Neurodevelopmental Outcomes in Preschool and School Aged Children With Biliary Atresia and Their Native Liver.

OBJECTIVES: The aim of the study was to assess neurodevelopmental outcomes among children with biliary atresia (BA) surviving with their native liver at ages 3 to 12 years and evaluate variables that associate with neurodevelopment. METHODS: Participants (ages 3-12 years) in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with Weschler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI-III, ages 3-5 years) and Weschler Intelligence Scale for Children, 4th edition (WISC-IV, ages 6-12 years). Continuous scores were analyzed using Kolmogorov-Smironov tests compared with a normal distribution (mean = 100 ±â€Š15). Effect of covariates on Full-Scale Intelligence Quotient (FSIQ) was analyzed using linear regression. RESULTS: Ninety-three participants completed 164 WPPSI-III (mean age 3.9) and 51 WISC-IV (mean age 6.9) tests. WPPSI-III FSIQ (104 ±â€Š14, P < 0.02), Verbal IQ (106 ±â€Š14, P < 0.001), and General Language Composite (107 ±â€Š16, P < 0.001) distributions were shifted higher compared with test norms. WISC-IV FSIQ (105 ±â€Š12, P < 0.01), Perceptual Reasoning Index (107 ±â€Š12, P < 0.01), and Processing Speed Index (105 ±â€Š10, P < 0.02) also shifted upwards. In univariate and multivariable analysis, parent education (P < 0.01) was a significant predictor of FSIQ on WPPSI-III and positively associated with WISC-IV FSIQ. Male sex and higher total bilirubin and gamma glutamyl transferase (GGT) predicted lower WPPSI-III FSIQ. Portal hypertension was predictive of lower WISC-IV FSIQ. CONCLUSIONS: This cohort of children with BA and native liver did not demonstrate higher prevalence of neurodevelopmental delays. Markers of advanced liver disease (higher total bilirubin and GGT for age ≤5 years; portal hypertension for age ≥6) correlate with lower FSIQ and may identify a vulnerable subset of patients who would benefit from intervention.

Health-Related Quality of Life in Children with Biliary Atresia Living with Native Livers.

INTRODUCTION: This study aimed to quantify and investigate factors affecting the health-related quality of life (HRQoL) in children with biliary atresia (BA) living with their native livers. MATERIALS AND METHODS: A cross-sectional study on the HRQoL using the PedsQL4.0 generic core scales in children with BA aged between 2 to 18 years followed up at the University Malaya Medical Centre (UMMC) in Malaysia was conducted. Two groups, consisting of healthy children and children with chronic liver disease (CLD) caused by other aetiologies, were recruited as controls. RESULTS: Children with BA living with their native livers (n = 36; median (range) age: 7.4 (2 to 18) years; overall HRQoL score: 85.6) have a comparable HRQoL score with healthy children (n = 81; median age: 7.0 years; overall HQRoL score: 87.4; P = 0.504) as well as children with CLD (n = 44; median age: 4.3 years; overall score: 87.1; P = 0.563). The HRQoL of children with BA was not adversely affected by having 1 or more hospitalisations in the preceding 12 months, the presence of portal hypertension, older age at corrective surgery (>60 days), a lower level of serum albumin (≤34 g/L) or a higher blood international normalised ratio (INR) (≥1.2). Children who had liver transplantation for BA did not have a significantly better HRQoL as compared to those who had survived with their native livers (85.4 vs 85.7, P = 0.960). CONCLUSION: HRQoL in children with BA living with their native livers is comparable to healthy children.

Brain network function during shifts in learning strategies in portal hypertension animals.

Patients with minimal hepatic encephalopathy exhibit early impairments in their ability to shift attentional set. We employed a task-switching protocol to evaluate brain network changes. Strategy switching requires the modification of both the relevant stimulus dimension and the required memory system. Rats were trained in an allocentric (A) and a cue-guided (C) task using a four-arm maze. To examine priming, we changed the order in which the tasks were presented. Five groups of animals were used: a SHAM (sham-operated) A-C group (n=10), a SHAM C-A group (n=8), a PH (portal hypertension) A-C group (n=8), PH C-A group (n=8), and a naïve group (n=10). The triple portal vein ligation method was used to create an animal model of the early evolutive phase of PH. The animals were tested in the four-arm radial water maze in a single 10-trial session each day for six days (three days for the allocentric task and three days for the cue-guided task). The metabolic activities of the brains were studied with cytochrome oxidase histochemistry, and brain network changes were assessed with principal component analysis. The behavioural results revealed significant increases in the numbers of correct choices across training days in all groups studied, and facilitation of the acquisition of the second task was present in the C-A groups. Moreover, different brain network activities were found; in the experimental groups, the performance of A-C switch involved the prefrontal cortex, and the key structures involved in the C-A switch in the other groups were the dentate gyrus of the dorsal hippocampus and the basolateral and central amygdala. These networks have a common nucleus of structures (i.e., the parietal cortex and the dorsal and ventral striatum), whereas other structures were specifically involved in each type of strategy, suggesting that these regions are part of both circuits and may interact with one another during learning.

