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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]-alpha, 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.

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.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.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/person5 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.ICT has good sensitivity/specificity for MHE diagnosis, is reliable and is equivalent to SPT for predicting OHE development.

Spontaneous bacterial peritonitis (SBP) is a frequent complication of cirrhosis. Bacterial contamination of ascites fluid leading to SBP is caused by bacterial translocation with subsequent bacteremia. Proton pump inhibitors (PPIs) suppress gastric acid secretion, allowing bacterial colonization of the upper gastrointestinal tract, and may predispose to bacterial overgrowth and translocation. The aim of this study was to determine whether PPI use in cirrhotics with ascites is associated with SBP.A retrospective case-control study was performed. Seventy cirrhotics admitted with paracentesis-proven SBP between 2002 and 2007 were matched 1:1 (for age and Child's class) with comparable cirrhotics with ascites who were admitted for conditions other than SBP. We excluded patients on chronic antibiotic prophylaxis or with antecedent gastrointestinal bleeding. Outpatient PPI use at the time of admission was compared between groups, and the effect of covariates was analyzed.Patients with SBP had a significantly higher rate of prehospital PPI use (69%) compared with ascitic cirrhotics hospitalized without SBP (31%, P = 0.0001). There was no significant difference in demographics, diabetes, etiology, or survival between groups. On multivariate analysis, PPI use was independently associated with SBP (odds ratio (OR) 4.31, confidence interval (CI) 1.34-11.7), and ascitic fluid protein was protective (OR 0.1, CI 0.03-0.25). In total, 47% of cirrhotic patients receiving PPI in this study had no documented indication for PPI treatment.PPI therapy is associated with SBP in patients with advanced cirrhosis. Prospective studies are needed to determine whether PPI avoidance can reduce the incidence of SBP and improve outcomes.

OBJECTIVES: Hepatic encephalopathy, both overt (OHE) and minimal (MHE), is associated with poor quality of life and fatigue. The aim of this study was to define the effect of fatigue on driving skills in MHE and OHE patients. METHODS: Cirrhotics and age/education-matched controls were administered a psychometric battery of tests to diagnose MHE. Cirrhotics with recent OHE on lactulose were also included. All subjects underwent a driving simulation; to assess fatigue, the second half performance was compared with the first half of the simulation. The outcomes were collisions, speeding, road excursions, and center crossings. Actual driving-associated fatigue was assessed by the American Medical Association (AMA) driver survey. RESULTS: A total of 100 cirrhotics (51 MHE, 27 no MHE, and 22 OHE) and 67 controls were included. A significantly higher proportion of OHE and MHE patients admitted to fatigue after actual driving on the AMA survey compared with no MHE patients (P=0.02). All patients who admitted to fatigue and none who denied fatigue on the AMA survey had simulator collisions. Psychometric and simulator performance in treated OHE patients was similarly impaired to MHE patients despite therapy. Within groups, a significant increase in collisions, speeding, and center crossings in the second half (P=0.01) was seen only in MHE patients. CONCLUSIONS: Psychometric and simulator performance in patients with recent OHE on treatment is similarly impaired as that of untreated MHE patients. Simulator performance in MHE worsens over time with fatigue. OHE and MHE patients had a higher rate of actual driving-associated fatigue on the AMA survey, which was significantly predictive of simulator collisions. Language: en

OBJECTIVES: MHE patients have impairment on driving tests. However, it is unclear whether this impairment is restricted to the testing environment or is associated with increased traffic violations and/or motor vehicle accidents. METHODS: An anonymous driving history and driving behavior questionnaire (DBQ: self-scored, best score 104), coded according to MHE status, was sent to 200 cirrhotics without overt hepatic encephalopathy and 100 age/education-matched controls. The questionnaire inquired about demographics, alcohol/illegal drug use, and violations/accidents within 1 and 5 yr. The cirrhotics had been divided into those with MHE (MHE+), without MHE (MHE-), and those not tested for MHE because of psychoactive drug use, on a previous study. RESULTS: Cirrhotics versus controls had similar driving duration, alcohol/illegal drug use but significantly higher percentage with violations within both 1 and 5 yr (25%vs 4%[5 yr]), 13%vs 2%[(1 yr]), accidents (17%vs 4%[5 yr]), 9%vs 1%[1 yr]), and both (34%vs 7%[5 yr], 18%vs 3%[1 yr]). MHE+ cirrhotics had significantly higher percentage with violations (36%[5 yr], 21%[1 yr]), accidents (33%[5 yr]), 17%[1 yr]), and both (53%[5 yr], 33%[1 yr]) versus other cirrhotics. DBQ score was significantly lower in cirrhotics than controls (92 vs 99). Within cirrhotics, DBQ score was highest in MHE-versus other groups. MHE+ status was the only risk factor (odds ratios: 4.2-7.6) for violations and for accidents on multivariate logistic regression. CONCLUSIONS: Cirrhotics have a higher self-reported occurrence of violations and accidents compared to controls. MHE+ a is strong predictor for violations and accidents. Prospective studies investigating the effect of MHE treatment on violations and accidents are warranted. Language: en