Reply to: "Post-TIPS OHE: Are we really making a mountain out of a molehill?"

To the Editor: We read with great interest the letter from Wang and colleagues1 and we are grateful for their positive comments on our paper on the impact of episodic overt hepatic encephalopathy (OHE) on survival in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS).2 We completely agree that the occurrence of overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) placement represents a relevant concern for hepatologists when proposing a TIPS to their patients. In fact, OHE is extremely frequent after a TIPS although persistent in a minority of patients. Post-TIPS OHE undoubtedly has a detrimental impact on patients’ quality of life and represents a burden for caregivers and the healthcare system. Data reported in our recent study2 indicate that the incidence of persistent post-TIPS OHE was higher in patients who died following TIPS, and our conclusions that post-TIPS OHE were not associated with higher mortality was based on patients with episodic OHE. In their letter, based on the available literature, Wang and colleagues3–5 raise two relevant issues, (i) whether the timing and frequency of OHE episode(s) and (ii) the grade of OHE affect prognosis. Nonetheless, we re-analyzed our study database to address both points raised by Wang et al..1 It should be noted that the relationship between the so-called early OHE (occurring within 3 months from TIPS) and survival3 was mainly related to the subgroup of patients with recurrent OHE, in agreement with our observation on the negative prognostic impact of recurrent/persistent OHE. In our patients, no significant differences in terms of survival were observed among those with early or late OHE and those with no episodes (Fig. 1A). Fig. 1 Fig. 1 The estimate of mortality post-TIPS, accounting for liver transplantation as a competing risk, by timing and severity of OHE. Show full captionFigure viewer As far as the relationship between severe post-TIPS OHE (grade 3-4) and survival is concerned, it should be considered that the negative prognostic impact of severe OHE was based on the observation of very few patients, specifically 17 in the study of Stewart et al.4 and 11 in that of Bettinger et al..5 Our data clearly indicate that in the context of episodic OHE, its severity was not associated with any differences in survival (Fig. 1B). Finally, the different population under investigation, considering that in our study a considerable fraction of patients received an undersized TIPS could have had an independent positive effect by preventing further potential detrimental effects of TIPS. In conclusion, the original and the present analyses mitigate concerns regarding the prognostic impact of post-TIPS episodic OHE. Nevertheless, further studies are needed to dissect the factors associated with the development of this potentially deadly complication. In fact, the occurrence of persistent OHE is still largely unpredictable. The sample size of future studies must be considerably large given the lower incidence of persistent post-TIPS OHE afforded by the increasing use of undersized endoprostheses. At this time, while physicians should still be cautious in stating that the onset of post-TIPS OHE will not influence prognosis, the risks associated with the development of OHE must be balanced with the benefits related to the high efficacy in the control of portal hypertensive complications.