Association of Hyponatremia and Encephalopathy in Patients with Chronic Liver Disease

Objective: To determine the association of hyponatremia in chronic liver disease patients with presentation of hepatic encephalopathy (HE) at Isra university Hospital Hyderabad. Methods: This study was cross sectional and carried out at medicine and gastroenterology department of Isra university Hospital Hyderabad and MMC MirpurKhas. Study duration was from September 2015 to March 2016. All the cases with age more than 25 years, both genders after diagnosis of chronic liver disease with sign and symptoms of Hepatic Encephalopathy were selected in this study. Blood sample for serum sodium level, was send to diagnostic laboratory of the hospital. Hyponatremia was classified as: 130– 135 mEqL (mild), 125–130 mEq/L (moderate) and < 125 mEq/L (severe). Hepatic encephalopathy was categorized according to the West Haven classifi1 Assistant Professor, Medicine Department of Isra University Hospital, Hyderabad. 2 Assistant Professor, Medicine Department of MMC, Mirpurkhas. 3 Assistant Professor, Medicine Department of MMC, Mirpurkhas. 4 Consultant General Physician, Liaquat University Hospital, Hyderabad. Date of Submission: 30-06-2016 Date of 1 Revision Received: 27-08-2016 Date of 2 Revision Received: 27-12-2016 Date of Acceptance for publication: 15-01-2017 Conflict of Interest: None Funding Source: None Contribution All Authors have contributed in Study Design, Data Collection, Data Analysis, Data Interpretation, Manuscript Writing and Approval. cation (4 grades) Results: Total number of cases was 80. Mean age was 48 + 8.5 years. 55 (68.5%) patients were male. Majority of cases, 55 (68.5%) patients were infected with HCV. 40% patients had normal level of sodium, 25% had mild, 20% had moderate while 15% patients had severe hyponatremia. On the grading of encephalopathy, 30 (37.5%) patients had grade 1 encephalopathy while 25/(31.2%) patients had grade 2, 15/(18.8%) had grade 3 while 10 (12.5%) patients hade grade 4. The serum sodium levels significantly decreased with increasing severity of hepatic encephalopathy (P = 0.001). Conclusion: We concluded that the hyponatremia is significantly linked with Hepatic Encephalopathy (HE) in patients having chronic liver disease (CLD).


Introduction
Chronic liver diseases (CLD) and its complications are the major health problem, due to big burden of Hepatitis C virus and Hepatitis B virus in the community 1 and it is also the commonest reason of death in Pakistani population.It is very common reason of admission to our hospitals. 2In the decompensation condition, cases having CLD generally present with ascites, jaundice, portal hypertension, gastrointestinal hemorrhage, spontaneous bacterial peritonitis and hepatic encephalopathy. 3About 30% of patients with CLD usually die due to Porto systemic encephalopathy. 4The clinical course of patients with CLD is frequently complicated due to increase in the renal function abnormalities and imbalance of electrolytes. 5n the body disturbance of the water is the main sign of advance cirrhosis, 6 This phenomena of distur-bance of water is linked to the existence of ascites and is characterized by the development of dilutional hyponatremia, which is a frequent complication and sequel of chronic liver disease. 5,7Recent study indicates that hyponatremia is a key prognostic factor in patients with CLD. 8 The prevalence of hyponatremia [serum Na < 130 mEq/L] in patients with cirrhosis with ascites is approximately 30%. 9The relationship between hyponatremia and severity of cirrhosis is associated with the development of complications.hepatic encephalopathy, hepatorenal syndrome and spontaneous bacterial peritonitis are more presented in cases having serum concentration < 130 mEq. 10 Furthermore in cases having ascites, those having hyponatremia have a lower diuretics response, higher frequency of refractory ascites, and frequent requirement of the therapeutic paracentesis. 11A study from Pakistan demonstrated 51.6% of CLD cases had serum sodium concentration below than the normal level. 5orroni et al, 12 reported that hyponatremia was in 30% of CLD cases.Hyponatremia can induce or aggravate Hepatic encephalopathy, leading to disease progression like seizures, coma and even brain death.The aim of this study was to evaluate the association of hyponatremia in chronic liver disease patients with presentation of hepatic encephalopathy.

