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ORIGINAL ARTICLE
Year : 2015  |  Volume : 28  |  Issue : 2  |  Page : 457-462

Study the relation between serum sodium and the model for end-stage liver disease score in patients with liver cirrhosis


1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Kafr El Sheikh Hepatology and Gastroenterology Center, Egypt

Date of Submission15-Aug-2014
Date of Acceptance19-Dec-2014
Date of Web Publication31-Aug-2015

Correspondence Address:
Muhammad AbdEl Hamid Shatat
Kafr El Sheikh Hepatology and Gastroenterology Center
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.163902

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  Abstract 

Objectives
The aim of the study was to evaluate the prevalence of hyponatremia in liver cirrhosis and the correlation between serum sodium and the Model for End-Stage Liver Disease (MELD) score in patients with liver cirrhosis.
Background
Hyponatremia (Na<135 mEq/l) is a common finding in advanced liver cirrhosis. Cirrhotic patients with hyponatremia have poor survival compared with cirrhotic normonatremic patients. There is an association between the presence of hyponatremia and the presence of certain liver cirrhosis complications such as hepatic encephalopathy, hepatorenal syndrome, and refractory ascites. Therefore, it was suggested that hyponatremia has a good predictive value of mortality in hepatic cirrhosis even with low MELD scores.
Patients and methods
In all, 100 patients with liver cirrhosis were enrolled in this study, 20% compensated and 80% decompensated. The decompensated group was subdivided into four subgroups according to the cause of admission.
Results
In compensated cirrhosis the prevalence of hyponatremia was 0/20 (0%), whereas that in decompensated cirrhosis was 47/80 (59%). Also the prevalence of hyponatremia differed according to the complication itself, being highest in hepatorenal syndrome and hepatic encephalopathy (74 and 71%, respectively) and the lowest in variceal bleeding (45%). In decompensated cirrhosis, there was strong inverse correlation between serum sodium and MELD score (r = −0.496 and P < 0.001), whereas there was no significant correlation in compensated cirrhosis (r = −0.324 and P = 0.163).
Conclusion
The importance of hyponatremia in advanced cirrhotic patients should not be overlooked because it may have a role in the prediction of survival in liver cirrhosis.

Keywords: hyponatremia, liver cirrhosis, Model for End-Stage Liver Disease score


How to cite this article:
Boghdady IM, Korah TE, Amin Elzorkany KM, Hamid Shatat MA. Study the relation between serum sodium and the model for end-stage liver disease score in patients with liver cirrhosis. Menoufia Med J 2015;28:457-62

How to cite this URL:
Boghdady IM, Korah TE, Amin Elzorkany KM, Hamid Shatat MA. Study the relation between serum sodium and the model for end-stage liver disease score in patients with liver cirrhosis. Menoufia Med J [serial online] 2015 [cited 2020 Apr 6];28:457-62. Available from: http://www.mmj.eg.net/text.asp?2015/28/2/457/163902


  Introduction Top


Hyponatremia is defined as a decrease in serum sodium concentration (Na + ) to less than 135 mEq/l. This disorder is commonly observed in up to 6% of hospitalized patients [1] . Hyponatremia is a common finding in patients with advanced cirrhosis [2] . Two types of hyponatremia were described in liver cirrhosis; the most important type is hypervolemic hyponatremia (dilutional hyponatremia), which is associated with large ascites (frequently refractory ascites) and edema [3] .

Several mechanisms are implicated in the impairment of solute-free water excretion in cirrhosis and in the subsequent development of hyponatremia, including reduced filtrate delivery to distal nephrons and hypersecretion of arginine vasopressin. Of these, reduced effective circulating volume owing to arterial splanchnic vasodilatation is considered the most important afferent factor in baroreceptor-mediated nonosmotic stimulation of vasopressin release from the neurohypophysis in cirrhosis [4] .

