|Year : 2016 | Volume
| Issue : 1 | Page : 37-42
Prevalence and predictors of spontaneous bacterial peritonitis: does low zinc level play any role?
Asmaa N Mohammad1, Laila M Yousef2, Hamdy S Mohamed3
1 Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Sohag University, Sohag, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt
3 Department of Internal Medicine, Faculty of Medicine, Sohag University, Sohag, Egypt
|Date of Submission||10-Nov-2015|
|Date of Acceptance||20-Dec-2015|
|Date of Web Publication||18-Apr-2016|
Asmaa N Mohammad
Lecturer in Sohag University, MD, Department Tropical Medicine and Gastroenterology, Sohag University, Sohag, Postal code: 82511
Source of Support: None, Conflict of Interest: None
Spontaneous bacterial peritonitis (SBP) is a frequent and life-threatening complication of cirrhosis. Several large studies have identified additional risk factors for the development of SBP. Zinc deficiency has been found to be frequent in cirrhotic patients.
Aim of the work
The aim of the present study was to evaluate the frequency, possible risk factors and the role of zinc in the development of first-time and recurrent SBP.
A total of 176 cirrhotic ascetic patients admitted to the Hepatology Department in Sohag University Hospital were enroled in the study. SBP peritonitis was diagnosed through history-taking and through examination and laboratory investigations, including ascetic fluid study and the detection of serum zinc level.
Of the 176 cirrhotic patients, SBP was diagnosed in 54 (31%); in total, 40 patients (23%) had single and 14 (8%) had recurrent episodes of SBP. Out of the 23 studied clinical and laboratory variables, we found that the prolonged use of proton pump inhibitor (PPI) (P = 0.001), lower prothrombin concentration (P = 0.03), ascetic protein level less than or equal to 1 g/dl (P < 0.0001) and zinc deficiency (P = 0.001) were independent risk factors for the development of SBP in cirrhotic patients; using multivariate analysis, only low protein in ascites less than or equal to 1 and low zinc status were predictors of SBP.
In our study, the frequency of SBP was 31%; overall, 23% of the patients had first-episode and 8% had recurrent SBP. The use of PPI, low platelet count, ascetic protein content and zinc deficiency were the predictors for the development of SBP; only low protein in ascites less than or equal to 1 and low zinc status were independent predictors of SBP.
Keywords: ascites, liver cirrhosis, spontaneous bacterial peritonitis, zinc
|How to cite this article:|
Mohammad AN, Yousef LM, Mohamed HS. Prevalence and predictors of spontaneous bacterial peritonitis: does low zinc level play any role?. Al-Azhar Assiut Med J 2016;14:37-42
|How to cite this URL:|
Mohammad AN, Yousef LM, Mohamed HS. Prevalence and predictors of spontaneous bacterial peritonitis: does low zinc level play any role?. Al-Azhar Assiut Med J [serial online] 2016 [cited 2017 Dec 17];14:37-42. Available from: http://www.azmj.eg.net/text.asp?2016/14/1/37/180461
| Introduction|| |
Spontaneous bacterial peritonitis (SBP) is a common and severe complication in cirrhotic patients with ascites. The incidence of SBP in cirrhosis has been reported to be 20% on an average, the mortality rate related to this complication being more than 50% ,,,. SBP is thought to appear as a consequence of the impaired defensive mechanisms against infection present in cirrhotic patients, such as depressed reticuloendothelial system phagocytic activity, impaired leukocyte function, reduced serum complement levels and low antibacterial activity of the ascetic fluid ,.
The SBP recurrence rate was about 51% in the 1980s . Over the years, several large studies identified additional risk factors for the development of SBP, such as a low protein concentration in ascites fluid , variceal haemorrhage, serum bilirubin level greater than 3.2 mg/dl, platelet count less than 98 000/mm 3 and previous SBP episodes ,,,.
It has recently been shown that among various nutrients, trace metals, such as zinc, are involved closely in the pathophysiology of liver cirrhosis ,,. Reliable parameters to predict the occurrence of SBP would help in the selection of appropriate patients who would benefit from selective intestinal decontamination.
