Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China

AIM:To construct normal values for the tests of the psychometric hepatic encephalopathy score(PHES)and to evaluate its usefulness in the diagnosis of minimal hepatic encephalopathy(MHE)among Chinese individuals with cirrhosis.METHODS:The five tests of PHES,number connection test-A(NCT-A),number connection test-B,serial dotting test,line tracing test and digit symbol test(DST),were administered to all enrolled subjects in a quiet room with sufficient light.Cirrhotic subjects with overt HE were excluded by the West-Haven criteria and a detailed neurological examination.Based on the nomograms of healthy volunteers,the patients were classified as having MHE when their PHES was less than-4.RESULTS:In total,146 healthy volunteers completed all the PHES tests.Age and education years were confirmed to be predictors of all five tests.In total,53patients with liver cirrhosis completed the PHES.Of the patients with liver cirrhosis,24(45.3%),22(41.5%)and 7(13.2%)had Child-Pugh grades A,B and C,respectively.MHE was diagnosed in 26 patients(49.1%).Compared with compensated cirrhotic patients(Child A),decompensated cirrhotic patients(Child B and C)had a higher proportion of MHE(65.5%vs 29.2%).No differences in age and education years were found between the MHE and non-MHE groups.NCT-A and DST were able to diagnose MHE with a sensitivity of 76.9%and a specificity of 96.3%(AUC=0.866,K=0.735).CONCLUSION:The proportion of MHE is associated with liver function.NCT-A and DST are simple tools that can be used for the diagnosis of MHE in China.     

Effects of L-carnitine in patients with hepatic encephalopathy

AIM: To evaluate the influence of L-carnitine on mental conditions and ammonia effects on patients with hepatic encephalopathy (HE). METHODS: One hundred and fifty patients (10 patients with alcoholism, 41 patients with hepatitis virus B infection, 78 patients with hepatitis C virus infection, 21 patients with cryptogenetic cirrhosis) meeting the inclusion criteria were randomized into group A receiving a 90-d treatment with L-carnitine (2 g twice a day) or into group B receiving placebo in double blind. RESULTS: At the end of the study period, a significant decrease in NH4 fasting serum levels was found in patients with hepatic encephalopathy (P<0.05) after the treatment with levocarnitine (LC). Significant differences were also found between symbol digit modalities test and block design in patients with hepatic encephalopathy (P<0.05). CONCLUSION: Results of our study suggest an important protective effect of L-carnitine against ammonia-precipitated encephalopathy in cirrhotic patients.     

Diagnostic value of fine motor deficits in patients with low-grade hepatic encephalopathy

AIM: The role of motor dysfunction in early diagnosis of low-grade hepatic encephalopathy remains uncertain. We performed a pilot study to comparatively investigate the kinematic characteristics of small and large rapid alternating movements in patients with liver cirrhosis and low-grade hepatic encephalopathy. METHODS: A kinematic analysis of alternating handwriting (7.5mm) and large drawing movements (DM, 175 mm) was performed in 30 patients with liver cirrhosis (no hepatic encephalopathy: n=10; minimal hepatic encephalopathy: n=9; grade I hepatic encephalopathy: n=11; healthy controls: n=12). The correlation between kinematic parameters, clinical neuro-psychiatric symptoms of cerebral dysfunction and the grade of encephalopathy was investigated. RESULTS: Both movement types, handwriting and drawing, were significantly slower in cirrhotic patients. In contrast to large DM, the deterioration of handwriting movements significantly correlated with the increase of symptoms of motor dysfunction and differentiated significantly within the group of cirrhosis patients corresponding to the degree of hepatic encephalopathy. CONCLUSION: The deterioration of fine motor control is an important symptom of low-grade hepatic encephalopathy. The kinematic analysis of handwriting allows the quantitative analysis of alterations of motor function and is a possible tool for diagnostics and monitoring of motor dysfunction in patients with low-grade hepatic encephalopathy.     

Clinical significance of serum expression of GROβ in esophageal squamous cell carcinoma

AIM:To determine the association between serum levels of growth-related gene product β(GROβ) and clinical parameters in esophageal squamous cell carcinoma(ESCC).METHODS:Using enzyme-linked immunosorbent assay,serum GROβ levels were measured in ESCC patients(n = 72) and healthy volunteers(n = 83).The association between serum levels of GROβ and clinical parameters of ESCC was analyzed statistically.RESULTS:The serum GROβ levels were much higher in ESCC patients than in healthy controls(median:645 ng/L vs 269...     

