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McGettigan B, Hernandez-Tejero M, Malhi H, Shah V. Immune Dysfunction and Infection Risk in Advanced Liver Disease. Gastroenterology 2025; 168:1085-1100. [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] [MESH Headings] [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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2
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Dorff EM, Crooker K, Teng T, Hickey T, HoddWells M, Sarathy A, Muniz S, Lor J, Chang A, Singh D, Dejace J, Riser E, Tompkins BJ, Hale AJ. Clinical Characteristics and Outcomes of Patients with Cirrhosis Who Develop Infective Endocarditis. Infect Dis Rep 2025; 17:37. [PMID: 40277964 PMCID: PMC12027125 DOI: 10.3390/idr17020037] [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: 03/10/2025] [Revised: 04/01/2025] [Accepted: 04/07/2025] [Indexed: 04/26/2025] Open
Abstract
Background: Infective endocarditis (IE) is an increasingly common infection that results in significant morbidity and mortality. An important but under-analyzed subpopulation of patients with IE are those with concomitant cirrhosis. This study compared the characteristics and outcomes of patients with and without cirrhosis who were hospitalized with IE. Methods: The authors conducted a retrospective cohort study in adult patients with IE admitted at a single center from 2010 to 2020, comparing outcomes between those with and without cirrhosis at the time of admission. Results: A total of 22 patients with a history of cirrhosis and 356 patients without a history of cirrhosis were included. Over a quarter (27.3%) of those with cirrhosis experienced a decompensation event within two years of their admission for IE. Clinical features, microbiology, and direct complications from IE were largely similar between groups. There was no significant difference in IE-related mortality rates between groups, although, in an overall survival analysis, the group with cirrhosis did have a higher risk of all-cause mortality at 2 years (HR = 2.85; p = 0.012). Conclusions: This study highlights that IE in patients with cirrhosis may contribute to or trigger decompensation events. Further research is warranted to better understand morbidity outcomes in patients with cirrhosis who develop IE.
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Affiliation(s)
- Erika M. Dorff
- Department of Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA; (E.M.D.)
| | - Kyle Crooker
- Department of Medicine, Henry Ford Hospital, Detroit, MI 48202, USA
| | - Torrance Teng
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Tess Hickey
- Department of Medicine, University of Utah Hospital, Salt Lake City, UT 84132, USA
| | - Max HoddWells
- Department of Medicine, Maine Medical Center, Portland, ME 04102, USA
| | - Ashwini Sarathy
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Sean Muniz
- Department of Emergency Medicine, University of Utah Hospital, Salt Lake City, UT 84132, USA
| | - Jennifer Lor
- Department of Medicine, Rush University Medical Center, Chicago, IL 60612, USA
| | - Amy Chang
- Department of Medicine, Highland Hospital, Oakland, CA 94602, USA
| | - Devika Singh
- Department of Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA; (E.M.D.)
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Jean Dejace
- Department of Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA; (E.M.D.)
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Elly Riser
- Department of Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA; (E.M.D.)
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Bradley J. Tompkins
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Andrew J. Hale
- Department of Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA; (E.M.D.)
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
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Schulz MS, Angeli P, Trebicka J. Acute and non-acute decompensation of liver cirrhosis (47/130). Liver Int 2025; 45:e15861. [PMID: 38426268 PMCID: PMC11815624 DOI: 10.1111/liv.15861] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 12/18/2023] [Accepted: 01/19/2024] [Indexed: 03/02/2024]
Abstract
In the traditional view, the occurrence of cirrhosis-related complications, such as hepatic encephalopathy, formation of ascites or variceal haemorrhage, marks the transition to the decompensated stage of cirrhosis. Although the dichotomous stratification into a compensated and decompensated state reflects a prognostic water-shed moment and remains to hold its prognostic validity, it represents an oversimplification of clinical realities. A broadening understanding of pathophysiological mechanisms underpinning decompensation have led to the identification of distinct prognostic subgroups, associated with different clinical courses following decompensation. Data provided by the PREDICT study uncovered three distinct sub-phenotypes of acute decompensation (AD). Moreover, acute-on-chronic liver failure (ACLF) has been established as a distinct clinical entity for many years, which is associated with a high short-term mortality. Recently, non-acute decompensation (NAD) has been proposed as a distinct pathway of decompensation, complementing current concepts of the spectrum of decompensation. In contrast to AD, NAD is characterized by a slow and progressive development of complications, which are often presented at first decompensation and/or in patients in an earlier stage of chronic liver disease. Successful treatment of AD or NAD may lead to a clinical stabilization or even the concept of recompensation. This review aims to provide an overview on current concepts of decompensation and to delineate recent advances in our clinical and pathophysiological understanding.
