The effects of poor sleep quality on cognitive function of patients with cirrhosis.

OBJECTIVES: This study was conducted to assess the ill-defined relationship between sleep quality and multiple, specific domains of cognitive function in patients with cirrhosis. METHODS: A comprehensive battery of neuropsychological tests (divided into six neurocognitive domains) and a standardized, validated measure of sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were administered to patients with cirrhosis and without evidence of overt hepatic encephalopathy, recruited from liver transplant and advanced liver disease clinics (n = 34). An inflammatory bowel disease (IBD) control group (n = 23) was similarly recruited and evaluated to control for the secondary effect of a chronic illness on cognition. PSQI global and component scores were used to predict cognitive function in each neurocognitive domain, using linear regression. RESULTS: Global PSQI scores were significantly higher (indicating poorer sleep quality) in the cirrhosis group (median [range] = 10 [1-19]) than in IBD controls = 5 (1-14); p = 0.002). After controlling for age and education, short duration of sleep was associated with impaired memory for patients with cirrhosis; the use of soporific agents was associated with poor visual-perceptual function in patients with IBD. CONCLUSIONS: Poor sleep was associated with worsening of the already impaired cognitive function of patients with cirrhosis.

The cognitive profile of depressed patients with cirrhosis.

OBJECTIVE: To determine whether patients with cirrhosis and depressive symptoms have a different neuropsychological cognitive profile from patients with cirrhosis without depressive symptoms in order to show that cirrhosis may not be the only cause for cognitive decline in patients with cirrhosis. METHOD: Adult outpatients with a diagnosis of cirrhosis based on histologic findings and clinical characteristics, who did not have clinically overt hepatic encephalopathy and who were being treated in the advanced liver disease and liver transplant clinics, were recruited for the study from May 2003 to May 2006. Patients underwent neuropsychological testing and evaluation for depression using the Beck Depression Inventory-II (BDI-II). Age-adjusted standard neuropsychological domain scores were compared between depressed (BDI-II score ≥ 14) and nondepressed (BDI-II score < 14) patients. RESULTS: Seventy-five subjects were included in the study. The 23 patients with depression were similar to the 52 nondepressed patients in level of education, age, and race; the laboratory parameters of international normalized ratio, bilirubin, creatinine, and albumin concentration; and Model for End-Stage Liver Disease scores. There was a higher percentage of women in the depressed group than in the nondepressed group, with a trend toward significance (52% vs 29%; P = .07). No etiology of liver disease was associated with depression. In linear regression analyses, decreases in cognitive function were associated with higher BDI-II scores for the domains of working memory (P = .026), with a trend toward significance for visual-perception (P = .056). Approximately 7% of the variability in working memory score was predicted using the BDI score. CONCLUSIONS: Depressive symptoms are associated with worsened cognitive function in cirrhosis.

Development of a three-factor neuropsychological approach for detecting minimal hepatic encephalopathy.

BACKGROUND: Minimal hepatic encephalopathy (HE) has profoundly negative effects on daily functioning ad quality of life. However, standard psychometric procedures have not been widely incorporated into efforts to develop a neuropsychological battery for this condition. AIMS: To establish the construct and diagnostic validity of a neuropsychological approach for the recognition of minimal HE in patients with cirrhosis. METHODS: A comprehensive battery of neuropsychological tests was administered to cirrhotic patients with at most grade 1 HE, recruited from the liver transplant and advanced liver disease clinics. An inflammatory bowel disease comparison group was similarly evaluated, thus controlling for the secondary effects of chronic illness on cognition. Testing results for the cirrhosis group were subjected to principal component analysis to establish the relevant cognitive constructs and associated measures. Factor analysis was applied to the neuropsychological battery of 20 tests to determine the cognitive factors to be used. Age-adjusted standardized neuropsychological factor scores were then compared for the two groups. RESULTS: Factor analysis revealed that our battery of 20 tests was measuring three cognitive factors. Based on the pattern of factor loadings, we labeled these important cognitive factors: global cognitive function; psychomotor speed; and learning and memory. Logistic regression revealed that only impaired psychomotor speed distinguished cirrhotics with no more than grade 1 HE from medically ill controls. CONCLUSIONS: The cirrhosis group was characterized by a pattern of preserved global cognitive functioning, mild memory impairment, and moderate psychomotor speed impairment. DISCUSSION: This distinctive pattern of focal psychomotor speed deficits is suggestive of subcortical pathway involvement in minimal HE.