There is a possible relationship between hyponatremia and the presence of hepatic encephalopathy [5] . Several lines of evidence also support the existence of a correlation between hyponatremia and hepatorenal syndrome (HRS) and bacterial infections such as spontaneous bacterial peritonitis [6] .

Hyponatremic cirrhotic patients have poor survival compared with those having normal serum sodium. Therefore, some studies incorporated serum sodium level in the scoring systems that evaluate the prognosis and risk of mortality in cirrhotic patients such as the Model for End-Stage Liver Disease (MELD) score [7],[8] . MELD-Na (MELD with the incorporation of serum sodium), I MELD (the integrated MELD), and MESO index (the MELD to sodium index) are examples of MELD-sodium-derived models [9] .

The aim of this work was to study the prevalence of hyponatremia and the correlation between serum sodium and MELD score in patients with liver cirrhosis.


  Patients and methods Top


This retrospective study was conducted on 100 patients with liver cirrhosis admitted to the medical ward at Kafr El Sheikh Hepatology and Gastroenterology Center from July 2013 to October 2013. The local ethics committee approved the study protocol. Formal consent was obtained from the patients or their relatives. The patients were divided into two groups: group 1 and group 2. Group 1 included 20 patients with compensated cirrhosis discovered accidently during routine clinical examination at an outpatient clinic; group 2 included 80 patients with decompensated cirrhosis, who were later subdivided into four subgroups according to the cause of admission as follows: 20 patients with hepatic encephalopathy as group 2a, 20 patients with variceal bleeding as group 2b, 20 patients with oliguria who were diagnosed with HRS as group 2c, and 20 patients with refractory ascites admitted for regular paracentesis as group 2d.

Diagnosis of liver cirrhosis was based on characteristic findings, including physical stigmata of cirrhosis, decreased serum albumin and increased serum globulin levels, and ultrasonographic findings of cirrhosis (nodular liver surface, coarsened echogenicity of liver parenchyma, enlarged spleen and/or ascites) [10] . The definition of decompensated cirrhosis was based on the presence of ascites or variceal bleeding or hepatic encephalopathy or HRS [11] .

Inclusion criteria included all patients with liver cirrhosis regardless of the cause. Exclusion criteria included the presence of hepatocellular carcinoma, acute fulminant hepatic failure, congestive heart failure, parenchymatous kidney disease, regular intake of thiazide or loop diuretics, and intrahepatic biliary duct dilatation. All patients were subjected to full history taking, full clinical examination, complete blood picture, kidney function tests, liver function tests, evaluation of serum sodium and serum potassium, and abdominal ultrasound; urine analysis was carried out in suspected HRS patients only to exclude proteinuria.

Serum sodium and serum potassium were measured by means of a Roche 9180 Electrolyte Analyzer; complete blood picture was measured with Sysmex KX-21, and MELD score was calculated using the formula: MELD = 9.57× loge (creatinine) +3.78× loge (total bilirubin) + 11.2× loge (INR) +6.43. We received help from the Mayo clinic website to calculate this formula http://www.mayoclinic.org.

Statistical evaluation

Data were collected and statistically analyzed using SPSS (Statistical Package for Social Sciences), version 13, for Windows. A P value less than 0.05 was considered statistically significant. Quantitative data were expressed as mean (X) and SD and analyzed. Fisher's exact test was used to compare qualitative variables between groups. Analysis of variance was used for comparison of means between different groups. The linear correlation coefficient test (r) was used for detection of correlation between two quantitative variables in one group, which could be positive or negative.


  Results Top


There were no significant differences among the studied groups as regards age [Table 1] and sex [Table 2] (P > 0.05).
Table 1 Age distribution in the studied groups

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Table 2 Sex distribution in the studied groups

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With regard to serum bilirubin concentrations, in group 1 the serum bilirubin concentration was 1.63 ± 0.48 mg/dl, whereas it was 5.95 ± 2.33 mg/dl in group 2a. In group 2b, the serum bilirubin level was 4.19 ± 2.19 mg/dl, whereas it was 12.46 ± 2.53 and 4.57 ± 1.68 mg/dl in groups 2c and 2d, respectively, denoting a significant statistical difference (P < 0.001). Groups 2a, 2b, 2c, and 2d had higher serum bilirubin levels compared with group 1. Further, group 2c had higher levels compared with groups 2a, 2b, and 2d.

