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Abstract Hepatic encephalopathy (HE) is a significant complication of cirrhosis and part of the CTP score. The UNOS database was queried for listings from February 2001 to February 2002 (CTP era) and February 2002 to February 2003 (MELD era). HE at listing, Grade III/IV HE at transplant, and 12-month posttransplant survival were compared. HE rate at listing was similar, whereas Grade III/IV HE at time of transplant was significantly lower in the MELD era. Waiting periods were shorter in the MELD era. Twelve-month posttransplant survival was lower in all patients with HE at listing (P < 0.0001) and for patients with Grade III/IV HE at transplant (P < 0.0001) in both eras. No significant change in posttransplant survival of HE patients was observed after MELD implementation. We conclude that (1) HE patients have worse posttransplant survival even after MELD; (2) MELD allows more rapid transplantation; and (3) rates of HE at listing have not changed since MELD implementation; however, rates of Grade III/IV HE at transplant have decreased. [ABSTRACT FROM AUTHOR]

Alcohol use disorder is a major cause of morbidity, which requires newer treatment approaches. We previously showed in a randomized clinical trial that alcohol craving and consumption reduces after fecal transplantation. Here, to determine if this could be transmitted through microbial transfer, germ-free male C57BL/6 mice received stool or sterile supernatants collected from the trial participants pre-/post-fecal transplant. We found that mice colonized with post-fecal transplant stool but not supernatants reduced ethanol acceptance, intake and preference versus pre-fecal transplant colonized mice. Microbial taxa that were higher in post-fecal transplant humans were also associated with lower murine alcohol intake and preference. A majority of the differentially expressed genes (immune response, inflammation, oxidative stress response, and epithelial cell proliferation) occurred in the intestine rather than the liver and prefrontal cortex. These findings suggest a potential for therapeutically targeting gut microbiota and the microbial-intestinal interface to alter gut-liver-brain axis and reduce alcohol consumption in humans. Gut microbiota composition is altered in patients with alcohol use disorder, and fecal microbiota transplant reduced alcohol craving in patients with alcohol use disorder and liver cirrhosis in a phase 1 clinical trial. Here the authors used stool samples collected in the trial to report that this phenotype is transmissible via microbial transfer to germ free mice, as assessed by reduced ethanol acceptance, intake and preference. [ABSTRACT FROM AUTHOR]

Background: Hepatic hydrothorax (HH) remains a difficult-to-treat complication of cirrhosis. Aim: To define the mortality, length of stay (LOS), and risk of ACLF in patients admitted with HH. Methods: We utilized the North American Consortium for the Study of End-stage Liver Disease, a prospective cohort of 2868 non-electively hospitalized patients with cirrhosis from 14 tertiary care hepatology centers in North America. A total of 121 patients who required an inpatient thoracentesis (HH group) were compared to 736 patients with refractory ascites without HH, and to 1639 patients without these complications (Other). Patients with a TIPS before or during admission were excluded. Results: There were no differences between the groups in age, gender, or liver disease etiology. Admission MELD (20.5, 21.6 vs. 18.7; p < 0.0001) was lower in HH than RA patients but lowest in other patients, respectively. In hospital, HH patients' rate of second infections and ICU transfer were the highest, and their LOS was the longest of all groups. Despite a similar mean discharge MELD compared to RA patients, the 90-day transplant rate was lower. Multivariable modeling showed patients with HH had an increased risk of ACLF (HR = 2.37 vs. RA, HR = 2.56 vs. Other; p = 0.01) even when controlling for MELD score, AKI, second infection, and history of prior 6-month hospitalization. Multivariable modeling also showed that HH increased the risk of inpatient mortality (HR = 2.22 vs. RA alone, HR = 2.31 vs. Other; p = 0.04). Conclusions: HH that required a therapeutic thoracentesis more than doubled the risk of ACLF and inpatient mortality among hospitalized patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Health education interventions are successful in modifying lifestyle. Functional health literacy (FHL) can determine patient adherence to clinic visits and procedures and may adversely impact the success of these interventions. Aims: We sought to evaluate the hypothesis that a health education intervention would improve compliance with hepatocellular cancer (HCC) screening and that poor FHL would reduce such compliance. Methods: We assessed FHL using a short version test of functional health literacy in adults (STOFHLA). Cirrhotic patients free of HCC were prospectively enrolled from clinics and provided an educational intervention consisting of focused physician-led discussion regarding cirrhosis and HCC, along with written material on these topics for the subject to review at home. Patients were subsequently followed for 6 months (prospective time period), and the same cohort's clinic/HCC screening behavior between 6 and 12 months prior to the educational intervention (retrospective time period) was compared. Results: In total, 104 cirrhotic patients (age 60.01 ± 8.58 years, 80% men, MELD 12.70 ± 5.76) were included. Of these, 89 (85.57%) of patients had educational level 12th grade and higher. There were 76% (n = 79) with adequate, while 24% (n = 25) had inadequate/marginal FHL on S-TOHFLA. The number of HCC-related imaging increased from 59 (56.7%) to 86 (82.6%, p < 0.0001) post-education in the prospective compared to prior time period which was similar regardless of FHL. Conclusions: While the educational intervention was successful in improving compliance with HCC screenings, FHL status did not impact the power of this intervention. Hence, the combination of specific verbal information, along with targeted written material, improved compliance with clinic visits and liver imaging for HCC. [ABSTRACT FROM AUTHOR]

