Amongst the complications of cirrhosis, acute variceal bleeding is one the most feared, as it is sudden, requires an intensive and prompt medical intervention and is charged with a variety of serious complications and a high mortality [9] [10]. Thus, significant efforts have been made during the past decades to evaluate the best prophylactic strategy. The latest guidelines recommend the use of NSBBs for patients with small varices and either NSBBs or EBL for patients with medium/large varices. Medical and endoscopic therapy are equivalent in preventing the first bleeding episode [11], and a few trials have evaluated the effect of the combination therapy compared to monotherapy. In 2005 Sarin et al randomized patients to receive EBL plus propranolol or EBL alone: during a follow-up period of 12 months, a non-significant difference in the actuarial probability of bleeding and bleed-related deaths was observed in the two groups [12]. Similarly, a retrospective study showed that adding NSBBs to EBL for primary prophylaxis did not modify bleeding rate nor mortality at 16 months. Besides, the two groups of patients were compared to another group of patients with cirrhosis treated with NSBBs only, from a previous study from the same Centre, and again no difference in bleeding rate or mortality was found [13]. On the other hand, another retrospective study [14] comparing bleeding rate and mortality in 504 cirrhotic patients with cirrhosis followed-up for a long period (mean 82 months) found that patients with propranolol plus EBL had a lower probability of first variceal bleeding with no difference in mortality compared to the ones in propranolol only regimen. It must be considered, though, that in this study the mean dose of propranolol administered was quite low, so the benefit of adding EBL to the NSBBs in terms of bleeding could result from an underlying inadequate beta-blocking.
According to international guidelines, once that a patient has started medical therapy, endoscopic screening is no more necessary [4], and no previous data have evaluated the possible benefits of adding EBL to the NSBBs regimen when an increased bleeding risk of the varices has been observed during the endoscopic follow-up of patients with cirrhosis. Therefore, the aim of this study was to evaluate if patients with worsening varices, defined as an increase in variceal size and the development of red signs, benefit, in terms of bleeding and survival, from adding EBL to the ongoing primary prophylactic treatment with NSBBs.
Interestingly, in our study, in patients treated only with NSBBs, the risk of first bleeding episode from varices during follow-up was similar to the one showed in the meta-analysis by D'Amico et al [15]. In the EBL plus NSBBs group, the number of bleeding episodes at 30 months was significantly lower than in NSBBs only group, while the survival rate was almost similar in the two groups, although a slight benefit in the NSBBs plus EBL group was observed at the multivariate analysis. The discrepancy between the prevalence of these two events in the two groups may be explained by a low rate of bleeding-related deaths due to a management of acute variceal bleeding optimized according to international guidelines, with services of urgent endoscopy available 24 hours a day, 7 days a week. If prospective randomized multicentric studies would confirm these data, these new insights could lead to a novel approach to the endoscopic follow-up and the subsequent treatment for primary prophylaxis of variceal bleeding in patients with cirrhosis.
Our study has limitations. The main one is that it was conducted retrospectively, and the decision to administer either NSBBs alone or NSBBs plus EBL depended on the choice of each single clinician. Secondly, our study is monocentric and includes a relatively small group of patients. Moreover, the cost-effectiveness of this diagnostic and therapeutic approach has not been evaluated.
In conclusion, our study shows that a strategy to implement the primary prophylaxis of oesophageal varices in patients with liver cirrhosis, adding EBL to NSBBs when at endoscopic control varices show an increased haemorrhagic risk, is effective in reducing the probability of first bleeding and might be effective in reducing mortality as well. If this benefit will be eventually confirmed in randomized studies, it will be necessary to re-evaluate the timing for periodic endoscopic screening of patients with cirrhosis and varices, which, at the present time, is not recommended once the patient has an ongoing primary prophylaxis with NSBBs.