With regard to serum creatinine concentrations, in group 1 the serum creatinine level was 0.89 ± 0.27 mg/dl, whereas it was 1.12 ± 0.52 mg/dl in group 2a. In group 2b, serum creatinine was 1.12 ± 0.4 mg/dl, whereas it was 3.63 ± 0.44 and 1.26 ± 0.56 mg/dl in groups 2c and 2d, respectively, denoting a significant statistical difference (P < 0.001). Group 2c had higher serum creatinine levels compared with the other groups.

With regard to international normalized ratio (INR), in group 1 INR was 1.15 ± 0.13, whereas it was 1.83 ± 0.65 in group 2a. In group 2b, INR was 1.81 ± 0.58, whereas it was 2.36 ± 0.75 and 1.76 ± 0.48 in groups 2c and 2d, respectively, denoting a significant statistical difference (P < 0.001). Groups 2a, 2b, 2c, and 2d had higher INR than group 1. Further, group 2c had higher INR than groups 2a, 2b, and 2d.

With regard to the MELD score, in group 1 the mean MELD score was 10.3 ± 1.341, whereas it was 21.75 ± 5.56 in group 2a. In group 2b, the mean MELD score was 19.1 ± 5.16, whereas it was 36.45 ± 3.74 and 20.15 ± 0.496 in groups 2c and 2d, respectively, denoting a significant statistical difference (P < 0.001). Groups 2a, 2b, 2c, and 2d had higher MELD score than group 1. Further, group 2c had higher MELD score than groups 2a, 2b, and 2d.

With regard to serum sodium levels, in group 1 the mean serum sodium level was 139.5 ± 4.236 mEq/l, whereas it was 128.85 ± 8.93 mEq/l in group 2a. In group 2b, the mean serum sodium level was 132.1 ± 8.9 mEq/l, whereas it was 8.1 ± 128.3 and 7.45 ± 129.65 mEq/l in groups 2c and 2d, respectively, denoting significant statistical difference (P < 0.001). Groups 2a, 2b, 2c, and 2d had lower serum sodium levels compared with group 1.

With regard to serum potassium levels, in group 1 the mean serum potassium level was 4.0 ± 0.679 mEq/l, whereas it was 4.1 ± 0.556 mEq/l in group 2a. In group 2b, the mean serum potassium was 3.945 ± 0.558 mEq/l, whereas it was 4.825 ± 0.546 and 3.8 ± 0.561 mEq/l in groups 2c and 2d, respectively, denoting a significant statistical difference (P < 0.001). Serum potassium levels were higher in group 2c than in other groups, but still within normal range.

With regard to serum aspartate transaminase (AST), in group 1 the mean serum AST was 58.35 ± 21.91 U/l, whereas it was 60.8 ± 20.983 U/l in group 2a. In group 2b, the mean serum AST was 54.85 ± 20.859 U/l, whereas it was 55.15 ± 17.242 and 52 ± 18.253 U/l in groups 2c and 2d, respectively, denoting a nonsignificant statistical difference (P = 0.675).

With regard to alanine transaminase (ALT), in group 1 the mean serum ALT was 60.7 ± 21.684 U/l, whereas it was 55.75 ± 22.33 U/l in group 2a. In group 2b, the mean serum ALT level was 57.95 ± 20.808 U/l, whereas it was 60.55 ± 14.634 and 56.2 ± 20.072 U/l in groups 2c and 2d, respectively, denoting a nonsignificant statistical difference (P = 0.896).

