Is bacterial DNA a better marker than endotoxin of bacterial translocation in decompensated cirrhosis?
Authors: Jiannis Vlachogiannakos, George Daikos, Ulrich Thalheimer, Andrew K. Burroughs, Spiros D. Ladas
Journal: Hepatology (2011)

Translocation of intestinal bacterial products deteriorates systemic and liver hemodynamics in patients with cirrhosis.1 We read with interest the report by Bellot etal.,2 who found that the presence of bacterial DNA (bactDNA) in patients with cirrhosis aggravates the systemic circulatory dysfunction and is associated with a more severe intrahepatic endothelial dysfunction. The same group previously reported that bactDNA is associated with increased serum inflammatory responses, independently of endotoxin. Therefore, the question arises whether bactDNA represents a more global marker of bacterial translocation compared to endotoxin in patients with advanced cirrhosis. We would like to raise some issues concerning the results of Bellot etal. and share the results of our investigations on the role of endotoxin and bactDNA in patients with decompensated cirrhosis. First, although patients with bactDNA had more profound systemic vasodilation than patients who were negative for bactDNA, baseline hepatic venous pressure gradient (HVPG) was similar in both groups. Second, plasma bactDNA concentration was not correlated with systemic hemodynamic parameters, thus calling into question the pivotal role of bactDNA in the hemodynamic disturbances of cirrhosis. We conducted a study to determine plasma endotoxin in 30 patients with cirrhosis who had ascites and to investigate the effect of intestinal decontamination on HVPG, through use of rifaximin for 28 days.3 Endotoxemia was common in this cohort of patients and was correlated with the severity of liver disease. Moreover, endotoxin levels decreased significantly after rifaximin administration, and the difference was correlated with the difference in HVPG values. Subsequently, we investigated the presence of bactDNA in the same blood samples. DNA was extracted with the QIAmpDNA Blood Minikit (Qiagen, Germany), and bactDNA was tested by polymerase chain reaction using specific primers for bacterial 16S ribosomal RNA. BactDNA was not detected in any blood sample from systemic or splanchnic circulation on days 0 and 29 after rifaximin administration. The method was validated in patients with bacteremia and all samples were positive for bacterial genomic fragments. We have no clear explanation why bactDNA was not detected in our patients. We may have missed transient episodes of bacterial translocation because we only monitored twice for bactDNA and with an interval of 28 days. Furthermore, rifaximin administration may have achieved elimination of bactDNA, but endotoxin was still present. However, regardless of issues of detection of bactDNA, according to our results, endotoxemia could represent a reliable marker of bacterial translocation in patients with decompensated cirrhosis. The presence of bacterial products and/or bactDNA might be an additional step in the sequence of events that further deteriorate portal hypertension, especially in the absence of viable bacteria or endotoxemia, but this needs further investigation. Jiannis Vlachogiannakos M.D.*, George Daikos M.D.*, Ulrich Thalheimer M.D. , Andrew K. Burroughs M.D. , Spiros D. Ladas M.D.*, * Hepatogastroenterology Unit, First Department of Propaedeutic Medicine, Medical School, Athens University, Laiko General Hospital, Athens, Greece, The Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK.