Original Article Precipitating Factors of Hepatic Encephalopathy Mohammad Tariq,* Saleem Iqbal,** Naji ullah Khan,* Rabia Basri*** From Department of Medicine, Khyber Teaching Hospital, Peshawar. *Post Graduate Trainee, **Senior Registrar, *Post Graduate Trainee, ***House Officer Correspondence: Received: Accepted: Dr. Mohammad Tariq, Medical B Unit, Khyber Teaching Hospital Peshawar, Pakistan. Mob: 0334-9171135 Email: drtariqkhattak@yahoo.com ABSTRACT Objective: To analyze the precipitating factors of hepatic encephalopathy (HE). Methods: Two hundred admitted patients with liver cirrhosis with HE from 1 st January 2006 to 30 th September 2006 were included in the study. Grades of HE and Child s Pugh classification was also determined. Results: Out of 200 patients, 106 (53%) were male and 94 (47%) female. Amongst the precipitating factors, 30% had constipation, 29% upper gastrointestinal bleed (GIB), 8% spontaneous bacterial peritonitis (SBP), 19.5% urinary tract infection (UTI), 2.5% lower respiratory tract infection and 3% had diarrhea. There was hyponatremia in 1.5% and hypokalemia in 4.5% patients. High protein diet in 0.5% and bromazepam intake in 1%
were presumed precipitating factors and 0.5% had antituberculous therapy induced liver injury. Conclusion: Constipation, gastrointestinal bleeding and infections were the most common precipitating factors of HE in our patients. (Rawal Med J 2009;34:95-97). Key Words: Hepatic Encephalopathy, liver cirrhosis, precipitating factors, portosystemic encephalopathy. INTRODUCTION Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, which develops due to acute or chronic liver diseases. It is functional in nature and potentially reversible and symptoms range from subtle personality changes to deep coma. 1 Diminished hepatic reserve results in impaired ability of liver to detoxify toxins that are absorbed from the bowel. 2 Accumulation of ammonia, predominantly as a result of poor hepatic function and portosystemic shunting, has traditionally been considered to have an important role in the pathogenesis of HE. 3 The level of ammonia in the arterial blood, however, is poorly correlated with the grade of HE. 4 Most episodes of HE in patients with cirrhosis are due to clinically apparent precipitating factors or the spontaneous development of portosystemic shunting. 3 These factors could be determined in 75.4% of chronic and 97.3% episodes of acute HE. 5 The frequency of risk factors for the
development of HE in patients with chronic liver disease was 47% due to infections, 30% due to GIT bleeding, 19% due to constipation, and 4% due to miscellaneous factors. 6 The overall in-hospital mortality was 29% 7 and mean time to come out of HE was 41.38 hours. 8 HE has been classified into four grades that range from grade I to IV 9 and identification of precipitating factors is helpful, as the neurological deficits are usually completely reversible upon their correction. 10 The aim of this study was to determine the frequency of precipitating factors for the development of HE in patients admitted with liver cirrhosis at our institution. PATIENTS AND METHODS We conducted a descriptive, cross sectional, prospective, single center study on 200 consecutive patients of HE admitted to the medical units of Khyber Teaching Hospital, Peshawar from 1 st January 2006 to September 2006. All patients who were 15 years or above in age with HE and liver cirrhosis were included. A detailed clinical history and meticulous physical examination of every patient was done. Diagnosis of HE was made on clinical basis. All relevant investigations including full blood count, urine microscopy, serum electrolytes, blood urea, serum creatinine, blood glucose, sonography and a chest radiograph were done. In the presence of ascites a diagnostic ascitic tap was also done to look for any evidence of spontaneous bacterial peritonitis (SBP).
Serum bilirubin, Alanine Aminotransferase (ALT) levels, serum albumin and prothrombin time were also done to help assess their Child-Pugh score. All patients were followed for the duration of their stay in hospital. Data were analyzed using SPSS version 11.0. RESULTS Out of 200 patients, 106 (53%) were males and 94 (47%) were females. Majority of the patients (67%) were in the age group of 41-50 years. Only one (0.5%) was below the age of 20 years (Table 1). Table 1. Age-wise distribution of 200 patients with HE. Age (years) Number of patients Percentage 11-20 1 0.5% 21-30 11 5.5% 31-40 15 7.5% 41-50 67 33.5% 51-60 63 31.5% 61-70 40 20% 71-80 3 1.5% Total 200 100.0% Large percentage had hepatitis C (Fig 1) and majority was in grade I and II HE (Table 2). All patients belonged to Child-Pugh class-b and C (Table 3).
