therapies.
Collapse
Affiliation(s)
- Madiha Khalid
- Department of Medicine, Orlando Health Medical Center, Orlando, FL 32806, United States
| | - Ritesh Neupane
- Department of Medicine, Penn State Health Milton S Hershey Medical Center, Hershey, PA 17033, United States
| | - Humayun Anjum
- Department of Medicine, University of North Texas, Denton, TX 76203, United States
| | - Salim Surani
- Department of Pulmonary Critical Care and Sleep Medicine, Texas A&M Health Science Center, Corpus Christi, TX 78405, United States.
| |
Collapse
|
|
30
|
Lahmer T, Peçanha-Pietrobom PM, Schmid RM, Colombo AL. Invasive fungal infections in acute and chronic liver impairment: A systematic review. Mycoses 2021; 65:140-151. [PMID: 34837414 DOI: 10.1111/myc.13403] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 11/06/2021] [Accepted: 11/15/2021] [Indexed: 12/18/2022]
Abstract
Patients with acute and chronic liver impairment are susceptible to invasive fungal infections such as candidemia and invasive pulmonary aspergillosis as a result of cirrhosis-associated immune dysfunction, humoral immunodeficiency, cell-mediated dysfunction and systemic inflammation. Besides classical risk factors for invasive fungal infection, acute-on-chronic liver failure, corticosteroid use, gastrointestinal bleeding, and prophylactic use of antibiotics are all additional conditions which are related to the potential development of fungal infections. Therefore, high-risk patients should be carefully followed by microbiological surveillance including cultures but also by imaging and fungal biomarkers for providing early diagnosis. Echinocandins are still the mainstay and first line antifungal therapy in cases of invasive candidiasis. Due to concerns of liver toxicity and in cases of renal impairment liposomal amphotericin B is a suitable alternative to voriconazole in patients with invasive pulmonary aspergillosis. Although, data of isavucoanzole and posaconazole use in those patients are also promising more specific studies in the subgroup of patients with liver impairment are needed. Especially, due to the late diagnosis and multiple organ dysfunction usually present in patients with liver impairment morbidity and mortality rates remain high. Based on the broad spectrum of diverse reports with varying content and quality and in some cases lack of evidence we performed a systematic review on this topic.
Collapse
Affiliation(s)
- Tobias Lahmer
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen, Universität München, Munich, Germany
| | - Paula M Peçanha-Pietrobom
- Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Roland M Schmid
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen, Universität München, Munich, Germany
| | - Arnaldo Lopes Colombo
- Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| |
Collapse
|
|
31
|
Khanam A, Kottilil S. Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management. Front Med (Lausanne) 2021; 8:752875. [PMID: 34820395 PMCID: PMC8606418 DOI: 10.3389/fmed.2021.752875] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 10/07/2021] [Indexed: 12/21/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a multifaceted condition with poor treatment options and high short-term mortality. ACLF can develop in patients with or without liver cirrhosis, where patients with decompensated cirrhosis display a higher risk of short-term mortality. Pathophysiological mechanisms include systemic inflammation due to bacterial and fungal infections and acute hepatic insult with drug, alcohol, and viral hepatitis. Cryptogenic factors also contribute to the development of ACLF. The clinical outcome of patients with ACLF gets further complicated by the occurrence of variceal hemorrhage, hepatorenal syndrome, hepatic encephalopathy, and systemic immune dysfunction. Regardless of the better understanding of pathophysiological mechanisms, no specific and definitive treatment is available except for liver transplantation. The recent approach of regenerative medicine using mesenchymal stem cells (MSCs) could be advantageous for the treatment of ACLF as these cells can downregulate inflammatory response by inducing antiinflammatory events and prevent hepatic damage and fibrosis by inhibiting hepatic stellate cell activation and collagen synthesis. Moreover, MSCs are involved in tissue repair by the process of liver regeneration. Considering the broad therapeutic potential of MSCs, it can serve as an alternative treatment to liver transplant in the near future, if promising results are achieved.
