Subclinical Hepatic Encephalopathy Patients Research Articles

Sub-clinical hepatic encephalopathy in cirrhotic patients is not aggravated by sedation with propofol compared to midazolam: A randomized controlled study

The risk of exacerbating sub-clinical hepatic encephalopathy (HE) by propofol has not been established. The aim of this study is to determine whether the use of propofol, for upper endoscopy in patients with cirrhosis, precipitates sub-clinical HE. Sixty-one patients with compensated HCV and HBV cirrhosis (CP score 5-6) were randomly selected and divided into two groups (intent-to-treat population) matched for age, gender, and BMI. The first group received a single propofol sedation (N = 31, age 57 ± 12, dose range 70-100 mg/procedure) and the second group (N = 30, age 56 ± 12, dose 3-6 mg/procedure) received a single midazolam sedation, all done by an anesthesiologist. All patients completed number connection test (NCT), cognitive function score, time to recovery, time to discharge sheets, and hemodynamic parameters before sedation, and at discharge from the endoscopy unit, 1h post-procedure. Thirty control subjects without cirrhosis were matched to the cirrhotic patients who received sedation with regard to age, gender, BMI, and education level. A total of 58/61 cirrhotic patients (95%) had sub-clinical encephalopathy before the endoscopy (mean NCT 84.7 ± 77 s, normal < 30 s). No patient developed overt HE after sedation. There were no differences between groups in the incidence of adverse effects, cognitive function, MELD score, CP score, oxygen saturation, or respiratory and heart rates before and after sedation. Propofol did not exacerbate minimal HE when compared to midazolam (NCT changed from 87.5 ± 62 s prior to sedation to 74.2 ± 58 s after sedation in the propofol group versus 72.8 ± 62 s before to 85.6 ± 72 s after sedation in the midazolam group; p < 0.01). Time to recovery (4.1 ± 1.9 min vs. 11.5 ± 5.0 min, p < 0.001), and time to discharge (38.0 ± 9 min vs. 110 ± 42 min, p < 0.001) were significantly shorter with propofol than midazolam. Pre- and post-procedure NCT (from 25 ± 20 s to 24 ± 20 s), cognitive function score (from 25 to 26), time to recovery (3.5 ± 1.0 min), and time to discharge (35 ± 10 min) did not change in the healthy controls. Sedation with propofol has a shorter time recovery and a shorter time to discharge than midazolam and does not exacerbate sub-clinical hepatic encephalopathy in patients with compensated liver cirrhosis.

L‐Ornithine‐l‐aspartate in the management of hepatic encephalopathy: A meta‐analysis

Hepatic encephalopathy continues to be a major clinical problem and the current decade has not witnessed major therapeutic breakthroughs in this area. L-ornithine-l-aspartate (LOLA) is not frequently used as there are still some reservations about its benefits. The present study aimed to assess the effectiveness and safety of LOLA in the management of hepatic encephalopathy. We used the method recommended by the Cochrane Collaboration to perform a meta-analysis of randomized controlled trials of LOLA therapy for hepatic encephalopathy including three randomized controlled trials. Three randomized trials randomizing 212 patients were included. LOLA versus placebo had a significant effect on improvement of hepatic encephalopathy (relative risk 1.89; 95% CI 1.32 to 2.71; P = 0.0005). This comparison showed no statistical heterogeneity (P = 0.85 and chi(2) = 0.09). Subgroup analysis showed that LOLA could be effective versus placebo in trials with grade I or II overt hepatic encephalopathy patients (relative risk 1.87; 95% CI 1.30 to 2.68; P = 0.0007) and had no significant effect in trials with subclinical hepatic encephalopathy patients (relative risk 1.69; 95% CI 0.72 to 3.94; P = 0.23). Adverse effects were observed in only three patients treated with LOLA in one report. LOLA benefited patients with overt hepatic encephalopathy (I or II), whereas these data do not support the use of LOLA for patients with subclinical hepatic encephalopathy.

