Leukocytes, Systemic Inflammation and Immunopathology in Acute-on-Chronic Liver Failure

Casulleras, Mireia; Zhang, Ingrid W; Clària, Joan

doi:10.3390/cells9122632

Cited by 94 publications

(67 citation statements)

References 116 publications

(172 reference statements)

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“…Albumin was taken up by leukocytes and localized in endosomes, where it inhibited Toll-like receptor signaling. In patients with acutely decompensated cirrhosis, albumin administration has been shown to reduce inflammation, and may therefore involve a direct effect of albumin on leukocytes [ 44 ].…”

Section: Bio-mechanistic Relationship Between Hypoalbuminemia and Infectionmentioning

confidence: 99%

Hypoalbuminemia as Surrogate and Culprit of Infections

Wiedermann¹

2021

IJMS

155

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Hypoalbuminemia is associated with the acquisition and severity of infectious diseases, and intact innate and adaptive immune responses depend on albumin. Albumin oxidation and breakdown affect interactions with bioactive lipid mediators that play important roles in antimicrobial defense and repair. There is bio-mechanistic plausibility for a causal link between hypoalbuminemia and increased risks of primary and secondary infections. Serum albumin levels have prognostic value for complications in viral, bacterial and fungal infections, and for infectious complications of non-infective chronic conditions. Hypoalbuminemia predicts the development of healthcare-associated infections, particularly with Clostridium difficile. In coronavirus disease 2019, hypoalbuminemia correlates with viral load and degree of acute lung injury and organ dysfunction. Non-oncotic properties of albumin affect the pharmacokinetics and pharmacodynamics of antimicrobials. Low serum albumin is associated with inadequate antimicrobial treatment. Infusion of human albumin solution (HAS) supplements endogenous albumin in patients with cirrhosis of the liver and effectively supported antimicrobial therapy in randomized controlled trials (RCTs). Evidence of the beneficial effects of HAS on infections in hypoalbuminemic patients without cirrhosis is largely observational. Prospective RCTs are underway and, if hypotheses are confirmed, could lead to changes in clinical practice for the management of hypoalbuminemic patients with infections or at risk of infectious complications.

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Section: Bio-mechanistic Relationship Between Hypoalbuminemia and Infectionmentioning

confidence: 99%

Hypoalbuminemia as Surrogate and Culprit of Infections

Wiedermann¹

2021

IJMS

155

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“…Under normal conditions, viable bacteria are killed by the immune system, and their components are released into the systemic circulation, leading to systemic inflammation without overt bacterial presence. During LT, using high-dose hormones and immunosuppressants to suppress immunity permits the translocation of intestinal bacteria, leading to bacterial infection and sepsis [36]. In addition, patients with organ failure have more severe systemic inflammation [37].…”

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein Is an Independent Predictor of 30-Day Bacterial Infection Post-Liver Transplantation

Shi

et al. 2021

Biomolecules

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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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“…Mireia Casulleras group reported that a systemic hyperin ammatory state is the main driver of widespread tissue and organ injury in patients with ACLF. The massive release of in ammatory mediators leads to severe tissue damage [22].Jiang Li [23] group con rmed that HBV exacerbate immune-metabolism disorder in HBV-ACLF patients. Therefore, we thought that although received 12 weeks antiviral therapy making HBV DNA load decrease to lower level, immune and metabolic disorder process still drive the development and progression of HBV-ACLF in the followed time, which was the reason of why these two groups achieved similar survival rate after 12 weeks treatment.…”

Section: Discussionmentioning

confidence: 99%

The Short-Term Efficacy of Tenofovir Alafenamide (TAF) in Acute-On-Chronic Liver Failure: A Single Center Experience

Liu

Dong

et al. 2021

Preprint

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Background and aims: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) reduce hepatic events and death in patients with acute-on-chronic liver failure (ACLF), but the efficacy of Tenofovir alafenamide (TAF) is less well studied. We aimed to assess the effectiveness of TAF in hepatitis B virus (HBV) related ACLF.Methods: We analyzed 106 patients with HBV-ACLF received TAF (25mg/d), ETV(0.5mg/d) for 12 weeks. The primary endpoints were overall mortality and liver transplantation (LT) at week 12. Other determined factors of biochemical response, virologic response, mortality rate, and drug safety and side-effect were also evaluated.Results: At 4 weeks and 12 weeks, patients received TAF got significantly higher HBV-DNA reduction (P<0.001), higher rate of HBV-DNA undetectbility (P<0.001), lower HBV-DNA level (P<0.001). Lower CTP scores (P=0.003) at 4 weeks in TAF group, but CTP scores showed no difference in two groups at 12 weeks (P=1.143). Lower ALT levels in TAF group at week 4 and week 12 (P=0.023, P<0.0001). The mortality rate was lower in TAF group after 4 weeks treatment(P=0.038), but two group got similar mortality rate at week 8 and week 12. As for reason cause death in HBV-ACLF patients, we found that two group patients developed similar rates of liver-related complications (P>0.05).Conclusions: The antiviral efficacy of TAF was superior than ETV for the treatment of HBV-related ACLF. TAF therapy reduced 4-week mortality rate in patients with HBV-related ACLF.

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Leukocytes, Systemic Inflammation and Immunopathology in Acute-on-Chronic Liver Failure

Cited by 94 publications

References 116 publications

Hypoalbuminemia as Surrogate and Culprit of Infections

Hypoalbuminemia as Surrogate and Culprit of Infections

C-Reactive Protein Is an Independent Predictor of 30-Day Bacterial Infection Post-Liver Transplantation

The Short-Term Efficacy of Tenofovir Alafenamide (TAF) in Acute-On-Chronic Liver Failure: A Single Center Experience

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