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Dose optimization of non-selective beta blockers among esophageal varices patients at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia: a hospital-based cross-sectional study

BMC Gastroenterology volume 25, Article number: 100 (2025) Cite this article

Abstract

Background

Gastroesophageal varices are portosystemic collaterals formed due to portal hypertension. The primary consequence and leading cause of death in cases of gastroesophageal varices is bleeding. Although variceal hemorrhage mortality has decreased due to early diagnosis of gastroesophageal varices, prophylaxis, and therapy, these procedures are still difficult to perform in many underdeveloped nations. When the dose of nonselective b-blockers is optimized to the highest acceptable dosage to reach the therapeutic goal, the benefit of reducing the risk of variceal bleeding is greatest. B-blocker optimization is unknown in our nation and Africa.

Objective

To assess the optimization rate of non-selective B-blockers and associated factors among esophageal varices patients following at the University of Gondar referral hospital.

Methods

A hospital-based cross-sectional study was conducted at the University of Gondar referral hospital GI clinic, North West Ethiopia. A total of 150 patients were taken with consecutive sampling and the target populations of the study were all adult esophageal varices patients who were on non-selective B-blockers at the GI follow-up clinic. Data were collected with a structured questionnaire and both descriptive and analytical data analysis was performed. Frequency, tables, and graphs were used to represent the data.

Results

A total of 150 patients were included in the study. From these 30.7% of patients took optimal doses of non-selective B -blockers. Patients with poor drug adherence (AOR = 4.293, [95% CI = 1.191–15.484], p-value = 0.026) and hospital admission in the last 01 year (AOR = 2.915, [95%CI = 1.076–7.893], P-value = 0.035) were significantly associated with sub-optimization of non-selective B- blockers.

Conclusion

Only one-third of patients received the optimal dose of non-selective B-blockers. Poor drug adherence and previous admission in the last year were significantly associated with sub-optimal dosing of non-selective B-blockers.

Peer Review reports

Introduction

Gastroesophageal varices are collateral blood vessels that develop due to portal hypertension [1]. Esophageal varices, a common complication of liver cirrhosis, are present in approximately half of the cirrhotic patients at the time of initial diagnosis [2, 3]. About 80% of all bleeding episodes in cirrhosis patients are caused by EV bleeding, a potentially fatal consequence of portal hypertension [4]. The yearly incidence of variceal bleeding varies between 5 and 15%, which poses a 5-to 20% risk of death [2, 5]. Without subsequent prophylaxis, patients who have survived acute esophageal variceal hemorrhage are highly susceptible to rebreeding, with a 70% occurrence rate possible [2, 6]. The most significant indicator of variceal bleeding is variceal size; other indicators include the presence of red wale markings on the variceal wall and the severity of liver impairment as classified by the Child–Pugh system [4, 7].

Early recurrent bleeding following initial EV bleeding is significantly associated with a greater incidence of bacterial infection (P = 0.043). Isolated bacteremia, pneumonia, spontaneous bacterial peritonitis, and urinary tract infection accounted for 8, 7, 5, and 4 cases, respectively, among the 24 affected patients. Patients without prophylactic antibiotics had a greater infection frequency (15/43, 34.9%) than patients who had antibiotics (9/54, 16.7%), but the difference was not statistically significant (P = 0.067) [8].

There is no correlation between the use of NSAIDs or antiulcer medications and bleeding EVs. But even if antiulcer medications shield the mucosa, "occasional" oral NSAID usage represents a significant step towards variceal hemorrhage in patients with bleeding GVs, particularly from FVs [9].

Therapy with non-selective beta-blockers (NSBBs) is the mainstay for treating portal hypertension. To lower the risk of variceal bleeding by decreasing the hepatic venous portal pressure gradient, nonselective b-blockers (NSBBs) are commonly administered [10]. NSBB therapy has demonstrated effectiveness in lowering variceal bleeding or re-bleeding in both primary and secondary prevention of variceal bleeding, either by itself or in combination with endoscopic band ligation [11]. It has also been demonstrated that NSBB therapy affects other outcomes, such as lowering the incidence of ascites [12, 13].

