Cerebral abnormalities in patients with cirrhosis detected by proton magnetic resonance spectroscopy and magnetic resonance imaging

Hepatic encephalopathy is a common problem in cirrhosis. The pathogenesis of this complication of advanced liver disease still remains unclear. Magnetic resonance spectroscopy was used to assess prospectively cerebral metabolism in 51 patients with histologically proven cirrhosis (Child-Pugh classes A, B, and C, 18, 18, and 15, respectively) and 36 healthy volunteers. According to the results of psychometric tests, overt hepatic encephalopathy, subclinical encephalopathy, and no encephalopathy were found in 14, 21, and 16 patients, respectively. Myoinositol/creatine ratios in gray (.36 +/- .17) and white (.35 +/- .22) matter voxel were reduced significantly (P < .0001) in cirrhotic patients compared with healthy volunteers (gray matter, .51 +/- .11; white matter, .64 +/- .16). In addition, patients showed a significant reduction (P = .024) in white matter choline/creatine ratio (.77 +/- .27) compared with controls (.92 +/- .25), and glutamine/glutamate level was elevated in cirrhotic patients compared with controls (gray matter, P < .0001; white matter, P = .036). Changes in cerebral myoinositol and glutamine/glutamate levels correlated significantly with the severity of hepatic encephalopathy (P < .0001). However, these metabolic alterations were also detected in patients without hepatic encephalopathy (normal psychometric test results). N-acetyl aspartate/creatine ratios did not differ between patients and controls. Magnetic resonance imaging detected bright basal ganglia in 37 patients, which correlated significantly with portal-systemic shunting and elevation of glutamine/glutamate, but not with the degree of hepatic encephalopathy. In conclusion, magnetic resonance imaging and spectroscopy showed that alterations of cerebral metabolism are common in patients with cirrhosis, even without evidence of clinical or subclinical hepatic encephalopathy.(Hepatology 1997 Jan;25(1):48-54)     

Propranolol does not alter cerebral blood flow and functions in cirrhotic patients without previous hepatic encephalopathy

Since it has been suggested that propranolol could lead to hepatic encephalopathy, we undertook a study to assess the effects of propranolol on cerebral blood flow and cerebral functions. Sixteen patients with alcoholic cirrhosis and large esophageal varices and without major hepatic dysfunction (Child-Pugh score less than 14) or previous hepatic encephalopathy were randomized to receive either propranolol or placebo. The following measurements were performed before and 15 min after single intravenous administration of 15 mg propranolol or placebo and again 1 week after chronic oral administration of propranolol 160 mg per day or placebo: cerebral blood flow by the xenon-133 inhalation technique, quantitative electroencephalogram, psychometric test (number connection test), arterial ammonia, pH and pCO2, resting and exercise heart rates (after single administration, electroencephalogram, number connection test and biochemical measurements were not performed). Cerebral blood flow was not significantly modified by treatment (propranolol group: 80 +/- 23 vs. 76 +/- 11 and 83 +/- 9; placebo group: 73 +/- 10 vs. 75 +/- 11 and 81 +/- 18 ml per 100 gm per min, respectively, before and after single and repeated administration). Likewise, neither of the two treatments significantly altered number connection test, quantitative electroencephalogram index, arterial ammonia, pH and pCO2. We conclude that, in this population of cirrhotic patients, propranolol did not alter cerebral blood flow or neuropsychological functions. As a consequence, hemodynamic alterations cannot be considered as causes of possible cerebral side effects of propranolol in cirrhotic patients without severe hepatic dysfunction and previous hepatic encephalopathy.     

