It is estimated that diseases of the liver account for nearly 2 million deaths globally. Studies have also shown that there has been an increase in the age standardised incidence of patients who suffer from decompensated cirrhosis of the liver 1, 2. The morbidity and mortality of the patients who suffer from cirrhosis of the liver is much lower than those patients who have hepatic decompensation along with cirrhosis of the liver. It is estimated that the one-year mortality may reach up to 50% in these patients. Also, it is noted that hepatic decompensation is one of the most important causes of hospitalization in patients with cirrhosis 3, 4, 5. Hepatic encephalopathy is the term used to describe the complex and variable changes in neuropsychiatric status that complicate liver disease. The defining feature is fulminant hepatic failure, and the multitude of metabolic abnormalities caused by loss of functioning hepatocyte mass 6, 7. There is evidence that overt hepatic encephalopathy and hyponatremia both have a higher mortality in patients who have cirrhosis of the liver 8. In comparison, hyponatremia is considered another important complication of decompensated liver cirrhosis and is said to be present in at least half of the patients who have been hospitalized for cirrhosis of liver hepatic decompensation. Studies have also shown that hyponatremia can be an independent predictor of mortality not only in patients who have cirrhosis of the liver that is decompensated but also in those patients who are acute on chronic liver 9. Sodium variations are a common electrolyte abnormality encountered in patients with chronic liver disease and more so when they develop, overt hepatic encephalopathy. A majority of patients with ethanol-related chronic liver disease progress to the decompensated state thereby developing hepatic encephalopathy either due to continued ethanol consumption, superadded infection or blood loss, etc., Analysis of the course and variation in the biochemical parameters during the disease process might help better understand and manage the disease process 10, 11.

In chronic liver disease owing to hepatic dysfunction patients develop hypoproteinaemia and thereby also progress to a state of fluid overload leading to dilutional hyponatraemia. As a feature of worsening hepatic dysfunction patients develop hepatic encephalopathy due to failure of degradation activity of the liver leading to the accumulation of toxic metabolites. Serum sodium levels in previous studies have been shown to be worse in a decompensated state when compared to compensated chronic liver disease. This study has been done to observe the fluctuations of serum sodium values in various grades of hepatic encephalopathy and also in patients with chronic liver disease, to ascertain the use of serum sodium as an indicator to the severity of hepatic encephalopathy and to observe the nominal variations in patients with chronic liver disease without the complication.

The aim of the study was to ascertain the use of serum sodium as an indicator to the severity and morbidity of hepatic encephalopathy and to observe the nominal variation in serial serum sodium levels during hepatic encephalopathy.

The objective of the study was to ascertain the association of serum sodium values as an indicator to the recovery and deterioration of hepatic encephalopathy.

This observational study was conducted at A.J. Institute of Medical Sciences and Research Centre, Mangalore, over a period of two years from 2022 to 2024. The study population included patients diagnosed with hepatic encephalopathy (HE), admitted to the Medicine Department in a decompensated state, i.e., Grade 2-4 as per West Haven criteria 12.

This observational study analyzed a total of 97 patients diagnosed with HE admitted in a decompensated state. Among the hepatic encephalopathy patients, 38.1% were aged 25-44 years, 44.3% were aged 45-64 years, 15.5% were aged 65-84 years, and 2.1% were aged 85 and above. Females constituted 24.7% & males 75.3% of the study participants.

In the study of hepatic encephalopathy patients, 74.2% were diagnosed with alcoholic cirrhosis, while 14.4% had HBV-associated cirrhosis. Autoimmune hepatitis and NASH each accounted for 3.1% of cases, with alcoholic hepatitis and HCV-associated cirrhosis both contributing 2.1% each. Wilson's disease was the least common, representing 1.0% of the patients (Figure 1).

Table 1 presents the serial changes in mean sodium levels from Day 0 to Day 7 in patients with hepatic encephalopathy. On Day 0, the mean sodium level was 126.794 ± 7.769mEq/L, which progressively decreased over time. By Day 2, the mean sodium level dropped to 124.588 ± 9.684 mEq/L, further declining to 123.392 ± 11.371 mEq/L on Day 4. On Day 7, the mean sodium level reached its lowest point at 122.196 ± 13.106 mEq/L. The analysis shows a significant decrease in sodium levels over the course of the study, with an F value of 49.24 and a p value of less than 0.001, indicating that the changes in sodium levels were statistically significant over time. This suggests that worsening hyponatremia is associated with disease progression in hepatic encephalopathy.

