Different Factors Correlated to Early Rebleeding in Cirrhotic Patients Treated by Variceal Band ligation versus Endoscopic Sclerotherapy

Results: There was no significant difference between the two groups as regards rate of early rebleeding (15.4% in group I vs 9.6% in group II P= 0.374). The rate of early rebleeding was significantly correlated to Child's score (r=+0.136 P=0.014), PT (r=+0.35 P<0.001), INR(r=+0.419 P<0.001), grade of OV (r=+0.233 P=0.001), risky signs (r=+0.179 P=0.001), units of blood received (r=+0.387 P<0.001), amount of ethanolamine oleate (r=+0.329 P=0.017) and number of rubber bands used (r= +0.245 P=0.039). Mortality rates showed also no significant difference during the six weeks of follow up ,(19.2% in group I vs 21% in group II P= 0.647), as well as mortality rates in rebleeding cases (37.5% in group I vs 40% in group II P=0.925). Conclusion: The factors that are strongly correlated to rate of early rebleeding after endoscopic management of OV are severely decompensated liver disease, larger OV size and presence of risky signs, use of more blood units during resuscitation, use of large amount of ethanolamine oleate during sclerotherapy and use of more rubber band during banding. Sclerotherapy and band ligation are comparable to each other in most outcomes especially early rebleeding and mortality.


INTRODUCTION
Portal hypertension commonly complicates liver cirrhosis and the development of oesophegeal varices is one of the major complications of portal hypertension [1].The prevalence of oesophegeal varices at diagnosis ranges from 0-10% in patients with compensated cirrhosis, to 60% to 80% in patients with decompensated cirrhosis and the reported mortality from variceal bleeding ranges from 17% to 57% [2].The progression from small to large varices occurs in 10% to 20% of cases annually [3].
Endoscopic treatment has become the principal first-line intervention in patients with bleeding oesophegeal varices, both during the acute event and for long-term therapy to prevent recurrent bleeding [4].
After control of the index bleed, there is a 40% chance of rebleeding with a similar mortality.The risk of rebleeding is greatest during the first few days after initial variceal hemorrhage [5].Survival after variceal bleeding depends largely on the rapidity and efficacy of initial primary hemostasis and the presence and severity of underlying liver disease and hepatic functional reserve [6].
Early rebleeding has been shown to be a strong predictor of mortality and recurrent variceal bleeding substantially increases the risk of complications which further contribute to mortality [6].Rapid and sustained control of variceal bleeding remains the principal imperative of endoscopic intervention [7].Several important clinical considerations influence the prognosis in individual patients.These include the natural history of the disease causing the portal hypertension, the location of the bleeding varices, residual hepatic function, the presence of associated systemic disease, continuing drug or alcohol abuse, patency of major splanchnic veins and the response to each specific treatment [8].
Until now, there has been no general consensus on the risk factors and measures to prevent early rebleeding in cirrhotic patients in Egypt.Variceal Band ligation and Endoscopic Sclerotherapy can be effective methods to manage variceal bleeding and may be prevent it primarily and secondarily.However, early recurrent bleeding as a vital complication after variceal band ligation and endoscopic sclerotherapy has not been studied fully.

Aim of the work:
The aim of the present study was to evaluate the different factors that can affect the rate of early rebleeding of early rebleeding after different endoscopic treatments of variceal bleeding which help better management of variceal bleeding. EIS was performed using a 25-gauge disposable injection needle for intravariceal and paravariceal injection.The sclerosant used was ethanolamineolyte. EVL was performed with PENTAX EG endoscope by the same experienced endoscopist using endoscopic ligating devices: an over tube or multi-band ligators.

Esophageal varices were graded into 4 grades as follows: [12]
 Grade I: small straight cords of varices continued to lower 1/3of the esophagus.
 Grade II: moderate sized clubbed varices with well-defined areas of normal mucosa between them, forming several distinct vertical cords and confined to lower third of esophagus.
 Grade III: gross varices extending into the proximal half of the esophagus, which is so large and tortuous, that normal mucosa may not be visible in between unless the esophagus is fully distended with air.
 Grade IV: varices are like those of grade III but with dilated capillaries on top or in between varices, (varix over varix).

Portal hypertensive gastropathy was classified as follows: [13]
 PHG grade I: mild reddening and congestive mucosa, no mosaic like pattern. PHG grade II: Severe redness and a fine reticular pattern separating the areas of raised edematous mucosa (mosaic like pattern) or fine speckling. PHG grade III: Point bleeding + grade II.

After endoscopy:
The patients used non selective beta blocker carvidalol for prevention of recurrent variceal bleeding, starting with 12.5 mg orally single daily dose as recommended by Banares et al. [14].
The patients were evaluated according to the presence or absence of the following symptoms: epigastric pain, heart burn, retrosternal chest pain, dysphagia, dyspepsia, and odynophagia upon discharge and during the follow up visits every two weeks.

