1 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: 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%
2 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
3 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 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 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).
4 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 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 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 % % % % % % % Total % 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).
5 Table 2. Grades of Hepatic Encephalopathy (N = 200). Grade of hepatic Number of patients Percentage encephalopathy Grade I % Grade II % Grade III % Grade IV % 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 % C % None of the patients had history of alcohol intake, recent surgery or shunt procedure.
6 Fig 1. Viral status in 200 patients with hepatic encephalopathy 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.
7 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 % Upper gastrointestinal bleeding % Urinary tract infection % Spontaneous bacterial peritonitis % Hypokalemia % Diarrhea 5 1 3% Lower respiratory tract infection % Hyponatremia % Sedative intake 0 2 1% Excessive protein intake % Antituberculous therapy induced % 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 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,
8 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 Diarrhea Gastrointestinal bleed Infections Hypokalemia Hyponatremia Increase protein intake Sedative intake Miscellaneous 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
9 for health education in patients with cirrhosis regarding the risk of HE and its precipitating factors and a proper dietary advice to them. REFERENCES 1. Haussinger D, Kircheis G. Hepatic encephalopathy. Schweiz Rundsch Med Prax. 2002;91: Lizardi-Cervera J, Almeda P, Guevara L, Urabe M. Hepatic encephalopathy: a review. Ann Hepatol. 2003;2: Riordan SM, Williams R. Treatment of hepatic encephalopathy. N Engl J Med. 1997;337: Blom HJ, Ferenci P, Grimm G, Yap SH, Tangerman A. The role of methanethiol in the pathogenesis of hepatic encephalopathy. Hepatology. 1991;13: Strauss E, da Costa MF. The importance of bacterial infections as precipitating factors of chronic hepatic encephalopathy in cirrhosis. Hepatogastroenterology. 1998;45: Mahboob F. Frequency of risk factors for hepatic encephalopathy in patients of chronic liver disease. Ann King Edward Med Coll. 2003;9: Sheikh A, Ahmed SI, Naseemullah M. Aetiology of hepatic encephalopathy and importance of upper gastrointestinal bleeding
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11 14. Alam I, Razaullah, Haider I, Humayun M, Taqweem MA, Nisar M. Spectrum of precipitating factors of hepatic encephalopathy in liver cirrhosis. Pak J Med Res. 2005;44: Ahmed H, Rehman M, Saeedi MI, Shah D. Factors precipitating hepatic encephalopathy in cirrhosis liver. J Postgrad Med Inst. 2001;151: Faloon WW, Evans GL. Precipitating factors in the genesis of hepatic coma. NY State J Med. 1970;70: Shaikh MA, Shaikh WM, Solangi GA, Abro H. Frequency and transmission mode of Hepatitis C virus in Northern Sindh. J Coll Physician Surg Pak. 2003;13: Fitz JG. Hepatic encephalopathy, hepatopulmonary syndromes, hepatorenal syndrome, coagulopathy and endocrine complications of liver disease. In: Feldman M, Friedman LS, Sleisenger MH, editors. Gastrointestinal and Liver Disease. 7th ed. Philadelphia: WB Saunders; 2002; Maqsood S, Saleem A, Iqbal A, Butt JA. Precipitating factors of hepatic encephalopathy: experience at Pakistan Institute Medical Sciences Islamabad. J Ayub Med Coll Abbottabad. 2006;18:57-61.
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