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.     

Prevalence of subclinical hepatic encephalopathy in cirrhotic patients in China

AIM:Subclinical hepatic encephalopathy (SHE) is a commoncomplication of liver diseases.The aim of this study wasto find out the normal value of psychometric test and toinvestigate the prevalence of SHE in Chinese patients withstabilized hepatic cirrhosis.METHODS:Four hundred and nine consecutive cirrhoticpatients without overt clinical encephalopathy werescreened for SHE by using number connection test part A(NCT-A) and symbol digit test (SDT).SHE was defined aspresence of at least one abnormal psychometric test.Theage-corrected normal values were defined as the mean±2times standard deviation (2SD),and developed in 356 healthypersons as normal controls.Four hundred and sixteenpatients with chronic viral hepatitis were tested as negativecontrols to assess the diagnostic validity of this test battery.RESULTS:There was no significant difference in NCTscores and SDT quotients between healthy controls andchronic hepatitis group (P>0.05).In all age subgroups,the NCT and SDT measurements of cirrhotic patientsdiffered significantly from those of the controls (P<0.05).When mean±2SD of SDT and NCT measurements fromhealthy control group was set as the normal range,229cirrhotic patients (29.1%) were found to have abnormalNCT-A and SDT tests,53 (13.0%) were abnormal only inSDT and 36 (8.8%) only in NCT-A.Taken together,SHEwas diagnosed in 208 (50.9%) cirrhotic patients by thistest 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<0.05).After theadjustment of age and residential areas required from thetests,no correlation was found in the rate of SHE andcauses of cirrhosis,education level and smoking habit.CONCLUSION:Psychometric tests are simple and reliableindicators for screening SHE among Chinese cirrhoticpatients.By using a NCT and SDT battery,SHE could befound in 50.9% of cirrhotic patients without overt clinicalencephalopathy.The prevalence of SHE is significantlycorrelated with the severity of liver functions.     

Rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity

AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene sequencing.RESULTS Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSION Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.     

Low phase angle is associated with the development of hepatic encephalopathy in patients with cirrhosis

AIM Evaluate the association between phase angle and the development of hepatic encephalopathy in the longterm follow-up of cirrhotic patients.METHODS This was a prospective cohort study. Clinical, nutritional and biochemical evaluations were performed. MannWhitney's U and χ2 tests were used as appropriate. Kaplan-Meier curves and Cox proportional Hazards analysis were used to evaluate the prediction and incidence of hepatic encephalopathy.RESULTS Two hundred and twenty were included; the most frequent etiology of cirrhosis was hepatitis C infection, 52% of the patients developed hepatic encephalopathy(18.6% covert and 33.3% overt); the main precipitating factors were infections and variceal bleeding. KaplanMeier curves showed a higher proportion of HE in the group with low phase angle(39%) compared to the normal phase angle group(13%)(P = 0.012). Furthermore, creatinine and phase angle remained independently associated to hepatic encephalopathy in the Cox regression multivariate analysis [hazard ratio = 1.80(1.07-3.03)]. CONCLUSION In our cohort of patients low phase angle was associated with an increased incidence of hepatic encephalopathy. Phase angle is a useful nutritional marker that evaluates cachexia and could be used as a part of the integral assessment in patients with cirrhosis.     

Incidence and clinical presentation of portal vein thrombosis in cirrhotic patients

BACKGROUND: Portal vein thrombosis (PVT) is due to many risk factors, but its pathogenesis is still not clearly understood. To identify the risk factors for PVT, we analyzed the clinical characteristics and complications associated with PVT in cir-rhotic patients.
METHODS: We studied patients with liver cirrhosis who were admitted to our unit from April 2009 to December 2014. The patients were divided into the PVT and non-PVT groups, and were compared by variables including gender, age, the etiology of cirrhosis, stage of cirrhosis, complications, imaging, and treatment.
RESULTS: PVT was found in 45 (9.8%) of 461 cirrhotic pa-tients admitted to our hospital. Most patients (45.9%) had hepatitis B virus (HBV)-related cirrhosis, with a similar dis-tribution of etiologies between the groups. However, there was no positive relationship between PVT and etiologies of cirrhosis. Most patients (71.5%) were in the stage of hepatic decompensation. No statistically signiifcant differences were found in complications including esophageal varices, ascites, and hepatic encephalopathy between the groups. However, there was a signiifcant positive correlation between hepatocel-lular carcinoma (HCC) and PVT (P<0.01). In 30 patients with PVT, thrombosis occurred in the portal vein and/or portal branches, 37.8% were diagnosed on ultrasound.
CONCLUSIONS: The incidence of PVT was 9.8%, mainly in patients with HBV-related cirrhosis. The development of PVT was associated with the severity of liver disease and HCC.     

