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Xiang Y, Mao W. Neutrophil-derived ratios as predictors of short-term mortality in HBV-associated decompensated cirrhosis. BMC Gastroenterol 2025; 25:404. [PMID: 40419938 DOI: 10.1186/s12876-025-03991-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Accepted: 05/13/2025] [Indexed: 05/28/2025] Open
Abstract
BACKGROUND Hepatitis B virus-associated decompensated cirrhosis (HBV-DC) is recognized as a critical illness with an increased risk of short-term mortality. Neutrophil-derived ratios, including neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-albumin ratio, neutrophil-to-high-density lipoprotein-cholesterol ratio, neutrophil-to-hemoglobin ratio, and neutrophil-to-platelet ratio, have emerged as potential prognostic markers in various liver diseases. The present study aimed to determine the effectiveness of these neutrophil-derived ratios for prediction of mortality in patients with HBV-DC. METHODS We conducted a retrospective analysis of HBV-DC patients at our hospital between April 2022 and April 2024. The study endpoint was the 30-day mortality rate. These neutrophil-derived ratios were calculated from data obtained during routine laboratory tests on admission. Disease severity was assessed using the Model for End-Stage Liver Disease (MELD) score. Multivariate regression analyses and receiver operating characteristic (ROC) curve analyses were conducted. RESULTS The study investigated 160 HBV-DC patients, of whom 23 (14.4%) experienced mortality within 30 days. Non-survivors exhibited markedly higher values for neutrophil-derived ratios than survivors. All neutrophil-derived ratios were associated with mortality in univariate analyses, but only NLR and MELD score remained as independent predictors of mortality in multivariate analyses. In the ROC analyses, NLR showed a similar prognostic value to MELD score. Moreover, both NLR and MELD score had high specificity for prediction of mortality in HBV-DC patients. CONCLUSIONS Among neutrophil-derived ratios, NLR stands out as a simple and reliable predictor of mortality in HBV-DC patients.
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Affiliation(s)
- Yang Xiang
- Department of Endocrinology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - WeiLin Mao
- Department of Clinical Laboratory, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, China.
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Wan X, Xu H, Li H, Zhong S, Lei Y, Deng H, Fu X, Zhou Z. Effectiveness and safety evaluation of terlipressin in the treatment of intestinal paralysis in end-stage liver disease. BMC Gastroenterol 2025; 25:286. [PMID: 40269714 PMCID: PMC12020273 DOI: 10.1186/s12876-025-03910-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Accepted: 04/17/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND AND AIMS Intestinal paralysis is a common complication in end-stage liver disease (ESLD), our aim is to assess the effectiveness and safety of low-dose terlipressin for treating intestinal paralysis in ESLD. METHODS The study was divided into two phases, in the exploratory phase, we retrospectively analyzed the clinical data of patients with intestinal paralysis treated with low-dose terlipressin and explored its efficacy. In the clinical research phase, we designed a prospective cohort study, patients with intestinal paralysis were categorized into terlipressin treatment group (low-dose terlipressin was added to the conventional treatment) and conventional treatment group according to their wishes. The remission of intestinal paralysis, time to symptom remission, and differences in adverse reactions were compared between the two groups. RESULTS In the exploratory phase, 26 patients were exposed to low-dose terlipressin, 12 were cured, 11 were moderately effective, and 3 were ineffective. The mean time to abdominal bloating remission was 2 days, and the time to anal flatus and feces passage was 1 day. In the clinical research phase, a total of 131 patients were included at baseline, with the exception of one patient who discontinued medication due to severe vomiting, resulting in a final total of 130 patients included in the analysis. The mean time to abdominal pain and bloating remission in the terlipressin treatment group (32/130) was demonstrably shorter compared to the conventional treatment group (98/130) (P < 0.001), the mean time to anal flatus and feces passage was also shorter (P < 0.001), and the remission rate was higher (P < 0.05). The incidence of adverse events was similar. CONCLUSIONS Low-dose terlipressin treatment could considerably increase intestinal paralysis remission in ESLD patients with intestinal paralysis, and have good safety.
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Affiliation(s)
- Xia Wan
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Department of Respiratory and Critical Care Medicine, Chongqing University Jiangjin Hospital, Chongqing, China
| | - Hua Xu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Department of Oncology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
| | - Hu Li
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Shan Zhong
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yu Lei
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Huan Deng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xiao Fu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Zhi Zhou
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
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Santana JG, Shewarega A, Nam D, Duncan J, Madoff DC, Hyder F, Coman D, Chapiro J. Molecular MRI of T-cell immune response to cryoablation in immunologically hot vs. cold hepatocellular carcinoma. JHEP Rep 2025; 7:101294. [PMID: 40028344 PMCID: PMC11870164 DOI: 10.1016/j.jhepr.2024.101294] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 11/22/2024] [Accepted: 11/28/2024] [Indexed: 03/05/2025] Open
Abstract
Background & Aims Increasing enthusiasm around integrating locoregional therapy with systemic immunotherapy in primary liver cancer underscores the need for non-invasive imaging biomarkers. In this study, we aimed to establish advanced molecular MRI tools for monitoring T-cell responses to cryoablation in murine models, distinguishing between immunologically "hot" and "cold" hepatocellular carcinoma (HCC). Methods Immunocompetent 7-10-week-old C57BL/6J and BALB/cJ mice (n = 18 each) received carbon tetrachloride for 12 weeks to induce cirrhosis. Intrinsically immunogenic Hepa1-6 ("hot") and non-immunogenic TiB75 ("cold") cells were orthotopically implanted into C57BL/6 or BALB/c mice, respectively, to generate focal HCC lesions. After one week, animals were randomly assigned to (A) partial cryoablation (pCryo) (1.2 mm cryoprobe, -40 °C) or (B) no treatment (n = 8 per group and tumor type). Gadolinium 160 (160Gd)-labeled CD8+ antibody was administered intravenously either 1 week after tumor induction (control) or 1-week post (pCryo) (treatment). T1-weighted MRI scans were performed using a 9.4 T MRI scanner. Radiological-pathological correlation included imaging mass cytometry and immunohistochemistry. Results pCryo-treated Hepa1-6 tumors displayed peritumoral ring enhancement on T1-weighted MRI with 160Gd-CD8, correlating with imaging mass cytometry signal patterns. Untreated Hepa1-6 tumors lacked such enhancement. Radiological-pathological correlation confirmed significantly increased tumor-infiltrating CD8+ T lymphocytes in pCryo Hepa1-6 tumors compared with untreated tumors (p <0.001), and a stronger local response compared with systemic lymph nodes (p = 0.0415). Increased T-lymphocyte infiltration was not observed in TiB75 tumors, as indicated by MRI and histopathology. Conclusion pCryo induced increased T-cell infiltration in Hepa1-6 tumors compared to TiB75 tumors. T1-weighted MRI, following 160Gd-CD8 antibody administration, reproducibly detected the ablation-induced changes. These findings encourage further investigation of MRI-based molecular imaging biomarkers to assess immune responses to local tumor therapies. Impact and implications This study successfully established reliable MR-based molecular imaging tools to visualize CD8+ anti-tumor specific T-cell infiltration following partial cryoablation (pCryo) in murine tumor models. The study's significance lies in advancing our understanding of immune responses within induced cirrhosis and distinguishing between "hot" and "cold" tumor phenotypes. The findings not only build upon previous proof-of-principle data but also extend this technology to include different immune cell types in hepatocellular carcinoma. The study reveals that pCryo may exert specific effects on the tumor microenvironment, augmenting the anti-tumor immune response in immunogenic tumors while displaying a weaker local effect in non-immunogenic tumors.
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Affiliation(s)
- Jessica Gois Santana
- Department of Biomedical Engineering, Yale University, New Haven, CT, United States
| | - Annabella Shewarega
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States
- Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, 10117 Berlin, Germany
| | - David Nam
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States
| | - James Duncan
- Department of Biomedical Engineering, Yale University, New Haven, CT, United States
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States
| | - David Craig Madoff
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States
- Department of Medicine, Section of Medical Oncology, 333 Cedar Street, New Haven, CT 06510 United States
- Department of Surgery, Section of Surgical Oncology, 333 Cedar Street, New Haven, CT 06510, United States
| | - Fahmeed Hyder
- Department of Biomedical Engineering, Yale University, New Haven, CT, United States
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States
| | - Daniel Coman
- Department of Biomedical Engineering, Yale University, New Haven, CT, United States
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States
| | - Julius Chapiro
- Department of Biomedical Engineering, Yale University, New Haven, CT, United States
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States
- Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, United States
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Moayedi J, Hashempour A, Musavi Z, Ghasabi F, Khodadad N, Davarpanah MA, Hasanshahi A. Assessment of human Herpes Virus-8 infection in Iranian cirrhotic patients on the waiting list for liver transplantation: A cross-sectional analysis. New Microbes New Infect 2024; 62:101496. [PMID: 39429733 PMCID: PMC11490846 DOI: 10.1016/j.nmni.2024.101496] [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: 06/24/2024] [Revised: 09/07/2024] [Accepted: 10/01/2024] [Indexed: 10/22/2024] Open
Abstract
Background Human Herpes Virus 8 (HHV-8) is involved in autoimmunity. However, its association with advanced liver disease has not been fully explained. Herein, the prevalence of HHV-8 viremia was assessed in Iranian liver transplant candidates with a confirmed diagnosis of cirrhosis. Methods This cross-sectional study was conducted on 230 patients with cryptogenic cirrhosis, virus-related cirrhosis, and autoimmune hepatitis, as well as 140 healthy blood donors from April 2022 to September 2023. The HHV-8 IgG antibody concentration and viral load were evaluated via ELISA and RT‒PCR, respectively. Results Anti-HHV-8 IgG antibodies were detected in 25 cirrhotic patients (10.8 %) and four healthy individuals (2.6 %) (p = 0.022). The majority of the seropositive patients had cryptogenic cirrhosis (20.4 %), followed by autoimmune hepatitis (13.1 %) and virus-related cirrhosis (4.7 %). The seropositivity of HHV-8 IgG antibody was significantly different among the etiologies of liver cirrhosis (p = 0.011). However, HHV-8 genomic DNA was not detected in the sera of the patients or healthy blood donors. Conclusion The role of HHV-8 infection in the development of posttransplant diseases, together with the higher seroprevalence of HHV-8 antibodies in cirrhotic patients than in healthy individuals, highlights the importance of both primary and latent infections in liver transplantation. Therefore, serological and molecular screening of HHV-8 is highly suggested for liver transplant candidates and organ donors. The possibility of antibody-mediated epitope mimicry in cryptogenic and autoimmune groups with moderate HHV-8 antibody positivity and negative viral loads may account for the development of advanced liver diseases.
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Affiliation(s)
- Javad Moayedi
- HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ava Hashempour
- HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Musavi
- HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farzaneh Ghasabi
- HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nastaran Khodadad
- HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohamad Ali Davarpanah
- HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Hasanshahi
- HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
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Ma Y, Wang J, Du L, Tang H. Association between the systemic immune-inflammation index and the outcome of liver fibrosis in patients with chronic hepatitis C. Front Med (Lausanne) 2024; 11:1486503. [PMID: 39659620 PMCID: PMC11628305 DOI: 10.3389/fmed.2024.1486503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 11/11/2024] [Indexed: 12/12/2024] Open
Abstract
Background Risk factors that influence the outcome of patients with chronic hepatitis C (CHC) are not fully understood. The systemic immune-inflammatory index (SII) is an independent prognostic factor for multiple diseases. However, the impact of the SII on the outcome of liver fibrosis is unclear. Methods This prospective real-world study enrolled patients with CHC treated with sofosbuvir/velpatasvir. Logistic regression models were used to investigate the relationship between the SII and the outcome of liver fibrosis in treatment-naive patients. Liver fibrosis was assessed using aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4). Results Of the 288 participants, the SII was 238.2 (153.0-358.2). The non-improved outcomes of liver fibrosis assessed with APRI (non-improved APRI) and FIB-4 (non-improved FIB-4) were 83.0 and 87.5%, respectively. Adjusted models showed that the SII was positively associated with non-improved APRI (adjusted OR (95% CI): 1.013 (1.009-1.017), p < 0.001) and FIB-4 (adjusted OR (95% CI): 1.004 (1.001-1.007), p = 0.012). Similarly, a higher SII was associated with a higher risk of non-improved APRI (adjusted OR (95% CI): 13.53 (5.60-32.68), p < 0.001) and FIB-4 (adjusted OR (95% CI): 5.69 (2.17-14.90), p < 0.001). The association with non-improved APRI was much more remarkable in patients with alanine aminotransferase <2 ULN, and the association with non-improved FIB-4 was remarkable in patients aged <50 years. Multiple imputation analyses confirmed the robustness of these results. Conclusion Our findings suggested that the SII was positively associated with non-improved outcomes of liver fibrosis in patients with CHC. These results need to be validated in large-scale prospective cohorts.
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Affiliation(s)
| | | | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
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Greenwald MA, Edwards N, Eastlund DT, Gurevich I, Ho APZ, Khalife G, Lin-Torre J, Thompson HW, Wilkins RM, Alrabaa SF. The American Association of Tissue Banks tissue donor screening for Mycobacterium tuberculosis-Recommended criteria and literature review. Transpl Infect Dis 2024; 26 Suppl 1:e14294. [PMID: 38852068 DOI: 10.1111/tid.14294] [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: 03/06/2024] [Revised: 04/12/2024] [Accepted: 04/25/2024] [Indexed: 06/10/2024]
Abstract
After two multistate outbreaks of allograft tissue-transmitted tuberculosis (TB) due to viable bone, evidence-based donor screening criteria were developed to decrease the risk of transmission to recipients. Exclusionary criteria, commentary, and references supporting the criteria are provided, based on literature search and expert opinion. Both exposure and reactivation risk factors were considered, either for absolute exclusion or for exclusion in combination with multiple risk factors. A criteria subset was devised for tissues containing viable cells. Risk factors for consideration included exposure (e.g., geographic birth and residence, travel, homelessness, incarceration, healthcare, and workplace) and reactivation (e.g., kidney disease, liver disease, history of transplantation, immunosuppressive medications, and age). Additional donor considerations include the possibility of sepsis and chronic illness. Donor screening criteria represent minimal criteria for exclusion and do not completely exclude all possible donor TB risks. Additional measures to reduce transmission risk, such as donor and product testing, are discussed but not included in the recommendations. Careful donor evaluation is critical to tissue safety.
