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Silpa C, Alomar T, Wong RJ. Temporal Trends of Fungal Infections in Cirrhotic Patients: A Retrospective Cohort Study 2016-2020. J Clin Exp Hepatol 2025; 15:102469. [PMID: 39850933 PMCID: PMC11750545 DOI: 10.1016/j.jceh.2024.102469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 11/27/2024] [Indexed: 01/25/2025] Open
Abstract
Background Patients with cirrhosis are susceptible to infections due to abnormalities in humoral and cell-mediated immunity. Fungal infections are associated with delayed diagnosis and high mortality rates, emphasizing the importance of performing fungal cultures and maintaining elevated levels of suspicion in this patient population. Methods This retrospective cohort study analyzes cirrhotic patients readmitted with bacterial and fungal infections and investigates outcomes, including in-hospital mortality and hospital resource utilization. Data was acquired from the Nationwide Readmission Database (NRD) from 2016 to 2020. Total hospital costs were calculated using HCUP Cost-to-Charge Ratio files and adjusted for inflation based on the Consumer Price Index (CPI) for medical care services in the U.S., with 2020 as the reference year. The NRD dataset lacks details like ascitic fluid cell counts, antifungal/antibacterial drugs used, and treatment responses, limiting the clinical insights that can be derived. Results The study analyzed 393,195 index hospitalizations. Among these, 102,505 account for 30-day and 157,079 account for 90-day readmissions. The 30-day and 90-day readmissions for spontaneous bacterial peritonitis (SBP) are 8478 and 15,690 respectively. The 30-day and 90-day readmissions for spontaneous fungal peritonitis (SFP) are 3106 and 5798 respectively. The mean age of patients was 57.9 years (standard deviation between 57.7 and 58.1). The mean length of stay (LOS) for SBP at 30 days is 9.4 days, while SFP has ranged from 14.9 to 32.3 days for various fungal infections. Aspergilloses have the longest LOS among SFP. There is an increased rate of mortality as well as hospital charges with SFP compared to SBP (P < 0.001). The 30-day index admission total charges for SBP are $42,258 and SFP are $51,739. The 30-day readmission total charges for SBP are 64, 266 and for SFP 89,913. Conclusions There is increased mortality, LOS, and hospital costs for SFP compared to SBP. It is important to consider SFP in the diagnostic workup for patients who do not respond to antibiotics. Early recognition and administration of antifungals can be associated with improved outcomes.
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Affiliation(s)
- Choday Silpa
- Creighton University School of Medicine-Phoenix Health Sciences Campus, Phoenix, AZ, United States
| | - Talal Alomar
- Creighton University School of Medicine-Phoenix Health Sciences Campus, Phoenix, AZ, United States
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Gupta T, Saini A, Gaur V, Goel A. Comparative Study of Terlipressin and Noradrenaline as Vasopressors in Patients With Acute-on-chronic Liver Failure and Septic Shock: A Randomized Controlled Trial. J Clin Exp Hepatol 2025; 15:102494. [PMID: 39980577 PMCID: PMC11836504 DOI: 10.1016/j.jceh.2024.102494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 12/15/2024] [Indexed: 02/22/2025] Open
Abstract
BACKGROUND Sepsis is the most common acute insult in patients with acute-on-chronic liver failure (ACLF), and circulatory failure portends a poor prognosis in them. AIM This study aimed to compare terlipressin and noradrenaline as first-line vasopressors in patients with ACLF and septic shock. METHODS This prospective, open-label, randomized controlled study was conducted from January 2021 to June 2022 at a tertiary care center. All patients presenting with ACLF as per the chronic liver failure consortium acute on chronic liver failure in cirrhosis study and septic shock were screened. Shock was defined as a mean arterial pressure (MAP) <65 mmHg/systolic blood pressure <90 mmHg. Patients with septic shock nonresponsive to crystalloids/colloids were randomized to receive terlipressin (group I) at 2.6 μg/kg/min and noradrenaline (group II) at 0.1 μg/kg/min. The primary outcome was an MAP >65 mmHg at 6 h. The secondary outcomes were 3-, 7-, 14-, and 28-day mortality, duration of hospital stay, cumulative dose of drug, and new events such as upper gastrointestinal bleed, acute kidney injury, jaundice, and hepatic encephalopathy within 28 days. RESULTS A total of 70 patients were randomized to group I (n = 35) and group II (n = 35). According to per-protocol analysis, a higher number of patients achieved an MAP > 65 mmHg at 6 h in group II (n = 23/31, 74%) than in group I (5/34, 14%) (P < 0.001). The 3-and 7-day mortality was significantly higher in group I than in group II, with no difference at 14 and 28 days. The 28-day mortality was highest in ACLF grade-3 in both group II (22/25, 88%) and group I (15/20, 75%). CONCLUSION Terlipressin did not prove to be noninferior to norepinephrine, and therefore, norepinephrine should be the first-line vasopressor in ACLF patients with septic shock. The mortality rate was highest in ACLF grade-3 patients in both the groups, irrespective of the initial response to vasopressors. This indicates that holistic management of these patients is most important.
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Affiliation(s)
- Tarana Gupta
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
| | - Anjali Saini
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
| | - Vaibhav Gaur
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
| | - Ashank Goel
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
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Yuan S, Taozhu W, Liu J, Zhang W, Xu Q, Zhu Y, Xiang T, Wu X. High glycosylated serum protein to high density lipoprotein cholesterol ratios are predictive of worse acute on chronic liver failure prognoses. Sci Rep 2025; 15:14288. [PMID: 40274908 PMCID: PMC12022105 DOI: 10.1038/s41598-025-91779-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 02/24/2025] [Indexed: 04/26/2025] Open
Abstract
Hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) could result in disrupted glucose and lipid homeostasis, but its associations with ACLF is not fully defined. Here, we incorporated biomarkers associated with HBV-ACLF prognoses into a predictive nomogram, and examined its short- and long-term predictive capabilities. Eight hundred sixty-one HBV-ACLF, 20 healthy, and 54 chronic hepatitis B (CH) patients were recruited; the 4 characteristics most strongly associated with HBV-ACLF prognoses (age, glycosylated serum protein [GSP], high-density lipoprotein cholesterol [HDL-c], international normalized ratio), identified by logistic regression (uni-, multivariate) and machine-learning based analyses, were incorporated into the predictive nomogram. The nomogram was, under receiver operating characteristic and calibration curve analyses, highly accurate in identifying ACLF patients with worse prognoses after 28- and 90-days; it also demonstrated good clinical utility under decision curve analysis. Furthermore, higher GSP/HDL-c (GHR) was associated with worse ACLF prognoses, plus higher 28- and 90-day cumulative risk of death under Kaplan-Meier analysis. Therefore, the nomogram was able to accurately identify ACLF patients, who also had high GHR, at high risk for adverse prognosis; consequently, both glucose and lipid metabolism indicators are equally important for determining ACLF prognoses, and could serve as valuable early diagnostic tools for tailored ACLF interventions.
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Affiliation(s)
- Songsong Yuan
- Jiangxi Medical Center for Critical Public Health Events, Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, People's Republic of China
| | - Wen Taozhu
- Jiangxi Medical Center for Critical Public Health Events, Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, People's Republic of China
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Juan Liu
- Jiangxi Medical Center for Critical Public Health Events, Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, People's Republic of China
| | - Wenfeng Zhang
- Jiangxi Medical Center for Critical Public Health Events, Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, People's Republic of China
| | - Qinglang Xu
- Jiangxi Medical Center for Critical Public Health Events, Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, People's Republic of China
| | - Ying Zhu
- Jiangxi Medical Center for Critical Public Health Events, Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, People's Republic of China
| | - Tianxin Xiang
- Jiangxi Medical Center for Critical Public Health Events, Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, People's Republic of China.
| | - Xiaoping Wu
- Jiangxi Medical Center for Critical Public Health Events, Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, People's Republic of China.
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Tatour M, Zuckerman E, Abu-Freha N, Hazzan R. Risk of hepatocellular carcinoma and cirrhosis decompensation in a large retrospective cohort of cirrhotic patients with autoimmune hepatitis. Sci Rep 2025; 15:13212. [PMID: 40240433 PMCID: PMC12003704 DOI: 10.1038/s41598-025-96342-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Accepted: 03/27/2025] [Indexed: 04/18/2025] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can lead to cirrhosis in up to 30% of patients. Cirrhotic patients are at risk of high morbidity and mortality due to cirrhosis decompensation and hepatocellular carcinoma (HCC). This retrospective study assessed the rates of decompensated cirrhosis and HCC in patients with AIH-related cirrhosis. A total of 774 AIH patients were included, with 40% developing cirrhosis. Over a median follow-up of 8.2 years (IQR 2.9-12.3), the annual incidence of decompensated cirrhosis was 4.25%, with a mean time of 8.2 years from cirrhosis diagnosis to decompensation. Nineteen cirrhotic patients (6.2%) developed HCC, with a yearly incidence rate of 0.63%. Most HCC cases occurred within the first years of cirrhosis diagnosis. The rate of decompensated cirrhosis in AIH patients was lower than in other cirrhotic liver diseases, suggesting AIH may follow a different clinical course. The annual incidence of HCC was also significantly lower than the threshold for HCC surveillance. This indicates the need to reassess current surveillance guidelines, particularly in the late years following a cirrhosis diagnosis.
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Affiliation(s)
- Mifleh Tatour
- Clalit Health Services, Northern Region, Tel Aviv, Israel.
- Department of Family Medicine, Clalit Health Services, Afula, Israel.
| | - Eli Zuckerman
- Institute of Liver Diseases, Lady Davis Carmel Medical Center, Haifa, Israel
- Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel
| | - Naim Abu-Freha
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer-Sheva, Israel
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Rawi Hazzan
- Clalit Health Services, Northern Region, Tel Aviv, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
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Gasperment M, Duhaut L, Terzi N, Gerard C, Haudebourg L, Demoule A, Randrianarisoa M, Castelain V, Sarfati S, Tamion F, Moal CL, Guitton C, Preda G, Galbois A, Vieille T, Piton G, Rudler M, Dumas G, Ait-Oufella H. Alcohol related hepatitis in intensive care units: clinical and biological spectrum and mortality risk factors: a multicenter retrospective study. Ann Intensive Care 2025; 15:53. [PMID: 40229464 PMCID: PMC11996726 DOI: 10.1186/s13613-025-01450-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 02/20/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND Alcohol related hepatitis is responsible for high morbidity and mortality, but little is known about the management of patients with hepatitis specifically in intensive care units (ICU). METHODS Retrospective study including patients with alcohol related hepatitis hospitalized in 9 French ICUs (2006-2017). Alcohol related hepatitis was defined histologically or by an association of clinical and biological criteria according to current guidelines. RESULTS 187 patients (median age: 53 [43-60]; male: 69%) were included. A liver biopsy was performed in 51% of cases. Patients were admitted for impaired consciousness (71%), sepsis (64%), shock (44%), respiratory failure (37%). At admission, median SOFA and MELD scores were 10 [7-13] and 31 [26-40] respectively. 63% of patients received invasive mechanical ventilation, 62% vasopressors, and 36% renal replacement therapy. 66% of patients received corticosteroids, and liver transplantation was performed in 16 patients (8.5%). ICU and in-hospital mortality were 37% and 53% respectively. By multivariate analysis, ICU mortality was associated with SOFA score (without total bilirubin) (SHR 1.08 [1.02-1.14] per one-point increase), arterial lactate (SHR 1.08 [1.03-1.13] per 1 mmol/L) and MELD score (SHR 1.09 [1.04-1.14] per 1 point), while employment was associated with increased survival (HR 0.49 [0.28-0.86]). After propensity score weighting, the use of corticosteroids did not affect ICU mortality in the overall population but had a beneficial effect in the subgroup of patients with histological proof. Patient prognosis was also better in responders assessed by Lille score at day 7 (OR 6.67 [2.44-20.15], p < 0.001). CONCLUSION Alcohol related hepatitis is a severe condition leading to high mortality in ICU patients. Severity of organ failure at admission are mortality risk factors. Outcome was significantly better in responders to corticosteroids therapy according to Lille score. Early referral to tertiary centers to discuss liver transplantation should more widely be considered.
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Affiliation(s)
- Maxime Gasperment
- Service de Médecine Intensive-Réanimation, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 184 Rue du Faubourg Saint-Antoine, Paris Cedex 12, 75571, France
| | - Léa Duhaut
- Service d'Hépatologie, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris, Villejuif, France
| | - Nicolas Terzi
- Service de Médecine Intensive-Réanimation, CHU Grenoble Alpes, Université Grenoble-Alpes, Grenoble, France
| | - Côme Gerard
- Service de Médecine Intensive-Réanimation, CHU Grenoble Alpes, Université Grenoble-Alpes, Grenoble, France
| | - Luc Haudebourg
- Service de Médecine Intensive-Réanimation, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Alexandre Demoule
- Service de Médecine Intensive-Réanimation, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Mialy Randrianarisoa
- Service de Médecine Intensive-Réanimation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Vincent Castelain
- Service de Médecine Intensive-Réanimation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Sacha Sarfati
- Service de Médecine Intensive-Réanimation, Hôpital Charles Nicolle, Rouen, France
| | - Fabienne Tamion
- Service de Médecine Intensive-Réanimation, Hôpital Charles Nicolle, Rouen, France
| | - Charlene Le Moal
- Service de Réanimation médico-chirurgicale, Hôpital du Mans, Le Mans, France
| | - Christophe Guitton
- Service de Réanimation médico-chirurgicale, Hôpital du Mans, Le Mans, France
| | - Gabriel Preda
- Service de Médecine Intensive-Réanimation, Hôpital Delafontaine, Saint-Denis, France
| | - Arnaud Galbois
- Service de Réanimation polyvalente, Hôpital privé Claude Galien, Quincy Sous-Sénart, France
| | - Thibault Vieille
- Service de Médecine Intensive-Réanimation, Hôpital Universitaire de Besançon, Besançon, France
| | - Gaël Piton
- Service de Médecine Intensive-Réanimation, Hôpital Universitaire de Besançon, Besançon, France
| | - Marika Rudler
- Service d'Hépato-Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Guillaume Dumas
- Service de Médecine Intensive-Réanimation, CHU Grenoble Alpes, Université Grenoble-Alpes, Grenoble, France
| | - Hafid Ait-Oufella
- Service de Médecine Intensive-Réanimation, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 184 Rue du Faubourg Saint-Antoine, Paris Cedex 12, 75571, France.
- Sorbonne Université, Paris, France.