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Affiliation(s)
- Martin S. Schulz
- Department of Internal Medicine BUniversity of MünsterMünsterGermany
| | - Paolo Angeli
- European Foundation for Study of Chronic Liver FailureBarcelonaSpain
| | - Jonel Trebicka
- Department of Internal Medicine BUniversity of MünsterMünsterGermany
- European Foundation for Study of Chronic Liver FailureBarcelonaSpain
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Sturm L, Schultheiss M, Stöhr F, Labenz C, Maasoumy B, Tiede A, Praktiknjo M, Seifert LL, Auer TA, Fehrenbach U, Piecha F, Harberts A, Kluwe J, Bruns T, Pollmanns MR, Chang J, Grobelski J, Jansen C, Meyer C, Reincke M, Rohrer C, Philipp Arbabi SR, Kimmann M, Ripoll C, Zipprich A, Hinrichs J, Koehler M, Trebicka J, Kloeckner R, Engelmann C, Thimme R, Bettinger D. Freiburg index of post-TIPS survival (FIPS) identifies patients at risk of further decompensation and ACLF after TIPS. J Hepatol 2025:S0168-8278(25)00067-4. [PMID: 39914747 DOI: 10.1016/j.jhep.2025.01.030] [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: 08/07/2024] [Revised: 01/15/2025] [Accepted: 01/23/2025] [Indexed: 04/04/2025]
Abstract
BACKGROUND & AIMS The Freiburg index of post-TIPS survival (FIPS) defines a high-risk group of patients with significantly reduced survival following transjugular intrahepatic portosystemic shunt (TIPS) implantation. However, the clinical hallmarks responsible for these patients' unfavorable outcome remain to be identified. Therefore, the present study aimed to characterize the clinical course after TIPS implantation according to the FIPS. METHODS A total of 1,359 patients with cirrhosis allocated to TIPS implantation for treatment of recurrent or refractory ascites or secondary prophylaxis of variceal bleeding from eight tertiary centers were retrospectively included. The patients' clinical course following TIPS placement was analyzed, stratified according to the FIPS. The primary study outcome was further decompensation within 90 days after TIPS; secondary outcomes were acute-on-chronic liver failure (ACLF) within 90 days and 1-year transplant-free survival. RESULTS Further decompensation after TIPS implantation was significantly more frequent in FIPS high-risk patients compared to low-risk patients (cumulative incidence function 0.58 vs. 0.38, p <0.001). Moreover, FIPS high-risk patients developed ACLF significantly more often (0.18 vs. 0.08; p = 0.008). Uni- and multivariable competing risk regression analyses confirmed that high-risk FIPS independently predicted further decompensation (subdistribution hazard ratio 1.974; 95% CI 1.531-2.544; p <0.001) and ACLF (subdistribution hazard ratio 2.586; 95% CI 1.449-4.616; p = 0.001) after TIPS. Importantly, further decompensation and ACLF after TIPS were associated with significantly reduced transplant-free survival. CONCLUSIONS The present study reveals that the FIPS predicts development of further decompensation and ACLF after TIPS implantation. These events are responsible for impaired transplant-free survival in FIPS high-risk patients. These results pave the way for the development of tailored clinical management strategies. IMPACT AND IMPLICATIONS Prognostication after transjugular intrahepatic portosystemic shunt (TIPS) implantation is challenging. Several clinical scores have been proposed in this context, such as the Freiburg index of post-TIPS survival (FIPS). The FIPS can identify a high-risk group of patients with significantly reduced survival after TIPS. However, to understand the reasons for these patients' unfavorable outcome, their clinical course after TIPS needs to be characterized. This study reveals that the FIPS predicts development of further decompensation and acute-on-chronic liver failure after TIPS implantation, which are responsible for the poor prognosis of FIPS high-risk patients. Therefore, the present results may be useful for tailored decision making in patients allocated to TIPS implantation.
