Admission levels and early changes in serum interleukin-10 are predictive of poor outcome in acute liver failure and decompensated cirrhosis

Berry, Phillip; Antoniades, Charalambos; Hussain, Munther J.; McPhail, Mark; Bernal, William; Vergani, Diego; Wendon, Julia

doi:10.1111/j.1478-3231.2010.02219.x

Cited by 62 publications

(49 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, sCD163 was an independent risk factor regardless of the disease severity and the extent of the pro‐inflammatory response, represented by MELD score, CRP and leucocyte count respectively. This finding is consistent with the observations that excessive anti‐inflammatory response, represented by interleukin‐10, interleukin‐6 or soluble tumour necrosis factor‐α receptor (sTNFR) and decreased monocyte HLA‐DR expression , has a significant negative impact on survival in cirrhosis, as recently reviewed by Albillos et al . .…”

Section: Discussionsupporting

confidence: 92%

Macrophage activation marker, soluble CD163, is an independent predictor of short‐term mortality in patients with cirrhosis and bacterial infection

Tornai

Vitális

Sipeki

et al. 2016

Liver International

View full text Add to dashboard Cite

Background & Aims Innate immune system dysfunction is common in advanced cirrhosis, with a central role of the monocyte/macrophage system. Monocytes and macrophages express the scavenger receptor CD163, which is regulated by inflammatory mediators. Cleavage of the receptor leads to the formation of soluble (s)CD163 that represents an anti‐inflammatory response. We aimed to study the clinical importance of sCD163 in cirrhosis. Methods Sera of 378 patients were assayed for sCD163 by ELISA [193 outpatients and 185 patients with acute decompensation (AD)]. A 5‐year follow‐up observational study was conducted to assess the possible association between sCD163 level and poor disease outcomes. Results sCD163 level was associated with disease severity, but not with the presence of varices or prior variceal bleeding. In outpatients, sCD163 level did not predict the development of disease‐specific complications or the long‐term mortality. In patients with AD episode, sCD163 level was significantly higher compared to outpatients but only in the presence of bacterial infection (INF) (AD‐INF:4586, AD‐NON‐INF:3792 and outpatients: 3538 ng/ml, P < 0.015 and P = 0.001, respectively). sCD163 level gradually increased according to severity of infection. During bacterial infections, high sCD163 level (>7000 ng/ml) was associated with increased mortality rate (42% vs. 17%, P < 0.001) and was identified as an independent predictor of 28‐day mortality (hazard ratio:2.96, 95% confidence intervals:1.27–6.95) in multivariate Cox‐regression model comprising aetiology, co‐morbidity, model for end‐stage liver disease score and leucocyte count as covariates. Conclusions High sCD163 level is useful to identify patients with high‐risk of death during an AD episode complicated by bacterial infection. This finding serves as an additional hint towards the significance of anti‐inflammatory response during bacterial infection.

show abstract

Section: Discussionsupporting

confidence: 92%

Macrophage activation marker, soluble CD163, is an independent predictor of short‐term mortality in patients with cirrhosis and bacterial infection

Tornai

Vitális

Sipeki

et al. 2016

Liver International

View full text Add to dashboard Cite

show abstract

“…Early after liver injury, pro‐inflammatory cytokines including tumour necrosis factor‐α (TNFα), interleukin (IL)‐1β and IL‐6 are proposed to lead to death by provoking multi‐organ system failure (MOSF). Later after liver injury, anti‐inflammatory cytokines including IL‐4 and IL‐10 counterbalance pro‐inflammatory cytokines and may lead to a compensatory anti‐inflammatory response, immunoparalysis and death because of sepsis .…”

mentioning

confidence: 99%

Effects of N‐acetylcysteine on cytokines in non‐acetaminophen acute liver failure: potential mechanism of improvement in transplant‐free survival

