Bacterial DNA and its consequences in patients with cirrhosis and culture negative, non neutrocytic ascites

ABSTRACT

The detection of bacterial DNA [BactDNA] in serum and ascitic fluid [AF] from patients with liver cirrhosis and ascites is interpreted as molecular evidence of intestinal bacterial translocation [BT] and considered sufficient to activate the cellular immune response leading to greater cytokine synthesis. In the present work we study whether BactDNA and Tumor necrosis factor-alpha [TNF- alpha] in cirrhotic patients with culture negative, non neutrocytic ascites have been implicated in various complications of cirrhosis such as hepatorenal syndrome [HRS], spontaneous bacterial peritonitis [SBP] and mortality. We studied 34 patients with liver cirrhosis and culture negative, non neutrocytic ascites [22 patients without BactDNA [group I] aged [48.3 +/- 7.85y] and 12 patients with BactDNA [group II], aged [49.7 +/- 6.5y]]. Full history and complete clinical examination were done with the following investigations in the first admission and subsequent admissions during follow up for 24 weeks complete blood picture, S. creatinine, S. bilirubin, S. albumin, S. transaminases [AIT and AST], AF and plasma TNF-alpha, AF protein and polymorphnuclear leucocytes [PMNL], both blood culture and AF aerobic and anaerobic cultivation, and detection of blood and ascitic fluid BactDNA using PCR. Plasma and ascitic TNF-alpha were significantly higher in cirrhotic patients with compared to those without BactDNA during first admission [54.5 +/- 22.56 vs 35.2 +/- 17.97; 123.2 +/- 49.32 vs 82.6 +/- 29.58 pg/ml respectively, P<0.05]. These changes became highly significant at the end of follow up of both groups [119.3 +/- 27.19 vs 40.2 +/- 16.08; 518.8 +/- 91.11 vs 97.6 +/- 17.81 pg/ml respectively, P<0.001]. There is non significant change of plasma and ascitic TNF-alpha in group I at first admission compared to those at the end of follow up [P>0.05]. However, in group II, there is highly significant increase in both plasma and ascitic TNF-alpha at the end of follow up compared to those at the first admission [P<0.001]. The relative risk of deaths, HRS and SBP were higher in patients with compared to those without BactDNA after follow up for 24 weeks [2.73, 27.37 and 18.18 respectively]. There were significant positive correlation between both plasma and ascitic TNF-alpha and each of serum creatinine and PMNL in the studied patients at the end of follow up. [r= 0.590, p= 0.002 ; r= 0.535, p= 0.005 ; r=0.499, p=0.009 ; r= 0.589, p= 0.002, respectively]. -Patients with BactDNA had more advanced liver disease after 24 weeks follow up compared to patients without BactDNA. We conclude that cirrhotic patients with culture negative, non neutrocytic ascites and BactDNA have significant higher level of AF and plasma TNF-alpha and higher risk of HRS, SBP and morality compared to those without BactDNA during follow up for 24 weeks which could suggest that both BactDNA and TNF-alpha have been implicated in these complications of liver cirrhosis