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Affiliation(s)
- Melissa A Greenwald
- American Association of Tissue Banks, McLean, Virginia, USA
- Uniformed Services University, Bethesda, Maryland, USA
- Donor Alliance, Denver, Colorado, USA
| | | | | | | | | | - Ghada Khalife
- Solvita, Dayton, Ohio, USA
- Wright State University, Dayton, Ohio, USA
| | - Janet Lin-Torre
- MTF Biologics, Edison, New Jersey, USA
- Department of Medicine, Cooperman Barnabas Medical Center, Livingston, New Jersey, USA
| | | | | | - Sally F Alrabaa
- University of South Florida, Morsani College of Medicine, Tampa, Florida, USA
- LifeLink Tissue Bank, Tampa, Florida, USA
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Peschel G, Happ N, Bornschein J, Weis F, Schmid S, Mueller M, Selgrad M. Liver cirrhosis is a risk-factor for Pneumocystis jirovecii associated mortality. Front Med (Lausanne) 2024; 11:1474835. [PMID: 39444818 PMCID: PMC11496259 DOI: 10.3389/fmed.2024.1474835] [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: 08/06/2024] [Accepted: 09/17/2024] [Indexed: 10/25/2024] Open
Abstract
Background Pneumocystis jirovecci pneumonia (PCP) is a life threating disease in immunodeficient patients. Liver cirrhosis itself can lead to immunodefiency, however little is known if Pneumocystis jirovecci infection affects the outcome of patients with liver cirrhosis. Aim We aimed to assess the predictors for Pneumocystis jirovecci-associated mortality in patients with Pneumocystis jirovecci infection treated at intensive care units. Methods A total of 151 patients hospitalized between January 2013 and November 2019 with a PCR-confirmed Pneumocystis jirovecci infection were retrospectively included in this study and analysed for clinical predictors for PCJ associated mortality. Results The overall mortality in our patient cohort was 60%. Out of 151 patients included in the analysis, 67 (44%) patients suffered from liver cirrhosis. Patients with an advanced liver cirrhosis (Child-Pugh class C) showed the highest mortality rate of 84.7%. The presence of a liver cirrhosis was associated with a significant increased risk of mortality (OR: 4.809) ([95%-CI: 2.32-9.97]; p < 0.001). There was a significant correlation of Meld score and mortality (r = 0.612, p < 0.001). Discussion To our knowledge, this study represents the largest evaluation of Pneumocystis jirovecci infection in patients with advanced liver cirrhosis. Cirrhosis associated immune dysfunction (CAID) describes the spectrum of immunological disturbances in patients with cirrhosis, which is linked to a heightened vulnerability to bacterial infections. Our data indicate a heightened susceptibility to fungal infections. Understanding the phenotypic manifestations of CAID could lead to immune-targeted therapies aimed at reducing infection susceptibility and decreasing CAID-associated mortality in cirrhosis patients.
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Affiliation(s)
- Georg Peschel
- Department of Internal Medicine I, University Hospital of Regensburg, Regensburg, Germany
- Department of Gastroenterology and Oncology, Hospital of Fürstenfeldbruck, Fürstenfeldbruck, Germany
| | - Nils Happ
- Department of Internal Medicine I, University Hospital of Regensburg, Regensburg, Germany
| | - Jan Bornschein
- Department of Internal Medicine I, University Hospital of Regensburg, Regensburg, Germany
- Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, Univeristy of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
| | - Florian Weis
- Department of Anaesthesiology-Grosshadern, University Hospital Munich, Munich, Germany
- Department of Anaesthesiology, Hospital of Fürstenfeldbruck, Fürstenfeldbruck, Germany
| | - Stephan Schmid
- Department of Internal Medicine I, University Hospital of Regensburg, Regensburg, Germany
| | - Martina Mueller
- Department of Internal Medicine I, University Hospital of Regensburg, Regensburg, Germany
| | - Michael Selgrad
- Department of Internal Medicine I, University Hospital of Regensburg, Regensburg, Germany
- Department of Gastroenterology and Oncology, Hospital of Fürstenfeldbruck, Fürstenfeldbruck, Germany
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Su Y, Zhou Q, Wu Q, Ding Y, Jiang M, Zhang X, Wang J, Wang X, Ge C. Infection‑associated bile acid disturbance contributes to macrophage activation in patients with cirrhosis. Mol Med Rep 2024; 30:150. [PMID: 38963032 PMCID: PMC11234163 DOI: 10.3892/mmr.2024.13274] [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: 02/23/2024] [Accepted: 05/23/2024] [Indexed: 07/05/2024] Open
Abstract
Cirrhosis impairs macrophage function and disrupts bile acid homeostasis. Although bile acids affect macrophage function in patients with sepsis, whether and how the bile acid profile is changed by infection in patients with cirrhosis to modulate macrophage function remains unclear. The present study aimed to investigate the changes in the bile acid profile of patients with cirrhosis and infection and their effects on macrophage function. Serum was collected from 20 healthy subjects, 18 patients with cirrhosis and 39 patients with cirrhosis and infection. Bile acid profiles were detected using high‑performance liquid chromatography‑triple time‑of‑flight mass spectrometer. The association between bile acid changes and infection was analysed using receiver operating characteristic (ROC) curves. Infection‑altered bile acids were used in combination with lipopolysaccharides (LPS) to stimulate RAW264.7/THP‑1 cells in vitro. The migratory capacity was evaluated using wound healing and Transwell migration assays. The expression of Arg‑1, iNOS, IκBα, phosphorylated (p‑)IκBα and p65 was examined with western blotting and immunofluorescence, Tnfα, Il1b and Il6 mRNA was examined with RT‑qPCR, and CD86, CD163 and phagocytosis was measured with flow cytometry. The ROC curves showed that decreased hyodeoxycholic acid (HDCA) and deoxycholic acid (DCA) levels were associated with infection. HDCA or DCA combined with LPS enhanced the phagocytic and migratory ability of macrophages, accompanied by upregulation of iNOS and CD86 protein expression as well as Tnfα, Il1b, and Il6 mRNA expression. However, neither HDCA nor DCA alone showed an effect on these phenotypes. In addition, DCA and HDCA acted synergistically with LPS to increase the expression of p‑IκBα and the intranuclear migration of p65. Infection changed the bile acid profile in patients with cirrhosis, among which the reduction of DCA and HDCA associated most strongly with infection. HDCA and DCA enhanced the sensitivity of macrophage function loss to LPS stimulation. These findings suggested a potential role for monitoring the bile acid profile that could help manage patients with cirrhosis and infection.
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Affiliation(s)
- Yong Su
- School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Qiaoling Zhou
- School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Qiong Wu
- School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Yijie Ding
- School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Meijie Jiang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China
| | - Xiaoyu Zhang
- Health Management Center, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Jia Wang
- Department of Pharmacy, Hefei First People's Hospital, Hefei, Anhui 230032, P.R. China
| | - Xinming Wang
- School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui 230032, P.R. China
| | - Chaoliang Ge
- School of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui 230032, P.R. China
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Bilolikar VK, Gleason B, Kripke L, Merrill R, Whitaker C, Handal J. Risk Factors Associated with Pyogenic Spinal Infections among Intravenous Drug Users and Nonusers. Adv Orthop 2024; 2024:9938159. [PMID: 39105127 PMCID: PMC11300094 DOI: 10.1155/2024/9938159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 06/15/2024] [Accepted: 07/04/2024] [Indexed: 08/07/2024] Open
Abstract
Purpose To identify the differences in patient factors, presentation, treatment course, and outcomes of intravenous drug users (IVDA) vs. nonusers (non-IVDA) presenting with pyogenic spinal infections. Study Design/Setting. Retrospective case series. Methods We identified all cases involving spinal infections at our institution between May 2017 and January 2023. Postsurgical infections were excluded, and patients were separated into IVDA and non-IVDA groups. The patient charts were reviewed and analyzed for statistical or clinically significant differences using RStudio (2019 version 3.6.2). Our institutional review board approved this study, IRB# 2020-277, iRISID-2023-1384. Results Fifty patients (29 males and 21 females) with primary pyogenic spinal infections were included in our study. There were fourteen patients (28.0%) in the IVDA group. The mean age in the IVDA group was 50.6 vs. 61.9 years (p < 0.05) in the non-IVDA group. The average length of stay (LOS) in the IVDA group was 15.8 vs. 14.0 days (p = 0.54) in the non-IVDA group, with no significant difference in readmissions or disposition. Twenty-three non-IVDA patients were diagnosed with diabetes, while eight IVDA patients had a psychiatric diagnosis (other than substance abuse). There were no significant differences in microbial isolate or the duration of antibiotics. Conclusion In our study population, there is a high incidence of intravenous drug abuse (IVDA), psychiatric disease, diabetes, and chronic kidney disease. Analysis shows a trend of two distinct patient populations. Patients without a history of IVDA were significantly older than those with IVDA and significantly more likely to have medical comorbidities including hyperlipidemia, diabetes, chronic kidney disease, and malignancy than those with IVDA history. Patients with IVDA were younger with significantly higher rates of smoking and psychiatric disorders. IVDA patients struggled to receive continued psychiatric/addiction treatment after discharge, an area for significant improvement. Due to a small sample size and single urban institution setting, this study may be underpowered to demonstrate differences in healthcare resource consumption.
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Affiliation(s)
- Vivek K. Bilolikar
- Thomas Jefferson UniversityJefferson Einstein Hospital, Philadelphia, PA, USA
| | - Brendan Gleason
- Thomas Jefferson UniversityJefferson Einstein Hospital, Philadelphia, PA, USA
| | - Lee Kripke
- Thomas Jefferson UniversityJefferson Einstein Hospital, Philadelphia, PA, USA
| | - Robert Merrill
- Thomas Jefferson UniversityJefferson Einstein Hospital, Philadelphia, PA, USA
| | - Colin Whitaker
- Thomas Jefferson UniversityJefferson Einstein Hospital, Philadelphia, PA, USA
| | - Jon Handal
- Thomas Jefferson UniversityJefferson Einstein Hospital, Philadelphia, PA, USA
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Mantzios PG, Spyropoulou P, Hatzianastasiou S, Efthymiou D, Filippopoulos E, Mamarelis C, Potsios C, Filioti K, Letsas CA. Pediococcus pentosaceus Endocarditis in a Patient With Recent Transcatheter Aortic Valve Implantation and Liver Cirrhosis: A Case Report and Review of the Literature. Cureus 2024; 16:e57509. [PMID: 38707070 PMCID: PMC11067400 DOI: 10.7759/cureus.57509] [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] [Accepted: 04/03/2024] [Indexed: 05/07/2024] Open
Abstract
Transcatheter aortic valve implantation (TAVI) is increasingly being used in the management of severe aortic stenosis, mainly in older and/or medically compromised patients, due to its minimally invasive nature. As in any valve replacement procedure, endocarditis is a recognized complication, more so in TAVI patients, in whom comorbidities are highly prevalent. We report the case of a 70-year-old male with a history of liver cirrhosis and a recent TAVI, who presented with recurrent fever and sustainedPediococcus pentosaceus bacteremia. The diagnosis of endocarditis was delayed, as the microorganism was initially discarded as a contaminant, given that Pediococci are rarely described as human pathogens. However, in cirrhotic patients, microbiota may cause intermittent bacteremia and thereby affect prosthetic valves. Transthoracic echocardiography was not helpful in validating the diagnosis, as is often the case in TAVI patients. Transesophageal echocardiography was deemed perilous, due to esophageal varices complicating the underlying cirrhosis. Therefore, endocarditis diagnosis was based on sustained bacteremia and Duke's criteria, including the presence of high fever, a predisposing cardiac lesion, splenic infarction, and the exclusion of an alternative diagnosis. Moreover, cirrhosis enhanced the side effects of treatment and led to the need for regimen changes and prolonged hospitalization. Given the precariousness of the situation, confirmation of treatment success by 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography-computed tomography (18F-FDG PET-CT) scan was sought. This is the first reported case of Pediococcus TAVI endocarditis in a cirrhotic patient, highlighting the unique challenges in the diagnosis and management of TAVI endocarditis in patients with co-existing conditions.
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Badal J, Badal B, Nawras M, Lee-Smith W, Stanley S, Hassan M, Ahmed Z. Diagnostic Paracentesis Within 1 Day Is Associated With Reduced Mortality and Length of Hospital Stay in Patients with Cirrhosis and Ascites. Dig Dis Sci 2024; 69:1454-1466. [PMID: 38217676 DOI: 10.1007/s10620-023-08249-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 10/09/2023] [Indexed: 01/15/2024]
Abstract
Spontaneous bacterial peritonitis (SBP) is the most common infection in patients with cirrhosis and is associated with high mortality. Although recent literature reports mortality benefits to early diagnostic paracentesis, current guidelines do not offer specific recommendations for how quickly diagnostic paracentesis should be performed in patients with cirrhosis and ascites who are admitted to the hospital. Therefore, we conducted a systematic review and meta-analysis to evaluate outcomes among patients admitted to the hospital with cirrhosis and ascites receiving paracentesis within ≤ 12, ≤ 1 day, and > 1 day. Eight studies with 116,174 patients were included in the final meta-analysis. The pooled risk of in-hospital mortality was significantly lower in patients who underwent early (≤ 12 h or ≤ 1 day) compared to delayed (> 12 h or > 1 day) paracentesis (RR: 0.69, p < 0.00001), and in patients who underwent paracentesis compared to no paracentesis (RR: 0.74, p < 0.00001). On subgroup analysis, in-hospital mortality was significantly lower in both paracentesis within ≤ 12 h (RR: 0.61, p = 0.02) vs. > 12 h, and within ≤ 1 day (RR: 0.70, p < 0.00001) vs. > 1 day. While there was a trend towards decreased mortality in those undergoing paracentesis within ≤ 12 h compared to ≤ 1 day, the difference did not reach statistical significance. The length of hospital stay was significantly shorter by 5.38 days in patients who underwent early (≤ 12 h) compared to delayed (> 12 h) paracentesis (95% CI 4.24-6.52, p < 0.00001). Early paracentesis is associated with reduced mortality and length of hospital stay. We encourage providers to perform diagnostic paracentesis in a timely manner, at least within 1 day of hospital admission, for all patients with cirrhosis and ascites.
