Optimality of 2-week Versus 4-week Intervals in Secondary Prophylaxis of Bleeding by Endoscopic Esophageal Variceal Ligation

• Cirrhotic patients after their first variceal hemorrhage have a risk (> 60 %) of recurrent bleeding within 1 year, and mortality from each rebleeding episode is roughly 20%.
• First-line therapy for the prevention of recurrent variceal hemorrhage is the combination of traditional NSBBs or carvedilol and EVL.
• The optimal time interval for EBL sessions remains without consensus owing to the limited evidence.
• Secondary preventive measures are administered to reduce variceal rebleeding, thereby improving patient survival and clinical outcome.

PATIENTS AND METHODS

Table (1): Comparison between group I and group II regarding demographic, clinical, and laboratory data.

This study aimed at determining the optimum interval between band ligation sessions done to manage variceal bleeding, the interval that achieves the balance between the benefit of rapid eradication of EVs and risk of complications due to frequent repeated sessions.

Patients were randomly allocated into two groups, with a total number of 204 (102 patients in each group). The patients were referred to endoscopy unit for control of the first attack of varices bleeding. Group I: 68 males and 34 females have undergone EVL sessions every 2 weeks till obliteration of EVs and Group II:  60 males and 42 females have undergone EVL sessions every 4 weeks till obliteration of EVs.

This study showed no significant differences between the two groups as regard age, sex, clinical findings as well as laboratory and sonographic data. Most of included cases in both groups were Child B classification (60.8 % in group I and  70.6 %  in group B) which agree with Butt et al., who stated that most of their patients presented with first attack variceal bleeding was Child-Pugh class B or C (84%) [10].

Most patients in our study denied previous history of endoscopic evaluation until this time when they presented with first variceal bleeding attack. This delay can be caused by the hesitation of both patients and health care providers to refer their patients to endoscopic evaluation when they are still well compensated in Child grade A. This hesitation may be because both patients and health care providers would consider endoscopy to be risky, expensive, and invasive. Hence, the importance of non-invasive diagnostic methods for EVs was stated by the Baveno VI and VII consensus [11,12], to avoid referring patients to unnecessary endoscopic evaluation and detect patients at high risk of EVs before they bleed and assign them for primary prophylaxis with EVL.  

In the present study, there was no significant differences between both groups as regard initial endoscopic evaluation (grade of EVs as well as presence of risky signs). This means that the two groups were comparable to each other and the absence of a third factor manipulating the final results is assured.

Comparison between the two groups in the later endoscopy sessions showed that group II had significantly higher grade of EVs starting from second till the fifth session. This means that there was a delay in the obliteration of EVs in this group enhancing the risk of rebleeding among those patients. However, there were no significant differences between the studied groups as regards neither rebleeding nor risky signs all through period of follow up except in the final endoscopy session when group II showed significantly higher rate of risky signs on EVs. The rate of variceal rebleeding in the session by session (follow up) showed no significant differences between two groups. However, overall rate of variceal rebleeding was higher in group II. This agreed with Sheibani et al., who discovered that increasing the time interval between follow up endoscopy sessions led to increase in the rate of variceal rebleeding in between sessions [13].

In our study, the most common causes of post-banding rehospitalization were re-bleeding, chest infection, urinary tract infections and spontaneous bacterial peritonitis among which variceal rebleeding was the most common cause of hospitalization in those patients. It is also worth saying that there was no significant difference between both groups as regard causes of hospitalization. In contrast, a case-control study by Harewood et al., compared patients in whom EVs rebleeding developed with those who did not rebleed. The median interval between banding sessions in the rebleeding group was 2 weeks. This disagreement may be because all patients in our study fall in the interquartile range of interval between EVL sessions of non-bleeders according to Harewood et al [14].

This study showed significantly higher rate of post-banding ulcer in group I patients noted starting from second to forth session. The decision to apply band ligation in patients with observed post-band ulcers in their follow up endoscopy sessions, was tailored according to the evaluation done by the endoscopist (regarding the number and depth of the ulcers), the more the depth and the more the ulcers were scattered, the more the decision to proceed was hindered. Moreover, the technique of banding was modified to be applied away from the edges of the pre-existing post-band ulcers. This significantly higher rate of post banding ulcer was not associated with any significant increase in the rate of rebleeding in those patients neither in the session by session follow up nor in the overall rate. On the contrary, the overall rate of rebleeding was higher in group II, the group with lower rate of post-banding ulcer. It was also worth noticing that the rate of different post banding symptoms like; dysphagia, odynophagia, heart burn or fever was also found to be insignificantly different in both groups this mean that this higher rate of post banding ulceration in group I had no specific symptoms in most instances. This finding comes in line with Sheibani et al., who stated that , there were no significant increase in the proportion of patients developing post band complication after 1 week or 2 week of EVL [13]. In another study by Wang et al.,  there was a significant increase of adverse events in the Monthly group than in Biweekly group [15].

In the current study regarding to eradication rate of EVs, there was no significant difference between both groups at 4 weeks and there was a high significant difference at 8 and 12 weeks with higher eradication rate in group I than in group II. Our findings are consistent with Sheibani et al, and Wang et al, who said that the shorter the interval between sessions, the faster the eradication of varices [13,15]. Similarly, most recommendation for primary prophylaxis, endoscopy with EVL should be repeated every 1 to 2 weeks until EVs obliteration [16]. In contrast, a study done by Yoshida et al., stated that EVL every two months was better for total EVs eradication [17]. British Society of Gastroenterology guideline recommended interval of 2 – 4 weeks for EVL [18]. However, these recommendations are based on older randomized trials of sclerotherapy, intervals employed in prior ligation trials, and retrospective observational studies of ligation [16,19].

In the present study, the mean number of sessions needed for EVs eradication in group I was 4.98 ± 1.46 and in group II was 5.07 ± 1.91 with no significant difference in between which partially agree with a study conducted in Morocco by Villanueva et al.,showed that number of session needed for variceal obliteration was from 1 to 8 sessions (mean 3) [20]. In another study by Wang et al., the mean number of sessions was 3.6 sessions to achieve EVs eradication for each patient [21]. Similarly, our findings were supported by a study by Alvi et al.,  and Khattak et al.,  in which majority of patients achieved complete eradication after 3 sessions or 4 session of band ligation [22,23]. In contrast, Shrestha et al., reported that EVs were eradicated after 2 sessions of band ligation and about 24 % of patients required just 1 session of EVL [24]. None of the patients in our study achieved EVs eradication after 1 session only.

This study has some limitations; it was a single-center study, and the sample size was relatively small. EVL is operator dependent. The endoscopist' experiences may have an impact on successful EVs eradication and complication after EVL. Also, patients not followed up after EVs eradication for detection of variceal recurrence. Large-scale multicenter trials are needed to confirm our results and to detect the optimal interval between EVL sessions.

In conclusion, the two weekly EVL schedule can help achieve EVs obliteration in shorter duration than 4 weekly schedule and lower overall rate of rebleeding without any significant increase in the post banding symptoms, complications, or rehospitalization.

Acknowledgment

The authors would thank all colleagues who helped to conduct this study.

Funding

None declared.

Conflict of interest

None declared.

Ethical consideration

Permission and official approval to carry out the study was obtained. All patients signed a written informed consent before inclusion into this study and the institutional ethical committee at Zagazig University, Faculty of Medicine approved the study (ZU-IRB #4084/15-10-2017). The study protocol conforms with the ethical guidelines of the 1975 Declaration of Helsinki.