Contrast-enhanced ultrasound evaluation of hepatic microvascular changes in liver diseases

AIM:To assess if software assisted-contrast-enhanced ultrasonography (CEUS) provides reproducible perfusion parameters of hepatic parenchyma in patients affected by chronic liver disease. METHODS:Forty patients with chronic viral liver disease, with (n = 20) or without (n = 20) cirrhosis, and 10 healthy subjects underwent CEUS and video recordings of each examination were then analysed with Esaote's Qontrast software. CEUS dedicated software Qontrast was used to determine peak (the maximum signal intensity), time to peak (TTP), region of blood value (RBV) proportional to the area under the time-intensity curve, mean transit time (MTT) measured in seconds and region of blood flow (RBF). RESULTS:Qontrast-assisted CEUS parameters displayed high inter-observer reproducibility (k coefficients of 0.87 for MTT and 0.90 TTP). When the region of interest included a main hepatic vein, Qontrast-calculated TTP was significantly shorter in cirrhotic patients (vs non-cirrhotics and healthy subjects) (71.0 ± 11.3 s vs 82.4 ± 15.6 s, 86.3 ± 20.3 s, P 0.05). MTTs in the patients with liver cirrhosis were significantly shorter than those of controls (111.9 ± 22.0 s vs 139.4 ± 39.8 s, P 0.05), but there was no significant difference between the cirrhotic and non-cirrhotic groups (111.9 ± 22.0 s vs 110.3 ± 14.6 s). Peak enhancement in the patients with liver cirrhosis was also higher than that observed in controls (23.9 ± 5.9 vs 18.9 ± 7.1, P = 0.05). There were no significant intergroup differences in the RBVs and RBFs. CONCLUSION:Qontrast-assisted CEUS revealed reproducible differences in liver perfusion parameters during the development of hepatic fibrogenesis.     

Clinical significance of serum IGF-I,IGF-II and IGFBP-3 in liver cirrhosis

AIM:To investigate the relationship between insulin-likegrowth factor-Ⅰ,-Ⅱ (IGF-Ⅰ and IGF-Ⅱ),IGF-binding protein 3(IGFBP-3) and Child-Pugh score in patients with liver cirrhosis,and to search for potential clinical markers of liver function.METHODS:Forty-four patients with advanced liver cirrhosisof viral origin were divided into 3 groups according to severityof cirrhosis (Child-Pugh score) and 38 healthy subjectsserved as controls.Serum levels of IGF-Ⅰ,IGF-Ⅱ and IGFBP-3 were measured by immunoradiometric assay.RESULTS:Serum IGF-Ⅰ,IGF-Ⅱ and IGFBP-3 levels weresignificantly lower in patients with cirrhosis than in controls,and serum concentrations of IGF-Ⅰ,IGF-Ⅱ and IGFBP-3 wereassociated with the severity of liver dysfunction,and droppedsharply during the progression of liver failure.Among these3 parameters,serum IGF-Ⅱ was the most sensitive andeffective indicator for liver dysfunction.Concentrations ofIGF-Ⅰ <30 ng/mL,IGF-Ⅱ <200 ng/mL and IGFBP-3 <6 ng/mLimplied a negative prognosis for patients with liver cirrhosis.CONCLUSION:Serum IGF-Ⅰ,IGF-Ⅱ and IGFBP-3 may providea new dimension in the assessment of liver dysfunction.Combined detection of serum IGF-Ⅰ,IGF-Ⅱ and IGFBP-3with Child-Pugh score is more effective in predicting prognosisthan Child-Pugh score alone.     

Frontal assessment battery: A tool for screening minimal hepatic encephalopathy?