Figure 2 shows the trends in serum sodium levels across patient outcomes. In patients discharged against medical advice (DAMA), the mean sodium levels showed a significant decline, dropping from 118.96 ± 0.92 on Day 0 to 112.96 ± 0.92 by Day 7. Similarly, in the expired group, the mean sodium level began at 123.38 ± 3.59 on Day 0 and gradually decreased to 112.78 ± 4.45 by Day 7. In contrast, patients in the Improved group exhibited a consistent increase in sodium levels, rising from 136.50 ± 1.54 on Day 0 to 139.50 ± 1.54 on Day 7. These findings underscore a clear pattern: while patients who either expired or left against medical advice experienced a progressive decline in sodium levels, those who showed clinical improvement demonstrated a steady increase. This suggests that rising sodium levels may be associated with better recovery outcomes, whereas declining sodium levels may indicate a worsening prognosis.

Patients who improved showed an increase in sodium levels, while those who expired or were discharged against medical advice (DAMA) exhibited decreasing sodium levels (Table 2).

Table 2 indicates significant changes in values from Day 0 to Day 7 across different outcomes. For those with DAMA (Discharged Against Medical Advice), the average decrement is 6.00 ± 0.00. In the expired group, the average decrement is 10.59 ± 2.11, reflecting a notable decrease. Conversely, the Improved group shows an average increment of 12.70 ± 2.08, indicating a significant increase in values. These findings highlight a clear pattern of reduction for DAMA andExpired outcomes, and an increase for those who improved (with an F value of 51.0 and a p-value less than 0.001)

Our study observed that 44.3% of HE patients were aged 45-64 years, 38.1% were aged 25-44 years, 15.5% were aged 65-84 years, and 2.1% were aged 85 and above. Males constituted 75.3% of the patients, while females accounted for 24.7%. This age distribution is consistent with the findings of Kim et al., who reported a significant prevalence of HE in middle-aged to older adults 13. Furthermore, the higher incidence of HE among males aligns with the observations of Lars Bosen et al., who noted a greater prevalence of HE in men 10.

Alcoholic cirrhosis was identified as the most common cause of HE in our study, accounting for 74.2% of cases. This was followed by HBV-associated cirrhosis (14.4%), with autoimmune hepatitis and NASH each contributing 3.1% of cases. Alcoholic hepatitis and HCV-associated cirrhosis each accounted for 2.1%, while Wilson's disease was the least common cause, representing 1.0% of the patients. These findings align with the study by Maqsood et al., which identified alcohol-related liver disease as the predominant cause of HE and highlighted the significance of hepatitis B and C as etiological factors 14.

Our study revealed a significant decrease in serum sodium levels over time in patients with hepatic encephalopathy (HE). The mean sodium level on Day 0 was 126.79 mEq/L, which dropped to 122.20 mEq/L by Day 7. The trends in sodium levels varied markedly across different patient outcomes. Patients discharged against medical advice (DAMA) had a mean sodium decrement of 6.00 mEq/L, while those who expired exhibited a greater decline, with a mean reduction of 10.59 mEq/L. In contrast, patients who improved showed an average sodium increase of 18.925 mEq/L. These findings highlight a statistically significant difference in sodium level changes across outcomes, with a p-value of less than 0.001.

This result aligns with a study by Guevera et al., which demonstrated that hyponatremia (serum sodium < 130 mEq/L) is a significant risk factor for developing overt HE in cirrhosis patients. The study suggested that hyponatremia is associated with lower brain concentrations of organic osmolytes, particularly myo-inositol, which are critical for brain function. Patients with reduced brain myo-inositol levels were more likely to develop overt HE, emphasizing the critical role of sodium levels in the pathogenesis and progression of HE 15. Similarly, Jong Hon Kim et al. found that even mild hyponatremia (serum sodium 131-135 mEq/L) was linked to severe complications such as higher HE grades, spontaneous bacterial peritonitis, and hepatic hydrothorax. Their study demonstrated that lower sodium levels were closely associated with impaired liver function, as indicated by higher Child-Pugh and MELD scores, and predicted worse clinical outcomes 12.

