Reply
Authors: I. Lisanne Holster, Eric T.T.L. Tjwa, Adriaan Moelker, Ernst J. Kuipers, Henk R. van Buuren
Journal: Hepatology (2016)

We are grateful to Dr. Lo for the interest in our work. The comments provide us with the opportunity to further clarify some aspects of our trial.1 Dr. Lo first remarks on the number of patients who switched therapy. This reflects the morbidity of patients and the lack of complete efficacy of either treatment. This phenomenon was also observed in previous similar trials. For instance, a crossover from endoscopic therapy to transjugular intrahepatic portosystemic shunt (TIPS) occurred in 17% of our patients1 and in 24%-29% of patients in previous trials.2 In theory, such a switch to TIPS after failure of initial endoscopic therapy may have blurred a potential survival difference between the two treatments. We anticipated this by incorporating treatment failure (i.e., switch to other treatment arm or death) as a secondary combined endpoint in our trial. Four patients randomized to the TIPS arm did not receive this treatment for reasons mentioned in our article, and 2 patients switched to endoscopic therapy because of hepatic encephalopathy. Therefore, we performed an "as-treated" analysis, in which patients were analyzed as if they were treated and censored the moment they switched therapy. The overall results were identical to those of the intention-to-treat analysis, except for the endpoint hepatic encephalopathy. The 4 patients allocated to TIPS who did not receive the allocated intervention had a lower incidence of hepatic encephalopathy, resulting in a significant difference between the endoscopic+β-blocker arm and the TIPS arm (6/39 versus 14/33, P = 0.017) in the as-treated analysis (Supporting Fig. S1).1 Second, Dr. Lo mentions that 38% in the endoscopy arm appeared to receive only one session of endoscopic therapy. This proportion should, however, be interpreted differently. The mean number of endoscopies per patient in the first year after the index endoscopy was 2.9. The majority (56%) of these follow-up procedures included variceal ligation, 5% included injection therapy, while in 38% of all follow-up procedures no further treatment was considered necessary, i.e., after 2.9 sessions on average. Third, at index endoscopy 5 patients were treated with sclerotherapy, a procedure that is generally considered less effective than band ligation with respect to prevention of rebleeding. In our study, variceal rebleeding occurred in only 1 patient, who was initially treated with sclerotherapy. Obviously, this cannot explain the substantial difference in rebleeding rates between the endoscopy+β-blocker and the TIPS arm. Finally, Dr. Lo addresses the problem of stent occlusion. This was indeed a major issue with the use of uncovered stents. However, with the currently used polytetrafluoroethylene-covered stents, patency rates have been shown to be excellent3 as reflected in our study with a 94% patency rate after 2 years. I. Lisanne Holster, M.D., Ph.D.1 Eric T.T.L. Tjwa, M.D., Ph.D.1 Adriaan Moelker, M.D., Ph.D.2 Ernst J. Kuipers, M.D., Ph.D.1 Henk R. van Buuren, M.D., Ph.D.1 Departments of 1Gastroenterology and Hepatology and 2Radiology Erasmus MC University Medical Centre Rotterdam, The Netherlands