Reply
Authors: Cristina Ripoll, Joan Genescà, Jaime Bosch
Journal: Hepatology (2014)

We thank Drs. Chen and Hou for the interest they have shown in our study. We agree with the limitations that they underline given the retrospective nature of the study.1 As they pointed out, patients with Barcelona Clinic Liver Cancer (BCLC) A/B without prophylaxis had a dismal outcome. However, since this subgroup includes only two patients, conclusions should be taken with extreme caution in this particular subset of patients. It is also possible that some patients died before starting secondary prophylaxis, as expected in the setting of variceal bleeding. Nevertheless, only patients who survived the acute bleeding episode (first 5 days) were considered eligible for the analysis of outcomes related to secondary prophylaxis. Due to the retrospective nature of the study, we can only speculate about the reasons why patients did not receive secondary prophylaxis. Given the high number of patients with BCLC C/D who did not receive prophylaxis, it is plausible to speculate that the responsible physician considered that these patients were too sick to benefit from prophylactic treatment. Indeed, as Drs. Chen and Hou emphasize, these patients had a higher Model for End-stage Liver Disease (MELD) (16 versus 13) and a borderline greater Child-Pugh score; this difference could have had an impact on the outcome. We would like to remark, however, that on multivariate analysis of lack of secondary prophylaxis, BCLC classification and liver failure as measured by Child-Pugh score were independent predictors of death. We agree with the concerns that Drs. Chen and Hou express regarding the grouping of BCLC C/D patients. This was done due to the similarities in the survival curves of these patients (see Supporting fig. 1 of the article). Taking into account the subjective nature of some aspects of this classification, such as the performance status, it is possible that the difference between BCLC C and D patients is not so clear-cut. We would like to underline that not all patients received the standard secondary prophylaxis in our study. In Spain, standard secondary prophylaxis is done with a combination of beta-blockers and endoscopic band ligation.2 Many patients received only beta-blockers as secondary prophylaxis, and only a minority of patients received endoscopic treatment as the sole prophylactic measure. The reason for this is not clear, but it could be due to the fact that endoscopic band ligation is perceived as a more aggressive option than beta-blocker therapy. Unfortunately, our study cannot answer the question of whether the administration of beta-blockers without endoscopic band ligation offers a better risk-benefit balance than standard secondary prophylaxis. However, we disagree with the comment made by Drs. Chen and Hou regarding the possible association between beta-blocker use and poor survival in patients with more advanced liver failure. The study they refer to3 is also a retrospective study with major baseline differences between groups, including the presence or absence of varices, which has a well-known impact on survival. In conclusion, we agree that the decision for secondary prophylaxis in patients with BCLC C/D should be made carefully, but our data suggest that secondary prophylaxis does offer a survival benefit in these patients. Physicians taking care of patients with advanced hepatocellular carcinoma should individualize therapies according to common sense and patient need. Cristina Ripoll, M.D.1 Joan Genescà, M.D.2 Jaime Bosch, M.D.3 1Servicio de Aparato Digestivo Hospital Universitario Gregorio Marañón IiSGM, CiberEHD Universidad Complutense Madrid, Spain 2Servicio Medicina Interna-Hepatología Hospital Universitari Vall d'Hebron Universidad Autónoma de Barcelona CiberEHD Barcelona, Spain 3Hepatic Hemodynamic Laboratory, Liver Unit Hospital Clínic IDIBAPS, CiberEHD University of Barcelona Barcelona, Spain