Stravitz

Sanyal

Reisch

et al. 2013

Liver International

View full text Add to dashboard Cite

Background N-Acetylcysteine (NAC) improves transplant-free survival in patients with non-acetaminophen acute liver failure (ALF) when administered in early stages of hepatic encephalopathy. The mechanisms of this benefit are unknown. Aim To determine whether NAC improves transplant-free survival in ALF by ameliorating the surge of pro-inflammatory cytokines. Methods Serum samples were obtained from 78 participants of the randomized, ALF Study Group NAC Trial with grade 1 or 2 hepatic encephalopathy on randomization. Concentrations of ten cytokines, chosen to represent a wide array of inflammatory responses, were determined by multiplex ELISA. Results In univariate analysis, predictors of transplant-free survival included NAC administration (P=0.012), admission bilirubin (P=0.003), INR (P=0.0002), grade 1 vs. grade 2 encephalopathy (P=0.006) and lower admission interleukin (IL)-17 concentrations (P=0.011). IL-17 levels were higher in patients with grade 2 vs. 1 encephalopathy on randomization (P=0.007) and in those who progressed to grade 3 or 4 encephalopathy over the following 7 days (P≤0.01). Stepwise multivariate logistic regression analysis identified only NAC administration and lower IL-17 concentrations as independent predictors of transplant-free survival. In patients with detectable IL-17 concentrations on admission, 78% of those who received NAC vs. 44% of those who received placebo had undetectable levels by day 3-5 (P=0.042), and the mean decrease in IL-17 concentrations between admission and late samples was significantly greater in patients who received NAC vs. placebo (P=0.045). Conclusions NAC may improve transplant-free survival in patients with non-acetaminophen ALF by ameliorating the production of IL-17, which is associated with progression of hepatic encephalopathy and poor outcome.

show abstract

“…In response to hepatic toxins such as acetaminophen, IL-6 levels can be rapidly released by resident hepatic cells, including Kupffer and dendritic cells (Connolly et al 2011; Lacour et al 2005). IL-6 can also serve as a prognostic biomarker for decreased survival in human acute liver failure (Berry et al 2010) and is a potential downstream mediator of acetaminophen-induced hepatic injury in mice (Bourdi et al 2007). While we did not directly examine other pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α or interleukin (IL)-1β, it is likely that those would also be elevated in acetaminophen-treated Mkp-1 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Mitogen-activated Protein Kinase Phosphatase (Mkp)-1 Protects Mice against Acetaminophen-induced Hepatic Injury

et al. 2012

View full text Add to dashboard Cite

c-Jun N-terminal kinase (JNK) activation promotes hepatocyte death during acetaminophen overdose, a common cause of drug-induced liver failure. While mitogen-activated protein kinase (MAPK) phosphatase (Mkp)-1 is a critical negative regulator of JNK MAPK, little is known about the role of Mkp-1 during hepatotoxicity. In this study, we evaluated the role of Mkp-1 during acute acetaminophen toxicity. Mkp-1+/+ and Mkp-1−/− mice were dosed ip with vehicle or acetaminophen at 300 mg/kg (for mechanistic studies) or 400 mg/kg (for survival studies). Tissues were collected 1–6 hr post 300 mg/kg dosing to assess glutathione levels, organ damage, and MAPK activation. Mkp-1−/− mice exhibited more rapid plasma clearance of acetaminophen than did Mkp-1+/+ mice, indicated by a quicker decline of plasma acetaminophen level. Moreover, Mkp-1−/− mice suffered more severe liver injury, indicated by higher plasma alanine transaminase activity and more extensive centrilobular apoptosis and necrosis. Hepatic JNK activity in Mkp-1−/− mice was higher than in Mkp-1+/+ mice. Finally, Mkp-1−/− mice displayed a lower overall survival rate and shorter median survival time after dosing with 400 mg/kg acetaminophen. The more severe phenotype exhibited by Mkp-1−/− mice indicates that Mkp-1 plays a protective role during acute acetaminophen overdose, potentially through regulation of JNK.

show abstract

Admission levels and early changes in serum interleukin-10 are predictive of poor outcome in acute liver failure and decompensated cirrhosis

Cited by 62 publications

References 34 publications

Macrophage activation marker, soluble CD163, is an independent predictor of short‐term mortality in patients with cirrhosis and bacterial infection

Macrophage activation marker, soluble CD163, is an independent predictor of short‐term mortality in patients with cirrhosis and bacterial infection

Effects of N‐acetylcysteine on cytokines in non‐acetaminophen acute liver failure: potential mechanism of improvement in transplant‐free survival

Mitogen-activated Protein Kinase Phosphatase (Mkp)-1 Protects Mice against Acetaminophen-induced Hepatic Injury

Contact Info

Product

Resources

About