Prevalence of subclinical hepatic encephalopathy in patients with cirrhosis determined by psychometric tests

OBJECTIVE: To investigate the prevalence of subclinical hepatic encephalopathy (SHE) in patients with stable hepatic cirrhosis.METHODS: One hundred and seventy‐five consecutive cirrhotic patients (mean age 53 years, range 27−72 years) without overt clinical encephalopathy were screened for SHE using the number connection test (NCT) part A and symbol digit test (SDT). Subclinical hepatic encephalopathy was defined as the presence of at least one abnormal psychometric test. The age‐corrected normal value was defined as the mean ± 2SD obtained from 356 subjects without liver disease and in normal mental condition. Illiterate patients and patients with concurrent use of alcohol or psychotropic drugs, and those with previous portosystemic shunt and were excluded.RESULTS: In different age subgroups, the NCT scores and SDT quotients for cirrhotic patients were significantly different compared with those for controls (P &lt; 0.05−0.001). Fifty patients (28.6%) were found to be abnormal in both the NCT and SDT, 16 (9.1%) patients were abnormal only in the SDT and 34 patients (19.4%) only in the NCT. Taken together, SHE was diagnosed in 100 patients (57.1%) by using the two tests. The prevalence of SHE increased from 46.8% and 53.0% in Child−Pugh grades A and B, to 76.6% in Child−Pugh grade C (P &lt; 0.05). No significant correlation was found between the development of SHE and the etiology of cirrhosis, patient age and smoking habit.CONCLUSION: By using a combination of NCT and SDT, SHE was diagnosed in 57.1% of cirrhotic patients without overt clinical encephalopathy. The prevalence of SHE was significantly correlated with the severity of liver cirrhosis.

Efficacy of L-Carnitine in Reducing Hyperammonaemia and Improving Neuropsychological Test Performance in Patients with Hepatic Cirrhosis

To determine the efficacy of L-carnitine in reducing hyperammonaemia and improving neuropsychological performance in patients with hepatic cirrhosis and subclinical hepatic encephalopathy (SHE). Randomised, parallel group, controlled trial. The study enrolled 31 patients with hepatic cirrhosis resulting from hepatitis C and/or hepatitis B, alcohol abuse and other causes. Patients randomised to active treatment, received oral L-carnitine 6 g/day in two divided doses for 4 weeks. Diagnosis of SHE was based on psychometric tests (subtests of the Wechsler Adult Intelligence Scale-Revised and the Halstead-Reitan Neuropsychological Test Battery) carried out at beginning and end of study. Serum ammonia levels were measured before treatment and weekly thereafter. A total of 27 patients completed the study. Sixteen patients received L-carnitine and 11 served as controls (no treatment). L-carnitine caused rapid and significant reductions in ammonia levels, sustained over the 4-week treatment period (mean reductions 60.1 and 1.4 (μmol/L in the treated and control groups, respectively). Normal ammonia levels were attained in 14 of 16 patients receiving L-carnitine. Based on psychometric test results, seven patients (43.7%) in the L-carnitine group and five (45.5%) in the control group had SHE at baseline. L-carnitine treatment for 4 weeks caused a net overall improvement in psychometric test results compared with controls. No clinically significant adverse events were reported and all patients receiving L-carnitine reported subjective improvements in their condition. RESULTS of this preliminary study indicate that L-carnitine reduces hyperammonaemia and improves the clinical symptoms of SHE in patients with hepatic cirrhosis.

Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis.