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Brar A, Garg A, Kohli I, Ravi S, Singh C, Sohal A, Alkotob ML. The Prevalence and Characteristics of Infective Endocarditis in Liver Transplant Recipients: Insights From National Inpatient Sample Database. Clin Cardiol 2025; 48:e70130. [PMID: 40223671 PMCID: PMC11995030 DOI: 10.1002/clc.70130] [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: 07/08/2024] [Revised: 02/01/2025] [Accepted: 03/18/2025] [Indexed: 04/15/2025] Open
Abstract
BACKGROUND Liver transplant (LT) recipients are immunocompromised and thus predisposed to various bacterial and fungal infections, including infective endocarditis (IE). The current paper aims to determine the prevalence, characteristics, and outcomes of IE in LT recipients. METHODS The National Inpatient Sample (NIS) data from 2016 to 2020 was used to identify LT recipients. Patients were separated into two groups based on the presence of IE. Information was collected on patient demographics, hospital characteristics, infections, comorbidities, and outcomes. Multivariate logistic regression was performed to assess the impact of IE on outcomes after adjusting for confounding factors. RESULTS A total of 170 650 patients who underwent LT were identified using NIS data from 2016 to 2020, of which 0.003% had IE. IE group had higher odds of in-hospital mortality [aOR 2.2 (95% CI 1.07-4.78)], Shock [aOR 2.7 (95% CI 1.61-4.65)], ICU admission [aOR 2.40 (95% CI 1.4-4.2)], longer Length of Stay [adj. Coeff- 3.4 days (95% CI -0.89-5.9, p < 0.008)], and higher hospitalization charges (adj. coeff-$65271.52, 95% CI $14 825-$115 718) than LT without IE group. CONCLUSION Staphylococcus was present in 18.6% of IE in LT, followed by enterococcus (12.8%) and gram-negative bacteria (9.8%). Concomitant IE was associated with increased in-hospital death, ICU stay, and shock. The IE group was also associated with increased LOS and total charges compared to the LT without IE. Although the prevalence of IE is low in LT recipients, its presence portends worse outcomes.
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Affiliation(s)
- Ajit Brar
- Department of Internal MedicineHurley Medical CenterFlintMichiganUSA
- Bloomberg School of Public HealthJohns Hopkins UniversityBaltimoreMarylandUSA
| | - Ayushi Garg
- Trident Medical CenterNorth CharlestonSouth CarolinaUSA
| | - Isha Kohli
- Graduate Program in Public Health, Icahn School of Medicine, Mount SinaiNew YorkNew YorkUSA
| | - Soumiya Ravi
- Department of Internal MedicineUniversity of ArizonaTucsonArizonaUSA
| | - Carol Singh
- Dayanand Medical College and HospitalLudhianaIndia
| | - Aalam Sohal
- Department of HepatologyLiver Institute NorthwestSeattleWashingtonUSA
| | - M Luay Alkotob
- Department of Internal Medicine, Division of CardiologyMichigan State University at Hurley Medical CenterFlintMichiganUSA
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Liu LN, Chang YF, Wang H. Correlations of three scoring systems with the prognosis of patients with liver cirrhosis complicated with sepsis syndrome. World J Gastrointest Surg 2025; 17:99570. [PMID: 40162414 PMCID: PMC11948096 DOI: 10.4240/wjgs.v17.i3.99570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/02/2024] [Accepted: 01/16/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Severe symptoms associated with sepsis syndrome (SS) are considered a severe threat, which not only increases therapeutic difficulty but also causes a prognostic mortality rate. However, at present, few related studies focused on the application of different score scales for disease and prognosis assessment in liver cirrhosis (LC) complicated with SS. AIM To determine the correlations of the model for end-stage liver disease (MELD), sequential organ failure assessment (SOFA), and modified early warning score (MEWS) points with the prognosis of patients with LC complicated with SS. METHODS This retrospective analysis included 426 LC cases from February 2019 to April 2022. Of them, 225 cases that were complicated with SS were assigned to the LC + SS group, and 201 simple LC cases were included in the LC group. Intergroup differences in MELD, SOFA, and MEWS scores were compared, as well as their diagnostic value for LC + SS. The correlations of the three scores with the prognosis of patients with LC + SS were further analyzed, as well as the related risk factors affecting patients' outcomes, after the follow-up investigation. RESULTS MELD, SOFA, and MEWS scores were all higher in the LC + SS group vs the LC group, and their combined assessment for LC + SS revealed a diagnostic sensitivity and a specificity of 89.66% and 90.84%, respectively (P < 0.05). The LC + SS group reported 58 deaths, with an overall mortality rate of 25.78%. Deceased patients presented higher MELD, SOFA, and MEWS points than those who survived (P < 0.05). MELD, SOFA, and MEWS scores were determined by COX analysis as factors independently affecting the prognosis of patients with LC + SS (P < 0.05). CONCLUSION MELD, SOFA, and MEWS effectively diagnosed LC in patients complicated with SS, and they demonstrated great significance in assessing prognosis, which provides a reliable prognosis guarantee for patients with LC + SS. However, their assessment effects remain limited, which is worthy of further investigation by more in-depth and rigorous experimental analysis.
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Affiliation(s)
- Li-Nan Liu
- Department of Emergency, Beijing Ditan Hospital Capital Medical University, Beijing 100102, China
| | - Yu-Fei Chang
- Department of Emergency, Beijing Ditan Hospital Capital Medical University, Beijing 100102, China
| | - Hui Wang
- Department of Emergency, Beijing Ditan Hospital Capital Medical University, Beijing 100102, China
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Torre A, Córdova-Gallardo J, Martínez-Sánchez FD. Hepatic encephalopathy: risk identification and prophylaxis approaches. Metab Brain Dis 2025; 40:138. [PMID: 40053146 DOI: 10.1007/s11011-025-01531-y] [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: 08/12/2024] [Accepted: 01/08/2025] [Indexed: 03/26/2025]
Abstract
Hepatic encephalopathy (HE) is a debilitating neurological condition associated with cirrhosis, characterized by cognitive impairment ranging from minimal to overt symptoms. It significantly impacts patients' quality of life and substantially burdens healthcare systems. This review examines current prophylactic strategies for HE, focusing on established treatments, emerging therapies, and predictive tools to identify high-risk patients. Traditional treatments such as lactulose and rifaximin remain the cornerstone of HE management, effectively reducing ammonia levels and preventing recurrence. However, novel approaches like L-ornithine L-aspartate, albumin infusions, and antioxidants like resveratrol show promise in further improving outcomes by addressing underlying pathophysiological mechanisms, including systemic inflammation and gut dysbiosis. Developing predictive models, such as the AMMON-OHE score and clinical-genetic risk assessments, enhances the ability to tailor preventive interventions to individual patient profiles. These advancements are crucial in mitigating the incidence of overt HE, reducing hospital admissions, and improving patient survival rates. The future of HE management lies in personalized medicine, targeting specific inflammatory and metabolic pathways, with the potential integration of genetic manipulation. Continued research is essential to refine these strategies, ultimately aiming to improve the prognosis and quality of life for cirrhotic patients at risk of HE.
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Affiliation(s)
- Aldo Torre
- Metabolic Unit, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubiran", Vasco de Quiroga 15, Belisario Domínguez Secc 16, Tlalpan, Ciudad de México, 14080, Mexico.
- Department of Gastroenterology, Medical Center ABC, Sur 136 116, Las Américas, Álvaro Obregón, 01120, Ciudad de México, Mexico.
| | - Jacqueline Córdova-Gallardo
- Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Escolar 411A, Copilco Universidad, Coyoacán, Ciudad de México, 04360, Mexico.
- Department of Hepatology, Hospital General "Dr. Manuel Gea González", Calz. de Tlalpan 4800, Belisario Domínguez Secc 16, Tlalpan, Ciudad de México, 14080, Mexico.
| | - Froylan David Martínez-Sánchez
- Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Escolar 411A, Copilco Universidad, Coyoacán, Ciudad de México, 04360, Mexico
- Department of Internal Medicine, Hospital General "Dr. Manuel Gea González", 14080 Mexico City, Mexico. Calz. de Tlalpan 4800, Belisario Domínguez Secc 16, Tlalpan, 14080, Ciudad de México, Mexico
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Piano S, Mahmud N, Caraceni P, Tonon M, Mookerjee RP. Mechanisms and treatment approaches for ACLF. Liver Int 2025; 45:e15733. [PMID: 37715608 PMCID: PMC12036731 DOI: 10.1111/liv.15733] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 08/03/2023] [Accepted: 09/02/2023] [Indexed: 09/17/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by decompensation of cirrhosis, severe systemic inflammation and organ failures. ACLF is frequently triggered by intra- and/or extrahepatic insults, such as bacterial infections, alcohol-related hepatitis or flares of hepatic viruses. The imbalance between systemic inflammation and immune tolerance causes organ failures through the following mechanisms: (i) direct damage of immune cells/mediators; (ii) worsening of circulatory dysfunction resulting in organ hypoperfusion and (iii) metabolic alterations with prioritization of energetic substrates for inflammation and peripheral organ 'energetic crisis'. Currently, the management of ACLF includes the support of organ failures, the identification and treatment of precipitating factors and expedited assessment for liver transplantation (LT). Early LT should be considered in patients with ACLF grade 3, who are unlikely to recover with the available treatments and have a mortality rate > 70% at 28 days. However, the selection of transplant candidates and their prioritization on the LT waiting list need standardization. Future challenges in the ACLF field include a better understanding of pathophysiological mechanisms leading to inflammation and organ failures, the development of specific treatments for the disease and personalized treatment approaches. Herein, we reviewed the current knowledge and future perspectives on mechanisms and treatment of ACLF.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine –DIMED, University and Hospital of Padova, Padova, Italy
| | - Nadim Mahmud
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Leonard Davis Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Unit of Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Marta Tonon
- Unit of Internal Medicine and Hepatology, Department of Medicine –DIMED, University and Hospital of Padova, Padova, Italy
| | - Rajeshwar Prosad Mookerjee
- Institute for Liver and Digestive Health, University College London, London, UK
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus C, Denmark
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10
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McGettigan B, Hernandez-Tejero M, Malhi H, Shah V. Immune Dysfunction and Infection Risk in Advanced Liver Disease. Gastroenterology 2025:S0016-5085(24)05694-4. [PMID: 39927926 DOI: 10.1053/j.gastro.2024.08.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 08/21/2024] [Accepted: 08/22/2024] [Indexed: 02/11/2025]
Abstract
The risk of microbial infections is increased in cirrhosis and other forms of advanced liver disease such as alcohol-associated hepatitis. Such infections may precipitate new or further decompensation and death, especially in patients with clinical features of acute-on-chronic liver failure. The severe immune dysfunction or "immune paralysis" caused by advanced liver disease is associated with high short-term mortality. However, the pathogenic mechanisms underlying immune dysfunction and immunodeficiency are incompletely understood. Evidence to date suggests a complex, dynamic process that perturbs the physiological roles of the liver as a master regulator of systemic immunity and protector against noxious effects of exogenous molecules in the portal vein flowing from the gut. Thus, in cirrhosis and severe alcohol-associated hepatitis, the ability of hepatocytes and intrahepatic immune cells to balance normal context-dependent dichotomous responses of tolerance vs immune activation is lost. Contributing factors include loss of the gut barrier with translocation of microbial products through the portal vein, culminating in development of functional defects in innate and adaptive immune cells, and generation of immune-regulatory myeloid cells that permit microbial colonization and infection. This review addresses key evidence supporting the paradigm of immune dysfunction as a risk for microbial infections and identifies potential therapeutic targets for intervention. The primary focus is on cirrhosis-associated immune dysfunction and alcohol-associated liver disease, because the bulk of available data are from these 2 conditions.
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Affiliation(s)
- Brett McGettigan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Maria Hernandez-Tejero
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Harmeet Malhi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Vijay Shah
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
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11
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Li B, Dai Y, Cai W, Sun M, Sun J. Monitoring of perioperative tissue perfusion and impact on patient outcomes. J Cardiothorac Surg 2025; 20:100. [PMID: 39871284 PMCID: PMC11771054 DOI: 10.1186/s13019-025-03353-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 01/19/2025] [Indexed: 01/29/2025] Open
Abstract
Monitoring perioperative tissue perfusion is crucial in clinical anesthesia to protect organs and ensure patient safety. Indicators like hemodynamic parameters, tissue metabolism, and microcirculation markers are used for assessment. Studies show intraoperative hypotension negatively impacts outcomes, though blood pressure alone may not reflect tissue perfusion accurately. Cardiac output is a more direct measure, with adequate levels generally indicating good perfusion. However, some conditions cause adequate cardiac output but inadequate perfusion. Non-quantitative markers like skin color and temperature, and quantitative indicators like tissue oxygen saturation and laser Doppler flowmetry, help assess microcirculation but can't fully evaluate systemic perfusion. Near-Infrared Spectroscopy (NIRS) monitors tissue oxygen metabolism, reflecting oxygen supply and consumption balance. Central venous oxygen saturation offers a better systemic overview but may not always indicate good perfusion, especially in sepsis. Lactic acid levels closely correlate with tissue perfusion and outcomes, with dynamic changes being more indicative than single measurements. Effective monitoring requires evaluating both macro- and microcirculation states and systemic metabolic levels to ensure optimal outcomes. Combining these measures provides a more accurate assessment of tissue perfusion and patient prognosis.
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Affiliation(s)
- Bin Li
- Department of Anesthesiology, Zhongda hospital, Southeast University, No. 87 Dingjiaqiao, Nanjing City, 210009, Jiangsu Province, China
| | - Yuchen Dai
- Southeast University School of Medicine, No. 87 Dingjiaqiao, Nanjing City, 210009, Jiangsu Province, China
| | - Wenlan Cai
- Southeast University School of Medicine, No. 87 Dingjiaqiao, Nanjing City, 210009, Jiangsu Province, China
| | - Menghan Sun
- Department of Anesthesiology, Zhongda hospital, Southeast University, No. 87 Dingjiaqiao, Nanjing City, 210009, Jiangsu Province, China
| | - Jie Sun
- Department of Anesthesiology, Zhongda hospital, Southeast University, No. 87 Dingjiaqiao, Nanjing City, 210009, Jiangsu Province, China.
- Southeast University School of Medicine, No. 87 Dingjiaqiao, Nanjing City, 210009, Jiangsu Province, China.
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12
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Li Y, Niu B, Liu J, Zhou H, Chen Z, Zhou Y, Wei Q, Jiao X, Mi Y, Li P. Bacterial infection adversely increases the risk of decompensation in patients with hepatitis B virus-related compensated cirrhosis: a retrospective study. BMC Infect Dis 2024; 24:1446. [PMID: 39695967 DOI: 10.1186/s12879-024-10306-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 12/04/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Hepatitis B virus related compensated cirrhosis generally has a favorable prognosis until decompensation occurs. Bacterial infections are prevalent in Hepatitis B virus related decompensated cirrhosis.Bacterial infection and decompensated hepatitis B cirrhosis are mutually reinforcing. And it also interacts with and promotes certain decompensation-related events. However, the impact of bacterial infections on the progression from compensated to decompensated cirrhosis in Hepatitis B patients remains unclear. METHODS We retrospectively analyzed the baseline characteristics of 1,011 patients with Hepatitis B virus related compensated cirrhosis. Using time-dependent regression analysis, we evaluated whether bacterial infections increase the risk of decompensation, defined as the occurrence of ascites, hepatic encephalopathy, or variceal bleeding. RESULTS A total of 1,011 patients were retrospectively analyzed over a median follow-up period of 79 months. Bacterial infections were observed in 89 patients (8.8%). Respiratory and urinary tract infections were the most common bacterial infections.Decompensation occurred in 44.9% of patients with bacterial infections, compared to 9% of those without BIs. Patients with bacterial infections had a higher risk of decompensation ([OR] 1.024; 95% CI 1.016-1.032; p < 0.001) than those without bacterial infections. CONCLUSION Our findings suggest that bacterial infections have a significant impact on the progression of hepatitis B virus related compensated cirrhosis, notably increasing the risk of decompensation.
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Affiliation(s)
- Yinglun Li
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Bin Niu
- Department of Infectious Diseases, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Jing Liu
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Hui Zhou
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Ze Chen
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Yibing Zhou
- Department of Scientific Research, Central Laboratory, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, Changshu, 215500, China
| | - Qian Wei
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Xue Jiao
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
- Clinical School of the Second People's Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuqiang Mi
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
- Tianjin Research Institute of Liver Diseases, Tianjin, China
| | - Ping Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China.
