Tumour necrosis factor-α and soluble Fas ligand as biomarkers in non-acetaminophen-induced acute liver failure

Singhal, Shashideep; Chakravarty, Anita; Das, Bhudev C.; Kar, Premashis

doi:10.1080/13547500903013664

Cited by 15 publications

(9 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16 And more recent studies have shown a correlation between CD95L levels and several human pathologies such as systemic lupus erythematosus, 17 toxic epidermal necrosis, acute pancreatitis, 18 acute hepatic failure 19 and burn injuries. 20 The influence of the initial phase of acute SCI on recovery or prognosis has not yet been researched.…”

Section: Discussionmentioning

confidence: 99%

Increase in soluble CD95L during subacute phases after human spinal cord injury: a potential therapeutic target

et al. 2012

View full text Add to dashboard Cite

Study design: A pilot study measuring the levels of serum-soluble CD95 ligand (CD95L) in eight spinal cord-injured patients. Objectives: To determine the soluble concentration of CD95L in spinal cord injury (SCI) patients after trauma. Methods: We collected blood samples from eight patients with acute traumatic SCI. Soluble CD95L serum levels were determined using an enzyme-linked immunosorbent assay. American Spinal Injury Association (ASIA) was determined according to ASIA classification. The patients were monitored, and venous blood was drawn after arrival at the hospital on the 1st and 3rd day and during the 1st, 2nd, 4th, 8th and 12th weeks after trauma. Results: The average patient age was 48.1 years (18-86 years). Three patients were paraplegic (two incomplete, one complete), five were quadriplegic (one complete, four incomplete). The serum concentration of soluble CD95L (sCD95L) decreased during the 1st week (41 ng l À1 ) and increased after the 2nd week in all eight patients. It peaked during the 4th week (68.5 ng l À1 ) and reached a plateau during the 12th week (76.2 ng l À1 ). There are many possible explanations for not being able to detect a statistical significance, one of course being the small sample size. Conclusion: Promising results for anti-CD95L therapy have already been documented in lab studies with rodents. Anti-CD95L blocks the pro-apoptotic and proinflammatory activity of membrane-bound CD95L during the acute phase of SCI. We observed that sCD95L levels are elevated during the subacute and intermediate phases of SCI. It would be of great interest to study a larger group of patients to determine whether higher sCD95 levels are correlated with improved or impaired neurological outcome or with increasing levels of autoimmune components in peripheral blood.

show abstract

Section: Discussionmentioning

confidence: 99%

Increase in soluble CD95L during subacute phases after human spinal cord injury: a potential therapeutic target

et al. 2012

View full text Add to dashboard Cite

show abstract

“…In studies of non-NAFLD liver diseases, sFasL has been used as a biomarker of hepatocytic apoptosis with some success. Elevated serum levels of sFasL distinguished patients with acute liver failure from those with acute hepatitis E or with sepsis alone [16]. Serum levels of sFasL were also higher in patients with chronic but not acute hepatitis B and were highest in patients with the greatest degree of infection [17].…”

Section: Discussionmentioning

confidence: 99%

Knowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis in NAFLD as an Example

et al. 2013

View full text Add to dashboard Cite

The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases.

show abstract

“…The balance between these two pathways determines the cell fate. Previous studies showed that elevated levels of serum TNF and over-expression of TNFR1 were observed and negatively correlated with the outcome in ALF patients [109,110,114], suggesting the pathogenic role of the TNF /TNFR1 signaling in human ALF. In parallel, treatment with adenovirus-mediated dominant negative form of the Fas-associated death domain (FADDdn), a downstream signaling molecule for Fas and TNFRs, inhibited the TNF /Galactosamine mediated hepatocellular apoptosis and significantly lowed the levels of serum transaminase in mice [114].…”

Section: Tumor Necrosis Factor (Tnf )/Tnfr Signalingmentioning

confidence: 96%

“…Fas may also exist as a soluble form (sFas), which can also be bound by FasL and antagonizes Fas-mediated apoptosis [108]. Notably, the expression of Fas is significantly up-regulated in apoptotic hepatocytes of ALF patients [109], and higher levels of serum FasL are also associated with the worse prognosis of ALF [110], indicating the potential involvement of Fas/FasL signaling in the pathogenesis of ALF., Song et al found that hydrodynamic tail vein injection of Fas-specific siRNA duplexes resulted in an efficient delivery of Fasspecific siRNA in majority of hepatocytes, dramatically down-regulation of Fas expression for more than 10 days in mouse hepatocytes [111]. Similarly, treatment with Fasspecific siRNA promoted the survival of animals with fulminant hepatitis induced by either intravenous injection of concanavalin (ConA) or intraperitoneal injection of agonistic Fas-specific antibody [111].…”

Section: Fas Ligang (Fasl)/fas Signalingmentioning

confidence: 98%

Gene Therapy for Acute Liver Failure

Zhu¹,

Li²,

Gao

2010

CGT

View full text Add to dashboard Cite

Acute liver failure (ALF) is a life-threatening medical emergency and occurs when the liver rapidly loses its function within a short period. ALF can develop secondary to a variety of causes. Currently, the orthotopic liver transplantation is the "Gold Standard" therapy for the disease. However, due to the limited availability of donor organs and rapid progression of the disease, the mortality of ALF remains high. Therefore, it is imperative to develop novel therapeutic reagents for ALF. Gene therapy by delivering a target gene to the patients appears to be a promising approach for the treatment of ALF. Here, we review the recent advance of gene therapy for ALF, focusing on the three technical elements, animal models, vehicles for gene delivery and technique for gene delivery, which are important for the success of gene therapy as well as the potential targets used for the treatment of ALF.

show abstract

Tumour necrosis factor-α and soluble Fas ligand as biomarkers in non-acetaminophen-induced acute liver failure

Abstract: The high levels of sFasL and TNF-alpha are associated with ALF. Following the trend of these cytokines can be useful in predicting death and timely referral to a transplant centre.

Cited by 15 publications

References 28 publications

Increase in soluble CD95L during subacute phases after human spinal cord injury: a potential therapeutic target

Increase in soluble CD95L during subacute phases after human spinal cord injury: a potential therapeutic target

Knowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis in NAFLD as an Example

Gene Therapy for Acute Liver Failure

Contact Info

Product

Resources

About