Table 2. Grades of Hepatic Encephalopathy (N = 200). Grade of hepatic Number of patients Percentage encephalopathy Grade I 58 29.0% Grade II 83 41.5% Grade III 38 19.0% Grade IV 21 10.5% Amongst the precipitating factors, constipation, gastrointestinal bleed (GIB) and infections were most commonly encountered (Table 4). Table 3. Child-pugh class of Hepatic Encephalopathy (N = 200). Child-Pugh class Number of patients Percentage A 0 0 B 67 33.5% C 133 66.5% None of the patients had history of alcohol intake, recent surgery or shunt procedure.
Fig 1. Viral status in 200 patients with hepatic encephalopathy. 100 80 60 40 20 Percent 0 Hepatitis B Virus+ Both B&C Positive Both B&C Negative Hepatitis C Virus+ Viral status Out of these 200 patients, 180 (90%) patients recovered from encephalopathy, six (3%) patients left against medical advice (LAMA) and 14 (7%) patients expired.
Table 4. Precipitating factors in 200 patients of Hepatic Encephalopathy and gender of patients (N = 200). Precipitating factor of hepatic encephalopathy Gender of the patients Percent of total patients P value Number of Number of females males Constipation 34 26 30% 0.589 Upper gastrointestinal bleeding 17 41 29% 0.035 Urinary tract infection 19 20 19.5% 0.000 Spontaneous bacterial peritonitis 10 6 8% 0.050 Hypokalemia 4 5 4.5% 0.000 Diarrhea 5 1 3% 0.000 Lower respiratory tract infection 1 4 2.5% 0.000 Hyponatremia 3 0 1.5% 0.000 Sedative intake 0 2 1% 0.286 Excessive protein intake 0 1 0.5% 0.000 Antituberculous therapy induced 1 0 0.5% 0.000 DISCUSSION Cirrhosis of liver is one of the common causes of morbidity and mortality world over. 11 HE is a major neuropsychiatric complication of cirrhosis and it s appearance is indicative of a poor prognosis, 12,13 as HE is the commonest cause of death in patients with liver cirrhosis. 14 A clearly defined precipitating factor is usually identified in most patients with HE, and the reversal or control of these factors is a key step in the management. 15 Our study had more male patients with majority of those 40-60 years old, as reported earlier. Constipation was the commonest factor responsible for 30% cases of HE in our patients, which is close to earlier published studies. 8,15 Constipation probably is the result of lack of consistent use of lactulose by our patients,
he. Precipitating factor of HE which may be because of its cost or patients did not find it a good laxative. Infections like SBP, urinary tract infection and lower respiratory tract infection were the 2 nd most common factor present in 30% of cases, as shown to be 28% in another study. 16 GIB was the third most important factor and was found in 29% of patients in our study, which is similar to 30% 6 and 33% 17 reported earlier. This study correlates well to the available national and international data (Table 5). Table 5. Comparison of frequency of different precipitating factors of Shaikh 18 Ahmed 16 Conn 9 Faloon 17 Alam 15 Mahboob 6 Present Study Constipation 52 52 3 6 32 19 30 Diarrhea 12 22 - - 40 5 3 Gastrointestinal 56 56 18 33 22 30 29 bleed Infections 15 28 4-24 47 30 Hypokalemia 70 68 9 18 18-4.5 Hyponatremia 28 28-36 - 1.5 Increase protein - 52 9-4 1 0.5 intake Sedative intake - - - - - 2 1 Miscellaneous - - - - - 4 0.5 Figures are percentages. Electrolyte imbalance was found in 12 (6%) patients, consistent with study of Conn et al 9 who reported it in 9%. We found diarrhea in 6 (3%), high protein intake in 1 (0.5%) and sedative intake in 2 (1%) patients, which are similar to studies reported already. 6,9 In conclusion, constipation, gastrointestinal bleeding and infections stand out as the most common precipitating factors of HE in almost all the studies. There is a definite need
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