Hyponatremia in Cirrhotic Patients in the Hepatology and Gastroenterology Department of Gabriel Touré University Hospital ()
1. Introduction
Cirrhosis, a serious liver disease with multiple etiologies, constitutes a significant public health problem worldwide due to its frequency and complications (portal hypertension, hepatic encephalopathy, hepatocellular carcinoma, hepatorenal syndrome) [1]. Hyponatremia is common in cirrhosis, especially in the presence of ascites. This hyponatremia is defined according to generally accepted consensus as a serum sodium level below 130 mmol/l [2]. Several studies have proven that hyponatremia is the most frequent hydro-electrolytic disorder during cirrhosis, occurring at an advanced stage of liver disease [3], it predisposes to the occurrence of hepatic encephalopathy [4]. Its incidence is 57% in hospitalized cirrhotic patients [5]. According to one study, 42% of patients undergoing liver transplantation had developed hyponatremia before transplantation [6]. Hyponatremia was observed in 6.07% of cirrhotic patients in China [7]. In Africa, 9% of cirrhotic patients presented with hyponatremia in Tunisia [8], and 15.8% in Côte d’Ivoire [9]. In Mali, a study on hepatic encephalopathy showed that the triggering factor of this hepatic encephalopathy was represented by hydro-electrolytic disorders in 22% of cases without specifying the type of disorder [10]. In the absence of studies on hyponatremia in cirrhotic patients, in our context, we initiated this work.
2. Patients and Methods
2.1. Study Location
It took place in the hepatogastroenterology department of the Gabriel Touré University Hospital.
2.2. Types and Period of Study
This was a prospective cross-sectional study conducted from January 2020 to June 2021.
2.3. Study Population
The study included all patients hospitalized in the department for cirrhosis.
Inclusion criteria: The following were included:
Patients who provided oral consent
Patients hospitalized in the hepatogastroenterology department for compensated or decompensated cirrhosis, diagnosed based on:
clinical findings (firm hepatomegaly with a sharp inferior border, or atrophic or normal-sized liver, ascites with or without lower limb edema, central venous catheter, jaundice),
ultrasound findings (multinodular liver with irregular contours, ultrasound signs of portal hypertension, portal vein dilation, splenomegaly, ascites, etc.)
endoscopic findings (esophageal varices, cardio-tuberositary varices, antral vascular ectasia, portal hypertensive gastropathy)
and laboratory findings (low prothrombin time, hypoalbuminemia, thrombocytopenia, anemia).
Cirrhotic patients who underwent serum sodium measurement
Exclusion criteria:
Patients hospitalized for reasons other than cirrhosis were not included.
Patients hospitalized with cirrhosis but without serum sodium measurement were not included.
Non-hospitalized patients were not included.
2.4. Ethical Considerations
Verbal consent from the patient or their family was obtained and Patient anonymity was guaranteed.
2.5. Study Methods
All patients meeting our inclusion criteria underwent a complete clinical examination, including an interview to look for medical history, functional signs such as physical asthenia, increased abdominal volume, and history of digestive bleeding.
2.5.1. Physical Examination
Looking for signs of portal hypertension (ascites, Collateral venous circulation, splenomegaly) and signs of hepatocellular insufficiency (spider angioma, jaundice, gynecomastia).
2.5.2. Paraclinical Examinations
Biological:
Blood ionogram: two criteria for hyponatremia have been defined:
Sodium < 130 mmol/L
Sodium between 131 - 135 mmol/L
Urea,
Prothrombin rate,
Complete blood count (CBC),
Total and conjugated bilirubin,
Serum creatinine and creatinine clearance,
Serological markers for hepatitis B and C,
Protein electrophoresis.
Morphological examinations
Fibroscopy: To look for signs of endoscopic portal hypertension (PH).
Ultrasound: To look for ultrasound signs of PH and liver morphological abnormalities.
2.6. Data Entry and Analysis
The data were collected on an individual survey form, entered and analyzed on the software “EPI-INFO version 7.2.4.0”. The Chi-square test was used to compare the proportions. The significance threshold was set at p < 0.05.