Decrease of regional cerebral blood flow in liver cirrhosis

OBJECTIVE: Alterations of regional cerebral blood flow (rCBF) in subjects with liver cirrhosis have not been fully evaluated. We evaluated quantitative changes in rCBF using single photon emission computed tomography (SPECT). METHODS: Twenty-eight Japanese patients with liver cirrhosis were enrolled in this study. None of them exhibited advanced hepatic encephalopathy at the time of examination. The cause of liver cirrhosis was viral infection in 26 patients; the cause was unknown in two patients. Child-Pugh classification of the patients was as follows: Group A, 12 patients; Group B, 12 patients; and Group C, four patients. The control group consisted of 25 age-matched healthy subjects. Radionuclide angiography was performed by rapid injection of Tc-99m ethyl cysteinate dimer (ECD) (740 MBq) via the right cubital vein, and then SPECT brain images were taken. Using the Patlak graphical method, rCBF values (ml/100 g per min) were calculated in the frontal, parietal, temporal and occipital lobes and cerebellum on SPECT images. RESULTS: The rCBF values were lower in cirrhotic patients than in controls, i.e. by 15% in the frontal lobe, by 12% in the parietal lobe, by 10% in the temporal and occipital lobes, and by 7% in the cerebellum. They decreased concomitantly with the severity of liver disease. A significant negative correlation was noted between rCBF values and Child-Pugh score in the frontal (P<0.01), parietal (P<0.05) and occipital lobes (P<0.01). rCBF values of each region were not correlated with age or with results of neuropsychological test. The degree of association between rCBF values and results of laboratory examination was generally poor. CONCLUSION: Patients with liver cirrhosis without advanced encephalopathy showed widespread reduction in rCBF; this reduction was particularly evident in the frontal lobe. Tc-99m ECD SPECT may be useful for evaluating cerebral functional changes in patients with liver cirrhosis.     

Cerebral vascular resistance assessed by transcranial color Doppler ultrasonography in patients with chronic liver diseases

BACKGROUND AND AIM: Cerebral hemodynamic derangement is well known in patients with liver cirrhosis. The advent of transcranial Doppler enables a non-invasive observation of cerebral hemodynamics. To evaluate the clinical usefulness we examined cross-sectionally and longitudinally cerebral hemodynamic parameters in patients with cirrhosis. METHODS: The subjects of the cross-sectional study were 117 patients with cirrhosis, 15 patients with chronic hepatitis and 25 healthy controls. The longitudinal study included 26 cirrhotic patients without encephalopathy, and 27 cirrhotic patients with encephalopathy. The pulsatility and resistive indices of the right middle cerebral artery were used as parameters of cerebral hemodynamics. RESULTS: Cerebral pulsatility and resistive indices were significantly higher in patients with cirrhosis (1.05 +/- 0.23, P < 0.0001 and 0.63 +/- 0.07, P < 0.0001, respectively) than in the controls (0.75 +/- 0.11 and 0.55 +/- 0.05, respectively) and patients with chronic hepatitis (0.81 +/- 0.11 and 0.52 +/- 0.05, respectively). Cerebral pulsatility and resistive indices were significantly related with the severity of liver cirrhosis. Patients with encephalopathy had higher cerebral pulsatility and resistive indices than patients without encephalopathy. In the longitudinal studies, cerebral pulsatility and resistive indices were changed in parallel with the severity of cirrhosis and encephalopathy. Cerebral pulsatility and resistive indices were significantly correlated with the blood ammonia level and serum levels of bilirubin and albumin. CONCLUSION: These cross-sectional and longitudinal studies showed that cerebral vascular resistance indices measured by using transcranial Doppler were increased in association with the severity of cirrhosis and encephalopathy. Cerebral pulsatility and resistive indices are real-time and useful parameters to assess and monitor cirrhotic patients.     