Collapse
Affiliation(s)
- Arshi Khanam
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States
| |
Collapse
|
|
32
|
Invasive Candidiasis in Liver Transplant Recipients: A Review. CURRENT FUNGAL INFECTION REPORTS 2021. [DOI: 10.1007/s12281-021-00426-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
|
|
33
|
Zhang X, Shen S, Dai X, Bi Y, Zhang J, Wu Y, Shi Y, Wei R, Gao H. Clinical Risk Score for Invasive Pulmonary Aspergillosis in Patients With Liver Failure: A Retrospective Study in Zhejiang. Front Med (Lausanne) 2021; 8:762504. [PMID: 34881264 PMCID: PMC8645556 DOI: 10.3389/fmed.2021.762504] [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: 08/22/2021] [Accepted: 10/11/2021] [Indexed: 11/13/2022] Open
Abstract
Purpose: The mortality of invasive pulmonary aspergillosis (IPA) in patients with liver failure was high. However, the prophylactic treatment in those patients with a high-risk factor in IPA has not been researched. Patients and methods: A multicenter, retrospective study was conducted in patients with liver failure. The study cohort of liver failure was randomly split into a training set for model development and the other served as the testing set for model verification. Multivariate analysis was performed to identify the risk factors of IPA. A weighted risk score for IPA was established. Anti-fungal treatment was prophylactically used in patients with medium and high IPA risk to evaluate the effect. Results: In total, 1,722 patients with liver failure were enrolled. Fifty-seven patients who received prophylactic treatment were excluded from the risk factor system study. About 1,665 patients were randomly split at a ratio of 2:1 into two datasets. Diabetes, glucocorticoids, plasma exchange, and hepatorenal syndrome (HRS) were risk factors in IPA in patients with liver failure, with weighted risk scores of 4, 7, 2, and 3, respectively. In the validation set and test set, the patients with risk scores of ≤ 3 presented low incidences of IPA at 4 and 2.7%. Patients with risk scores of 4-5 had an IPA incidence of 7.6% and 10.1%, and could be considered as a medium-risk group (p < 0.01 vs. the group with scores of ≤ 3), whereas those with risk scores of >5 manifested a significantly higher IPA incidence of 21.2 and 12.7%, who were considered a high-risk group (p < 0.01 vs. the groups with scores of 4-5 and >5, respectively). The IPA risk scores in the training set and the testing set were also analyzed by the ROC with an area under the ROC of 0.7152 and 0.6912. In this study, 57 patients received antifungal prophylaxis; the incidence of IPA was 1.8%, which was significantly lower after prophylactic antifungal therapy (p < 0.001). Conclusions: A weighted risk score for patients with liver failure, complicated with IPA, was established and confirmed in the testing cohort. Voriconazole prophylactic treatment to patients with liver failure with medium and high IPA risk can effectively prevent Aspergillus infection.
Collapse
Affiliation(s)
- Xuan Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Sijia Shen
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Xiahong Dai
- Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
| | - Yunjiao Bi
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Junjie Zhang
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Yuhao Wu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Yishang Shi
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Runan Wei
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Hainv Gao
- Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
| |
Collapse
|
|
34
|
Verma N, Roy A, Singh S, Pradhan P, Garg P, Singh M. Factors determining the mortality in cirrhosis patients with invasive candidiasis: a systematic review and meta-analysis. Med Mycol 2021; 60:6420248. [PMID: 34734272 DOI: 10.1093/mmy/myab069] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 10/11/2021] [Accepted: 11/01/2021] [Indexed: 11/14/2022] Open
Abstract
The impact of invasive candidiasis (IC) on the outcomes in the non-conventional high-risk cirrhosis population is poorly characterized. Therefore, we reviewed the outcomes and their influencing factors in cirrhosis patients with IC. PubMed, Embase, Ovid, CINHAL, and Web of Science were searched for full-text observational studies describing mortality due to IC in cirrhosis. We did a systematic review and random-effects meta-analysis to pool the point-estimate and comparative-odds of mortality. The estimate's heterogeneity was explored on sub-groups, outliers-test, and meta-regression. We evaluated the asymmetry in estimates on funnel plot and Eggers regression. Quality of studies was assessed on the New-Castle Ottawa scale.Of 3143 articles, 13 studies (611 patients) were included (good/fair quality: 6/7). IC patients were sick with a high model for end-stage liver disease (MELD: 27.0) and long hospital stay (33.2 days). The pooled-mortality was 54.7% (95% CI: 41.3-67.5), I2: 80%, P<0.01. Intensive care unit (ICU) admission (P<0.001), site of infection; viz. peritonitis and candidemia (P = 0.014) and high MELD of cases (P = 0.029) were predictors of high mortality. The odds of mortality due to IC was 4.4 times higher than controls and was 8.5 and 3.3 times higher than non-infected, and bacterially-infected controls. Studies in ICU-admitted (OR: 6.3) or acute-on-chronic liver failure (ACLF, OR: 5.0) patients had numerically higher odds of mortality than all-hospitalized cirrhosis patients (OR: 4.0). In conclusion, substantially high mortality is reported in cirrhosis patients with IC. ICU admission, ACLF, high MELD, peritonitis, and candidemia are key factors determining high mortality in cirrhosis patients with IC. LAY SUMMARY We report a high mortality rate of 55% in patients with liver cirrhosis and invasive candidiasis. Higher odds (4.4 times) of death, especially in patients with ACLF (5 times) or ICU admission (6.3 times) were seen. Candida peritonitis and candidemia are associated with high mortality in cirrhosis.
