Abstract
Objectives:
Spontaneous bacterial peritonitis is a potentially fatal complication and a serious sequel occurring in patients with cirrhotic ascites. Although the complications of cirrhotic ascites are high and lethal, there was limited information on the burden and risk factors of spontaneous bacterial peritonitis in Ethiopia and the study setting. Our study aims to determine the prevalence of spontaneous bacterial peritonitis and associated factors among patients with cirrhotic ascites attending public hospitals in Harari region, eastern Ethiopia, from December 15 to 31, 2022.
Methods:
An institution-based retrospective cross-sectional study was conducted among randomly selected 319 patients with cirrhotic ascites attending public hospitals in Harari region from January 1, 2021 to December 15, 2022. Data were extracted from individual medical records, patient cards, and follow-up charts using a semi-structured questionnaire/checklist. Data were entered using EpiData version 3.1 and analyzed using the Statistical Package for Social Science version 22. Bivariable and multivariable logistic regression analyses were conducted to identify factors associated with spontaneous bacterial peritonitis. An adjusted odds ratio (with 95% confidence interval) was used to report the adjusted association, and statistical significance was declared at p < 0.05.
Results:
The prevalence of spontaneous bacterial peritonitis was 34.8% (95% confidence interval: 30.1%–40.2%). In this study, gastrointestinal bleeding (adjusted odds ratio = 1.99 (1.13–3.50)), alcohol intake (adjusted odds ratio = 2.17 (1.02–4.65)), hepatitis infection (adjusted odds ratio = 1.95 (1.09–3.46)), serum electrolytes abnormalities (adjusted odds ratio = 6.36 (3.61–11.23)), and low peritoneal fluid protein (adjusted odds ratio = 4.52 (2.51–8.12)) were important factors associated with spontaneous bacterial peritonitis.
Conclusions:
More than one out of three patients with cirrhotic ascites had spontaneous bacterial peritonitis in eastern Ethiopia. In this study, alcohol intake, gastrointestinal bleeding, hepatitis, electrolyte imbalances, and low levels of peritoneal fluid protein were predictors of spontaneous bacterial peritonitis. Reducing alcohol intake, preventing hepatitis infection and cirrhotic complications, and managing serum electrolytes and peritoneal fluid protein levels would be essential to prevent and reduce the risks of spontaneous bacterial peritonitis and its lethal consequences. Therefore, a prospective large-scale study is crucial to understanding the burden and associated factors with spontaneous bacterial peritonitis in patients with cirrhotic ascites. Furthermore, improving access to diagnostic tools such as ultrasound in local health facilities and providing short training for local health providers to guide early diagnosis and treatment of spontaneous bacterial peritonitis.
Introduction
Spontaneous bacterial peritonitis (SBP) is a life-threatening complication that affects 3.5%–10% of patients with cirrhosis and ascites, and it poses a high mortality risk if not promptly diagnosed and treated.1–3
SBP is defined as a bacterial infection of the ascitic fluid in the absence of a surgical etiology, and without any identifiable intra-abdominal treatable source of infection.4,5 Ascites is commonly the first decompensation-defining event with 5%–10% of patients with compensated cirrhosis. 6 The development of ascites is associated with a reduction in 5-year survival from 80% to 30%. In part, this may be due to patients with ascites being prone to additional complications such as SBP, hyponatremia, hepatorenal syndrome, and nutritional imbalances with further clinical decline. 7
Chronic liver disease (CLD) refers to a spectrum of liver conditions lasting more than 6 months, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. 8
Among these, cirrhosis represents irreversible liver damage, typically diagnosed with the help of abdominal ultrasound or other imaging modalities.9,10 SBP is a serious and potentially life-threatening complication that frequently occurs in patients with cirrhotic ascites.5,11
The pathogenesis of SBP involves the interaction of gut microbiota, increased intestinal permeability, bacterial translocation, and immune deficiency, which may be acquired or conferred by genetic susceptibility. 11 These factors act as pathophysiological culprits for the development of SBP in patients with cirrhotic ascites. Several factors were associated with an increased risk of SBP, including gastrointestinal bleeding (GIB), poor liver function, low ascitic fluid protein levels, prior SBP, and a history of hospitalization.12,13
The clinical presentation of SBP varies from patient to patient. It may include local symptoms such as abdominal pain, vomiting, or diarrhea, but can also occur without local symptoms, and instead present with signs of liver function deterioration, hepatic encephalopathy, renal failure, or septic shock. In some cases, SBP may even be asymptomatic.10,13
