|Year : 2019 | Volume
| Issue : 3 | Page : 130-136
Clinical Profile of Patients with Hepatic Encephalopathy in Cirrhosis of Liver
Shilpa Bawankule1, Sunil Kumar1, Abhay Gaidhane2, Mahalaque Quazi3, Aman Pratap Singh1
1 Department of Medicine, JNMC, Wardha, Maharashtra, India
2 Department of Community Medicine, JNMC, Wardha, Maharashtra, India
3 Department of Physiology, JNMC, Wardha, Maharashtra, India
|Date of Submission||05-Jun-2019|
|Date of Decision||15-Jul-2019|
|Date of Acceptance||30-Jul-2019|
|Date of Web Publication||2-May-2020|
Dr. Aman Pratap Singh
Room No. T11, Raghobaji Boys Hostel, AVBRH, Sawangi (M), Wardha, Maharashtra
Source of Support: None, Conflict of Interest: None
Backgroud: Hepatic encephalopathy (HE) is defined as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction, after exclusion of other known causes of brain disease. In India hepatic encephalopathy is considered as indicator of poor prognosis in patients of cirrhosis of liver with 1 year survival in just 42% patients and 3 year survival in 23% of patients. Aim and Objective: Study clinical profile for adverse outcome in patients of hepatic encephalopathy due to cirrhosis of liver. Methods and Methodology: This was a cohort type of study done for a period of 2 years from September 2016 to September 2018 on a study population of 130 patients. Cirrhosis of liver was confirmed by ultrasound of liver. Results: Study included 130 patients of HE secondary to cirrhosis of liver, 82% were males, 44% and 45 % of patients were in grade 2 and grade 3 of West Haven criteria respectively. Icterus, ascites and asterexis were present in almost 65% patients. Cirrhosis was associated with alcohol dependence among 75% of patients followed by NAFLD in 6.15% of patients. Other unknown causes were among 19(14.62%) patients. In our study lactulose was found as the leading treatment modality in 73.84% of patients. Conclusion: Most of the patients were in grade III of HE, alcohol was the most common etiology of cirrhosis, icterus was the most common sign of liver cell failure, most common drug used was lactulose.
Keywords: Alcohol dependence, cirrhosis of liver, hepatic encephalopathy, lactulose, nonalcoholic fatty liver disease
|How to cite this article:|
Bawankule S, Kumar S, Gaidhane A, Quazi M, Singh AP. Clinical Profile of Patients with Hepatic Encephalopathy in Cirrhosis of Liver. J Datta Meghe Inst Med Sci Univ 2019;14:130-6
|How to cite this URL:|
Bawankule S, Kumar S, Gaidhane A, Quazi M, Singh AP. Clinical Profile of Patients with Hepatic Encephalopathy in Cirrhosis of Liver. J Datta Meghe Inst Med Sci Univ [serial online] 2019 [cited 2020 Nov 28];14:130-6. Available from: http://www.journaldmims.com/text.asp?2019/14/3/130/283605
| Introduction|| |
Hepatic encephalopathy (HE) describes a wide range of neuropsychiatric abnormalities which are the result of hepatic insufficiency or portosystemic shunting. HE can be broadly classified into overt HE (in which neurologic and neuropsychiatric abnormalities are detected using bedside examinations and bedside tests) or minimal HE (where mental status is normal and neurologic examination is normal in conjunction with abnormalities on psychometric testing).,,
Overt HE will occur in 30%–40% of patients suffering from cirrhosis of liver, and incidence rate of HE is as high as 30%–50% in patients who undergo transjugular intrahepatic portosystemic shunting (TIPS), whereas 60% of patients suffering from cirrhosis are likely to develop minimal HE., Very poor prognosis and reduced survival are the two basic outcomes after the onset of HE in patients of cirrhosis of liver.
Although some of the precise details about the cause of HE remains unknown, a general consensus has been achieved regarding raised levels of ammonia and its central role in the disease by acting as a neurotoxin that results in astrocyte swelling.
Cirrhosis and chronic liver disease were found to be the 10th leading cause of death for men and the 12th for women in the United States in 2001, killing about 27,000 people each year. In India, in patients with cirrhosis, HE is often considered an indicator of poor prognosis, with 1- and 3-year survival after its first occurrence being 42% and 23%, respectively, in the absence of liver transplantation. Furthermore, the cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity are very high.
Moreover, the etiology of cirrhosis of liver and precipitating factors of HE is by far not very well-documented in the literature currently available for central India.
The aim of this study is to determine the clinical profile and risk factors for adverse outcome in patients of HE due to cirrhosis of liver.