The natural history of subclinical hepatic encephalopathy (SHE) is unknown. The present study was conducted to study the prevalence and the natural history of SHE in patients with cirrhosis of the liver. One hundred and sixty-five patients with cirrhosis of the liver were studied. A total of nine psychometric tests (trail making and Wechsler adult intelligence scale-performance (WAIS-P) tests) were administered. Subclinical hepatic encephalopathy was present if two or more psychometric tests were abnormal. Seventy-two patients (SHE 40, without SHE 32) also underwent serial psychometric testing on follow-up visits at 6-8 week intervals. Subclinical hepatic encephalopathy was present in 103 (62.4%) patients. The number and figure connection, block design and picture completion tests were the most useful in the detection of SHE. Severity of SHE, as assessed by the number of abnormal tests, was greater in patients with more severe liver disease. During follow up, SHE tended to persist or worsen in patients with poorer liver function. Although other clinical complications were similar in different groups, overt hepatic encephalopathy developed more commonly in those patients who had SHE at entry compared to those who did not (22.6 vs 5.6%, P = 0.044). Among the patients with SHE, the development of overt hepatic encephalopathy was more common in patients with Child's score of > 6 than with Child's score of <or= 6 (40 vs 5%, P = 0.019). We conclude that SHE is common in cirrhosis. The natural history of SHE is worse in patients with advanced cirrhosis and SHE probably predisposes the cirrhotic patient to overt hepatic encephalopathy.

Auditory P300 event-related potentials and number connection test for evaluation of subclinical hepatic encephalopathy in patients with cirrhosis of the liver: a follow-up study.

The P300 event-related potentials (P3ERP) have been recently advocated for detection of cognitive disturbances in early encephalopathy. However, no systematic follow-up study has been conducted to understand the clinical significance of subclinical hepatic encephalopathy (SHE) detected by this or other methods. The present study was therefore undertaken to examine the diagnostic usefulness of auditory P3ERP in the detection of SHE, to compare it with that of the number connection test (NCT), and to investigate the clinical outcome of patients with SHE in terms of progression to overt encephalopathy. P300 event-related potential latencies were measured and the NCT time was recorded in 81 non-encephalopathic cirrhotic patients (Aged 43.8 +/- 11 years, 23 alcoholic and 58 non-alcoholics) attending the outpatient department at our tertiary care hospital (All India Institute of Medical Sciences Hospital). Cut-off values for abnormality in the tests were developed from age-, sex- and education-matched controls. Patients were followed up at regular intervals for the development of overt encephalopathy, and the identifiable precipitating factors were noted. The P3ERP latencies (363 +/- 34 msec vs 349 +/- 23 msec), as well as NCT time (54.6 +/- 30.6 s vs 39.5 +/- 15.8 s) were significantly prolonged (P< 0.01) in patients with liver cirrhosis when compared with the non-cirrhotic controls. The P3ERP defects were seen in 24.6% of cirrhotic patients, while NCT time was prolonged in 19.7% of the patients. Nearly 43% of the patients with SHE progressed to overt encephalopathy within a mean duration of 5 months, while only 3.9% of the non-SHE patients did so. Of the patients who developed overt encephalopathy, 64.2% had P3ERP latency prolongations while 35.7% had abnormal NCT. The results of the present study suggest that P3ERP and NCT are valid tools for the screening of SHE in cirrhotic patients as there is a greater likelihood of overt encephalopathy development in patients with an abnormality detected by these tests than in patients with no such abnormality.

Risk of sedation for upper GI endoscopy exacerbating subclinical hepatic encephalopathy in patients with cirrhosis