AIM To apply the Frontal Assessment Battery to cirrhotic patients with or without overt hepatic encephalopathy(OHE) and controls. METHODS The frontal assessment battery(FAB) was applied to 87 patients with liver cirrhosis(16 with and 71 without OHE) and 40 control subjects without cirrhosis treated at the alcohol and liver outpatient clinics and the gastroenterology ward of the Cassiano Ant?nio de Moraes University Hospital(Hospital Universitário Cassiano Ant?nio de Moraes- HUCAM), Espírito Santo, Brazil.RESULTS The average FAB score was lower for the cirrhotic than for the non-cirrhotic patients(10.6 ± 3.67 vs 12.25 ± 2.72, P = 0.015). The FAB score was lower for the cirrhotic patients with OHE than for the patients without OHE(8.25 ± 4.55 vs 11.14 ± 3.25, P = 0.027). The total FAB score was lower for the cirrhotic patients without OHE than for the non-cirrhotic patients, although this difference was not significant(11.14 ± 3.25 vs 12.25 ± 2.72, P = 0.067). Nevertheless, the difference in the scores on the subtest that assessed the ability to inhibit a response previously conditioned to a stimulus was significant(1.72 ± 0.93 vs 2.2 ± 0.85, P = 0.011).CONCLUSION The present study indicates that the FAB is a promising tool for outpatient minimal HE screening and the assessment of HE severity.     

T cell immune response is correlated with fibrosis and inflammatory activity in hepatitis B cirrhotics

AIM: To explore the relationship among interferon-γ(IFN-γ) activity, fibrogenesis, T cell immune responses and hepatic inflammatory activity. METHODS: Peripheral blood samples from a total of 43 hepatitis B cirrhotic patients (LC) and 19 healthy controls (NC) were collected to measure their serum levels of IFN-γ, interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-10 (IL-10) and three serological markers of fibrosis including hyaluronic acid (HA), procol-lagen typeⅢpeptide (PⅢP), and typeⅣcollagen were measured using a double antibody sandwich ELISA. Also, serum total bilirubin (TB) and alanine aminotransferase (ALT) were measured by routine measures. RESULTS: The concentrations of serological markers of fibrosis in patients with active cirrhosis (ALC) were significantly higher than those in stationary liver cirrhosis (SLC) or NC groups. The levels of serological markers in HBeAg-positive patients were significantly higher than those in HBeAg-negative patients. In SLC and ALC patients, a negative linear correlation was found between IFN-γlevels and the serological markers of fibrosis. IFN-γand IL-2 levels in the ALC group were significantly higher than those in the SLC and NC groups, but the statistical difference was not significant between the latter two. In contrast, IL-10 levels in the SLC group were significantly higher than that in the NC group, but no significant difference was found between SLC and ALC groups. The sIL-2R level was elevated gradually in all these groups, and the differences were significant. Positive linear correlations were seen between IFN-γactivity and ALT levels (r=0.339, P < 0.05), and IL-2 activity and TB levels (r=0.517, P < 0.05). SIL-2R expression was positively correlated with both ALT and TB levels (r=0.324, 0.455, P < 0.05), whereas there was no statistically significant correlation between IL-10 expression and serum ALT and TB levels (r = -0.102, -0.093, P > 0.05). Finally, there was a positive correlation between IFN-γand IL-2 levels. CONCLUSION: T cell immune responses are correlated with fibrosis and hepatic inflammatory activity and may play an important role in liver cirrhosis.     

The effects of Helicobacter pylori infection on hyperammonaemia and hepatic encephalopathy in cirrhotic patients

Objective To evaluate the relationship among Helicobacter pylori (Hp) infection, blood ammonia concentrations , and hepatic encephalopathy (HE) status, and to investigate the effect of Hp eradication on blood ammonia levels and hepatic encephalopathy status in cirrhotic patients. Methods From July 2003 to Jan 2005, cirrhotic patients in 5 regions of Zhejiang Province were enrolled. Patients were evaluated for the demographic checklists, number connection test, Hp infection, liver impairment level, blood ammonia concentrations and he-     

Relationship between pre-TIPS hepatic hemodynamics and postoperative incidence of hepatic encephalopathy

