Transjugular intrahepatic portosystemic stent-shunts (TIPS) have been increasingly used for the treatment of the complications of portal hypertension. A meta-analysis of randomized controlled trials confirms the superiority of TIPS over the endoscopic treatments in the prevention of variceal rebleeding but without any improvement in mortality [13]. Additionally, TIPS is effective in the resolution of refractory ascites in some patients [13]. But it remains unclear as to whether there is any survival advantage [14]. Hepatic encephalopathy is thought to result from intestinally derived toxins that bypass the normal metabolic pathways of the liver, either because of shunting of portal vein blood flow away from the liver parenchyma as in TIPS patients or because of the inability of the liver to handle such substances because of chronic hepatocellular disease. Certainly, both of these factors may play a role in patients with cirrhosis, with either one being more important [15].
Many studies have focused on the relevant factors of HE, but the effects of pre-/post-TIPS factors were found to be contradictory. The factors include pre-TIPS, age, liver function, pre-TIPS HE, Child score, and the direction of flow in the portal vein. In this study, we found that the occurrence of post-TIPS HE was closely related to the pre-TIPS portal blood flow direction; the low incidence of post-TIPS HE was observed in patients with hepatofugal portal blood flow (n = 2) 10%, but high incidence in those with prograde (hepatopetal) portal blood flow (n = 9) 29%, indicating that the pre-TIPS pattern of blood flow may greatly affect the occurrence of post-TIPS HE [16].
In the study done by Zuckerman et al. [17], the occurrence of HE after TIPS was independent of central venous pressures; portosystemic gradients (before and after TIPS); the direction of blood flow (before and after TIPS) in the right, left, and main portal veins; and the presence of encephalopathy after TIPS, and this is contrary to our results [17].
In a similar study done by Deng et al., the incidence of post-TIPS HE in the hepatofugal group 16% was lower than that in hepatopetal group 37%, which agrees with our study [18].
Many studies agree that age more than 60 years old increases the incidence of post-TIPS HE. Sanyal et al. [19] stated that increasing age was significantly associated with encephalopathy, which agrees with our study [20].
In this study, we found that Child score was very important in the post-TIPS incidence of HE, with the Child score increasing, the more the post-TIPS incidence of HE. In this study, 4 patients had Child score A, none of them had post-TIPS HE; 44 patients had Child score B, 9 had post-TIPS HE; and 2 patients had Child score C, two had post-TIPS HE.
In a similar study by Sanyal et al., increasing Child class is significantly associated with post-TIPS HE, which agrees with our study [19].
Careful selection of patients for elective TIPS insertion is crucial, as is the experience of the center performing this procedure. TIPS is not recommended in patients with serum bilirubin > 3 mg/dl and low platelet count, current hepatic encephalopathy or chronic hepatic encephalopathy, concomitant active infection, progressive renal failure, severe systolic or diastolic dysfunction, or pulmonary hypertension.
In another study by Somberg et al., post-TIPS HE is associated with multivariate like hypoalbuminemia (albumin is one of the main variables in assessing Child score) [21].
In this study, we found that pre-TIPS incidence of HE is associated with post-TIPS incidence of HE as two patients had pre-TIPS HE and the two patients had post-TIPS HE. In another study, those patients who developed clinically evident HE were significantly more likely to have a past history of encephalopathy and tended to be male [8, 22].
Past history of encephalopathy along with increasing age has previously been identified as important variables increasing the risk of post-TIPS HE [19] that goes with our study.
In another study, the mean age difference between patients with TIPS-related encephalopathy and other patients was not statistically significant (P = 0.11 (> 0.05)). The statistical power of this test was only 0.35; therefore, we cannot guarantee that TIPS-related encephalopathy is independent of age, and a large sample would be required [23].
In this study, we found that there was no any significant difference between causes of TIPS in patients with portal hypertension and post-TIPS incidence of HE, except in HRS cases; we had 2 cases, and the two cases developed post-TIPS HE.
In a similar study by Zuckerman et al., the cause of liver disease had no interrelationship with patients with TIPS-related HE, which agrees with our study in general [17].
In another study by Oliviero et al., serum creatinine level was the only variable related to the development of refractory HE at the logistic multivariate analysis. That agrees also with our study in the HRS cases, but we think that this issue needs more studies with more cases for more accurate results [24].
According to the hepatic artery RI, normally, when portal perfusion decreases, hepatic arterial blood may increase to maintain the relative invariableness of liver blood supply. This mechanism is called hepatic arterial buffer response (HABR). In this study, we found that before TIPS, the hepatic artery RI of patients of hepatopetal flow (0.61 ± 0.11) was significantly lower than that of hepatofugal group (0.75 ± 0.79) (P value 0.005).
In a similar study by Deng et al., the hepatic artery RI of the patients before TIPS was lower than that of the patients with prograde flow, indicating the difference of post-TIPS intrahepatic hemodynamics, and this agree with our study [18].
Also, we found in this study that the hepatic artery RI in the hepatopetal group decreases after TIPS (0.6 ± 0.11 before to 0.59 ± 0.07 after) but less than that in the hepatofugal group (0.75 ± 0.79 before to 0.57 ± 0.07 after) (P = 002); this indicates that there is a great change in the hemodynamics in the patient of the hepatofugal group after TIPS.
In a similar study by Deng et al. [18], hepatic hemodynamics of patients with hepatofugal portal flow only changed a little after TIPS and was still dependent on the hepatic artery perfusion. Therefore, the RI of the hepatic artery was changed a little before and after TIPS, and this contrary to our study; although in patients with hepatofugal flow, large spontaneous portosystemic anastomosis could be found, and more importantly, the long-term existence of small to large pre-TIPS spontaneous portosystemic anastomoses might enable the cerebrum to adapt to some neurotoxic substances in the blood, which causes HE [18]. The lack of control subjects, however, does limit the ability to evaluate this approach.
According to post-TIPS hemodynamics and mean arterial blood pressure (MAP) before and after in this study, we found that MAP of patients with hepatofugal flow (76.8 ± 7.1) was less than those with hepatopetal flow (80.9 ± 7.5); also, we found that the MAP decreased after TIPS, and the decrease was more in patients with hepatopetal flow more than that of hepatofugal flow. All these results indicate that there is an alteration in the hemodynamic in patients post-TIPS more in patients with hepatopetal flow, and this may explain the high rate of post-TIPS HE.
Another study showed that the average MAP was (92 mmHg) before TIPS; a tendency of MAP to increase after TIPS replacement was noted (100 mmHg), but the difference was not significant. Two months later, it decreased to a value lower than the baseline (85 mmHg), and this agrees with our study [25].
HE is a well-known complication of patients with liver cirrhosis after portosystemic shunt. In recent years, TIPS has been accepted as minimally invasive therapy for complications of portal hypertension recurrent bleeding from varices, refractory ascites, and liver failure due to Budd-Chiari syndrome. Because TIPS resembles a surgical side-to-side shunt, an increased rate of HE can be seen after TIPS; the higher incidence of HE after TIPS has attracted the interest of researches in investigating the causative factors for HE. Besides, predicting factors of HE after TIPS have been much controversial.