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Affiliation(s)
- Lukas Sturm
- Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Germany
| | - Michael Schultheiss
- Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Germany
| | - Fabian Stöhr
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany
| | - Christian Labenz
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Anja Tiede
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Michael Praktiknjo
- Department of Medicine B, Gastroenterology, Hepatology, Endocrinology, Infectious Diseases, Universitätsklinikum Münster, Münster, Germany
| | - Leon Louis Seifert
- Department of Medicine B, Gastroenterology, Hepatology, Endocrinology, Infectious Diseases, Universitätsklinikum Münster, Münster, Germany; Center for Clinical and Translational Science, The Rockefeller University, New York, USA
| | - Timo Alexander Auer
- Department of Radiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Uli Fehrenbach
- Department of Radiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Felix Piecha
- I. Department of Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Martinistr. 42, 20246, Hamburg, Germany
| | - Aenne Harberts
- I. Department of Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Martinistr. 42, 20246, Hamburg, Germany
| | - Johannes Kluwe
- I. Department of Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Martinistr. 42, 20246, Hamburg, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | | | - Johannes Chang
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Jakub Grobelski
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Christian Jansen
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
| | - Carsten Meyer
- Department of Radiology, University Hospital, University Bonn, Bonn, Germany
| | - Marlene Reincke
- Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany
| | - Charlotte Rohrer
- Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany
| | - Sina Rastin Philipp Arbabi
- Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany
| | - Markus Kimmann
- Department of Medicine B, Gastroenterology, Hepatology, Endocrinology, Infectious Diseases, Universitätsklinikum Münster, Münster, Germany
| | - Cristina Ripoll
- Internal Medicine IV, Department for Gastroenterology, Hepatology, Interdisciplinary Endoscopy and Infectious Diseases, Jena University Hospital, Friedrich-Schiller University, Jena, Germany
| | - Alexander Zipprich
- Internal Medicine IV, Department for Gastroenterology, Hepatology, Interdisciplinary Endoscopy and Infectious Diseases, Jena University Hospital, Friedrich-Schiller University, Jena, Germany
| | - Jan Hinrichs
- St. Bernward Krankenhaus, Klinik für diagnostische und interventionelle Radiologie und Neuroradiologie, Hildesheim, Germany
| | - Michael Koehler
- Department of Radiology, University Hospital Muenster, Muenster, Germany
| | - Jonel Trebicka
- Department of Medicine B, Gastroenterology, Hepatology, Endocrinology, Infectious Diseases, Universitätsklinikum Münster, Münster, Germany
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University of Lübeck, Lübeck, Germany
| | - Cornelius Engelmann
- Charité - Universitaetsmedizin Berlin; Campus Virchow Klinikum; Department of Hepatology and Gastroenterology, Berlin, Germany
| | - Robert Thimme
- Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany
| | - Dominik Bettinger
- Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany.
