Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis

Tilg, Herbert; Jalan, Rajiv; Kaser, Arthur; Davies, Nathan; Offner, Felix; Hodges, Stephen; Ludwiczek, Othmar; Shawcross, Debbie L.; Zoller, Heinz; Alisa, A; Mookerjee, Rajeshwar P.; Graziadei, Ivo; Datz, Christian; Trauner, Michael; Schuppan, Detlef; Obrist, Peter; Vogel, Wolfgang; Williams, Roger

doi:10.1016/s0168-8278(02)00442-7

Cited by 212 publications

(143 citation statements)

References 33 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…17 The lower limit for the detection of the cytokines was 3 pg/mL. The intra-assay CV was 5.4%-6.4%.…”

Section: Cytokinesmentioning

confidence: 88%

“…Current strategies for treating AH include the administration of immunosuppressive agents such as corticosteroids and, more recently, anti-tumor necrosis factor (TNF)␣ strategies, which may further potentiate susceptibility to infection. The results of studies using these drugs in patients with AH are conflicting, 14,15 and although there are some data showing benefits from anti-TNF␣ strategies, 16,17 one trial showed increased risk of infection and mortality, which resulted in early trial termination. 18 To reconcile the apparent paradox, we assessed whether neutrophils exist in a primed or fully activated state in patients with different alcoholic liver diseases [alcoholic cirrhosis and AH superimposed on cirrhosis (cirrhosisϩAH)] and studied the association of this with the development of infection and clinical outcome.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome

et al. 2007

Self Cite

View full text Add to dashboard Cite

Mortality in patients with alcoholic hepatitis (AH) remains high, and although corticosteroids are widely used for treatment, the results vary considerably. In AH, neutrophils are primed and infiltrate the liver to produce injury, but paradoxically, the main cause of death in such patients is infection. Our prospective study addressed this paradox of primed neutrophils on the one hand and increased risk of infection on the other. We hypothesized that the full activation of neutrophils by a humoral factor such as endotoxin renders them unable to respond to further bacterial challenge. We analyzed neutrophil oxidative burst and phagocytosis in whole blood by fluorescence-activated cell sorting analysis in 63 alcoholic patients with cirrhosis and patients with cirrhosis with superimposed AH (cirrhosis؉AH). In 16 patients, ex vivo studies determined whether the removal of endotoxin restored neutrophil function. A resting burst greater than or equal to 5%, indicating neutrophil activation and a reduced phagocytic capacity lower than 42%, was associated with significantly greater risk of infection, organ failure, and mortality. This defective neutrophil function was transmissible through patients' plasma to normal neutrophils, and patients' neutrophil function could be restored by normal plasma. The ex vivo removal of endotoxin from patients' plasma decreased the resting burst and increased the phagocytic function. Conclusions: Our study provides the rationale for a goal-directed approach to the management of patients with cirrhosis and AH, in which the assessment of neutrophil function may be an important biomarker to select patients for immunosuppressive therapy. The neutrophil dysfunction in cirrhosis and AH is reversible, with endotoxin-removal strategies providing new targets for intervention. (HEPATOLOGY 2007;46:831-840.)

show abstract

“…17 The lower limit for the detection of the cytokines was 3 pg/mL. The intra-assay CV was 5.4%-6.4%.…”

Section: Cytokinesmentioning

confidence: 88%

mentioning

confidence: 99%

Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…[24] Anti-TNF-α antibody, infliximab, is also effective in severe AH patients. [25] These results suggest that TNF-α plays an important role in the progression of ALD.…”

Section: Structural Organization Of the Liver And Cytokines Potentialmentioning

confidence: 83%

Physiological potential of cytokines and liver damages

Mannaa¹,

Abdel-Wahhab²

2016

View full text Add to dashboard Cite

Cytokines are soluble extracellular small molecular weight protein or peptide. They are produced by virtually every nucleated cell type in response to injurious stimuli to control body metabolism, infection, inflammation and tissue or neuronal damage; therefore acting as messengers between tissues and the immune system; and participating in many physiological processes through their either anti-inflammatory or pro-inflammatory characteristics. Many cytokines have multiple cellular sources and targets, as well as many natural inducers and inhibitors. In pathophysiological conditions and during the early phase of chronic liver diseases, agent like virus, bacteria, parasites, ethanol, or toxins, induce secretion of cytokines at high levels. The presence of cytokine antagonists and soluble cytokine receptors, often released in concert with their respective cytokine agonist, presents additional complexity to interpretation.

show abstract

“…Based on an mDF of 63 and a GAHS of 9, a corticosteroid regimen was instituted and then slowly progressive tapered down, on the basis of progressive clinical, laboratory and radiological improvement. At present, prognostic scores for AAH may orient the patient management, even if the use of steroids in this setting has recently been challenged by pertinent metanalytic data [24] while other treatments, such as anabolic steroids, pentoxifylline and infliximab, are still under investigation [25][26][27] . To complete the liver disease staging and to obtain data useful in the follow up, our patient underwent also a transient elastography (FibroScan ® ).…”

Section: Discussionmentioning

confidence: 99%

“Pseudotumoral” hepatic pattern in acute alcoholic hepatitis: A case report

Tenca

Massironi

Colli³

et al. 2009

WJG

View full text Add to dashboard Cite

In acute alcoholic hepatitis (AAH), a "pseudotumoral" appearance of the liver parenchyma on computed tomography (CT) scan has been reported. The main findings are hypervascularized areas closely similar to those observed in large hepatocellular carcinomas. We report a case of a patient affected by AAH with an unusual appearance of these "pseudotumoral" areas on CT scan, close resembling a metastatic cancer rather than a primary hepatocellular carcinoma. In fact, in contrast with previous reports, the picture was characterized by the presence of many inhomogeneous, hypoattenuated areas highlighted during both preand post-contrast phases. Moreover, we report the first description of "pseudotumoral" lesions on ultrasound scan. This patient was successfully treated with corticosteroids, even if many controversies still exist regarding their efficacy in this setting.

show abstract

Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis

Cited by 212 publications

References 33 publications

Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome

Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome

Physiological potential of cytokines and liver damages

“Pseudotumoral” hepatic pattern in acute alcoholic hepatitis: A case report

Contact Info

Product

Resources

About