Background: Cirrhosis is associated with poor health-related quality of life (HRQOL), cognitive dysfunction (CD), and lack of coordination leading to falls. Tandem gait (TG; heel-toe) can be used to assess coordination. The impact and relationship between CD, TG and falls pre-/post-liver transplant (LT) is unclear. We aimed to determine the impact of LT on CD, abnormal TG, and HRQOL in cirrhosis. Methods: We analyzed patients who underwent complete neurological examination, cognitive testing by psychometric hepatic encephalopathy score (PHES), and HRQOL assessment using sickness impact profile (SIP). All patients were followed for 1 post-LT visit at 6 or 12 months post-LT for clinical course and falls. Change in CD, TD, and falls pre-/post-LT were compared. Results: Off 131 recruited, 61 patients completed all visits. Majority were men (84%), with HCV etiology (34%). Pre-LT: Abnormal TG trended towards increased falls (OR 3.3, P = 0.08). Forty-nine % had abnormal TG, 61% had CD, 32.7% had CD + abnormal TG, 62% had prior OHE, and 14.7% had falls. Abnormal and normal TG patients had similar ages, BMI, sex, education level, and MELD scores. Abnormal TG group had higher prior overt HE (P = 0.03) and worse physical SIP score (P = 0.008). Post-LT: There was sustained improvement in CD, HRQOL, falls, and TG post-LT more at 12 than 6 months in all patients. Patients who had abnormal TG pre-LT continued to have a worse PHES (P = 0.0064) and physical SIP score (P = 0.008) compared to normal pre-LT TG patients. Conclusion: After LT, there is a sustained improvement in coordination measured via tandem gait, accompanied by a lower rate of falls. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of coronary artery disease (CAD) is high among patients with cirrhosis; however, the impact of it on cardiovascular disease (CVD) is not known. The aim of the current study was to evaluate CVD events in patients with cirrhosis and impact of cirrhosis on biomarkers of atherogenesis. Methods: The study included 682 patients with decompensated cirrhosis referred for liver transplantation (LT) evaluation between 2010 and 2017. All patients were followed until they experienced a CVD event, non-cardiac death, liver transplantation or last follow-up. To evaluate mechanistic link, patients with NASH cirrhosis were propensity matched 1:2 to non-cirrhosis NASH patients and biomarkers of atherogenic risk were compared. Results: The composite CVD outcome occurred in 23(3.4%) patients after a median follow-up period of 585 days (IQR 139, 747). A strong association between presence of any CAD and CVD event was noted (HR = 6.8, 95% CI 2.9, 15.9) that was independent of age, gender, BMI, and MELD score. In competing risk model, the combined rate of LT and non-cardiac was significantly higher when compared to the rate of CVD events. Marker of insulin resistance and inflammation-related markers were similar in patients with and without cirrhosis. Patients with cirrhosis were more likely to have reduced VLDL, sdLDL-C, LDL-C, and triglycerides. Interestingly, patients with cirrhosis had an increase in serum HDL-2, the anti-atherogenic lipoprotein, and adiponectin, a protective serum adipokine. Conclusion: The risk of CVD events in patients with cirrhosis is low and may potentially be due to improvement in markers of atherogenic risk. [ABSTRACT FROM AUTHOR]