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Affiliation(s)
- Joyce Badal
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
- UNC Faculty Physicians Center, 100 Eastowne Drive, Chapel Hill, NC, 27514, USA.
| | - Bryan Badal
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, VA, USA
| | - Mohamad Nawras
- University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | | | - Sara Stanley
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toledo Medical Center, Toledo, OH, USA
| | - Mona Hassan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toledo Medical Center, Toledo, OH, USA
| | - Zohaib Ahmed
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toledo Medical Center, Toledo, OH, USA
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Burtis AEC, DeNicola DMC, Ferguson ME, Santos RG, Pinilla C, Kriss MS, Orlicky DJ, Tamburini BAJ, Gillen AE, Burchill MA. Antigen-driven CD8 + T cell clonal expansion is a prominent feature of MASH in humans and mice. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.03.20.583964. [PMID: 38562766 PMCID: PMC10983976 DOI: 10.1101/2024.03.20.583964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
Background and Aims Chronic liver disease due to metabolic dysfunction-associated steatohepatitis (MASH) is a rapidly increasing global epidemic. MASH progression is a consequence of the complex interplay between inflammatory insults and dysregulated hepatic immune responses. T lymphocytes have been shown to accumulate in the liver during MASH, but the cause and consequence of T cell accumulation in the liver remain unclear. Our study aimed to define the phenotype and T cell receptor diversity of T cells from human cirrhotic livers and an animal model of MASH to begin resolving their function in disease. Approach and Results In these studies, we evaluated differences in T cell phenotype in the context of liver disease we isolated liver resident T cell populations from individuals with cirrhosis and a murine model of MASH. Using both 5' single cell sequencing and flow cytometry we defined the phenotype and T cell receptor repertoire of liver resident T cells during health and disease. Conclusions MASH-induced cirrhosis and diet-induced MASH in mice resulted in the accumulation of activated and clonally expanded T cells in the liver. The clonally expanded T cells in the liver expressed markers of chronic antigenic stimulation, including PD1 , TIGIT and TOX . Overall, this study establishes for the first time that T cells undergo antigen-dependent clonal expansion and functional differentiation during the progression of MASH. These studies could lead to the identification of potential antigenic targets that drive T cell activation, clonal expansion, and recruitment to the liver during MASH.
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Dibos M, Triebelhorn J, Schneider J, Rasch S, Schmid RM, Lahmer T, Mayr U. Herpes Simplex Virus Bronchopneumonitis in Critically Ill Patients with Acute on Chronic Liver Failure: A Retrospective Analysis. Viruses 2024; 16:419. [PMID: 38543784 PMCID: PMC10974938 DOI: 10.3390/v16030419] [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: 01/17/2024] [Revised: 03/01/2024] [Accepted: 03/05/2024] [Indexed: 05/23/2024] Open
Abstract
(1) Background: Critically ill patients are frequently diagnosed with pulmonary Herpes simplex virus-1 (HSV) reactivation, which then can lead to HSV bronchopneumonitis and is associated with higher mortality and longer mechanical ventilation. For the particular subgroup of critically ill patients with acute on chronic liver failure (ACLF), however, the impact of HSV reactivation is unknown. We investigated the impact of HSV reactivation in these patients. (2) Methods: We conducted a retrospective analysis, evaluating data from 136 mechanically ventilated patients with ACLF between January 2016 and August 2023. Clinical parameters were compared between patients with and without HSV bronchopneumonitis. (3) Results: 10.3% were diagnosed with HSV bronchopneumonitis (HSV group). Mortality did not differ between the HSV and non-HSV group (85.7% vs. 75.4%, p = 0.52). However, the clinical course in the HSV group was more complicated as patients required significantly longer mechanical ventilation (14 vs. 21 days, p = 0.04). Furthermore, fungal superinfections were significantly more frequent in the HSV group (28.6% vs. 6.6%, p = 0.006). (4) Conclusions: Mortality of critically ill patients with ACLF with HSV bronchopneumonitis was not increased in spite of the cirrhosis-associated immune dysfunction. Their clinical course, however, was more complicated with significantly longer mechanical ventilation.
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Affiliation(s)
- Miriam Dibos
- Department of Internal Medicine II, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany
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Ayoub M, Tomanguillo J, Faris C, Anwar N, Chela H, Daglilar E. SARS-CoV-2 Infection Is an Independent Risk Factor for Decompensation in Cirrhosis Patients. Diseases 2024; 12:46. [PMID: 38534970 PMCID: PMC10968826 DOI: 10.3390/diseases12030046] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/20/2024] [Accepted: 02/21/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND SARS-CoV-2 causes varied gastrointestinal symptoms. Cirrhosis patients face higher mortality rates from it, especially those with decompensated cirrhosis. This study examines SARS-CoV-2's impact on decompensation in previously compensated cirrhotic patients. METHODS We analyzed the Global Collaborative Network, comprising 98 healthcare organizations across sixteen countries, using TriNetX's deidentified research database. Compensated cirrhosis patients were split into two groups: one with SARS-CoV-2-positive patients and another testing negative. Using a 1:1 propensity score matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then assessed decompensation, mortality, and GI bleed at 1 and 3 months. RESULTS Out of 252,631 identified compensated cirrhosis patients, 27.3% (69,057) tested SARS-CoV-2-positive, while 72.6% (183,574) remained negative. Post PSM, 61,963 patients were in each group. SARS-CoV-2-positive patients showed significantly higher decompensation rates (4.4% vs. 1.9% at 1 month; 6% vs. 2.6% overall). Rates of complications, like ascites, SBP, HE, and HRS, increased notably. Mortality (2.5% vs. 1.7% at 1 month; 3.6% vs. 2.7% at 3 months) and GI bleed (1.3% vs. 0.9% at 1 month; 1.9% vs. 1.2% at 3 months) were also elevated in SARS-CoV-2 patients. CONCLUSIONS SARS-CoV-2 increases decompensation over 2-fold in compensated cirrhosis patients and raises mortality and increases rates of complications at 1 and 3 months.
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Affiliation(s)
- Mark Ayoub
- Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA;
| | - Julton Tomanguillo
- Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA;
| | - Carol Faris
- Department of General Surgery, Marshall University, Huntington, WV 25755, USA
| | - Nadeem Anwar
- Division of Gastroenterology and Hepatology, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (N.A.); (H.C.)
| | - Harleen Chela
- Division of Gastroenterology and Hepatology, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (N.A.); (H.C.)
| | - Ebubekir Daglilar
- Division of Gastroenterology and Hepatology, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (N.A.); (H.C.)
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Liu S, Zhao Q, Wang Z, Zhao B, Zhang X. Albumin‑bilirubin grade is an independent prognostic factor for small lung cell cancer. Mol Clin Oncol 2024; 20:12. [PMID: 38213660 PMCID: PMC10777464 DOI: 10.3892/mco.2023.2710] [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: 07/10/2023] [Accepted: 11/13/2023] [Indexed: 01/13/2024] Open
Abstract
Albumin-bilirubin (ALBI) grade was first described in 2015 as an indicator of liver dysfunction in patients with hepatocellular carcinoma. ALBI grade has been reported to have prognostic value in several malignancies including non-small cell lung cancer (NSCLC). The present study aimed to explore the prognostic impact of ALBI grade in patients with small cell lung cancer (SCLC). It retrospectively analyzed 135 patients with SCLC treated at Hebei General Hospital between April 2015 and August 2021. Patients were divided into two groups according to the cutoff point of ALBI grade determined by the receiver operating characteristic (ROC) curve: Group 1 with pre-treatment ALBI grade ≤-2.55 for an improved hepatic reserve and group 2 with ALBI grade >-2.55. Kaplan-Meier and Cox regression analysis were performed to assess the potential prognostic factors associated with progression free survival (PFS) and overall survival (OS). Propensity score matching (PSM) was applied to eliminate the influence of confounding factors. PFS and OS (P<0.001) were significantly improved in group 1 compared with in group 2. Multivariate analysis revealed that sex (P=0.024), surgery (P=0.050), lactate dehydrogenase (LDH; P=0.038), chemotherapy (P=0.038) and ALBI grade (P=0.028) are independent risk factors for PFS and that surgery (P=0.013), LDH (P=0.039), chemotherapy (P=0.009) and ALBI grade (P=0.013) are independent risk factors for OS. After PSM, ALBI grade is an independent prognostic factor of PFS (P=0.039) and OS (P=0.007). It was concluded that ALBI grade was an independent prognostic factor in SCLC.
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Affiliation(s)
- Shicheng Liu
- Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050000, P.R. China
| | - Qingtao Zhao
- Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050000, P.R. China
| | - Zengming Wang
- Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050000, P.R. China
- Graduate School, Hebei North University, Zhangjiakou, Hebei 075000, P.R. China
| | - Bin Zhao
- Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050000, P.R. China
- Graduate School, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
| | - Xiaopeng Zhang
- Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050000, P.R. China
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Cao J, Liu JH, Wise SG, Fan J, Bao S, Zheng GS. The role of IL-36 and 37 in hepatocellular carcinoma. Front Immunol 2024; 15:1281121. [PMID: 38312834 PMCID: PMC10834741 DOI: 10.3389/fimmu.2024.1281121] [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: 08/21/2023] [Accepted: 01/05/2024] [Indexed: 02/06/2024] Open
Abstract
Hepatocellular carcinoma (HCC) has garnered considerable attention due to its morbidity and mortality. Although the precise mechanisms underlying HCC tumorigenesis remain to be elucidated, evidence suggests that host immunity plays a pivotal role in its development. IL-36 and IL-37 are important immunoregulatory cytokines classified as pro-inflammatory and anti-inflammatory respectively. In the context of HCC, the downregulation of intrahepatic IL-36 is inversely correlated with cirrhosis, but positively correlated with 5-year survival rates, suggesting that IL-36 offers protection during HCC development. However, IL-36 may lose its hepatoprotective effects as the disease progresses to HCC in the context of dysregulated immunity in cirrhotic patients. Substantially increased circulating IL-36 in HCC patients is likely a systemic response to HCC stimulation, but is insufficient to suppress progression towards HCC. Intrahepatic IL-37 is suppressed in HCC patients, consistent with the inverse correlation between intrahepatic IL-37 and the level of AFP in HCC patients, suggesting IL-37 exerts hepatoprotection. There is no significant difference in IL-37 among differentiations of HCC or with respect to clinical BCLC stages or cirrhosis status in HCC patients. However, IL-37 protection is demonstrated in an IL-37 transfected HCC animal model, showing significantly reduced tumour size. IL-36/37 may inhibit HCC by enhancing M1 tumour-associated macrophages while not affecting M2 macrophages. The interplay between IL-36 (pro-inflammatory) and IL-37 (anti-inflammatory) is emerging as a crucial factor in host protection against the development of HCC. Further research is needed to investigate the complex mechanisms involved and the therapeutic potential of targeting these cytokines in HCC management.
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Affiliation(s)
- Juan Cao
- Basic Medical College, Gansu University of Chinese Medicine, Lanzhou, China
- Department of Public Health, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, China
| | - Jun-Hong Liu
- Department of Public Health, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, China
- Gansu Provincial Integrated Traditional Chinese and Western Medicine Digestive Disease Clinical Research Centre, Lanzhou, China
| | - Steven G. Wise
- School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Jingchun Fan
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China
| | - Shisan Bao
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China
| | - Gui-Sen Zheng
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China
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17
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Feng G, Valenti L, Wong VWS, Fouad YM, Yilmaz Y, Kim W, Sebastiani G, Younossi ZM, Hernandez-Gea V, Zheng MH. Recompensation in cirrhosis: unravelling the evolving natural history of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2024; 21:46-56. [PMID: 37798441 DOI: 10.1038/s41575-023-00846-4] [Citation(s) in RCA: 87] [Impact Index Per Article: 87.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/05/2023] [Indexed: 10/07/2023]
Abstract
Recompensation has gained increasing attention in the field of cirrhosis, particularly in chronic liver disease with a definite aetiology. The current global prevalence of obesity and nonalcoholic fatty liver disease (NAFLD) is increasing, but there is currently a lack of a clear definition for recompensation in NAFLD-related cirrhosis. Here, we provide an up-to-date perspective on the natural history of NAFLD, emphasizing the reversible nature of the disease, summarizing possible mechanisms underlying recompensation in NAFLD, discussing challenges that need to be addressed and outlining future research directions in the field. Recompensation is a promising goal in patients with NAFLD-related cirrhosis, and further studies are needed to explore its underlying mechanisms and uncover its clinical features.
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Affiliation(s)
- Gong Feng
- Xi'an Medical University, Xi'an, China
- The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Luca Valenti
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Precision Medicine, Biological Resource Center and Department of Transfusion Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Yasser Mahrous Fouad
- Department of Endemic Medicine and Gastroenterology, Faculty of Medicine, Minia University, Minia, Egypt
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
| | - Won Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Zobair M Younossi
- Inova Medicine Services, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, USA
| | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic Barcelona,-IDIBAPS, University of Barcelona, Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
- Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China.
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Kumar D, Taha Yaseen R, Panezai MQ, Naeem MU, Ismail H, Majid Z, Mehmood N, Ali Khalid M, Lail G, Hassan Luck N. Ascitic Fluid Lactate Level as a Predictor of Mortality in Cirrhotic Patients Having Spontaneous Bacterial Peritonitis (SBP). Cureus 2024; 16:e53243. [PMID: 38425592 PMCID: PMC10903966 DOI: 10.7759/cureus.53243] [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] [Accepted: 01/30/2024] [Indexed: 03/02/2024] Open
Abstract
Introduction Limited studies are available for predicting mortality in patients with spontaneous bacterial peritonitis (SBP) based on ascitic fluid analysis. Recently, a proposition has been made regarding the role of ascitic fluid lactate as a better prognostic indicator of mortality in cirrhotic patients with SBP. Therefore, we aimed to evaluate the utility of ascitic fluid lactate in predicting mortality in cirrhotic patients with SBP. Methods This was a prospective, observational study that was conducted in the Hepato-Gastroenterology Department of Sindh Institute of Urology and Transplantation (SIUT), Karachi from 1 January 2022 to 31 December 2022. All the patients having liver cirrhosis with ascites, aged between 18 and 65 years, and presenting with fever and/or abdominal pain were recruited in the study in the first six months (i.e., from 1 January 2022 to 30 June 2022) and were followed for six more months for the outcome. However, those patients on dialysis or those with hepatocellular carcinoma, any other malignancy as per a history of solid organ transplant, a history of HIV infection, or those underlying systemic sepsis or infections other than SBP were excluded from the study. The presence or absence of SBP was confirmed by doing the ascitic fluid analysis. Ascitic fluid lactate levels were also requested in each patient. Mortality was assessed at one, two, three, and six months, respectively. All the data were analyzed using SPSS version 23.0. The area under the receiver operating curve (AUROC) was obtained for ascitic fluid lactate for predicting mortality in SBP. At an optimal cutoff, the diagnostic accuracy of ascitic fluid lactate was obtained. Results The total number of cirrhotic patients included in the study was 123. The majority of the patients belong to Child Turcotte Pugh (CTP) class C (n = 88; 71%). Two third of the patients (65.8%; n = 81) had viral hepatitis i.e., hepatitis B, D, and/or C, as the cause of cirrhosis. Overall mortality was observed in 51(41.5%) patients. Ascitic fluid lactate was significantly raised in patients with SBP than in patients with non-SBP (p = 0.004). The AUROC of ascitic fluid lactate was highest at three months (AUROC = 0.88) followed by six months (AUROC = 0.84), two months (AUROC = 0.804), and one month (AUROC=0.773). At an optimal cut-off of more than or equal to 22.4 mg/dl, ascitic fluid lactate had a sensitivity of 84.9%, specificity of 85.7%, positive predictive value (PPV) of 97.3%, negative predictive value of 42.8% with diagnostic accuracy of 85% in predicting overall mortality in patients with SBP. On sub-analysis, the diagnostic accuracy of ascitic fluid lactate was highest at six months followed by at three, two, and one month, respectively. Conclusion Ascitic fluid lactate showed a good diagnostic utility in predicting the overall mortality in patients with SBP with the best diagnostic accuracy in predicting long-term (six months) mortality. However, further studies are required to validate our results.