Objectives were to study the severity and precipitating factors of HE in patients with cirrhosis of liver, to study association of prognostic indicators (CTP score and MELD score) and mortality and morbidity among patients with HE in cirrhosis of liver at 90 days, to study etiology of cirrhosis of liver, to find out risk factors associated with adverse outcome in patients of HE due to cirrhosis of liver, to identify the treatment protocol in patients with HE in cirrhosis of liver.
| Methodology|| |
All patients of cirrhosis of liver admitted in medicine ward and intensive care unit (ICU) of Acharya Vinoba Bhave Rural Hospital Sawangi (Meghe) were considered for the study. This was a cohort type of study. The study was conducted for 2 years from September 2016 to September 2018. Inclusion criteria for the study were the persons who have been diagnosed with cirrhosis of liver (confirmed by ULTRASOUND).
Patients showing any one signs of HE such as:
- Flapping tremors (tremor of the hand when the wrist is extended called asterixis) or abnormal movements
- Drowsiness or severe confusion
- Strange behavior or severe personality changes
- Slowed or sluggish movement
- Coma: unconscious and unresponsive.
Exclusion criteria for the study was setup which included the patients who presented with acute fulminant hepatitis and noncirrhotic portal hypertension/TIPS or surgical portosystemic shunts, patients who had central nervous system manifestations (e.g., prior cerebrovascular event and dementia) or intake of toxins (e.g., benzodiazepines) that would make the neurological examination difficult, and patients who had terminal disease (e.g., advanced hepatocarcinoma).
A structured questionnaire was used for data collection like name, age, sex, hospital registration no, address and occupation. Detailed history of patients alcohol intoxication assessed by CAGE scoring, hepatitis B and hepatitis C examination was done, where viral etiology was considered superior to the history of alcohol due to its severity, patients were evaluated according to the West Haven criteria, they were also examined for signs of liver cell failure, laboratory investigations including liver and kidney function tests, coagulation profile, and serum ammonia and finally treatment protocol of these patients were documented.
- Cirrhosis: cirrhosis of liver can be defined as chronic liver injury leading to fibrous bands formation which surrounds the regenerative nodules whose development can be acknowledged on histological basis which eventually leads to conditions such as portal hypertension and end-stage liver disease
- HE: it is defined as a range of neuropsychiatric manifestations in patients with hepatic dysfunction, after exclusion of neurological cause.,
Grading for HE was done as follows:
West Haven criteria
These criteria are based on severity:
- Grade 0: Normal
- Grade I: Mild impairment: sleep alterations, subtly impaired intellectual function, heightened irritability, metabolic tremor, and impaired muscular coordination
- Grade II: Moderate impairment: lethargy, grossly impaired intellectual function, disorientation to time, inappropriate or bizarre behavior, slurred speech, hypoactive reflexes, and ataxia
- Grade III: Severe impairment: somnolence, confusion, disorientation, paranoia or anger, clonus
- Grade IV: Coma: unconsciousness and dilated pupils
- Jaundice-as per history was given by the patient, history of yellowish discoloration of the eyes, and urine was taken for the same
Jaundice can be defined as serum bilirubin levels of >2.5–3 mg/dL along with a clinical picture of yellowish skin and sclera or both.
- Gynecomastia-appears due to the benign proliferation of male glandular breast tissue
With increase in the size of the mammary glands by >1 associated with tenderness around it.
- Ascites-free fluid in peritoneal cavity, clinically evident when more than or equal to 1.5 l by examination maneuver such as shifting dullness (volume of ascitic fluid >1000 ml), horseshoe dullness (at least 500 ml of fluid volume is required), and fluid thrill (massive ascites) or by ultrasound examination showing free fluid in the abdominal sac (fluid <500 ml can also be detected)
- Testicular atrophy-also called hypogonadism due to direct effect of alcohol or iron in case of hemochromatosis
On clinical examination, the examiner palpates both the testis and observes unequal diameters on both sides, also the patient may give a history of failure to feel or palpate one or both of the testes during the last few months or so.
- Asterixis-asynchronous flapping movement of dorsiflexed hands
- Dupuytren's contracture-fibrosis and contraction of the palmar fascia [Figure 1], [Figure 2], [Figure 3], [Figure 4].
| Observation and Results|| |
[Table 1] shows the baseline characteristics of the study population. In our study of 130 patients, the mean age of cirrhotic patients was 43.99 years and ranged from 15 to 80 years in which 107 patients were male and 23 patients were female.
Of 130 patients, 92 patients gave a positive history of alcohol, whereas 38 patients had no prior history of alcohol intake.