Background: Little is known about patients discharged to hospice following hospitalization for complications of cirrhosis.Aim: We sought to understand the current pattern of hospice utilization in patients with cirrhosis by evaluating the North American Consortium for the Study of End-stage Liver Disease (NACSELD) cohort.Methods: Patients with cirrhosis from 14 tertiary-care hepatology centers across North America non-electively hospitalized and prospectively enrolled were evaluated. Exclusion criteria included HIV infection, transplantation or non-hepatic malignancy. Random computer-based propensity score matching was undertaken in a 1:2 ratio based on admission MELD score ± 3 points.Results: Totally, 2718 patients were enrolled, 5% (N = 132) were discharged to hospice, 6% (N = 171) died, and the rest were discharged alive. Patients discharged to hospice were older (60 vs. 57 years, p = 0.04), less likely to have had SBP (13% vs. 28%, p = 0.002) and be listed for liver transplantation (11% vs. 26%, p = 0.0007). Features, on multivariable modeling, associated with increased probability of discharge to hospice as opposed to being discharged alive: grade-3-4 hepatic encephalopathy, a higher Child-Turcotte-Pugh (CTP) score, and a higher discharge serum creatinine; however, a higher serum sodium, being listed for transplant and being prescribed rifaximin or a statin were protective from hospice discharge.Conclusion: Patients with more advanced liver disease, hepatic encephalopathy, renal dysfunction, and those not candidates for liver transplantation were more likely to be discharged to hospice. However, in this sick multinational cohort of cirrhotic inpatients, it seems that hospice is markedly underutilized (5%) since 25% of patients not discharged to hospice died within 6 months. [ABSTRACT FROM AUTHOR]

Previous studies demonstrate an association between activation of the maternal immune system during pregnancy and increased risk of neurodevelopmental psychiatric conditions, such as schizophrenia and autism, in the offspring. Relatively recent findings also suggest that the gut microbiota plays an important role in shaping brain development and behavior. Here we show that maternal immune activation (MIA) accomplished by infection with a mouse-adapted influenza virus during pregnancy induced up-regulation of frontal cortex serotonin 5-HT2A receptor (5-HT2AR) density in the adult offspring, a phenotype previously observed in postmortem frontal cortex of schizophrenic subjects. 5-HT2AR agonist-induced head-twitch behavior was also augmented in this preclinical mouse model. Using the novel object recognition (NOR) test to evaluate cognitive performance, we demonstrate that MIA induced NOR deficits in adult offspring. Oral antibiotic treatment of prepubertal mice prevented this cognitive impairment, but not increased frontal cortex 5-HT2AR density or psychedelic-induced head-twitch behavior in adult MIA offspring. Additionally, gut microbiota transplantation from MIA mice produced behavioral deficits in antibiotic-treated mock mice. Adult MIA offspring displayed altered gut microbiota, and relative abundance of specific components of the gut microbiota, including Ruminococcaceae, correlated with frontal cortex 5-HT2AR density. Together, these findings provide a better understanding of basic mechanisms by which prenatal insults impact offspring brain function, and suggest gut-brain axis manipulation as a potential therapeutic approach for neurodevelopmental psychiatric conditions. [ABSTRACT FROM AUTHOR]