- Tianjin Research Institute of Liver Diseases, Tianjin, China.
- Second Department of Integrated Traditional Chinese and Western Medicine, Tianjin Second People's Hospital, Tianjin, China.
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13
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Girish V, Maiwall R. Revisiting septic shock in cirrhosis: a call for personalized management. Expert Rev Gastroenterol Hepatol 2024; 18:795-813. [PMID: 39744868 DOI: 10.1080/17474124.2024.2443813] [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: 09/24/2024] [Accepted: 12/14/2024] [Indexed: 01/12/2025]
Abstract
INTRODUCTION Patients with cirrhosis are known to be prone to infections. Infections can trigger organ failures and decompensations in cirrhosis. Septic shock can increase mortality by fourfold and cause hemodynamic imbalances, adding to the already hyperdynamic circulation. Management of septic shock in cirrhosis can be tricky due to this complex interplay of altered hemodynamics, immune function, and coagulation. AREAS COVERED In this review, we explore the pathophysiological basis, screening, monitoring and management of septic shock in cirrhosis. We also explore novel biomarkers, the growing challenge of multidrug-resistant pathogens and novel and adjunctive therapies. Finally, we propose an algorithm for the management of septic shock in cirrhosis. We conducted a comprehensive search of electronic databases such as PubMed, Web of Science, and Cochrane Library using the keywords and MeSH terms like 'septic shock,' 'cirrhosis,' 'liver disease,' 'sepsis' among others. The search was restricted to peer-reviewed articles in English. EXPERT OPINION The difficulties in managing septic shock in cirrhosis are discussed, emphasizing personalized approaches over protocol-driven care. Fluid and vasopressor management, antibiotic timing and selection, the role of adjunctive therapies, the importance of lactate clearance, gut failure, and the need for further research in this population are highlighted.
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Affiliation(s)
- Vishnu Girish
- Department of Hepatology, Institute of liver and biliary sciences, Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of liver and biliary sciences, Delhi, India
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14
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Rodríguez-Negrete EV, Gálvez-Martínez M, Sánchez-Reyes K, Fajardo-Felix CF, Pérez-Reséndiz KE, Madrigal-Santillán EO, Morales-González Á, Morales-González JA. Liver Cirrhosis: The Immunocompromised State. J Clin Med 2024; 13:5582. [PMID: 39337069 PMCID: PMC11432654 DOI: 10.3390/jcm13185582] [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: 07/26/2024] [Revised: 09/11/2024] [Accepted: 09/17/2024] [Indexed: 09/30/2024] Open
Abstract
Systemic inflammation and immunodeficiency are important components of cirrhosis-associated immune dysfunction (CAID), the severity of which is dynamic, progressive, and associated with the greater deterioration of liver function. Two inflammation phenotypes have been described: low-grade and high-grade systemic inflammation. Both of these phenotypes are related to liver cirrhosis function; thus, high-grade inflammation is correlated with the severity of hepatic insufficiency, bacterial translocation, and organic insufficiency, with which the risk of infections increases and the prognosis worsens. Bacterial translocation (BT) plays a relevant role in persistent systemic inflammation in patients with cirrhosis, and the prophylactic employment of antibiotics is useful for reducing events of infection and mortality.
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Affiliation(s)
- Elda Victoria Rodríguez-Negrete
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico; (E.V.R.-N.); (M.G.-M.); (C.F.F.-F.); (K.E.P.-R.)
- Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico;
| | - Marisol Gálvez-Martínez
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico; (E.V.R.-N.); (M.G.-M.); (C.F.F.-F.); (K.E.P.-R.)
| | - Karina Sánchez-Reyes
- Servicio de Cirugía General, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico;
| | - Carlos Fernando Fajardo-Felix
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico; (E.V.R.-N.); (M.G.-M.); (C.F.F.-F.); (K.E.P.-R.)
| | - Karla Erika Pérez-Reséndiz
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico; (E.V.R.-N.); (M.G.-M.); (C.F.F.-F.); (K.E.P.-R.)
| | | | - Ángel Morales-González
- Escuela Superior de Cómputo, Instituto Politécnico Nacional, Unidad Profesional “A. López Mateos”, Ciudad de México 07738, Mexico
| | - José Antonio Morales-González
- Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico;
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15
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Terbah R, Koshy AN, Majumdar A, Vaz K, Testro A, Sinclair M. Long-Term Continuous Terlipressin Infusion Improves Cardiac Reserve in Patients With Decompensated Cirrhosis. Clin Gastroenterol Hepatol 2024:S1542-3565(24)00778-X. [PMID: 39209185 DOI: 10.1016/j.cgh.2024.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 08/06/2024] [Accepted: 08/13/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND AND AIMS Cardiac dysfunction is a key factor in the pathogenesis of hepatorenal syndrome, for which terlipressin is the recommended first-line treatment. This study investigates whether long-term terlipressin can ameliorate the subclinical cardiac dysfunction observed in decompensated cirrhosis. METHODS Twenty-two patients with decompensated cirrhosis and ascites enrolled in a prospective study of home continuous terlipressin infusion were included. Cardiac function was assessed using dobutamine stress echocardiogram before and after 12 weeks of terlipressin. The primary outcome was the impact of terlipressin on cardiac reserve, the change in cardiac output (CO) in response to stress. RESULTS The median age was 61 years (interquartile range, 56-64 years), the median Model for End-Stage Liver Disease score was 15 (interquartile range, 12.3-17.0), and 72.7% were male. The increase in CO in response to low-dose dobutamine was significantly higher following terlipressin (↑4.0 L/min [↑57.8%]) as compared with baseline (↑1.8 L/min [21.3%]) (P = .0001). The proportion of patients with impaired cardiac reserve (defined by ΔCO <25% after low-dose dobutamine) reduced from 81.8% at baseline to 40.9% after terlipressin, (P = .02), driven primarily by improvement in inotropic function. Resting CO decreased significantly after terlipressin from 8.9 ± 2.2 L/min to 7.2 ± 1.8 L/min (normal range 5-6 L/min) (P < .001), due to a decrease in stroke volume from 108 to 86 mL/beat (P = .006). CONCLUSIONS Long-term continuous terlipressin infusion resulted in a significant increase in cardiac reserve and attenuation of the hyperdynamic state usually observed in decompensated cirrhosis. These data provide important mechanistic insight into the pathogenesis and reversibility of cardiac dysfunction in cirrhosis. Future studies are required to evaluate whether long-term terlipressin can prevent hepatic decompensating events such as hepatorenal syndrome in high-risk individuals. Australian New Zealand Clinical Trials Registry, Number: ACTRN12619000891123.
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Affiliation(s)
- Ryma Terbah
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia
| | - Anoop N Koshy
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia; Department of Cardiology, Austin Health, Heidelberg, Australia
| | - Avik Majumdar
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia
| | - Karl Vaz
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia
| | - Adam Testro
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia
| | - Marie Sinclair
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia.
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16
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Batra N, Gaidhane SA, Kumar S, Acharya S. Outcome Predictors of Acute-on-Chronic Liver Failure: A Narrative Review. Cureus 2024; 16:e61655. [PMID: 38966452 PMCID: PMC11223737 DOI: 10.7759/cureus.61655] [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: 03/02/2024] [Accepted: 06/04/2024] [Indexed: 07/06/2024] Open
Abstract
Complications of acute-on-chronic liver failure (ACLF) include increased short-term mortality. Extrahepatic organ failures result from chronic liver disease and acute hepatic injury. This combination characterizes end-stage liver disease. Its rapid progression makes it challenging for hepatologists and intensivists to treat. The varied definitions of this condition lead to varied clinical presentations. Hepatic or extrahepatic failures are more prevalent in chronic hepatitis B or cirrhosis patients who receive an additional injury. Numerous intensity parameters and prognosis ratings, including those for hepatitis B virus (HBV), have been developed and verified for various patients and causes of the disease. Liver regeneration, liver transplantation (LT), or antiviral therapy for HBV-related ACLF are the main treatment aims for various organ failures. LT is the best treatment for HBV-ACLF. In some HBV-related ACLF patients, nucleos(t)ide analogs and artificial liver assistance may enhance survival. Combining epidemiological and clinical studies, this review updates our understanding of HBV-ACLF's definition, diagnosis, epidemiology, etiology, therapy, and prognosis.
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Affiliation(s)
- Nitish Batra
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Shilpa A Gaidhane
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sunil Kumar
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sourya Acharya
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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17
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Lin HR, Liao QX, Lin XX, Zhou Y, Lin JD, Xiao XJ. Development of a nomogram for predicting in-hospital mortality in patients with liver cirrhosis and sepsis. Sci Rep 2024; 14:9759. [PMID: 38684696 PMCID: PMC11059344 DOI: 10.1038/s41598-024-60305-1] [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: 11/19/2023] [Accepted: 04/21/2024] [Indexed: 05/02/2024] Open
Abstract
In this study, we aimed to investigate the risk factors associated with in-hospital mortality in patients with cirrhosis and sepsis, establish and validate the nomogram. This retrospective study included patients diagnosed with liver cirrhosis and sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV). Models were compared by the area under the curve (AUC), integrated discriminant improvement (IDI), net reclassification index (NRI) and decision curve analysis (DCA). A total of 1,696 patients with cirrhosis and sepsis were included in the final cohort. Our final model included the following 9 variables: age, heartrate, total bilirubin (TBIL), glucose, sodium, anion gap (AG), fungal infections, mechanical ventilation, and vasopressin. The nomogram were constructed based on these variables. The AUC values of the nomograms were 0.805 (95% CI 0.776-0.833), which provided significantly higher discrimination compared to that of SOFA score [0.684 (95% CI 0.647-0.720)], MELD-Na [0.672 (95% CI 0.636-0.709)] and ABIC [0.674(95% CI 0.638-0.710)]. We established the first nomogram for predicting in-hospital mortality in patients with liver cirrhosis and sepsis based on these factors. This nomogram can performs well and facilitates clinicians to identify people at high risk of in-hospital mortality.
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Affiliation(s)
- Hai-Rong Lin
- Department of Intensive Care Unit, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China
- Department of Intensive Care Unit, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
| | - Qiu-Xia Liao
- Department of Intensive Care Unit, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China
- Department of Intensive Care Unit, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
| | - Xin-Xin Lin
- Department of Intensive Care Unit, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China
- Department of Intensive Care Unit, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
| | - Ye Zhou
- Department of Intensive Care Unit, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China
- Department of Intensive Care Unit, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
| | - Jian-Dong Lin
- Department of Intensive Care Unit, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China
- Department of Intensive Care Unit, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
| | - Xiong-Jian Xiao
- Department of Intensive Care Unit, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China.
- Department of Intensive Care Unit, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
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18
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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Xiang Z, Song Y, Liu J, Xu C, Zhou Z, Li J, Su R, Shu W, Lu Z, Wei X, Yang J, Yang Y, Zheng S, Xu X. Impact of preoperative infection on the outcomes of liver transplant recipients: a national propensity score-matched retrospective cohort study in China. Int J Surg 2024; 110:2196-2206. [PMID: 38285095 PMCID: PMC11019992 DOI: 10.1097/js9.0000000000001114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 01/09/2024] [Indexed: 01/30/2024]
Abstract
BACKGROUND Impact of preoperative infection on liver transplantation (LT) needs further investigation. MATERIALS AND METHODS From 1 January 2015 to 31 December 2022, 24 122 eligible patients receiving LT were enrolled from the China Liver Transplant Registry database. The outcomes of LT were compared after using the propensity score-matched analysis. RESULTS Compared to the noninfection group, patients in the infection group were more likely to have postoperative effusion, infection, abdominal bleeding, and biliary complications (all P <0.01), and they had shorter 30-day, 90-day survival, and overall survival (all P <0.01). Cox proportional hazards regression analysis revealed that MELD score and cold ischemia time were risk factors for the overall survival in the infection group (both P <0.05). Besides, compared to the nonpulmonary group, patients in the pulmonary group were more likely to have postoperative effusion and infection (both P <0.0001), and less likely to have postoperative abscess and early allograft dysfunction (both P <0.05). Patients in the nonabdominal group also had a higher proportion of postoperative infection than those in the abdominal group ( P <0.05). Furthermore, compared to the number=1 group, patients in the number ≥2 group were more prone to postoperative effusion and infection (both P <0.01), and they also had shorter 30-day and 90-day survival (both P <0.05). CONCLUSION Preoperative infection can result in a higher incidence of early postoperative complications and shorter survival in liver transplant recipients. The types and number of infection sites will also influence the prognosis of liver transplant recipients.
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Affiliation(s)
- Ze Xiang
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | - Yisu Song
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | - Jianrong Liu
- Surgical Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou
| | - Chenhao Xu
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | - Zhisheng Zhou
- National Center for Healthcare Quality Management in Liver Transplant
| | - Jiarui Li
- Zhejiang University School of Medicine
| | - Renyi Su
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | - Wenzhi Shu
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | - Zhengyang Lu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
| | | | - Jiayin Yang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center
| | - Shusen Zheng
- NHC Key Laboratory of Combined Multi-organ Transplantation
- National Center for Healthcare Quality Management in Liver Transplant
- Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou
| | - Xiao Xu
- Zhejiang University School of Medicine
- NHC Key Laboratory of Combined Multi-organ Transplantation
- National Center for Healthcare Quality Management in Liver Transplant
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20
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Sohal A, Kohli I, Chaudhry H, Singh I, Arora K, Kalra S, Dukovic D, Roytman M. Vaccine-Preventable Illness Leads to Adverse Outcomes in Liver Transplant Recipients. Dig Dis Sci 2024; 69:588-595. [PMID: 38030833 DOI: 10.1007/s10620-023-08202-x] [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: 07/24/2023] [Accepted: 11/19/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND Liver transplant recipients (LTR) and patients with chronic liver disease (CLD) are at an increased risk of infections. AIMS The objective of our study was to assess the incidence, and impact of vaccine preventable illness (VPI) on outcomes in LTR. METHODS National Inpatient Sample (NIS) 2016-2020 was used to identify adults (age > 18) hospitalized LTR using ICD-10 codes. Data were collected on patient demographics, hospital characteristics, etiology of liver disease, hepatic decompensations and outcomes. Patients were stratified into two groups based on the presence or absence of VPI. Multivariate logistic regression analysis was performed to identify the association between VPI and outcomes. RESULTS Out of 170,650 hospitalized LTR, 13.5% of the patients had VPI. The most common VPI was noted to be influenza (10.7%), followed by pneumococcal infection (2.7%). Incidence of mortality (6.9% vs. 1.6%, p < 0.001), ICU admissions (14.3% vs. 3.4%, p < 0.001), and acute kidney injury (AKI) (43.7% vs 37.35%, p < 0.001) was higher in the VPI group. CONCLUSION More than 13% of the LT hospitalizations had concomitant VPI. VPI in LTR was associated with worse outcomes. Our data suggests the need to identify factors associated with reduced vaccination rates and identify strategies to improve vaccination rates and responses in these patients.
