Gene expression of interleukin 18 in unstimulated peripheral blood mononuclear cells of patients with alcoholic cirrhosis

Hanck, C

doi:10.1136/gut.49.1.106

Cited by 27 publications

(21 citation statements)

References 37 publications

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“…If liver histology was not available, patients in whom the serum gamma-glutamyl transpeptidase level fell during a 2-month period of observation prior to study entry were excluded to avoid inclusion of patients with possible alcoholic hepatitis, as previously described. 26 Exclusion criteria also included a history within the previous 6 weeks of factors that may have influenced gut flora and circulating endotoxin and ammonia levels, including infection, treatment with antibiotics, lactulose or immunomodulatory drugs, and gastrointestinal hemorrhage. 24 In addition to intercurrent infection and gastrointestinal hemorrhage, patients with other possible causes of reversible hepatic functional decompensation, such as drug-related hepatotoxicity and choledocholithiasis, were excluded.…”

Section: Methodsmentioning

confidence: 99%

Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis

Liu¹,

Duan²,

Ha³

et al. 2004

Hepatology

566

429

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Minimal hepatic encephalopathy (MHE) is an important disorder that may seriously impair daily functioning and quality of life in patients with cirrhosis. Treatment with lactulose is of benefit. The possible role of synbiotics (probiotics and fermentable fiber) has not been assessed. We screened 97 consecutive cirrhotic patients without overt hepatic encephalopathy for MHE using the number connection test and measurement of brainstem auditory evoked potentials. MHE, defined by abnormality on at least one test modality, was present in 58 (60%) patients. Fifty-five of these patients with MHE were randomized to receive a synbiotic preparation (n ‫؍‬ 20), fermentable fiber alone (n ‫؍‬ 20), or placebo (n ‫؍‬ 15) for 30 days. Cirrhotic patients with MHE were found to have substantial derangements in the gut microecology, with significant fecal overgrowth of potentially pathogenic Escherichia coli and Staphylococcal species. Synbiotic treatment significantly increased the fecal content of non-urease-producing Lactobacillus species at the expense of these other bacterial species. Such modulation of the gut flora was associated with a significant reduction in blood ammonia levels and reversal of MHE in 50% of patients. Synbiotic treatment was also associated with a significant reduction in endotoxemia. The Child-Turcotte-Pugh functional class improved in nearly 50% of cases. Treatment with fermentable fiber alone was also of benefit in a substantial proportion of patients. In conclusion, treatment with synbiotics or fermentable fiber is an alternative to lactulose for the management of MHE in patients with cirrhosis.

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Section: Methodsmentioning

confidence: 99%

Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis

Liu¹,

Duan²,

Ha³

et al. 2004

Hepatology

566

429

View full text Add to dashboard Cite

show abstract

“…32 Patients were considered to have alcohol-related cirrhosis if alcohol intake had been in excess of 80 g/day in men and 30 g/day in women for more than 5 years and if testing for viral, metabolic, and immune etiologies was negative. 17 Only patients who had been abstinent from alcohol for at least 3 months were included, because alcohol influences the sensitivity of macrophages to endotoxin and the production of TNF-␣ by PBMCs. 33,34 Patients with histologic features of alcoholic hepatitis were excluded.…”

Section: Methodsmentioning

confidence: 99%

“…Because TNF-␣ is cleared by the kidney, patients with renal insufficiency (serum creatinine Ͼ120 mol/L) were also excluded. 5,17,35 Thirty-two age-and sex-matched, asymptomatic volunteers with no history of liver disease, alcohol intake less than 20 g/day, and normal liver function test results served as controls. Informed written consent was obtained from each patient.…”

Section: Methodsmentioning

confidence: 99%

Peripheral Blood Mononuclear Cell Expression of Toll–Like Receptors and Relation to Cytokine Levels in Cirrhosis

et al. 2003

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Activation of macrophages by endotoxin is assumed responsible for increased circulating tumor necrosis factor ␣ (TNF-␣) and soluble TNF receptor (sTNFR) levels in cirrhosis. Relevant to this is expression of Toll-like receptor (TLR) 4 and TLR2, which is critically involved in production of TNF-␣ in response to endotoxin and Gram-positive microbial stimuli, respectively. The first studies on this in cirrhosis are reported here. In 36 cirrhotic patients and 32 controls, we measured (1) circulating endotoxin, TNF-␣, and sTNFR levels; (2) peripheral blood mononuclear cell (PBMC) expression of TLR4 and TLR2, and (3) in vitro TNF-␣ production by PBMCs stimulated with endotoxin or Staphylococcus aureus enterotoxin B (SEB). PBMC expression of TLR2, circulating TNF-␣ levels, and in vitro TNF-␣ production were reassessed after supplementation with a synbiotic regimen known to increase intestinal levels of Gram-positive bacteria. Endotoxin, TNF-␣, and sTNFR levels were significantly increased in cirrhosis. Endotoxin levels did not correlate significantly with other parameters. PBMC expression of TLR2 but not TLR4 was significantly up-regulated in cirrhosis and correlated significantly with serum TNF-␣ and sTNFR levels. In vitro TNF-␣ production by PBMCs stimulated by SEB was significantly blunted. Supplementation with the synbiotic regimen resulted in significant up-regulation of PBMC expression of TLR2. Serum TNF-␣ levels were further increased and in vitro TNF-␣ production further reduced in most patients. In conclusion, up-regulation of PBMC expression of TLR2 but not TLR4 occurs in cirrhosis, which implies, contrary to previous assumptions, an important stimulatory role for Gram-positive microbial components but not endotoxin. TLR2 likely contributes to increased circulating TNF-␣ and sTNFR levels in cirrhosis.

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“…Increased translocation from the gut lumen and reduced hepatic clearance have each been proposed to predispose to endotoxaemia in this situation [157,158]. In the clinical setting, increased circulating levels of endotoxin have been documented in patients with chronic liver disease, even in the absence of overt infection [29,[159][160][161][162][163][164]. Based on experiences in experimental animals, it has been assumed that endotoxaemia is a major cause of the raised pro-inflammatory cytokine levels found in this group [157,[165][166][167].…”

Section: Intestinal Flora Pro-inflammatory Cytokines and Vasoactive mentioning

confidence: 99%

The intestinal flora and bacterial infection in cirrhosis

Riordan

Williams

2006

Journal of Hepatology

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Gene expression of interleukin 18 in unstimulated peripheral blood mononuclear cells of patients with alcoholic cirrhosis

Cited by 27 publications

References 37 publications

Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis

Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis

Peripheral Blood Mononuclear Cell Expression of Toll–Like Receptors and Relation to Cytokine Levels in Cirrhosis

The intestinal flora and bacterial infection in cirrhosis

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