Reply
Authors: Karim J. Halazun, Rachel E. Patzer, Abbas A. Rana, Benjamin Samstein, Robert S. Brown, Jean C. Emond
Journal: Hepatology (2015)

We thank the authors for their interest. Our article presents evidence, on a population-based level, that waiting time impacts survival in hepatocellular carcinoma (HCC), and we hypothesize that this may occur as a result of dropout of aggressive tumors in long waiting time regions (LWTRs).1 The lack of tumor biology and pathological data is a major limitation; however, our data are corroborated by the work of others on the influence of time on HCC outcomes; specifically, shorter waiting times are associated with increased recurrence rates and worse post-transplant survival.2, 3 Availability of these data is essential to further understand the best management of HCC and should be analyzed as the collection of explant pathology by United Network for Organ Sharing (UNOS) continues. Transarterial chemoembolization (TACE) in our study was not an independent predictor of outcome, and we cannot confirm that increased use of TACE in the LWTR improves outcomes. Furthermore, the limited data on TACE in the UNOS make it impossible to analyze this effect. We suggest that patients transplanted within their first cycle of Model for End-Stage Liver Disease exceptions likely do not receive as many treatments as those who wait longer, possibly influencing outcomes. It is a reasonable hypothesis that an effective tumor response to TACE is a favorable prognostic factor that bears further testing. With respect to unmeasured confounders, such as tumor biology, that might explain the effect, it would be surprising that the short waiting time regions would inadvertently be enriching their HCC population with high-risk tumors by any means other than rapid transplantation. Though propensity score matching may be useful, many have argued that there is little advantage of such an analysis over traditional multivariable regression analysis, especially in large data sets.4, 5 Epidemiologists and statisticians suggest that careful selection of covariates is more important than the type of analysis used.4, 5 Nonetheless, we conducted a propensity analysis, using the variables suggested by the authors, to examine whether waiting time was associated with post-transplant survival, as our results suggested. The hazard ratio (HR; for waiting <6 vs. ≥6 months) using traditional multivariable-adjusted analyses was 1.22 (P = 0.001; 95% confidence interval [CI]: 1.12-1.47). After using the propensity score analysis, the HR was 1.25 (P < 0.001; 95% CI: 1.06-1.39). Therefore, short waiting time remains an important predictor of worse survival, even after propensity adjustment. Karim J. Halazun, M.D.1 Rachel E. Patzer, Ph.D., M.P.H.1 Abbas A. Rana, M.D.2 Benjamin Samstein, M.D.3 Robert S. Brown, Jr., M.D., M.P.H.3 Jean C. Emond, M.D.3 1Emory Transplant Center Emory University Hospital Atlanta GA 2Division of Abdominal Transplantation and Division of Hepatobiliary Surgery Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, TX 3Center for Liver Disease and Transplantation Columbia University Medical Center NY Presbyterian Hospital New York, NY