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5
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Dibos M, Mayr U, Triebelhorn J, Schmid RM, Lahmer T. [Infections and liver cirrhosis]. Med Klin Intensivmed Notfmed 2024; 119:465-469. [PMID: 39120610 DOI: 10.1007/s00063-024-01168-2] [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: 07/08/2024] [Revised: 07/10/2024] [Accepted: 07/10/2024] [Indexed: 08/10/2024]
Abstract
End-stage liver disease is a life-threatening clinical syndrome combined with a state of immune dysfunction. In this constellation patients are prone to bacterial, fungal and viral infections associated with markedly increased morbidity and mortality rates. Bacterial infections are the most prevalent kind of infection in patients with end-stage liver disease accounting for nearly 30%. The evolving rates of multidrug resistant organisms present enormous challenges in treatment strategies. Therefore, the urgent needs for prevention, early detection strategies and widespread treatment options are a necessity to handle the rising incidence of infection complications in end-stage liver disease.
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Affiliation(s)
| | | | | | | | - Tobias Lahmer
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Deutschland.
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6
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Incicco S, Angeli P, Piano S. Infectious Complications of Portal Hypertension. Clin Liver Dis 2024; 28:525-539. [PMID: 38945641 DOI: 10.1016/j.cld.2024.03.007] [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] [Indexed: 07/02/2024]
Abstract
Patients with cirrhosis and clinically significant portal hypertension are at high risk of developing bacterial infections (BIs) that are the most common trigger of acute decompensation and acute-on-chronic liver failure. Furthermore, after decompensation, the risk of developing BIs further increases in an ominous vicious circle. BIs may be subtle, and they should be ruled out in all patients at admission and in case of deterioration. Timely administration of adequate empirical antibiotics is the cornerstone of treatment. Herein, we reviewed current evidences about pathogenesis, clinical implications and management of BIs in patients with cirrhosis and portal hypertension.
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Affiliation(s)
- Simone Incicco
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy.
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7
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Piano S, Bunchorntavakul C, Marciano S, Rajender Reddy K. Infections in cirrhosis. Lancet Gastroenterol Hepatol 2024; 9:745-757. [PMID: 38754453 DOI: 10.1016/s2468-1253(24)00078-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 03/04/2024] [Accepted: 03/04/2024] [Indexed: 05/18/2024]
Abstract
Cirrhosis is an immune dysfunction state, and as such, patients with cirrhosis are susceptible to bacterial, fungal, and viral infections. Because of infection, these patients have a propensity to develop multiorgan failure, which is associated with high mortality. Bacterial infections are the most prevalent type of infection in patients with cirrhosis, with the prevalence of bacterial infections in patients admitted for an acute decompensating event ranging from 24% to 29%. Together with invasive fungal infections, bacterial infections are the most severe. Multidrug-resistant organisms have been evolving at a rapid and alarming rate around the world, which presents enormous challenges. The development of effective measures for the prevention, early detection, and treatment of infections in patients with cirrhosis is challenging, given the rising incidence of infections in this patient population.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
| | | | - Sebastian Marciano
- Department of Clinical Investigation, Italian Hospital, Buenos Aires, Argentina
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA.
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Saner FH, Raptis DA, Alghamdi SA, Malagó MM, Broering DC, Bezinover D. Navigating the Labyrinth: Intensive Care Challenges for Patients with Acute-on-Chronic Liver Failure. J Clin Med 2024; 13:506. [PMID: 38256640 PMCID: PMC10816826 DOI: 10.3390/jcm13020506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 01/07/2024] [Accepted: 01/14/2024] [Indexed: 01/24/2024] Open
Abstract
Acute-on-chronic liver failure (ACLF) refers to the deterioration of liver function in individuals who already have chronic liver disease. In the setting of ACLF, liver damage leads to the failure of other organs and is associated with increased short-term mortality. Optimal medical management of patients with ACLF requires implementing complex treatment strategies, often in an intensive care unit (ICU). Failure of organs other than the liver distinguishes ACLF from other critical illnesses. Although there is growing evidence supporting the current approach to ACLF management, the mortality associated with this condition remains unacceptably high. In this review, we discuss considerations for ICU care of patients with ACLF and highlight areas for further research.