Purpose of Review: The burden of malnutrition is high in patients with cirrhosis, especially in those with hepatic encephalopathy (HE). This has a bearing on increased morbidity and mortality. Heightened attention needs to be paid to screen the patients at high nutritional risk both in the outpatient and hospitalized settings. This review summarizes the current evidence for nutritional support in HE patients and compares the recommendations about nutritional requirement as laid out by various organizations. Recent Findings: On survey of the literature, there is a consensus on avoiding protein restriction of the diets in HE patients along with uniform recommendations on caloric requirements. An exciting field of manipulating the gut microbiome in nutritional sciences may hold promise as well as there may be a future role for branched chain amino acids in nutritional management of HE patients. Summary: Even though the data suggest that nutritional improvement lead to better outcomes including lower readmission rates in cirrhosis, operationalizing these into practice remains a challenge. To achieve this, a multi-disciplinary approach with nutritional education of the frontline care providers, earlier nutritional risk screening of patients, involvement of the nutrition professionals as part of the team, and repeated dietary counseling for the patient and caregiver/s is required. Ultimately, this may need more focus, resource allocation, and uniform guidelines across all countries to make this a success. [ABSTRACT FROM AUTHOR]

Covert hepatic encephalopathy (CHE) affects cognition in a multidimensional fashion. Current guidelines recommend performing Psychometric Hepatic Encephalopathy Score (PHES) and a second test to diagnose CHE for multi-center trials. We aimed to determine if a two-test combination strategy improved CHE diagnosis agreement, and accuracy to predict overt hepatic encephalopathy (OHE), compared to single testing. Cirrhotic outpatients without baseline OHE performed PHES, Inhibitory Control Test (ICT), and Stroop EncephAlapp (StE) at three centers. Patients were followed for OHE development. Areas under the receiver operation characteristic curve (AUROC) were calculated. We included 437 patients (399 with follow-up data). CHE prevalence varied with testing strategy: PHES+ICT 18%, ICT + StE 25%, PHES+StE 29%, ICT 35%, PHES 37%, and StE 54%. Combination with best test agreement was PHES+StE (k = 0.34). Sixty patients (15%) developed OHE. Although CHE by StE showed the highest sensitivity to predict OHE, PHES and PHES+StE were more accurate at the expense of a lower sensitivity (55%, AUROC: 0.587; 36%, AUROC: 0.629; and 29%, AUROC: 0.623; respectively). PHES+ICT was the most specific (85%) but all strategies including ICT showed sensitivities in the 33-45% range. CHE diagnosis by PHES (HR = 1.79, p = 0.04), StE (HR = 1.69, p = 0.04), and PHES+StE (HR = 1.72, p = 0.04), were significant OHE predictors even when adjusted for prior OHE and MELD. Our results demonstrate that combined testing decreases CHE prevalence without improving the accuracy of OHE prediction. Testing with PHES or StE alone, or a PHES+StE combination, is equivalent to diagnose CHE and predict OHE development in a multi-center setting. [ABSTRACT FROM AUTHOR]

Background: In veterans, post-traumatic stress disorder (PTSD) is often associated with substance abuse, which in turn can lead to cirrhosis. Cirrhotic patients are prone to cognitive impairment, which is typically due to covert hepatic encephalopathy (CHE), but can also be affected by PTSD. The aim was to define the impact of PTSD on cognitive performance and the diagnosis of CHE in cirrhotic patients.Methods: Outpatient veterans with cirrhosis underwent two separate modalities for CHE cognitive testing [Psychometric Hepatic Encephalopathy Scale (PHES) and Inhibitory Control Test (ICT)]. ICT tests for inhibitory control and response inhibition, while PHES tests for attention and psychomotor speed. Comparisons were made between patients with/without PTSD. Multivariable logistic regression with CHE on PHES and CHE on ICT as dependent variables including prior OHE, demographics, PTSD and psychotropic medications was performed.Results: Of 402 patients with cirrhosis, 88 had evidence of PTSD. Fifty-five of these were on psychoactive medications, 15 were undergoing psychotherapy, while no specific PTSD-related therapy was found in 28 patients. Cirrhotic patients with/without PTSD were statistically similar on demographics and cirrhosis severity, but cirrhotic subjects with PTSD had a higher frequency of alcoholic cirrhosis etiology and psychotropic drug use. PTSD cirrhosis had higher ICT lure and switching errors (NCT-B response), but on regression, there was no significant impact of PTSD on CHE diagnosis using either the ICT or PHES.Conclusions: Veterans with cirrhosis and PTSD have a higher frequency of psychotropic drug use and alcoholic cirrhosis etiology. CHE diagnosis using PHES or ICT is not affected by concomitant PTSD. [ABSTRACT FROM AUTHOR]