Follow up:
The follow up of the patients was done every 2 weeks for 6weeks as regards the following:

Statistical analysis:
Data were checked, entered and analyzed using SPSS version 19 EPI-INFO 6 and for data processing and statistic.Numerical data were expressed as mean and standard deviation and the comparison between numerical data is done with simple t test for normally distributed data and with Mann Whitney U test when data distribution is skewed.We used number and percentage to express categorial data and chisquare test to compare them.The correlation between numerical data was done by Spearman's correlation coefficient.The correlation between numerical and categorical data used Spearman's rank correlation.

RESULTS
Comparison between the two studied groups as regards age, gender distribution, incidence of diabetes, hypertension and bilharziasis revealed no significant differences as shown in table (1).Table (1) shows also that there were no significant differences as regards the cause of cirrhosis and the previous use of primary prophylaxis.
Table (2) shows that there were no significant differences between the studied groups as regards the liver and spleen size as detected by sonography.There were also no significant differences between the two studied groups as regards portal vein diameter and velocity as well as hepatic artery resistive index measured by coloured doppler, as shown in table (2).Table (2) also shows that there were no significant differences between the two groups as regards all laboratory parameters.
Comparison between the studied groups as regards the endoscopic examination revealed no significant differences between the two groups as regards grade of OV, number of cords, grade of PHG and incidence of duodenopathy at the beginning of the study as shown in table (3).
Table (4) compares the studied groups as regards the incidences of the common post-endoscopy symptoms encountered by the patients and shows that there were no significant differences as regards any of these symptoms.
Table (5) compares the studied groups as regards rate and causes of rebleeding and mortality rate and shows that there were no significant differences between them.Correlation between the rate of rebleeding and study parameters revealed that the rate of rebleeding has significant positive correlation with Child's score, PT, INR, grade of OV, presence of risky signs, number of units of blood transfused during resuscitation, amount of sclerosing agent and number of rubber bands used as shown in table (6).Size and extent of esophageal varices seen at index endoscopy were also significantly positively correlated to the rebleeding.This result agrees with Benedeto-Stojanov et al. who found that primary variceal bleeding was present in 50% patients with medium and in 65.38% patients with large varices [33].There was no bleeding in patients with small varices.Also, our result agrees with Xu et al. who found that the extent and size of varices are independent risk factors for early rebleeding.Varices that extend along the entire esophagus are much more dangerous than varices that are limited to the middle and lower part.Moreover, a greater extent of varices often means that more rubber bands are needed, increasing the possibility of rebleeding [21].It also agrees with Varghese, et al. who stated that higher grades of varices, presence of cherry-red spots and fundal varices predict variceal bleed in patients with liver cirrhosis [37].The only exception to this is a study done by Koch et al. who found that 35% of patients with small varices bled, while only 20% of patients with large varices also bled.This difference because of small sample size, most cases were child class A and longer duration of follow up (36 months) [38].
In our study; there was significant positive correlation between rebleeding and presence of risky signs on varices.All early rebleeding cases in both groups had risky signs on varices at index endoscopy.This agrees with the study of the Northern Italian Endoscopic Club (NIEC) has shown that endoscopic finding of "red signs" is related to the variceal bleeding [39].Also, Benedeto-Stojanov et al. has shown that endoscopic finding of "red signs" is related to the variceal bleeding.The "red signs" were found in 85% of large varices with bleeding [33].
There was positive significant correlation between rebleeding and the amount of EO injected in sclerotherapy group and number of rubber bands used in band ligation group.This agrees with Xu et al. who found that the number of rubber bands was an independent risk factor for re-bleeding after EVL.Therefore, for varices which were in the mild to moderate class, it may not be reasonable to launch many rubber bands.For severe varices, however, it's usually unavoidable to use more bands [21].

CONCLUSION
Sclerotherapy is associated with higher incidence of rebleeding than band ligation.Most cases of early rebleeding occur during the first 2 weeks of follow up and were due to development of sclerosant or post banding ulcers.Early rebleeding in both groups was correlated to child pugh classification grade (early rebleeding more in child class C>child class B>child class A), elevated coagulation parameters (elevation in PT, INR) among studied groups, grade of oesophegeal varices: Most cases of early rebleeding cases had esophageal varices grade IV and presence of risky signs on varices.No significant correlation between rebleeding and ascites, PV diameter and color Doppler studies could be detected.No statistically significant difference between endoscopic sclerotherapy and band ligation regarding post endoscopy complications could be detected.No significant differences between scleotherapy and band ligation as regards overall mortality or mortality after rebleeding.

Table ( 1
): Demographic data, cause of cirrhosis and comorbidity # Chi-square •independent t test *Mann-Whitney U test, NS non significant

Table ( 3
): Endoscopic findings in both groups at the beginning of the study and after two weeks