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Affiliation(s)
- Fuat H. Saner
- Organ Transplant Center of Excellence, King Faisal Specialized Hospital & Research Center, Riyadh 12111, Saudi Arabia; (D.A.R.); (S.A.A.); (M.M.M.); (D.C.B.)
| | - Dimitri A. Raptis
- Organ Transplant Center of Excellence, King Faisal Specialized Hospital & Research Center, Riyadh 12111, Saudi Arabia; (D.A.R.); (S.A.A.); (M.M.M.); (D.C.B.)
| | - Saad A. Alghamdi
- Organ Transplant Center of Excellence, King Faisal Specialized Hospital & Research Center, Riyadh 12111, Saudi Arabia; (D.A.R.); (S.A.A.); (M.M.M.); (D.C.B.)
| | - Massimo M. Malagó
- Organ Transplant Center of Excellence, King Faisal Specialized Hospital & Research Center, Riyadh 12111, Saudi Arabia; (D.A.R.); (S.A.A.); (M.M.M.); (D.C.B.)
| | - Dieter C. Broering
- Organ Transplant Center of Excellence, King Faisal Specialized Hospital & Research Center, Riyadh 12111, Saudi Arabia; (D.A.R.); (S.A.A.); (M.M.M.); (D.C.B.)
| | - Dmitri Bezinover
- Department of Anesthesiology and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA;
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9
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Lemos GT, Terrabuio DRB, Nunes NN, Song ATW, Oshiro ICV, D'Albuquerque LAC, Levin AS, Abdala E, Freire MP. Pre-transplant multidrug-resistant infections in liver transplant recipients-epidemiology and impact on transplantation outcome. Clin Transplant 2024; 38:e15173. [PMID: 37877950 DOI: 10.1111/ctr.15173] [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: 05/30/2023] [Revised: 09/22/2023] [Accepted: 10/17/2023] [Indexed: 10/26/2023]
Abstract
BACKGROUND Cirrhotic patients are highly exposed to healthcare services and antibiotics. Although pre-liver transplantation (LT) infections are directly related to the worsening of liver function, the impact of these infections on LT outcomes is still unclear. This study aimed to identify the effect of multidrug-resistant microorganism (MDRO) infections before LT on survival after LT. METHODS Retrospective study that included patients who underwent LT between 2010 and 2019. Variables analyzed were related to patients' comorbidities, underlying diseases, time on the waiting list, antibiotic use, LT surgery, and occurrences post-LT. Multivariate analyses were performed using logistic regression, and Cox regression for survival analysis. RESULTS A total of 865 patients were included; 351 infections were identified in 259 (30%) patients, of whom 75 (29%) had ≥1 pre-LT MDRO infection. The most common infection was spontaneous bacterial peritonitis (34%). The agent was identified in 249(71%), 53(15%) were polymicrobial. The most common microorganism was Klebsiella pneumoniae (18%); the most common MDRO was ESBL-producing Enterobacterales (16%), and carbapenem-resistant (CR) Enterobacterales (10%). Factors associated with MDRO infections before LT were previous use of therapeutic cephalosporin (p = .001) and fluoroquinolone (p = .001), SBP prophylaxis (p = .03), ACLF before LT (p = .03), and days of hospital stay pre-LT (p < .001); HCC diagnosis was protective (p = .01). Factors associated with 90-day mortality after LT were higher MELD on inclusion to the waiting list (p = .02), pre-LT MDRO infection (p = .04), dialysis after LT (p < .001), prolonged duration of LT surgery (p < .001), post-LT CR-Gram-negative bacteria infection (p < .001), and early retransplantation (p = .004). CONCLUSION MDRO infections before LT have an important impact on survival after LT.