Material and Methods
This study was cross sectional and carried out at medicine and gastroenterology department of Isra university Hospital Hyderabad and MMC Mirpur Khas.Study duration was 7 months from September 2015 to March 2016.All the cases with age more than 25 years, both genders, after diagnosis of chronic liver disease with sign and symptoms of hepatic encephalopathy were selected in this study.All the cases on diuretic therapy, with hepatocellular carcinoma, with diabetes, hypertension (HTN), heart failure and chronic kidney disease (CKD) were excluded from the study.Detailed history, clinical examination and various routine and necessary investigations were done in all cases.After that blood sample for serum sodium level, was sent to diagnostic laboratory of the hospital.The demographic profile of the patients was noted.The severity of decrease sodium concentration was assessed as normal serum sodium [Na+] level is 135-145mmol/L and the value < 135 was labeled as low or hyponatremia.The severity of hyponatremia was categorized as: 130-135 mEqL (mild), 125-130 mEq/L (moderate) and < 125 mEq/L (severe).The hepatic encephalopathy was graded according to the West Haven classification (4 grades).Grades I-II were taken as mild to moderate encephalopathy, while grades III-IV were taken as severe encephalopathy.All the data regarding age, gender, serum sodium concentration, presence of hepatic encephalopathy were recorded.All the data were entered into SPSS 16.0 version and were analyzed by using the same software.

Results
Total number of cases was 80. Mean age was 48 + 8.5 years.Males were found in the majority as compared to females.Regarding virology status of cases, HCV patients were most common, 10 patients had HBV while 15 patients were infected by both HCV and HBV (Table 1).According to classification of hyponatremia, majority of the patients had normal level of sodium, 25% had mild, 20% had moderate while 15% patients had severe hyponatremia (Fig. 1).
On the grading of encephalopathy, mostly patients were found with grade 1 encephalopathy while 25 patients had grade 2, 15 patients had grade 3 while 10 patients hade grade 4 encephalopathy (Fig. 2).
In the results of this study serum sodium level sig-

Discussion
Hepatic encephalopathy (HE) is commonest and serious complications of cirrhosis and is also the main reason of mortality. 13Hyponatremia can induce or aggravate HE, leading to disease progression and even death. 14,15In this study total number of cases was 80. Mean age was 48 ± 8.5 years.55 (68.5%) patients were male while 25 (31.5%)patients were female.Similarly Qureshi MA et al. 16 reported that of 202 In this study 40% patients had normal level of sodium, 25% had mild, 20% had moderate while 15% patients had severe hyponatremia.As well as Sulehria SB et al. 17 reported that 129 (51.6%) patients had hyponatremia due to chronic liver disease, while 121(48.4%)had no hyponatremia.In a Korean study 18 prevalence of hyponatremia (less than serum sodium ≤ 135 mmol/L) was 47.9% in hospitalized patients.
In the results of this study decreases of serum sodium level is very important in CLD and its severity is significantly associated with severity of hepatic encephalopathy p = value 0.001.Similarly Samiullah Shaikh et al. 19 stated that the greater frequency of hyponatremia was seen in patients having hepatic encephalopathy.In another study, the severity of hyponatremia, particularly at sodium level ≤ 130 mmol/L, corresponded to increase the risks of ascites, hepatic encephalopathy and other complications of cirrhosis, as compared those with the serum sodium level ≤ 136 mmol/L. 15,20ssociation between HE and serum sodium levels may be described as; severe liver failure in cases with level of serum sodium< 130 meq/l, and these both events may be pathophysiologically associated. 21Decreased sodium level in cases having CLD, is associated with are mark able reduction of organic osmolytes in the cerebral concentration, that probably reflect compensatory osmo regulatory mechanisms against cell swelling. 22,23

Conclusion
We concluded that the hyponatremia is significantly associated with hepatic encephalopathy in patients having chronic liver disease.Therefore it is recom-mended that every patient who presents with chronic liver disease should be investigated for hyponatremia to identify patients at high risk of complications including hepatic encephalopathy.