Physicians taking care of patients with advanced HCC after a VB episode should individualize therapies according to clinical practice, common sense, and patient needs. Some may judge that the survival benefit in these BCLC C and D patients who received secondary prophylaxis is not clinically relevant Atezolizumab manufacturer (average, 3 months) and that more-interventional therapies (banding ligation) should be avoided, taking into account the possible adverse effects. Nevertheless, this survival benefit is similar to the survival benefit offered with sorafenib treatment in BCLC C patients,

which also has side effects, which may affect quality of life. The present study, showing a global survival effect of prophylaxis patients with advanced HCC, provides further evidence to indicate prophylaxis in this subgroup of patients as long as their clinical condition

allows them to do so. There are several setbacks to the study. Some patients with very advanced HCC and UGI bleeding were not included in the study because no endoscopy was performed. This could lead to some bias in the results, because it is probable that these patients who were not included would be the ones who would be most likely to die. However, the decision to exclude these patients from the study was based on several MAPK Inhibitor high throughput screening reasons. First, although suspected, the cause of the bleeding was not proven because endoscopy was not performed. It is well established that approximately one third of UGI bleeding

episodes MCE in patients with cirrhosis are the result of other causes, rather than esophageal varices.[40, 41] Second, most likely, the patients who would not receive endoscopy would probably be the sickest ones and therefore with the most dismal outcome. Therefore, inclusion of these patients in the analysis might further enhance the differences in the outcomes of VB in patients with and without HCC. Furthermore, and although it seems that patients with HCC without secondary prophylaxis were more sick than the ones who received secondary prophylaxis, which may have influenced the physician’s opinion, it could be that there are other factors that influenced this decision that are not included in the analysis. Unfortunately, the study design does not allow analysis of the effect of sorafenib treatment on variceal bleeding. It has been established, both in animal and human studies, that sorafenib has a portal hypotensive effect, perhaps through an inhibition of angiogenesis.[42, 43] Therefore, there could be an effect of the administration of this drug on the outcomes. In the present study, sorafenib was administered exclusively to patients with advanced HCC; therefore, it is logical to speculate that lack of sorafenib could further worsen the outcome of these patients, who already have a dismal prognosis. Another limitation of the study is the uneven distribution of the etiologies among patients with and without HCC.