Mental status impairment in patients with West Haven grade zero hepatic encephalopathy: the role of HCV infection

Background In patients with cirrhosis, subclinical hepatic encephalopathy, which negatively affects the activity of daily living, is often unidentified. In a multicenter observational study, we investigated the possibility of detecting minimal neurological changes consistent with subclinical hepatic encephalopathy by using the Trail Making Test in a cohort of patients with liver cirrhosis at hospital admission. Methods Seventy-seven consecutive patients with liver cirrhosis were studied (mean age, 69.5 ± 9.1; 95% confidence interval, 67.5–71.6 years). In all patients, possible encephalopathy was investigated according to the West Haven criteria. All those free of any sign of encephalopathy (West Haven 0) were also studied by the Trail Making Test forms A and B. The Child-Pugh score was determined in all patients, and results were compared with the West Haven stage. Exclusion criteria were use of benzodiazepine, beta adrenergic blockers, alcohol, or antiepileptic drugs, or coexistence of depression, dementia, Parkinson's disease, or chronic or acute cerebral vasculopathy. Results Of the 77 patients, 44 (57.1%, 23 men and 21 women) had West Haven score 0, but among these, 26 (59.1%) were diagnosed with mental impairment likely linked to minimal hepatic encephalopathy. Severity of liver disease correlated with the presence of likely minimal hepatic encephalopathy, because the prevalence of abnormal Trail Making Test results increased from 22.2% in Child-Pugh A, to 63.4% and 74.0% in Child-Pugh B and C, respectively. Conclusions The investigation of patients with cirrhosis by the West Haven test is not sufficient to identify subclinical forms of encephalopathy. The Trail Making Test (a simple, inexpensive test) in our series evidenced poor psychometric performance in more than half of the patients who were free of manifest encephalopathy. Subclinical hepatic encephalopathy was present mostly in patients with HCV-related cirrhosis. Detecting minimal hepatic encephalopathy in patients with cirrhosis may help improve their quality of life.     

Prevalence of subclinical hepatic encephalopathy in cirrhotic patients in China

AIM: Subclinical hepatic encephalopathy (SHE) is a common complication of liver diseases. The aim of this study was to find out the normal value of psychometric test and to investigate the prevalence of SHE in Chinese patients with stabilized hepatic cirrhosis.METHODS: Four hundred and nine consecutive cirrhotic patients without overt clinical encephalopathy were screened for SHE by using number connection test part A (NCT-A) and symbol digit test (SDT). SHE was defined as presence of at least one abnormal psychometric test. The age-corrected normal values were defined as the mean&#177;2times standard deviation (2SD), and developed in 356 healthypersons as normal controls. Four hundred and sixteen patients with chronic viral hepatitis were tested as negative controls to assess the diagnostic validity of this test battery.RESULTS: There was no significant difference in NCT scores and SDT quotients between healthy controls and chronic hepatitis group (P&gt;0.05). In all age subgroups,the NCT and SDT measurements of cirrhotic patients differed significantly from those of the controls (P&lt;0.05).When mean&#177;2SD of SDT and NCT measurements from healthy control group was set as the normal range, 119 cirrhotic patients (29.1%) were found to have abnormal NCT-A and SDT tests, 53 (13.0%) were abnormal only in SDT and 36 (8.8%) only in NCT-A. Taken together, SHE was diagnosed in 208 (50.9%) cirrhotic patients by this test battery. The prevalence of SHE increased from 39.9% and 55.2% in Child-Pugh‘s grade A and B groups to 71.8% in Child-Pugh‘s grade C group (P&lt;0.05). After the adjustment of age and residential areas required from the tests, no correlation was found in the rate of SHE and causes of cirrhosis, education level and smoking habit.CONCLUSION: Psychometric tests are simple and reliable indicators for screening SHE among Chinese cirrhotic patients. By using a NCT and SDT battery, SHE could be found in 50.9% of cirrhotic patients without overt clinical encephalopathy. The prevalence of SHE is significantly correlated with the severity of liver functions.     