3. Results
During the study period, we collected data on 1052 hospitalizations in the hepatogastroenterology department of the Gabriel Touré University Hospital, including 220 cirrhotic patients (20.91%). Among these 220 patients, 79 had hyponatremia (35.90%), with 16.36% having a serum sodium level < 130 mmol/L and 19.54% having a level between 131 and 135 mmol/L. The mean age was 50.89 ± 13.79 years (range 20 - 80 years). The male-to-female ratio was 1.55. Altered mental status was the most frequent reason for consultation (49.36%), followed by ascites (Table 1). More than half of the patients had hyponatremia within the first 6 months of the disease (Table 2). A low prothrombin rate was found in 36 patients or 45.57%. Hypoalbuminemia was present in 35 patients or 44.31%, hyperbilirubinemia in 40 patients or 50.63% and thrombocytopenia in 41.77% of patients (Table 3). The majority of patients, 60.75%, were classified as Child C (severe cirrhosis) and 35.45% as Child B (decompensated cirrhosis). Hepatitis B was the dominant etiology in the patients. Hepatic encephalopathy was present in 21.52% of patients with serum sodium levels < 130 mmol/L, compared with 30.34% of patients with serum sodium levels between 130 and 135 mmol/L; ascites was present in 35.44% of patients with serum sodium levels < 130 mmol/L compared to 45.57% with a serum sodium level between 130 - 135 mmol/l, and esophageal varices in 35.44% of patients with a serum sodium level < 130 mmol/l compared to 45.57% with a serum sodium level between 130 - 135 mmol/l in our study. Hyponatremia was associated with the severity of liver disease (Table 4). Hyponatremia was associated with the severity of liver disease (Table 4). After 18 months of follow-up, 58 patients, or 73.42%, died, including 44.30% within 1 to 6 months after the diagnosis of hyponatremia (Table 5).
Table 1. Distribution of patients according to reason for consultation.
Reason for consultation |
Effective |
Percentage % |
Disorder of consciousness |
26 |
53.1 |
Ascite |
9 |
18.4 |
Abdominal pain |
3 |
6.1 |
Hematemesis |
3 |
6.1 |
Fever |
2 |
4.1 |
Jaundice |
3 |
6.1 |
Vomiting |
2 |
4.1 |
Rectal bleeding |
1 |
2 |
Total |
49 |
100 |
Table 2. Distribution of patients according to the duration of hyponatremia and the diagnosis of cirrhosis.
Onset of the disease |
Effective |
Percentage % |
<1 month |
5 |
10.2 |
1 - 6 months |
25 |
51 |
7 - 12 months |
8 |
16.3 |
>12 months |
11 |
22.5 |
Total |
49 |
100 |
Table 3. Distribution of patients according to biological signs.
Biologies |
|
Staff |
Percentage % |
TP (%) (n = 49) |
≥50 |
27 |
55.10 |
<50 |
22 |
44.90 |
Albumin (g/l) (n = 49) |
>35 |
8 |
16.33 |
28 - 35 |
18 |
36.73 |
<28 |
23 |
46.94 |
Blood glucose (mmol/l) (n = 49) |
0.70 - 1.10 |
39 |
79.59 |
>1.26 |
10 |
20.41 |
serum creatinine (µmol/l) (n = 49) |
≤120 |
29 |
59.18 |
>120 |
20 |
40.82 |
Creatinine clearance (n = 49) |
80 - 130 |
32 |
65.31 |
<80 (ml/mn) |
17 |
34.69 |
Urea (mmol/l) (n = 49) |
<2.5 |
14 |
28.57 |
2.5 - 7.5 |
20 |
40.82 |
>7.5 |
15 |
30.61 |
Ag HBs (n = 50) |
Positive |
46 |
92 |
Negative |
4 |
8 |
Anti-HCV Ac (n = 50) |
Positive |
4 |
8 |
Negative |
46 |
92 |
Bilirubin (µmol/l) |
<35 |
8 |
16.33 |
35 - 50 |
13 |
26.53 |
>50 |
28 |
57.14 |
Platelets (10) |
≤150 |
23 |
46.94 |
≥150 |
26 |
53.06 |
Hemoglobin level (g/dl) |
≤12 g/dl |
39 |
79.59 |
≥12 g/dl |
10 |
20.41 |
Table 4. Comparison of cirrhosis characteristics in the two groups.