Preliminary report of the Hepatic Encephalopathy Assessment Driving Simulator (HEADS) score.

INTRODUCTION: Audiovisual simulations of real-life driving (ie, driving simulators) have been used to assess neurologic dysfunction in a variety of medical applications. However, the use of simulated driving to assess neurologic impairment in the setting of liver disease (ie, hepatic encephalopathy) is limited. OBJECTIVES: The aim of this analysis was to develop a scoring system based on simulated driving performance to assess mild cognitive impairment in cirrhotic patients with hepatic encephalopathy. METHODS: This preliminary analysis was conducted as part of the Hepatic Encephalopathy Assessment Driving Simulator (HEADS) pilot study. Cirrhotic volunteers initially underwent a battery of neuropsychological tests to identify those cirrhotic patients with mild cognitive impairment. Performance during an audiovisually simulated course of on-road driving was then compared between mildly impaired cirrhotic patients and healthy volunteers. A scoring system was developed to quantify the likelihood of cognitive impairment on the basis of data from the simulated on-road driving. RESULTS: Mildly impaired cirrhotic patients performed below the level of healthy volunteers on the driving simulator. Univariate logistic regression and correlation models indicated that several driving simulator variables were significant predictors of cognitive impairment. Five variables (run time, total map performance, number of collisions, visual divided attention response, and average lane position) were incorporated into a quantitative model, the HEADS scoring system. The HEADS score (0-9 points) showed a strong correlation with cognitive impairment as measured by area under the receiver-operator curve (.89). CONCLUSION: The HEADS system appears to be a promising new tool for the assessment of mild hepatic encephalopathy.

Minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (MHE), formerly known as subclinical hepatic encephalopathy, is the mild cognitive impairment commonly seen in patients who have cirrhosis. Current understanding suggests that MHE forms part of the spectrum of hepatic encephalopathy, although this remains to be proven. Although traditionally viewed as having negligible clinical significance, MHE has a significant impact on quality of life. MHE often goes undiagnosed because in many patients there is no evidence of clinically overt signs of impaired cognition. In addition, the diagnostic criteria for MHE have not been standardized, which means that the exact characteristics of MHE remain in question. This Review focuses on the pathogenesis and neuropsychological findings (incorporating neuroimaging) of MHE, as well as the effect of MHE on quality of life and survival, and developments in treatment.

Hepatic encephalopathy as a predictor of survival in patients with end-stage liver disease.

Hepatic encephalopathy (HE) is an important component of hepatic decompensation, which reduces survival in patients with cirrhosis. The Model for End-Stage Liver Disease (MELD) score has been used to predict survival of patients with cirrhosis. The aims of this study were to determine whether HE is a predictor of survival of patients with cirrhosis and to examine the degree to which HE may add to the survival prediction of MELD. Patients with end-stage liver disease whose data were included in 2 databases were included in the analysis: 223 patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) insertion, and 271 patients hospitalized with hepatic decompensation. In univariate analysis, HE grade 3 or higher was associated with a 3.7-fold (95% confidence interval, 1.9-7.3, P<0.01) increase in the risk of death in the TIPS patients and HE grade 2 or higher was associated 3.9-fold increase (95% confidence interval [95% CI], 2.6-5.7, P<0.01) in hospitalized patients. As expected, MELD and Child-Turcotte-Pugh scores (with and without HE included) were also markedly associated with survival. When HE (grade 2 or higher) and MELD were considered together, HE remained strongly statistically significant in the hospitalized patients (hazard ratio=2.6, 95% CI, 1.7-3.8, P<0.01). The effect became smaller in the TIPS patients (hazard ratio=1.1; 95% CI, 0.7-1.6, P=0.76). In conclusion, this retrospective study demonstrates that HE is an important event in the natural history of cirrhosis that affects subsequent survival of patients. HE may provide additional prognostic information independent of MELD, which warrants prospective validation.

Hepatic encephalopathy: a dynamic or static condition.