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Affiliation(s)
- Danish Kumar
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, PAK
| | - Raja Taha Yaseen
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, PAK
| | - Muhammad Qaiser Panezai
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, PAK
| | - Muhammad Usman Naeem
- Department of Gastroenterology, Sheik Zayed Hospital, Lahore, PAK
- Department of Hepatology, Sheik Zayed Hospital, Lahore, PAK
| | - Hina Ismail
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, PAK
| | - Zain Majid
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, PAK
| | - Nasir Mehmood
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, PAK
| | - Muhammad Ali Khalid
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, KARACHI, PAK
| | - Ghulamullah Lail
- Department of Medicine: Gastroenterology, Jinnah Medical & Dental College, Karachi, PAK
| | - Nasir Hassan Luck
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, PAK
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Pétursson I, Amabile A, Degife E, Morrison A, Waldron C, Bin Mahmood SU, Ragnarsson S, Krane M, Geirsson A. Outcomes of patients with advanced liver disease undergoing cardiac surgery. JTCVS OPEN 2023; 16:532-539. [PMID: 38204635 PMCID: PMC10774984 DOI: 10.1016/j.xjon.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 06/16/2023] [Accepted: 07/06/2023] [Indexed: 01/12/2024]
Abstract
Objective Liver disease (LD) is considered a risk factor for inferior outcomes in general and cardiac surgery, yet current cardiac surgery risk estimators exclude LD, and literature on the topic remains scant. We sought to evaluate whether the presence of advanced LD is associated with inferior outcomes following cardiac surgery. Methods This single-center, retrospective, observational study included 285 patients diagnosed with LD who underwent cardiac surgery in 2010 to 2020. The cohort contained 3 groups, Child-Turcotte-Pugh (CTP) class A (n = 219), CTP early-class B (n = 34), and CTP advanced-class B (n = 32). A model for end-stage liver disease score of 12.7 points (determined using a receiver-operating characteristic curve analysis on 30-day mortality) dichotomized class B into early- and advanced-groups. Univariate and multivariate logistic regression analyses were performed to identify predictors of 30-day mortality. Results Patients in CTP advanced-class B had the longest length of stay (14 days), highest incidence of prolonged ventilation (46.9%), renal failure (21.9%), 30-day mortality (18.8%), and in-hospital mortality (18.8%). Incidence of ≥1 postoperative complication was higher in CTP advanced-class B (59.4%), compared with CTP class A (37.9%) and CTP early-class B (38.2%). Multivariate logistic regression analysis demonstrated that female sex (odds ratio, 3.01; 95% CI, 1.07-8.77; P = .037) and peripheral vascular disease (odds ratio, 4.01; 95% CI, 1.33-12.2; P = .013) were independent predictors of 30-day mortality in patients with advanced LD. Conclusions Severity of LD influences perioperative outcomes following cardiac surgery. Our data suggest that patients in CTP class A and selected patients in CTP class B (model for end-stage liver disease score <12.7) can undergo surgery with acceptable risk.
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Affiliation(s)
- Ingi Pétursson
- Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland
| | - Andrea Amabile
- Division of Cardiac Surgery, Yale School of Medicine, New Haven, Conn
| | - Ellelan Degife
- Division of Cardiac Surgery, Yale School of Medicine, New Haven, Conn
| | - Alyssa Morrison
- Division of Cardiac Surgery, Yale School of Medicine, New Haven, Conn
| | - Christina Waldron
- Division of Cardiac Surgery, Yale School of Medicine, New Haven, Conn
| | | | | | - Markus Krane
- Division of Cardiac Surgery, Yale School of Medicine, New Haven, Conn
| | - Arnar Geirsson
- Division of Cardiac Surgery, Yale School of Medicine, New Haven, Conn
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Hakimian D, Amer J, Jammal A, Shafrir A, Milgrom Y, Masarowah M, Hazou W, Ishay Y, Imam A, Francis A, Khalaileh A, Safadi R. Weaker SARS-CoV-2 vaccine responses in nonalcoholic fatty liver disease with advanced liver fibrosis. Vaccine X 2023; 15:100359. [PMID: 37885772 PMCID: PMC10598407 DOI: 10.1016/j.jvacx.2023.100359] [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: 05/19/2022] [Revised: 07/23/2023] [Accepted: 07/24/2023] [Indexed: 10/28/2023] Open
Abstract
Background SARS-CoV-2 vaccine responses that could harbor potential risks to chronic liver diseased patients. Aims To assess immune response following Pfizer's SARS-CoV-2 vaccine in patients with different liver fibrosis severities of nonalcoholic fatty liver disease (NAFLD). Methods Clinical and histological (NAS-score and fibrosis stage) characteristics of NAFLD patients before vaccine were correlated with serologic vaccine responses of two doses of the BNT162b2. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed on day seven following immunization (Liaison assay). Results The mean-age of patients (n = 157) was 56.9 ± 13.2 years (46.5 % males). 94.8 % had a positive response (anti-S levels ≥ 19 AU/ml). The anti-S cutoff of 200 AU/ml used to separate strong vs. weak responses. A strong response (anti-S titers ≥ 200 AU/ml) was observed in 93/157 (59.2 %) patients with a mean-age of 53.1 ± 13.8 years (45.2 % males). A weak response (anti-S titers < 200 AU/ml) was observed in 64/157 (40.8 %) cases with a mean-age of 62.3 ± 10.2 years (p < 0.0001). The strong response subgroup had lower metabolic comorbidities, including glucose hemostasis, hypertension, and dyslipidemia (p < 0.04). Moreover, the strong response subgroup had fibrosis stages F0-F2 (75.3 % vs. 56.3 %) and lower rates of advanced stages F3-F4 (24.7 % vs. 43.8 %). The F0-F2 subgroups had significantly higher rates of strong responses than the F3-F4 stages. The anti-S ≥ 200 and anti-S ≥ 400 AU/ml response achieved in 66 % and 36.8 % of the F0-F2 population was significantly higher than the 45.1 % (p = 0.006) and 23.5 % (p = 0.05) in the F3-F4 population, respectively. The Fib-4 calculations and Fibroscan evaluations were consistent with histologic fibrosis assessment. Conclusion Advanced liver fibrosis (assessed by histology, Fib-4, or Fibroscan) is a risk factor for lower response to Pfizer's BNT162b2 vaccine, and patients should be prioritized for the vaccine booster against SARS-CoV-2.
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Affiliation(s)
- David Hakimian
- Hadassah Medical Center, Liver insitute, Hadassah-Hebrew University Medical Center, Israel
| | - Johnny Amer
- Hadassah Medical Center, Liver insitute, Hadassah-Hebrew University Medical Center, Israel
| | - Alaa Jammal
- Hadassah Medical Center, Liver insitute, Hadassah-Hebrew University Medical Center, Israel
| | - Asher Shafrir
- Hadassah Medical Center, Liver insitute, Hadassah-Hebrew University Medical Center, Israel
| | - Yael Milgrom
- Hadassah Medical Center, Liver insitute, Hadassah-Hebrew University Medical Center, Israel
| | - Mohammad Masarowah
- Hadassah Medical Center, Liver insitute, Hadassah-Hebrew University Medical Center, Israel
| | - Wadi Hazou
- Hadassah Medical Center, Liver insitute, Hadassah-Hebrew University Medical Center, Israel
- Hadassah Medical Center, Department of Surgery, Jerusalem, Israel
| | - Yuval Ishay
- Hadassah Medical Center, Liver insitute, Hadassah-Hebrew University Medical Center, Israel
| | - Ashraf Imam
- Hadassah Medical Center, Department of Surgery, Jerusalem, Israel
| | - Adi Francis
- Hadassah Medical Center, Cardiac Care Unit, Holy Family Hospital, Bar-Ilan University, Nazareth, Israel
| | - Abed Khalaileh
- Hadassah Medical Center, Department of Surgery, Jerusalem, Israel
| | - Rifaat Safadi
- Hadassah Medical Center, Liver insitute, Hadassah-Hebrew University Medical Center, Israel
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21
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Alfar R, Napoleon JV, Shahriar I, Finnell R, Walchle C, Johnson A, Low PS. Selective reprogramming of regulatory T cells in solid tumors can strongly enhance or inhibit tumor growth. Front Immunol 2023; 14:1274199. [PMID: 37928524 PMCID: PMC10623129 DOI: 10.3389/fimmu.2023.1274199] [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: 08/08/2023] [Accepted: 09/26/2023] [Indexed: 11/07/2023] Open
Abstract
Folate receptor delta (FRδ) has been used as a biomarker for regulatory T cells (Tregs), because its expression is limited to Tregs and ovum. Although FRδ is unable to bind folate, we have used molecular docking software to identify a folate congener that binds FRδ with high affinity and have exploited this FRδ-specific ligand to target attached drugs (imaging agents, immune activators, and immune suppressors) specifically to Tregs in murine tumor xenografts. Analysis of treated tumors demonstrates that targeting of a Toll-like receptor 7 agonist inhibits Treg expression of FOXP3, PD-1, CTLA4, and HELIOS, resulting in 40-80% reduction in tumor growth and repolarization of other tumor-infiltrating immune cells to more inflammatory phenotypes. Targeting of the immunosuppressive drug dexamethasone, in contrast, promotes enhanced tumor growth and shifts the tumor-infiltrating immune cells to more anti-inflammatory phenotypes. Since Tregs comprise <1% of cells in the tumor masses examined, and since the targeted drugs are not internalized by cancer cells, these data demonstrate that Tregs exert a disproportionately large effect on tumor growth. Because the targeted drug did not bind to Tregs or other immune cells in healthy tissues, the data demonstrate that the immunosuppressive properties of Tregs in tumors can be manipulated without causing systemic toxicities associated with global reprogramming of the immune system.
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Affiliation(s)
- Rami Alfar
- Department of Chemistry, Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN, United States
| | - John V. Napoleon
- Department of Chemistry, Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN, United States
| | - Imrul Shahriar
- Department of Chemistry, Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN, United States
| | - Richard Finnell
- Departments of Molecular and Cellular Biology, Molecular and Human Genetics and Medicine, Baylor College of Medicine, Houston, TX, United States
| | - Cole Walchle
- Department of Chemistry, Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN, United States
| | - Austin Johnson
- Department of Chemistry, Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN, United States
| | - Philip S. Low
- Department of Chemistry, Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN, United States
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22
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Richards-Jones L, Patel P, Jagpal PK, Lowrie R, Saunders K, Burwood S, Shrestha S, Paudyal V. Provision of drug and alcohol services amidst COVID-19 pandemic: a qualitative evaluation on the experiences of service providers. Int J Clin Pharm 2023; 45:1098-1106. [PMID: 36971897 PMCID: PMC10042098 DOI: 10.1007/s11096-023-01557-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 02/14/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND The impact of COVID-19 pandemic on the provision of drug and alcohol (D&A) services and associated outcomes have been under-researched. AIM This study aimed to understand the experiences of service providers in relation to how drug and alcohol (D&A) services were affected during COVID-19 pandemic, including the adaptations made and lessons learnt for the future. METHOD Focus groups and semi-structured interviews were conducted with participants from various D&A service organisations across the UK. Data were audio recorded, followed by transcription and thematic analysis. RESULTS A total of 46 participants representing various service providers were recruited between October and January 2022. The thematic analysis identified ten themes. COVID-19 required significant changes to how the treatment was provided and prioritised. Expansion of telehealth and digital services were described, which reduced service wait times and increased opportunities for peer network. However, they described missed opportunities for disease screening, and some users risked facing digital exclusion. Participants who provided opiate substitution therapy service spoke of improving service provider/user trust following the shift from daily supervised treatment consumption to weekly dispensing. At the same time, they feared fatal overdoses and non-adherence to treatment. CONCLUSION This study demonstrates the multifaceted impact of the COVID-19 pandemic on UK-based D&A service provisions. The long-term impact of reduced supervision on Substance Use Disorder treatment and outcomes and any effect of virtual communications on service efficiency, patient-provider relationships and treatment retention and successes are unknown, suggesting the need for further study to assess their utility.
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Affiliation(s)
- Levi Richards-Jones
- School of Pharmacy, College of Medical and Dental Sciences, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
| | - Priya Patel
- School of Pharmacy, College of Medical and Dental Sciences, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
| | - Parbir Kaur Jagpal
- School of Pharmacy, College of Medical and Dental Sciences, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
| | - Richard Lowrie
- Pharmacy and Prescribing Support Unit, NHS Glasgow and Clyde, Glasgow, G76 7AT, UK
| | | | | | - Sunil Shrestha
- School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor, Malaysia
| | - Vibhu Paudyal
- School of Pharmacy, College of Medical and Dental Sciences, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
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23
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Al-Dury S, Waldenström J, Ringlander J, Einarsdottir S, Andersson M, Hamah Saed H, Waern J, Martner A, Hellstrand K, Lagging M. Catch-up antibody responses and hybrid immunity in mRNA vaccinated patients at risk of severe COVID-19. Infect Dis (Lond) 2023; 55:744-750. [PMID: 37395287 DOI: 10.1080/23744235.2023.2230289] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 06/22/2023] [Accepted: 06/22/2023] [Indexed: 07/04/2023] Open
Abstract
BACKGROUND The immunogenicity of repeated vaccination and hybrid immunity in vulnerable patients remains unclear. METHODS We studied the impact of iterative Covid-19 mRNA vaccination and hybrid immunity on antibody levels in immunosuppressed subjects. Patients with liver cirrhosis (n = 38), survivors of allogeneic haematopoietic stem cell transplantation (allo-HSCT) (n = 36) and patients with autoimmune liver disease (n = 14) along with healthy controls (n = 20) were monitored for SARS-CoV-2-S1 IgG after their 1st-3rd vaccine doses, 31 of whom became infected with the Omicron variant after the 2nd dose. Ten uninfected allo-HSCT recipients received an additional 4th vaccine dose. RESULTS Unexpectedly, immunosuppressed patients achieved antibody levels in parity with controls after the 3rd vaccine dose. In all study cohorts, hybrid immunity (effect of vaccination and natural infection) resulted in approximately 10-fold higher antibody levels than vaccine-induced immunity alone. CONCLUSIONS Three doses of the Covid-19 mRNA vaccine entailed high antibody concentrations even in immunocompromised individuals, and hybrid-immunity resulted further augmented levels than vaccination alone. Clinical trial registration: EudraCT 2021-000349-42.
