Reply to: Does encephalopathy with early onset after TIPS impact on mortality?

We read with great interest the letter from Hartl and colleagues (1) and we are grateful for their positive comments to our paper on the impact of episodic overt hepatic encephalopathy (OHE) on survival in cirrhotic patients submitted to transjugular intrahepatic portosystemic shunt (TIPS) (2). We completely agree that Landmark analysis is the statistical method to avoid immortal time bias (3-4), and according to Hartl et al. suggestions we conducted cumulative incidence analysis by setting landmarks at 1, 3 and 6 months after TIPS-implantation, respectively. These landmarks were chosen to represent early onset, mid-term and long-term onset of OHE, respectively. LT was considered as a competing event. OHE after TIPS was defined as new onset of HE grade ≥2. Similarly to Hartl et al., when dichotomizing the cohort for the incidence of OHE at 3 and 6 months after TIPS, there was no difference in mortality between these two groups of patients (Figure). Figure Figure Cumulative incidences of mortality after TIPS implantation. Show full captionFigure viewer As far as patients with OHE 1 month after TIPS, in Austrian cohort, they exhibited a significantly higher mortality in cumulative incidence analysis comparing to patients who not developed OHE. Contrary to Harthl et al. findings, in our patients, no significant differences in terms of survival were observed among patients with early OHE (1 month) and those with no episodes (Figure). This different result could depend on a difference between the two groups in terms of MELD, etiology, indication for TIPS and incidence of liver failure after TIPS. In conclusion, we showed that post-TIPS OHE occurring at 1, 3 and 6 months after TIPS in landmark analysis do not impact on mortality, supporting the initial findings (2). Nevertheless, further studies are needed to confirm these results and intensive research of factors improving patient selection, and allowing risk stratification remains crucial to ameliorate the quality of life of patients and caregivers and to avoid undermining the positive effects of TIPS on survival.