Early diagnosis of SBP is essential for improving outcomes, as a delay in starting antibiotic treatment is associated with an increased mortality (Arabi et al., 2012; Piano et al., 2016).14,15 SBP is diagnosed when the ascitic fluid culture grows pathogenic bacteria, the ascitic fluid cell (polymorphonuclear neutrophil (PMN)) count ⩾250 cells/mm3 with no evidence of surgically treatable intra-abdominal sources of infection. 16
As the presentation of SBP is variable, a delay in instituting therapy can lead to increased mortality. A diagnostic paracentesis should be performed as soon as a patient with cirrhosis and ascites is hospitalized emergently for any reason, even in the absence of suggestive infection 17 and whenever a patient (hospitalized or not) develops signs suggestive of infection, antibiotics should be started empirically in all patients with ascites.3,6,18
The burden of SBP is substantial in a developing nation where conventional medical protocols are implemented, contributing to an increased patient population substantially at risk for nosocomial infections due to long-term hospitalization.19,20
In resource-limited countries, including Ethiopia, SBP poses a significant public health problem as it is associated with high mortality and morbidity among patients with cirrhotic ascites. In addition, Limited access to healthcare, delayed diagnosis, and lack of diagnostic tools exacerbate the burden of SBP. Despite the burden of CLD in Ethiopia, there is a lack of prior studies on SBP, indicating the prevalence and determinants of these infections, particularly in the Harari region. Therefore, this study aimed to assess the prevalence of SBP and associated factors among patients with cirrhotic ascites attending public hospitals in Harari region, eastern Ethiopia.
Methods
Study design and study setting
The institutional-based retrospective cross-sectional study was conducted in the Harari region from December 15 to 31, 2022. Harari region is located 526 km to eastern of Addis Ababa, the capital of Ethiopia. According to the population projection for 2022, the town has 276,000 estimated total population, 139,000 are males. According to the Regional Health Bureau report, 2022, there are two public hospitals, eight health centers, and one regional laboratory. The study was conducted at two public hospitals in the Harari region: Hiwot Fana Comprehensive Specialized University Hospital (HFCSUH) and Jugal General Hospital (JGH).
Populations
All adult patients with cirrhotic ascites attending public hospitals in the Harari region were the source population. Adult patients with cirrhotic ascites attending public hospitals from January 1, 2021 to December 15, 2022, were the study population. All randomly selected adult patients with cirrhotic ascites attending public hospitals during the study period were included in the study. Those patients whose medical records were incomplete, documented previous antibiotic use within 2 weeks due to other infections, and patients with ascites caused by non-cirrhotic causes were excluded from the study.
Sample size determination and sampling
The sample size was calculated by Epi Info version 7.1 (CDC, 1980, Georgia, USA) using a single population proportion formula considering the following assumptions: 95% confidence interval (CI), 5% marginal error, and 25.24% proportion of cirrhotic ascites 21 with a 10% nonresponse rate. The total minimum required sample size was 319 patients with cirrhotic ascites.
Two public health facilities were selected. First, the registration numbers of all patients with cirrhotic ascites attending these hospitals from January 1, 2021 to December 15, 2022 were traced from the hospital’s admission and discharge log book and then listed as a sampling frame. Among the total of 936 patients who were diagnosed with cirrhosis during the study period, data of 837 patients were found to have ascites, and 582 were eligible for the study based on inclusion criteria (365 from HFCSUH and 217 from JGH). Then, the sample size was proportionally allocated to each hospital based on the number of eligible patients (200 to HFCSUH and 119 to JGH). Finally, eligible patient charts were selected using simple random sampling from each hospital.
Data collection tool and procedure
Semi-structured questionnaires/checklists adapted from national patient registries, patient cards, and follow-up charts and data were extracted by reviewing patients’ medical records over a month. The questionnaire contains information about the sociodemographic characteristics of patients, clinical factors, treatment-related factors, and SBP. The hospital registration book of the medical ward was used to get the card numbers of all patients with cirrhotic ascites attending the hospital during the study period. After getting the registration number, the patient’s chart review was retrieved from the record documentation office. Eight data collectors collected the data under two supervisors (Supplemental Material).
