Predictors of early rebleeding and mortality after acute variceal haemorrhage in patients with cirrhosis

doi:10.4236/ojgas.2013.37056

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Open Journal of Gastroenterology, 2013, 3, 317-321 OJGas

http://dx.doi.org/10.4236/ojgas.2013.37056 Published Online November 2013 (http://www.scirp.org/journal/ojgas/)

Predictors of early rebleeding and mortality after acute

variceal haemorrhage in patients with cirrhosis*

Iliass Charif#, Kaoutar Saada, Ihsane Mellouki, Mounia El Yousfi, Dafr Allah Benajah,

Mohamed El Abkari, Adil Ibrahimi, Nourdin Aqodad

Department of Hepatology and Gastroenterology, Hassan II University Hospital, Faculty of Medicine and Pharmacy, Sidi Moham-

med Ben Abdellah University of Fez, Fez, Morocco

Email: #[email protected]

Received 25 September 2013; revised 26 October 2013; accepted 14 November 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

The upper gastrointestinal bleeding from esophageal

or gastric varices is the most dangerous complication

of portal hypertension. The purpose of this study was

to identify the predictors of early rebleeding and mor-

tality after a bleeding episode. Patients and Methods:

It was a retrospective study including 215 patients

admitted in our department of hepatology and gas-

troenterology at the Hassan II University Hospital of

Fez, from January 2001 to January 2010. Results:

The mean age of our patients was 51 years. Thirty

percent of patients had cirrhosis due to virus (B or C).

The majority of patients (79%) had only esophageal

varices. Fifty patients (23%) had a bleeding recur-

rence. Twenty-five patients (11.5%) died during the

first ten days, of which 52% had presented rebleeding

(p = 0.01). In 30% of cases, the rebleeding was secon-

dary to a fall of pressure ulcers. Univariate analysis

showed that early mortality of patients was signifi-

cantly associated with advanced age (p = 0.018), low

prothrombin time (PT) (p = 0.022), low serum sodium

(p = 0.03), low platelet count (p = 0.05), and elevated

transaminases (p = 0.02). Conclusion: The survival of

cirrhotic patients after a bleeding episode was influ-

enced by advanced age, a low rate of PT, of serum

sodium, and of the platelet count, and elevated trans-

aminases.

Keywords: Cirrhosis; Portal Hypertension;

Gastrointestinal Bleeding; Esophageal Varices

1. INTRODUCTION

The upper gastrointestinal bleeding from esophageal var-

ices is one of the most dangerous complications of portal

hypertension, with a consistently high morbidity and

mortality [1,2]. Despite advances in the management of

variceal bleeding, mortality following a bleeding epi-

sode in cirrhotic patients has decreased by only 20%

[3,4]. Several risk factors associated with mortality after

a bleeding episode were identified. These factors are:

active bleeding during the initial endoscopy, venous

pressure gradient, portal vein thrombosis, alcoholic liver

disease, bilirubin, albumin, hematocrit, transaminases,

encephalopathy, hepatocellular carcinoma and Child

Pugh score [5,6]. Many of these data were collected from

retrospective studies where mortality after variceal

bleeding was greater than 50%. But these studies have

included a relatively small number of patients, or groups

with no standard treatment especially concerning the use

of antibiotics [5,7,8]. Several prognostic scores have

been developed in cirrhotic patients with variceal bleed-

ing. Currently, the most used are the Child-Pugh score

and MELD. Recent studies have demonstrated the ability

of these scores to predict early mortality in these patients

[9]. Given the significant changes in the natural history

of cirrhosis from the broad and standardized use of anti-

biotic prophylaxis and endoscopic treatment, and given

the etiological feature of cirrhosis in our population

characterised by the high prevalence of viral cirrhosis,

we have found that it is very interesting to investigate

predictor factors of rebleeding and those involved in the

short-term survival of cirrhotic patients with variceal

bleeding.

2. PATIENTS AND METHODS

2.1. Study Population

We present a retrospective study of patients with cirrho-

sis and variceal bleeding, admitted in our department of

hepatology and gastroenterology at the University Hos-

*Conflicts of interest: No conflicts of interest.

#Corresponding author.

OPEN ACCESS

I. Charif et al. / Open Journal of Gastroenterology 3 (2013) 317-321

318

pital of Fez, between January 2001 and January 2010.

We have included only patients presenting a first bleed-

ing episode. The diagnosis of cirrhosis was based on the

combination of clinical, biological, endoscopic and ultra-

sonographic criteria. The diagnosis of variceal bleeding

was confirmed by the presence of hematemesis and/or

melena at admission of our patients, and the presence of

varices at endoscopy with or without active bleeding and

without any other causes of bleeding highlighted in the

endoscopy. All patients were treated by esophageal

varices ligature associated with an antibiotic prophylaxis

based on cephalosporins, and transfusion if necessary.