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Affiliation(s)
- Samer Al-Dury
- Department of Medicine, Gastroenterology and Hepatology Unit, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Jesper Waldenström
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
| | - Johan Ringlander
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
| | - Sigrun Einarsdottir
- Department of Hematology and Coagulation, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Markus Andersson
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Hevar Hamah Saed
- Department of Medicine, Gastroenterology and Hepatology Unit, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Johan Waern
- Department of Medicine, Gastroenterology and Hepatology Unit, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Anna Martner
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Kristoffer Hellstrand
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
| | - Martin Lagging
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
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24
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Palushi A, Choi B. Cryptococcal Meningitis Diagnosed With Lumbar Puncture in an Emergency Department Patient With Acute Delirium. Cureus 2023; 15:e45603. [PMID: 37868464 PMCID: PMC10588541 DOI: 10.7759/cureus.45603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 09/18/2023] [Indexed: 10/24/2023] Open
Abstract
Cryptococcal meningitis is a life-threatening fungal infection of the central nervous system. It primarily affects immunocompromised individuals, particularly those with advanced HIV/AIDS, but can occur in people of all ages. Risk factors include solid organ transplantation, hematological malignancies, immunosuppressive medications, and primary immunodeficiency disorders. We describe a case of a 68-year-old male with atypical risk factors for cryptococcal meningitis who presented acutely delirious with a negative diagnostic workup aside from a positive cerebrospinal fluid (CSF) meningitis screen reporting Cryptococcus neoformans/gattii. While the rate of lumbar puncture (LP) in the ED has drastically decreased over the years, we emphasize the importance of considering its diagnostic value in emergency department settings in patients with atypical presentations.
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Affiliation(s)
- Ambra Palushi
- Emergency Medicine, American University of Antigua, Coolidge, ATG
| | - Bryan Choi
- Emergency Medicine, Philadelphia College of Osteopathic Medicine, Dover, USA
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25
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Yao L, Hu X, Yuan M, Zhang Q, Liu P, Yang L, Dai K, Jiang Y. IGF2-NR4A2 Signaling Regulates Macrophage Subtypes to Attenuate Liver Cirrhosis. J Clin Transl Hepatol 2023; 11:787-799. [PMID: 37408817 PMCID: PMC10318280 DOI: 10.14218/jcth.2022.00392] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 10/18/2022] [Accepted: 11/20/2022] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND AND AIMS Liver cirrhosis can lead to liver failure and eventually death. Macrophages are the main contributors to cirrhosis and have a bidirectional role in regulating matrix deposition and degradation. Macrophage-based cell therapy has been developed as an alternative to liver transplantation. However, there is insufficient evidence regarding its safety and efficacy. In this study, we aimed to explore the effect of combining insulin-like growth factor 2 (IGF2) with bone marrow-derived macrophages (BMDMs) to treat mice with liver cirrhosis. METHODS We assessed liver inflammation, fibrosis regression, liver function, and liver regeneration in mice with CCl4-induced cirrhosis and treated with BMDM only or IGF2 + BMDM. We performed in vitro experiments in which activated hepatic stellate cells (HSCs) were co-cultured with macrophages in the presence or absence of IGF2. The polarity of macrophages and the degree of inhibition of HSCs were examined. The effect of IGF2 on macrophages was also verified by the overexpression of IGF2. RESULTS Combining IGF2 with BMDM reduced liver inflammation and fibrosis and increased hepatocyte proliferation. Combining IGF2 with BMDM was more effective than using BMDM alone. In vitro experiments demonstrated that IGF2 inhibited HSCs activation by upregulating NR4A2 to promote the anti-inflammatory macrophages phenotype. IGF2 also increased the synthesis of matrix metalloproteinases (MMPs) by macrophages, which may explain why administering IGF2 combined with BMDM was more effective than administering BMDM only. CONCLUSIONS Our study provides a theoretical basis for the future use of BMDM-based cell therapy to treat liver cirrhosis.
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Affiliation(s)
- Lichao Yao
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xue Hu
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Mengqin Yuan
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Qiuling Zhang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Pingji Liu
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Lian Yang
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Kai Dai
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yingan Jiang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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26
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Papa A, Covino M, De Lucia SS, Del Gaudio A, Fiorani M, Polito G, Settanni CR, Piccioni A, Franceschi F, Gasbarrini A. Impact of COVID-19 in individuals with and without pre-existent digestive disorders with a particular focus on elderly patients. World J Gastroenterol 2023; 29:4099-4119. [PMID: 37475841 PMCID: PMC10354572 DOI: 10.3748/wjg.v29.i26.4099] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/10/2023] [Accepted: 03/20/2023] [Indexed: 07/10/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) has several extrapulmonary symptoms. Gastrointestinal (GI) symptoms are among the most frequent clinical manifestations of COVID-19, with severe consequences reported in elderly patients. Furthermore, the impact of COVID-19 on patients with pre-existing digestive diseases still needs to be fully elucidated, particularly in the older population. This review aimed to investigate the impact of COVID-19 on the GI tract, liver, and pancreas in individuals with and without previous digestive diseases, with a particular focus on the elderly, highlighting the distinctive characteristics observed in this population. Finally, the effectiveness and adverse events of the anti-COVID-19 vaccination in patients with digestive disorders and the peculiarities found in the elderly are discussed.
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Affiliation(s)
- Alfredo Papa
- CEMAD, Center for Diagnosis and Treatment of Digestive Diseases, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma 00168, Italy
- CEMAD, Università Cattolica del Sacro Cuore, Roma 00168, Italy
| | - Marcello Covino
- Department of Emergency, Università Cattolica del Sacro Cuore - Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome 00168, Italy
- Emergency Medicine, Università Cattolica del Sacro Cuore, Roma 00168, Italy
| | - Sara Sofia De Lucia
- CEMAD, Center for Diagnosis and Treatment of Digestive Diseases, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma 00168, Italy
| | - Angelo Del Gaudio
- CEMAD, Center for Diagnosis and Treatment of Digestive Diseases, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma 00168, Italy
| | - Marcello Fiorani
- CEMAD, Center for Diagnosis and Treatment of Digestive Diseases, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma 00168, Italy
| | - Giorgia Polito
- CEMAD, Center for Diagnosis and Treatment of Digestive Diseases, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma 00168, Italy
| | - Carlo Romano Settanni
- Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS - Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Andrea Piccioni
- Department of Emergency, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma 00168, Italy
| | - Francesco Franceschi
- Department of Emergency, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma 00168, Italy
- Department of Emergency, Università Cattolica del Sacro Cuore, Roma 00168, Italy
| | - Antonio Gasbarrini
- CEMAD, Center for Diagnosis and Treatment of Digestive Diseases, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma 00168, Italy
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27
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Mitrovic N, Sabanovic M, Vujovic A, Jovanovic J, Nikolic N, Jug M, Todorovic N, Filipovic A, Milosevic I. Influence of chronic liver diseases on the course and outcome of COVID-19. PLoS One 2023; 18:e0288350. [PMID: 37450541 PMCID: PMC10348559 DOI: 10.1371/journal.pone.0288350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 06/24/2023] [Indexed: 07/18/2023] Open
Abstract
INTRODUCTION Coronavirus disease of 2019 (COVID-19) is a global health problem. The impact of chronic liver diseases on the course and outcome of COVID-19 is still the subject of research. The aim of this study was to show the characteristics of COVID-19 patients with chronic liver diseases, and to establish the risk factors for unfavourable outcome. METHODS A retrospective observational study was conducted at the Infectious Disease Clinic in Belgrade, Serbia, and included 80 patients with chronic liver diseases and COVID-19 within a time frame of two years (between 15 March 2020 and 15 March 2022). Characteristics of the affected persons, as well as the risk factors for a fatal outcome, were analyzed. RESULTS Of the 80 subjects in the study, 23.8% had chronic viral hepatitis, 12.5% autoimmune liver diseases and alcoholic liver disease respectively, 30% had non-alcoholic fatty liver disease, while 11.2% had chronic liver diseases of unknown aetiology. A total of 33.7% had cirrhosis, 6.3% hepatocellular carcinoma and 5% had liver transplants. A total of 92.5% of respondents had pneumonia (21.2% were critically ill). A deterioration of chronic liver disease was registered among 33.7% of patients, and decompensation in 3.8%; 76.3% patients recovered, while 23.7% had a lethal outcome. Risk factors for lethal outcome by univariate analysis were: alcoholic liver disease, cirrhosis, increased transaminases values prior to COVID-19, malignancy, severe pneumonia and dyspnea. In a multivariate analysis, the presence of liver cirrhosis (OR = 69.1, p = 0.001) and severe pneumonia (OR = 22.3, p = 0.006) remained independently predictive for lethal outcome. CONCLUSION These findings will help with the evaluation of COVID-19 patients who have chronic liver diseases and will improve their risk stratification.
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Affiliation(s)
- Nikola Mitrovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Department of Hepatology, Clinic for Infectious and Tropical Disease, University Clinical Centre of Serbia, Belgrade, Serbia
| | - Milos Sabanovic
- Department of Hepatology, Clinic for Infectious and Tropical Disease, University Clinical Centre of Serbia, Belgrade, Serbia
| | - Ankica Vujovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Department of Hepatology, Clinic for Infectious and Tropical Disease, University Clinical Centre of Serbia, Belgrade, Serbia
| | - Jaroslava Jovanovic
- Department of Hepatology, Clinic for Infectious and Tropical Disease, University Clinical Centre of Serbia, Belgrade, Serbia
| | - Natasa Nikolic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Department of Hepatology, Clinic for Infectious and Tropical Disease, University Clinical Centre of Serbia, Belgrade, Serbia
| | - Martina Jug
- Department of Hepatology, Clinic for Infectious and Tropical Disease, University Clinical Centre of Serbia, Belgrade, Serbia
| | - Nevena Todorovic
- Department of Hepatology, Clinic for Infectious and Tropical Disease, University Clinical Centre of Serbia, Belgrade, Serbia
| | - Ana Filipovic
- Department of Hepatology, Clinic for Infectious and Tropical Disease, University Clinical Centre of Serbia, Belgrade, Serbia
| | - Ivana Milosevic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Department of Hepatology, Clinic for Infectious and Tropical Disease, University Clinical Centre of Serbia, Belgrade, Serbia
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Alqurashi R, Alobida H, Albathi A, Aldraihem M. Disseminated nocardiosis in a patient with alcoholic liver cirrhosis: a case report. BMC Infect Dis 2023; 23:445. [PMID: 37393238 DOI: 10.1186/s12879-023-08421-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 06/23/2023] [Indexed: 07/03/2023] Open
Abstract
BACKGROUND Nocardia are Gram-positive, aerobic, filamentous bacteria that can cause localized or disseminated infections. Immunocompromised patients are at a higher risk of developing Nocardia infection and further dissemination of the disease. To date, limited data have documented the relationship between nocardiosis and alcoholic liver disease. CASE PRESENTATION We report the case of a 47-year-old man with a known history of alcoholic liver cirrhosis. The patient presented to our emergency department with redness, swelling in the left eye, and diminished bilateral vision. Fundus examination of the left eye was obscured, while that of the right eye was consistent with subretinal abscess. Therefore, endogenous endophthalmitis was suspected. Imaging revealed two ring-enhancing lesions in the brain, and multiple bilateral small cystic and cavitary lung lesions. Unfortunately, the left eye eventually eviscerated due to the rapid progression of the disease. Cultures from the left eye were positive for Nocardia farcinica. The patient was started on imipenem, trimethoprim/sulfamethoxazole, and amikacin based on culture sensitivity. The patient's hospitalization course was complicated by his aggressive and advanced condition, which led to his death. CONCLUSIONS Although the patient's condition initially improved with the recommended antibiotic regimens, it led to death owing to the patient's advanced condition. Early detection of nocardial infection in patients with typical or atypical immunosuppressive conditions may improve overall mortality and morbidity. Liver cirrhosis disrupts cell-mediated immunity and may increase the risk of Nocardia infection.
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Affiliation(s)
- Rewaa Alqurashi
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia.
| | - Husam Alobida
- Department of Infectious Disease, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Abdullah Albathi
- Department of Radiology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Moneera Aldraihem
- Department of Neurology, King Fahad Medical City, Riyadh, Saudi Arabia
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29
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Falabello de Luca AC, Marinho GB, Franco JB, Tenório JDR, Andrade NS, Batista AM, Mamana AC, Tozetto-Mendoza TR, Pérez Sayáns M, Braz-Silva PH, Ortega KL. Quantification of Torque Teno Virus (TTV) in plasma and saliva of individuals with liver cirrhosis: a cross sectional study. Front Med (Lausanne) 2023; 10:1184353. [PMID: 37425326 PMCID: PMC10325656 DOI: 10.3389/fmed.2023.1184353] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Accepted: 06/06/2023] [Indexed: 07/11/2023] Open
Abstract
Introduction Torque teno virus (TTV) has been pointed as an endogenous marker of immune function, the objective of this study was to investigate the TTV viral load in plasma and saliva of cirrhotic individuals and correlate it with clinical characteristics. Methods Blood, saliva, clinical data from records and laboratory tests were collected from 72 cirrhotic patients. Plasma and saliva were submitted to real-time polymerase chain reaction for quantification of TTV viral load. Results The majority of the patients presented decompensated cirrhosis (59.7%) and 47.2% had alterations in the white blood series. TTV was identified in 28 specimens of plasma (38.8%) and in 67 specimens of saliva (93.0%), with median values of TTV copies/mL of 90.6 in plasma and 245.14 in saliva. All the patients who were positive for TTV in plasma were also positive in saliva, with both fluids having a moderately positive correlation for the presence of TTV. There was no correlation between TTV viral load, either in plasma or in saliva, and any of the variables studied. Conclusion TTV is more frequently found and in greater amount in the saliva than in the plasma of cirrhotic patients. There was no correlation between TTV viral load and clinical parameters.