Serum ammonia values of all 130 patients were analyzed, and the mean value was found to be 116.73 with values ranging from 50 to 412.
According to the West Haven criteria for HE on admission, of 130 participants, 11 were found to be in Grade I, 57 patients were found to be in Grade II, and 61 patients came under Grade III of the criteria, whereas only one patient was found to be under Grade IV [Graph 1].
In [Table 2], according to our study in population of 130 patients, 66.15% of persons had icterus, 66.15% of persons had ascites, 65.38% of persons had asterixis, ecchymotic patches were present in 43.85% of persons, fetor hepaticus was present in 41.54% of patients, gynecomastia was present in 38.46% of patients, male pattern baldness was present in 20.77% of patients, spider naevi were present in 17.69% of patients, Dupuytren's contracture was present in 8.46% of patients, purpura was present in 6.92% of patients, testicular atrophy was present in 4.62% of patients, paper-money skin was present in 3.85% of patients, and leukonychia was present in 0.77% of patients.
|Table 2: Distribution of patients according to clinical signs of liver failure|
Click here to view
Hence, in our study population, icterus, ascites, and asterixis were three leading signs of liver cell failure present in almost 65% of patients followed by ecchymotic patches, fetor hepaticus, and gynecomastia.
In [Table 3], lactulose was used as treatment modality in 96 (73.84%) persons, l-ornithine-l-aspartate was used in 46 (35.38%) patients, cefotaxim was used in 53 (39.23%) persons, mannitol was used in 47 (36.15) persons, and rifaximin was used for treating 81 (62.30%) patients of HE in the study population.
|Table 3: Distribution of patients according to the treatment protocol in the patients of hepatic encephalopathy|
Click here to view
Hence, lactulose and rifaximin were the two most common treatment modalities used in our study setup followed by cefotaxim and mannitol [Graph 2].
Distribution of patients according to etiology of cirrhosis of liver
[Table 4] reports the distribution of patients according to the etiology of cirrhosis of liver. In our study population of 130 patients, 98 patients were found to be alcoholic which was significantly higher in males (97 persons) than in females (one person) (P = 0.0001 S). Hepatitis B surface antigen status was positive in three persons of which two were male and one was a female. According to our study, HCV was found positive in a male person. NFLD status was positive in 8 persons of which five were male persons and three were female. Wilson's disease was found to be positive in 1 female patient which was significantly higher (P = 0.030 S) than that in male patients. Nineteen persons suffered from cryptogenic cirrhosis and were significantly higher in females (17 persons) than in males (2 persons) (P = 0.0001 S).
|Table 4: Distribution of patients according to etiology of cirrhosis of liver|
Click here to view
[Table 5] shows the laboratory parameters of all the patients with cirrhosis of liver. In our study population of 130 patients, minimum value of serum bilirubin was 0.57 and 10.52 was the maximum value with a mean of 3.66. Conjugated bilirubin ranged from 0.14 to 7.20 with a mean value of 1.71 and unconjugated bilirubin ranged from 0.16 to 5.40 with a mean value of 1.94. Minimum value of total protein in our study was 3.60, and maximum value was 8.80 with the mean value of 6.49. Serum albumin ranged from 1.20 to 4.80 with the mean value of 2.87; also serum globulin was analyzed with minimum value and maximum value of 1.80 and 6.40, respectively, with the mean value of 3.62. In our study population, minimum and maximum values of serum urea were 20 and 166, respectively, with the mean value of 41.69. Serum creatinine values ranged from 0.44 to 8.44 in 130 study participants with a mean value of 1.28. Minimum value of serum sodium in our population was found to be 124 and maximum value was 154 and with the mean of 137.13. Serum potassium values were documented where the minimum value was 2.20 and maximum was 6.39 with the mean of 4.10. Prothrombin time (PT) was also studied in 130 patients where the minimum value was found to be 11.30 and maximum value of 41.00 with a mean value of 18.72. In our population, the international normalized ratio ranged from 1 to 3.28 with a mean value of 1.54. Activated partial thromboplastin time values recorded in our study ranged from 29.10 to 70.30 with a mean value of 37.41. Serum ammonia was analyzed with minimum value of 50 and the maximum value was 412 with a mean value of 116.73.
| Discussion|| |
The present cohort study titled “Clinical profile for adverse outcomes in patients with HE in Cirrhosis of Liver” was carried out in the Department of Medicine, Jawaharlal Nehru Medical College and associated Acharya Vinoba Bhave rural hospital, Sawangi (Meghe), Wardha, Maharashtra, over 2 years from September 2016 to September 2018.
The study was conducted to determine the clinical profile of a patient suffering with HE in cirrhosis of liver. The components studied were signs of liver cell failure, etiology of cirrhosis, and treatment used among these patients.