A response is offered the article "Decompensated cirrhosis and microbiome interpretation," by Jasmohan S. Bajaj, Naga S. Betrapally and Patrick M. Gillevet which appears within the issue. An overview of the research conducted on liver cirrhosis through the analysis of the human microbiome and stool metagenomics is provided.

Background: Patient-Reported Outcomes Measurement Information System (PROMIS) tools can identify health-related quality of life (HRQOL) domains that could differentially affect disease progression. Cirrhotics are highly prone to hospitalizations and re-hospitalizations, but the current clinical prognostic models may be insufficient, and thus studying the contribution of individual HRQOL domains could improve prognostication.Aim: Analyze the impact of individual HRQOL PROMIS domains in predicting time to all non-elective hospitalizations and re-hospitalizations in cirrhosis.Methods: Outpatient cirrhotics were administered PROMIS computerized tools. The first non-elective hospitalization and subsequent re-hospitalizations after enrollment were recorded. Individual PROMIS domains significantly contributing toward these outcomes were generated using principal component analysis. Factor analysis revealed three major PROMIS domain groups: daily function (fatigue, physical function, social roles/activities and sleep issues), mood (anxiety, anger, and depression), and pain (pain behavior/impact) accounted for 77% of the variability. Cox proportional hazards regression modeling was used for these groups to evaluate time to first hospitalization and re-hospitalization.Results: A total of 286 patients [57 years, MELD 13, 67% men, 40% hepatic encephalopathy (HE)] were enrolled. Patients were followed at 6-month (mth) intervals for a median of 38 mths (IQR 22-47), during which 31% were hospitalized [median IQR mths 12.5 (3-27)] and 12% were re-hospitalized [10.5 mths (3-28)]. Time to first hospitalization was predicted by HE, HR 1.5 (CI 1.01-2.5, p = 0.04) and daily function PROMIS group HR 1.4 (CI 1.1-1.8, p = 0.01), independently. In contrast, the pain PROMIS group were predictive of the time to re-hospitalization HR 1.6 (CI 1.1-2.3, p = 0.03) as was HE, HR 2.1 (CI 1.1-4.3, p = 0.03).Conclusions: Daily function and pain HRQOL domain groups using PROMIS tools independently predict hospitalizations and re-hospitalizations in cirrhotic patients. [ABSTRACT FROM AUTHOR]

Background: Women have lower serum creatinine values than men for similar renal function.Aims: We aimed to determine the differential effect of baseline, peak, and delta creatinine between genders on outcomes in infected hospitalized cirrhotic patients.Methods: North American Consortium for the Study of End-Stage Liver Disease is a 15-center consortium of tertiary care hepatology centers prospectively enrolling infected cirrhotic inpatients. Baseline, peak, and delta creatinine during hospitalization were compared between genders, and their impact on overall survival, transplant-free survival, probability of transplantation, and need for renal replacement therapy (RRT) was analyzed.Results: In total, 532 patients with cirrhosis (males = 59% median admission MELD = 20) had significantly lower median baseline (1.07 vs. 1.30 mg/dL, p < 0.0001) and peak creatinine (1.47 vs. 1.59 mg/dL, p = 0.024) in women than men during hospitalization for an infection, but both genders had similar delta creatinine levels (0.30 vs. 0.30 mg/dL, p = 0.957). Thirty-day mortality was similar between genders. RRT was not used more often in women (19 vs. 12%, p = 0.050), and women were 1.8 times more likely than men to receive RRT at the same creatinine (p = 0.028). Both peak and delta creatinine significantly predicted 6-month overall and transplant-free survival (p < 0.0001), but the probability of liver transplantation was affected by the interaction between gender and both peak and delta creatinine.Conclusions: Infected hospitalized cirrhotic women are significantly more likely than men to receive RRT at similar creatinine levels. Gender-specific differences in baseline, peak, and delta creatinine need further investigation to determine whether women need acute kidney injury treatment at lower creatinine thresholds than men. [ABSTRACT FROM AUTHOR]

