scholarly journals Prognostic Role of Bacterial and Fungal Infections in Patients With Liver Cirrhosis With and Without Acute-on-Chronic Liver Failure: A Prospective 2-Center Study

2020 ◽  
Vol 7 (11) ◽  
Author(s):  
Michele Bartoletti ◽  
Maurizio Baldassarre ◽  
Marco Domenicali ◽  
Russell E Lewis ◽  
Maddalena Giannella ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Observational Study ◽  
Liver Failure ◽  
Prospective Observational Study ◽  
Fungal Infections ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Term Survival

Abstract Background Bacterial and fungal infections (BFIs) are frequent in patients with cirrhosis and often trigger acute-on-chronic liver failure (ACLF). This prospective observational study aims to describe the interactions between BFI and ACLF in terms of mortality and related risk factors. Methods We performed a 2-center prospective observational study enrolling hospitalized patients with cirrhosis admitted for acute decompensation. Data were recorded at admission and during hospitalization. Survival was recorded up to 1 year. Results Among the 516 patients enrolled, 108 (21%) were infected at admission, while an additional 61 patients (12%) developed an infection during hospital stay. In the absence of ACLF, the 1-year mortality rate of patients with BFI did not differ from that of patients without BFI (33% vs 31%; P = .553). In contrast, those with ACLF triggered or complicated by BFI had a significantly higher mortality rate than those who remained free from BFI (75% vs 54%; P = .011). Competing risk analysis showed that the negative impact of ACLF-related BFI on long-term prognosis was independent from Model for End-stage Liver Disease (MELD) incorporating serum sodium concentration score, comorbidity, and basal C-reactive protein level. Finally, multivariable logistic regression showed that higher MELD score (P < .001), QuickSOFA score ≥2 points (P = .007), and secondary bloodstream (P = .022) and multidrug-resistant pathogen isolation (P = .030) were independently associated with ACLF in patients with BFI. Conclusions This large prospective study indicated that the adverse impact of BFI on long-term survival in decompensated cirrhosis is not universal but is limited to those patients who also develop ACLF. Both disease severity and microbiological factors predispose infected decompensated patients to ACLF.

scholarly journals Good Tolerance of Citrate Accumulation due to Plasma Exchange among Patients with Acute-on-Chronic Liver Failure: A Prospective, Observational Study

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yuanji Ma ◽  
Yan Xu ◽  
Fang Chen ◽  
Ying Wang ◽  
Lang Bai ◽  
...  
Keyword(s):  
Observational Study ◽  
Liver Failure ◽  
Plasma Exchange ◽  
Prospective Observational Study ◽  
Meld Score ◽  
Chronic Liver ◽  
Ionized Calcium ◽  
Chronic Liver Failure ◽  
Citrate Accumulation ◽  
The Mean

Aim. To assess the tolerance of citrate accumulation due to plasma exchange (PE) among patients with acute-on-chronic liver failure (ACLF). Methods. A prospective, observational study was conducted among patients with ACLF who received heparin anticoagulation during PE-centered therapy without filtration and dialysis. Citrate accumulation was defined as the value of total calcium (Catot) to ionized calcium (Caion) ratio (Catot/Caion) greater than or equal to 2.5 (Catot/Caion≥2.5). Results. Fifty-four patients were enrolled. The mean age and MELD score were 50.0 ± 11.3 years old and 25 ± 7, respectively. Thirty-three patients had liver cirrhosis. The total 3-month survival rate was 57.4% (31/54). The mean Catot/Caion at the time before PE was 2.05 ± 0.14. Catot/Caion≥2.5 occurred in 100.0% (54/54) and 29.6% (16/54) of patients with mean Catot/Caion of 4.34 ± 1.52 and 2.36 ± 0.32 immediately after PE and 1 hour after PE, respectively, and these levels were much higher than those before PE (p<0.01). However, all values returned to lower than 2.5 by the next morning with no difference from those before PE (2.10 ± 0.14 versus 2.05 ± 0.14, p>0.05). Hypocalcemia (ionized calcium) and mild alkalosis were the main metabolic alterations. No symptoms associated with hypocalcemia occurred. Conclusions. Citrate accumulation is well tolerated by patients with ACLF who receive PE-centered therapy without filtration and dialysis. This study is regeristed with ChiCTR-OOC-17013618.

scholarly journals Acute-On-Chronic Liver Failure Defined by Asian Pacific Association for the Study of the Liver Should Include Decompensated Cirrhosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Manman Xu ◽  
Ming Kong ◽  
Pengfei Yu ◽  
Yingying Cao ◽  
Fang Liu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Failure ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Asian Pacific ◽  
Long Term Mortality

