Nucleotide-Binding Oligomerization Domain-Containing Protein 2 Variants in Patients with Spontaneous Bacterial Peritonitis.

BACKGROUND: The occurrence of spontaneous bacterial peritonitis (SBP) is significantly increased in carriers of nucleotide-binding oligomerization domain-containing protein 2 (NOD2) variants, suggesting that local immune alterations might be implicated in bacterial translocation (BT). AIMS: We aimed to assess the role of the NOD2 gene in conferring susceptibility to SBP. We also sought to determine whether levels of serum interleukin-6 (IL-6), lipopolysaccharide-binding protein, and soluble TNF-α receptor, along with the presence of bacterial DNA (bactDNA) in ascitic fluid, are appropriate markers for BT in patients with liver cirrhosis and SBP. METHODS: A cohort of 171 patients was divided into two groups: patients with SBP (n = 82) and those without SBP (n = 89). The presence of the most common NOD2 variants (p.R702W, p.G908R, and c.3020insC) was determined in these patients. RESULTS: We detected the p.G908R variant in four patients (4.9 %) of the SBP group. No significant difference was observed between the SBP and non-SBP groups for NOD2 risk variants. The frequency of bactDNA in ascitic fluid was higher for patients with NOD2 variants than for patients without variants (p = 0.021). Serum IL-6 levels in the SBP group were higher than those in the non-SBP group. CONCLUSIONS: The frequent detection of bactDNA in ascites of patients with the p.G908R variant suggests there is a strong association between NOD2 risk variants and BT in SBP patients. In addition, increased serum IL-6 levels and bactDNA in ascitic fluid could be considered surrogate markers for BT in patients with cirrhosis.

Effects of rifaximin on bacterial translocation in thioacetamide-induced liver injury in rats.

Intestinal bacterial overgrowth (IBO) and increased mucosal permeability are suggested to increase bacterial translocation (BT) in liver injury. Rifaximin (RIF) is a minimally absorbed oral antimicrobial agent that restores gut microflora imbalance. The aim of the present study was to investigate the effects of RIF on BT frequency in thioacetamide (TAA)-induced liver injury. Group 1 was the control. In group 2 (TAA), rats received TAA daily for 3 days. In group 3 (TAA + RIF), RIF was commenced on the same day as the first dose of TAA. In group 4 (RIF), rats received only RIF. Ileal aspirate Escherichia coli counts were significantly lower in the TAA + RIF group than in TAA group. There was no difference in BT frequency between the TAA and TAA + RIF groups. Our results suggest that factors such as intestinal barrier dysfunction and impaired host immune shield, apart from IBO, play an important role in BT in this model.

An antibody of TNF-alpha did not prevent thioacetamide-induced hepatotoxicity in rats.

Tumor necrosis factor (TNF)-α antibodies have been shown to reduce liver damage in different models. We investigated the effects of infliximab (a TNF-α antibody) on liver damage in thioacetamide (TAA)-induced hepatotoxicity in rats. Group 1 (n = 8) was the control group. In group 2 (n = 8), the TAA group, the rats received 300 mg/kg intraperitoneal (ip) TAA daily for 2 days. In group 3 (n = 8), the TAA + Infliximab (INF) group, infliximab (5 mg/kg ip daily) was administered 48 hours before the first dose of TAA daily for 2 days and was maintained for 4 consecutive days. In group 4 (n = 8), the INF group, the rats received only ip infliximab (5 mg/kg) daily. Livers were excised for histopathological and biochemical tests (thiobarbituric-acid-reactive substances [TBARS], and myeloperoxidase [MPO]). Serum ammonia, aspartate transaminase (AST), alanine transaminase (ALT), TNF-α, liver TBARS and MPO levels, and liver necrosis and inflammation scores in the TAA group were significantly higher than in the control and INF groups (all p < 0.01). All parameters except AST were not significantly different between TAA and TAA + INF. In conclusion, our results suggest that oxidative stress plays an important role in TAA-induced hepatotoxicity, and infliximab does not improve oxidative liver damage.

Hypovolemia-related gastric tissue damage in the setting of upper gastrointestinal bleeding.