Hepatic encephalopathy (HE) is a neuropsychiatric disorder associated with portal hypertension. The mechanism of this disorder is still being characterized and the management has relied primarily on lowering the amount of ammonia present in the gastrointestinal tract or reversing liver disease by replacing the diseased liver. It is, however, not established that all the effects of hepatic encephalopathy are reversed by liver transplantation. In this review, we have outlined the mechanisms underlying HE and the pros and cons of reversibility of HE.

Neuroimaging in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a poorly defined, complex neuropsychological disorder that often accompanies portal hypertension. Although the mechanisms underlining HE and the characterization of HE are still under investigation, the information derived from functional neuroimaging of patients with HE complemented by laboratory investigation and neuropsychological and neurophysiological studies have clarified much of the neuroanatomical defects. In this review, we have provided an outline of the understood mechanisms of HE and the associated findings on neuroimaging.

Ascites after liver transplantation--a mystery.

Ascites after liver transplantation, although uncommon, presents a serious clinical dilemma. The hemodynamic changes that support the development of ascites before liver transplantation are resolved after transplant; therefore, persistent ascites (PA) after liver transplantation is unexpected and poorly characterized. The aim of this study was to define the clinical factors associated with PA after liver transplantation. This was a retrospective case-control analysis of patients who underwent liver transplantation at the University of Pennsylvania. PA occurring for more than 3 months after liver transplantation was confirmed by imaging studies. PA was correlated with multiple recipient and donor variables, including etiology of liver disease, preoperative ascites, prior portosystemic shunt (PS), donor age, and cold ischemic (CI) time. There were 2 groups: group 1, cases with PA transplanted from November 1990 to July 2001, and group 2, consecutive, control subjects who underwent liver transplantation between September 1999 and December 2001. Both groups were followed to censoring, May 2002, or death. Twenty-five from group 1 had ascites after liver transplantation after a median follow-up of 2.6 years. In group 1 vs group 2 (n = 106), there was a male predominance 80% vs 61% (P =.10) with similar age 52 years; chronic hepatitis C virus (HCV) was diagnosed in 88% vs 44% (P <.0001); preoperative ascites and ascites refractory to treatment were more prevalent in group 1 (P =.0004 and P =.02, respectively), and CI was higher in group 1, (8.5 hours vs 6.3 hours, P =.002). Eight of the 25 (group 1) had portal hypertension with median portosystemic gradient 16.5 mm Hg (range, 16-24). PS was performed in 7 of 25 cases, which resulted in partial resolution of ascites. The development of PA after liver transplantation is multifactorial; HCV, refractory ascites before liver transplantation, and prolonged CI contribute to PA after liver transplantation.

Grading portal gastropathy: validation of a gastropathy scoring system.

OBJECTIVES: The specific aim of this study was to independently evaluate the reproducibility and validity of the Baveno portal hypertensive gastropathy (PHG) grading system. METHODS: This is a prospective study of 100 consecutive patients with cirrhosis and portal gastropathy. An endoscopy was performed at entry on all subjects and on 70 patients during follow-up (median 15 months). Interobserver reproducibility was assessed by the kappa statistic. Patients with PHG-related bleeding were compared with those without bleeding. The relationship of PHG-related bleeding to the PHG score was assessed by a receiver operating characteristic curve and by multiple logistic regression analysis. RESULTS: Interobserver agreement about the presence of the mosaic pattern and red marks was high (kappa >0.75). However, the agreement about the extent of the lesion was poorer (kappa = 0.4-0.45). There was a stepwise increase in PHG-related bleeding risk with increasing PHG scores. Multiple logistic regression confirmed that the PHG score independently correlated with PHG-associated bleeding (OR = 2.5, 90% CI = 1.4-4.6, p < 0.009). During follow-up, red marks developed de novo in one of 70 patients. The severity of red marks worsened in five of 25 patients, whereas they disappeared in eight of 62 individuals. Nodular lesions in the antrum were found in five subjects. The risks of recurrent bleeding during follow-up were related to severe PHG scores (>4), presence of gastric antral vascular ectasia, and nodular lesions in the antrum. CONCLUSIONS: The PHG scoring system is reproducible and accurately reflects the risks of PHG-related bleeding in patients with cirrhosis.