Non-selective B-blockers are beneficial in reducing variceal bleeding when the dose is titrated to the highest tolerated dosage to achieve the therapeutic aim [13,14,15]. In Ethiopia and throughout Africa, the level of B-blocker optimization is unknown. The optimization rate was a pitiful 9.8% when it was done in Texas, USA [16], so doing this study is crucial in our setup; we used mainly medical management (B-blockers) in managing esophageal varices. This study highlights scientific gaps in the management of patients with esophageal varices in rural areas of Ethiopia and may provide guidance for enhanced quality of care. Additionally, the findings can serve as a baseline for further research in this area. This study primarily aimed to assess the optimization rate of non-selective B-blockers for the prevention of variceal bleeding and associated factors.

Methods and materials

Study design, period, and area

Between May 10 and September 20, 2022, a cross-sectional study was conducted in a hospital setting for patients with esophageal varices who were getting care at the University of Gondar Comprehensive Specialized Hospital in Gondar, Northwest Ethiopia. The town of Gondar is located in the Amhara region in northern Ethiopia, 748 km from Addis Ababa, the country’s capital.

Population + -

The study population was all adult esophageal varices patients attending the University of Gondar GI follow-up clinic during the study period.

Inclusion and exclusion criteria

All adults (age ≥ 18 years) esophageal varices patients who were on Non-selective B-blockers and had follow-up at the University of Gondar Comprehensive Specialized Hospital GI clinic. Esophageal varices patients who took NSBBs less than 03 months [17] and patients who had an incomplete medical record were excluded from the study.

Variables

The independent variables are Socio-demographic variables (age, sex, marital status, residency, level of education, income), health-related behaviors (smoking, alcohol intake, additional salt intake), clinical characteristics (cirrhosis and its grading, HSS, Portal vein thrombosis, previous hospitalization, Size of varices). Comorbidities (Cardiac diseases, HTN, DM, CKD, Hyperthyroidism), medications used (loop diuretics, ACEIs, K-sparing diuretics, lactulose, adherence, and side effects), Investigations (Cr, Na + , Hemoglobin, endoscopy) and the dependent variable is dose optimization of non-selective B-blockers.

Sample size calculation and sampling technique

Using a single population proportion formula (n = (Zα/2)2 p (1-p)/d2), the sample size was determined to be 136 with a 10% non-respondent rate, resulting in a final sample size of 150. The study participants were recruited using a consecutive sampling procedure, and the rate of optimal use of NSBBs was taken from a study conducted in Texas, USA; with a confidence level of 95% and marginal error of 5% [18].

Operational definitions

Esophageal varices was defined as diagnosis by upper GI endoscopy [19].

The severity of CLD was assessed by the CTP (Child Turcotte Pugh) score which is a well-validated score and the Japanese Research Society for Portal Hypertension (JRSPH) system was used for a grade of varices [20].

The optimal dosage of each NSBB for treatment of esophageal varices includes propranolol 160 mg/day for patients who had ascites and 320 mg for patients without ascites, Carvedilol 12.5 mg/day or the dose that decreases PR by 25% from baseline or 55-60 bpm [16, 21].

Good and poor drug adherence was assessed by the standard drug adherence tool (Brief Medication Questionnaire); which is a well-validated score [22].

Patients were considered to have alcoholic liver diseases if they had a history of ingestion of more than 3 standard drinks daily (for males) or 2 standard drinks daily (for females) and ongoing significant alcohol drinking was considered if they still drinking these amounts of alcohol [23, 24].

Participants who smoked < 100 cigarettes during their lifetime were classified as never smokers. Current smokers were defined as those who currently smoke and who reported having smoked more than 100 cigarettes in their lifetime. Former or past smokers were defined as those who reported having smoked > 100 cigarettes in their lifetime, but who no longer smoked at all at the time of the health checkup examination [25].

Patients taking more than 01 teaspoons of table salt (06 g of table salt or 02 g of sodium) per day had more salt intake than the recommended [26, 27].

Data collection procedure and quality control

One physician and two nurses used a standardized questionnaire to gather data. A self-prepared questionnaire was used to interview patients about their sociodemographic data, history of alcohol consumption, history of smoking, history of salt intake, history of any hospital admissions within the previous year, adverse effects of drugs, and adherence. The patient’s medical records were obtained using the proper data extraction format.

