Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: Still a major problem
Authors: Oliviero Riggio, Stefania Angeloni, Lorenzo Ridola
Journal: Hepatology (2010)

We read with interest the letter by Bai et al. We agree that hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) is still a major problem. In fact, post-TIPS HE incidence ranges from 30%-55% within the first year1-3 and, when TIPS is constructed with polytetrafluoroethylene-covered stents, HE seems to be not confined to the first postoperative period.3 Moreover, 8% of patients who undergo TIPS may experience a severe form of HE which requires the reduction of the shunt diameter.3 The authors criticized the suggestion that there is no convincing evidence of an effective pharmacological treatment in the prevention of HE because of the small sample size of our randomized controlled trial (RCT).4 However, in our study, the expected effect (40% versus 10%) used for the sample size calculation was chosen taking into account that the comparison was versus a no-treatment group and not between two groups with active treatments. We were convinced that the demonstration of any minor difference in terms of efficacy between active treatment and no treatment is clinically meaningless. The study of Sharma et al.,5 which was conducted on patients without TIPS, hypothesized a 40% difference between the active treatment and the no-treatment groups. Moreover, Bai et al. suggest a further note of caution in accepting the results of our RCT, in which low-absorbable disaccharides were ineffective in the prevention of HE after TIPS because, in the study of Sharma et al., the same treatment was able to prevent the recurrence of HE in patients without TIPS. Although the hypothesis involving the primary role of the gut-derived neurotoxins, especially ammonia, in the pathogenesis of HE in patients with or without TIPS is worth proposing, we believe that opening of a TIPS constitutes a completely different scenario that makes HE particularly difficult to prevent. In fact, further compromise of first-pass hepatic clearance of ammonia is to be expected. Additionally, the increase in splanchnic blood flow occurring after TIPS may enhance the delivery of ammonia into the systemic circulation. Another factor to be considered is the up-regulation of intestinal glutaminase activity, which has been reported after experimental portosystemic shunt procedures.6 This enzyme is responsible for the large amount of ammonia generated by the small intestine. Accordingly, one might anticipate that in the immediate aftermath of a TIPS procedure, more "intense" HE therapy might be needed to prevent overt episodes of HE than in patients who are not subjected to TIPS. In our opinion, the different results of the above studies underline the need for including homogeneous patients with specific risk factors in studies aimed at HE prophylaxis. Also of interest is the hypothesis of a novel adjustable stent system that is able to modulate the portacaval pressure gradient (PPG) to reduce the incidence of HE. Given that this hypothetical device could be created in the near future, it is very difficult to establish which PPG values should be reached to avoid HE and, at the same time, to control the complications of portal hypertension. We have recently completed a RCT comparing the use of stents of different diameter (10 mm versus 8 mm)7 which showed that the smaller stents led to a significantly less efficient control of complications of portal hypertension compared to the standard 10-mm stent diameter. Therefore, the modulation of the hypothetical device could be very difficult, at least in terms of diameter. Another difficulty is that the value of PPG required to avoid the occurrence of HE is unknown. Moreover, immediately after the procedure, the amount of blood reaching the heart increases rapidly with a consequent rise in the right atrium and in the central venous pressure.8, 9 The heart's adaptation to this new hemodynamic condition may occur in a variable time.8, 9 Consequently, the PPG value measured immediately after TIPS opening does not remain stable over time. It is therefore difficult to be able to modulate an unstable PPG to reach an unknown value. For these reasons, we believe that, unfortunately, HE will remain a major problem after TIPS until new treatments for the prevention of HE will become available. Oliviero Riggio*, Stefania Angeloni*, Lorenzo Ridola*, * II Gastroenterologia, Dipartimento di Medicina Clinica, "Sapienza" Università di Roma, Rome Italy.