BACKGROUND/AIMS: Much is known about the gastric tissue damage that is associated with hypovolemic stress, but gastrointestinal bleeding due to gastric injury and further gastric injury due to hypovolemia have not been evaluated in previous research. The aim of this study was to assess oxidative gastric tissue damage specifically linked to hypovolemia in patients with upper gastrointestinal bleeding. METHODS: The study included 30 patients who presented with acute upper gastrointestinal bleeding and 30 controls. Each patient's history and laboratory findings were recorded, and multiple biopsies of the gastric antrum were obtained at diagnostic endoscopy on admission (day 1) and five days later. A set of antral biopsies was also collected from each control subject. Each tissue specimen was analyzed for levels of glutathione peroxidase, superoxide dismutase and catalase activity, and level of malondialdehyde. RESULTS: First day glutathione peroxidase, superoxide dismutase and catalase levels were significantly lower and malondialdehyde levels were higher than on the 5th day, and 1st day and 5th day levels were significantly different from controls (p<0.05). A moderate level of correlation was detected between catalase and hemoglobin (r:-0.59) and hematocrit (r:-0.61) and between malondialdehyde and systolic blood pressure (p:0.58), hematocrit (r:0.45) and hemoglobin (r:0.49). CONCLUSIONS: In this study, gastric tissue oxidative markers showed antral oxidative changes to be significantly correlated with patients' hemodynamics. Oxidative stress may not be a clinical condition but it obviously shows gastric tissue damage and may explain many of the patients' additional diagnosis of gastric erosions. Interestingly, the oxidative change does not completely recover even on the 5th day.

Gastric tissue oxidative changes in portal hypertension and cirrhosis.

Gastric mucosal lesions are very common in portal hypertension and cirrhosis. The aim of this study was to assess for oxidative gastric tissue damage in cirrhosis and evaluate relations with portal hypertension and cirrhosis parameters. The study included 30 patients with cirrhosis and 30 controls. Each patient's history, physical examination, and laboratory findings were recorded, and multiple biopsies of the gastric antrum were obtained at endoscopy. A set of antral biopsies was also collected from each control subject. Each tissue specimen was analyzed for levels of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) activity and level of malondialdehyde (MDA). Patients' gastric GPX, SOD, and CAT levels were significantly lower, and MDA levels were higher, than in the control group. The GPX activity level in the specimens was moderately negatively correlated with portal vein diameter (P<0.05, r=-0.45) and spleen length (P<0.05, r=-0.45). In this study gastric tissue oxidative markers showed that antral oxidative factors worsen in cirrhosis. Oxidative stress may not be a clinical condition but it obviously shows gastric tissue damage and may explain many patients' gastric lesions and hemorrhage.

The relationship of heart rate variability with severity and prognosis of cirrhosis.

Many studies have demonstrated that cirrhosis is frequently associated with autonomic dysfunction. The aim of this study was to test autonomic dysfunction in cirrhotic patients by analyzing heart rate variability (HRV), to determine whether or not the degree of autonomic dysfunction is correlated with the severity of disease, and, also, to compare the changes of HRV between survivor and nonsurvivor groups after 2-year follow-up periods. HRV was analyzed using 24-hr ECG recording in 30 cirrhotic patients and 28 normal controls. The changes in HRV parameters including mean normal-to-normal (N-N) interbeat intervals (mean NN), standard deviation of all N-N intervals (SDNN), standard deviation of the average of N-N intervals for each 5-min period over 24 hr (SDANN), root mean square succesive differences (r-MSSD; msec), and percentage of adjacent N-N intervals that are >50 msec apart (pNN50), all as time domain parameters, were evaluated. The cirrhotic patients were also evaluated according to Child-Pugh classification scores as markers of the disease severity. The time-domain measures of HRV in cirrhotic patients were significantly reduced compared with those in the control group (for all parameters; P < 0.001). The severity of disease was associated with reduced HRV measures (for all parameters; P < 0.001). After the 2-year follow-up periods, HRV measurements in cirrhotic patients were significantly much lower in nonsurvivors than in survivors (P < 0.001 for all). We conclude that increasing severity of cirrhosis is associated with a reduction in HRV. This finding may be an indicator of poor prognosis and mortality for cirrhosis.