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Affiliation(s)
- Gabriela T Lemos
- Department of Infectious Diseases, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
| | - Debora R B Terrabuio
- Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, Sao Paulo, Brazil
| | - Nathalia N Nunes
- Department of Infectious Diseases, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
| | - Alice T W Song
- Division of Liver and Gastrointestinal Transplant, Hospital das Clínicas, Department of Surgery, University of São Paulo School of Medicine, Sao Paulo, Brazil
| | - Isabel C V Oshiro
- Working Committee for Hospital Epidemiology and Infection Control, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
| | - Luiz Augusto C D'Albuquerque
- Division of Liver and Gastrointestinal Transplant, Hospital das Clínicas, Department of Surgery, University of São Paulo School of Medicine, Sao Paulo, Brazil
| | - Anna S Levin
- Department of Infectious Diseases, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
| | - Edson Abdala
- Department of Infectious Diseases, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
| | - Maristela P Freire
- Department of Infectious Diseases, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
- Working Committee for Hospital Epidemiology and Infection Control, University of São Paulo School of Medicine Hospital das Clínicas, Sao Paulo, Brazil
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10
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Abstract
Ascites is the most common complication of cirrhosis, with 5-year mortality reaching 30%. Complications of ascites (ie, spontaneous bacterial peritonitis, hepatorenal syndrome, recurrent/refractory ascites, and hepatic hydrothorax) further worsen survival. The development of ascites is driven by portal hypertension, systemic inflammation, and splanchnic arterial vasodilation. Etiologic treatment and nonselective beta-blockers can prevent ascites in compensated cirrhosis. The treatment of ascites is currently based on the management of fluid overload (eg, diuretics, sodium restriction, and/or paracenteses). In selected patients, long-term albumin use, norfloxacin prophylaxis, and transjugular intrahepatic portosystemic shunt reduce the risk of further decompensation and improve survival.
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de Mattos ÂZ, Simonetto DA, Terra C, Farias AQ, Bittencourt PL, Pase THS, Toazza MR, de Mattos AA, Alliance of Brazilian Centers for Cirrhosis Care – the ABC Group. Albumin administration in patients with cirrhosis: Current role and novel perspectives. World J Gastroenterol 2022; 28:4773-4786. [PMID: 36156923 PMCID: PMC9476855 DOI: 10.3748/wjg.v28.i33.4773] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 06/05/2022] [Accepted: 07/05/2022] [Indexed: 02/06/2023] Open
Abstract
Mortality in cirrhosis is mostly associated with the development of clinical decompensation, characterized by ascites, hepatic encephalopathy, variceal bleeding, or jaundice. Therefore, it is important to prevent and manage such complications. Traditionally, the pathophysiology of decompensated cirrhosis was explained by the peripheral arterial vasodilation hypothesis, but it is currently understood that decompensation might also be driven by a systemic inflammatory state (the systemic inflammation hypothesis). Considering its oncotic and nononcotic properties, albumin has been thoroughly evaluated in the prevention and management of several of these decompensating events. There are formal evidence-based recommendations from international medical societies proposing that albumin be administered in individuals with cirrhosis undergoing large-volume paracentesis, patients with spontaneous bacterial peritonitis, those with acute kidney injury (even before the etiological diagnosis), and those with hepatorenal syndrome. Moreover, there are a few randomized controlled trials and meta-analyses suggesting a possible role for albumin infusion in patients with cirrhosis and ascites (long-term albumin administration), individuals with hepatic encephalopathy, and those with acute-on-chronic liver failure undergoing modest-volume paracentesis. Further studies are necessary to elucidate whether albumin administration also benefits patients with cirrhosis and other complications, such as individuals with extraperitoneal infections, those hospitalized with decompensated cirrhosis and hypoalbuminemia, and patients with hyponatremia.