Regarding serum albumin, in group 1 the mean serum sodium was 3.72 ± 0.47 g/dl, while it was 2.3 ± 0.6 g/dl in group 2a. In group 2b, the mean serum sodium was 2.3 ± 0.53 g/dl while it was 2.27 ± 0.64 and 1.98 ± 0.52 g/dl in groups 2c and 2d respectively, denoting a significant statistical difference (P < 0.001). Groups 2a, 2b, 2c and 2d have lower serum albumin than group 1.

With regard to the prevalence of hyponatremia in liver cirrhosis, in group 1 the prevalence of hyponatremia was 0%, whereas in group 2 the prevalence was 47/80 (59%). The prevalence of hyponatremia differed according to the complication, being highest in HRS and hepatic encephalopathy (70 and 65%, respectively) and lowest in refractory ascites and variceal bleeding patients (55 and 45%, respectively). There was significant negative correlation between serum sodium and MELD score in group 2a (r = −0.789 and P<0.001), group 2b (r = −0.732 and P<0.001), group 2c (r = −0.655 and P = 0.002), and group 2d (r=−0.698 and P = 0.001). As regards coefficient correlation, significant correlation was seen in group 2 [all decompensated cirrhotic patients (n = 80), r = −0.496 and P < 0.001], but there was no significant correlation in group 1 [Figure 1] [Figure 2] [Figure 3] [Figure 4].
Figure 1: Pie chart showing the prevalence of hyponatremia in compensated cirrhotic patients (group 1) (n = 20)

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Figure 2: Pie chart showing the prevalence of hyponatremia in decompensated cirrhotic patients (group 2) (n = 80)

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Figure 3: Scatter chart showing the relation between serum sodium and Model for End-Stage Liver Disease (MELD) score in compensat ed patients (group 1) (n = 20)

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Figure 4: Scatter chart showing the relation between serum sodium and Model for End-Stage Liver Disease (MELD) score in decompensated cirrhotic patients (group 2) (n = 80)

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  Discussion Top


The presence of hyponatremia (Na < 135 mEq/l) is greatly associated with the presence of liver cirrhosis complications (decompensation). Hyponatremia was not detected in patients with compensated cirrhosis, whereas it was seen in about 59% (47/80) of decompensated patients in the present study.

Similar results were obtained by other studies. These studies were conducted on randomly chosen decompensated cirrhotic patients only. In the study conducted by Angeli et al. [12] on 997 patients with liver cirrhosis having ascites, the prevalence of hyponatremia was 49.4%. In the study by Kim et al. [13] conducted on 188 cirrhotic patients with ascites the prevalence of hyponatremia was 47.9%. In the study by Shaikh et al. [14] conducted on 217 cirrhotic ascitic patients the prevalence of hyponatremia was 51.6%. Khalil et al. [15] showed a prevalence of hyponatremia of 65.5% among 200 decompensated cirrhotic patients.

The prevalence of hyponatremia in our study may be slightly higher than that seen in most of the above-mentioned studies. That is because our study focused on certain complications that may have an association with hyponatremia unlike other studies that were conducted on randomly chosen decompensated cirrhotic patients.

Although the prevalence of hyponatremia was associated with decompensated cirrhosis, this association increased markedly in certain major cirrhosis complications - for example, among patients with hepatic encephalopathy about 65% were hyponatremic; among patients with HRS about 70% were hyponatremic; and among patients with refractory ascites about 55% were hyponatremic; among patients with variceal bleeding, hyponatremic patients constituted about 45%.

These associations was investigated by several researchers like Angeli et al. [12] , Shaikh et al. [14] , Kim et al. [13] , and Khalil et al. [15] . These studies, unlike the present study, grouped the decompensated cirrhotic patients into three groups according to serum sodium concentrations (normonatremic group, serum sodium ≥ 135 mEq/l; mild hyponatremic group, serum sodium between 130 and 135 mEq/l; and severe hyponatremic group, serum sodium ≤ 130 mEq/l).

