Spectrum of Precipitating factors of Hepatic Encephalopathy in liver cirrhosis

Transcription

1 Pakistan J. Med. Res. Vol. 44, No. 2, 2005 Spectrum of Precipitating factors of Hepatic Encephalopathy in liver cirrhosis Intekhab Alam, Razaullah, Iqbal Haider, M Humayun, M Amjad Taqweem, Muhammad Nisar Department of Medicine, PGMI, Lady Reading Hospital, Peshawar. ABSTRACT Objectives: To ascertain the spectrum of precipitating factors of hepatic encephalopathy in patients with liver cirrhosis. Design: descriptive study. Place and duration of the study: The study was conducted in the department of medicine, medical B unit of Postgraduate Medical Institute, Lady Reading Hospital, Peshawar over six months. Patients and Procedures: All patients with cirrhosis of liver(cl) of more than 12 years of age, manifesting signs of hepatic encephalopathy (HE) were included and those who had acute fulminant hepatitis or had noncirrhotic portal hypertension were excluded from the study. Detailed history, clinical examination and thorough investigations were done to look for any precipitating factor and the findings were recorded on a proforma. Results: Fifty patients (32 males and 18 females) were enrolled. 47 patients had hepatitis B, C or both positive. 64% were in the age group of years and 76% were having either grade III or IV coma. Thirty three (66%) patients had asterixis which was found to be a sensitive index for the diagnosis of HE in patients who were not in coma. Jaundice and Ascites were other common presenting features. Electrolytes imbalance in 28(56%) patients, diarrhea in 20(40%), constipation in 16(32%), infections in 12(24%) and gastrointestinal bleed in 11(22%) patients were amongst the commonest precipitating factors. None gave the history of alcoholism or recent surgery Conclusions: Occurrence of precipitating factors for HE in patients with CL is a common phenomenon and all such patients must be hospitalized to ascertain and manage such factors. Key words: Cirrhosis liver, Hepatic Encephalopathy, Precipitating factors. ORIGINAL ARTICLE H INTRODUCTION epatic encephalopathy is a well-recognized clinical complication of cirrhosis of liver (CL) and the presence and prompt identification of well-defined precipitating factors is extremely important in diagnosis and treatment of this fatal condition. About 30% of patients with cirrhosis die in hepatic coma 1. CL is attaining epidemic proportions in Pakistan due to a very high prevalence of hepatitis B and C in our community 2,3. Hepatic Encephalopathy (HE) is a major neuropsychiatric complication of CL and it s appearance is indicative of a poor prognosis 4,5. Patients with CL may have either a chronic neuropsychiatric state due to portal-systemic shunting (portosystemic encephalopathy, PSE) or have an acute episode with some precipitating factor labeled as HE. The PSE group usually presents with personality changes and gradual intellectual deterioration and have a relatively better survival than those who develop HE acutely due to some precipitating factor (100% vs %) 6. Acutely developing HE presents with disturbed consciousness progressing through a confusional state to stupor and coma. However, the prognosis in the latter group can be improved if the precipitating factors are recognized early and managed accordingly. In patients with otherwise stable cirrhosis, hepatic encephalopathy often follows a clearly identifiable precipitating event. Perhaps the most common predisposing factor is gastrointestinal bleeding (GIB) 7, which leads to an increase in the production of ammonia and other nitrogenous substances in the gut. GIB contributes approximately gms of proteins per 100 ml of the blood and is responsible for 18-34% of cases of portosystemic encephalopathy 8. Excess dietary, especially animal protein intake 9 may also precipitate HE through the same mechanism. Other common factors are vomiting, diarrhea, over-diuresis 10 or very large paracentesis 11. They not only lead to hemodynamic disturbances like hypovolemia and shock resulting in impaired renal, hepatic and cerebral blood flow 12 but also lead to electrolytes imbalance leading to Hypokalemic alkalosis and hypoxia. Hypovolemia and shock often lead to hepatorenal syndrome and azotemia that may precipitate or aggravate HE 10. Systemic alkalosis causes Pak J Med Res 96