Operational definition
SBP: SBP is diagnosed using a PMN count of ⩾250 cells/μl in ascitic fluid with the absence of a surgically treatable intra-abdominal source of infection. 16
GIB: Bleeding from esophageal varices due to portal hypertension as a complication of cirrhosis. 22
Hepatitis: Hepatitis positive in this study indicates the patients have been infected with at least hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg), negative if the patient was not infected with both HBsAg and HCV. 23
Liver function test abnormalities: It was measured using five dichotomous items, each rated ‘1’ when abnormal and ‘0’ ‘normal’ and then, the composite index score was computed from five items, and the LFT was ‘abnormal’ when the participants were abnormal with at least one test and ‘normal’ unless otherwise.
Electrolyte abnormality/imbalance: It was measured using two dichotomous items, each rated ‘1’ when abnormal and ‘0’ ‘normal’ and then, composite index score was computed from two items, and the Electrolyte abnormality was ‘abnormal’ when the participants were abnormal with at least one test and ‘normal’ unless otherwise. 24
Glasgow coma scale: Glasgow coma scale provides a structured method for assessment of the level of consciousness. A Glasgow coma scale <15 indicates some level of impaired consciousness, and a Glasgow coma scale of 15 indicates full consciousness. 25
Data quality control
To maintain the data quality, a well-designed data extraction checklist was used. Data collectors were given training before data collection on how to use the data extraction format to collect information from a patient’s medical record. We pretested the tools on 5% of the total sample to check the validity of the questionnaire. The data collectors and supervisors were trained for 2 days on the objectives of the study and data collection techniques. During data collection, strict supervision of data collectors and validation of collected data were applied.
Data processing and analysis
After checking for completeness, data were entered intoEpidata version 3.1 (EpiData Association, 1990, Denmark) and transported to Statistical Package for Social Science version 22 (IBM corporation, 2009, New York, USA) for analysis. Descriptive statistics such as frequencies, mean, and standard deviation were used to characterize the participants. Bivariable and multivariable logistic regression analyses were conducted to identify factors associated with SBP. On bivariable all factors with a p value of 0.25 were selected as candidate variables for multivariable logistic regression. The model fitness was confirmed using Hosmer-Lemeshow goodness-of-fit tests with a p > 0.05. Backward LR was used to identify the statistical significance of the variables. Adjusted odds ratio (AOR) with a 95% CI was used to report the association, and the significance was declared at p < 0.05.
Results
Sociodemographic characteristics of participants
A total of 319 patients participated in the study. The mean (± SD) age was 39 (± 14.9) years, and 40.1% of patients were in the 18–30 years age group. One hundred seventy-nine (56.1%) participants were male, and more than three-fourths of patients (77.3%) were living in rural areas (Table 1).
Sociodemographic characteristics of patients with cirrhotic ascites attending public hospitals of Harari region, eastern Ethiopia, from January 1, 2021 to December 15, 2022 (n = 319).
Clinical characteristics of the participants
All participants, 319 (100%), had abdominal swelling. About 39.2% of the participants had GIB, regarding vital signs at presentation, 32.6% of the patients had an abnormal blood pressure (hypo/hypertension), 36.1% had tachycardia, and 23.2% had abnormal temperature (Table 2).
Clinical characteristics of patients with cirrhotic ascites attending public hospitals in Harari region, eastern Ethiopia, from January 1, 2021 to December 15, 2022 (n = 319).
GIB: gastrointestinal bleeding.
Laboratory and clinical diagnosis
All patients had imaging evidence of cirrhosis by abdominal ultrasound and had at least one abnormal liver function test. On complete blood count (CBC), 29.8% of the patients had leukopenia, anemia was identified in 76.6% of the patients, and thrombocytopenia was seen in 61.8% of patients. Regarding the etiology of cirrhosis, 45.8% of patients were positive for hepatitis infection (HBsAg and HCV), and 39.5% had electrolyte disturbance (Table 3).
Laboratory and imaging characteristics of patients with cirrhotic ascites attending public hospitals in Harari region, eastern Ethiopia, from January 1, 2021 to December 15, 2022 (n = 319).
PMN: polymorphonuclear neutrophil; RFT: renal function test; WBC: white blood cell.
Prevalence of SBP
The prevalence of SBP among patients with cirrhotic ascites in this study was 111 (34.8%; 95% CI: 30.10%–40.20%).