Collapse
Affiliation(s)
- Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Akash Roy
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
| | - Shreya Singh
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Pranita Pradhan
- Department of Internal Medicine, Government Medical College and Hospital, Chandigarh, 160012, India
| | - Pratibha Garg
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Meenu Singh
- Department of Internal Medicine, Government Medical College and Hospital, Chandigarh, 160012, India
| |
Collapse
|
|
35
|
Verma N, Singh S, Singh M, Chauhan A, Pradhan P, Jaiswal N, Chakrabarti A, Singh M. Global epidemiological burden of fungal infections in cirrhosis patients: a systematic review with meta-analysis. Mycoses 2021; 65:266-284. [PMID: 34724269 DOI: 10.1111/myc.13387] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 10/26/2021] [Accepted: 10/28/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND & AIMS Fungal infections (FIs) have serious implications, yet understated in cirrhosis. Therefore, we reviewed the epidemiology and trends of FIs among cirrhotics. METHODS Four electronic-databases were searched for full-text articles describing prevalence of FIs in cirrhosis. Studies from post-transplant, malignancy and classical-immuno-deficiency patients were excluded. A random-effects meta-analysis was done to pool estimates of FIs (overall, and by type and infection-site), and their variation(I2 ) was explored on moderator-analysis and meta-regression. Risk of bias and asymmetry in estimates was assessed by a checklist and Eggers-regression, respectively.(CRD42019142782) RESULTS: Thirty-four low-risk and four moderate-risk studies (31984 cirrhotics) were included. Pooled-estimates of overall-FIs (17 studies), invasive fungal infections (IFIs; 17 studies), invasive-candidiasis (23 studies), and invasive-aspergillosis (16 studies) in cirrhosis were 10.2%(6.0-16.9), 9.5%(5.4-16.2), 4.0%(2.0-8.0) and 2.8%(1.5-5.3); respectively (I2 >90%;each). Site of FIs in decreasing order of pooled-prevalence was pulmonary, urinary-tract, bloodstream, peritoneal, esophageal, and cerebral. Geographic differences in these estimates were remarkable, with highest burden of overall-FIs from Belgium, USA, and India. Non-albicans-Candida and Aspergillus infections have increased over the last-decade in cirrhosis. Intensive-care-unit (ICU)-admitted and acute-on-chronic liver failure (ACLF) patients had the highest prevalence of IFIs. MELD-score(cases), bias-score, and sample size across studies were the predictors of variance in overall-FI-estimates. Diabetes, steroid and broad-spectrum antibiotic-exposure, and multiple organ failures were the common predispositions reported in patients with FIs. CONCLUSIONS FIs impose a substantial burden in cirrhosis. ACLF and ICU-admission should be considered as a host factor for defining IFIs. Epidemiology of FIs can guide interpretation of biomarkers and antifungal treatment in cirrhosis.
Collapse
Affiliation(s)
- Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shreya Singh
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manvi Singh
- Indian Council of Medical Research Center for Evidence-Based Child Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Anil Chauhan
- Indian Council of Medical Research Center for Evidence-Based Child Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pranita Pradhan
- Indian Council of Medical Research Center for Evidence-Based Child Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nishant Jaiswal
- Indian Council of Medical Research Center for Evidence-Based Child Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Arunaloke Chakrabarti
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Meenu Singh
- Indian Council of Medical Research Center for Evidence-Based Child Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| |
Collapse
|
|
36
|
Verma N, Singh S, Syal A, Pradhan P, Singh M, Singh M. Invasive aspergillosis is a critical determinant of mortality in cirrhosis: a systematic review with meta-analysis. Med Mycol 2021; 59:1092-1100. [PMID: 34308965 DOI: 10.1093/mmy/myab044] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/06/2021] [Accepted: 07/23/2021] [Indexed: 12/15/2022] Open
Abstract
Invasive fungal infections pose a severe threat in unconventional immunocompromised hosts such as cirrhosis. Herein we review the impact of invasive aspergillosis (IA) on the prognosis of cirrhosis patients. An electronic search for full-text articles describing IA in cirrhosis was conducted and the disease outcomes and mortality (point-estimate and comparative risk) were pooled on random-effects meta-analysis. Of 4127 articles, 11 studies (9 with good/fair and 2 with poor quality) were included. IA was associated with high disease severity and multi-organ failures in cirrhosis. The pooled-mortality of IA was 81.8% (95%CI: 64.3-91.8, I2 = 59%, p<0.01). Estimate's-heterogeneity (I2) was explored through sub-groups, meta-regression, and influential diagnostics. Mortality estimates were higher among subgroups of acute-on-chronic liver failure (ACLF, 86.4%) and intensive care unit (ICU)-admitted patients (84.0%). The odds of mortality related to IA were 8.9 times higher than controls and much higher in ACLF (OR: 22.5) and ICU-admitted patients (OR: 36.4). The odds of mortality in IA were 4.1, 12.9, and 48.6 times higher than bacterial, no-fungal infections, and no-infection controls. There was no asymmetry in mortality-estimates or odds ratios and mortality in IA was high irrespective of country of origin, site of infection, proven or probable category, and quality of study. Thus, IA is associated with very high mortality in cirrhosis patients, especially in ACLF and ICU-admitted patients. Intensive research is needed for the rapid diagnosis and treatment of IA in cirrhosis.
Collapse
Affiliation(s)
- Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shreya Singh
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Arshi Syal
- Department of Internal Medicine, Government Medical College and Hospital, Chandigarh, India
| | - Pranita Pradhan
- Indian Council of Medical Research Center for Evidence-Based Child Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manvi Singh
- Indian Council of Medical Research Center for Evidence-Based Child Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Meenu Singh
- Indian Council of Medical Research Center for Evidence-Based Child Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| |
Collapse
|
|
37
|
Cao Y, Fan Y, Wang Y, Liu X, Xie W. Acute-on-chronic Liver Failure in a Patient with Candida Endophthalmitis: A Case Report. J Clin Transl Hepatol 2021; 9:447-451. [PMID: 34221931 PMCID: PMC8237134 DOI: 10.14218/jcth.2020.00092] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 02/19/2021] [Accepted: 03/01/2021] [Indexed: 12/14/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a risk factor for fungal infection. Endogenous fungal endophthalmitis is a serious, sight-threatening disease. Common causes include immunocompromised state and intravenous drug use, permitting opportunistic pathogens to reach the eye through the blood stream. We report a case of Candida endophthalmitis in a 47 year-old woman who was admitted to our hospital with ACLF and poorly controlled diabetes. In addition, she was treated with glucocorticoids due to severe jaundice. After treatment for ACLF, the patient experienced fever with blurred vision in the left eye and was diagnosed with candidemia, endogenous Candida endophthalmitis in the left eye, and chorioretinitis in the right eye. Systemic and topical antifungal treatment was administered based on the positive Candida albicans test in intraocular fluid using second-generation sequencing. The patient underwent vitrectomy in the left eye and C. albicans was confirmed in vitreous cultures. Follow-up visit, at 6 weeks after the operation, showed only light perception in the left eye and stable visual acuity in the right eye. Physicians should be aware of endogenous fungal endophthalmitis in patients with ACLF, especially those with Candida infection, a history of glucocorticoid use, and diabetes. A dilated retinal examination should be performed by an ophthalmologist if ACLF patients develop fever and fungal infection.