Background: Hepatic encephalopathy (HE) is considered reversible regarding mental status but may not be cognitively in single-center studies.Aim: To evaluate persistence of learning impairment in prior HE compared to those who never experienced HE (no-HE) in a multicenter study.Methods: A total of 174 outpatient cirrhotics from three centers (94 Virginia, 30 Ohio, and 50 Rome; 36 prior HE) underwent psychometric hepatic encephalopathy score (PHES) and inhibitory control (ICT) testing at baseline and then at least 7 days apart. ICT learning (change in 2nd half lures compared to 1st half) was compared between patient groups at both visits. Change in the PHES individual sub-tests and total score between visits was compared in both groups. US versus Italian trends were also analyzed.Results: HE patients had worse PHES and ICT results compared to no-HE patients at baseline. Significant improvement (1st half 7.1 vs. 2nd half 6.2, p < 0.0001) was observed in no-HE, but not in HE (1st half 7.9 vs. 2nd half 7.8, p = 0.1) at baseline. At retesting (median 20 days later), no-HE patients continued with significant learning (1st half 6.0 vs. 2nd half 5.4, p < 0.0001), while HE patients again did not improve (1st half 7.8 vs. 2nd half 6.9, p = 0.37). Between visits, no-HE patients improved significantly on four PHES sub-tests and overall score, while HE patients only improved on two sub-tests with similar overall PHES score. Trends were similar between US and Italian subjects.Conclusion: In this multicenter study, prior HE patients showed persistent significant learning impairment compared to those without prior HE, despite adequate medical therapy. This persistent change should increase efforts to reduce the first HE episode. [ABSTRACT FROM AUTHOR]

A response by Jasmohan S. Bajaj and colleagues to a letter to the editor about their article "The multidimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers in the 2011 issue is presented.

Health-related quality of life (HRQOL) is an important determinant of prognosis in cirrhosis and hepatic encephalopathy (HE). However due to inherent cognitive dysfunction, insight into HRQOL severity in patients with liver disease may be impaired. To assess insight into HRQOL using PROMIS tools compared to norms in cirrhotic patients. PROMIS tools are validated HRQOL instruments that test the domains of anger, anxiety, depression, physical function, pain behavior/impact, sleep disturbances/impairment, and social activities/roles, compared to US-norms. Patients were administered the PROMIS tools, the results of which were reviewed using a visual comparison with thed norms. Then two Likert scales from 0 to 10 per domain were administered that inquired about (1) Surprise Intensity: 0-4: not surprised, 5-10: surprised; and (2) Expectancies: 0-4: results better than expected, 5:10: as/worse than expected. Comparisons between HE/no-HE were also performed. 203 cirrhotic patients (57 yrs., 62 % men, MELD 12, 83 HE) were included. All HE patients were controlled on therapy. Prior HE patients were significantly impaired on all PROMIS domains ( p < 0.01) except anger, compared to the re st. The majority (76-85 %) were not surprised with their placement vis-à-vis the norms. Similarly, a majority (59-61 %) thought their results were worse or as expected. However, a third of patients found that their PROMIS results were better than expected. Prior HE status did not significantly impact expectations or surprise based on placement with the norms. The majority of cirrhotic patients, regardless of prior HE, have good insight regarding their HRQOL issues. [ABSTRACT FROM AUTHOR]

