Jose Franco

Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test.

Patients with minimal hepatic encephalopathy (MHE) have impaired driving skills, but association of MHE with motor vehicle crashes is unclear. Standard psychometric tests (SPT) or inhibitory control test (ICT) can be used to diagnose MHE. The aim was to determine the association of MHE with crashes and traffic violations over the preceding year and on 1‐year follow‐up. Patients with cirrhosis were diagnosed with MHE by ICT (MHEICT) and SPT (MHESPT). Self and department‐of‐transportation (DOT)‐reports were used to determine crashes and violations over the preceding year. Agreement between self and DOT‐reports was analyzed. Patients then underwent 1‐year follow‐up for crash/violation occurrence. Crashes in those with/without MHEICT and MHESPT were compared. 167 patients with cirrhosis had DOT‐reports, of which 120 also had self‐reports. A significantly higher proportion of MHEICT patients with cirrhosis experienced crashes in the preceding year compared to those without MHE by self‐report (17% vs 0.0%, P = 0.0004) and DOT‐reports (17% vs 3%, P = 0.004, relative risk: 5.77). SPT did not differentiate between those with/without crashes. A significantly higher proportion of patients with crashes had MHEICT compared to MHESPT, both self‐reported (100% vs 50%, P = 0.03) and DOT‐reported (89% vs 44%, P = 0.01). There was excellent agreement between self and DOT‐reports for crashes and violations (Kappa 0.90 and 0.80). 109 patients were followed prospectively. MHEICT patients had a significantly higher future crashes/violations compared to those without (22% vs 7%, P = 0.03) but MHESPT did not. MHEICT (Odds ratio: 4.51) and prior year crash/violation (Odds ratio: 2.96) were significantly associated with future crash/violation occurrence. Conclusion: Patients with cirrhosis and MHEICT have a significantly higher crash rate over the preceding year and on prospective follow‐up compared to patients without MHE. ICT, but not SPT performance is significantly associated with prior and future crashes and violations. There was an excellent agreement between self‐ and DOT‐reports. (HEPATOLOGY 2009.)

Probiotic Yogurt for the Treatment of Minimal Hepatic Encephalopathy

OBJECTIVES:Minimal hepatic encephalopathy (MHE), the preclinical stage of overt hepatic encephalopathy (OHE), is a significant condition affecting up to 60% of cirrhotics. All MHE therapies modify gut microflora, but consensus regarding MHE treatment and long-term adherence studies is lacking. The aim was to determine the effect of probiotic supplementation in the form of a food item, probiotic yogurt, on MHE reversal and adherence.METHODS:Nonalcoholic MHE cirrhotics (defined by a standard psychometric battery) were randomized with unblinded allocation to receive probiotic yogurt (with proven culture stability) or no treatment (no Rx) for 60 days in a 2:1 ratio. Quality of life (short form [SF]-36), adherence, venous ammonia, model of end-stage liver disease (MELD) scores, and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6) were also measured. Outcomes were MHE reversal using blinded scoring, OHE development, and adherence.RESULTS:Twenty-five patients (17 yogurt, 8 no Rx; 84% Child class A) were enrolled. A significantly higher percentage of yogurt patients reversed MHE compared to no Rx patients (71% vs 0%, P= 0.003, intention-to-treat). Yogurt patients demonstrated a significant improvement in number connection test-A (NCT-A), block design test (BDT), and digit symbol test (DST) compared to baseline/no Rx group. Twenty-five percent of no Rx versus 0% of yogurt patients developed OHE during the trial. Eighty-eight percent of yogurt patients were adherent. No adverse effects or change in covariates were observed. All patients who completed the yogurt arm were agreeable to continue yogurt for 6 months if needed.CONCLUSIONS:This trial demonstrated a significant rate of MHE reversal and excellent adherence in cirrhotics after probiotic yogurt supplementation with potential for long-term adherence.