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Affiliation(s)
- Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, 3216 NE 45Th Pl, Suite 212, Seattle, WA, 98105, USA.
| | - Isha Kohli
- Graduate Program in Public Health, Icahn School of Medicine, Mount Sinai, New York, NY, USA
| | - Hunza Chaudhry
- Department of Internal Medicine, University of California, San Francisco, Fresno, CA, USA
| | | | - Kirti Arora
- Dayanand Medical College and Hospital, Ludhiana, India
| | - Shivam Kalra
- Dayanand Medical College and Hospital, Ludhiana, India
| | - Dino Dukovic
- Ross University of Medical Sciences, Miramar, FL, USA
| | - Marina Roytman
- Department of Gastroenterology and Hepatology, University of California, San Francisco, Fresno, CA, USA
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21
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Chen Y, Yang L, Li X. Advances in Mesenchymal stem cells regulating macrophage polarization and treatment of sepsis-induced liver injury. Front Immunol 2023; 14:1238972. [PMID: 37954578 PMCID: PMC10634316 DOI: 10.3389/fimmu.2023.1238972] [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: 07/23/2023] [Accepted: 10/17/2023] [Indexed: 11/14/2023] Open
Abstract
Sepsis is a syndrome of dysregulated host response caused by infection, which leads to life-threatening organ dysfunction. It is a familiar reason of death in critically ill patients. Liver injury frequently occurs in septic patients, yet the development of targeted and effective treatment strategies remains a pressing challenge. Macrophages are essential parts of immunity system. M1 macrophages drive inflammation, whereas M2 macrophages possess anti-inflammatory properties and contribute to tissue repair processes. Mesenchymal stem cells (MSCs), known for their remarkable attributes including homing capabilities, immunomodulation, anti-inflammatory effects, and tissue regeneration potential, hold promise in enhancing the prognosis of sepsis-induced liver injury by harmonizing the delicate balance of M1/M2 macrophage polarization. This review discusses the mechanisms by which MSCs regulate macrophage polarization, alongside the signaling pathways involved, providing an idea for innovative directions in the treatment of sepsis-induced liver injury.
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Affiliation(s)
- Yuhao Chen
- Department of Emergency Medicine, West China Second Hospital of Sichuan University, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Sichuan, China
| | - Lihong Yang
- Department of Emergency Medicine, West China Second Hospital of Sichuan University, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Sichuan, China
| | - Xihong Li
- Department of Emergency Medicine, West China Second Hospital of Sichuan University, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Sichuan, China
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22
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Shang Y, Widman L, Ebrahimi F, Ludvigsson JF, Hagström H, Wester A. Risk of infections in non-alcoholic fatty liver disease: A nationwide population-based cohort study. Liver Int 2023; 43:2142-2152. [PMID: 37475642 DOI: 10.1111/liv.15680] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/07/2023] [Accepted: 07/09/2023] [Indexed: 07/22/2023]
Abstract
BACKGROUND AND AIMS Previous literature suggests an association between non-alcoholic fatty liver disease (NAFLD) and infections. We aimed to determine the rate and risk of severe infections in NAFLD compared to the general population. METHODS In this population-based cohort study, we used national registers to identify all patients with a hospital-based diagnosis of NAFLD in Sweden 1987-2020 (n = 14 869). The patients were matched with ≤10 comparators from the general population for age, sex, municipality, and calendar year (n = 137 145). Cox regression was used to estimate hazard ratios (HR) for infections in patients with NAFLD compared to comparators. Cumulative incidences were calculated while accounting for competing risks (non-infection death and liver transplantation). RESULTS Severe infections leading to death or hospitalization occurred in 1990 (13.4%) patients with NAFLD and 9899 (7.2%) comparators during a median of 4.5 and 6.1 years of follow-up, respectively. The rate of severe infections per 1000 person-years was higher in patients with NAFLD (21.0) than comparators (9.1) independently of components related to the metabolic syndrome (adjusted HR 1.9, 95% CI = 1.8-2.0). Infection-related mortality was also higher in NAFLD compared to comparators (adjusted HR 1.8, 95% CI = 1.6-2.2). The 10-year cumulative incidence of severe infections was 16.6% (95% CI = 15.8-17.4) in NAFLD and 8.0% (95% CI = 7.8-8.2) in comparators. CONCLUSION NAFLD was associated with severe infections and infection-related mortality, independently of components associated with the metabolic syndrome. Increased clinical vigilance of severe infections in NAFLD may diminish the risk of premature death.
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Affiliation(s)
- Ying Shang
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Linnea Widman
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Fahim Ebrahimi
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Gastroenterology and Hepatology, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Hannes Hagström
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
- Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden
| | - Axel Wester
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
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23
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Bai Z, Méndez-Sánchez N, Romeiro FG, Mancuso A, Philips CA, Tacke F, Basaranoglu M, Primignani M, Ibrahim M, Wong YJ, Nery FG, Teschke R, Ferreira CN, Muñoz AE, Pinyopornpanish K, Thevenot T, Singh SP, Mohanty A, Satapathy SK, Ridola L, Maruyama H, Cholongitas E, Levi Sandri GB, Yang L, Shalimar, Yang Y, Villa E, Krag A, Wong F, Jalan R, O’Brien A, Bernardi M, Qi X. Use of albumin infusion for cirrhosis-related complications: An international position statement. JHEP Rep 2023; 5:100785. [PMID: 37456673 PMCID: PMC10339261 DOI: 10.1016/j.jhepr.2023.100785] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 04/06/2023] [Accepted: 04/18/2023] [Indexed: 07/18/2023] Open
Abstract
BACKGROUND & AIMS Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. METHODS Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. RESULTS Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. CONCLUSIONS Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. IMPACT AND IMPLICATIONS Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion.
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Affiliation(s)
- Zhaohui Bai
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic and Foundation, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Andrea Mancuso
- Medicina Interna 1, Azienda di Rilievo Nazionale ad Alta Specializzazione Civico-Di Cristina-Benfratelli, Palermo, Italy
| | - Cyriac Abby Philips
- Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, India
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Metin Basaranoglu
- Division of Gastroenterology, Department of Internal Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Massimo Primignani
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Mostafa Ibrahim
- Department of Gastroenterology and Hepatology, Theodor Bilharz Research Institute, Cairo, Egypt
| | - Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Filipe Gaio Nery
- Serviço de Cuidados Intensivos, Unidade de Cuidados Intermédios Médico-Cirúrgica, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Germany
| | - Carlos Noronha Ferreira
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria-Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
| | - Alberto E. Muñoz
- Sección Hepatología, Hospital Dr. Carlos B. Udaondo. Ciudad Autónoma de Buenos Aires, Argentina
| | - Kanokwan Pinyopornpanish
- Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Thierry Thevenot
- Centre Hospitalier Universitaire de Besançon, Hôpital Jean Minjoz, Service d’Hépatologie et de Soins Intensifs Digestifs, Besançon, France
| | | | - Arpan Mohanty
- Section of Gastroenterology, Boston Medical Center, Boston, MA, USA
| | - Sanjaya K. Satapathy
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine for Hofstra/Northwell Health, Manhasset, New York, USA
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Hitoshi Maruyama
- Department of Gastroenterology, Juntendo University, Hongo, Bunkyo-ku, Tokyo, Japan
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Li Yang
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Yongping Yang
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Erica Villa
- Department of Gastroenterology, University of Modena & Reggio Emilia and Azienda Ospedaliero-Universitaria di Modena, Italy
| | - Aleksander Krag
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Florence Wong
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, University College London, London, UK
| | | | - Mauro Bernardi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - the Liver Cirrhosis-related Complications (LCC)-International Special Interest Group
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
- Liver Research Unit, Medica Sur Clinic and Foundation, National Autonomous University of Mexico, Mexico City, Mexico
- Internal Medicine Department, Botucatu Medical School, São Paulo, Brazil
- Medicina Interna 1, Azienda di Rilievo Nazionale ad Alta Specializzazione Civico-Di Cristina-Benfratelli, Palermo, Italy
- Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, India
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
- Division of Gastroenterology, Department of Internal Medicine, Bezmialem Vakif University, Istanbul, Turkey
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Gastroenterology and Hepatology, Theodor Bilharz Research Institute, Cairo, Egypt
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Serviço de Cuidados Intensivos, Unidade de Cuidados Intermédios Médico-Cirúrgica, Centro Hospitalar Universitário do Porto, Porto, Portugal
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Germany
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria-Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
- Sección Hepatología, Hospital Dr. Carlos B. Udaondo. Ciudad Autónoma de Buenos Aires, Argentina
- Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Centre Hospitalier Universitaire de Besançon, Hôpital Jean Minjoz, Service d’Hépatologie et de Soins Intensifs Digestifs, Besançon, France
- Kalinga Gastroenterology Foundation, Odisha, India
- Section of Gastroenterology, Boston Medical Center, Boston, MA, USA
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine for Hofstra/Northwell Health, Manhasset, New York, USA
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy
- Department of Gastroenterology, Juntendo University, Hongo, Bunkyo-ku, Tokyo, Japan
- First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Division of General Surgery and Liver Transplantation, San Camillo Hospital, Rome, Italy
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Department of Gastroenterology, University of Modena & Reggio Emilia and Azienda Ospedaliero-Universitaria di Modena, Italy
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, University College London, London, UK
- Division of Medicine, Royal Free Campus, London, UK
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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24
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Guimarães L, Piedade J, Duarte J, Baldin C, Victor L, Costa B, Veiga Z, Alcântara C, Fernandes F, Pereira G. Hepatic Encephalopathy in Cirrhotic Patients With Bacterial Infections: Frequency, Clinical Characteristics, and Prognostic Relevance. J Clin Exp Hepatol 2023; 13:559-567. [PMID: 37440943 PMCID: PMC10333941 DOI: 10.1016/j.jceh.2023.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 01/06/2023] [Indexed: 07/15/2023] Open
Abstract
Background/Objectives Bacterial infections (BIs) are well-recognized precipitants of hepatic encephalopathy (HE). Nevertheless, there is a paucity of data in patients with HE associated with BI. Our aim was to describe clinical characteristics, recurrence, and prognosis of HE in patients with BI. Methods A prospective study with inclusion of hospitalized cirrhotic patients with BI, followed until discharge, death, or liver transplantation. Results 172 patients (age 57 ± 13, model of end-stage liver disease [MELD]-sodium 22 ± 8) were included. Infections were more commonly due to spontaneous bacterial peritonitis and cellulitis (22% and 23%), non-nosocomial (70%), and associated with systemic inflammatory response syndrome and septic shock in 40% and 9%, respectively. HE was diagnosed in 66 patients (grade ≥2 in 58%). In multivariate analysis, MELD-sodium, albumin, and prior HE were associated with HE at diagnosis of BI. Recurrence of HE was diagnosed in 30 patients (median 13 [interquartile range 5-22] days), more commonly manifested as overt HE (90% vs. 60% at first episode, P = 0.012) and more frequently in patients with hyponatremia (54% vs. 27% for patients without, P < 0.001). In-hospital mortality was 34% and was more common for patients with HE (51% vs. 22%, P < 0.001), irrespective of grade, and for those with recurrence (63% vs. 42%, P < 0.001). In multivariate analysis, HE at diagnosis of infection and MELD-sodium were predictors of mortality. Conclusions HE is frequent in cirrhotic patients with BI and is associated with severity of liver disease, but not with infection. These patients are at increased risk of short-term HE recurrence, especially those with hyponatremia. The presence and recurrence of HE, independent of severity, are associated with in-hospital mortality.
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Affiliation(s)
- Lívia Guimarães
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital (Ministry of Health), Rio de Janeiro, Brazil
| | - Juliana Piedade
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital (Ministry of Health), Rio de Janeiro, Brazil
| | - Joana Duarte
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital (Ministry of Health), Rio de Janeiro, Brazil
| | - Caroline Baldin
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital (Ministry of Health), Rio de Janeiro, Brazil
| | - Lívia Victor
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital (Ministry of Health), Rio de Janeiro, Brazil
| | - Barbara Costa
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital (Ministry of Health), Rio de Janeiro, Brazil
| | - Zulane Veiga
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital (Ministry of Health), Rio de Janeiro, Brazil
| | - Camila Alcântara
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital (Ministry of Health), Rio de Janeiro, Brazil
| | - Flávia Fernandes
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital (Ministry of Health), Rio de Janeiro, Brazil
- Estácio de Sá University, School of Medicine (IDOMED), Rio de Janeiro, Brazil
| | - Gustavo Pereira
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital (Ministry of Health), Rio de Janeiro, Brazil
- Estácio de Sá University, School of Medicine (IDOMED), Rio de Janeiro, Brazil
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25
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Ndomba N, Soldera J. Management of sepsis in a cirrhotic patient admitted to the intensive care unit: A systematic literature review. World J Hepatol 2023; 15:850-866. [PMID: 37397933 PMCID: PMC10308287 DOI: 10.4254/wjh.v15.i6.850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 05/22/2023] [Accepted: 05/31/2023] [Indexed: 06/25/2023] Open
Abstract
BACKGROUND Sepsis is a severe medical condition that occurs when the body's immune system overreacts to an infection, leading to life-threatening organ dysfunction. The "Third international consensus definitions for sepsis and septic shock (Sepsis-3)" defines sepsis as an increase in sequential organ failure assessment score of 2 points or more, with a mortality rate above 10%. Sepsis is a leading cause of intensive care unit (ICU) admissions, and patients with underlying conditions such as cirrhosis have a higher risk of poor outcomes. Therefore, it is critical to recognize and manage sepsis promptly by administering fluids, vasopressors, steroids, and antibiotics, and identifying and treating the source of infection. AIM To conduct a systematic review and meta-analysis of existing literature on the management of sepsis in cirrhotic patients admitted to the ICU and compare the management of sepsis between cirrhotic and non-cirrhotic patients in the ICU. METHODS This study is a systematic literature review that followed the PRISMA statement's standardized search method. The search for relevant studies was conducted across multiple databases, including PubMed, Embase, Base, and Cochrane, using predefined search terms. One reviewer conducted the initial search, and the eligibility criteria were applied to the titles and abstracts of the retrieved articles. The selected articles were then evaluated based on the research objectives to ensure relevance to the study's aims. RESULTS The study findings indicate that cirrhotic patients are more susceptible to infections, resulting in higher mortality rates ranging from 18% to 60%. Early identification of the infection source followed by timely administration of antibiotics, vasopressors, and corticosteroids has been shown to improve patient outcomes. Procalcitonin is a useful biomarker for diagnosing infections in cirrhotic patients. Moreover, presepsin and resistin have been found to be reliable markers of bacterial infection in patients with decompensated liver cirrhosis, with similar diagnostic performance compared to procalcitonin. CONCLUSION This review highlights the importance of early detection and management of infections in cirrhosis patients to reduce mortality. Therefore, early detection of infection using procalcitonin test and other biomarker as presepsin and resistin, associated with early management with antibiotics, fluids, vasopressors and low dose corticosteroids might reduce the mortality associated with sepsis in cirrhotic patients.
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Affiliation(s)
- Nkola Ndomba
- Acute Medicine, University of South Wales, Cardiff CF37 1DL, United Kingdom
| | - Jonathan Soldera
- Acute Medicine, University of South Wales, Cardiff CF37 1DL, United Kingdom.
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Abstract
Patients with cirrhosis frequently require admission to the intensive care unit (ICU). Common indications for admission to ICU include one or more reasons of sepsis, shock due to any cause, acute gastrointestinal bleeding, and altered mentation either due to hepatic encephalopathy, alcohol withdrawal/intoxication, or metabolic encephalopathy. The appropriate critical care of an individual can determine the outcomes of these sick patients. The Airway, Breathing, Circulation, Disability (ABCD) approach to a patient admitted to ICU includes airway, breathing, circulation, and disability management. In this review, the authors discuss the common indications for ICU admission in a patient with cirrhosis and also their management.