Collapse
Affiliation(s)
- Ying Cao
- Center of Liver Diseases, Capital Medical University Affiliated to Beijing Ditan Hospital, Beijing, China
| | - Ying Fan
- Center of Liver Diseases, Capital Medical University Affiliated to Beijing Ditan Hospital, Beijing, China
| | - Yanbin Wang
- Center of Liver Diseases, Capital Medical University Affiliated to Beijing Ditan Hospital, Beijing, China
| | - Xiyao Liu
- Department of Ophthalmology, Capital Medical University Affiliated to Beijing Ditan Hospital, Beijing, China
| | - Wen Xie
- Center of Liver Diseases, Capital Medical University Affiliated to Beijing Ditan Hospital, Beijing, China
- Correspondence to: Wen Xie, Center of Liver Diseases, Capital Medical University Affiliated to Beijing Ditan Hospital, No. 8, Jingshun East Street, Chaoyang District, Beijing 100015, China. ORCID: https://orcid.org/0000-0002-7314-8175. Tel: +86-10-84322816, Fax: +86-10-84322818, E-mail:
| |
Collapse
|
|
38
|
Cui F, Luo P, Bai Y, Meng J. A Novel Diagnostic Method for Invasive Fungal Disease Using the Factor G Alpha Subunit From Limulus polyphemus. Front Microbiol 2021; 12:658144. [PMID: 34262536 PMCID: PMC8275026 DOI: 10.3389/fmicb.2021.658144] [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: 01/25/2021] [Accepted: 04/28/2021] [Indexed: 11/25/2022] Open
Abstract
Deaths due to invasive fungal disease (IFD) have been increasing every year. Early and rapid detection is important to reduce the mortality rate associated with IFD. In this study, we explored a novel diagnostic method for detecting IFD, which involves the G Factor α subunit (GFαSub) from Limulus polyphemus. The GFαSub double-sandwich method was developed to detect (1,3)-β-D-glucans in human serum using purified GFαSub and horseradish peroxidase-labeled GFαSub. The GFαSub double-sandwich method and the G test were performed and compared. Using GFαSub sequence analysis, the expression plasmid pET30a-GFαSub252-668 was synthesized, and GFαSub252-668 was expressed and purified via isopropyl-β-d-thiogalactoside induction and nickel-nitrilotriacetic acid affinity. The optimization method was established via the orthogonal method. Using this method, the sera of 36 patients with IFD and 92 volunteers without IFD underwent detection, and the receiver operating characteristic curve of the GFαSub252-668 double-sandwich method was described. The sensitivity and specificity of the GFαSub252-668 double-sandwich method were 91.67 and 82.61%, respectively, and there was good correlation with the G test for the serum specimens of 36 patients with pulmonary IFD (R 2 = 0.7592). In conclusion, our study suggests that the GFαSub252-668 double-sandwich method was satisfactory at detecting IFD cases. This method can be promoted and further developed as a novel method for diagnosing IFD.
Collapse
Affiliation(s)
- Fang Cui
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Luo
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yao Bai
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jiangping Meng
- Assisted Reproductive Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| |
Collapse
|
|
39
|
Pharmacokinetics and Antifungal Activity of Echinocandins in Ascites Fluid of Critically Ill Patients. Antimicrob Agents Chemother 2021; 65:e0256520. [PMID: 33972242 DOI: 10.1128/aac.02565-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The pharmacokinetics and antifungal activity of the echinocandins anidulafungin (AFG), micafungin (MFG), and caspofungin (CAS) were assessed in ascites fluid and plasma of critically ill adults treated for suspected or proven invasive candidiasis. Ascites fluid was obtained from ascites drains or during paracentesis. The antifungal activity of the echinocandins in ascites fluid was assessed by incubation of Candida albicans and Candida glabrata at concentrations of 0.03 to 16.00 μg/ml. In addition, ascites fluid samples obtained from our study patients were inoculated with the same isolates and evaluated for fungal growth. These patient samples had to be spiked with echinocandins to restore the original concentrations because echinocandins had been lost during sterile filtration. In ascites fluid specimens of 29 patients, echinocandin concentrations were below the simultaneous plasma levels. Serial sampling in 20 patients revealed a slower rise and decline of echinocandin concentrations in ascites fluid than in plasma. Proliferation of C. albicans in ascites fluid was slower than in culture medium and growth of C. glabrata was lacking, even in the absence of antifungals. In CAS-spiked ascites fluid samples, fungal CFU counts moderately declined, whereas spiking with AFG or MFG had no relevant effect. In ascites fluid of our study patients, echinocandin concentrations achieved by therapeutic doses did not result in a consistent eradication of C. albicans or C. glabrata. Thus, therapeutic doses of AFG, MFG, or CAS may result in ascites fluid concentrations preventing relevant proliferation of C. albicans and C. glabrata, but do not warrant reliable eradication.