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Affiliation(s)
- Ângelo Zambam de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Douglas Alano Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, United States
| | - Carlos Terra
- Department of Gastroenterology, State University of Rio de Janeiro, Rio de Janeiro 20550-170, Brazil
| | | | | | - Tales Henrique Soares Pase
- Internal Medicine Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Marlon Rubini Toazza
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Angelo Alves de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
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Piano S, Reiberger T, Larrue H, Bureau C. Prevention of Further Decompensation in Patients With Ascites. PORTAL HYPERTENSION VII 2022:549-562. [DOI: 10.1007/978-3-031-08552-9_49] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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13
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Zhang IW, López-Vicario C, Duran-Güell M, Clària J. Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts. Front Mol Biosci 2021; 8:772174. [PMID: 34888354 PMCID: PMC8650317 DOI: 10.3389/fmolb.2021.772174] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 11/04/2021] [Indexed: 12/12/2022] Open
Abstract
Mitochondria are entrusted with the challenging task of providing energy through the generation of ATP, the universal cellular currency, thereby being highly flexible to different acute and chronic nutrient demands of the cell. The fact that mitochondrial diseases (genetic disorders caused by mutations in the nuclear or mitochondrial genome) manifest through a remarkable clinical variation of symptoms in affected individuals underlines the far-reaching implications of mitochondrial dysfunction. The study of mitochondrial function in genetic or non-genetic diseases therefore requires a multi-angled approach. Taking into account that the liver is among the organs richest in mitochondria, it stands to reason that in the process of unravelling the pathogenesis of liver-related diseases, researchers give special focus to characterizing mitochondrial function. However, mitochondrial dysfunction is not a uniformly defined term. It can refer to a decline in energy production, increase in reactive oxygen species and so forth. Therefore, any study on mitochondrial dysfunction first needs to define the dysfunction to be investigated. Here, we review the alterations of mitochondrial function in liver cirrhosis with emphasis on acutely decompensated liver cirrhosis and acute-on-chronic liver failure (ACLF), the latter being a form of acute decompensation characterized by a generalized state of systemic hyperinflammation/immunosuppression and high mortality rate. The studies that we discuss were either carried out in liver tissue itself of these patients, or in circulating leukocytes, whose mitochondrial alterations might reflect tissue and organ mitochondrial dysfunction. In addition, we present different methodological approaches that can be of utility to address the diverse aspects of hepatocyte and leukocyte mitochondrial function in liver disease. They include assays to measure metabolic fluxes using the comparatively novel Biolog’s MitoPlates in a 96-well format as well as assessment of mitochondrial respiration by high-resolution respirometry using Oroboros’ O2k-technology and Agilent Seahorse XF technology.
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Affiliation(s)
- Ingrid W Zhang
- Biochemistry and Molecular Genetics Service, Hospital Clínic-IDIBAPS, Barcelona, Spain.,European Foundation for the Study of Chronic Liver Failure (EF Clif) and Grifols Chair, Barcelona, Spain
| | - Cristina López-Vicario
- Biochemistry and Molecular Genetics Service, Hospital Clínic-IDIBAPS, Barcelona, Spain.,European Foundation for the Study of Chronic Liver Failure (EF Clif) and Grifols Chair, Barcelona, Spain.,CIBERehd, Barcelona, Spain
| | - Marta Duran-Güell
- Biochemistry and Molecular Genetics Service, Hospital Clínic-IDIBAPS, Barcelona, Spain.,European Foundation for the Study of Chronic Liver Failure (EF Clif) and Grifols Chair, Barcelona, Spain
| | - Joan Clària
- Biochemistry and Molecular Genetics Service, Hospital Clínic-IDIBAPS, Barcelona, Spain.,European Foundation for the Study of Chronic Liver Failure (EF Clif) and Grifols Chair, Barcelona, Spain.,CIBERehd, Barcelona, Spain.,Department of Biomedical Sciences, University of Barcelona, Barcelona, Spain
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Yu J, Shi X, Ma J, Chen R, Dong S, Lu S, Wu J, Yan C, Wu J, Zheng S, Li L, Xu X, Cao H. C-Reactive Protein Is an Independent Predictor of 30-Day Bacterial Infection Post-Liver Transplantation. Biomolecules 2021; 11:1195. [PMID: 34439862 PMCID: PMC8391373 DOI: 10.3390/biom11081195] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/04/2021] [Accepted: 08/07/2021] [Indexed: 12/12/2022] Open