Measurements of height, weight, mid-upper arm circumference, heart rate, and blood pressure were taken as part of the physical examination. To gather pertinent medical histories, such as comorbidities and consequences from chronic liver disease, patient records were examined. The baseline heart rate was taken from the chart, and the heart rate on the day the B blocker was started was used. Laboratory findings, including creatinine, hemoglobin, and sodium, that were completed within a year were examined.

A manual sphygmomanometer was used to take blood pressure while the subject was sitting and then while standing. The closest centimeter was used to measure height. A calibrated equipment was used to measure weight to the nearest kilogram of body weight.

Data quality assurance

All data collectors received training on the goal, applicability of the study, and confidentiality of information to guarantee the quality of the data. The English version of the questionnaire was created using reviewed literature. Of the total number of patients with esophageal varices, 10% underwent pretest data collection. Patients who took part in the pretesting were excluded from the actual data gathering. To prevent duplication, specific markers were added to the chart after the data was collected.

Data analysis and interpretation

The investigator cleaned and examined the data for consistency. Following coding, the data was imported into Epidata version 4.6 and exported to IBM SPSS version 26 for further analysis. Descriptive statistics and bi-variable logistic regression were used to assess the effect of the different factors on the dependent variable. After that, for those variables with a p-value less than 0.2, multivariable logistic regression was used to control the confounding effect. The dependent variable was considered to have statistically significant associations with variables that had a p-value of less than 0.05. The degree of association between the independent and dependent variables was displayed using an OR with a 95% confidence interval.

Ethical clearance

This research was conducted under the Declaration of Helsinki. Permission was obtained from the Department of Internal Medicine and ethical clearance was received from the institutional review board of the University of Gondar’s College of Medicine and Health Sciences (Ethical Clearance Reference number: SOM/1670/14/2022). The research subjects gave their informed consent. The value of confidentiality was upheld. There were no therapeutic or diagnostic procedures carried out for the study’s objectives; instead, it is an observational study.

Results

Sociodemographic characteristics and health-related behaviors

One hundred eighty-two patients were screened and 32 patients were excluded based on the exclusion criteria.150 patients were eligible for inclusion from them 78 percent (78%) of patients were males. The mean age of patients at diagnosis was 39.97 (SD ± 12.92) years and seventy-six percent (76%) were from rural areas. Seventy-eight percent (78%) of patients were married and 30% of patients learn up to primary school. Fourteen percent (14%) of patients were taking additional salt and only 01 patient had a history of cigarette smoking (Table 1).

Table 1 Sociodemographic characteristics and health-related behaviors of patients with esophageal varices at UOGCSH GI follow-up clinic from May to September 2022 (n = 150)
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Clinical and medication-related characteristics

Most patients’ standing and sitting systolic blood pressure (SBP) was between 90 and 139mmhg (98.7% and 90%) with mean of 101.9(SD + 9.96) and 99.7 (SD + 11.29) respectively. Diastolic blood pressure (DBP) was between 60mmg and 89mmhg (98.7% and 93.3%) with mean of 65.37mmhg (SD + 7.19) and 63.93mmhg (SD + 7.41) respectively. Patients’ weight, height, and mid-upper arm circumference (MUAC) were measured and body mass index (BMI) was calculated. Thirty-four percent (34%) of patients’ BMI was below 18.5 kg/m2 with a mean of 19 kg/m2 (SD + 1.61) and 43.3% of patients’ mid-upper arm circumference (MUAC) was below 23 cm with a mean of 21.76 cm (SD + 2.30). Most patients had F2 and F3 esophageal varices (35.3% and 41.3%) respectively. 53.3% of esophageal varices were caused by HSS and 45.3% were due to chronic liver disease (CLD) of different etiologies. 57.3% of patients had cirrhosis, of which 68.6% had child Pugh class A and B cirrhosis. Identified causes of CLD were HBV (25.58%), HSS (20.93%), ALD (23.25%), HCV (18.60%), UNKOWN (8.14%), and others (3.49%) (Fig. 1) Distribution of the cause of CLD at UOGCSH GI follow-up clinic 2022). The most identified complications were ascites (84%) followed by PVT (10%), HRS (6%), and HE (5.3%). Around Forty percent (40%) of patients had admission over the last 01 year, of which 88.33% had one admission and 11.67% had more than one admission with a mean of 1.22(SD + 0.64). 62.7% of the patients were on B-blockers for more than 24 months with a mean of 27.82(SD + 20.44 months). Comorbidities were identified in only 8.6% of patients, the most common were CKD (4.7%) followed by HTN (1.3%) and DM (1.3%) (Table 2).