Collapse
|
|
40
|
Shishido AA, Vostal A, Mayer R, Ho CY, Baddley JW. Diagnosis of central nervous system invasive aspergillosis in a liver transplant recipient using microbial cell-free next generation DNA sequencing. Transpl Infect Dis 2021; 23:e13592. [PMID: 33655668 DOI: 10.1111/tid.13592] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 02/06/2021] [Accepted: 02/14/2021] [Indexed: 12/20/2022]
Abstract
Invasive aspergillosis (IA) is an important opportunistic infection among patients with liver disease and liver transplants. Diagnosis of IA may be challenging, especially among patients with central nervous system infection. Herein, we demonstrate the utility of next-generation sequencing of microbial cell-free DNA in the diagnosis of fungal brain abscess in a liver transplant recipient.
Collapse
Affiliation(s)
- Akira A Shishido
- Division of Infectious Diseases, University of Maryland Medical Center, Baltimore, MD, USA
| | - Alexander Vostal
- Division of Infectious Diseases, University of Maryland Medical Center, Baltimore, MD, USA
| | - Romana Mayer
- Department of Pathology, University of Maryland, Baltimore, MD, USA
| | - Cheng-Ying Ho
- Department of Pathology, University of Maryland, Baltimore, MD, USA
| | - John W Baddley
- Division of Infectious Diseases, University of Maryland Medical Center, Baltimore, MD, USA
| |
Collapse
|
|
41
|
Kamani L, Kalwar H. Fungal urinary tract infection among chronic liver disease patients with hepatic encephalopathy and its treatment outcomes. JGH Open 2021; 5:213-218. [PMID: 33553658 PMCID: PMC7857284 DOI: 10.1002/jgh3.12470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 10/25/2020] [Accepted: 11/21/2020] [Indexed: 11/07/2022]
Affiliation(s)
- Lubna Kamani
- Department of Gastroenterology Liaquat National Hospital Karachi Pakistan
| | - Hamid Kalwar
- Department of Gastroenterology Liaquat National Hospital Karachi Pakistan
| |
Collapse
|
|
42
|
Ferrarese A, Cattelan A, Cillo U, Gringeri E, Russo FP, Germani G, Gambato M, Burra P, Senzolo M. Invasive fungal infection before and after liver transplantation. World J Gastroenterol 2020; 26:7485-7496. [PMID: 33384549 PMCID: PMC7754548 DOI: 10.3748/wjg.v26.i47.7485] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 11/15/2020] [Accepted: 11/29/2020] [Indexed: 02/06/2023] Open
Abstract
Invasive infections are a major complication before liver transplantation (LT) and in the early phase after surgery. There has been an increasing prevalence of invasive fungal disease (IFD), especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure, who suffer from a profound state of immune dysfunction and receive intensive care management. In such patients, who are listed for LT, development of an IFD often worsens hepatic and extra-hepatic organ dysfunction, requiring a careful evaluation before surgery. In the post-transplant setting, the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis, even if several major issues still remain, such as duration, target population and drug type(s). Nevertheless, the development of IFD in the early phase after surgery significantly impairs graft and patient survival. This review outlines presentation, prophylactic and therapeutic strategies, and outcomes of IFD in LT candidates and recipients, providing specific considerations for clinical practice.
Collapse
Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Annamaria Cattelan
- Tropical and Infectious Disease Unit, Padua University Hospital, Padua 35128, Italy
| | - Umberto Cillo
- Padua University Hospital, Hepatobiliary Surgery and Liver Transplant Center, Padua 35128, Italy
| | - Enrico Gringeri
- Padua University Hospital, Hepatobiliary Surgery and Liver Transplant Center, Padua 35128, Italy
| | | | - Giacomo Germani
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| |
Collapse
|
|
43
|
Zhai XR, Tong JJ, Wang HM, Xu X, Mu XY, Chen J, Liu ZF, Wang Y, Su HB, Hu JH. Infection deteriorating hepatitis B virus related acute-on-chronic liver failure: a retrospective cohort study. BMC Gastroenterol 2020; 20:320. [PMID: 32993547 PMCID: PMC7526233 DOI: 10.1186/s12876-020-01473-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 09/25/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Infection is common in acute-on-chronic liver failure (ACLF), which may worsen the clinical condition and prognosis. However, the characteristics of infection and its influence on prognosis in hepatitis B virus related ACLF (HBV-ACLF) as defined by the European Association for the Study of the Liver (EASL) have not been clarified. We aimed to investigate the characteristics of infection and its influence on mortality in patients with HBV-ACLF defined by EASL in China. METHODS We performed a retrospective cohort study in patients with HBV-ACLF defined by EASL in a single center from January 2015 to December 2017. These patients were divided into two groups with and without infection. The incidence, sites of infection, isolated strains, and risk factors associated with mortality were evaluated. RESULTS A total of 289 patients were included, among them 185 (64.0%) were diagnosed with an infection. The most common type of infection was pneumonia (55.7%), followed by spontaneous bacterial peritonitis (47.6%) and others. The gram-negative bacteria were the most frequent (58.3%). Patients with one, two, and three or more infection sites had a gradually increasing incidence of sepsis (P < 0.01), septic shock (P < 0.001), and ACLF-3 (P < 0.05). Also, patients with infection isolated one, two, and three or more strains showed a growing incidence of sepsis (P < 0.01) and septic shock (P < 0.001). Patients with infection showed a significantly higher 28-day mortality than those without (P < 0.01), especially in patients with ACLF-3. Infection was identified as an independent risk factor for 28-day mortality in all HBV-ACLF patients. Pneumonia and sepsis were identified as independent predictors of 28-day mortality for patients with infection. CONCLUSIONS Infection is associated with severe clinical course and high mortality in HBV-ACLF defined by EASL. The increased number of infection sites or isolated strains was associated with the occurrence of sepsis and septic shock. Pneumonia and sepsis were independent predictors for mortality in HBV-ACLF patients with infection.
