| Abstract|| |
Background/Aim: Hepatic encephalopathy (HE) is a frequent complication of liver cirrhosis, and its development heralds a poor prognosis as it is associated with shortened patients' survival. Reversibility of the precipitating factors of HE is of prognostic significance. This work was designed to study the precipitating factors of HE in patients with liver cirrhosis at Mansoura Specialized Medical Hospital, Egypt. Materials and Methods: A total of 237 consecutive known chronic liver disease patients, presented with signs and symptoms of hepatic encephalopathy, were admitted in the hepatology unit of Mansoura Specialized Medical Hospital from September 2009 to September 2010. The precipitating factors of hepatic encephalopathy were identified with the aid of clinical examination and appropriate investigations. Grades of HE and Child-Pugh scores were determined. Results: The precipitating factors of HE in our studied cases were upper GI bleeding in 87 patients (36.7%), advanced HCC in 43 patients (18.14%), infections in 37 patients (15.61%), excess protein intake in 27 patients (11.39%), electrolyte imbalance in 7 patients (2.95%), and altered bowel habits in 33 patients (13.92%). Males were commonly affected by HCC (P < 0.05) and upper GI bleeding more than female patients (P < 0.05). Male patients were commonly presented with HE (63.29%), and this gender difference reached a statistical significance among those presented with upper GI bleeding (P < 0.05) and HCC (P < 0.05). Upper GI bleeding, advanced HCC, and infections were the leading causes of death with a higher prevalence in grade IV comatose (P < 0.05), child C (P < 0.05), male patients (P < 0.05). Conclusions: Our data revealed that upper GI bleeding, advanced HCC, and infections are the main precipitating factors of HE as well as the major leading causes of death in patients with liver cirrhosis. Priority should be given to control these factors by allocation of the hospital funds, medications, and human efforts. Implementation of an effective screening program for early HCC detection all over the country should be on the top of the official health concerns.
Keywords: Hepatic encephalopathy, liver cirrhosis, precipitating factors
|How to cite this article:|
Gad YZ. Precipitating factors of hepatic encephalopathy: An experience at Mansoura Specialized Medical Hospital, Egypt. Ann Trop Med Public Health 2012;5:330-4
|How to cite this URL:|
Gad YZ. Precipitating factors of hepatic encephalopathy: An experience at Mansoura Specialized Medical Hospital, Egypt. Ann Trop Med Public Health [serial online] 2012 [cited 2020 Feb 19];5:330-4. Available from: http://www.atmph.org/text.asp?2012/5/4/330/102044
| Introduction|| |
He may be defined as an alteration of the central nervous system function because of hepatic insufficiency, in the absence of other neurological disorders.  HE continues to be a major clinical problem and may develop either due to acute liver failure or due to a precipitant in a cirrhotic patient, or it could happen as a result of prolonged portosystemic shunting.  In acute liver failure, patients succumb to a neurologic death, with brain edema and intracranial hypertension.  Survival of patients with portosystemic encephalopathy is better than those developing HE acutely in cirrhotic patients (100% vs. 70%).  Further improvement of prognosis would be achieved by an early recognition and management of precipitating factors. 
Commonly recognized precipitating factors include gastrointestinal bleeding, infection, azotaemia, constipation, electrolyte imbalance,  and high protein diet.
Usage of drugs as sedatives,  tranquilizers, analgesics and diuretics, fulminant hepatic injury, and large volume paracentesis have been all considered to precipitate encephalopathy in an otherwise stable cirrhotic patient. Depressed cerebral function due to hepatic failure of clearance of gut-derived substances is probably an accepted explanation.  However, the exact pathogenic mechanism involved is still unknown.
| Aim of the Study|| |
A trial to study the precipitating factors of HE in patients with liver cirrhosis during the study period at an Egyptian medical center.
| Materials and Methods|| |
A total of 237 consecutive known chronic liver disease patients, presented with signs and symptoms of hepatic encephalopathy, were admitted in the hepatology unit of Mansoura Specialized Medical Hospital from September 2009 to September 2010.
A detailed clinical history of each patient was taken from a close accompanying relative regarding the present and the past illnesses with a special stress on gastrointestinal bleeding, fever, constipation, high protein diet, recent trauma, surgery, or abdominal paracentesis. Questions were asked about recent intake of alcohol, sedatives, tranquilizers, analgesics, or cough mixtures.