2 an increase in the amount of nonionic ammonia (NH3) relative to ammonium ions (NH4+). Only nonionic ammonia readily crosses the blood-brain barrier and accumulates in the central nervous system. Hypokalemia also directly stimulates renal ammonia production. Drugs like narcotics, tranquilizers, sedatives and diuretics can also cause hepatic encephalopathy 13,14. Various infections such as urinary tract, chest and spontaneous bacterial peritonitis are frequent causes of morbidity in cirrhosis, including the development of HE 15. Moreover constipation, surgery and super imposed acute liver disease may also lead to the onset of HE 6. In the management of patients with CL and HE it is prudent to stage the overt encephalopathy into grades that range from grade I to IV 16 and then try to identify and treat the precipitating factors. In the presence of the latter the neurological deficits are usually completely reversible upon their correction 17 and the prognosis is better if the precipitant can be treated, for instance, infection, diuretic overdose or hemorrhage. These patients usually come back with hepatic encephalopathy due to lack of counseling to the patients and their attendants regarding these precipitating factors by their attending physicians. This study was carried out with the main objective of ascertaining the most common precipitating factor and their frequency in a group of patients presenting with hepatic encephalopathy in diagnosed cases of cirrhosis liver of any etiology. Another objective was to see the constellation of presenting clinical features in such cases. PATIENTS AND PROCEDURES This was a hospital based descriptive study. All patients with cirrhosis of liver, manifesting signs of hepatic encephalopathy were hospitalized in medical B unit of Lady Reading Hospital, Peshawar. All patients who were more than 12 years of age were included and those who had acute fulminant hepatitis or had noncirrhotic portal hypertension were excluded from the study. Past medical record, clinical signs of CL and an unequivocal ultrasonography report favoring the diagnosis of CL were relied for the diagnosis of CL. Data collection and analysis A questionnaire was designed and used for data collection. A detailed clinical history of the patients was taken regarding their present and past illness, specifically enquiring about fever, GI bleeding including hematemesis and malena, constipation, high protein diet and any surgery. Detailed drugs history especially about the use of diuretics, sedatives, nonsteroidal anti-inflammatory drugs and cough syrups was taken. Past history of jaundice, bleeding, edema and encephalopathy was also taken. Patients were examined with special attention to jaundice, anemia, fever, fetor hepaticus and asterixis. Hemodynamic status with signs of dehydration was also noted. Peripheral edema and degree of ascites (if present) was recorded and encephalopathy was graded according to the following criteria. Table 1. Table 1: Grades of hepatic encephalopathy. Grade Mental St a t u s Asterixis I Euphoric or depression, mild confusion, slurred speech, disordered sleep + / II Lethargy, moderate confusion + III IV Marked confusion, incoherent speech, sleeping but arousable Coma, initially responsive to noxious stimuli, later unresponsive All relevant investigations including full blood count, Urine microscopy, serum electrolytes, blood urea and serum creatinine, blood glucose and a chest radiograph were done. Serum bilirubin, Alanine Aminotransferase (ALT) levels, Serum Albumin and Prothrombin time were also done to help assess their Child-Pugh score. Table 2. Table 2: Child Pugh scoring chart. ASCITES Parameter ENCEPHALOPATHY Numerical score None None BILIRUBIN (mg/dl) < 2.0 mg/dl ALBUMIN (gm/dl) PROTHROMBIN TIME (seconds increased) > 3.5 gm/dl Slight Slight to Moderate + Moderate to severe Moderate to severe 2-3 mg/dl > 3.0 mg/dl 2.8-3,5 gm/dl < 2.8 gm/dl >6 Total numerical score Child-Pugh Class 5-6 A 7-9 B C An abdominal ultrasound was done in all cases for liver size, parenchymal echogenicity, portal vein Vol 44, No. 2,

3 diameter, spleen size and for the detection of ascites. In the presence of ascites a diagnostic ascitic tap was also done to look for any evidence of spontaneous bacterial peritonitis. RESULTS A total of 50 patients, 32 (64%) male and 18(36%) female patients with CL suffering from HE were studied for different precipitating factors. The patients represented from all parts of NWFP. Fifteen (30%) patients were Afghan refugees. Majority of the patients (64%) were in the age group of years. Only 1 patient was below the age of 20 years. Fourteen (28%) patients were HBsAg positive, 24(48%) were HCV antibodies positive, 9(18%) were both B&C positive, while 3 (6%) patients were both B&C negative. Fourty (80%) patients presented with marked confusion, disorientation and coma and the remaining 10 were diagnosed on the basis of the presence of Asterixis alone. When they were classified according to the grades of encephalopathy Thirty-three (66%) patients, who were not in coma, had asterixis. Overall 45(90%) patients had icterus All those (29 patients) who had grade III or IV HE were icteric, while 38(76%) also had moderate to massive ascites, however peripheral edema was positive in 28(56%) cases. Low-grade fever (up to 100 o F) was present only in 10(20%) patients, while the rest of the patients were a febrile. Splenomegaly was found in 40(80%) cases. Grade IV, 17 (34%) Grade I, 12 (24%) There was hyponatremia (serum Na + concentration <130meq/L) in 19(38%) and hypokalemia (serum K + <3.5meq/L) in 9(18%) patients. Amongst other precipitating factors Infection in 12(24%), high protein diet in 2(4%), therapeutic paracentesis in 2(4%) and bromazepam intake in one patient were also presumed precipitating factors. Amongst the infections, spontaneous bacterial peritonitis (SBP) was found in 8(16%) patients, urinary tract infection (UTI) in 2(4%) patients while another 2(4%) patients had lobar pneumonia and septicemia. None of the patient had history of alcohol or any recent surgery or shunt procedure. Table 3. Table 3: Frequency of precipitating factors. Precipitating factor n(50) %age Diarrhea Hyponatremia Constipation Infections GIB Hypokalemia 9 18 Miscellaneous 6 12 Clotting abnormalities was quite common in 34 patients having a PT of >4 seconds difference. Thirty patients had serum albumin of < 3 and using these parameters the whole group of 50 patients were scored on Child-Pugh scoring system as follows: Table 4. Table 4: Frequency of child-pugh score. Child-Pugh Class n(50) percentage numerical score A None B C DISCUSSION Grade III, 12 (24%) Grade II, 9 (18%) Grade I Grade II Grade III Grade IV Figure 1: Classification of patients according to the grades of encephalopathy. Thirty-six (72%) patients had some bowel disturbance [20(40%) had diarrhea and/or vomiting while 16(32%) had constipation]. Eleven (22%) presented with gastrointestinal bleed and all were shown to be bleeding from esophageal varices on upper GI endoscopy. In majority of the patients with HE, a clearly defined precipitating factor usually is identified, and the reversal or control of these factors is a key step in the management. In our study that was conducted on 50 patients of CL presenting with HE, all possible important factors which could be responsible for precipitation or aggravation of HE were looked for and analyzed. Males (64%) outnumbered the female patients (36%), with majority of the patients (64%) in their 3 rd or 4 th decade of life. This tendency is similar to that reported by others where males are 6 times more prone to develop and suffer from liver disease.. On the other hand in the western world alcoholism is the main cause of CL where there is definite male preponderance to the extent of 77:33, making it the fourth commonest cause of death in males in USA 19. Pak J Med Res 98