A direct correlation has been found between the impairment of the local defensive mechanisms of ascites (assessed by either the opsonic activity or the total protein concentration in ascetic fluid) and the risk of SBP in cirrhotic patients hospitalized with ascites ,.
If zinc becomes deficient for some reason, a number of problems, including growth disorder, cognitive disorder and compromised immune function, can occur ,,. Research has revealed that the increased plasma glucocorticoid level and the decreased cellular zinc content in zinc-deficient animals contribute to a reduction in the B-cell and T-cell compartments by inducing apoptotic loss of precursor and immature B-cells in the bone marrow and of pre-T-cells in the thymus . Previous studies by Prasad demonstrate that mild zinc deficiency in humans induces an imbalance in ex-vivo cytokine secretion by peripheral blood mononuclear cells despite maintenance of normal numbers of total leucocytes and B-lymphocytes and T-lymphocytes . Therefore, zinc deficiency is responsible for recurrent infections due to compromised immune function .
Many factors are potentially responsible for zinc deficiency in patients with liver cirrhosis, such as disturbed zinc absorption by the digestive tract, increases in zinc excretion through urine and the use of diuretics increasing zinc excretion through urine ,,. Albumin is the major plasma carrier of zinc, and the amount of zinc transported in the blood depends not on zinc but on the availability of albumin . Zinc deficiency may be attributed to the reduced albumin level in liver cirrhosis patients .
The aim of our study was to evaluate the rate of occurrence of first-episode and recurrent SBP, to investigate the predictors of SBP in cirrhotic ascetic patients and to identify whether there was a possible role for zinc deficiency in these patients.
| Patients and Methods|| |
This cross-sectional study was conducted in the Sohag University Hospital after obtaining approval from the local ethics committee. All 176 cirrhotic ascetic patients admitted to Hepatology Department signed a written consent. As each patient was admitted, we obtained a detailed history, carried out a complete physical examination and took abdominal ultrasound to confirm the presence of liver cirrhosis and to detect ascites. In addition, we tapped the abdomen to measure the total protein concentration and cell count in ascetic fluid. On the first day of hospitalization, complete blood count was determined using the Beckman Synchron CX5 Autoanalyzer System. Standard liver and kidney function tests were conducted using the CEII – DYN 3700 [Table 1].
SBP was diagnosed when a patient had ascetic fluid polymorphnuclear count greater than 250/mm 3, and had an absence of clinical, laboratory, radiological or ultrasonographical data suggesting secondary peritonitis. Because ascetic fluid cultures are negative in a proportion of SBP ,, the isolation of causative organisms was not considered essential for the diagnosis of SBP.
Zinc levels were estimated by using the Colorimetric kit method (Saito M., Makino T.). Estimation of zinc in serum was done using the colorimetric assay. Normal zinc value in males is 60–110 μg/dl and in females it is 60–107 μg/dl .
Data were analysed using STATA intercooled, version 9.2. Quantitative data were presented as mean and SD. Qualitative data were presented as number and percentage. Logistic regression analysis was used to calculate odds ratio and P value. When odds ratio could not be calculated, the χ2-test was used to calculate the P value. P value less than 0.05 was considered significant.
| Results|| |
The present study comprised 176 patients [mean age: 55.66 ± 9.10 years; age range: 14–69 years; 110 men (62.5%) and 66 women (37.5%)].
The aetiology of cirrhosis was hepatitis C virus in 107 patients (60.8%), hepatitis B virus in six patients (3.41%) and one patient (0.57%) was infected by both hepatitis B and C viruses; the rest were infected with neither hepatitis B nor C. As regards Child–Pugh score, 153 patients (86.93%) were class C and 23 patients (13.07%) were class B.
Of 176 cirrhotic patients, SBP was diagnosed in 54 patients (31%); in total, 40 patients (23%) had single, whereas 14 (8%) suffered from recurrent episodes of SBP. Out of the patients with SBP, 41 (75.9%) presented with hepatic encephalopathy, eight (14.8%) with fever and 16 (29.6%) with abdominal tenderness.