Collapse
Affiliation(s)
- Xing-Ran Zhai
- Peking University 302 Clinical Medical School, Beijing, China
| | - Jing-Jing Tong
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | - Hong-Min Wang
- Peking University 302 Clinical Medical School, Beijing, China
| | - Xiang Xu
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiu-Ying Mu
- Peking University 302 Clinical Medical School, Beijing, China
| | - Jing Chen
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | - Zi-Feng Liu
- Medical School of Chinese PLA, Beijing, China
| | - Yu Wang
- Medical School of Chinese PLA, Beijing, China
| | - Hai-Bin Su
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jin-Hua Hu
- Peking University 302 Clinical Medical School, Beijing, China
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| |
Collapse
|
|
44
|
Candida Infections in Immunocompetent Hosts: Pathogenesis and Diagnosis. CURRENT FUNGAL INFECTION REPORTS 2020. [DOI: 10.1007/s12281-020-00392-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
|
|
45
|
Bartoletti M, Rinaldi M, Pasquini Z, Scudeller L, Piano S, Giacobbe DR, Maraolo AE, Bussini L, Del Puente F, Incicco S, Angeli P, Giannella M, Baldassarre M, Caraceni P, Campoli C, Morelli MC, Cricca M, Ambretti S, Gentile I, Bassetti M, Viale P. Risk factors for candidaemia in hospitalized patients with liver cirrhosis: a multicentre case-control-control study. Clin Microbiol Infect 2020; 27:276-282. [PMID: 32360775 DOI: 10.1016/j.cmi.2020.04.030] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 04/20/2020] [Accepted: 04/23/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The aim of this study was to evaluate the risk factors for candidaemia in patients with liver cirrhosis. METHODS This was a case-control-control (1:2:2) study performed in four Italian tertiary centres from 2006 to 2015. Cases were patients with liver cirrhosis developing candidaemia. For every case of candidaemia we enrolled two additional patients undergoing blood cultures for suspected infection yielding isolation of a bacterial pathogen (control A) and two additional patients undergoing blood cultures for suspected infection yielding negative results (control B). Patients were matched according to age, sex and model for end stage liver disease at hospital admission. RESULTS During the study period 90 cases, 180 controls A and 180 controls B were included. At multivariate analysis assessed by means of multinomial conditional regression models, factors independently associated with candidaemia were previous (<30 days) acute-on-chronic liver failure (relative risk ratio (RRR) 2.22 (95% confidence interval (CI) 1.09-4.54), p = 0.046), previous(<30 days) gastrointestinal endoscopy (RRR 2.38 (95% CI 1.19-4.78) p = 0.014), previous(<30 days) antibiotic treatment for at least 7 days (RRR 2.74 (95% CI 1.00-7.48), p = 0.049), presence of central venous catheter (RRR 2.77 (95% CI 1.26-6.09, p = 0.011), total parenteral nutrition (RRR 3.90 (95% CI 1.62-9.40), p = 0.002) at infection onset and length of in-hospital stay >15 days (RRR 4.63 (95% CI 2.11-10.18), p <0.001] Conversely, rifaximin treatment was associated with lower rate of candidaemia (RRR 0.38 (95% CI 0.19-0.77), p = 0.007). Multivariable analysis for 30-day mortality showed that patients with isolation of Candida spp. from blood cultures had worse outcome when compared with controls even though the difference did not reach a statistical significance (hazard ratio 1.64 (95% 0.97-2.75) p = 0.06). CONCLUSIONS We identified previous antibiotic use, gastrointestinal endoscopy or acute-on-chronic liver failure and presence of central venous catheter especially for parenteral nutrition as independent factors associated with candidaemia. Surprisingly, chronic rifaximin use was a protective factor.