Factors associated with SBP
In the bivariable analysis, age, hospital types, regions, GIB, electrolyte disturbance, peritoneal fluid protein level, alcohol intake, and hepatitis infection were selected candidate variables for the multivariable analysis model. In multivariate analysis, alcohol intake, Hepatitis infection, GIB, electrolyte disturbance, and peritoneal fluid protein level were significant determinants of SBP among patients with cirrhotic ascites.
Patients with cirrhotic ascites who consume alcohol were 2.2 times more likely to develop SBP (AOR = 2.17, 95% CI: 1.02–4.65) than those who did not consume alcohol. The odds of SBP development among patients with cirrhotic ascites with hepatitis infection were almost two times higher than those without hepatitis (AOR = 1.95, 95% CI: 1.09–3.46). Patients with cirrhotic ascites who have electrolyte disturbance were 6.4 times more likely to develop SBP (AOR = 6.4, 95% CI: 3.61–11.23) compared to their counterparts. Patients present with GIB were two times at higher risk of developing SBP as those who don’t have GIB (AOR = 1.99, 95% CI: 1.13–3.50). A cirrhotic ascites patient with low peritoneal fluid protein (<1) was 4.5 times more at risk of developing SBP compared to those with peritoneal fluid protein (⩾1; AOR = 4.52, 95% CI: 2.51–8.12; Table 4).
Bivariable and multivariable logistic regression of factors associated with SBP among patients with cirrhotic ascites attending public hospitals in Harari region, eastern Ethiopia, from January 1, 2021 to December 15, 2022 (n = 319).
AOR: adjusted odds ratio; CI: confidence interval; COR: crude odds ratio; GIB: gastrointestinal bleeding; RFT: renal function test; SBP: spontaneous bacterial peritonitis.
Discussion
This study assessed the prevalence and associated factors of SBP among patients with cirrhotic ascites attending public hospitals in the Harari region. The prevalence of SBP among patients with cirrhotic ascites was 34.8%. Alcohol intake, Hepatitis infection, GIB, electrolyte disturbance, and peritoneal fluid protein level were the major predictors of SBP among patients with cirrhotic ascites.
This finding (34.8%) was comparable with studies done in Nepal 29.29%, Pakistan (38.0%), 26 and 34.4% in the United States. 27
The findings of this study were higher than the study conducted in Bahirdar, Ethiopia 22.5%, Tunisia 11%, 28 Ghana 25.24%, 20 India 20.4%, 29 Israel 16.7%, 30 and France 11.7%. 31 This might be due to differences in the study population; most of the patients in our study are from rural areas, there was a delay in seeking early medical care, and they presented to hospitals with advanced cirrhosis. In addition, this may be due to infrastructural differences, with developed countries having better health care systems. Furthermore, the variation in types of health care and differences in the behavior of the participants, for example, the study conducted in France, were among asymptomatic patients. 31
The current study findings were lower compared to the study done in Nigeria (67.7%). 32 This might be due to sample size variation and differences in methods of diagnosis; they used culture for the diagnosis of SBP, which enables to diagnosis of SBP in asymptomatic patients with low ascetic fluid cell count. Furthermore, they employed clinical diagnosis to confirm the instances, which may have increased the prevalence when compared to ours, which did not.
According to the findings of this study, patients with GIB were significantly associated with higher odds of SBP. This was in line with the study done in India, 29 Israel, 30 and Pakistan. 33 This might be due to variceal bleeding is one of the features of advanced cirrhosis, and the co-occurrence of complications of cirrhosis, which might increase the risk of development of SBP. 34
In this study, having a hepatitis infection is strongly associated with the prevalence of SBP. This finding was similar to the study done in Ghana 21 and India. 29 This might be due to hepatitis disrupting the liver’s ability to filter blood, leading to increased pressure in the abdominal veins, which can result in ascites. This leads to altering fluid dynamics, resulting in an environment where bacteria can more easily enter and cause infection, leading to SBP.4,35
In this study, electrolyte disturbances (such as hypernatremia, hypokalemia, and hyperkalemia) showed a strong association with SBP. This study is consistent with the study done in India, 29 Australia, 36 and Spain. 37 The reason for the similarity is that these factors were related to the adverse effects of diuretic agents such as loop diuretics and aldosterone antagonists.3,38 In addition, hyponatremia and hypokalemia can contribute to SBP by impairing the body’s defenses against infection, disrupting the normal barrier function of the peritoneum, creating an environment that favors bacterial growth and translocation, and increasing susceptibility to SBP.3,36
Other factors associated with SBP were low peritoneal fluid protein. This finding is in line with studies done in Indian and Nigeria, which reported that low peritoneal fluid protein of <1 g/dl was associated with SBP.29,32 This might be due to the patients with a low level of peritoneal fluid protein having the lowest concentration of opsonin in the ascetic fluid, the proteins important in the phagocytosis, and their decrement increases the risk of development of SBP. 4
Limitations of the study
The study has many strengths, along with some limitations, including a lack of generalizability to private hospital settings, being a retrospective cross-sectional study, and a lack of a culture of peritoneal fluid.