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Affiliation(s)
- Mahathi Avadhanam
- Department of Emergency Medicine, Queen Elizabeth hospital, London, UK
| | - Anand V Kulkarni
- Department of Hepatology, AIG Hospitals, Gachibowli, Hyderabad, India-500032.
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Jiang Y, Fan C, Dang Y, Zhao W, Lv L, Lou J, Li L, Ding H. Clinical Characteristics and Early Diagnosis of Spontaneous Fungal Peritonitis/Fungiascites in Hospitalized Cirrhotic Patients with Ascites: A Case-Control Study. J Clin Med 2023; 12:3100. [PMID: 37176540 PMCID: PMC10179646 DOI: 10.3390/jcm12093100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 03/24/2023] [Accepted: 04/20/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Spontaneous fungal peritonitis (SFP) and fungiascites is less well-recognized and described in patients with liver cirrhosis. The aims of this study were to determine the clinical characteristics, prognosis, and risk factors of cirrhotic patients with SFP/fungiascites and to improve early differential diagnosis with spontaneous bacterial peritonitis (SBP). METHODS This was a retrospective case-control study of 54 cases of spontaneous peritonitis in cirrhotic patients (52 SFP and 2 fungiascites) with fungus-positive ascitic culture. Fifty-four SBP cirrhotic patients with bacteria-positive ascitic culture were randomly enrolled as a control group. A nomogram was developed for the early differential diagnosis of SFP and fungiascites. RESULTS Hospital-acquired infection was the main cause of SFP/fungiascites. Of the 54 SFP/fungiascites patients, 31 (57.41%) patients carried on with the antifungal treatment, which seemed to improve short-term (30-days) mortality but not long-term mortality. Septic shock and HCC were independent predictors of high 30-day mortality in SFP/fungiascites patients. We constructed a predictive nomogram model that included AKI/HRS, fever, (1,3)-β-D-glucan, and hospital-acquired infection markers for early differential diagnosis of SFP/fungiascites in cirrhotic patients with ascites from SBP, and the diagnostic performance was favorable, with an AUC of 0.930 (95% CI: 0.874-0.985). CONCLUSIONS SFP/fungiascites was associated with high mortality. The nomogram established in this article is a useful tool for identifying SFP/fungiascites in SBP patients early. For patients with strongly suspected or confirmed SFP/fungiascites, timely antifungal therapy should be administered.
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Affiliation(s)
- Yingying Jiang
- Department of Hepatology and Gastroenterology, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
| | - Chunlei Fan
- Department of Hepatology and Gastroenterology, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
| | - Yan Dang
- Clinical Laboratory Center, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
| | - Wenmin Zhao
- Department of Hepatology and Gastroenterology, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
| | - Lingna Lv
- Department of Hepatology and Gastroenterology, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
| | - Jinli Lou
- Clinical Laboratory Center, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
| | - Lei Li
- Department of Hepatology and Gastroenterology, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
| | - Huiguo Ding
- Department of Hepatology and Gastroenterology, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
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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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Feredj E, Audureau E, Boueilh A, Fihman V, Fourati S, Lelièvre JD, Gallien S, Grimbert P, Matignon M, Melica G. Impact of a Dedicated Pretransplant Infectious Disease Consultation on Respiratory Tract Infections in Kidney Allograft Recipients: A Retrospective Study of 516 Recipients. Pathogens 2023; 12:pathogens12010074. [PMID: 36678422 PMCID: PMC9867402 DOI: 10.3390/pathogens12010074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/19/2022] [Accepted: 12/24/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Respiratory tract infections (RTIs) are a leading cause of death after kidney transplant. Preventive strategies may be implemented during a dedicated infectious disease consultation (IDC) before transplantation. Impact of IDC on RTIs after transplant has not been determined. METHODS We conducted a monocentric retrospective cohort analysis including all kidney transplant recipients from January 2015 to December 2019. We evaluated the impact of IDC on RTIs and identified risk and protective factors associated with RTIs. RESULTS We included 516 kidney transplant recipients. Among these, 145 had an IDC before transplant. Ninety-five patients presented 123 RTIs, including 75 (61%) with pneumonia. Patient that benefited from IDC presented significantly less RTIs (p = 0.049). RTIs were an independent risk factor of mortality (HR = 3.64 (1.97-6.73)). Independent risk factors for RTIs included HIV (OR = 3.33 (1.43-7.74)) and HCV (OR = 3.76 (1.58-8.96)). IDC was identified as an independent protective factor (OR = 0.48 (0.26-0.88)). IDC prior to transplantation is associated with diminished RTIs and is an independent protective factor. RTIs after kidney transplant are an independent risk factor of death. Implementing systematic IDC may have an important impact on reducing RTIs and related morbidity and mortality.
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Affiliation(s)
- Elsa Feredj
- Infectious Disease Department, Groupe Hospitalier Henri-Mondor/Albert Chenevier, Assistance Publique-Hôpitaux de Paris (AP-HP), 94010 Créteil, France
- IMRB (Institut Mondor de Recherche Biomédicale), Université Paris-Est-Créteil (UPEC), INSERM U955, Equipe 16, 94010 Créteil, France
- Correspondence:
| | - Etienne Audureau
- Department of Public Health, Hôpitaux Universitaires Henri Mondor, Assistance Publique—Hôpitaux de Paris, 94010 Créteil, France
| | - Anna Boueilh
- Nephrology and Renal Transplantation Department, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Assistance Publique-Hôpitaux de Paris (AP-HP), 94010 Créteil, France
| | - Vincent Fihman
- Virology, Bacteriology and Infection Control Units, Clinical Microbiology Department, AP-HP (Assistance Publique-Hôpitaux de Paris, 94010 Créteil, France
- IMRB (Institut Mondor de Recherche Biomédicale), VIC (Virologie Immunité Cancer), DHU (Département Hospitalo-Universitaire), Université Paris-Est-Créteil (UPEC), INSERM U955, Equipe 18, 94010 Créteil, France
- Ecole Vétérinaire de Maison Alfort, EA Dynamyc, Université Paris Est Créteil, 94000 Créteil, France
| | - Slim Fourati
- Virology, Bacteriology and Infection Control Units, Clinical Microbiology Department, AP-HP (Assistance Publique-Hôpitaux de Paris, 94010 Créteil, France
- IMRB (Institut Mondor de Recherche Biomédicale), VIC (Virologie Immunité Cancer), DHU (Département Hospitalo-Universitaire), Université Paris-Est-Créteil (UPEC), INSERM U955, Equipe 18, 94010 Créteil, France
| | - Jean-Daniel Lelièvre
- Infectious Disease Department, Groupe Hospitalier Henri-Mondor/Albert Chenevier, Assistance Publique-Hôpitaux de Paris (AP-HP), 94010 Créteil, France
- IMRB (Institut Mondor de Recherche Biomédicale), Université Paris-Est-Créteil (UPEC), INSERM U955, Equipe 16, 94010 Créteil, France
| | - Sébastien Gallien
- Infectious Disease Department, Groupe Hospitalier Henri-Mondor/Albert Chenevier, Assistance Publique-Hôpitaux de Paris (AP-HP), 94010 Créteil, France
- Ecole Vétérinaire de Maison Alfort, EA Dynamyc, Université Paris Est Créteil, 94000 Créteil, France
| | - Philippe Grimbert
- Nephrology and Renal Transplantation Department, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Assistance Publique-Hôpitaux de Paris (AP-HP), 94010 Créteil, France
- IMRB (Institut Mondor de Recherche Biomédicale), VIC (Virus-Immunité-Cancer), DHU (Département Hospitalo-Universitaire), Université Paris-Est-Créteil (UPEC), INSERM U955, Equipe 21, 94010 Créteil, France
- Clinical Investigation Center-Biotherapies 504, Groupe Hospitalier Henri-Mondor/Albert Chenevier Assistance Publique-Hôpitaux de Paris (AP-HP), 94010 Créteil, France
| | - Marie Matignon
- Nephrology and Renal Transplantation Department, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Assistance Publique-Hôpitaux de Paris (AP-HP), 94010 Créteil, France
- IMRB (Institut Mondor de Recherche Biomédicale), VIC (Virus-Immunité-Cancer), DHU (Département Hospitalo-Universitaire), Université Paris-Est-Créteil (UPEC), INSERM U955, Equipe 21, 94010 Créteil, France
| | - Giovanna Melica
- Infectious Disease Department, Groupe Hospitalier Henri-Mondor/Albert Chenevier, Assistance Publique-Hôpitaux de Paris (AP-HP), 94010 Créteil, France
- IMRB (Institut Mondor de Recherche Biomédicale), Université Paris-Est-Créteil (UPEC), INSERM U955, Equipe 16, 94010 Créteil, France
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B Hadi Y, Khan RS, Lakhani DA, Khan AY, Jannat RU, Khan AA, Naqvi SF, Obeng G, Kupec JT, Singal AK. Antibiotic Prophylaxis for Upper Gastrointestinal Bleed in Liver Cirrhosis; Less May Be More. Dig Dis Sci 2023; 68:284-290. [PMID: 35467310 DOI: 10.1007/s10620-022-07481-0] [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: 07/23/2021] [Accepted: 03/07/2022] [Indexed: 02/01/2023]
Abstract
INTRODUCTION Administration of antibiotics in patients with cirrhosis and upper gastrointestinal bleeding has been shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics. Seven days of antibiotics are generally recommended but very few studies have compared antibiotic duration to clinical outcomes in current available scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on patient outcomes. METHODS We conducted a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010 to 2018. Patients were divided into three cohorts based on duration of antibiotic administration for prophylaxis: 1-3 days of antibiotics, 4-6 days of antibiotics and 7 days or more of antibiotics. Rates of infection diagnosis within 30 days, rebleeding, and mortality were compared between the three groups with Chi square, Fisher Exact and Kruskall-Wallace tests. Multivariable analysis was conducted to evaluate independent risk factors for infection. RESULTS Medical charts of 980 patients with cirrhosis and upper GI bleeding during the study period were reviewed. A total of 303 with upper gastrointestinal bleeding were included in the final sample, of these 243 patients received antibiotics for prophylaxis and were included for analysis. Seventy-seven patients received antibiotic therapy for 3 days or less, 69 patients for 4-6 days, and 97 patients longer than 6 days. The three groups were well matched in demographic and clinical variables. Twenty-seven patients developed infections within 30 days of bleeding. MELD-Na score at presentation and presence of ascites were associated with infection within 30 days. Rates of infection were not statistically different between the three antibiotic groups (p = 0.78). In the thirty days following the GI bleed, pneumonia was the most diagnosed infection (eleven patients) followed by urinary tract infections (eight patients). Four patients developed spontaneous bacterial peritonitis and three were diagnosed with bacteremia. There was no difference in time to infection (Kruskall Wallace test p = 0.75), early re-bleeding (p = 0.81), late re-bleeding (p = 0.37) and in-hospital mortality (p = 0.94) in the three groups. Six patients in the cohort developed C. Difficile infection; no patient in the short antibiotic group developed C. Difficile infection. CONCLUSION Short course of antibiotics for prophylaxis (3 days) appears safe and adequate for prophylaxis in patients with cirrhosis with upper gastrointestinal bleeding if there is no active infection.
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Affiliation(s)
- Yousaf B Hadi
- Department of Medicine, West Virginia University, Morgantown, USA
| | | | - Dhairya A Lakhani
- Department of Radiology, Ruby Memorial Hospital, West Virginia University, 1 Medical Center Drive, Morgantown, WV, 26506, USA.
| | - Ali Y Khan
- West Virginia University, Morgantown, USA
| | | | - Adnan Aman Khan
- Section of Gastroenterology, Department of Medicine, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, USA
| | | | | | - Justin T Kupec
- Department of Medicine, West Virginia University, Morgantown, USA
| | - Ashwani K Singal
- Sanford School of Medicine, University of South Dakota, Sioux Falls, USA
- Avera Transplant Institute, Sioux Falls, SD, USA
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31
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Velasque MJSG, Branchini G, Catarina AV, Bettoni L, Fernandes RS, Da Silva AF, Dorneles GP, da Silva IM, Santos MA, Sumienski J, Peres A, Roehe AV, Kohek MBDF, Porawski M, Nunes FB. Fish Oil - Omega-3 Exerts Protective Effect in Oxidative Stress and Liver Dysfunctions Resulting from Experimental Sepsis. J Clin Exp Hepatol 2023; 13:64-74. [PMID: 36647406 PMCID: PMC9840085 DOI: 10.1016/j.jceh.2022.07.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 06/24/2022] [Accepted: 07/03/2022] [Indexed: 01/19/2023] Open
Abstract
Background Sepsis is a severe global health problem, with high morbidity and mortality. In sepsis, one of the main affected organs is the liver. Hepatic alterations characterize a negative prognostic. Omega-3 fatty acids (ω3), eicosapentaenoic acid, and docosahexaenoic acid, are part of the main families of polyunsaturated fatty acids. ω3 has been used in studies as sepsis treatment and as a treatment for non-alcoholic liver disease. Aim We aimed to evaluate the effects of treatment with fish oil (FO) rich in ω3 on liver changes and damage resulting from experimental sepsis. Methodology A model of severe sepsis in Wistar rats was used. Oxidative stress in the liver tissue was evaluated by means of tests of thiobarbituric acid reactive substances, 2,7-dihydrodichlorofluorescein diacetate , catalase, and glutathione peroxidase, in the serum TBARS, DCF, thiols and, to assess liver dysfunction, alanine aminotransferase and aspartate aminotransferase. Hepatic tissue damage was evaluated using H&E histology. Results In assessments of oxidative stress in liver tissue, a protective effect was observed in the tests of TBARS, DCF, CAT, and GPx, when compared the sepsis versus sepsis+ω3 groups. Regarding the oxidative stress in serum, a protective effect of treatment with ω3 was observed in the TBARS, DCF, and thiols assays, in the comparison between the sepsis and sepsis+ω3 groups. ω3 had also a beneficial effect on biochemical parameters in serum in the analysis of ALT, creatinine, urea, and lactate, observed in the comparison between the sepsis and sepsis+ω3 groups. Conclusion The results suggest ω3 as a liver protector during sepsis with an antioxidant effect, alleviating injuries and dysfunctions.
