Lipopolysaccharide (LPS) and endothelin- (ET-) 1 may aggravate portal hypertension by increasing intrahepatic resistance and splanchnic blood flow. In the portal vein, after TIPS shunting, LPS and ET-1 were significantly decreased. Our study suggests that TIPS can benefit cirrhotic patients not only in high hemodynamics related variceal bleeding but also in intestinal bacterial translocation associated complications such as endotoxemia.
Portal hypertension is a complication of liver cirrhosis. Cirrhotic nodules lead to altered intrahepatic architecture and are the initiating, irreversible pathophysiological feature of cirrhosis. The major pathophysiological mechanisms of portal hypertension are increased intrahepatic resistance and increased splanchnic blood flow, so intrahepatic vascular contraction and increased splanchnic blood flow may be key therapeutic targets in portal hypertension [
Bacterial translocation is a common problem and plays an important role in the pathogenesis and complications in patients with decompensated cirrhosis [
Transjugular intrahepatic portosystemic shunt (TIPS) is an important interventional procedure for treatment of the complications of advanced cirrhosis that have failed with medical management [
We studied 30 consecutive patients with portal hypertension at high risk of acute variceal bleeding who underwent TIPS at Jinling Hospital, Nanjing, China, between October 2013 and December 2014. Patients had severe esophageal varices upon endoscopy, had more than one episode of variceal bleeding, and had failed drug or endoscopic treatment. Diagnosis of cirrhosis was established by a combination of biochemical, clinical, ultrasonographic, and liver histological findings. The etiology of cirrhosis was alcohol in three patients, chronic Budd-Chiari syndrome in three patients, and viral hepatitis B in 24 patients. No alcohol abuse was detected 2 months before the procedure. The clinical indications for TIPS include repeated variceal bleeding despite appropriate secondary prophylaxis
Blood samples were taken from the right atrium, hepatic vein, and portal vein before insertion of the TIPS stent and 7 days after the TIPS procedure (Figures
Hepatic venous blood samples were taken under guidance of X-rays.
Portal venous blood samples were taken under guidance of X-rays.
TIPS was performed as described previously [
Statistical analysis was performed with SPSS for Windows version 17. Quantitative variables are displayed as medians if not otherwise indicated. We used Student’s
The Ethics Committee of Jinling Hospital approved this study. Written informed consent was obtained from each patient prior to the study.
The demographic and biochemical characteristics of the patients are listed in Table
Basic characteristics of patients (plus/minus are means ± SD).
Gender (male/female) | 24/6 |
Age (years) | 52.5 ± 11.8 |
INR | 1.3 (1.1–1.48) |
Serum ALAT (U/L) | 26.8 ± 13.5 |
Plasma albumin (g/L) | 36 ± 4.29 |
Plasma creatinine (s) | 87 (50–108) |
Child-Pugh class (A/B/C) | 5/18/7 |
Cirrhosis aetiology ( |
|
HBV | 24 |
Chronic Budd-Chiari | 3 |
Alcohol | 3 |
Indication | |
Refractory ascites | 25 |
Recurrent variceal bleeding | 19 |
AST: aspartate aminotransferase; INR: international normalized ratio.
Before TIPS, LPS level did not differ significantly between portal vein and hepatic vein plasma: 88 (56–105) versus 92 (54–110) pg/mL. In the portal vein, LPS level decreased significantly from
Portal venous plasma LPS concentration before and 5–7 days after TIPS procedure depicted as dot plots, illustrating median, range, and 50% interval with 25th and 75th percentile. The level of LPS in portal vein was decreased from
Portal venous plasma ET-1 concentration before and 5–7 days after TIPS procedure depicted as dot plots, illustrating median, range, and 50% interval with 25th and 75th percentile. The level of ET-1 in portal vein was decreased from
Regression analysis showed no significant correlation between right atrial and portal venous levels of LPS and ET-1 and PVPG before and after TIPS insertion. However, when compared with the PVPG at the time during TIPS insertion and 7 days after TIPS, PVPG decreased significantly from 10 (8–16) to 8 (6–14) mmHg
The reduction level of LPS was correlated with the reduction of the PVPG 7 days after the TIPS insertion (Spearman’s
The main findings of the present study were as follows. We found no intrahepatic gradient of LPS before TIPS placement. LPS and ET-1 levels were decreased in the portal vein after TIPS insertion. During the time before TIPS and after TIPS, there was a correlation between the reduction in portal venous LPS and the reduction in PVPG.
Bacterial translocation is defined as the passage of both viable and nonviable bacteria and bacterial products, such as endotoxin. It is common in decompensated cirrhosis and may be an important pathogenic event in several complications of cirrhosis [
We found reduced LPS levels in the portal vein; thus, TIPS may reduce LPS levels in the portal vein after stent insertion, possibly as a result of reducing the PVPG. Portal hypertension may be an important factor in the development of small bowel mucosal changes [
We found that ET-1 level was decreased in the portal vein after TIPS insertion. ET-1 may play an important role in liver disease, especially in circulatory disorders such as portal hypertension and ischemia. ET-1 acts as a paracrine hormone and its plasma levels could represent an overflow of locally produced peptides [
The reduction in portal venous LPS was well correlated with the reduction in PVPG after the TIPS procedure. Binding of ET-1 to ET-B receptors results in activation of eNOS and production of NO, which lead to vasodilation at the sinusoidal level [
It should be noted that the concentrations in our study have a preliminary character because of the limited numbers and the heterogeneous nature of the patients (e.g., different Child-Pugh classes, ascites, and acute bleeding). Additionally, the blood samples were measured before and 7 days after TIPS insertion separately, so the concentration may be attributed to the different times when the blood samples were obtained [
In conclusion, we observed that, after the TIPS procedure, LPS and ET-1 levels in the portal vein both were decreased and the reduction in portal venous LPS was well correlated with the reduction in PVPG. Our study suggests that TIPS can benefit cirrhotic patients not only in high hemodynamics related variceal bleeding but also in intestinal bacterial translocation associated complications such as endotoxemia.
Lipopolysaccharide
Endothelin-1
Transjugular intrahepatic portosystemic shunt
Enzyme linked immunosorbent assay
Nitric oxide
Endothelial nitric oxide synthase
Portal venous pressure gradient.
The authors declare that there is no conflict of interests regarding the publication of this paper.
Jiaxiang Meng and Qing Wang contributed equally to this work.