|
|
Group |
Group |
P |
OR (95% CI) |
|
|
Na < 130 |
Na [130 - 135] |
|
|
N (22) |
N (27) |
Viral etiology |
22 (100%) |
27 (100%) |
0.28 |
|
Average duration of cirrhosis progression |
6.7 months |
5.4 months |
|
|
β-blocker |
1 (4.5%) |
3 (11.1%) |
0.40 |
0.38 |
Diuretic |
9 (41%) |
17 (63%) |
0.12 |
0.40 |
Esophageal varices grade II and III |
21 (95.4%) |
27 (100%) |
0.26 |
|
Ascites |
17 (77.3%) |
25 (92.4%) |
0.12 |
0.27 |
Hepatic encephalopathy |
12 (54.5%) |
17 (63%) |
0.11 |
0.35 |
Hemorrhage |
1 (4.5%) |
7 (26%) |
0.04 |
0.13 |
Hepatocellular carcinoma |
2 (9%) |
1 (4%) |
0.43 |
2.60 |
Child-Pugh Stage C |
19 (86.36%) |
10 (27.03%) |
0.00001 |
17.10 |
Table 5. Distribution of patients according to overall survival.
Death interval |
Effective |
Percentage % |
<1 month |
7 |
17.95 |
1 - 6 months |
24 |
61.54 |
7 - 12 months |
3 |
7.69 |
>12 months |
5 |
12.82 |
4. Discussion
This prospective study, conducted from January 2020 to June 2021, included 220 cirrhotic patients, 79 of whom had hyponatremia. Patients were included based on non-invasive criteria commonly used for the diagnosis of cirrhosis, despite the challenges involved.
Study limitations:
The single-center nature of the study may limit the generalizability of the results.
Our sample size was limited due to the high cost of laboratory tests, making diagnosis and patient follow-up difficult.
The unavailability of treatments such as albumin can influence the observed prognosis
The mean age was 50.89 ± 13.79 years, with a range of 20 to 80 years. This result is comparable to that of Rym et al. [11], who reported a mean age of 58 years. The prevalence of hyponatremia was 16.36% if the serum sodium level was <130 mmol/L and 19.54% if it was between 131 and 135 mmol/L. Rym et al. reported a lower prevalence of 10.5% for a serum sodium level < 130 mmol/L and 31.4% for a sodium level ≤ 135 mmol/L [11]. In the literature, the prevalence of hyponatremia was 21.6% for a sodium level < 130 mmol/L and 49.4% for a level between 131 and 135 mmol/L [3]. This can be explained by the fact that the cirrhotic patients included in our series had more severe cirrhosis than those in other studies. Regarding risk factors, the occurrence of hyponatremia is classically correlated with the severity of the disease as assessed by Child-Pugh scores [3] [4] in our study. These data corroborate our results and are comparable to that found by G Boroni et al. as well as Somberg JC [12] [13]. Hepatic encephalopathy was present in 21.52% of patients with a serum sodium < 130 mmol/l versus 30.34% with a serum sodium between 130 - 135 mmol/l; ascites in 35.44% of patients with a sodium level < 130 mmol/l 65 Hyponatremia in cirrhotic patients in the hepatogastroenterology department of the Gabriel Touré University Hospital against 45.57% with a sodium level between 130 - 135 mmol/l and esophageal varices in 35.44% of patients with a sodium level < 130 mmol/l against 45.57% with a sodium level between 130 - 135 mmol/l in our study. These results were similar to those of Kim JH et al. [14]. In fact, the severity of hyponatremia, particularly at serum sodium concentrations < 130 mmol/L, corresponded to higher risks of developing severe ascites and severe hepatic encephalopathy, compared to the risks in patients with serum sodium ≥ 130 mmol/L. In agreement with previous reports, serum sodium concentration was not associated with the presence of varicose veins. The overall survival at 18 months was 26.58%, comparable to that of Rym et al., who had an overall survival of 22.5% [11].
5. Conclusion
Cirrhosis remains a significant concern for clinicians, particularly hepatogastroenterologists. Diagnosis is very often delayed. The complications to which it predisposes are varied and serious. The occurrence of electrolyte disturbances, including hyponatremia, confirms this severity. Hyponatremia is a poor prognostic factor in chronic liver diseases; it is associated with the severity of liver disease. Therapeutic options are limited in our setting. Survival at 18 months was shortened in our study.