In agreement with our study, Angeli et al. [12] found prospectively a clear inverse relationship between serum sodium levels and frequency of HRS. Also, Shaikh et al. [14] found prospectively that the frequency of HRS was strongly associated with low serum sodium concentration, as 8/13 patients with refractory ascites with severe hyponatremia developed HRS during follow-up as compared with one patient with mild hyponatremia and none with normal serum sodium concentration. In contrast to our study, this inverse relationship between serum sodium levels and HRS was found retrospectively by Kim et al. [13] and Khalil et al. [15] to be statistically insignificant among the three groups. However, all of the above studies confirmed the association between hyponatremia and hepatic encephalopathy.

The relationship between hepatic encephalopathy and serum levels may be explained on the basis of more severe liver failure among patients with serum sodium less than 130 mEq/l, and the possibility that the two events may be pathophysiologically linked. Low serum sodium levels in patients with cirrhosis are associated with a remarkable reduction in the cerebral concentration of organic osmolytes that probably reflect compensatory osmoregulatory mechanisms against cell swelling [16] .

The pathophysiology of association between HRS, refractory ascites, and hyponatremia can be explained by increased body fluid resulting from the impairment of solute-free water excretion. Further, it has been shown that hyponatremia is a major risk factor for the development of HRS in patients with refractory ascites. This increased risk for HRS may be related to a more severe circulatory dysfunction in patients with hyponatremia compared with patients without hyponatremia [17] .

With regard to the correlation between serum sodium and MELD score in the studied populations, our study showed that there was no significant correlation in compensated cirrhosis (r = −0.324, with P > 0.05) but there was a strong inverse correlation in decompensated cirrhosis (r = −0.496 and P < 0.001). In agreement with this study, Khalil et al. [15] and Wang et al. [18] demonstrated a significant correlation between serum sodium and MELD score in decompensated cirrhotic patients.

As arginine vasopressin release is a primary cause of hyponatremia in cirrhosis, several vasopressin receptor antagonists have been evaluated in treating hyponatremia in patients with cirrhosis/ESLD and other conditions characterized by hypervolemia - for example, heart failure. These include the intravenous dual V1A/V2-receptor antagonist conivaptan, and the oral V2-receptor antagonists lixivaptan (VPA-985), satavaptan, and tolvaptan. Currently, only conivaptan and tolvaptan are approved for increasing serum sodium in patients with hypervolemic or euvolemic hyponatremia in the USA [19] .

One limitation of this study was that it did not assess the effect of serum sodium concentration on the risk for developing complications but simply examined the concurrent presence of complications and sodium levels in a retrospective analysis.

Further prospective studies are needed to determine the clinical significance of hyponatremia and identify its correlation with the incidence of possible complications. Moreover, studies should be conducted on incorporating serum sodium in new liver cirrhosis prognostic models and on demonstrating the efficacy of other sodium-incorporated models such as MELD-Na, MESO index, and IMELD scores [Table 3] [Table 4] [Table 5].
Table 3 Comparison among studied groups as regards serum bilirubin, serum creatinine, international normalized ratio, Model for End-Stage Liver Disease score, serum Na+, serum K+, serum alanine transaminase, serum aspartate transaminase, and serum albumin

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Table 4 Prevalence of hyponatremia in each group

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Table 5 Correlations between serum sodium and model for end-stage liver disease score in the studied groups

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  Conclusion Top


Hyponatremia is a common problem in liver cirrhosis, especially advanced cirrhosis. The study showed that there is an association between hyponatremia and the presence of certain complications of liver cirrhosis including hepatic encephalopathy, refractory ascites, and HRS. Also hyponatremia was associated with a higher severity of cirrhosis assessed by MELD scores. Management of hyponatremia may decrease the incidence and severity of liver cirrhosis complications and improve the quality of life of the patients. Thus, greater focus should be directed toward the use of vasopressin receptor antagonists as a line of treatment in complicated cirrhotic patients with hyponatremia without salt overload.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

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