4 This is in spite of the fact that females are more prone to develop alcoholic liver disease 20. Observations may just be a manifestation of the gender bias in our society where males are given preference over females for therapy and hospitalization 21. As far as the frequency of HCV is concerned, our findings are in conformation with other studies, which also emphasize the fact that HCV is a rapidly growing problem and has already overtaken HBV in the etiogenesis of CL in Pakistan 22. Amongst the clinical features, jaundice in 90%, altered conscious state (ranging from confusion to coma) in 80%, splenomegaly in 80%, and Ascites in 76% were the most common presenting features in our patients with HE. Congregation of all these bad prognostic signs is of no surprise if the decompensated nature of the CL of these selected patients is taken into account. The latter fact can be confirmed Child-Pugh score of our patients, 35(70%) of whom were in Child-Pugh Class C and the remaining were in class B. Similarly majority of our patients had higher grades of encephalopathy with 17(34%) in grade IV, 12(24%) in grade III, 9(18%) in grade II while 12(24%) had grade I HE. Table 5: Comparison of the frequency of different precipitating factors. Shaikh S 21 Hameed 24 Souheil 36 (n-100) Aisha 25 (n=100) Conn 27 (n=100) Faloon 28 (n=39) Present study GIB CONS DIAR INFEC K + N + EDP 56% 52% 12% 15% 70% 28% - 56% 52% 22% 28% 68% 28% 52% 18% 3% - 3% 11% - 9% 76% 36% - 52% % 3% - 4% 9% - 9% 33% 6% % % 32% 40% 24% 18% 38% 4% Electrolyte imbalance, which also correlates with the severity of the liver disease 23 was found in 28 (56%) patients and may be considered, as discussed above, not only a precipitant but also a manifestation of advance nature of cirrhosis in our patients. Among them, 19(38%) patients had hyponatremia while 9 (18%) had hypokalemia. All of them were on diuretics and 20 of them also had associated diarrhea and/or vomiting and two of them had also undergone therapeutic paracentesis. All these factors are known to lead to electrolyte imbalance in patients with CL and caution must be exercised while putting these patients on diuretics and while managing these patients with gastroenteritis by checking their serum electrolytes frequently and to manage them accordingly. Similar conclusion was made by Hameed et al 24 in a study which was conducted in the same center in a different unit. On the other hand GIB and infections remained the most common precipitating factors in other studies conducted in the province of Punjab 25. For a comparison of the frequency of different precipitating factors in different national and international studies is given in the following Table 5: As shown in the Table GIB, GI disturbances especially constipation and infections stand out as the most common precipitant of HE in almost all the studies. Comparatively the frequency of GIB is lower in our patients than in studies conducted elsewhere in Pakistan. Still, it consistently poses a substantial risk to cirrhotic patients as a precipitant for HE. We think that more and more endoscopy facilities should be available nationwide for prompt contol of GIB. GI upset and rate of infections are less frequent in the series of patients studied in Ibadan, Nigeria 26 by Souheil and in western studies done by Conn 27 and Faloon 28. This may be the reflection of good nutritional status and hygienic conditions of their patients as compared to our patients. In our study patients are usually severely malnourished not only because of the disease but also because of food faddism and taboos regarding their diet in our society. Because of the latter, we have seen that not only their friends and relatives but also illinformed doctors and practitioners impose strict dietary restrictions on these patients that leads to anorexia and malnutrition which also lowers down their immunity making them more susceptible to infections. Constipation probably is also the result of lack of consistent use of lactulose by our patients, which may be because it is costly or that patients do not find it a good laxative. There is a definite need for health education in patients who are diagnosed as a patient of cirrhosis liver regarding the risk of HE and its precipitating factors and a constant need and effort to avert them at all costs. Proper dietary advice must be an integral part of all counseling protocols to chronic liver disease patients. REFERENCES 1. 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