Background: The risk of exacerbating subclinical hepatic encephalopathy associated with the administration of sedative drugs in patients with cirrhosis undergoing diagnostic upper gastrointestinal (GI) endoscopy for portal hypertension remains to be determined. Methods: Ten adult patients with cirrhosis completed number connection tests before sedation for endoscopy and at discharge from the endoscopy unit 2 hours post-procedure. Control patients consisted of five patients with cirrhosis undergoing the same procedure for the same indication who did not receive sedation and 12 patients with no evidence of liver disease who received sedation before diagnostic endoscopy for a variety of GI complaints. The control populations were age, gender, education level, and, in the case of patients with cirrhosis, Child Pugh's score matched to the patients with cirrhosis who received sedation. Results: The mean (± SEM) age of patients with cirrhosis who received sedation was 59.6 ± 3.8 years. Seven of the ten (70%) were men. Their mean Child Pugh's score was 7.2 ± 1.5. Nine of the ten (90%) had abnormal baseline number connection tests results (mean for the group 52.3 ± 6.7 seconds) the extent of which correlated with Child Pugh's scores ( p < 0.005). Individually, the baseline number connection tests results were normal in one (10%), mild in six (60%), moderate in one (10%), and severe in two (20%). After the procedure (before discharge) the mean number connection tests result was 61.5 ± 7.9 seconds ( p = 0.01 when compared with baseline). The results were now normal in none (0%), mild in four (40%), moderate in four (40%), and severe in two (20%). Pre- and post-procedure number connection tests results did not change in the non-sedated cirrhotic or sedated non-liver disease control patients. Conclusions: The results of this study indicate that (1) the majority of patients with cirrhosis and suspected portal hypertension have evidence of subclinical hepatic encephalopathy, (2) the extent of encephalopathy correlates with the Child Pugh's score, (3) sedation with midazolam for upper GI endoscopy exacerbates the encephalopathy, and (4) this adverse effect is still evident 2 hours after the procedure. (Gastrointest Endosc 1999;49:690-4.)

Lactulose improves psychometric testing in cirrhotic patients with subclinical encephalopathy

Therapeutic trials suggest that lactulose is an effective treatment of acute and chronic encephalopathy in cirrhotic patients. As it is likely that portal-systemic shunting and hepatocellular dysfunction are associated with some degree of neurological dysfunction, 14 patients with cirrhosis and documented portal-systemic shunting, but without detectable encephalopathy, were randomized to treatment with either lactulose 20 g t.d.s., or lactose 20 g t.d.s. as placebo, for a 15-day period. Monitoring included manually administered and computer-based psychometric testing, the results of which were correlated with a battery of biochemical and functional parameters. There was no correlation between biochemical or functional parameters and psychometric testing. There was a close correlation between the time required to complete the number connection test and both the number of errors and the duration of errors at sinusoid testing. Lactulose therapy resulted in a significant improvement, assessed by the number connection test and the race track test. Our data suggest that lactulose therapy might improve subclinical hepatic encephalopathy in patients with cirrhosis and portal-systemic shunting.

The diagnosis of subclinical hepatic encephalopathy in patients with cirrhosis using neuropsychological tests and automated electroencephalogram analysis

Neuropsychological tests used for the assessment of subclinical hepatic encephalopathy (SHE) may overdiagnose SHE because scores are usually not corrected for age. The aim of this study was to estimate the prevalence of SHE using two easy administrable psychometric tests (Number Connection Test part A [NCT-A], Symbol Digit Test [SDT]) with age-related normal values. In addition, spectral electroencephalogram (EEG) was used, which is the in-house electrophysiological method for quantifying encephalopathy. One hundred and thirty-seven consecutive patients (mean age 49 years, range 17-77) with cirrhosis without any clinical signs of encephalopathy, were screened for SHE. In addition, the Child-Pugh score and the arterial blood ammonia were determined. Patients with concurrent use of alcohol, benzodiazepines or anti-epileptics were excluded. Fifty percent of the patients had an abnormal NCT according to the standard recommended procedure, in contrast only 7% of the patients had an abnormal NCT when scores corrected for age were used. Combining the results of the spectral EEG and the psychometric tests corrected for age yielded a higher prevalence of SHE (23%) than when each test method was used alone (17% vs. 10% abnormal, respectively). Severity of liver disease correlated with the presence of SHE, because the prevalence of abnormal tests increased from 14% in Child-Pugh grade A to 45% in Child-Pugh grade B or C. Age above 40 years and an elevated blood ammonia level were significant determinants related to an abnormal EEG. We conclude that the NCT uncorrected for age markedly overdiagnoses SHE and, therefore, should not be used as a test for the screening of SHE. Using a combination of spectral EEG and two psychometric tests with age-corrected normal values a low prevalence of SHE in patients with Child A liver cirrhosis is found. Older patients with an elevated arterial ammonia are more prone to develop SHE than younger patients with an equal arterial ammonia concentration. (Hepatology 1996 Sep;24(3):556-60)