Using univariate analysis we found that the long-term use of PPIs was significantly more in the SBP group (P = 0.001). Prothrombin concentration (mean 42.9 ± 14.81), protein level in ascetic fluid (mean 1.21 ± 0.52) and zinc level less than 60 were all significantly lower in the same group (P = 0.03, 0.001, P < 0.0001, respectively).
We took a cutoff point of 1 g/dl as regards protein level of ascites. According to the mean result and the results of previous studies ,,,, we found this level a strong predictor of SBP (P < 0.0001) [Table 2].
Using multivariate analysis for those significant variables, only low protein in ascites less than or equal to 1 g/dl and zinc level less than 60 μg/dl were independent predictors of SBP [Table 3].
|Table 3: Multivariate analysis for significant factors in univariate analysis predicting SBP|
Click here to view
| Discussion|| |
We aimed to study the prevalence and risk factors predicting the presence of SBP. Of the studied 176 cirrhotic patients, the prevalence of SBP was 31% (54 patients); in total, 40 patients (23%) had single, whereas 14 (8%) had recurrent episodes of SBP; this result is near to that obtained by some previous studies ,,,, but many other studies determined either much lower prevalence rate , or higher ,.
Using univariate analysis we found that the long-term use of PPIs was significantly more in the SBP group. This result was in agreement with that of a study by O'Leary et al.  who found that patients hospitalized with cirrhosis and receiving PPIs for long periods are at high risk for subsequent infections. Severe hypochlorhydria generated by PPI use leads to bacterial colonization and increased susceptibility to enteric bacterial infection , encourages growth of the gut microflora, increases bacterial translocation and alters various immunomodulatory and anti-inflammatory effects ,,,,,.
In the current study we found that a low prothrombin concentration at mean value of 42.9 ± 14.81% was a risk for SBP, a result similar to that obtained in other studies ,. On the other hand, studies by Guarner et al. , Andreu et al.  and Jamil et al.  found no relation between prothrombin activity and SBP risk.
Most of the preceding studies showed that low protein level in ascetic fluid was a predictor for the occurrence or recurrence of SBP and took 1 g/dl as a cutoff point for risk factor ,,,,,.
In the present study, we found that the ascetic fluid protein was significantly lower in SBP group with a mean level of 1.21 ± 0.52 g/dl, and thus we took a cutoff point of 1 g/dl, which was a significant predictor of the presence of SBP; many studies found results in agreement with it ,,,,.
In addition, using multivariate analysis, ascetic fluid protein level less than or equal to 1 g/dl was an independent risk factor for SBP.
Other factors have been found to be risky for first-time or recurrent SBP in previous studies, such as high bilirubin level ,,, low platelet count , low serum albumin level , increased serum aspartate aminotransferase levels  and Child–Pugh stage C, but these factors were not significantly different between the two groups in the present study.
There were some studies that examined the role of trace elements in immune function and susceptibility to infection ,,. Thus, several investigations in animals point to the possible implication of zinc in immune deficiency states such as T-cell defects . Zinc appears to influence both lymphocyte and neutrophil function . In humans, zinc is an important micronutrient for the immune function, and zinc deficiency is responsible for the impairment of the overall immune function and resistance to infection .
In our study, we were concerned with the role of zinc deficiency and susceptibility to SBP. There were many factors in cirrhotic patient that may lead to zinc deficiency, such as disturbed zinc absorption by the digestive tract, increases in zinc excretion in urine, the use of diuretics increasing zinc excretion through urine ,, and hypoalbuminemia in cirrhotic patients . The bacterial translocation, which is the probable cause of SBP in cirrhotic patient, was attributed partially to defective immune system .
In the current study, we found that the zinc level was significantly lower in the patients with SBP, and by using multivariate analysis, zinc deficiency was found to be the independent predictor of the occurrence of SBP. To the best of our knowledge, no other study discussing the role of zinc in patients with SBP has been conducted so far.
| Conclusion|| |
The frequency of SBP in the present study was 31%. Overall, 23% of the included patients had first-episode and 8% had recurrent SBP. The use of PPI, low platelet count, ascetic protein content and zinc deficiency were the predictors for the development of SBP. Only low protein in ascites less than or equal to 1 g/dl and low zinc status were independent predictors of SBP.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]