Fig. 1
figure 1

Distribution of the cause of CLD at UOGCSH GI follow-up clinic 2022

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Table 2 Clinical characteristics of patients with esophageal varices at UOGCSH GI follow-up clinic from May to September 2022 (n = 150)
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The patients’ mean; hemoglobin level was 10.44 g/dl (SD + 2.94), creatinine 0.75 mg/dl (SD + 0.57) and sodium was 135.11 meq/l (SD + 4.45). Sixty percent (60%) of patients’ hemoglobin was below 12.00 g/dl and 12.7% was below 7.00 g/dl. 92.7% of patients’ creatinine was below 1.2 mg/dl, 62.7% of patients’ sodium was between 135 mmol/L and 145 mmol/L and 12.7% of patients’ sodium was below 130 mmol/L. Sixty-six percent (66%) of patients were taking Lasix with a mean dose of 32.73 mg (SD + 24.81) and 80.7% of patients were taking spironolactone with a mean dose of 73.14 mg (SD + 36.96). 53.54% of patients were on Lasix below 40 mg and 61.98% of patients were on spironolactone below the dose of 100 mg. The patients were on propranolol with a mean dose of 68 mg (SD + 30.08). Most of the patients (86.67%) were on propranolol 80 mg and below. Only 5 patients (3.3%) and 1 patient (0.7%) were on lactulose and enalapril respectively. For twenty-two patients (14.7%) endoscopic variceal ligation was done. Adverse drug reactions of propranolol were asked and 11(7.3%) patients had easy fatigability, 3(2%) patients had dizziness, and 1(0.7%) patient had sleep disturbance, but none of these side effects led patients to drug discontinuation (Table 3).

Table 3 Laboratory and medication-related characteristics of patients with esophageal varices at UOGCSH GI follow-up clinic 2022
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Patients’ drug adherence was analyzed by the standard drug adherence tool (Brief Medication Questionnaire); seventy-eight percent (78%) of patients had good adherence and the rest 22% of patients had poor medication adherence.

Optimization of non-selective B-blockers

Around ninety-six percent (96%) of baseline heart rate was between 60 to 100 bpm with a mean of 88.82 bpm (SD + 8.12) and 94.7% of current heart rate was between 60 to 100 bpm with a mean of 71.74 bpm (SD + 10.29) and change of mean from baseline to current was 17.08 bpm. 18.7% of patients’ current heart rate was between 55 to 60 bpm and 12% of patients resting heart rate was decreased by more than 25% from the baseline. Patients who were taking the maximal dose of propranolol was 2 (1.33%) (Table 4). This study showed that 30.7% of patients fulfilled the criteria for non-selective B-blocker optimization, which was a current heart rate between 55 to 60 and a heart rate decrement by 25% from the baseline resting heart rate (Fig. 2) optimization of non-selective B-blockers among esophageal varices patients at UOGCSH GI follow-up clinic 2022).

Table 4 Optimization of non-selective B -blockers
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Fig. 2
figure 2

Optimization of non-selective B-blockers among esophageal varices patients in UOGCSH GI follow-up clinic 2022

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Factors associated with dose optimization of non-selective B-blockers

In simple binary logistic regression from independent variables, ten variables (underweight, wasting, and cirrhosis, admission in the last 01 year, ascites, use of Lasix and spironolactone, and a dose of Lasix more than 40 mg, hyponatremia, and poor drug adherence) were significantly associated with optimization of non-selective B-blockers. Significant variables in simple binary logistic regression were entered into multiple binary logistic regressions. In multiple logistic regression, poor drug adherence and admission in the last year were found to be significantly associated with the optimization of non-selective B-blockers at a p-value of < 0.05. Patients with poor drug adherence were four times more likely to be sub-optimal non-selective B-blocker usage (AOR = 4.293, [95% CI = 1.191–15.484], p-value = 0.026) and admission in the last year was three times more likely to be sub-optimal usage of NSBBs (AOR = 2.915, [95%CI = 1.076–7.893], P-value = 0.035) (Table 5).