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Key Words
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- CAT, catalase
- DCF, 2,7-dihydrodichlorofluorescein diacetate
- DHA, docosahexaenoic acid
- EPA, eicosapentaenoic acid
- FO, fish oil
- GPx, glutathione peroxidase
- GTO, oxaloacetic transaminase
- GTP, pyruvic transaminase
- HE, Hematoxylin and Eosin
- ICON, Intensive Care Over Nations
- ICU, intensive care unit
- IFN- γ, interferon gamma
- Liver injury
- RNS, reactive nitrogen species
- ROS, reactive oxygen species
- TBARS, Thiobarbituric Acid Reactive Substances
- TGF-β, transforming growth factor beta
- TNF-α, tumor necrosis factor alpha
- antioxidant
- inflammation
- omega-3
- oxidative stress
- sepsis
- ω3, omega-3
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Affiliation(s)
- Mary J. Soares Gonçalves Velasque
- Graduate Program in Pathology – Laboratory of Computational, Molecular, and Cellular Biophysics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Gisele Branchini
- Graduate Program in Pathology – Laboratory of Computational, Molecular, and Cellular Biophysics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Anderson V. Catarina
- Graduate Program in Pathology – Laboratory of Computational, Molecular, and Cellular Biophysics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Lais Bettoni
- Graduate Program in Pathology – Laboratory of Computational, Molecular, and Cellular Biophysics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Renata S. Fernandes
- Graduate Program in Health Sciences – Laboratory of Translational Physiology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | | | - Gilson P. Dorneles
- Laboratory of Cellular and Molecular Immunology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Igor Martins da Silva
- Laboratory of Cellular and Molecular Immunology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Maeli A. Santos
- Laboratory of Cellular and Molecular Immunology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Juliana Sumienski
- Laboratory of Immunology and Microbiology - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil
| | - Alessandra Peres
- Laboratory of Cellular and Molecular Immunology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Adriana V. Roehe
- Graduate Program in Pathology – Laboratory of Pathology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Maria B. da Fonte Kohek
- Laboratory of Cellular and Molecular Immunology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Marilene Porawski
- Laboratory of Behavioral and Metabolic Physiology – Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Fernanda B. Nunes
- Graduate Program in Pathology – Laboratory of Computational, Molecular, and Cellular Biophysics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
- Laboratory of Inflammation and Cellular Biophysics - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil
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Rashed E, Soldera J. CLIF-SOFA and CLIF-C scores for the prognostication of acute-on-chronic liver failure and acute decompensation of cirrhosis: A systematic review. World J Hepatol 2022; 14:2025-2043. [PMID: 36618331 PMCID: PMC9813844 DOI: 10.4254/wjh.v14.i12.2025] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/18/2022] [Accepted: 11/07/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a syndrome characterized by decompensation in individuals with chronic liver disease, generally secondary to one or more extra-hepatic organ failures, implying an elevated mortality rate. Acute decompensation (AD) is the term used for one or more significant consequences of liver disease in a short time and is the most common reason for hospital admission in cirrhotic patients. The European Association for the Study of Liver-Chronic-Liver Failure (EASL-CLIF) Group modified the intensive care Sequential Organ Failure Assessment score into CLIF-SOFA, which detects the presence of ACLF in patients with or without AD, classifying it into three grades. AIM To investigate the role of the EASL-CLIF definition for ACLF and the ability of CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD scores for prognosticating ACLF or AD. METHODS This study is a literature review using a standardized search method, conducted using the steps following the guidelines for reporting systematic reviews set out by the PRISMA statement. For specific keywords, relevant articles were found by searching PubMed, ScienceDirect, and BioMed Central-BMC. The databases were searched using the search terms by one reviewer, and a list of potentially eligible studies was generated based on the titles and abstracts screened. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS Most of the included studies used the EASL-CLIF definition for ACLF to identify cirrhotic patients with a significant risk of short-term mortality. The primary outcome in all reviewed studies was mortality. Most of the study findings were based on an area under the receiver operating characteristic curve (AUROC) analysis, which revealed that CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD scores were preferable to other models predicting 28-d mortality. Their AUROC scores were higher and able to predict all-cause mortality at 90, 180, and 365 d. A total of 50 articles were included in this study, which found that the CLIF-SOFA, CLIF-C ACLF and CLIF-C AD scores in more than half of the articles were able to predict short-term and long-term mortality in patients with either ACLF or AD. CONCLUSION CLIF-SOFA score surpasses other models in predicting mortality in ACLF patients, especially in the short-term. CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD are accurate short-term and long-term mortality prognosticating scores.
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Affiliation(s)
- Ebrahim Rashed
- Acute Medicine, University of South Wales, Cardiff CF37 1DL, United Kingdom
| | - Jonathan Soldera
- Acute Medicine, University of South Wales, Cardiff CF37 1DL, United Kingdom.
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Karimi A, Pourreza S, Vajdi M, Mahmoodpoor A, Sanaie S, Karimi M, Tarighat-Esfanjani A. Evaluating the effects of curcumin nanomicelles on clinical outcome and cellular immune responses in critically ill sepsis patients: A randomized, double-blind, and placebo-controlled trial. Front Nutr 2022; 9:1037861. [PMID: 36562037 PMCID: PMC9763722 DOI: 10.3389/fnut.2022.1037861] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 11/21/2022] [Indexed: 12/12/2022] Open
Abstract
Introduction In sepsis, the immune system is overreacting to infection, leading to organ dysfunction and death. The purpose of this study was to investigate the impacts of curcumin nanomicelles on clinical outcomes and cellular immune responses in critically ill sepsis patients. Method For 10 days, 40 patients in the intensive care units (ICU) were randomized between the nano curcumin (NC) and placebo groups in a randomized study. We evaluated serum levels of biochemical factors, inflammatory biomarkers, the mRNA expression levels of FOXP3, NLRP-3, IFN-γ, and NF-κp genes in the PBMCs, and clinical outcomes before the beginning of the supplementation and on days 5 and 10. Results NLR family pyrin domain containing 3 (NLRP3), interferon gamma (IFN-γ), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA expression levels significantly P = 0.014, P = 0.014, and P = 0.019, respectively) decreased, but forkhead box P3 (FOXP3) mRNA expression levels increased significantly (P = 0.008) in the NC group compared to the placebo group after 10 days. NC supplementation decreased serum levels of IL-22, IL-17, and high mobility group box 1 (HMGB1) (P < 0.05). Nevertheless, biochemical factors and nutritional status did not differ significantly (P > 0.05). NC supplementation resulted in decreased sequential organ failure assessment and multiple organ dysfunction syndromes scores, while it did not have significant impacts on length of stay in the ICU, systolic blood pressure, diastolic blood pressure, a saturation of oxygen (%), and respiratory rate (breaths/min) PaO2/FiO2 (p > 0.05). Conclusion For critically ill patients with sepsis, NC supplementation may be an effective therapeutic strategy. More randomized clinical trials involving longer follow-up periods and different doses are needed to achieve the best results.
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Affiliation(s)
- Arash Karimi
- Department of Clinical Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sanaz Pourreza
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdi Vajdi
- Student Research Committee, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ata Mahmoodpoor
- Department of Anesthesiology and Intensive Care, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sarvin Sanaie
- Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mozhde Karimi
- Department of Immunology, School of Medicine, Tarbiat Modares University, Tehran, Iran
| | - Ali Tarighat-Esfanjani
- Department of Clinical Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Fang CH, Ravindra V, Akhter S, Adibuzzaman M, Griffin P, Subramaniam S, Grama A. Identifying and analyzing sepsis states: A retrospective study on patients with sepsis in ICUs. PLOS DIGITAL HEALTH 2022; 1:e0000130. [PMID: 36812596 PMCID: PMC9931346 DOI: 10.1371/journal.pdig.0000130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 09/20/2022] [Indexed: 11/12/2022]
Abstract
Sepsis accounts for more than 50% of hospital deaths, and the associated cost ranks the highest among hospital admissions in the US. Improved understanding of disease states, progression, severity, and clinical markers has the potential to significantly improve patient outcomes and reduce cost. We develop a computational framework that identifies disease states in sepsis and models disease progression using clinical variables and samples in the MIMIC-III database. We identify six distinct patient states in sepsis, each associated with different manifestations of organ dysfunction. We find that patients in different sepsis states are statistically significantly composed of distinct populations with disparate demographic and comorbidity profiles. Our progression model accurately characterizes the severity level of each pathological trajectory and identifies significant changes in clinical variables and treatment actions during sepsis state transitions. Collectively, our framework provides a holistic view of sepsis, and our findings provide the basis for future development of clinical trials, prevention, and therapeutic strategies for sepsis.
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Affiliation(s)
- Chih-Hao Fang
- Department of Computer Science, Purdue University, West Lafayette, IN, United States of America
- * E-mail: (C-HF); (AG)
| | - Vikram Ravindra
- Department of Computer Science, University of Cincinnati, Cincinnati, OH, United States of America
| | - Salma Akhter
- Regenstrief Center for Healthcare Engineering, Purdue University, West Lafayette, IN, United States of America
| | - Mohammad Adibuzzaman
- Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon, United States of America
| | - Paul Griffin
- Department of Industrial Engineering, Penn State University, University Park, PA, United States of America
| | - Shankar Subramaniam
- Department of Bioengineering, University of California, San Diego, La Jolla, CA, United States of America
| | - Ananth Grama
- Department of Computer Science, Purdue University, West Lafayette, IN, United States of America
- * E-mail: (C-HF); (AG)
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Forceville X, Van Antwerpen P, Annane D, Vincent JL. Selenocompounds and Sepsis-Redox Bypass Hypothesis: Part B-Selenocompounds in the Management of Early Sepsis. Antioxid Redox Signal 2022; 37:998-1029. [PMID: 35287478 DOI: 10.1089/ars.2020.8062] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Significance: Endothelial barrier damage, which is in part caused by excess production of reactive oxygen, halogen and nitrogen species (ROHNS), especially peroxynitrite (ONOO-), is a major event in early sepsis and, with leukocyte hyperactivation, part of the generalized dysregulated immune response to infection, which may even become a complex maladaptive state. Selenoenzymes have major antioxidant functions. Their synthesis is related to the need to limit deleterious oxidant redox cycling by small selenocompounds, which may be of therapeutic cytotoxic interest. Plasma selenoprotein-P is crucial for selenium transport from the liver to the tissues and for antioxidant endothelial protection, especially against ONOO-. Above micromolar concentrations, sodium selenite (Na2SeO3) becomes cytotoxic, with a lower cytotoxicity threshold in activated cells, which has led to cancer research. Recent Advances: Plasma selenium (<2% of total body selenium) is mainly contained in selenoprotein-P, and concentrations decrease rapidly in the early phase of sepsis, because of increased selenoprotein-P binding and downregulation of hepatic synthesis and excretion. At low concentrations, Na2SeO3 acts as a selenium donor, favoring selenoprotein-P synthesis in physiology, but probably not in the acute phase of sepsis. Critical Issues: The cytotoxic effects of Na2SeO3 against hyperactivated leukocytes, especially the most immature forms that liberate ROHNS, may be beneficial, but they may also be harmful for activated endothelial cells. Endothelial protection against ROHNS by selenoprotein-P may reduce Na2SeO3 toxicity, which is increased in sepsis. Future Direction: The combination of selenoprotein-P for endothelial protection and the cytotoxic effects of Na2SeO3 against hyperactivated leukocytes may be a promising intervention for early sepsis. Antioxid. Redox Signal. 37, 998-1029.
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Affiliation(s)
- Xavier Forceville
- Medico-surgical Intensive Care Unit, Great Hospital of East Francilien - Meaux site, Meaux, France.,Clinical Investigation Centre (CIC Inserm1414) CHU de Rennes - Université de Rennes 1, Rennes, France
| | - Pierre Van Antwerpen
- Pharmacognosy, Bioanalysis and Drug Discovery and Analytical Platform of the Faculty of Pharmacy, Univesité libre de Bruxelles (ULB), Bruxelles, Belgium
| | - Djillali Annane
- Service de Réanimation Médicale, Hôpital Raymond Poincaré (APHP), Garches, France.,U1173 Lab. of Inflammation & Infection, (Fédération Hospitalo-Universitaire) FHU SEPSIS, Université Paris Saclay-campus (Université de Versailles Saint-Quentin-en-Yvelines) UVSQ, Versailles, France
| | - Jean Louis Vincent
- Department of Intensive Care, Erasme University Hospital, Université libre de Bruxelles, Brussels, Belgium
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Kaltenbach MG, Tapper EB. High Preoperative Fibrosis-4 Index Is Associated With Postoperative Mortality: An Argument to Look for Advanced Liver Disease Before Surgery. Anesth Analg 2022; 135:954-956. [PMID: 36269985 DOI: 10.1213/ane.0000000000006130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Melissa G Kaltenbach
- From the Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
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Alcohol-Related Liver Disease: An Overview on Pathophysiology, Diagnosis and Therapeutic Perspectives. Biomedicines 2022; 10:biomedicines10102530. [PMID: 36289791 PMCID: PMC9599689 DOI: 10.3390/biomedicines10102530] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/01/2022] [Accepted: 10/08/2022] [Indexed: 11/19/2022] Open
Abstract
Alcohol-related liver disease (ALD) refers to a spectrum of liver manifestations ranging from fatty liver diseases, steatohepatitis, and fibrosis/cirrhosis with chronic inflammation primarily due to excessive alcohol use. Currently, ALD is considered as one of the most prevalent causes of liver disease-associated mortality worldwide. Although the pathogenesis of ALD has been intensively investigated, the present understanding of its biomarkers in the context of early clinical diagnosis is not complete, and novel therapeutic targets that can significantly alleviate advanced forms of ALD are limited. While alcohol abstinence remains the primary therapeutic intervention for managing ALD, there are currently no approved medications for treating ALD. Furthermore, given the similarities and the differences between ALD and non-alcoholic fatty liver disease in terms of disease progression and underlying molecular mechanisms, numerous studies have demonstrated that many therapeutic interventions targeting several signaling pathways, including oxidative stress, inflammatory response, hormonal regulation, and hepatocyte death play a significant role in ALD treatment. Therefore, in this review, we summarized several key molecular targets and their modes of action in ALD progression. We also described the updated therapeutic options for ALD management with a particular emphasis on potentially novel signaling pathways.
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Colchicine overdose impairs the capacity of Kupffer cells to clear foreign particles and endotoxins. Arch Toxicol 2022; 96:3067-3076. [PMID: 36102954 PMCID: PMC9525399 DOI: 10.1007/s00204-022-03353-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 08/01/2022] [Indexed: 02/07/2023]
Abstract
AbstractColchicine is an anti-inflammatory drug with a narrow therapeutic index. Its binding to tubulin prevents microtubule polymerization; however, little is known about how depolymerization of microtubules interferes with the phagocytosis function of Kupffer cells (KC). Here, we applied functional intravital imaging techniques to investigate the influence of microtubule disruption by colchicine on KC morphology, as well as its capacity to clear foreign particles and bacterial lipopolysaccharide (LPS) in anesthetized mice. Intravital imaging of KC in healthy mice showed the typical elongated morphology, localization at the luminal side of the sinusoidal endothelial cells, and moving cell protrusions. In contrast, at colchicine doses of 1 mg/kg and higher (intraperitoneal), KC appeared roundish with strongly reduced protrusions and motility. To study the functional consequences of these alterations, we analyzed the capacity of KC to phagocytose fluorescent nanospheres (100 nm-size) and LPS. After tail vein injection, the nanospheres formed aggregates of up to ~ 5 µm moving along the sinusoidal bloodstream. In controls, the nanosphere aggregates were rapidly captured by the Kupffer cell protrusions, followed by an internalization process that lasted up to 10 min. Similar capture events and internalization processes were observed after the administration of fluorescently labeled LPS. In contrast, capture and internalization of both nanospheres and LPS by KC were strongly reduced in colchicine-treated mice. Reduced phagocytosis of LPS was accompanied by aggravated production of inflammatory cytokines. Since 0.4 mg/kg colchicine in mice has been reported to be bio-equivalent to human therapeutic doses, the here-observed adverse effects on KC occurred at doses only slightly above those used clinically, and may be critical for patients with endotoxemia due to a leaky gut–blood barrier.