心理测验、视觉诱发电位检测亚临床肝性脑病的价值

探讨心理测验、视觉诱发电位检测在亚临床肝性脑病 (SHE)诊断中的意义。对 4 5例肝硬化患者及 30例正常人进行数字连接试验 (NCT) ,视觉诱发电位 (VEP)检测。研究其在亚临床肝性脑病诊断中的应用价值。肝硬化组NCT异常占 5 6 % (2 5 / 4 5 ) ,VEP异常占 4 9% (2 2 / 4 5 ) ,NCT和 (或 )VEP异常占 71% (32 / 4 5 ) ,两者均异常 33% (15 /4 5 ) ;对照组NCT异常占 30 % (9/ 30 ) ,VEP异常占 2 7% (8/ 30 )。两组比较差异有显著性意义 (P <0 0 5 )。NCT和VEP可用于诊断SHE ,联合检测可提高SHE检出率 ,对预防肝性脑病的发生有重要意义     

Neurophysiological evidence of cognitive impairment in patients without hepatic encephalopathy after transjugular intrahepatic portosystemic shunts

OBJECTIVES: We aimed to test the hypothesis that subclinical cognitive brain dysfunction in cirrhotic patients would deteriorate after a transjugular intrahepatic portosystemic shunt (TIPS) in the absence of clinically detectable hepatic encephalopathy. METHODS: Out of 49 consecutive cirrhotic patients receiving elective TIPS for recurrent variceal hemorrhage, we identified 22 patients who were not encephalopathic and had not undergone liver transplantation at 6-month follow-up and confirmed TIPS patency by Doppler ultrasound. Patients were tested before and 6 months after TIPS implantation using event-related (P300) cognitive evoked potentials, late somatosensory median nerve (N70) potentials, and standard psychometric tests (Mini-Mental State and trailmaking test A). Twenty-two age-matched healthy subjects served as controls. RESULTS: Relative to controls, patients showed significantly impaired P300 and N70 latencies and abnormal psychometric test results at baseline. Six months after the TIPS, a further impairment of P300 latency was observed (p = 0.005), whereas no relevant changes in N70 latency and psychometric test results occurred. CONCLUSIONS: In cirrhotic patients with portal hypertension, neurophysiological signs of cognitive brain dysfunction are detectable in the absence of hepatic encephalopathy. A further subclinical deterioration of cognitive processing was observed 6 months after the TIPS. These findings demonstrate an aggravation of subclinical hepatic encephalopathy after a TIPS.     

Increased oro-cecal transit time in grade I or II hepatic encephalopathy

The pathogenic mechanisms of hepatic encephalopathy remain to be elucidated. It has been suggested that a digestive motor disorder could promote the absorption of toxins produced within the lumen and thus enhance hepatic encephalopathy. AIM: To evaluate oro-cecal transit time in cirrhotic patients with and without hepatic encephalopathy. METHODS: Hospitalized patients with alcoholic cirrhosis without encephalopathy and with spontaneous grade I and II encephalopathy were included. Severity of hepatic encephalopathy was assessed clinically and the Child-Pugh score was used to describe cirrhosis severity. Nine healthy volunteers constituted a control group. Oro-cecal transit time was measured with the sulfasalazine test. RESULTS: Twenty-eight patients (mean age 62.5 +/- 8.5 years) were included. Ten had hepatic encephalopathy of unknown cause and 18 were free of hepatic encephalopathy. Oro-cecal transit time was significantly longer in patients with hepatic encephalopathy (641 +/- 350 min) compared to patients without hepatic encephalopathy (298 +/- 96; P<0.05) and to controls (354 +/- 90; P<0.05). Oro-cecal transit time was comparable for each Child-Pugh score and was not different between the two grades of hepatic encephalopathy. CONCLUSION: Oro-cecal transit time is longer in alcoholic cirrhosis patients with hepatic encephalopathy. This digestive motor disorder provides a partial explanation of hepatic encephalopathy of unknown etiology.     