All included patients had no history of alcohol intake, with negative HIV serology, and no suspected cerebro-vascular accidents on initial evaluation.
Exclusion criteria: 1 - Patients with intracranial lesions such as subdural hematoma, cerebral hemorrhage, cerebral infarction, brain abscess, meningitis, or encephalitis. 2- Patients with hypoxia, hypercarbia, uremia, ketoacidosis, fulminant hepatic failure, neuropsychiatric disorders, and post-seizure encephalopathy were also excluded.
The diagnosis of liver cirrhosis was based on clinical, biochemical, ultrasonographic, or liver histological data obtained from the in-hospital patients' data records.
All patients were carefully examined with special stress on the presence of jaundice, spider naevi, parotid enlargement, anemia, ascites, flapping tremors, lower limb edema, and gynecomastia. Encephalopathy was graded according to the clinical criteria given in [Table 1].
The traditional laboratory investigations were carried out for each patient including liver function tests, renal function tests, full blood count, serum electrolytes, random blood glucose, complete urine analysis, and the coagulation profile.
An admission chest radiography and abdominal ultrasonography, to assess liver, splenic size and echogenicity, and portal vein diameter were performed. A guided diagnostic tap was performed for ascites, if present.
Child's score for each patient was assessed according to the Child-Pugh scoring criteria as shown in [Table 2].
Chi-square test was used to assess differences among the studied groups. P < 0.05 was considered to be statistically significant. Statistical analyzes were made using SPSS 15.0 (SPSS, Chicago, IL, USA).
| Results|| |
This observational, cross-sectional study was conducted on 237 consecutive patients with liver cirrhosis presented with signs and symptoms of hepatic encephalopathy in the hepatology unit at Mansoura Specialized Medical Hospital. All patients (150 males and 87 females) were above 18 years with an age range (22-77 years), no history of alcohol intake, with negative HIV serology, and no cerebro-vascular lesions or other incriminated metabolic derangements.
The etiology of liver cirrhosis in the studied patients was post-hepatitis C in 135 cases (61.03%), post-hepatitis B in 57 cases (22.07%), cryptogenic in 35 cases (14.28%), autoimmune hepatitis (AIH) in 7 cases (1.29%), primary biliary cirrhosis (PBC) in 3 cases only (1.29%) as shown in [Table 3].
The precipitating factors of HE in our studied cases were upper GI bleeding in 87 patients (36.7%), advanced HCC in 43 patients (18.14%), infections in 37 patients (15.61%), excess protein intake in 27 patients (11.39%), electrolyte imbalance in 7 patients (2.95%), and altered bowel habits in 33 patients (13.92%). Males were commonly affected by HCC (P < 0.05) and upper GI bleeding more than female patients (P < 0.05) as shown in [Table 4].
|Table 4: The precipitating factors of hepatic encephalopathy in relation to the gender of the studied cases|
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Male patients were commonly presented with HE (63.29%), and this gender difference reached a statistical significance among those presented with upper GI bleeding (P - value < 0.05) and HCC (P -value < 0.05). 20-40 years-age group was the most commonly affected group (44.3%) and male patients constitute (61.9%) of this age group as shown in [Table 5].
|Table 5: Age and gender distribution in patients presented with different grades of hepatic encephalopathy|
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Child C patients constituted the majority (64.97%) of the whole admitted patients, and most of them were males (57.14%) while Child B and Child A patients constituted (42.19%, 5.06%, respectively) of all patients as shown in [Table 6].
|Table 6: Age and gender distribution in patients with hepatic encephalopathy relation to child's class|
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Upper GI bleeding, advanced HCC, and infections were the leading causes of death with a higher prevalence in grade IV comatose (P - value < 0.05), Child C (P - value < 0.05), male patients (P - value < 0.05) as shown in [Table 7].
|Table 7: Patients' Mortality in relation to the Child-Pugh score and grade of hepatic encephalopathy|
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| Discussion|| |
In developing countries, the number of patients with chronic endemic diseases, especially liver diseases, is progressively increasing because of inadequate education, poverty, and poor hygienic conditions. In medical wards, many patients with complicated liver cirrhosis are encountered daily in clinical practice.
Liver cirrhosis is one of the most common causes of morbidity and mortality all over the world.  HE is a major neuropsychiatric complication of cirrhosis, and its appearance is indicative of poor prognosis. , A well-defined precipitating factor is usually identified in most of patients with HE, and control of these factors is a key step in overall management. 