Collapse
Affiliation(s)
- M Bartoletti
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
| | - M Rinaldi
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Z Pasquini
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; Clinica Malattie Infettive, Dipartimento di Scienze Biomediche e Sanità Pubblica, Università Politecnica delle Marche, Azienda Ospedaliera Universitaria, Ospedali Riuniti Umberto I-Lancisi-Salesi, Ancona, Italy
| | - L Scudeller
- Scientific Direction IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milano, Italy
| | - S Piano
- Unit of Internal Medicine and Hepatology Department of Medicine-DIMED University of Padova, Padova, Italy
| | - D R Giacobbe
- Department of Health Sciences, University of Genoa, Genoa, Italy; Clinica Malattie Infettive, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy
| | - A E Maraolo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - L Bussini
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - F Del Puente
- Department of Health Sciences, University of Genoa, Genoa, Italy; Clinica Malattie Infettive, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy
| | - S Incicco
- Unit of Internal Medicine and Hepatology Department of Medicine-DIMED University of Padova, Padova, Italy
| | - P Angeli
- Unit of Internal Medicine and Hepatology Department of Medicine-DIMED University of Padova, Padova, Italy
| | - M Giannella
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - M Baldassarre
- Sant'Orsola-Malpighi University Hospital, Center for Applied Biomedical Research (CRBA), University of Bologna, Bologna, Italy
| | - P Caraceni
- Sant'Orsola-Malpighi University Hospital, Center for Applied Biomedical Research (CRBA), University of Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - C Campoli
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - M C Morelli
- End-stage liver disease Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - M Cricca
- Operative Unit of Microbiology Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - S Ambretti
- Operative Unit of Microbiology Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - I Gentile
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - M Bassetti
- Department of Health Sciences, University of Genoa, Genoa, Italy; Clinica Malattie Infettive, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy
| | - P Viale
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| |
Collapse
|
|
46
|
Liu CR, Li YP, Feng DD, Dang SS. Hot topics and difficult problems in diagnosis and treatment of end-stage liver disease with fungal infection. Shijie Huaren Xiaohua Zazhi 2020; 28:203-209. [DOI: 10.11569/wcjd.v28.i6.203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Chen-Rui Liu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Ya-Ping Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Dan-Dan Feng
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Shuang-Suo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| |
Collapse
|
|
47
|
New Triazole NT-a9 Has Potent Antifungal Efficacy against Cryptococcus neoformans In Vitro and In Vivo. Antimicrob Agents Chemother 2020; 64:AAC.01628-19. [PMID: 31791946 DOI: 10.1128/aac.01628-19] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Accepted: 11/21/2019] [Indexed: 12/15/2022] Open
Abstract
In the past decades, the incidence of cryptococcosis has increased dramatically, which poses a new threat to human health. However, only a few drugs are available for the treatment of cryptococcosis. Here, we described a leading compound, NT-a9, an analogue of isavuconazole, that showed strong antifungal activities in vitro and in vivo NT-a9 showed a wide range of activities against several pathogenic fungi in vitro, including Cryptococcus neoformans, Cryptococcus gattii, Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata, and Candida parapsilosis, with MICs ranging from 0.002 to 1 μg/ml. In particular, NT-a9 exhibited excellent efficacy against C. neoformans, with a MIC as low as 0.002 μg/ml. NT-a9 treatment resulted in changes in the sterol contents in C. neoformans, similarly to fluconazole. In addition, NT-a9 possessed relatively low cytotoxicity and a high selectivity index. The in vivo efficacy of NT-a9 was assessed using a murine disseminated-cryptococcosis model. Mice were infected intravenously with 1.8 × 106 CFU of C. neoformans strain H99. In the survival study, NT-a9 significantly prolonged the survival times of mice compared with the survival times of the control group or the isavuconazole-, fluconazole-, or amphotericin B-treated groups. Of note, 4 and 8 mg/kg of body weight of NT-a9 rescued all the mice, with a survival rate of 100%. In the fungal-burden study, NT-a9 also significantly reduced the fungal burdens in brains and lungs, while fluconazole and amphotericin B only reduced the fungal burden in lungs. Taken together, these data suggested that NT-a9 is a promising antifungal candidate for the treatment of cryptococcosis infection.
Collapse
|
|
48
|
Lin S, Han L, Li D, Wang T, Wu Z, Zhang H, Xiao Z, Wu Y, Huang J, Wang M, Zhu Y. The Association between Meteorological Factors and the Prevalence of Acute-on-chronic Liver Failure: A Population-based Study, 2007-2016. J Clin Transl Hepatol 2019; 7:341-345. [PMID: 31915603 PMCID: PMC6943211 DOI: 10.14218/jcth.2019.00044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 11/13/2019] [Accepted: 12/06/2019] [Indexed: 12/04/2022] Open
Abstract
Background and Aims: The aim of this study was to investigate the effect(s) of meteorological factors on the prevalence of acute-on-chronic liver failure (ACLF) based on 10-years' worth of population data. Methods: We retrospectively collected ACLF case data from January 2007 to December 2016 from three major hospitals in Fuzhou City, China. Climatic data, including rainfall, mean temperature, differences in temperature (delta temperature) and mean humidity for each month were downloaded from the China Climatic Data Service Center. Following data collection, Poisson regression analysis was used to estimate the effect(s) of climatic factors on the risk of the prevalence of ACLF. Results: The population consisted of a total of 3510 cases, with a mean age of 44.7 ± 14.8 years-old and with 79.8% being male. Upon analyzing the population data, we found a growing trend and seasonal pattern of monthly counts of ACLF-related hospitalization throughout the past decade. Specifically, the primary peak of ACLF prevalence was in January and the secondary peak was in July. Poisson regression showed mean temperature (risk ratio = 0.991, 95%CI = 0.986-0.996) and mean humidity (risk ratio = 1.011, 95%CI = 1.006-1.017) to be independently correlated with the monthly cases of ACLF. The results suggest that every unit increase of mean temperature (1°C) and mean humidity (1%) are associated with 0.991- and 1.011-fold changes of ACLF cases, respectively. Rainfall and delta temperature did not appear to affect the prevalence of this disease. Conclusions: The hospitalization for ACLF peaks in January and July. Low temperature and high humidity appear to function as factors contributing to this seasonal pattern.