The prognostic significance of subclinical hepatic encephalopathy

OBJECTIVE: Subclinical hepatic encephalopathy may have prognostic significance with regard to the development of clinical hepatic encephalopathy and survival. METHODS: We studied 116 consecutive patients with histologically proven cirrhosis of the liver for subclinical hepatic encephalopathy, using Number Connection Test A, Digit Symbol Test, and spectral analysis of the electroencephalogram. RESULTS: Twenty-five patients (22%) were diagnosed as having subclinical hepatic encephalopathy. Patients with subclinical hepatic encephalopathy were older, had a higher Child-Pugh score, and more often had esophageal or gastric varices and episode(s) of clinical hepatic encephalopathy in their history. During a median follow-up of 29 months (range, 1-49 months), patients with subclinical hepatic encephalopathy significantly more often had episodes of clinical hepatic encephalopathy; survival, however, was similar to that of patients without subclinical hepatic encephalopathy, and was determined mainly by the Child-Pugh score. The Child-Pugh score was also superior to subclinical hepatic encephalopathy in predicting episodes of clinical hepatic encephalopathy. CONCLUSIONS: The prognostic significance of subclinical hepatic encephalopathy appears limited.     

Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis

BACKGROUND/AIMS: To measure cerebral benzodiazepine receptor binding using (11)C-flumazenil positron emission tomography in patients with stable chronic hepatic encephalopathy, who were also characterised by proton magnetic resonance spectroscopy. METHODS: Six abstinent patients of mean age 61 years with alcohol related cirrhosis and grade I-II hepatic encephalopathy and 11 matched healthy volunteers were studied. Each patient's encephalopathy was defined according to clinical, psychometric, electroencephalographic, and magnetic resonance spectroscopy criteria. Using positron emission tomography, the brain volume of distribution of (11)C-flumazenil was obtained; this reflects benzodiazepine receptor availability. Proton magnetic resonance spectra were acquired at 1.5 T using a multivoxel technique; peak area ratios were calculated for choline, glutamine/glutamate, N-acetylaspartate, and creatine resonances. RESULTS: The mean volume of distribution of (11)C-flumazenil was significantly higher in the cortex, cerebellum, and the basal ganglia in the patients compared with controls (p<0.001). In the patient group, the mean glutamine/glutamate to creatine ratio was significantly increased and the mean choline to creatine ratio was significantly decreased in all brain areas, compared with healthy volunteers. However, the N-acetylaspartate to creatine ratio was unchanged compared with controls. CONCLUSIONS: The spectroscopy results reflect the cerebral metabolic derangement associated with hepatic encephalopathy. Stable grade I-II chronic hepatic encephalopathy in alcohol related cirrhosis may be associated with increased cerebral benzodiazepine receptor availability. However, a direct effect of previous chronic exposure to alcohol cannot be excluded.     

Evaluation of Cingulate Gyrus Blood Flow in Patients With Liver Cirrhosis

Although neuropsychological tests are commonly applied to detect minimal hepatic encephalopathy (HE) in patients with liver cirrhosis (LC), they provide no information about the cerebral regions involved. Recently, it has been reported that some populations of alcoholic cirrhotics, with mild HE, have reduced cerebral metabolic rate for glucose in bifrontal cortices and in the anterior cingulate gyrus. We evaluated the degree of reduction in blood flow at the anterior cingulate gyrus and the frontal lobes in cirrhotic patients who underwent single photon emission computed tomography (SPECT). Data were obtained from 47 cirrhotic patients and 47 subjects without LC. Three radiologists unaware of the results of laboratory tests visually evaluated the transaxial, coronal, and sagittal views of SPECT. The area and the degree of blood flow reduction in the anterior cingulate gyrus and frontal lobes were scored. Reduced blood flow in the anterior cingulate gyrus was observed in most LC patients. In patients without overt HE, poor performance in neuropsychological tests was correlated with reduced cerebral blood flow in the anterior cingulate gyrus. Blood flow in the anterior cingulate gyrus as measured by SPECT may be a simple and good indicator of cerebral functional changes in patients with LC.     

Does liver-disease aetiology have a role in cerebral blood-flow alterations in liver cirrhosis?