Earlier studies in developing countries found upper gastrointestinal (GI) bleeding to the most common precipitant for HE in 56%, 67% in their series , while others found this precipitant in only 33% of cases. ,
In this work, upper GI bleeding was the most common identified precipitating factor of HE in 36.7 of cases. Increased ammonia production by the gut urease-forming bacteria and/or reduced hepatic perfusion would explain the occurrence of HE in gut bleeders. Prophylactic use of B-blockers and nitrates for non-bleeders, along with implementation of the available endoscopic facilities for variceal eradication, are strongly advised for variceal bleeders.
Hepatocelullar carcinoama (HCC) was the second common precipitant of HE in this study (18.14%); a serious data necessitating a second look regarding the efficiency of the screening program of early HCC detection in our locality. Unavailable equipments, resources, and costs at the primary care centers are responsible in part. Inadequate knowledge motivations to reach screening facilities at the widespread tertiary health care centers are considered also.
In eastern series, infections come in the second place as an important HE precipitant.  While in the West, infections were blamed in 3%-4% in cases only. 
In this work, frequency of infections (15.61%), like spontaneous bacterial peritonitis, upper and lower respiratory tract infections, may probably reflect the hygienic, nutritional, and the immune status of the studied cases. Thus, magnifying the role of the caring physicians, especially in primary health care centers, in filling these observed patients' health status gaps.
Other gut-related disturbances like constipation [22 patients (9.28%)] and diarrhea [11 patients (4.64%)] are implicated as HE precipitants in this study. Constipation probably results from lack of adherence to lactulose prescriptions due its cost or intolerance to its side effects. Its overdose or patient to patient variation in response, may lead to diarrhea. Judicious use of prescribed laxatives prevents constipation and may probably nullify the issue of excess protein intake as a significant cause of HE precipitation in this study [27 patients (11.39%)], in addition to strict adherence to health education regulations of course.
Electrolyte imbalance is a considerable precipitating factor of HE in our study [7 patients (2.95%)]. Most of involved cases were Child C and received diuretics to control their fluid overload state. Dilutional hyponatremia is a feature of advanced Child C cases. Findings of anemia, thrombocytopenia, and hypoalbuminemia correspond well with advanced stage of cirrhosis.  Vomiting and/ or diarrhea may be associated. Here, regular checking of serum electrolytes, for further management accordingly, is considered.
In this work, male patients (63.29%) suffered form HE, and this gender difference was a statistical significant among those presented with upper GI bleeding (P < 0.05) and HCC (P < 0.05). Western studies stated that males are more prone to develop liver disease where alcoholism is the main cause, making alcoholic liver disease is the fourth common leading cause of death in USA.  Eastern studies suggest that male predominance may be a manifestation of gender bias in their society where males are given preference over females for therapy and hospitalization.  Our results would be explained by the fact that females seek medical care, at an earlier stage of liver disease, in our society and males become more affected by complicated cirrhosis. In this work, most of the studied patients (81.01%) were of viral origin and, an HCV infection (56.96%) is the main inciting viral agent. This finding is supported by studies confirming that HCV is a rapidly growing problem and has already undertaken HBV in the etiogenesis of liver disease. 
In this work, the mortality rate in our studied cases was 32.48%, which is close to that reported in other series.  Upper GI bleeding, advanced HCC, and infections were the main causes of death with a higher prevalence in grade IV comatose (P < 0.05), Child C (P < 0.05), and male patients (P < 0.05) with liver cirrhosis.
| Conclusion|| |
Our data revealed that upper GI bleeding, advanced HCC, and infections are the main precipitating factors of HE as well as the major leading causes of death in patients with liver cirrhosis. Priority should be given to control these factors by allocation of the hospital funds, medications, and human efforts. Implementation of an effective screening program for early HCC detection all over the country should be on the top of the official health concerns. Early identification and management of interferon-treatable HCV+ve candidates would be of value in this respect.
| Acknowledgements|| |
Special thanks to professor: Fardous A. Ramadan; professor of internal medicine, Mansoura Specialized Medical Hospital, Mansoura Faculty of Medicine, Mansoura, Egypt, for her critical advice and support.
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Yahia Z Gad
Assistant Professor of Internal Medicine, Mansoura Specialized Medical Hospital, Mansoura University, Mansoura
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]