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Xu X, Yu X, Gong K, Tu H, Yao J, Lan Y, Ye S, Weng H, Shi Y, Sheng J. Acute decompensation events differentially impact the risk of nosocomial infections and short-term outcomes in patients with cirrhosis. Front Med (Lausanne) 2022; 9:962541. [PMID: 36059822 PMCID: PMC9428487 DOI: 10.3389/fmed.2022.962541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 08/01/2022] [Indexed: 11/23/2022] Open
Abstract
Aims This research aimed to evaluate the influence of acute decompensation (AD) events upon admission on the subsequent risk of nosocomial infections (NIs) and the synergy between AD and the following NIs on the short-term outcome. Methods A total of 419 hospitalized individuals with cirrhosis and AD participated in the current study. Various AD events at admission and outcomes in patients with or without NIs were compared. The logistic regression and Cox proportional hazards models were designed for NIs development and liver transplant (LT)-free mortality at 28 and 90 days, respectively. Results During hospitalization, 91 patients developed NIs. Notably, a higher proportion of patients with NIs had jaundice (52.7 vs. 30.5%; p < 0.001) and bacterial infections (37.4 vs. 20.7%; p = 0.001) at admission compared to patients without NIs, while a lower proportion suffered gastrointestinal hemorrhage (16.5 vs. 36.6%; p < 0.001). Multivariate analysis revealed that jaundice was independently linked with the development of NIs (OR, 2.732; 95% CI: 1.104–6.762). The 28-day (16.5 vs. 7.3%; p = 0.008) and 90-day (27.5 vs. 15.9%; p = 0.011) LT-free mortality rates of patients with NIs were significantly higher than those without NIs. According to the Cox proportional hazards model, jaundice remained an independent risk factor for 90-day death (HR, 5.775; 95% CI: 1.217–27.397). The connection between total bilirubin and 90-day mortality was nonlinear, and a 6 mg/mL threshold was proposed. Conclusion The types of AD events differentially predispose to risk of NIs. Presenting jaundice at admission is independently associated with NIs occurrence and increased 90-day mortality of patients with NIs. Antibiotic prophylaxis may benefit this specific subset of patients.
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40
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Zhang S, Lu S, Li Z. Extrahepatic factors in hepatic immune regulation. Front Immunol 2022; 13:941721. [PMID: 36052075 PMCID: PMC9427192 DOI: 10.3389/fimmu.2022.941721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/28/2022] [Indexed: 11/13/2022] Open
Abstract
The liver is a site of complex immune activity. The hepatic immune system tolerates harmless immunogenic loads in homeostasis status, shelters liver function, while maintaining vigilance against possible infectious agents or tissue damage and providing immune surveillance at the same time. Activation of the hepatic immunity is initiated by a diverse repertoire of hepatic resident immune cells as well as non-hematopoietic cells, which can sense "danger signals" and trigger robust immune response. Factors that mediate the regulation of hepatic immunity are elicited not only in liver, but also in other organs, given the dual blood supply of the liver via both portal vein blood and arterial blood. Emerging evidence indicates that inter-organ crosstalk between the liver and other organs such as spleen, gut, lung, adipose tissue, and brain is involved in the pathogenesis of liver diseases. In this review, we present the features of hepatic immune regulation, with particular attention to the correlation with factors from extrahepatic organ. We describe the mechanisms by which other organs establish an immune association with the liver and then modulate the hepatic immune response. We discuss their roles and distinct mechanisms in liver homeostasis and pathological conditions from the cellular and molecular perspective, highlighting their potential for liver disease intervention. Moreover, we review the available animal models and methods for revealing the regulatory mechanisms of these extrahepatic factors. With the increasing understanding of the mechanisms by which extrahepatic factors regulate liver immunity, we believe that this will provide promising targets for liver disease therapy.
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Affiliation(s)
- Shaoying Zhang
- National-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Clinical Medical Research Center for Liver and Spleen Diseases, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
- Shaanxi International Cooperation Base for Inflammation and Immunity, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Shemin Lu
- National-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
- Shaanxi International Cooperation Base for Inflammation and Immunity, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an, China
| | - Zongfang Li
- National-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Clinical Medical Research Center for Liver and Spleen Diseases, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
- Shaanxi International Cooperation Base for Inflammation and Immunity, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
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41
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Kulkarni AV, Premkumar M, Arab JP, Kumar K, Sharma M, Reddy ND, Padaki NR, Reddy RK. Early Diagnosis and Prevention of Infections in Cirrhosis. Semin Liver Dis 2022; 42:293-312. [PMID: 35672014 DOI: 10.1055/a-1869-7607] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Strategies to prevent infection and improve outcomes in patients with cirrhosis. HAV, hepatitis A virus; HBV, hepatitis B virus; COVID-19, novel coronavirus disease 2019; NSBB, nonselective β-blocker; PPI, proton pump inhibitors.Cirrhosis is a risk factor for infections. Majority of hospital admissions in patients with cirrhosis are due to infections. Sepsis is an immunological response to an infectious process that leads to end-organ dysfunction and death. Preventing infections may avoid the downstream complications, and early diagnosis of infections may improve the outcomes. In this review, we discuss the pathogenesis, diagnosis, and biomarkers of infection; the incremental preventive strategies for infections and sepsi; and the consequent organ failures in cirrhosis. Strategies for primary prevention include reducing gut translocation by selective intestinal decontamination, avoiding unnecessary proton pump inhibitors' use, appropriate use of β-blockers, and vaccinations for viral diseases including novel coronavirus disease 2019. Secondary prevention includes early diagnosis and a timely and judicious use of antibiotics to prevent organ dysfunction. Organ failure support constitutes tertiary intervention in cirrhosis. In conclusion, infections in cirrhosis are potentially preventable with appropriate care strategies to then enable improved outcomes.
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Affiliation(s)
- Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Juan P Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Karan Kumar
- Department of Hepatology, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India
| | - Mithun Sharma
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Nageshwar D Reddy
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Nagaraja R Padaki
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Rajender K Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
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Wang Y, Shen W, Huang F, Yu C, Xi L, Gao J, Yin M, Liu X, Lin J, Liu L, Zhang H, Zhu J, Hong Y. HDL-C levels added to the MELD score improves 30-day mortality prediction in Asian patients with cirrhosis. J Int Med Res 2022; 50:3000605221109385. [PMID: 35836382 PMCID: PMC9290124 DOI: 10.1177/03000605221109385] [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] [Indexed: 11/16/2022] Open
Abstract
Objectives Lower high-density lipoprotein cholesterol (HDL-C) levels have been observed in chronic liver disease patients. The aim of this study was to develop a model that incorporates HDL-C levels and the Model for End-stage Liver Disease (MELD) score to predict 30-day mortality in Asian cirrhosis patients. Methods Cirrhosis patients were recruited from two hospitals in this retrospective observational study. Propensity score matching was used. The model’s performance was evaluated, including its ability to predict 30-day mortality, accuracy, and clinical utility. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. Results The HDL-C + MELD model showed good ability to predict 30-day mortality (area under the curve, 0.784; sensitivity, 0.797; specificity, 0.632), which was better than that of the MELD score alone. It also showed good calibration and a net benefit for all patients, which was better than that of the MELD score, except at the threshold probability. NRI and IDI results confirmed that adding HDL-C levels to the MELD score improved the model’s performance in predicting 30-day mortality. Conclusion We added HDL-C levels to the MELD score to predict 30-day mortality in Asian patients with cirrhosis. The HDLC + MELD model shows good ability to predict 30-day mortality and clinical utility.
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Affiliation(s)
- Yue Wang
- Department of Hepatology, The Fifth People's Hospital of Suzhou, Suzhou, China
| | - Wenjuan Shen
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Fang Huang
- Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chenyan Yu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Liting Xi
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jingwen Gao
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Minyue Yin
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiaolin Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jiaxi Lin
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Lu Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Huixian Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jinzhou Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yu Hong
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Kim JH, Jun BG, Lee M, Lee HA, Kim TS, Heo JW, Moon DH, Kang SH, Suk KT, Kim MY, Kim YD, Cheon GJ, Baik SK, Kim DJ, Choi DH. Reappraisal of sepsis-3 and CLIF-SOFA as predictors of mortality in patients with cirrhosis and infection presenting to the emergency department: A multicenter study. Clin Mol Hepatol 2022; 28:540-552. [PMID: 35526859 PMCID: PMC9293608 DOI: 10.3350/cmh.2021.0169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 05/02/2022] [Accepted: 05/03/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND/AIMS Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) have been advocated to be used in defining sepsis in the general population. We aimed to compare the Sepsis-3 criteria and Chronic Liver Failure-SOFA (CLIF-SOFA) scores as predictors of in-hospital mortality in cirrhotic patients admitted to the emergency department (ED) for infections. METHODS A total of 1,622 cirrhosis patients admitted at the ED for infections were assessed retrospectively. We analyzed their demographic, laboratory, and microbiological data upon diagnosis of the infection. The primary endpoint was inhospital mortality rate. The predictive performances of baseline CLIF-SOFA, Sepsis-3, and qSOFA scores for in-hospital mortality were evaluated. RESULTS The CLIF-SOFA score proved to be significantly better in predicting in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.80; 95% confidence interval [CI], 0.78-0.82) than the Sepsis-3 (AUROC, 0.75; 95% CI, 0.72-0.77, P<0.001) and qSOFA (AUROC, 0.67; 95% CI, 0.64-0.70; P<0.001) score. The CLIF-SOFA, CLIF-C-AD scores, Sepsis-3 criteria, septic shock, and qSOFA positivity were significantly associated with in-hospital mortality (adjusted hazard ratio [aHR], 1.24; 95% CI, 1.19-1.28; aHR, 1.13; 95% CI, 1.09-1.17; aHR, 1.19; 95% CI, 1.15-1.24; aHR, 1.88; 95% CI, 1.42-2.48; aHR, 2.06; 95% CI, 1.55-2.72; respectively; all P<0.001). For CLIF-SOFA scores ≥6, in-hospital mortality was >10%; this is the cutoff point for the definition of sepsis. CONCLUSION Among cirrhosis patients presenting with infections at the ED, CLIF-SOFA scores showed a better predictive performance for mortality than both Sepsis-3 criteria and qSOFA scores, and can be a useful tool of risk stratification in cirrhotic patients requiring timely intervention for infection.
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Affiliation(s)
- Ji Hyun Kim
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
- Department of Gastroenterology, Kangwon National University Hospital, Chuncheon, Korea
| | - Baek Gyu Jun
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, Korea
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Hye Ah Lee
- Clinical Trial Center, Ewha Womans University Seoul Hospital, Seoul, Korea
| | - Tae Suk Kim
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
- Department of Gastroenterology, Kangwon National University Hospital, Chuncheon, Korea
| | - Jeong Won Heo
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Da Hye Moon
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Seong Hee Kang
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Young Don Kim
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Gab Jin Cheon
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Dae Hee Choi
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
- Department of Gastroenterology, Kangwon National University Hospital, Chuncheon, Korea
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Ning Q, Chen T, Wang G, Xu D, Yu Y, Mao Q, Li T, Li L, Li J, Lu X, Li J, Li Z, Zhang W, Xiao Y, Meng Q, Mi Y, Shang J, Yu Y, Zhao Y, Zhao C, Zhao H, Huang J, Peng J, Tang H, Tang X, Hu J, Hu B, Guo W, Zheng B, Chen B, Zhang Y, Wei J, Sheng J, Chen Z, Wang M, Xie Q, Wang Y, Wang FS, Hou J, Duan Z, Wei L, Jia J. Expert Consensus on Diagnosis and Treatment of End-Stage Liver Disease Complicated with Infections. INFECTIOUS DISEASES & IMMUNITY 2022; 2:168-178. [DOI: 10.1097/id9.0000000000000055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Indexed: 10/13/2023]
Abstract
Abstract
End-stage liver disease (ESLD) is a life-threatening clinical syndrome that markedly increases mortality in patients with infections. In patients with ESLD, infections can induce or aggravate the occurrence of liver decompensation. Consequently, infections are among the most common complications of disease progression. There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus. This consensus assembled up-to-date knowledge and experience across Chinese colleagues, providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.
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Affiliation(s)
- Qin Ning
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Tao Chen
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Guiqiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, China
| | - Dong Xu
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yanyan Yu
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, China
| | - Qing Mao
- Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing 400038, China
| | - Taisheng Li
- Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jun Li
- Department of Infectious Disease, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China
| | - Xiaoju Lu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Jiabin Li
- Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, Hefei 230031, China
| | - Zhiwei Li
- Department of Infectious Diseases, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110801, China
| | - Wenhong Zhang
- Department of Infectious Diseases, Institute of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Yonghong Xiao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Qinghua Meng
- Department of Severe Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Yuqiang Mi
- Nankai University Second People's Hospital, Tianjin 300071, China
| | - Jia Shang
- Department of Infectious Disease, People's Hospital of Henan Province, Zhengzhou 450003, China
| | - Yunsong Yu
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China
| | - Yingren Zhao
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
| | - Caiyan Zhao
- Department of Infectious Diseases, Third Affiliated Hospital of Hebei Medical University, Shijiazhuang 050051, China
| | - Hong Zhao
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, China
| | - Jianrong Huang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jie Peng
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Xiaoping Tang
- Research Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China
| | - Jinhua Hu
- Liver Failure Treatment and Research Center, The Fifth Medical Center, China PLA General Hospital, Beijing 100039, China
| | - Bijie Hu
- Department of Infectious Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China
| | - Wei Guo
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Bo Zheng
- Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034, China
| | - Baiyi Chen
- Department of Infectious Diseases, The First Hospital of China Medical University, Shenyang 110002, China
| | - Yuexin Zhang
- Center of Infectious Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China
| | - Jia Wei
- Department of Infectious Disease, The Second People's Hospital, Kunming 650201, China
| | - Jifang Sheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Zhi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Minggui Wang
- Department of Infectious Diseases, Institute of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Yuming Wang
- Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing 400038, China
| | - Fu-Sheng Wang
- Liver Failure Treatment and Research Center, The Fifth Medical Center, China PLA General Hospital, Beijing 100039, China
| | - Jinlin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Zhongping Duan
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Lai Wei
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University Hepatology Institute, Peking University People's Hospital, Beijing 100044, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medial University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis & National Clinical Research Center for Digestive Diseases, Beijing 100050, China
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Sehgal R, Maiwall R, Rajan V, Islam M, Baweja S, Kaur N, Kumar G, Ramakrishna G, Sarin SK, Trehanpati N. Granulocyte-Macrophage Colony-Stimulating Factor Modulates Myeloid-Derived Suppressor Cells and Treg Activity in Decompensated Cirrhotic Patients With Sepsis. Front Immunol 2022; 13:828949. [PMID: 35720398 PMCID: PMC9205181 DOI: 10.3389/fimmu.2022.828949] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 05/03/2022] [Indexed: 11/28/2022] Open
Abstract
Background Decompensated cirrhosis patients are more prone to bacterial infections. Myeloid-derived suppressor cells (MDSCs) expand in sepsis patients and disrupt immune cell functions. Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy helps in restoring immune cell functions and resolving infections. Its role in MDSC modulation in cirrhosis with sepsis is not well understood. Methods A total of 164 decompensated cirrhotic—62 without (w/o), 72 with sepsis, and 30 with sepsis treated with GM-CSF—and 15 healthy were studied. High-dimensional flow cytometry was performed to analyze MDSCs, monocytes, neutrophils, CD4 T cells, and Tregs at admission and on days 3 and day 7. Ex vivo co-cultured MDSCs with T cells were assessed for proliferation and apoptosis of T cells and differentiation to Tregs. Plasma factors and mRNA levels were analyzed by cytokine-bead assay and qRT-PCR. Results Frequencies of MDSCs and Tregs were significantly increased (p = 0.011 and p = 0.02) with decreased CD4 T cells (p = 0.01) in sepsis than w/o sepsis and healthy controls (HCs) (p = 0.000, p = 0.07, and p = 0.01) at day 0 and day 7. In sepsis patients, MDSCs had increased IL-10, Arg1, and iNOS mRNA levels (p = 0.016, p = 0.043, and p = 0.045). Ex vivo co-cultured MDSCs with T cells drove T-cell apoptosis (p = 0.03, p = 0.03) with decreased T-cell proliferation and enhanced FOXP3+ expression (p = 0.044 and p = 0.043) in sepsis compared to w/o sepsis at day 0. Moreover, blocking the MDSCs with inhibitors suppressed FOXP3 expression. GM-CSF treatment in sepsis patients significantly decreased MDSCs and FOXP3+ Tregs but increased CD4 T-cell functionality and improved survival. Conclusion MDSCs have an immunosuppressive function by expanding FOXP3+ Tregs and inhibiting CD4+ T-cell proliferation in sepsis. GM-CSF treatment suppressed MDSCs, improved T-cell functionality, and reduced Tregs in circulation.