BACKGROUND: Studies using brain-imaging techniques have shown changes in regional blood flow (rCBF) in patients with liver cirrhosis. It remains unknown whether the aetiology of liver disease accounts for these changes. AIMS: To evaluate whether the aetiology of liver cirrhosis is associated with different patterns of rCBF. MATERIALS AND METHODS: A total of 50 patients with end-stage liver disease and no overt encephalopathy were studied. Thirteen age-matched subjects admitted to the neurology department for headache were used as controls. Exclusion criteria were focal brain lesions, severe brain atrophy and any abnormalities found on computed tomography scan suggesting other central nervous system diseases, alcohol intake or use of neuroactive drugs for at least 6 months. rCBF was assessed using single-positron-emission tomography (SPECT) with 99mTc-hexamethylpropylene amine oxime (99mTc-HM-PAO) as a tracer in all patients and controls. The Mann-Whitney U test was used for statistical analysis. RESULTS: The liver-disease aetiology was as follows: alcoholic (A) in 19 patients; viral (V) (hepatitis B virus, hepatitis D virus, hepatitis C virus) in 14 patients; alcoholic with concomitant viral (A + V) in five patients; and cholestatic (C) (primary biliary cirrhosis, primary sclerosing cholangitis) in 12 patients. SPECT showed significantly lower rCBF in cirrhotic patients than in controls for most cortical and subcortical regions and in alcoholic and viral patients than in cholestatic liver disease patients for some cortical regions. When patients were grouped according to previous alcohol abuse (including cases with a concomitant viral aetiology), rCBF was significantly lower in the frontal superior, medial and temporal inferior regions in the alcoholic group. CONCLUSIONS: Cerebral blood flow is significantly lower in patients with liver cirrhosis than in controls and, among cirrhotics, it is lower in alcoholic and viral cirrhosis than in cholestatic liver disease. In patients with previous alcohol abuse, cerebral blood flow was significantly more reduced in the frontal and temporal regions compared with patients without previous alcohol abuse.     

Quantitative testing of liver function in patients with cirrhosis due to chronic hepatitis C to assess disease severity

BACKGROUND/AIMS: Quantitative testing of liver function (QTLF) may allow a prognostic assessment of patients with various liver diseases. However, there are insufficient data about patients with liver cirrhosis due to hepatitis C. PATIENTS/METHODS: 86 consecutive patients (58 males, 28 females, age: 48.3 +/- 11.7 years) with chronic hepatitis C (HCV RNA pos.) underwent sonographically guided liver biopsy to confirm the diagnosis of cirrhosis. QTLF included aminopyrine breath test (microsomal liver function), galactose elimination capacity (cytosolic liver function), sorbitol clearance (liver plasma flow) and indocyanine green clearance (liver perfusion). Values were correlated with the Child-Pugh classification. RESULTS: 55% of the patients (n=47) had cirrhosis of Child-Pugh grade A, 28% of grade B (n=24) and 17% of grade C (n=15). QTLF showed a steady decrease from Child-Pugh grade A to grade B and to grade C. Contrary to markedly reduced tests of metabolic liver function in Child-Pugh grade patients, surrogate tests of hepatic perfusion were at the lower normal limit. All QTLF were significantly reduced in Child-Pugh grade B and C patients compared to healthy controls. Differences between the three Child grades were significant. CONCLUSION: In patients with cirrhosis due to hepatitis C, QTLF correlated inversely with Child-Pugh grades. Since in cirrhosis of grade A, surrogate tests of hepatic perfusion remained at the lower normal limit, whereas those of metabolic function were decreased, QTLF may be a tool to predict prognosis or complications in early cirrhosis due to chronic hepatitis C.     