BACKGROUND: Hepatic encephalopathy (HE) is one of the complications that have limited the effectiveness of transjugular intrahepatic portosystemic shunt (TIPS) most significantly. Up to the present, the predicting factors of HE post-TIPS have been debated controversially. This study was undertaken to verify the relationship between pre-TIPS intrahepatic hemodynamics and the incidence of post-TIPS HE. METHODS: The hepatic blood dynamics was evaluated in 41 patients with liver cirrhosis before TIPS and at one month after TIPS by ultrasonography. The patients were divided into two groups according to Doppler findings before TIPS: group 1, patients with prograde portal flow, and group 2, patients with hepatofugal or back-forth portal flow. The clinical characteristics (age, sex, etiology of liver disease, pre-TIPS Child-Pugh score, incidence of pre-TIPS HE, and portacaval pressure gradient), incidence of post TIPS HE, and pre-/post-TIPS hepatic arterial resistant index (RI) in the two groups were compared. The independent prognostic value of pre-TIPS variables for the onset of HE after TIPS, including age, Child-Pugh score, presence of HE before TIPS, and the pattern of portal flow, was tested with a multiple-factor regression analysis. RESULTS: No significant difference in age, etiology of liver disease, indications of TIPS placement, incidence of HE before TIPS, and portacaval gradient before and after TIPS was observed between the two groups; but liver failure was more severe in group 2 (P<0.05). The incidence of post-TIPS HE in group 2 was significantly lower than that in group 1 (P<0.01). Pre-TIPS, the RI of the hepatic artery in group 1 was significantly higher than that in group 2 (P<0.01). However, TIPS induced a significantly decreased RI in group 1 (P <0.01), but not in group 2. Multiple-factor regression analysis demonstrated that the pattern of portal flow before TIPS was closely associated with the onset of post TIPS HE. CONCLUSIONS: Pre-TIPS intrahepatic hetnodynamics is closely related to the incidence of post-TIPS HE. Hepatic hetnodynamics of patients with hepatofugal portal blood flow only changes a little after TIPS and still provides compensatory blood supply of the hepatic artery, and the hepatic function is less affected. Hence HE is unlikely. Hepatic hemodynamics of patients with prograde portal blood flow changes a lot after TIPS, and dual blood supply of the portal vein and hepatic artery changes into compensatory blood supply of the hepatic artery, and hepatic function suffers greatly in a short time. Thus HE is mostly likely.     

Correlation of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function in Chinese patients with chronic hepatitis C virus infection

AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their potential clinical implications. METHODS: Forty-two chronic HCV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed statistically. RESULTS: The mean of serum leptin levels in patients with chronic hepatitis C, HCV-associated cirrhosis, HCV-associated HCC and control groups was (6.13±3.94), (5.25±4.21), (4.17±0.28), and (3.59±3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis C was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum alanine aminotransferase (ALT) levels were closely-correlated with BMI in patients with chronic hepatitis C. CONCLUSION: HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.     

Endozepine-4 levels are increased in hepatic coma

AIM:To evaluate the serum levels of endozepine-4,their relation with ammonia serum levels,the grading of coma and the severity of cirrhosis,in patients with hepatic coma. METHODS:In this study we included 20 subjects with Hepatic coma,20 subjects with minimal hepatic encephalopathy(MHE) and 20 subjects control. All subjects underwent blood analysis,Child Pugh and Model for End- stage liver disease(MELD) assessment,endozepine-4 analysis. RESULTS:Subjects with hepatic coma showed significant difference in endozepine-4(P 0.001) and NH3 levels(P 0.001) compared both to MHE and controls patients. Between NH3 and endozepine-4 we observed a significant correlation(P = 0.009; Pearson correlation 0.570). There was a significant correlation between endozepine-4 and MELD(P = 0.017; Pearsoncorrelation = 0.529). In our study blood ammonia concentration was noted to be raised in patients with hepatic coma,with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia(P 0.001). In patients with grade Ⅳ hepatic coma,endozepine levels were significantly higher compared to other groups. CONCLUSION:This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion,data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations.     