Conclusion
The prevalence of SBP among patients with cirrhotic ascites attending public hospitals in the Harari region was high (34.8%). Low peritoneal fluid protein, Hepatitis infection, and electrolyte imbalance were the leading factors contributing to the development of SBP. Therefore, a prospective large-scale study is crucial to understanding the burden and associated factors with SBP in patients with cirrhotic ascites. Providing continuous health education for the community about the complications of cirrhosis to improve early healthcare-seeking behavior is extremely important. Improving laboratory-based diagnostic investigations, such as culture services and organ function tests for patients with cirrhotic ascites in public health facilities, is very important for early diagnosis of SBP and in decreasing mortality. Reducing alcohol intake, preventing hepatitis infection and cirrhotic complications, and managing serum electrolytes and peritoneal fluid protein levels would be essential to prevent and reduce the risks of SBP and its lethal consequences. Furthermore, improving access to diagnostic tools such as ultrasound in local health facilities and providing short training for local health providers to guide early diagnosis and treatment of SBP.
Supplemental Material
sj-docx-1-smo-10.1177_20503121251366773 – Supplemental material for Spontaneous bacterial peritonitis and associated factors among patients with cirrhotic ascites attending public hospitals in Harari region, eastern Ethiopia
Supplemental material, sj-docx-1-smo-10.1177_20503121251366773 for Spontaneous bacterial peritonitis and associated factors among patients with cirrhotic ascites attending public hospitals in Harari region, eastern Ethiopia by Yimaje Mohammed, Tekabe Abdosh, Kirubel Minsamo Mishore, Mohammed Ahmed, Hassen Abdi Adem, Ahmedin Aliyi Usso, Rudwan Yasin Abrahim, Abdulhakim Ahmed Siyo and Alo Edin in SAGE Open Medicine
Footnotes
Acknowledgements
We thank the participants for their valuable contribution. The authors acknowledged Haramaya University for providing the opportunity to conduct the study. We appreciated the HFCSUH and JGH for giving the background information and medical records.
Ethical considerations
Ethical clearance was obtained from the Institutional Health Research Ethics Review Committee of the College of Health and Medical Sciences, Haramaya University with reference number (ref. no. IHRERC/211/2022) on December 7, 2022. The ethical clearance approval letters were submitted to Hiwot Fana Comprehensive Specialized University Hospital and Jugal General Hospital administrators.
Consent to participate
Ethical clearance was obtained from the Institutional Health Research Ethics Review Committee of the College of Health and Medical Sciences, Haramaya University, with reference number (Ref.no: IHRERC/211/2022). Written informed consent was obtained from hospital administrators before data collection was started. Therefore, due to the nature of the study (retrospective cross-sectional study), the written informed consent from the participants was not available; the Institutional Review Board (IHRERC) waived the participants’ written informed consent, but information gained from the patient’s medical records was held anonymous and confidential. To ensure participants’ confidentiality, names or personal identifiers were not included in the written questionnaires, and all the data collected during the study were kept confidential.
Author contributions
Y.M., T.A., K.M.M., M.A., H.A.A., A.A.U., R.Y.A., A.A.S., and A.E. participated in the conception of the idea, development, and amendment of the proposal, data collection, analysis, and writing up the draft results. M.A., H.A.A., and A.A.U. reanalyzed statistical analysis, drafted, edited, and revised the draft and final version of the article. All authors read and approved the final article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data availability statement
Data that supports the findings is available from the corresponding author on reasonable request.
Supplemental material
Supplemental material for this article is available online.
References
Supplementary Material
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