Proton magnetic resonance spectroscopy (1H-MRS) findings for the brain in patients with liver cirrhosis reflect the hepatic functional reserve

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) has been used to assess the metabolic changes in the brain in patients with liver cirrhosis. Decreased myo-inositol and increased glutamine levels were noted to be the most sensitive spectroscopic markers for cirrhotic patients with hepatic encephalopathy (HE). The purpose of this study was to assess how the abnormalities seen on the 1H-MRS of the brain in patients with liver cirrhosis are related to clinical and laboratory parameters. METHODS: In a prospective study, localized 1H-MRS was performed in the basal ganglia and parietal white matter regions in liver cirrhosis patients with (n = 48) and without (n = 52) HE and chronic hepatitis (CH) (n = 15), and in normal controls (n = 20). RESULTS: Among cirrhotic patients, the myo-inositol levels were significantly lower (p < 0.01) and the glutamine levels were higher (p < 0.05) for patients with HE than for those without HE. The myo-inositol and glutamine levels, respectively, were inversely (r = -0.50; p < 0.001) and linearly (r = 0.50; p < 0.001) related to the Child-Pugh score. However, by subgroup analysis of Child-Pugh class C patients, there were no significant differences in the myo-inositol and glutamine levels between cirrhotic patients with (n = 40) and without HE (n = 24). A follow-up study of eight cirrhotic patients with HE showed no significant differences in the myo-inositol and glutamine levels after clinical improvement of HE. CONCLUSIONS: The abnormalities seen on the 1H-MRS of the brain of patients with liver cirrhosis are not likely to reflect the severity of HE or acute alteration in the level of consciousness. Rather, we believe they represent the chronic metabolic derangement of the brain associated with hepatic functional reserve.     

Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy

OBJECTIVES: In patients with compensated liver cirrhosis the clinical repercussions of detecting subclinical hepatic encephalopathy (SHE) are unclear. We present a long-term follow-up study in cirrhotic patients to examine the relationship between SHE and subsequent episodes of overt hepatic encephalopathy. METHODS: A total of 63 cirrhotic patients were studied by Number Connection Test and auditory evoked potentials. We determined glutamine, ammonia, zinc, glutamate, urea, and ratio of branched chain amino acids to aromatic amino acids, and Child-Pugh classification. RESULTS: Of 63 patients, 34 (53%) exhibited SHE. Nineteen out of 63 (30%) developed overt hepatic encephalopathy during follow-up. Hepatic encephalopathy in follow-up was related to alcoholic etiology, ammonia, glutamine, zinc, ratio of branched chain amino acids to aromatic amino acids, liver function, presence of esophageal varices, and detection of SHE (84% of patients who exhibited hepatic encephalopathy in follow-up showed SHE). In Cox-regression, glutamine levels, SHE, esophageal varices, and Child-Pugh class were the independent variables related to hepatic encephalopathy in follow-up. CONCLUSIONS: SHE (defined on the basis of number connection test or auditory evoked potentials alteration) could predict a subsequent episode of overt hepatic encephalopathy. Lower glutamine levels, presence of esophageal varices, and liver dysfunction were also related to the development of overt hepatic encephalopathy.     

Screening of subclinical hepatic encephalopathy

BACKGROUND/AIMS: Subclinical hepatic encephalopathy adversely affects daily functioning. The aim of this study was to determine which elements of daily life have predictive value for subclinical hepatic encephalopathy. METHODS: The study was performed in 179 outpatients with liver cirrhosis. Subclinical hepatic encephalopathy was diagnosed using psychometric tests with normal values corrected for age (Number Connection Test A and the Digit Symbol Test) and automated analysis of the electroencephalogram (EEG). Daily functioning was measured with the Sickness Impact Profile (SIP), a quality of life questionnaire, containing 136 statements. Patients with and without SHE were compared for differences in response to all statements by univariate analysis, and subsequently by multivariate analysis of potential discriminating statements. RESULTS: SHE was diagnosed in 48 patients (27%). Thirty-six statements were significantly more often true for patients with subclinical hepatic encephalopathy. Multivariate analysis showed that five statements of the SIP, related to alertness, sleep and rest, fine motor skills and work, have independent predictive power for subclinical hepatic encephalopathy. CONCLUSION: Combining these statements predictive for subclinical hepatic encephalopathy with patient characteristics enables physicians to assess the probability of subclinical hepatic encephalopathy in the individual cirrhotic patient at the bedside or in the outpatient clinic.     