During the study period, no patients had received treat-

ment with vasoactive drugs. We did not take into account

the experience of the operator who performed the hae-

mostatic action.

2.2. Variables Studied

All patients had received a biological assessment within

24 hours after the bleeding episode.

The variables studied were: age, sex, presence of as-

cites, encephalopathy, the presence of active bleeding,

lesions found at endoscopy, the platelet count, transami-

nases, prothrombin, the etiology of cirrhosis and child.

Rebleeding was defined according to the criteria of

Baveno V [10].

Early mortality was defined as death within 6 weeks

after the bleeding episode.

2.3. Statistical Methods

We conducted a descriptive analysis of data using the

Epi Info system and analytical one using the “t” Student

test. We have considered p < 0.05 as a significant value.

3. RESULTS

Between January 2001 and January 2010, 215 patients

with cirrhosis were included. The clinical characteristics

of patients are shown in Table 1. The average age was

51 years old, with an equal number of men and women.

Forty-one percent of patients had viral cirrhosis B and

18% had viral cirrhosis C, 67% of patients had Child B

and 22% had Child C. Forty-nine percent of patients had

ascites. The majority of patients (82%) had esophageal

varices alone, and 18% had esophageal varices asso-

ciated with gastric varices. Active bleeding at initial en-

doscopy was found in 66 patients (30%). The mean he-

moglobin level at admission was 8.7 g/dl, 42% of pa-

tients had received a blood transfusion during the first 24

hours of hospitalization (Table 1).

Fifty patients (23%) had rebleeding. Univariate analy-

sis showed that rebleeding was significantly associated

with the presence of a lowered prothrombin time (p =

0.05). Ascites was noted in 40% of patients with recur-

rence of bleeding (p = 0.1). The mean hemoglobin level

was 8.7 (p = 0.2), with an average number of units

transfused 2 (p = 0.1). The mean bilirubin was 16.85% (p

= 0.41). 60% of patients with recurrence had a Child B (p

= 0.2). Active bleeding at initial endoscopy was noted in

34% of cases (p = 0.3) (Table 2).

Twenty five (11.5%) patients died during the first ten

days, whose 52% had presented rebleeding (p = 0.01);

30% were secondary to an ulcer fall (p = 0.4). Univariate

analysis showed also that early mortality of patients was

significantly associated with advanced patients age (p =

0.018), low prothrombin time (p = 0.022), low serum

sodium (p = 0.03), low platelet count (p = 0.05), and

elevated transaminases (p = 0.02) (Table 3).

4. DISCUSSION

The rate of rebleeding in our study was 23% , this rate is

lower than that reported by Wang M et al. [11] in 2011

(35.8%) and Ben-Ari Z et al. [12] in 1999 (44%), but

approximately equal to that reported in the study of Krig

JE et al. [13] in 2009 (24%). This difference could be

due to a difference in treatment methods. Ben-Ari Z and

colleagues [12] treated their patients by blood transfu-

Table 1. Clinical and biological characteristics of the study

population (N = 215).

Number of patients 215

Male 107 (50%)

Mean age 51 ans

Child

24 (11%)

145 (67%)

48 (22%)

Cause of bleeding

Esophageal varices

Gastric varices + esophageal varices

215 (82%)

37 (18%)

Clinical caracteristics of bleeding

Melena

Hematemesis

Hématemesis + melena

127

Etiology of cirrhosis

Virus B

Virus C

Others

89 (41%)

38 (18%)

88 (41%)

Mean Hemoglobin (g/dl) 8.7

Natremia (meq/l) 135.7

Ascites 105

Transfusion in the first 24 hours 92 (24%)

Average number of units transfused 1.17

Varices with red signs 149

Varices with actif bleeding 66 (30%)

I. Charif et al. / Open Journal of Gastroenterology 3 (2013) 317-321 319

Table 2. Predictors of rebleeding: univariate analysis.

No rebleeding:

N = 165

Rebleeding:

N = 50 p

Mean age (an) 51 ans 50 ans 0.7

Male (%) 50% 50% 0.5

Ascites 85 (51%) 20 (40%) 0.1

Hepatic encephalopathy 11 (6%) 3 (6%) 0.5

Active bleeding 49 (29.7%) 17 (34%) 0.6

Esophageal varices

grade III 68 (41%) 18 (36%) 0.5

Gastric varices 27 (16%) 10 (20%) 0.5

Platelets 107,805 109,608 0.8

Glutamopyruvate

Transférase (GPT) 48 68 0.2

Prothrombin time 70% 59% 0.05

Child A

Child B

Child C

17 (10%)

107 (64%)

43 (26%)

6 (12%)

34 (68%)

6 (12%)

0.6

0.2

0.03

Table 3. Predictors of early mortality: univariate analysis.