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Affiliation(s)
- Rashi Sehgal
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
- Amity Institute of Biotechnology, Amity University, Noida, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vijayaraghavan Rajan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Mojahidul Islam
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sukriti Baweja
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Navkiran Kaur
- Amity Institute of Biotechnology, Amity University, Noida, India
| | - Guresh Kumar
- Department of Clinical Research and Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Gayatri Ramakrishna
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K. Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
- *Correspondence: Nirupma Trehanpati, ; ; Shiv K. Sarin, ;
| | - Nirupma Trehanpati
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
- *Correspondence: Nirupma Trehanpati, ; ; Shiv K. Sarin, ;
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Jiang J, Liu D, Wang Y, Li W, Hong Z, An J, Qiao S, Xie Z. Glaucocalyxin a protect liver function via inhibiting platelet over-activation during sepsis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 100:154089. [PMID: 35398736 DOI: 10.1016/j.phymed.2022.154089] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 03/23/2022] [Accepted: 03/28/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) is a perennial herb, and is traditionally used as folk medicine for treating inflammatory diseases and cancer. Gaucocalyxin A (GLA) is an ent‑kaurane diterpenoid that is isolated from the aerial parts of R. japonica (Burm. f.) var. glaucocalyx (Maxim.). In a recent study, we found that GLA protects against acute liver dysfunction induced by Escherichia coli, which is likely related to its anti-inflammatory effects. However, the mechanism by which GLA protects liver injury during sepsis is unknown. AIM To evaluate the anti-inflammatory function of GLA and its regulatory effect on platelet function. METHOD An in vivo model of sepsis was established by inoculating mice with E. coli. Live function and platelet activation were evaluated through standard assays. The levels of pro-inflammatory factors were measured through ELISA and qRT-PCR. RESULTS GLA alleviated liver dysfunction in the mouse model of sepsis. GLA-treated mice displayed lower complement activation and liver dysfunction after E. coli infection. GLA alleviated the decrease in peripheral platelet counts by inhibiting their clearance by Kupffer cells in liver. Furthermore, GLA inhibited platelet activation through the RIP1/RIP3/AKT pathway and downregulated C3aR expression on the platelets, thereby inhibiting liver injury and dysfunction due to excessive complement activation. CONCLUSION GLA can inhibit platelet activation by reducing surface expression of C3aR, which protect the liver from injury induced by excessive complement activation. GLA is a novel therapeutic agent for controlling sepsis-related liver dysfunction.
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Affiliation(s)
- Jiang Jiang
- Department of Nuclear Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Dengping Liu
- Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Yuanyuan Wang
- Department of Intensive Care Unit, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Wei Li
- Cyrus Tang Hematology Center, Soochow University, Suzhou, China
| | - Zhihui Hong
- Department of Nuclear Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Jianzhong An
- Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Shigang Qiao
- Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China; Faculty of Anesthesiology, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Zhanli Xie
- Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
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IL-1R1 blockade attenuates liver injury through inhibiting the recruitment of myeloid-derived suppressor cells in sepsis. Biochem Biophys Res Commun 2022; 620:21-28. [DOI: 10.1016/j.bbrc.2022.06.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/08/2022] [Accepted: 06/10/2022] [Indexed: 11/23/2022]
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Qi X, Bai Z, Zhu Q, Cheng G, Chen Y, Dang X, Ding H, Han J, Han L, He Y, Ji F, Jin H, Li B, Li H, Li Y, Li Z, Liu B, Liu F, Liu L, Lin S, Ma D, Meng F, Qi R, Ren T, Shao L, Tang S, Tang Y, Teng Y, Wang C, Wang R, Wu Y, Xu X, Yang L, Yuan J, Yuan S, Yang Y, Zhao Q, Zhang W, Yang Y, Guo X, Xie W. Practice guidance for the use of terlipressin for liver cirrhosis-related complications. Therap Adv Gastroenterol 2022; 15:17562848221098253. [PMID: 35601800 PMCID: PMC9121451 DOI: 10.1177/17562848221098253] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 04/12/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis-related complications has been recognized during recent years. This article aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis-related complications. METHODS Hepatobiliary Study Group of the Chinese Society of Gastroenterology of the Chinese Medical Association and Hepatology Committee of the Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. RESULTS Overall, 10 major guidance statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. CONCLUSION The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis-related complications.
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Affiliation(s)
- Xingshun Qi
- Department of Gastroenterology, General
Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang 110015,
Liaoning, China
| | - Zhaohui Bai
- Department of Gastroenterology, General
Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and
Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Qiang Zhu
- Department of Gastroenterology, Shandong
Provincial Hospital Affiliated to Shandong First Medical University, Jinan,
China
| | - Gang Cheng
- Department of Life Sciences and
Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Yu Chen
- Difficult and Complicated Liver Diseases and
Artificial Liver Center, Beijing You’an Hospital, Capital Medical
University, Beijing, China
| | - Xiaowei Dang
- Department of Hepatobiliary and Pancreatic
Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou,
China
| | - Huiguo Ding
- Department of Gastrointestinal and Hepatology,
Beijing You’An Hospital, Capital Medical University, Beijing, China
| | - Juqiang Han
- Institute of Liver Disease, The 7th Medical
Centre of Chinese People Liberation Army General Hospital, Beijing,
China
| | - Lei Han
- Department of Hepatobiliary Surgery, General
Hospital of Northern Theater Command, Shenyang, China
| | - Yingli He
- Department of Infectious Diseases, First
Affiliated Teaching Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Fanpu Ji
- Department of Infectious Diseases, The Second
Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Hongxu Jin
- Department of Emergency Medicine, General
Hospital of Northern Theater Command, Shenyang, China
| | - Bimin Li
- Department of Gastroenterology, The First
Affiliated Hospital of Nanchang University, Nanchang, China
| | - Hongyu Li
- Department of Gastroenterology, General
Hospital of Northern Theater Command, Shenyang, China
| | - Yiling Li
- Department of Gastroenterology, First
Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhiwei Li
- Department of Hepato-Biliary Surgery, Shenzhen
Third People’s Hospital, Shenzhen, China
| | - Bang Liu
- Department of Hepatobiliary Disease, 900
Hospital of the Joint Logistics Team, Fuzhou, China
| | - Fuquan Liu
- Department of Interventional Radiology,
Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Lei Liu
- Department of Gastroenterology, Tangdu
Hospital of the Fourth Military Medical University, Xi’an, China
| | - Su Lin
- Liver Research Center, The First Affiliated
Hospital of Fujian Medical University, Fuzhou, China
| | - Dapeng Ma
- Department of Critical Care Medicine, The
Sixth People’s Hospital of Dalian, Dalian, China
| | - Fanping Meng
- Department of Infectious Diseases, The Fifth
Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ruizhao Qi
- Department of General Surgery, The Fifth
Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Tianshu Ren
- Department of Pharmacy, General Hospital of
Northern Theater Command, Shenyang, China
| | - Lichun Shao
- Department of Gastroenterology, Air Force
Hospital of Northern Theater Command, Shenyang, China
| | - Shanhong Tang
- Department of Gastroenterology, General
Hospital of Western Theater Command, Chengdu, China
| | - Yufu Tang
- Department of Hepatobiliary Surgery, General
Hospital of Northern Theater Command, Shenyang, China
| | - Yue Teng
- Department of Emergency Medicine, General
Hospital of Northern Theater Command, Shenyang, China
| | - Chunhui Wang
- Department of Hepatobiliary Surgery, General
Hospital of Northern Theater Command, Shenyang, China
| | - Ran Wang
- Department of Gastroenterology, General
Hospital of Northern Theater Command, Shenyang, China
| | - Yunhai Wu
- Department of Critical Care Medicine, Sixth
People’s Hospital of Shenyang, Shenyang, China
| | - Xiangbo Xu
- Department of Gastroenterology, General
Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and
Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Ling Yang
- Department of Gastroenterology, Union
Hospital, Tongji Medical College, Huazhong University of Science and
Technology, Wuhan, China
| | - Jinqiu Yuan
- Clinical Research Center, The Seventh
Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Shanshan Yuan
- Department of Gastroenterology, Xi’an Central
Hospital, Xi’an, China
| | - Yida Yang
- Collaborative Innovation Center for Diagnosis
and Treatment of Infectious Diseases, The First Affiliated Hospital,
Zhejiang University School of Medicine, Hangzhou, China
| | - Qingchun Zhao
- Department of Pharmacy, General Hospital of
Northern Theater Command, Shenyang, China
| | - Wei Zhang
- Department of Hepatobiliary Surgery, General
Hospital of Northern Theater Command, Shenyang, China
| | - Yongping Yang
- Department of Liver Disease, The Fifth Medical
Center of Chinese PLA General Hospital, 100 West Fourth Ring Middle Road,
Beijing 100039, China
| | - Xiaozhong Guo
- Department of Gastroenterology, General
Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang 110015,
Liaoning, China
| | - Weifen Xie
- Department of Gastroenterology, Changzheng
Hospital, Naval Medical University, Shanghai 200003, China
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Chang YC, Chen JS, Yin CH, Shin-Jung Lee S, Chen WC. Candidemia in hospitalized cirrhotic patients with bloodstream infection: A retrospective analysis and brief summary of published studies. J Chin Med Assoc 2022; 85:295-303. [PMID: 35259132 DOI: 10.1097/jcma.0000000000000695] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Candidemia is a life-threatening condition; however, the predictive markers for candidemia and mortality are inadequate in cirrhotic patients. This study was conducted to propose candidate predictors for the occurrence of candidemia and 30-day mortality in hospitalized cirrhotic patients with bloodstream infection (BSI) and review the related literature. METHODS Cirrhotic patients with BSI between January 2011 and March 2020 were screened from the databank of a medical center and eligible patients were enrolled. Patients were separated into candidemia and bacteremia groups according to the results of blood cultures. Baseline characteristics, clinical presentation, and biochemistry data were collected at this time, as were microbiological data, medical management, use of antimicrobial agents, and outcome of the patients. The parameters and 30-day mortality were compared between candidemia and bacteremia groups. A combination of the MeSH terms and text terms related to candidemia and cirrhosis was searched in the electronic databases. RESULTS Four hundred and sixty cirrhotic patients with BSI were enrolled. Thirty-five patients with candidemia (7.6%) were identified. Nosocomial infection, intensive care unit (ICU) admission, antibiotics exposure ≥14 days, white cell count >10 K/mm3, and model for end-stage liver disease (MELD) score >24 were associated with candidemia. The 30-day mortality was 65.7% in the candidemia group and 37.9% in the bacteremia group (p = 0.001). Nosocomial infection, ICU admission, hepatoma, hepatic encephalopathy, international normalized ratio ≥1.2, platelet ≤150 K/mm3, estimated glomerular filtration rate <60 mL/min/1.73m2, and MELD score >24 were associated with 30-day mortality. Six studies were identified. The results were consistent with our findings regarding low incidence of candidemia, and relevant risk factors are listed. CONCLUSION Candidemia had low incidence but high mortality in hospitalized cirrhotic patients with BSI. New predictors were proposed for the occurrence of candidemia and 30-day mortality in these patients.
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Affiliation(s)
- Yu-Chen Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Jin-Shuen Chen
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Chun-Hao Yin
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Susan Shin-Jung Lee
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Institute of Biomedical Sciences, College of Science, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC
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50
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Chan YC, Chen CL, Wang CC, Lin CC, Yong CC, Chiu KW, Wu KL. Extremity risk factors of sepsis for gastrointestinal endoscopy in patients with liver cirrhosis. BMC Gastroenterol 2022; 22:54. [PMID: 35139804 PMCID: PMC8826657 DOI: 10.1186/s12876-022-02124-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 01/27/2022] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Liver cirrhosis is a well-known risk factor of sepsis after emergent gastrointestinal (GI) endoscopy. Elective GI endoscopy before living donor liver transplantation (LDLT), however, may also carry the septic risk among these patients. METHODS This retrospective study reviewed the medical records of 642 cirrhotic recipients who underwent GI endoscopy from 2008 to 2016. We analyzed the incidence and risk factors of post-endoscopy sepsis during 2008-2012 (experience cohort). Our protocol changed after 2013 (validation cohort) to include antibiotic prophylaxis. RESULTS In experience cohort, 36 cases (10.5%) of the 342 LDLT candidates experienced sepsis within 48 h after endoscopy. The sepsis rate was significantly higher in patients with hepatic decompensation than patients without (22.2% vs. 9.6% vs. 2.6% in Child C/B/A groups respectively; ×2 = 20.97, P < 0.001). Using multivariate logistic regression analysis, the factors related to post-endoscopy sepsis were the Child score (OR 1.46; 95% CI 1.24-1.71), Child classes B and C (OR 3.80 and 14.13; 95% CI 1.04-13.95 and 3.97-50.23, respectively), hepatic hydrothorax (OR 4.85; 95% CI 1.37-17.20), and use of antibiotic prophylaxis (OR 0.08; 95% CI 0.01-0.64). In validation cohort, antibiotics were given routinely, and all cases of hepatic hydrothorax (n = 10) were drained. Consequently, 4 (1.3%) episodes of sepsis occurred among 300 LDLT candidates, and the incidence was significantly lower than before (1.3% vs. 10.5%, P < 0.001). CONCLUSIONS Patients with decompensated cirrhosis and hepatic hydrothorax have higher risk of sepsis following endoscopy. In advanced cirrhotic patients, antibiotic prophylaxis and drainage of hydrothorax may be required to prevent sepsis before elective GI endoscopy.
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Affiliation(s)
- Yi-Chia Chan
- Liver Transplantation Center, and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, 83303, Kaohsiung, Taiwan
| | - Chao-Long Chen
- Liver Transplantation Center, and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, 83303, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center, and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, 83303, Kaohsiung, Taiwan
| | - Chih-Che Lin
- Liver Transplantation Center, and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, 83303, Kaohsiung, Taiwan.
| | - Chee-Chien Yong
- Liver Transplantation Center, and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, 83303, Kaohsiung, Taiwan
| | - King-Wah Chiu
- Liver Transplantation Center, and Department of Internal Medicine, Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Keng-Liang Wu
- Liver Transplantation Center, and Department of Internal Medicine, Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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