肝炎肝硬化患者骨髓TPO、GM—CSF表达与外周血细胞的关系

目的探讨骨髓内环境造血因子血小板生成素（TPO）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）在肝炎肝硬化患者骨髓液中的表达及其与外周血细胞的关系。方法选取31例肝炎肝硬化患者和15例健康对照组,晨起空腹采血、检测血常规、肝脏功能、肝炎病毒标志物,并行骨髓穿刺术,取骨髓液、离心分离,用双抗体夹心ELISA法检测骨髓液中TPO、GM-CSF浓度。结果肝炎肝硬化患者骨髓液TPO浓度与外周血血小板计数呈负相关（r=-0.496,P〈0.05）。骨髓液TPO的浓度在肝炎肝硬化组和对照组分别为（90.756±30.92）pg/ml、（118.414±49.232）pg/ml,二者之间有差异,但差异无统计学意义。肝脏功能按照Child-Pugh分为A、B、C级,分别与对照组比较,发现随肝脏损害加重,TPO浓度呈下降趋势,但差异无统计学意义。GM-CSF的浓度在肝硬化组和对照组之间差异无统计学意义。结论肝炎肝硬化患者骨髓内环境TPO浓度降低可能是外周血血小板计数减少的原因之一。肝脏功能状态及GM-CSF与外周血细胞计数变化的关系还有待进一步研究。     

神经诱发电位对肝硬化患者亚临床肝性脑病的诊断意义

目的:探讨神经诱发电位对肝硬化亚临床脑病的诊断价值。方法:用神经诱友电位仪检测29例失代偿期肝硬化患者视觉诱发电位(VEP)与脑干听觉诱发电位(BAEP)的变化。结果:29例肝硬化患者中,VEP异常12例(41.4％),BAEP异常14例(48.3％),总异常率为65.5％。结论:诱发电位检查对于肝硬化亚临床肝性脑病是一种客观而又敏感的方法。     

Plasma erythropoietin level in patients with cirrhosis and its relationship to the severity of cirrhosis and renal function

BACKGROUND AND AIM: The level of plasma erythropoietin (EPO) in patients with cirrhosis is controversial. It is known that overproduction of nitric oxide (NO) plays, in part, a role for the development of peripheral arterial vasodilatation in cirrhosis with portal hypertension. It has also been hypothesized that a possible interaction is noted between endogenous EPO and NO production. The current study was undertaken to evaluate the relationship between plasma EPO levels and the severity of liver disease, hemodynamic values, renal functions, and plasma nitrate/nitrite levels in patients with cirrhosis. METHODS: The authors measured the biochemistry, plasma EPO and nitrate/nitrite levels in 67 patients with cirrhosis (Child-Pugh class A in 23 and Child-Pugh class B and C in 44) and compared their values with those in 34 healthy subjects. Systemic and splanchnic hemodynamic measurements and effective renal plasma flow were obtained from cirrhotic patients. RESULTS: Plasma EPO and nitrate/nitrite levels were significantly increased in patients with cirrhosis compared with healthy subjects. Additionally, plasma EPO values were higher in cirrhotic patients with ascites or with anemia than in those without ascites or without anemia, respectively. Plasma EPO levels were positively correlated to the hepatic venous pressure gradient (HVPG) and Child-Pugh score, negatively correlated to the renal and hepatic blood flows, but were not correlated to nitrate/nitrite level and systemic vascular resistance in cirrhotic patients. Multiple regression analysis showed that HVPG and renal plasma flow were independent predictors for the elevated EPO level in cirrhotic patients. CONCLUSIONS: Plasma EPO levels were increased in patients with cirrhosis compared with those in healthy subjects. The increase in plasma EPO levels is related to the degree of portal hypertension, the severity of cirrhosis and the renal plasma flow. In contrast, the EPO levels had no correlation to the nitrate/nitrite levels and systemic vascular resistance in patients with cirrhosis.