Collapse
Affiliation(s)
- Su Lin
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Lifen Han
- Department of Infectious Disease, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Dongliang Li
- Department of Hepatobiliary Disease, 900 Hospital of PLA, Fuzhou, Fujian, China
| | - Ting Wang
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Zimu Wu
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Haoyang Zhang
- School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China
| | | | - Yinlian Wu
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Jiaofeng Huang
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Mingfang Wang
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Yueyong Zhu
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| |
Collapse
|
|
49
|
Roy A, Verma N, Ahuja CK. Intracranial invasive mycosis mimicking hepatic encephalopathy in a patient with cirrhosis. BMJ Case Rep 2019; 12:12/11/e231548. [PMID: 31776153 DOI: 10.1136/bcr-2019-231548] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
A 45-year-old man with alcohol-related decompensated cirrhosis presented with jaundice, fever, headache and altered sensorium. At presentation, he had tachycardia, disorientation to time and place, asterixis, icterus and upgoing plantar response. Investigations showed anaemia, thrombocytopenia, leucocytosis, hyperbilirubinemia and elevated arterial ammonia. Despite management with antihepatic coma measures and normalisation of ammonia, broad-spectrum antibiotics, 20% albumin, the patient worsened. On day 3, the patient developed generalised tonic-clonic seizure prompting mechanical ventilation. Examination showed right proptosis, chemosis and pupillary anisocoria. MRI brain showed multifocal infarcts in the right temporal lobe, right cerebellum and brainstem with inflammation in the right orbit, infratemporal fossa with right internal carotid artery thrombosis, and suspicious maxillary sinus thickening. Nasal scrapings showed aseptate fungal hyphae and serum galactomannan index was positive. Despite receiving liposomal amphotericin-B, patient had an unfavourable outcome. Intracranial invasive mycosis can mimic hepatic encephalopathy and is associated with high mortality in cirrhotics. A high index of suspicion, positive biomarkers and diagnostic radiology may provide the key to the diagnosis.
Collapse
Affiliation(s)
- Akash Roy
- Hepatology, Post Graduate Institute of Medical Education and Research (PIGMER), Chandigarh, India
| | - Nipun Verma
- Hepatology, Post Graduate Institute of Medical Education and Research (PIGMER), Chandigarh, India
| | - Chirag Kamal Ahuja
- Neuroradiology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| |
Collapse
|
|
50
|
Huang CH, Pang LT, Xu LC, Ge TT, Xu QM, Chen Z. Risk factors, clinical features, and short-term prognosis of spontaneous fungal peritonitis in cirrhosis: A matched case-control study. World J Clin Cases 2019; 7:2438-2449. [PMID: 31559280 PMCID: PMC6745339 DOI: 10.12998/wjcc.v7.i17.2438] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 07/12/2019] [Accepted: 07/27/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Spontaneous peritonitis is one of the most common infectious complications in cirrhotic patients with ascites. Spontaneous fungal peritonitis (SFP) is a type of spontaneous peritonitis that is a less recognized but devastating complication in end-stage cirrhosis. Although high mortality was previously noted, scant data are available to fully define the factors responsible for the occurrence of SFP and its mortality.
AIM To illustrate the differences between SFP and spontaneous bacterial peritonitis (SBP) and discuss the risk factors for the occurrence of SFP and its short-term mortality.
METHODS We performed a matched case-control study between January 1, 2007 and December 30, 2018. Patients with SFP were included in a case group. Sex-, age-, and time-matched patients with SBP were included in a control group and were further divided into control-1 group (positive bacterial culture) and control-2 group (negative bacterial culture). The clinical features and laboratory parameters, severity models, and prognosis were compared between the case and control groups. Logistic regression analysis was used to determine the risk factors for occurrence, and the Cox regression model was used to identify the predictive factors for short-term mortality of SFP.
RESULTS Patients with SFP exhibited more severe systemic inflammation, higher ascites albumin and polymorphonuclear neutrophils, and a worsened 15-d mortality than patients in the control groups. Antibiotic administration (case vs control-1: OR = 1.063, 95%CI: 1.012-1.115, P = 0.014; case vs control-2: OR = 1.054, 95%CI: 1.014-1.095, P = 0.008) remarkably increased the occurrence of SFP or fungiascites. Hepatorenal syndrome (HR = 5.328, 95%CI: 1.050-18.900) and total bilirubin (μmol/L; HR = 1.005, 95%CI: 1.002-1.008) represented independent predictors of SFP-related early mortality.
CONCLUSION Long-term antibiotic administration increases the incidence of SFP, and hepatorenal syndrome and total bilirubin are closely related to short-term mortality.
Collapse
Affiliation(s)
- Chun-Hong Huang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Lan-Tian Pang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Li-Chen Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Tian-Tian Ge
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Qiao-Mai Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Zhi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| |
Collapse
|