Background and Aims: Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver disease with high short-term mortality. The inclusion or exclusion of previously decompensated cirrhosis (DC) in the diagnostic criteria of ACLF defined by the Asian Pacific Association for the Study of the Liver (APASL-ACLF) has not been conclusive. We aimed to evaluate the prognostic impact of decompensated cirrhosis in ACLF.Methods: We retrospectively collected a cohort of patients with a diagnosis of APASL-ACLF (with or without DC) hospitalized from 2012 to 2020 at three liver units in tertiary hospitals. Baseline characteristics and survival data at 28, 90, 180, 360, 540, and 720 days were collected.Results: Of the patients assessed using APASL-ACLF criteria without the diagnostic indicator of chronic liver disease, 689 patients were diagnosed with ACLF, of whom 435 had no decompensated cirrhosis (non-DC-ACLF) and 254 had previously decompensated cirrhosis (DC-ACLF). The 28-, 90-, 180-, 360-, 540-, and 720-day mortality were 24.8, 42.9, 48.7, 57.3, 63.4, and 68.1%, respectively, in DC-ACLF patients, which were significantly higher than in non-DC-ACLF patients (p &lt; 0.05). DC was independently associated with long-term (180/360/540/720 days) but not short-term (28/90 days) mortality in patients with ACLF. Age, total bilirubin, international normalized ratio, and hepatic encephalopathy were independent risk factors for short- and long-term mortality risk in ACLF patients (p &lt; 0.05).Conclusions: Patients with DC-ACLF have a higher mortality rate, especially long-term mortality, compared to non-DC-ACLF patients. Therefore, DC should be included in the diagnostic criteria of APASL-ACLF and treated according to the ACLF management process.

scholarly journals Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

2021 ◽  
Vol 8 ◽  
Author(s):  
Arshi Khanam ◽  
Shyam Kottilil
Keyword(s):  
Liver Failure ◽  
Fungal Infections ◽  
Chronic Liver ◽  
Definitive Treatment ◽  
Decompensated Cirrhosis ◽  
Variceal Hemorrhage ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Pathophysiological Mechanisms ◽  
Short Term Mortality

Acute-on-chronic liver failure (ACLF) is a multifaceted condition with poor treatment options and high short-term mortality. ACLF can develop in patients with or without liver cirrhosis, where patients with decompensated cirrhosis display a higher risk of short-term mortality. Pathophysiological mechanisms include systemic inflammation due to bacterial and fungal infections and acute hepatic insult with drug, alcohol, and viral hepatitis. Cryptogenic factors also contribute to the development of ACLF. The clinical outcome of patients with ACLF gets further complicated by the occurrence of variceal hemorrhage, hepatorenal syndrome, hepatic encephalopathy, and systemic immune dysfunction. Regardless of the better understanding of pathophysiological mechanisms, no specific and definitive treatment is available except for liver transplantation. The recent approach of regenerative medicine using mesenchymal stem cells (MSCs) could be advantageous for the treatment of ACLF as these cells can downregulate inflammatory response by inducing antiinflammatory events and prevent hepatic damage and fibrosis by inhibiting hepatic stellate cell activation and collagen synthesis. Moreover, MSCs are involved in tissue repair by the process of liver regeneration. Considering the broad therapeutic potential of MSCs, it can serve as an alternative treatment to liver transplant in the near future, if promising results are achieved.

The Prediction of in‐Hospital Mortality in Decompensated Cirrhosis with Acute‐on‐Chronic Liver Failure

2021 ◽  
Author(s):  
Florence Wong ◽  
K Rajender Reddy ◽  
Puneeta Tandon ◽  
Jennifer C Lai ◽  
Nishita Jagarlamudi ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Liver Failure ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure

scholarly journals Inhibition of glutamine synthetase in monocytes from patients with acute-on-chronic liver failure resuscitates their antibacterial and inflammatory capacity

Gut ◽  
2018 ◽  
Vol 68 (10) ◽  
pp. 1872-1883 ◽  
Author(s):  
Hannelie Korf ◽  
Johannie du Plessis ◽  
Jos van Pelt ◽  
Sofie De Groote ◽  
David Cassiman ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Liver Failure ◽  
Bacterial Infections ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Phenotypic Characterisation ◽  
Severity Scores ◽  
Aclf Patient

ObjectiveAcute-on-chronic liver failure (ACLF) is associated with dysfunctional circulating monocytes whereby patients become highly susceptible to bacterial infections. Here, we identify the pathways underlying monocyte dysfunction in ACLF and we investigate whether metabolic rewiring reinstates their phagocytic and inflammatory capacity.DesignFollowing phenotypic characterisation, we performed RNA sequencing on CD14+CD16− monocytes from patients with ACLF and decompensated alcoholic cirrhosis. Additionally, an in vitro model mimicking ACLF patient-derived features was implemented to investigate the efficacy of metabolic regulators on monocyte function.ResultsMonocytes from patients with ACLF featured elevated frequencies of interleukin (IL)-10-producing cells, reduced human leucocyte antigen DR isotype (HLA-DR) expression and impaired phagocytic and oxidative burst capacity. Transcriptional profiling of isolated CD14+CD16− monocytes in ACLF revealed upregulation of an array of immunosuppressive parameters and compromised antibacterial and antigen presentation machinery. In contrast, monocytes in decompensated cirrhosis showed intact capacity to respond to inflammatory triggers. Culturing healthy monocytes in ACLF plasma mimicked the immunosuppressive characteristics observed in patients, inducing a blunted phagocytic response and metabolic program associated with a tolerant state. Metabolic rewiring of the cells using a pharmacological inhibitor of glutamine synthetase, partially restored the phagocytic and inflammatory capacity of in vitro generated- as well as ACLF patient-derived monocytes. Highlighting its biological relevance, the glutamine synthetase/glutaminase ratio of ACLF patient-derived monocytes positively correlated with disease severity scores.ConclusionIn ACLF, monocytes feature a distinct transcriptional profile, polarised towards an immunotolerant state and altered metabolism. We demonstrated that metabolic rewiring of ACLF monocytes partially revives their function, opening up new options for therapeutic targeting in these patients.

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