Our study included 130 patients of HE secondary to cirrhosis of liver.
The mean age of the study population was 44 years, and most of them were male, i. e., 82% of total patients and 44% and 45% of patients were in Grade 2 and Grade 3 of the West Haven criteria of HE, respectively.
Cirrhosis of liver was associated with alcohol dependence in 70% of patients. In the current study population, icterus, ascites, and asterixis were three leading signs of liver cell failure present in almost 65% of patients followed by ecchymotic patches, fetor hepaticus, and gynecomastia.
Cirrhosis was associated with alcohol dependence among 98 (75%) patients followed by nonalcoholic fatty liver disease in eight (6.15%) patients, hepatitis B in three (2.31%) patients, and hepatitis C in one (0.77%) patient only. Other unknown causes were among 19 (14.62%) patients.
In our study population of 130 patients, 82.31% of patients were male and 17.69% were female, and the mean age of our study was 44 years. Over all patients were of younger age group, i.e., in the fourth decade affected with HE. This can have a significant effect on the family economy as well as on social stability.
In the study by Res et al., 50 patients were enrolled with 64% of males and 36% of females and the mean age was 48 years. In the study by Taseer et al., 80% were male and 20% were female out of 50 patients included in the study with the mean age of 47.45 years. These findings were similar to our results.
Newer insights into the pathogenesis of HE has led to newer approaches in its management, though these are yet to be widely applied, particularly in the resource-poor nations, documentation of its profile, including precipitating factors will go a long way in formulating rational strategies in its management, including prophylaxis in view of the reported poor outcome.
The patients in this study were nursed in the open ward, and this was largely due to financial constraints. In our setting, usually, healthcare costs are borne by the patients and payment often has to be made before some facilities are made available for use. Management in an ICU, as well as employment of the newer therapeutic measures, may have improved the outcome.
In our study, lactulose was used as treatment modality in 73.84% of patients and the second-most common drug used in the treatment of HE is rifaximin in 62.30% of patients.
In a study by Qazi Arisar et al. done at Aga Khan university stated that lactulose is the most commonly prescribed agent to relieve constipation in patients with chronic liver disease.
Etiology of cirrhosis is one of the important parameters involved in the progression of the disease as it can help in identifying and removing the cause of disease.
In our study, total 130 patients were studied of which 75.38% of patients were found to be alcoholic followed by NFLD, present in 6.15% of patients which was the second-most common cause of cirrhosis of liver in our patients. Nearly 14.62% of patients were attributed to causes which were unknown or could not be diagnosed. Male predominance was seen in patients suffering from alcoholic cirrhosis of liver, whereas females were predominantly present in the group where the diagnosis could not be made and the cause remained unknown (cryptogenic) for cirrhosis of liver.
Our findings, when compared with studies done in different countries, show that alcoholism is clearly the leading cause of cirrhosis of liver and hence awareness among people toward alcohol abstinence can significantly alter the course of cirrhosis in our study setup. These findings were contrary to the ones done in countries like Pakistan where hepatitis C virus infection was the leading cause of cirrhosis of liver. On the other hand, in the Western world, alcoholism is the main cause of liver cirrhosis where there is definite male preponderance to the extent of 77:33, making it the fourth-most common cause of death in males in the USA.,,,
These parameters were helpful in identifying the different precipitating factors responsible for worsening the course of disease, hyperbilirubinemia, hypoalbuminemia, deranged renal profile (hepatorenal syndrome), hypokalemia, hyponatremia, deranged coagulation profile, and hyperammonemia are the most common findings.
It is very clear from the above findings that almost two-third of the patients have coagulopathy; more than half of the study population have hyperammonemia, hypoalbuminemia, and hyperbilirubinemia. Patients with cirrhosis have a variety of hematological, vascular, and other defects that increase their morbidity and mortality rates, in the majority of the patients PT was prolonged and serum albumin levels were low. PT may be prolonged due to failure to absorb fat-soluble Vitamin K or due to failure of synthesis of prothrombin and other liver-derived factors, prolonged PT is a relatively late manifestation of liver disease clearly indicating the advancement of liver cirrhosis in our patients by the time of their presentation in the hospital, findings of our study were consistent with those of Maqsood et al. where 86% of the patients had hypoalbuminemia and 44% of the patients suffered with coagulopathy [Table 6] and [Table 7].
|Table 6: Comparison of different national and international studies in view of etiology (values in percentage)|
Click here to view
|Table 7: Parameters helpful in identifying the different precipitating factors responsible for worsening the course of disease|
Click here to view
Findings of hypoalbuminemia correspond well with advanced stages of cirrhosis. High urea and creatinine in majority of our patients highlight the fact that azotemia is an important pathogenic contributor to the onset of HE.