Patients survived

N = 190

Patients died

N = 25 (11.6%) p

Age (an) 50.53 58.84 0.018

Male (%) 51% 40% 0.3

Ascites 91 (48%) 14 (56%) 0.5

Hepatic

encephalopathy 10 (5.2%) 4 (16%) -

Rebleeding 37 (19.5%) 13 (52%) 0.01

Platelets 132,590 105,053 0.05

Prothrombin time 69% 57% 0.02

Glutamopyruvate

Transférase (GPT) 44.6 114 0.02

Serum albumin 30 25 0.19

Serum creatinine 9.68 11.39 0.45

Natremia 136 132 0.03

Child A

Child B

Child C

245 (13.2%)

126 (96.6%)

31 (17%)

2 (14.2%)

6 (42.8%)

0.5

sions and vasoactive drugs, and if failure, sclerosis of

esophageal varices was performed. In the study of Wang

M et al. [11], patients were also treated with blood trans-

fusions, vaso active drugs and anti acids. However, Krige

JE and colleagues [13] treated their patients by sclerosis

of esophageal varices. In our study, all patients were

treated by endoscopic band ligation. The comparison

between these series allows us to conclude that endo-

scopic therapy may be effective in cirrhotic patients with

bleeding esophageal varices, this should be confirmed by

other studies. In the study by Wong et al. [11], univariate

analysis revealed that a low albumin levels, high white

blood cell count, score of Child B and C, the presence of

ascites, and encephalopathy were predictors of rebleed-

ing in cirrhotic patients, these results were similar to

those found in several studies [14-18]. In our study, these

factors were not significantly associated with rebleeding,

and only a low rate of prothrombin was a predictor of

recurrence. This result implies that the severity of co-

agulopathy may play a critical role in rebleeding. In the

series of K Bambha et al. [19], the MELD score and the

presence of platelet plug on varicose veins in the initial

endoscopy were predictive of rebleeding. Stratification

of patients according to the MELD score (MELD ≥ 18

points, MELD < 18 points) revealed a significant in-

crease in the risk of rebleeding in patients with a MELD

score ≥ 18 points. Currently, there is no well-established

model to accurately predict the survival of cirrhotic pa-

tients after an episode of gastrointestinal bleeding due to

rupture of esophageal varices. One of the difficulties is

that the prognosis for these patients is influenced not

only by the severity of the bleeding episode itself, but

also by the severity of the underlying liver disease. In our

series, the advanced age of patients was predictive of

mortality in the first six weeks after the bleeding episode,

this was consistent with the series of Sempere L et al.

[20] who found that age ≥ 65 years was significantly

associated with early mortality. This factor is probably

related to some factors found in the elderly population,

mainly the duration of progression of liver disease, and

the greater difficulty of management of recurrent de-

compensation [21]. In this series, the presence of HCC,

the incidence of infection during the bleeding episode, a

Child score ≥ 10 and MELD score ≥ 18 were also asso-

ciated with early mortality. Some authors suggest that the

development of HCC may accelerate the course of liver

disease [22]. These patients often have a portal vein

thrombosis, rebleeding after endoscopic treatment and

thus a higher risk of early mortality. This high mortality

rate is probably secondary to the advanced state of the

underlying cirrhosis and the difficulty of mastering portal

hypertension resulting [23-25]. In the series of Bamba K

et al, advanced Child score, MELD score ≥ 18, the

number of units transfused during the first 24 hours, the

presence of ascites, an active bleeding at initial endo-

scopy, high transaminase levels and low serum sodium

were predictive of early mortality. The last two parame-

ters were also found in our study, which was consistent

with other studies [26]. The occurrence of rebleeding

during the first five days after the bleeding was signifi-

cantly associated with early mortality in our series, a

I. Charif et al. / Open Journal of Gastroenterology 3 (2013) 317-321

320

factor also reported in the series of Kamba et al. [19].

5. CONCLUSION

The degree of liver cell failure influenced the occurrence

of rebleeding after an episode of variceal bleeding in

cirrhotic patients. The advanced age of patients, low

prothrombin time, low rates of serum sodium and of

platelets count, and high transaminase rate were predic-

tors of early mortality in these patients.

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OPEN ACCESS

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