Abstract
The relationship between aseptic systemic inflammation and postoperative bacterial infection is unclear. We investigated the correlation of systemic inflammation biomarkers with 30-day clinically significant bacterial infections (CSI) after liver transplantation (LT). This retrospective study enrolled 940 patients who received LT and were followed for 30 days. The primary end point was 30-day CSI events. The cohort was divided into exploratory (n = 508) and validation (n = 432) sets according to different centers. Area under the receiver operated characteristic (AUROC) and Cox regression models were fitted to study the association between baseline systemic inflammation levels and CSI after LT. A total of 255 bacterial infectious events in 209 recipients occurred. Among systemic inflammation parameters, baseline C-reactive protein (CRP) was independently associated with 30-day CSI in the exploratory group. The combination of CRP and organ failure number showed a good discrimination for 30-day CSI (AUROC = 0.80, 95% CI, 0.76-0.84) and the results were confirmed in an external verification group. Additionally, CRP levels were correlated with bacterial product lipopolysaccharide. In conclusion, our study suggests that pre-transplantation CRP is independent of other prognostic factors for 30-day CSI post-LT, and can be integrated into tools for assessing the risk of bacterial infection post-LT or as a component of prognostic models.
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Affiliation(s)
- Jiong Yu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; (J.Y.); (X.S.); (J.M.); (J.W.); (C.Y.); (S.Z.); (L.L.)
- National Clinical Research Center for Infectious Diseases, 79 Qingchun Rd., Hangzhou 310003, China
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Rd., Hangzhou 310003, China
| | - Xiaowei Shi
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; (J.Y.); (X.S.); (J.M.); (J.W.); (C.Y.); (S.Z.); (L.L.)
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou 310003, China; (R.C.); (S.D.); (J.W.)
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Jing Ma
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; (J.Y.); (X.S.); (J.M.); (J.W.); (C.Y.); (S.Z.); (L.L.)
- National Clinical Research Center for Infectious Diseases, 79 Qingchun Rd., Hangzhou 310003, China
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Rd., Hangzhou 310003, China
| | - Ronggao Chen
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou 310003, China; (R.C.); (S.D.); (J.W.)
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Siyi Dong
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou 310003, China; (R.C.); (S.D.); (J.W.)
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Sen Lu
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
| | - Jian Wu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; (J.Y.); (X.S.); (J.M.); (J.W.); (C.Y.); (S.Z.); (L.L.)
- National Clinical Research Center for Infectious Diseases, 79 Qingchun Rd., Hangzhou 310003, China
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Rd., Hangzhou 310003, China
| | - Cuilin Yan
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; (J.Y.); (X.S.); (J.M.); (J.W.); (C.Y.); (S.Z.); (L.L.)
| | - Jian Wu
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou 310003, China; (R.C.); (S.D.); (J.W.)
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Shusen Zheng
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; (J.Y.); (X.S.); (J.M.); (J.W.); (C.Y.); (S.Z.); (L.L.)
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou 310003, China; (R.C.); (S.D.); (J.W.)
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Lanjuan Li
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; (J.Y.); (X.S.); (J.M.); (J.W.); (C.Y.); (S.Z.); (L.L.)
- National Clinical Research Center for Infectious Diseases, 79 Qingchun Rd., Hangzhou 310003, China
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Rd., Hangzhou 310003, China
| | - Xiao Xu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; (J.Y.); (X.S.); (J.M.); (J.W.); (C.Y.); (S.Z.); (L.L.)
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou 310003, China; (R.C.); (S.D.); (J.W.)
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Hongcui Cao
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; (J.Y.); (X.S.); (J.M.); (J.W.); (C.Y.); (S.Z.); (L.L.)
- National Clinical Research Center for Infectious Diseases, 79 Qingchun Rd., Hangzhou 310003, China
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Rd., Hangzhou 310003, China
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