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Affiliation(s)
| | - Gabriella Bueno Marinho
- Special Care Dentistry Centre (CAPE), Department of Stomatology, University of São Paulo, São Paulo, Brazil
| | - Juliana Bertoldi Franco
- Division of Dentistry, Clinics Hospital, University of São Paulo, School of Medicine, São Paulo, Brazil
| | - Jefferson da Rocha Tenório
- Special Care Dentistry Centre (CAPE), Department of Stomatology, University of São Paulo, São Paulo, Brazil
- Department of Pathology and Oral Diagnosis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Natália Silva Andrade
- Special Care Dentistry Centre (CAPE), Department of Stomatology, University of São Paulo, São Paulo, Brazil
- Department of Dentistry, Federal University of Sergipe, Lagarto, Sergipe, Brazil
| | - Alexandre Mendes Batista
- Laboratory of Virology, Institute of Tropical Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Ana Carolina Mamana
- Laboratory of Virology, Institute of Tropical Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Tânia Regina Tozetto-Mendoza
- Laboratory of Virology, Institute of Tropical Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Mário Pérez Sayáns
- Oral Medicine, Oral Surgery and Implantology Unit, MedOralRes Group, University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Paulo Henrique Braz-Silva
- Laboratory of Virology, Institute of Tropical Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil
| | - Karem L. Ortega
- Special Care Dentistry Centre (CAPE), Department of Stomatology, University of São Paulo, São Paulo, Brazil
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Liatsos GD. SARS-CoV-2 induced liver injury: Incidence, risk factors, impact on COVID-19 severity and prognosis in different population groups. World J Gastroenterol 2023; 29:2397-2432. [PMID: 37179584 PMCID: PMC10167898 DOI: 10.3748/wjg.v29.i16.2397] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 02/17/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
Liver is unlikely the key organ driving mortality in coronavirus disease 2019 (COVID-19) however, liver function tests (LFTs) abnormalities are widely observed mostly in moderate and severe cases. According to this review, the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5% to 96.8% worldwide. The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West. Multifactorial mechanisms are implicated in COVID-19-induced liver injury. Among them, hypercytokinemia with "bystander hepatitis", cytokine storm syndrome with subsequent oxidative stress and endotheliopathy, hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury. Liver hypoxia may also contribute under specific conditions, while direct hepatocyte injury is an emerging mechanism. Except for initially observed severe acute respiratory distress syndrome corona virus-2 (SARS-CoV-2) tropism for cholangiocytes, more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy (EM). The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA, S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization. New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery, suggesting a post-COVID-19 persistent live injury.
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Affiliation(s)
- George D Liatsos
- Department of Internal Medicine, Hippokration General Hospital, Athens 11527, Attiki, Greece
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Patnaik SK, Mohanty S, Mishra D, Kanungo M, Patil S, Teja RG, Uthansingh K, Narayan J, Sahu MK, Pati GK. A Prospective Study on the Clinical Significance of Infections in a Hospital Setting Among the Cirrhotic Patients and Their Outcomes. Cureus 2023; 15:e37912. [PMID: 37220470 PMCID: PMC10200015 DOI: 10.7759/cureus.37912] [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] [Accepted: 04/16/2023] [Indexed: 05/25/2023] Open
Abstract
Aim and objectives The infection of microbial agents in cirrhosis has increased due to poor immunity, which increases morbidities and mortalities worldwide. The present study aimed to assess the incidence, the type of infections, the pattern of resistance, and the course of hospitalization among cirrhotic patients in the Eastern coastal region. Methodology The study was a descriptive cross-sectional study, and the current study was undertaken for 24 months at the Department of Gastroenterology and Hepatobiliary Sciences, IMS, and SUM. Hospital, Bhubaneswar. Consecutive cirrhotic patients admitted with bacterial infection were prospectively evaluated, and the infection patterns were accessed. The data were collected in a well-structured proforma designed by our study team. Results Out of the total 200 cases, a fraction of 72.5% of males outnumbered the females; the mean age of presentation was 59 ± 12 years. A fraction of 59% of cases had the habit of consuming alcohol which amounted to the predominant etiological factor for cirrhosis, followed by non-alcoholic steatohepatitis (NASH). Urinary tract infection (UTI) and spontaneous bacterial peritonitis (SBP) were more common types of infections in the healthcare-associated (HCA) group; however, pneumonia and skin and soft tissue infections (SSTI) were predominant types of infections in community-acquired (CA) group. The model for end-stage liver disease (MELD) scores were not significantly different amongst the three groups with infections at the time of Diagnosis infection and at the time of hospitalization. However, the MELD scores were substantially higher at the time of infection diagnosis than the MELD scores at the time of admission amongst the three groups with infection. Conclusion The present study showed that infections in cirrhosis were relatively common. Due to increasing resistance patterns, the judicious usage of antibiotics in cirrhosis could be the need of the hour.
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Affiliation(s)
- Swarup K Patnaik
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Sambedana Mohanty
- Community Medicine, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Debakanta Mishra
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Manjit Kanungo
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Srinith Patil
- Gastroenterology, ESIC Medical College, Gulbarga, IND
| | | | - Kanishka Uthansingh
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Jimmy Narayan
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Manoj K Sahu
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Girish K Pati
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
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Ali FE, Abd El-Aziz MK, Sharab EI, Bakr AG. Therapeutic interventions of acute and chronic liver disorders: A comprehensive review. World J Hepatol 2023; 15:19-40. [PMID: 36744165 PMCID: PMC9896501 DOI: 10.4254/wjh.v15.i1.19] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/17/2022] [Accepted: 12/21/2022] [Indexed: 01/16/2023] Open
Abstract
Liver disorders are one of the most common pathological problems worldwide. It affects more than 1.5 billion worldwide. Many types of hepatic cells have been reported to be involved in the initiation and propagation of both acute and chronic liver diseases, including hepatocytes, Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells (HSCs). In addition, oxidative stress, cytokines, fibrogenic factors, microRNAs, and autophagy are also involved. Understanding the molecular mechanisms of liver diseases leads to discovering new therapeutic interventions that can be used in clinics. Recently, antioxidant, anti-inflammatory, anti-HSCs therapy, gene therapy, cell therapy, gut microbiota, and nanoparticles have great potential for preventing and treating liver diseases. Here, we explored the recent possible molecular mechanisms involved in the pathogenesis of acute and chronic liver diseases. Besides, we overviewed the recent therapeutic interventions that targeted liver diseases and summarized the recent studies concerning liver disorders therapy.
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Affiliation(s)
- Fares Em Ali
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt.
| | | | - Elham I Sharab
- Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Adel G Bakr
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
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Liptak P, Nosakova L, Rosolanka R, Skladany L, Banovcin P. Acute-on-chronic liver failure in patients with severe acute respiratory syndrome coronavirus 2 infection. World J Hepatol 2023; 15:41-51. [PMID: 36744167 PMCID: PMC9896507 DOI: 10.4254/wjh.v15.i1.41] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/03/2022] [Accepted: 11/29/2022] [Indexed: 01/16/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a significant impact on the lives of millions of people, especially those with other concomitant diseases, such as chronic liver diseases. To date, seven coronaviruses have been identified to infect humans. The main site of pathological action of these viruses is lung tissue. However, a substantial number of studies have proven that SARS-CoV-2 shows affinity towards several organs, including the gastrointestinal tract and the liver. The current state of evidence points to several proposed mechanisms of liver injury in patients with COVID-19 and their combination. Liver impairment is considered to be the result of the direct effect of the virus on the hepatic tissue cells, a systemic reaction consisting of inflammation, hypoxia and cytokine storm, drug-induced liver injury, with the possible contribution of a perturbed gut-liver axis. Reactivation of chronic hepatic disease could be another factor for liver impairment in patients with SARS-CoV-2 infection. Acute-on-chronic liver failure (ACLF) is a relatively new syndrome that occurs in 10%–30% of all hospitalized patients with chronic liver disease. It is crucial to recognize high-risk patients due to the increased morbidity and mortality in these cases. Several published studies have reported virus infection as a trigger factor for ACLF. However, to date, there are few relevant studies describing the presence of ACLF in patients with acute SARS-CoV-2 infection. In this minireview we summarize the current state of knowledge regarding the relation between ACLF and acute SARS-CoV-2 infection.
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Affiliation(s)
- Peter Liptak
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Lenka Nosakova
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Robert Rosolanka
- Clinic of Infectology and Travel Medicine, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Lubomir Skladany
- Department of Internal Medicine II, Division Hepatology, Gastroenterology and Liver Transplantation, FD Roosevelt University Hospital of Slovak Medical University, Banska Bystrica 97517, Slovakia
| | - Peter Banovcin
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
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Al-Rawi TSS, Al-Ani RM. Liver dysfunction-related COVID-19: A narrative review. World J Meta-Anal 2023; 11:5-17. [DOI: 10.13105/wjma.v11.i1.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/25/2022] [Accepted: 12/14/2022] [Indexed: 01/11/2023] Open
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He T, Ling N, Zhang G, Xiang D, Hu P, Peng M, Cai D, Zhang D, Chen M, Ren H. Decreased antibody response to influenza vaccine with an enhanced antibody response to subsequent SARS-CoV-2 vaccination in patients with chronic hepatitis B virus infection. Immun Inflamm Dis 2023; 11:e759. [PMID: 36705404 PMCID: PMC9803931 DOI: 10.1002/iid3.759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 12/12/2022] [Accepted: 12/14/2022] [Indexed: 01/01/2023] Open
Abstract
INTRODUCTION Influenza or SARS-CoV-2 vaccination is especially recommended for people with underlying diseases. For the large number of patients with chronic hepatitis B virus infection (CHB), studies on their immune responses to these vaccines are still lacking. METHODS A total of 57 CHB patients and 19 healthy controls (HCs) receiving inactivated influenza vaccination were prospectively followed up. Influenza-specific immunoglobulin G (IgG) antibodies (anti-H1N1, anti-H3N2, and anti-B IgG), antibody-secreting cells (ASCs), and circulating T follicular helper cells were assessed simultaneously. Eight CHB patients subsequently got inactivated SARS-CoV-2 vaccination during 1-year follow-up, and levels of serum antibodies against SARS-CoV-2 were further analyzed. RESULTS On day 28 after influenza vaccination, three influenza antibodies levels appeared to be lower in CHB patients than in HCs. And anti-H1N1 IgG level was significantly decreased in cirrhotic patients (p < .05). Anti-H1N1 IgG levels (day 28) were positively correlated with ASC frequencies (day 7) (p < .05), and negatively correlated with cirrhosis and hepatitis B surface antigen levels (p < .05). Anti-SARS-CoV-2 antibodies were higher in patients with influenza vaccination history than in patients without the history (p < .05). Moreover, positive correlations existed between influenza vaccination history and anti-SARS-CoV-2 antibody levels (p < .01). CONCLUSIONS CHB patients, especially those with cirrhosis, appeared to have a decreased antibody response to inactivated influenza vaccine. A history of inactivated influenza vaccination within 1 year before inactivated SARS-CoV-2 vaccination might induce stronger anti-SARS-CoV-2 antibody response.
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Affiliation(s)
- Taiyu He
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
| | - Ning Ling
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
| | - Gaoli Zhang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
| | - Dejuan Xiang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
| | - Peng Hu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
| | - Mingli Peng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
| | - Dachuan Cai
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
| | - Dazhi Zhang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
| | - Min Chen
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
| | - Hong Ren
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
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Beran A, Mhanna A, Mhanna M, Hassouneh R, Abuhelwa Z, Mohamed MFH, Sayeh W, Musallam R, Assaly R, Abdeljawad K. Real-world effectiveness of COVID-19 vaccination in liver cirrhosis: a systematic review with meta-analysis of 51,834 patients. Proc AMIA Symp 2023; 36:151-156. [PMID: 36876272 PMCID: PMC9980592 DOI: 10.1080/08998280.2023.2165344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
SARS-CoV-2 vaccinations were found to be highly effective in phase 3 clinical trials. However, these trials have not reported data regarding the subgroup of liver disease or excluded patients with liver disease. The effectiveness of COVID-19 vaccines among liver cirrhosis (LC) patients is unclear. We conducted this meta-analysis to assess the effectiveness of SARS-CoV-2 vaccination in LC patients. A comprehensive literature search was conducted to include all the relevant studies that compared the outcomes of LC patients who received SARS-CoV-2 vaccines vs. unvaccinated patients. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated by the Mantel-Haenszel method within a random-effect model. Four studies with 51,834 LC patients (20,689 patients received at least one dose vs 31,145 were unvaccinated) were included. COVID-19-related complications, including hospitalization (RR 0.73, 95% CI 0.59-0.91, P = 0.004), mortality (RR 0.29, 95% CI 0.16-0.55, P = 0.0001), and need for invasive mechanical ventilation (RR 0.29, 95% CI 0.11-0.77, P = 0.01), were significantly lower in the vaccinated group compared to the unvaccinated group. SARS-CoV-2 vaccination in LC patients reduced COVID-19-related mortality, intubation, and hospitalization. SARS-CoV-2 vaccination is highly effective in LC. Further prospective studies, preferably randomized controlled trials, are necessary to validate our findings and determine which vaccine is superior in patients with LC.
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Affiliation(s)
- Azizullah Beran
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana
| | - Asmaa Mhanna
- Department of Pediatrics, ProMedica Hospital, Toledo, Ohio
| | | | - Ramzi Hassouneh
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana
| | - Ziad Abuhelwa
- Department of Internal Medicine, University of Toledo, Toledo, Ohio
| | - Mouhand F H Mohamed
- Department of Internal Medicine, Warren Alpert Medical School, Brown University, Providence, Rhode Island
| | - Wasef Sayeh
- Department of Internal Medicine, University of Toledo, Toledo, Ohio
| | - Rami Musallam
- Department of Internal Medicine, St. Vincent Charity Medical Center, Cleveland, Ohio
| | - Ragheb Assaly
- Department of Internal Medicine, University of Toledo, Toledo, Ohio
| | - Khaled Abdeljawad
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana
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Mark JD, Park T, Velez Quinones V, Isaac S. Rare extension of pancreatic pseudocyst with Mycobacterium abscessus into the iliopsoas muscle. BMJ Case Rep 2022; 15:e252777. [PMID: 36319038 PMCID: PMC9628508 DOI: 10.1136/bcr-2022-252777] [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] [Accepted: 10/14/2022] [Indexed: 11/07/2022] Open
Abstract
Pancreatic pseudocyst is a well-known complication of both acute and chronic pancreatitis. Although extension into other anatomical sites is common, extension into the retrofascial space causing an iliopsoas abscess is exceedingly rare. Although its low incidence creates a diagnostic challenge for clinicians, early diagnosis is essential to prevent significant complications and poor patient outcomes. We present a case of iliopsoas abscess with unusual culture fluid growth in the setting of acute on chronic pancreatitis secondary to extension of a pancreatic pseudocyst. We also offer a brief review of the literature and pathophysiology of the condition.