Lactulose for minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction.

BACKGROUND/AIMS: Minimal hepatic encephalopathy (MHE) is common in patients with extrahepatic portal vein obstruction (EHPVO). There is no study on the treatment of MHE using lactulose in patients with EHPVO. PATIENTS AND METHODS: Consecutive EHPVO patients were assessed by psychometric (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), and critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were treated with lactulose and psychometric tests, CFF, and were reassessed after 3 months. RESULTS: Of the 70 patients screened, the prevalence of abnormal psychometric test was as follows: NCT-A (41%), NCT-B (53%), DST (38%), SDT (40%), and LTT (44%). Thirty patients (43%) had two or more than two abnormal (>2 SD) psychometry tests. Lactulose improved MHE in 16/30 (53%) of patients after 3 months of treatment. Arterial ammonia decreased after lactulose treatment compared to baseline (83.7±19.1 vs. 65.1±19.3 µmol/l, P=0.001). A total of 9 (75%) of 12 patients with large spontaneous shunt and 7 (39%) of 18 patients without spontaneous shunt improved with lactulose (P=0.07). CFF in patients with MHE (n=30) was significantly lower than those without MHE (n=40) (38.1±2.4 vs. 41.5±3.1 Hz, P=0.01). CFF was less than 38 Hz in 21 (70%) of 30 patients before treatment and in 10 (33%) patients after lactulose therapy in MHE patients. All patients could tolerate lactulose without any significant side effects. Four patients (13%) developed transient diarrhea in whom dose needed reduction, 3 (10%) did not like its taste but have continued, and 2 (6%) developed abdominal bloating sensation. CONCLUSIONS: Lactulose is effective in the treatment of MHE in patients with EHPVO.

Brain metabolism and spatial memory are affected by portal hypertension.

Portal hypertension is a major complication of cirrhosis that frequently leads to a neuropsychiatric disorder that affects cognition. The present study was undertaken in order to compare the performance of sham-operated rats (SHAM) and portal hypertension rats (PH) in reference memory tasks in the Morris water maze (MWM). Two groups of animals were used: SHAM group (n=12) was used as a control group and PH group (n=12) by the triple portal vein ligation method was used as an animal model of early evolutive phase of PH. The portal pressure was measured in the splenic parenchyma. Our work shows that spatial learning in the MWM is not impaired in PH group although this group showed a one-day delay in the task acquisition compared to the SHAM group. We assessed the brain metabolic activity of the animals by means of cytochrome c-oxidase (COx) histochemistry. Significant changes were found in the CA3, dentate gyrus, basolateral, medial, lateral and central amygdala, showing lower COx activity in the PH group as compared to the SHAM group in all cases. We found no changes in metabolic activity in prefrontal cortex and CA1 area between groups. In fact, different neural networks were shown according to the execution level of the subjects. The early PH evolution induced changes in brain metabolic activity without biggest alterations in spatial memory.

[Improvement of outcomes and quality of life of patients with portal esophagogastric bleedings due to using endoscopic haemostatic methods].

Effectiveness of endoscopic haemostatic methods for acute esophagogastric bleedings of portal genesis was analyzed. Under study there were indices of survival and mean life span of 157 patients divided into two groups: main and of comparison. Considerable improvement was established in indices of survival and mean life span in patients of the main group, where haemostatic methods were used for hemostasis. The patients of the main group had higher level of quality of life in long-term periods of follow-up, longer kept ability to work, physical activity and self-service.

Impact of hepatopulmonary syndrome on quality of life and survival in liver transplant candidates.

BACKGROUND & AIMS: Hepatopulmonary syndrome (HPS) affects 10%-30% of patients with cirrhosis and portal hypertension, but the impact on functional status, quality of life, and survival is poorly defined. We assessed the impact of HPS in patients evaluated for liver transplantation. METHODS: We performed a prospective multicenter cohort study of patients being evaluated for liver transplantation in 7 academic centers in the United States. Patients with HPS (defined as an increased alveolar-arterial oxygen gradient with intrapulmonary vasodilation) were compared with those without HPS in terms of demographics and clinical variables. New York Heart Association functional class, quality of life, and survival were assessed. RESULTS: Seventy-two patients with HPS and 146 patients without HPS were compared. There were no differences in age, sex, or etiology or severity of liver disease between the groups; however, patients with HPS were less likely to have a history of smoking (P = .03). Patients with HPS had worse New York Heart Association functional class (P = .005) and had significantly worse quality of life in certain domains compared with patients without HPS. In addition, patients with HPS also had a significantly increased risk of death compared with patients without HPS despite adjustment for age, sex, race/ethnicity, Model for End-Stage Liver Disease score, and liver transplantation (adjusted hazard ratio = 2.41; 95% confidence interval, 1.31-4.41; P = .005). CONCLUSIONS: HPS was associated with a significant increase in risk of death as well as worse functional status and quality of life in patients evaluated for liver transplantation.

Minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction.

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is associated with poor quality of life and increased work disability in cirrhotic patients. Its prevalence in extrahepatic portal vein obstruction (EHPVO) is not known. We studied the prevalence of MHE in EHPVO patients and utility of critical flicker frequency (CFF) for diagnosing MHE. PATIENTS AND METHODS: Thirty-four EHPVO patients with a history of variceal bleed (age 23.2 +/- 11.2 yr, M:F 22:12) diagnosed by either Doppler US or MR angiography, which demonstrated portal vein obstruction and/or portal vein cavernoma, were evaluated by psychometry (number connection tests A, B or figure connection tests A, B) and P300 auditory event-related potential (P300ERP). CFF was also evaluated. MHE was diagnosed by abnormal psychometry (>2 standard deviation [SD]) and/or P300ERP (>2.5 SD). RESULTS: Prevalence of MHE (N = 12) was 35.3%. Of 34 patients, P300ERP was abnormal (380.0 +/- 28.9 msec) in 11 (32%), psychometry in 9 (26.4%), both P300ERP and psychometry in 8 (23.5%), and CFF <38 Hz in 7 (21%) patients. Six (67%) patients with abnormal psychometry and 7 (64%) with abnormal P300ERP had CFF below 38 Hz. CFF had sensitivity (75%), specificity (96%), positive predictive value (86%), negative predictive value (93%), and diagnosis accuracy of 91% when compared to patients with both abnormal psychometry and P300ERP. The venous ammonia level was higher in patients with MHE (83.1 +/- 29.7 vs 44.7 +/- 16.1 micromol/L, P < 0.001) compared to patients without MHE. Spontaneous shunts were present in 67% of patients with MHE compared to 14% of non-MHE patients. MHE was more common in patients with spontaneous shunts (72.7%vs 17.4%, P= 0.001) than without spontaneous shunts. CONCLUSIONS: Prevalence of MHE in EHPVO patients is 35.3%, and CFF alone can reliably diagnose 88% of MHE patients with both abnormal psychometry and P300ERP. However, in view of the relatively low number of patients with MHE, the usefulness of CFF in this setting awaits confirmatory studies.

Survival and quality of life after portal blood flow preserving procedures in patients with portal hypertension and liver cirrhosis.

Between 1979 and 1991, 156 patients with histologically proven liver cirrhosis, good liver function, and bleeding portal hypertension underwent operation with portal blood flow preserving procedures (selective shunts: 101; Sugiura-Futagawa: 55). Long-term results of the procedures and the quality of life of the 145 patients who survived the operation were studied. During the observation period (range 3 to 156 months), 28 patients died. The main causes of death were liver failure and hepatoma. Twenty-three patients were lost for follow-up. Twenty-six patients (18%) developed 1 or more encephalopathic episodes. Four patients (3%) experienced rebleeding. One hundred eight patients (74%) had a good quality of life, and 26 (18%) had a poor quality of life. Eleven (15%) of 73 patients with a history of alcoholism continued drinking. Five-year survival for the selective shunt group was 81% and for the devascularization group was 83%. In 81% of the patients, portal blood flow was maintained. It is concluded that both procedures are effective in the long-term. Most patients are able to rehabilitate from the use of alcohol, and most of them have a good quality of life. For patients with good liver function (whose main problem is bleeding), surgery is the best choice of treatment.

[Ambulatory diagnosis and therapy control of portasystemic encephalopathy in patients with liver cirrhosis]. / Ambulante Diagnose und Therapiekontrolle der portosystemischen Enzephalopathie bei Patienten mit Leberzirrhose.

The Number Connection Test (NCT) by Harold O. Conn was tested for its usefulness for diagnosis and treatment control of portasystemic encephalopathy in out-patients. For this purpose in 30 patients with liver cirrhosis the time in the NCT was determined and the serum ammonia level (NH3) was measured before the treatment with lactulose and neomycin was started. Moreover, 12 clinical symptoms and 10 laboratory parameters were tested for correlation with the NCT-time. We found a positive correlation between the NCT-time and NH3 serum level. For the prediction of the NCT-time the multiple linear regression yielded the combination of NH3 with the proof of ascites and palmar erythema as the best subset of predictor variables. By means of the NCT the effectiveness of the treatment with lactulose and neomycin was demonstrated. We recommend the NCT for the clinical routine in particular for the early diagnosis and for treatment control of portasystemic encephalopathy in patients with liver cirrhosis.

Portal-systemic encephalopathy: neuropsychiatric manifestations.

Portal-systemic encephalopathy, which occurs as a consequence of cirrhosis of the liver, is associated with a variety of neuropsychiatric symptoms. Problems related to the differential diagnosis and medical management of portal-systemic encephalopathy, as compared to other more usual psychiatric disorders, are discussed. Also addressed are issues of particular concern to psychiatry, such as the use of pharmacotherapeutics and the rehabilitation of alcoholism, which are commonly seen in individuals with portal-systemic encephalopathy and liver disease, as well as in the general psychiatric patient population.