Limitation of the study
Due to the high costs of imaging patients in this study, we did not have brain computerized tomographic scan to exclude primary neurological disease; however, most of these patients had preexisting liver disease.
The intake of protein in the diet could not be assessed as precipitating factor in our study due to lack of guidance regarding nutritional supplements for the patient or unavailability of a nutritionist, which acted as a limitation for our study.
Liver biopsy could not be done to confirm the histological diagnosis of the patients of cirrhosis of liver, due to lack of technical requirements and reluctance of patients and their relatives toward such procedure.
Poor follow-up compliance of the patients was a huge limitation in our study setup, due to the illiterate and negligent behavior of the patients during the follow-up period, this is the same reason associated with poor compliance of the patients toward medications and their routine hospital visits.
| Conclusion|| |
In the present study, alcohol was found to be the leading cause of cirrhosis of liver followed by NFLD.
In our study, the most common clinical feature associated was icterus, ascites, asterixis, and ecchymotic patches.
Our study showed that the most commonly used treatment for HE is lactulose and rifaximin.
Financial support and sponsorship
The study was financially supported by JNMC, Sawangi (M), Wardha, Maharashtra, India.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Liere V, Sandhu G, DeMorrow S. Recent advances in hepatic encephalopathy. F1000Res 2017;6:1637.
Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, et al.
Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the study of liver diseases and the EUROPEAN association for the study of the liver. Hepatology 2014;60:715-35.
Wijdicks EF. Hepatic encephalopathy. N
Engl J Med 2016;375:1660-70.
Bajaj JS. Review article: The modern management of hepatic encephalopathy. Aliment Pharmacol Ther 2010;31:537-47.
Anderson RN, Smith BL. Deaths: Leading causes for 2001. Natl Vital Stat Rep 2003;52:1-85.
Maqsood S, Saleem A, Iqbal A, Butt JA. Precipitating factors of hepatic encephalopathy: Experience at Pakistan institute of medical sciences Islamabad. J Ayub Med Coll Abbottabad 2006;18:58-62.
Alam I, Razaullah, Haider I, Humayun M, Taqweem MA. Spectrum of precipitating factors of hepatic encephalopathy in liver cirrhosis. Pak J Med Res 2005;44:96-100.
Mohan DK, Hemamalini G, Ejpmr KS, Clinical study of patients presenting with hepatic encephalopathy with special reference to outcome and etiology. Eur J Pharm and Med Res 2016;3:392-4.
Taseer IU, Mahmood MA, Ch MN, Safdar S, Ijaz A. Frequency of precipitating factors of hepatic encephalopathy in patients with chronic liver disease PJMHS 2014;8:899-900.
Onyekwere CA, Ogbera AO, Hameed L. Chronic liver disease and hepatic encephalopathy: Clinical profile and outcomes. Niger J Clin Pract 2011;14:181-5.
] [Full text]
Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008;371:838-51.
Toris GT, Bikis CN, Tsourouflis GS, Theocharis SE. Hepatic encephalopathy: An updated approach from pathogenesis to treatment. Med Sci Monit 2011;17:RA53-63.
Patidar KR, Bajaj JS. Covert and overt hepatic encephalopathy: Diagnosis and management. Clin Gastroenterol Hepatol 2015;13:2048-61.
Roche SP, Kobos R. Jaundice in the adult patient. Am Fam Physician 2004;69:299-304.
Vergara-Gómez M, Flavià-Olivella M, Gil-Prades M, Dalmau-Obrador B, Córdoba-Cardona J. Diagnosis and treatment of hepatic encephalopathy in Spain: Results of a survey of hepatologists. Gastroenterol Hepatol 2006;29:1-6.
Faloon WW, Evans GL. Precipitating factors in genesis of hepatic coma. N
Y State J Med 1970;70:2891-6.
Kirnake V, Arora A, Sharma P, Goyal M, Chawlani R, Toshniwal J, et al
. Non-invasive aspartate aminotransferase to platelet ratio index correlates well with invasive hepatic venous pressure gradient in cirrhosis. Indian J Gastroenterol 2018;37:335-41. doi: 10.1007/s12664-018-0879-0. Epub 2018 Sep 3.
Jain J, Singh R, Banait S, Verma N, Waghmare S. Magnitude of peripheral neuropathy in cirrhosis of liver patients from central rural India. Ann Indian Acad Neurol 2014;17:409-15. doi: 10.4103/0972-2327.144012. [Full text]
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]