Clinical significance of serum IGF-Ⅰ, IGF-Ⅱ and IGFBP-3 in liver cirrhosis

AIM: To investigate the relationship between insulin-like growth factor-Ⅰ, -Ⅱ (IGF-Ⅰ and IGF-Ⅱ), IGF-binding protein 3(IGFBP-3) and Child-Pugh score in patients with liver cirrhosis,and to search for potential clinical markers of liver function.METHODS: Forty-four patients with advanced liver cirrhosis of viral origin were divided into 3 groups according to severity of cirrhosis (Child-Pugh score) and 38 healthy subjects served as controls. Serum levels of IGF-Ⅰ, IGF-Ⅱ and IGFBP-3 were measured by immunoradiometric assay.RESULTS: Serum IGF-Ⅰ, IGF-Ⅱ and IGFBP-3 levels were significantly lower in patients with cirrhosis than in controls,and serum concentrations of IGF-Ⅰ, IGF-Ⅱ and IGFBP-3 were associated with the severity of liver dysfunction, and dropped sharply during the progression of liver failure. Among these 3 parameters, serum IGF-Ⅱ was the most sensitive and effective indicator for liver dysfunction. Concentrations of IGF-Ⅰ &lt;30 ng/mL, IGF-Ⅱ &lt;200 ng/mL and IGFBP-3 &lt;6 ng/mL implied a negative prognosis for patients with liver cirrhosis.CONCLUSION: Serum IGF-Ⅰ, IGF-Ⅱ and IGFBP-3 may provide a new dimension in the assessment of liver dysfunction.Combined detection of serum IGF-Ⅰ, IGF-Ⅱ and IGFBP-3 with Child-Pugh score is more effective in predicting prognosis than Child-Pugh score alone.     

Natural history of covert hepatic encephalopathy: An observational study of 366 cirrhotic patients

AIM To explore the natural history of covert hepatic encephalopathy(CHE) in absence of medication intervention.METHODS Consecutive outpatient cirrhotic patients in a Chinese tertiary care hospital were enrolled and evaluated for CHE diagnosis. They were followed up for a mean of 11.2 ± 1.3 mo. Time to the first cirrhosis-related complications requiring hospitalization, including overt HE(OHE), resolution of CHE and death/transplantation, were compared between CHE and no-CHE patients. Predictors for complication(s) and death/transplantation were also analyzed.RESULTS A total of 366 patients(age: 47.2 ± 8.6 years, male: 73.0%) were enrolled. CHE was identified in 131 patients(35.8%). CHE patients had higher rates of death and incidence of complications requiring hospitalization, including OHE, compared to unimpaired patients. Moreover, 17.6% of CHE patients developed OHE, 42.0% suffered persistent CHE, and 19.8% of CHE spontaneously resolved. In CHE patients, serum albumin 30 g/L(HR = 5.22, P = 0.03) was the sole predictor for developing OHE, and blood creatinine 133 μmol/L(HR = 4.75, P = 0.036) predicted mortality. Child-Pugh B/C(HR = 0.084, P 0.001) and OHE history(HR = 0.15, P = 0.014) were predictors of spontaneous resolution of CHE.CONCLUSION CHE exacerbates, persists or resolves without medication intervention in clinically stable cirrhosis. Triage of patients based on these predictors will allow for more cost-effect management of CHE.     

Pituitary hormone circadian rhythm alterations in cirrhosis patients with subclinical hepatic encephalopathy

AIM： To analyze pituitary hormone and melatonin circadian rhythms, and to correlate hormonal alterations with clinical performance, hepatic disease severity and diagnostic tests used for the detection of hepatic encephalopathy in cirrhosis. METHODS： Twenty-six patients with cirrhosis were enrolled in the study. Thirteen patients hospitalized for systemic diseases not affecting the liver were included as controls. Liver disease severity was assessed by the Child-Pugh score. All patients underwent detailed neurological assessment, electroencephalogram （EEG）, brain magnetic resonance imaging （MRI）, assays of pi- tuitary hormone, cortisol and melatonin, and complete blood chemistry evaluation. RESULTS： Pituitary hormone and melatonin circadian patterns were altered in cirrhosis patients without clinical encephalopathy. Circadian hormone alterations were different in cirrhosis patients compared with controls. Although cortisol secretion was not altered in any patient with cirrhosis, the basal cortisol levels were low and correlated with EEG and brain MRI abnormalities. Melatonin was the only hormone associated with the severity of liver insufficiency. CONCLUSION： Abnormal pituitary hormone and melatonin circadian patterns are present in cirrhosis before the development of hepatic encephalopathy. These abnormalities may be early indicators of impending hepatic encephalopathy. Factors affecting the human biologic clock at the early stages of liver insufficiency require further study.