Table 5 Factors associated with optimization of non-selective B-blockers among esophageal varices patients in UOGCSH GI follow-up clinic 2022
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Discussion

One of the most common side effects of liver cirrhosis is esophageal varices, which affects around half of the cirrhotic patients at the time of diagnosis [6, 28, 29]. Variceal hemorrhage is one of the potentially fatal effects of portal hypertension [30]. Approximately 70% of variceal bleed survivors re-bleed within a year [31]. The primary treatment approach for preventing esophageal variceal bleeding and re-bleeding is the use of non-selective beta-blockers (NSBBs), which are affordable, have few contraindications, and cause relatively little intolerance. After a two-year median follow-up, it has been demonstrated that non-selective beta-adrenergic blockers (propranolol or nadolol) lower the risk of initial variceal bleeding (from 24 to 15%) and mortality (from 27 to 23%) [32]. To achieve the therapeutic goal, NSBBs should be titrated to the maximum tolerated dosage. Nevertheless, these life-saving medications were not optimized in most of the studies [2, 16]. However only around one-third of patients treated with propranolol can achieve an important reduction in the hepatic venous pressure gradient, making them safe to be considered as such [2, 33].

This may be the first study in Ethiopia and Africa that tried to assess the rate of optimization and its associated factors of NSBBs. This study showed that the rate of optimization of non-selective B blockers is 30.7%. This result is higher than the study conducted in the United States (9.8%) [16]. Even though the result is higher than the studies done in China (22.7%), in this study they used a 20% decrement in resting heart rate as a target for optimization [2]. Many studies used HVPG as a hemodynamic response; a study done in India showed a reduction in HVPG by 10.2% [33]. The potential explanation for the greater number could be a difference in the study population and the time gap of the study. Another explanation is that, due to our limited endoscopic intervention (EVL) setup, we may strictly monitor patients for taking medical treatment (NSBBs) and timely dose titration.

According to this study, sub-optimization of non-selective B blockers was significantly associated with poor drug adherence. This finding is in line with a study conducted in China that found a statistically significant difference in the rate of response to NSBBs between groups with good and poor adherence (50.0% [37/74] versus 22.7% [5/22], P = 0.024) [2]. Clinical outcomes usually improve with adherence rates above 80%. In contrast, poor adherence to treatment might lead to higher medical expenses, reduced effectiveness, and early illness recurrence. Patients should take NSBBs consistently and long-term to prevent esophageal variceal bleeding, as adherence to NSBBs is critical to both clinical outcome and prognosis in cirrhotic patients who require long-term NSBB therapy. Additionally, cirrhotic patients’ health-related quality of life can be enhanced by adhering to NSBBs. Conversely, missing a dose of medication was associated with an increased chance of cirrhosis-related symptoms returning [2].

This study also showed that hospital admission in the last 01 year had a statistically significant association with the optimization of non-selective B blockers in the management of esophageal varices. This might be due to the occurrence of different complications of chronic liver diseases like ascites, and spontaneous bacterial peritonitis due to non-optimization of B blockers [2, 34]. The other explanation might be titration of b blockers is difficult in acute settings. In another study done in the USA, there was no difference in patients who had admissions in the number of patients who were taking non-selective B blockers, but they didn’t analyze dose titration or dose optimization. In that study, variceal hemorrhage and hepatic encephalopathy contribute to the majority of readmission [34].

The other variables like patient age, use of Lasix and spironolactone, BMI and MUAC, etiology of cirrhosis and child Pugh class, size of varices, CLD complications like ascites, Hepatic encephalopathy, hepatorenal syndrome, portal vein thrombosis and both sitting and standing BP had no statistically significant association with the rate of non-selective b blockers optimization which is consistent with different studies previously done [5, 21]. Even in one study using a combination of propranolol and spironolactone may reduce portal pressure in a better way than monotherapy with propranolol, so in that study using in combination had a higher rate of hemodynamic response than b blockers alone [33, 35].