Inhibitory Control Test for the Diagnosis of Minimal Hepatic Encephalopathy

BACKGROUND & AIMS Minimal hepatic encephalopathy (MHE) is difficult to diagnose. The Inhibitory Control Test (ICT) measures response inhibition and has diagnosed MHE with 90% sensitivity and specificity in a selected population; high lure and low target rates indicated poor ICT performance. We studied the reliability and validity of ICT for MHE diagnosis. METHODS ICT was compared with a psychometric battery (standard psychometric tests [SPT]) for MHE diagnosis and overt hepatic encephalopathy (OHE) prediction. ICT was administered twice for test-retest reliability, before/after transvenous intrahepatic portosystemic shunting (TIPS), and before/after yogurt treatment. The time taken by 2 medical assistants (MA) to administer ICT was recorded and compared with that of a psychologist for cost analysis. RESULTS One hundred thirty-six cirrhotic patients and 116 age/education-matched controls were studied. ICT (>5 lures) had 88% sensitivity for MHE diagnosis with 0.902 area under the curve for receiver operating characteristic. MHE-positive patients had significantly higher ICT lures (11 vs 4, respectively, P = .0001) and lower targets (92% vs 97%, respectively, P = .0001) compared with MHE-negative patients. The test/retest reliability for ICT lures (n = 50, r = 0.90, P = .0001) was high. ICT and SPT were equivalent in predicting OHE (21%). ICT lures significantly worsened after TIPS (n = 10; 5 vs 9, respectively; P = .02) and improved after yogurt supplementation (n = 18, 10 vs 5, respectively; P = .002). The MAs were successfully trained to administer ICT; the time required for test administration and the associated costs were smaller for ICT than for SPT. CONCLUSIONS ICT is a sensitive, reliable, and valid test for MHE diagnosis that can be administered inexpensively by MAs.

Navigation skill impairment: Another dimension of the driving difficulties in minimal hepatic encephalopathy

Patients with minimal hepatic encephalopathy (MHE) have attention, response inhibition, and working memory difficulties that are associated with driving impairment and high motor vehicle accident risk. Navigation is a complex system needed for safe driving that requires functioning working memory and other domains adversely affected by MHE. The aim of this study was to determine the effect of MHE on navigation skills and correlate them with psychometric impairment. Forty‐nine nonalcoholic patients with cirrhosis (34 MHE+, 15 MHE−; divided on the basis of a battery of block design, digit symbol, and number connection test A) and 48 age/education‐matched controls were included. All patients underwent the psychometric battery and inhibitory control test (ICT) (a test of response inhibition) and driving simulation. Driving simulation consisted of 4 parts: (1) training; (2) driving (outcome being accidents); (3) divided attention (outcome being missed tasks); and (4) navigation, driving along a marked path on a map in a “virtual city” (outcome being illegal turns). Illegal turns were significantly higher in MHE+ (median 1; P = 0.007) compared with MHE−/controls (median 0). Patients who were MHE+ missed more divided attention tasks compared with others (median MHE+ 1, MHE−/controls 0; P = 0.001). Similarly, accidents were higher in patients who were MHE+ (median 2.5; P = 0.004) compared with MHE− (median 1) or controls (median 2). Accidents and illegal turns were significantly correlated (P = 0.001, r = 0.51). ICT impairment was the test most correlated with illegal turns (r = 0.6) and accidents (r = 0.44), although impairment on the other tests were also correlated with illegal turns. Conclusion: Patients positive for MHE have impaired navigation skills on a driving simulator, which is correlated with impairment in response inhibition (ICT) and attention. This navigation difficulty may pose additional driving problems, compounding the pre‐existing deleterious effect of attention deficits. (HEPATOLOGY 2008.)

Inhibitory Control Test Is a Simple Method to Diagnose Minimal Hepatic Encephalopathy and Predict Development of Overt Hepatic Encephalopathy

OBJECTIVES:To compare inhibitory control test (ICT), a simple/rapid test of attention, to a standard psychometric battery (SPT) to diagnose minimal hepatic encephalopathy (MHE) and predict development of overt hepatic encephalopathy (OHE) in cirrhotic patients.METHODS:Fifty nonalcoholic cirrhotics and 50 age/educational-status-matched controls were given ICT and SPT in the same sitting. Performance impaired beyond two standard deviations of controls was considered MHE in cirrhotics. ICT results (lure/target response and lures/person) were compared between controls and cirrhotics and within cirrhotics with/without MHE. Receiver-operating characteristic analysis was used to study ICT for MHE diagnosis. Twenty subjects were administered SPT and ICT twice to assess test–retest reliability. All cirrhotics were followed routinely for the development of OHE.RESULTS:Cirrhotics performed worse than controls on SPT and ICT. Using SPT, 39 cirrhotics had MHE. ICT was administered faster than SPT (15 vs 37 min). Cirrhotics with MHE had significantly higher lure (28% vs 3%) and lower target response (91% vs 96%) compared with those without MHE. Lure/person >5 had 90% sensitivity/specificity for MHE diagnosis. AUC for receiver-operating characteristic for lures alone was 95.8%. Lure and target responses were highly correlated (r = 0.9) between sessions showing high test–retest reliability. Five (10%) patients developed OHE on f/u of 26 ± 10 months; all five had been diagnosed with MHE using ICT and SPT. None of the five patients with discordant results on SPT and ICT developed OHE.CONCLUSIONS:ICT has good sensitivity/specificity for MHE diagnosis, is reliable and is equivalent to SPT for predicting OHE development.