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Affiliation(s)
- Justin David Mark
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, Florida, USA
| | - Travis Park
- Department of Internal Medicine, HCA Florida JFK Hospital, Atlantis, Florida, USA
| | | | - Shaun Isaac
- Department of Internal Medicine, HCA Florida JFK Hospital, Atlantis, Florida, USA
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Drácz B, Czompa D, Müllner K, Hagymási K, Miheller P, Székely H, Papp V, Horváth M, Hritz I, Szijártó A, Werling K. The Elevated De Ritis Ratio on Admission Is Independently Associated with Mortality in COVID-19 Patients. Viruses 2022; 14:2360. [PMID: 36366457 PMCID: PMC9692894 DOI: 10.3390/v14112360] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 10/24/2022] [Accepted: 10/25/2022] [Indexed: 02/01/2023] Open
Abstract
Liver damage in COVID-19 patients was documented as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels or an elevated AST/ALT ratio, known as the De Ritis ratio. However, the prognostic value of the elevated De Ritis ratio in COVID-19 patients is still unknown. The aim of our study was to evaluate the prognostic value of the De Ritis ratio compared to other abnormal laboratory parameters and its relation to mortality. We selected 322 COVID-19 patients in this retrospective study conducted between November 2020 and March 2021. The laboratory parameters were measured on admission and followed till patient discharge or death. Of the 322 COVID-19 patients, 57 (17.7%) had gastrointestinal symptoms on admission. The multivariate analysis showed that the De Ritis ratio was an independent risk factor for mortality, with an OR of 29.967 (95% CI 5.266-170.514). In ROC analysis, the AUC value of the the De Ritis ratio was 0.85 (95% CI 0.777-0.923, p < 0.05) with sensitivity and specificity of 80.6% and 75.2%, respectively. A De Ritis ratio ≥1.218 was significantly associated with patient mortality, disease severity, higher AST and IL-6 levels, and a lower ALT level. An elevated De Ritis ratio on admission is independently associated with mortality in COVID-19 patients, indicating liver injury and cytokine release syndrome.
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Affiliation(s)
- Bálint Drácz
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary
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Yoshida Y, Chu S, Fox S, Zu Y, Lovre D, Denson JL, Miele L, Mauvais-Jarvis F. Sex differences in determinants of COVID-19 severe outcomes - findings from the National COVID Cohort Collaborative (N3C). BMC Infect Dis 2022; 22:784. [PMID: 36224551 PMCID: PMC9555705 DOI: 10.1186/s12879-022-07776-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 10/04/2022] [Accepted: 10/10/2022] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVE The impact of comorbidities and biomarkers on COVID-19 severity vary by sex but have not yet been verified in population-based studies. We examined the association of comorbidities, inflammatory biomarkers, and severe outcomes in men and women hospitalized for COVID-19. DESIGN This is a retrospective cohort analysis based on the National COVID Cohort Collaborative (N3C). We included 574,391 adult patients admitted for COVID-19 at hospitals or emergency rooms between 01/01/2020 and 12/31/2021. METHODS We defined comorbidities at or before the first admission for COVID-19 by Charlson Comorbidity Index (CCI) and CCI components. We used the averaged lab values taken within 15 days before or after the admission date to measure biomarkers including c-reactive protein (CRP), ferritin, procalcitonin, N-terminal pro b-type natriuretic peptide (NT proBNP), d-dimer, absolute lymphocyte counts, absolute neutrophil counts, and platelets. Our primary outcome was all-cause mortality; secondary outcomes were invasive mechanical ventilation (IMV) and hospital length of stay (LOS). We used logistic regression adjusted for age, race, ethnicity, visit type, and medications to assess the association of comorbidities, biomarkers, and mortality disaggregating by sex. RESULTS Moderate to severe liver disease, renal disease, metastatic solid tumor, and myocardial infarction were the top four fatal comorbidities among patients who were hospitalized for COVID-19 (adjusted odds ratio [aOR] > 2). These four comorbid conditions remained the most lethal in both sexes, with a higher magnitude of risk in women than in men (p-interaction < 0.05). Abnormal elevations of CRP, ferritin, procalcitonin, NT proBNP, neutrophil, and platelet counts, and lymphocytopenia were significantly associated with the risk of death, with procalcitonin and NT proBNP as the strongest predictors (aOR > 2). The association between the abnormal biomarkers and death was stronger in women than in men (p-interaction < 0.05). CONCLUSION There are sex differences in inpatient mortality associated with comorbidities and biomarkers. The significant impact of these clinical determinants in women with COVID-19 may be underappreciated as previous studies stressed the increased death rate in male patients that is related to comorbidities or inflammation. Our study highlights the importance and the need for sex-disaggregated research to understand the risk factors of poor outcomes and health disparities in COVID-19.
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Affiliation(s)
- Yilin Yoshida
- Section of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of Medicine, 1430 Tulane Ave. New Orleans, 70112, New Orleans, LA, USA.
| | - San Chu
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Sarah Fox
- School of Science and Engineering, Tulane University, New Orleans, LA, USA
| | - Yuanhao Zu
- Department of Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
| | - Dragana Lovre
- Section of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of Medicine, 1430 Tulane Ave. New Orleans, 70112, New Orleans, LA, USA
| | - Joshua L Denson
- Pulmonary and Critical Care, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA
| | - Lucio Miele
- Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Franck Mauvais-Jarvis
- Section of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of Medicine, 1430 Tulane Ave. New Orleans, 70112, New Orleans, LA, USA
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40
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Characteristics of COVID-19 Infection in a Hospitalized Autoimmune Hepatitis Patient. Pathogens 2022; 11:pathogens11091054. [PMID: 36145486 PMCID: PMC9501835 DOI: 10.3390/pathogens11091054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/12/2022] [Accepted: 08/18/2022] [Indexed: 01/08/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a major public health worldwide. Hepatic dysfunction has been seen in patients with COVID-19 and could be related to a viral cytopathic effect, an exacerbated immune reaction, or drug-induced liver damage. Currently, routine modification of immunosuppressive therapy in patients with autoimmune hepatitis (AIH) before and after SARS-CoV-2 infection remains an important topic to be discussed. However, there is little evidence about this thematic to support any recommendation. Here, we described a case report in which the use of an immunosuppressive drug by a patient with diagnosed AIH might have influenced the COVID-19 clinical course with altered laboratory hematological and biochemical parameters during infection.
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Aquino-Matus J, Uribe M, Chavez-Tapia N. COVID-19: Current Status in Gastrointestinal, Hepatic, and Pancreatic Diseases—A Concise Review. Trop Med Infect Dis 2022; 7:tropicalmed7080187. [PMID: 36006279 PMCID: PMC9415805 DOI: 10.3390/tropicalmed7080187] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/09/2022] [Accepted: 08/09/2022] [Indexed: 01/08/2023] Open
Abstract
The gastrointestinal tract plays an important role in the pathogenesis of COVID-19. The angiotensin-converting enzyme 2 receptor and the transmembrane protease serine 2 receptor bind and activate SARS-CoV-2 and are present in high concentrations throughout the gastrointestinal tract. Most patients present with gastrointestinal symptoms and/or abnormal liver function tests, both of which have been associated with adverse outcomes. The mechanisms of liver damage are currently under investigation, but the damage is usually transient and nonsevere. Liver transplantation is the only definitive treatment for acute liver failure and end-stage liver disease, and unfortunately, because of the need for ventilators during the COVID-19 pandemic, most liver transplant programs have been suspended. Patients with gastrointestinal autoimmune diseases require close follow-up and may need modification in immunosuppression. Acute pancreatitis is a rare manifestation of COVID-19, but it must be considered in patients with abdominal pain. The gastrointestinal tract, including the liver and the pancreas, has an intimate relationship with COVID-19 that is currently under active investigation.
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Kim JA, Park SJ, Choi S, Chang J, Jeong S, C Ahn J, Lee G, Son JS, Park SM. Association of the presence of allergic disease with subsequent risk of liver cancer in a nationwide retrospective cohort among Koreans. Sci Rep 2022; 12:9856. [PMID: 35701586 PMCID: PMC9198066 DOI: 10.1038/s41598-022-14147-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 04/27/2022] [Indexed: 11/24/2022] Open
Abstract
A number of studies have proposed an inverse association between allergic diseases and risk of cancer, but only a few studies have specifically investigated the risk of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the association of allergic diseases with risk of primary liver cancer. We conducted a retrospective cohort study of the Korean National Health Insurance Service database consisted of 405,512 Korean adults ages 40 and above who underwent health screening before January 1st, 2005. All participants were followed up until the date of liver cancer, death, or December 31st, 2013, whichever happened earliest. Those who died before the index date or had pre-diagnosed cancer were excluded from the analyses. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for risk of primary liver cancer according to the presence of allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis. The aHR (95% CI) for overall liver cancer among allergic patients was 0.77 (0.68–0.87) compared to those without allergic disease. Allergic patients had significantly reduced risk of HCC (aHR, 0.72; 95% CI 0.62–0.85) but not ICC (aHR, 0.95; 95% CI 0.73–1.22). The presence of allergies was associated with significantly lower risk of liver cancer among patients whose systolic blood pressure is lower than 140 mmHg (aHR, 0.64; 95% CI 0.62–0.78 for overall liver cancer; aHR, 0.64; 95% CI 0.52–0.78 for HCC) but this effect was not observed among patients whose systolic blood pressure is higher than 140 mmHg (aHR, 0.91; 95% CI 0.71–1.18 for overall liver cancer; aHR, 0.91; 95% CI 0.71–1.18 for HCC) The aHR (95% CI) for overall liver cancer of allergic patients with and without chronic hepatitis virus infection were 0.60 (95% CI 0.44–0.81) and 0.77 (95% CI 0.64–0.93), respectively. In addition, allergic patients without cirrhosis showed significantly lower risk of overall liver cancer (aHR, 0.73; 95% CI 0.63–0.83). Patients with allergic diseases have significantly lower risk of primary liver cancer compared to those without allergic diseases, which supports the rationale for immunotherapy as an effective treatment for liver cancer.
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Affiliation(s)
- Ji Ah Kim
- Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, South Korea
| | - Sun Jae Park
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, South Korea
| | - Seulggie Choi
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, South Korea
| | - Jooyoung Chang
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, South Korea
| | - Seogsong Jeong
- Department of Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, 13488, Korea
| | - Joseph C Ahn
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Gyeongsil Lee
- Department of Family Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Joung Sik Son
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, South Korea.
| | - Sang Min Park
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, South Korea. .,Department of Family Medicine, Seoul National University Hospital, Seoul, South Korea.
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Correlation between the Lymphocyte-To-Monocyte Ratio (LMR) and Child–Pugh and MELD/MELDNa Scores in Vietnamese Patients with Liver Cirrhosis. GASTROENTEROLOGY INSIGHTS 2022. [DOI: 10.3390/gastroent13020019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022] Open
Abstract
Objectives: This study aims to determine cirrhotic patients’ clinical and laboratory characteristics, thereby examining the correlation between lymphocyte-to-monocyte ratio and Child–Pugh and MELD/MELDNa scores. Methods: A cross-sectional study with an analysis of 153 patients admitted to the Department of Gastroenterology–Clinical Hematology at Can Tho Central General Hospital. Data were collected via patient interviews and medical records. Results: The included patients were more likely to be male (66.7%) and were ≥60 years old (51.6%). Excessive alcohol consumption and hepatitis B were the dominant causes of cirrhosis (35.3% and 34.0%). The clinical and laboratory characteristics were similar to previous studies in cirrhotic patients. The mean Child score was 9.3 ± 2.1, including 9.8% of patients with Child A, 44.4% for Child B, and 45.8% for Child C. The mean MELD and MELDNa scores were 16.9 ± 7.1 and 19.4 ± 8.1, respectively. The mean lymphocyte-to-monocyte ratio (LMR) is 2.0 ± 2.2 (from 0.09 to 25.3), being negatively correlated with the other scores (Pearson correlation coefficients were −0.238; −0.211 and −0.245, respectively, all p-values < 0.01). Patients with LMR below 3.31 were more likely to be classified as Child–Pugh B and C. Conclusion: The correlation between LMR with Child–Pugh, MELD, and MELDNa scores was weak and negative.
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Elnaggar M, Abomhya A, Elkhattib I, Dawoud N, Doshi R. COVID-19 and liver diseases, what we know so far. World J Clin Cases 2022; 10:3969-3980. [PMID: 35665122 PMCID: PMC9131221 DOI: 10.12998/wjcc.v10.i13.3969] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 10/15/2021] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) pneumonia outbreak started in December 2019. On March 12, 2020, the World Health Organization (WHO) declared that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a pandemic, and as of May 2021, SARS-CoV-2 has infected over 167.3 million patients, including 3.4 million deaths, reported to WHO. In this review, we will focus on the relationship between SARS-CoV-2 infection and the liver. We will discuss how chronic liver diseases affect the COVID-19 disease course and outcomes. We will also discuss the SARS-CoV-2 effects on the liver, mechanisms of acute liver injury, and potential management plans.