Strengths and limitations of the study

Since this study is the first study in Ethiopia as well as in Africa to identify the gaps in dose escalation of B blockers in the management of esophageal varices, it will improve our practice in the management of patients and it will be a milestone for further studies. Most of our patients have been managed with only B blockers because of a shortage of variceal ligation bands, since this study has identified the factors that are associated with sub-optimization of medical management with B blockers, we can improve the rate of optimization by improving the gaps identified. However, a relatively small sample size of patients may underestimate the overall prevalence of optimization of non-selective B blockers. Though the standard way of determining the hemodynamic response after using NSBBs is HVPG; the Pulse rate was used because of its unavailability in our setup. Due to the small size of patients, it was difficult to analyze each variable like complications of CLD. Physician-related factors for not adhering to the guideline to titrate the dose for patients are not addressed and need further study. The study population is limited to patients attending the clinic during the specific study period; changes in patient behavior, healthcare policies, or disease management practices outside this framework may not be reflected in the findings.

Conclusion

This study suggests a baseline for non-selective B-blocker dose optimization in treating individuals with esophageal varices, which is still considered a priority. In patients with esophageal varices, it is recommended to optimize the dose of NSBBs generally. This underlines the continuous need for these efforts. More work needs to be done to reduce these modifiable risk factors, as this study showed that sub-optimization of non-selective B blockers was significantly associated with poor medication adherence and prior hospitalization within the preceding year. To completely understand the impact of those parameters on dose optimization and associated factors among patients with esophageal varices, prospective studies with a large sample size are preferable.

Data availability

Data Availability The data set is available with authors and can be obtained from the corresponding author upon reasonable request.

Abbreviations

ALD:

Alcoholic Liver Diseases

CLD:

Chronic Liver Diseases

Cr:

Creatinine

CTP:

Child Turcotte Pugh

EGD:

Esophagogastroduodenoscopy

EV:

Esophageal Varices

EVL:

Endoscopic Variceal Ligation

GEV:

Gastroesophageal Varices

GV:

Gastric Varices

HBV:

Hepatitis B Virus

HCV:

Hepatitis C Virus

HE:

Hepatic Encephalopathy

HSS:

Hepatosplenic Schistosomiasis

NSBB:

Non Selective Beta Blocker

PH:

Portal Hypertension

PVT:

Portal Vein Thrombosis

SBP:

Spontaneous Bacterial Peritonitis

UoG:

University of Gondar

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Acknowledgements

The authors are grateful to the study participants, data collectors, and supervisors.

Funding

According to the authors, the research was conducted without any commercial or financial links that could be perceived as a potential conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences, University of Gondar, POBOX: 196, Gondar, Ethiopia

    Getachew Sahile Alemu, Segenet Bizuneh Mengistu, Yonas Gedamu, Eleni Ayele, Hiwot Alemu Admas, Endalkachew Belayneh Melese, Desalew Getahun Ayalew & Gebrehiwot Lema Legese

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  1. Getachew Sahile Alemu
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Contributions

Author contribution statement Conceptualization, G.S.A., E.B.M., E.A., S.B.M., H.A.A., G.L.L.,D.G.A.,Y.G.;Data curator, Formal analysis, Investigation, Methodology, Y.G., D.G.A, G.L.L, G.S.A; Resources, Software, Supervision, Validation, Visualization, Writing original draft,G.S.A.,H.A.A.,G.L.L.

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Correspondence to Getachew Sahile Alemu.

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The University of Gondar’s College of Medicine and Health Sciences institutional review board reviewed and authorized the studies involving human subjects (Ethical Clearance Reference number: SOM/1670/14/2022). To take part in this study, the patients/participants gave their written, informed consent.

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Alemu, G.S., Mengistu, S.B., Gedamu, Y. et al. Dose optimization of non-selective beta blockers among esophageal varices patients at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia: a hospital-based cross-sectional study. BMC Gastroenterol 25, 100 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12876-025-03708-2

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Keywords

BMC Gastroenterology

ISSN: 1471-230X

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