Chemoembolization in patients at high risk: Results and complications

PURPOSE Transarterial chemoembolization (TACE) has become a standard treatment option for unresectable hepatocellular carcinoma (HCC) and is often used to palliate hepatic metastases. Many patients who are candidates for TACE present with poor hepatic reserve, advanced tumor stage with major portal vein (PV) invasion or thrombosis, and/or biliary dilation. These factors have been associated with a poor prognosis and increased complications after chemoembolization. Accordingly, these patients are classified as being at high risk and may not be considered for therapy. The aim of this study is to evaluate the results of TACE in these patients. MATERIALS AND METHODS Over a period of 5 years, 141 patients underwent 355 TACE procedures. Thirty-six patients (26%) were in the high-risk group as a result of major PV thrombosis, increased serum bilirubin level (>2 mg/dL), and/or intrahepatic biliary dilation. HCC was the underlying tumor in 60% of patients. Thirty-seven percent of patients had Child-Pugh class B/C disease. Patients in the high-risk group received more selective embolization with fewer particles and fewer procedures (2.0 vs 2.7; P < .04). RESULTS Patients in the high-risk group were more likely to have HCC (83% vs 51%; P < .01) and were also more likely to have advanced disease according to Child-Pugh classification versus patients in the low-risk group (49% vs 20%; P < .01). The overall complication rate was 4.3%, with no significant difference in complication rate between groups (3.2% vs 8.2%; P = .12). The overall 30-day mortality rate was 2.3%, and no significant difference in 30-day mortality rate was observed between the high- and low-risk groups (5.5% vs 1.4%; P = .11). A trend toward increased survival in the low-risk group did not reach statistical significance. CONCLUSIONS These data suggest that patients with advanced disease and decreased hepatic reserve who are treated with TACE exhibit no significant increase in morbidity or mortality and no significant decrease in survival. With variations in technique, TACE can be performed safely in patients with the relative risk factors that may classify them in high-risk groups.

A noninvasive clinical scoring model predicts risk of nonalcoholic steatohepatitis in morbidly obese patients

BackgroundA simple model to predict nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease is desirable to optimize the selection of patients for liver biopsy. We investigated a large group of morbidly obese patients to derive a scoring system based on simple clinical and laboratory variables.MethodsConsecutive subjects undergoing bariatric surgery and without evidence of other liver disease or significant alcohol use underwent intraoperative liver biopsy. Demographic, clinical, and biochemical variables were collected. A scoring model was derived using variables found to be independent predictors of NASH. The scores were divided into four risk categories (low, intermediate, high, and very high). Positive and negative predictive values (PPV/NPV) were derived for each category and the area under the receiver operator curve (AUROC) was calculated.ResultsA total of 253 subjects were included: 52 (20.6%) had NASH, 116 (45.8%) had simple steatosis, and 85 (33.6%) had normal liver histology. Only ten subjects (19% of NASH group) had significant (≥ stage 2) fibrosis. Multivariate analysis identified diabetes, abnormal ALT, and hypertriglyceridemia as independent predictors of NASH. Sleep apnea showed a strong trend toward significance and was also included in the model. This model showed a NPV of 89.7% in the low risk category and a PPV of 75% in the very high risk category, with AUROC of 0.76.ConclusionsA simple scoring system performs well in predicting NASH and can be used in the clinic to optimize the selection of morbidly obese patients for liver biopsy.

High-dose vitamin E supplementation does not diminish ribavirin-associated haemolysis in hepatitis C treatment with combination standard alpha-interferon and ribavirin

Background : Ribavirin is associated with haemolytic anaemia. Antioxidants have been reported to decrease severity of this anaemia.

Role of antiviral therapy in the prevention of hepatocellular carcinoma.

Infection with hepatitis B and/or hepatitis C virus is strongly associated with hepatocellular carcinoma (HCC). HCC likely develops through a sequence of chronic inflammation to fibrosis to cirrhosis and, eventually, dysplasia. Medical therapies aimed at the prevention of HCC are predicated on the interruption of this sequence by means of antiviral therapy. In this review, the authors summarize the available experience with prophylactic medical therapies and a number of questions that remain unanswered. Overall, although it appears that interferon-alpha therapy is beneficial in the prevention of HCC in patients with viral hepatitis, more experience is required before definitive recommendations can be made.

Disruption of sleep architecture in minimal hepatic encephalopathy and ghrelin secretion

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