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Affiliation(s)
- Mohamed Elnaggar
- Department of Internal Medicine, University of Nevada Reno School of Medicine, Reno, NV 89052, United States
| | - Ahmed Abomhya
- Department of Internal Medicine, The Brooklyn Hospital Center, Brooklyn, NY 11200, United States
| | - Ismail Elkhattib
- Department of Internal Medicine, University of Connecticut, Farmington, CT 06030, United States
| | - Nabila Dawoud
- Department of Internal Medicine, University of Kentucky, Lexington, KY 40508, United States
| | - Rajkumar Doshi
- Department of Cardiology, St Joseph's University Medical Center, Paterson, NJ 07503, United States
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Prevalence of Elizabethkingia meningoseptica Infections and their Resistant Pattern in Tertiary Care Hospital. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.2.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Elizabethkingia meningoseptica a rare pathogen in earlier times has been accused to infect the immunocompromised, preterm neonates, the patients exposed to longterm antibiotics and intensive care units. The apparent resistance of the multidrug Elizabethkingia meningoseptica affects the selection of appropriate antibacterial agents against it. The current study attempts to determine the prevalence of E. meningoseptica infections and consider the sensitivity pattern in a tertiary care hospital. A prospective study of prevalence of E. meningoseptica in a tertiary care hospital from March 2020 to March 2021 i.e over a period of 1 year. Patient clinical data as well as ABST patterns were collected and analyzed. Out of total 1813 patient’s samples E. meningoseptica was isolates from 21 cases (1.15%). Average age was 61.42 years, with males most likely to be infected (52.38%). All the adult patients had underlying diseases, obstructive gall bladder diseases (n=7, 33.33%) which included choledocholithiasis, obstructive jaundice, cholangitis and carcinoma gallbladder. Urinary tract diseases (n=8, 38.09%) which include chronic kidney disease (CKD) and acute kidney disease (AKD), pneumonia (n=11, 52.38%) including urosepsis and other diseases AML (n=1, 04.7%). Susceptibility tests showed 100% in vitro against few antimicrobials like cefepime, meropenem and amikacin which can be utilized to treat most common Gram-negative bacterial infections. Isolates are usually the completely sensitive to minocycline. E. meningoseptica is a rising microbe in intensive care setup due to its resistance pattern.
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de Jesus RP, de Carvalho JF, de Oliveira LPM, Cunha CDM, Alves TCHS, Vieira STB, Figueiredo VM, Bueno AA. Metabolic and nutritional triggers associated with increased risk of liver complications in SARS-CoV-2. World J Hepatol 2022; 14:80-97. [PMID: 35126841 PMCID: PMC8790394 DOI: 10.4254/wjh.v14.i1.80] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 07/28/2021] [Accepted: 12/22/2022] [Indexed: 02/06/2023] Open
Abstract
Obesity, diabetes, cardiovascular and respiratory diseases, cancer and smoking are risk factors for negative outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can quickly induce severe respiratory failure in 5% of cases. Coronavirus disease-associated liver injury may occur during progression of SARS-CoV-2 in patients with or without pre-existing liver disease, and damage to the liver parenchyma can be caused by infection of hepatocytes. Cirrhosis patients may be particularly vulnerable to SARS-CoV-2 if suffering with cirrhosis-associated immune dysfunction. Furthermore, pharmacotherapies including macrolide or quinolone antibiotics and steroids can also induce liver damage. In this review we addressed nutritional status and nutritional interventions in severe SARS-CoV-2 liver patients. As guidelines for SARS-CoV-2 in intensive care (IC) specifically are not yet available, strategies for management of sepsis and SARS are suggested in SARS-CoV-2. Early enteral nutrition (EN) should be started soon after IC admission, preferably employing iso-osmolar polymeric formula with initial protein content at 0.8 g/kg per day progressively increasing up to 1.3 g/kg per day and enriched with fish oil at 0.1 g/kg per day to 0.2 g/kg per day. Monitoring is necessary to identify signs of intolerance, hemodynamic instability and metabolic disorders, and transition to parenteral nutrition should not be delayed when energy and protein targets cannot be met via EN. Nutrients including vitamins A, C, D, E, B6, B12, folic acid, zinc, selenium and ω-3 fatty acids have in isolation or in combination shown beneficial effects upon immune function and inflammation modulation. Cautious and monitored supplementation up to upper limits may be beneficial in management strategies for SARS-CoV-2 liver patients.
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Affiliation(s)
- Rosangela Passos de Jesus
- Postgraduate Program in Food, Nutrition and Health at the School of Nutrition of the Federal University of Bahia, Salvador 40.110-150, Bahia, Brazil
| | | | | | - Carla de Magalhães Cunha
- Postgraduate Program in Food, Nutrition and Health at the School of Nutrition of the Federal University of Bahia, Salvador 40.110-150, Bahia, Brazil
| | - Thaisy Cristina Honorato Santos Alves
- Postgraduate Program in Food, Nutrition and Health at the School of Nutrition of the Federal University of Bahia, Salvador 40.110-150, Bahia, Brazil
| | - Sandra Tavares Brito Vieira
- Postgraduate Program in Food, Nutrition and Health at the School of Nutrition of the Federal University of Bahia, Salvador 40.110-150, Bahia, Brazil
| | - Virginia Maria Figueiredo
- Department of Gastroenterology, IPEMED, Ipemed Faculty of Medical Sciences, Salvador 40170-110, Bahia, Brazil
| | - Allain Amador Bueno
- College of Health, Life and Environmental Sciences, University of Worcester, Worcester WR2 6AJ, United Kingdom
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Mallik M, Singhai A, Khadanga S, Ingle V. The Significant Morbidity and Mortality Indicators in Patients of Cirrhosis. Cureus 2022; 14:e21226. [PMID: 35174029 PMCID: PMC8841014 DOI: 10.7759/cureus.21226] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2022] [Indexed: 02/07/2023] Open
Abstract
Background: Cirrhosis progression varies greatly from patient to patient due to a variety of factors, including hepatic reserve, cirrhosis etiology, and the presence of hepatocellular cancer. As a result, determining a prognosis in a patient with cirrhosis remains a difficult task. For nearly three decades, the Child-Pugh score (CPS) has been the gold standard for determining the prognosis of cirrhosis. In the last two decades, many prognostic models and scores like a model for end-stage liver disease (MELD), chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score, peripheral blood lymphocyte to monocyte ratio (LMR) have been presented to predict prognosis in patients with cirrhosis and to choose the best therapy option. The aim of our study is to determine which score is more effective in predicting three-month mortality and whether these scores are equally effective in predicting short-term outcomes. Materials & methods: In this hospital-based longitudinal study, we analyzed 140 patients with cirrhosis of liver visiting All India Institute of Medical Sciences Bhopal between July 2019 and July 2020. All the 140 patients were followed up for three months to establish short-term outcomes. The blood investigations were done at the time of presentation from all the patients and after three months in the survivors. Various scores were calculated. Results: The majority of patients (47%) were in Child-Pugh class C. Mean MELD score was 13.54, LMR score was 1.96 and CLIF-SOFA score was 5. The total bilirubin, serum creatinine, international normalized ratio (INR), total leukocyte count, absolute monocyte count, CPS, MELD, CLIF-SOFA were significantly higher in a non-surviving group as compared to the surviving group, whereas the albumin and LMR significantly decreased in the non-surviving group. On performing multivariate regression, LMR and CLIF-SOFA were significant independent risk factors of mortality after adjusting for confounding factors. All the parameters had significant discriminatory power to predict mortality. Discriminatory power of CLIF-SOFA (AUC 0.808; 95% CI: 0.733 to 0.870) was excellent and discriminatory power of CPS (AUC 0.792; 95% CI: 0.716 to 0.856), MELD score (AUC 0.765; 95% CI: 0.685 to 0.832) and LMR (AUC 0.75; 95% CI: 0.669 to 0.819) was acceptable. Among all the parameters, CLIF-SOFA was the best predictor of mortality at a cut-off point of >5 with 80.80% chances of correctly predicting mortality. Conclusion: The significant morbidity and mortality indicators are high total bilirubin, high creatinine, high INR, high TLC, low platelet count, and low albumin. Among the various scores, CLIF-SOFA is a better predictor of mortality and morbidity. Low LMR and high CLIF-SOFA are significant independent risk factors of mortality at three months.
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48
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Khalaf SA, Patel P, Caruso CR, Parrett T, Bran A. CNS Histoplasmosis as a Gliosarcoma mimicker: The diagnostic dilemma of solitary brain lesions. IDCases 2022; 27:e01364. [PMID: 35024338 PMCID: PMC8724962 DOI: 10.1016/j.idcr.2021.e01364] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 12/14/2021] [Accepted: 12/15/2021] [Indexed: 11/24/2022] Open
Abstract
Histoplasmosis is usually a benign, self-limited disease with lungs predilection. However, it might manifest as a disseminated disease in immunocompromised individuals. The involvement of the central nervous system (CNS) accounts for about 5–10% of cases with disseminated disease. Isolated histoplasmosis of the CNS is rare, and the literature shows only a few reported cases. By imaging studies, it usually presents as an isolated ring-enhancing lesion. Its spectrum of symptoms ranges from acute severe infection to progressive chronic meningitis, which delays the initial diagnosis, correct work-up and initiation of appropriate therapy. We present a case of a 57-year-old man from the Midwest of the United States who misdiagnosed with Gliosarcoma in 2019, for which he underwent appropriate management for Gliosarcoma. Presented for follow-up after new neurological symptoms; worsening in ring-enhancing brain lesions was found on magnetic resonance image MRI. After a re-examination of surgical pathological cases, histoplasmosis of the CNS was diagnosed. Failure of diagnosis CNS histoplasmosis early can lead to poor outcome and decrease chances of recovery.
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Affiliation(s)
- Suha Abu Khalaf
- University of Missouri, Division of Infectious Diseases, Columbia, MO, USA
| | - Paragkumar Patel
- University of Missouri, Division of Infectious Diseases, Columbia, MO, USA
| | - Carla R Caruso
- University of Missouri, Department of Pathology and Anatomical Sciences, Columbia, MO, USA
| | - Timothy Parrett
- University of Missouri, Department of Pathology and Anatomical Sciences, Columbia, MO, USA
| | - Andres Bran
- University of Missouri, Division of Infectious Diseases, Columbia, MO, USA
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Philips CA, Rela M, Soin AS, Gupta S, Surendran S, Augustine P. Critical Update on the Diagnosis and Management of COVID-19 in Advanced Cirrhosis and Liver Transplant Recipients. J Clin Transl Hepatol 2021; 9:947-959. [PMID: 34966658 PMCID: PMC8666374 DOI: 10.14218/jcth.2021.00228] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/15/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
The novel coronavirus disease 2019 (COVID-19) pandemic has impacted health care worldwide, with specific patient populations, such as those with diabetes, cardiovascular disease, and chronic lung disease, at higher risk of infection and others at higher risk of disease progression. Patients with decompensated cirrhosis fall into the latter category and are a unique group that require specific treatment and management decisions because they can develop acute-on-chronic liver failure. In liver transplant recipients, the atypical immunity profile due to immunosuppression protects against downstream inflammatory responses triggered by COVID-19. This exhaustive review discusses the outcomes associated with COVID-19 in patients with advanced cirrhosis and in liver transplant recipients. We focus on the immunopathogenesis of COVID-19, its correlation with the pathogenesis of advanced liver disease, and the effect of immunosuppression in liver transplant recipients to provide insight into the outcomes of this unique patient population.
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Affiliation(s)
- Cyriac Abby Philips
- Department of Clinical and Translational Hepatology and The Monarch Liver Laboratory, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva, Kerala, India
| | - Mohamed Rela
- Institute of Liver Disease and Liver Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Arvinder Singh Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Gurgaon, India
| | - Subhash Gupta
- Max Centre for Liver and Biliary Sciences, Max Saket Hospital, New Delhi, India
| | - Sudhindran Surendran
- Gastrointestinal Surgery and Solid Organ Transplantation, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Philip Augustine
- Gastroenterology and Advanced GI Endoscopy, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva, Kerala, India
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50
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Arya P, Kumar U, Sharma S, Durgappa M, Guleria A, Raj R, Pande G, Kumar D. Targeted NMR-based serum metabolic profiling of serine, glycine and methionine in acute-on-chronic liver failure patients: Possible insights into mitochondrial dysfunction. ANALYTICAL SCIENCE ADVANCES 2021; 2:536-545. [PMID: 38715854 PMCID: PMC10989557 DOI: 10.1002/ansa.202000167] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 05/18/2021] [Accepted: 05/30/2021] [Indexed: 06/11/2024]
Abstract
Background A recent study based on blood metabolomics analysis revealed inflammation-associated mitochondrial dysfunction as a potential mechanism underlying acute-on-chronic liver failure (ACLF) in cirrhotic patients. Serine, glycine, and methionine serve to maintain a healthy immune system and adequately sustain mitochondrial functionality in hepatocytes for regulating redox homeostasis through the production of antioxidant glutathione (GSH). Based on this, we hypothesized that the circulatory levels of serine, glycine and methionine will be altered in ACLF patients due to acute worsening of hepatic function and may provide novel insights into the mitochondrial dysfunction as well. Methods The circulatory concentrations of serine, glycine, and methionine were estimated in the sera of 40 ACLF patients and 49 normal controls (NC) subject using 1D 1H-CPMG NMR spectra recorded at 800 MHz NMR spectrometer. The resulting metabolite concentrations were compared using unpaired Student t-test and p-value < 0.05 was considered as the criterion of statistical significance. The diagnostic potential and statistical correlations were established using receiver-operating-characteristic (ROC) curve analysis and Pearson-r method, respectively. Results Circulating levels of serine and glycine were significantly decreased in ACLF patients (Ser = 23.06 ± 1.67 µM and Gly = 83.11±7.52 µM) compared to NC subjects (Ser = 55.61 ± 2.28 µM and Gly = 156.9±7.16 µM) with p-value < 0.0001, whereas those of methionine were significantly increased in ACLF (22.60 ± 2.49 µM) compared to NC subjects (=14.63 ± 0.85 µM) with p-value < 0.0015. Further, the ROC analysis yielded satisfactory sensitivity and specificity for serine, glycine, and methionine-to-glycine ratio (MGR) with area under ROC (AUROC) curve values equal to: 0.95 [95%CI = 0.91-0.99] for Ser; 0.87 [95%CI = 0.79-0.95] for Gly; and 0.90 [95%CI = 0.83-0.97] for MGR. Conclusion Compared to NC subjects, the sera of ACLF patients were characterized by hypermethioninemia and aberrantly decreased levels of serine and glycine suggesting mitochondrial dysfunction as the possible mechanism for disturbed redox homeostasis and therefore depressed immune system in ACLF.
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Affiliation(s)
- Payal Arya
- Centre of Biomedical Research (CBMR)Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)LucknowUttar Pradesh226014India
| | - Umesh Kumar
- Centre of Biomedical Research (CBMR)Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)LucknowUttar Pradesh226014India
| | - Supriya Sharma
- Department of Surgical GastroenterologySanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)LucknowUttar Pradesh226014India
| | - Manjunath Durgappa
- Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)LucknowIndia
| | - Anupam Guleria
- Centre of Biomedical Research (CBMR)Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)LucknowUttar Pradesh226014India
| | - Ritu Raj
- Centre of Biomedical Research (CBMR)Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)LucknowUttar Pradesh226014India
| | - Gaurav Pande
- Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)LucknowIndia
| | - Dinesh Kumar
- Centre of Biomedical Research (CBMR)Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)LucknowUttar Pradesh226014India
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