The sodium level decline observed in non-survivors and DAMA patients may be attributed to several factors. As liver disease progresses, the liver's capacity to regulate electrolytes diminishes, leading to sodium and water imbalances. Advanced liver disease is commonly associated with complications like ascites, which exacerbates sodium retention and dilutional hyponatremia. Hepatorenal syndrome, a severe complication of liver cirrhosis, results in renal vasoconstriction and reduced renal perfusion, impairing the kidneys' ability to excrete free water, which further contributes to hyponatremia. The use of diuretics to manage ascites and edema also contributes to sodium imbalances, further reducing serum sodium levels. Additionally, hyponatremia leads to a reduction in brain organic osmolytes, particularly myo-inositol, which are crucial for maintaining neuronal cell volume and function, thus worsening the neurological symptoms of HE.

Sodium levels among HE patients showed a significant association with clinical outcomes. Patients who improved exhibited a steady increase in sodium levels from Day 0 to Day 7, while those who expired or were discharged against medical advice (DAMA) experienced a continuous decline. Specifically, the mean sodium levels on Day 0 were 118.96 mEq/L for DAMA patients, 123.38 mEq/L for those who expired, and 120.575 mEq/L for those who improved. By Day 7, these values had decreased to 112.96 mEq/L for DAMA patients and 112.78 mEq/L for expired patients, while those who improved showed an increase to 139.50 mEq/L. This significant variation in sodium levels across the different groups correlates directly with their clinical outcomes, suggesting that sodium levels are a key prognostic factor.

This association between sodium levels and patient outcomes is supported by a study by Lars Bosen et al., which found that lower serum sodium levels at admission were associated with higher rates of HE and increased mortality 10. Their study emphasized that the hazard for HE increases linearly with each mmol/L decrease in serum sodium, underscoring the crucial role of sodium levels in predicting HE severity and patient survival. Similarly, findings by Vishwadeep Ahluwalia et al. highlight that hyponatremia significantly impacts the health-related quality of life in cirrhotic patients 16. Their research showed that patients with hyponatremia, irrespective of HE presence, experienced worse physical and psychosocial health-related quality of life scores, reflecting the broader impact of sodium imbalances on patient well-being.

Hyponatremia in HE patients is often caused by impaired renal water excretion, a condition exacerbated by the use of diuretics commonly prescribed to manage ascites and edema in cirrhotic patients. The progressive decline in sodium levels observed in non-survivors and DAMA patients reflects the severity of liver and renal dysfunction. As liver disease progresses, the kidneys’ ability to excrete free water diminishes, leading to water retention and dilutional hyponatremia. Diuretic use further disrupts the electrolyte balance by promoting sodium excretion while reducing fluid overload. In contrast, the improvement in sodium levels among survivors may be attributed to successful medical interventions, including careful fluid management, diuretic adjustments, and treatment of underlying infections or complications that exacerbate hyponatremia. Nutritional support and medications that enhance renal perfusion may also contribute to improved sodium levels and patient outcomes. Therefore, regular monitoring and timely intervention for hyponatremia are critical in managing HE patients, as evidenced by the significant differences in sodium level trends among the DAMA, expired, and improved groups.

This study highlights the crucial role of serum sodium levels in predicting the severity and outcomes of hepatic encephalopathy (HE). The data demonstrated that lower sodium levels are strongly associated with higher morbidity and mortality, particularly in patients who were discharged against medical advice or expired. This finding supports existing literature that highlights hyponatremia as a key factor in the progression of HE. In contrast, patients who improved showed a steady increase in sodium levels, suggesting effective management of their condition. The study emphasizes the importance of regular monitoring and timely intervention for hyponatremia, along with other biochemical abnormalities such as elevated bilirubin, hypoalbuminemia, and elevated liver enzymes, which were common among our study population. These findings reinforce the need for targeted therapeutic strategies to correct electrolyte imbalances and improve patient outcomes. Overall, our study provides valuable insights into the biochemical profiles of HE patients and highlights the critical need for comprehensive management of both liver dysfunction and its systemic complications to enhance survival rates and quality of life for these patients.