Overt hepatic encephalopathy (OHE) and covert hepatic encephalopathy (CHE) are two clinically distinct entities that are at the end of the spectrum of cognitive impairment due to portal hypertension. They are fraught with diagnostic and treatment challenges, but both could result in serious complications if not intervened upon in a timely fashion. CHE has been recognized as a harbinger to OHE providing an opportunity to intervene. There are numerous diagnostic strategies for CHE, and most require specialized equipment, trained personnel, and time. Diagnosis of OHE is significantly easier compared to CHE. As such, the psychometric tests have been more favored due to less dependence on specialized equipment and personnel, and their ability to be equally reliable compared to neuropsychological tests. While we have learned more about the pathophysiology of hepatic encephalopathy, our treatment modalities have not evolved as much. A collaborative approach to management, with development of easier reliable tests, will help us combat this epidemic. [ABSTRACT FROM AUTHOR]

Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. Hypothesis: Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. Methods: Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. Results were compared before/after rifaximin. Results: 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92 % medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia( p = 0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Despite the high prevalence of covert hepatic encephalopathy (CHE) in cirrhotics without previous overt HE (OHE), its independent impact on predicting clinically relevant outcomes is unclear. The aim of this study was to define the impact of CHE on time to OHE, hospitalization, and death/transplant in prospectively followed up patients without previous OHE.METHODS:Outpatient cirrhotics without OHE were enrolled and were administered a standard paper-pencil cognitive battery for CHE diagnosis. They were systematically followed up and time to first OHE development, hospitalization (liver-related/unrelated), and transplant/death were compared between CHE and no-CHE patients at baseline using Cox regression.RESULTS:A total of 170 cirrhotic patients (55 years, 58% men, 14 years of education, Model for End-Stage Liver Disease (MELD 9), 53% hepatitis C virus (HCV), 20% nonalcoholic etiology) were included, of whom 56% had CHE. The entire population was followed up for 13.0±14.6 months, during which time 30% developed their first OHE episode, 42% were hospitalized, and 19% had a composite death/transplant outcome. Age, gender, etiology, the MELD score, and CHE status were included in Cox regression models for time to first OHE episode, hospitalization, death, and composite death/transplant outcomes. On Cox regression, despite controlling for MELD, those with CHE had a higher risk of developing OHE (hazard ratio: 2.1, 95% confidence interval 1.01-4.5), hospitalization (hazard ratio: 2.5, 95% confidence interval 1.4-4.5), and death/transplant (hazard ratio: 3.4, 95% confidence interval 1.2-9.7) in the follow-up period.CONCLUSIONS:Covert HE is associated with worsened survival and increased risk of hospitalization and OHE development, despite controlling for the MELD score. Strategies to detect and treat CHE may improve these risks. [ABSTRACT FROM AUTHOR]

The treatment of hepatic encephalopathy (HE) is complex and therapeutic regimens vary according to the acuity of presentation and the goals of therapy. Most treatments for HE rely on manipulating the intestinal milieu and therefore antibiotics that act on the gut form a key treatment strategy. Prominent antibiotics studied in HE are neomycin, metronidazole, vancomycin and rifaximin. For the management of the acute episode, all antibiotics have been tested. However the limited numbers studied, adverse effects (neomycin oto- and nephrotoxicity, metronidazole neurotoxicity) and potential for resistance emergence (vancomycin-resistant enterococcus) has limited the use of most antibiotics, apart from rifaximin which has the greatest evidence base. Rifaximin has also demonstrated, in conjunction with lactulose, to prevent overt HE recurrence in a multi-center, randomized trial. Despite its cost in the US, rifaximin may prove cost-saving by preventing hospitalizations for overt HE. In minimal/covert HE, rifaximin is the only systematically studied antibiotic. Rifaximin showed improvement in cognition, inflammation, quality-of-life and driving simulator performance but cost-analysis does not favor its use at the current time. Antibiotics, especially rifaximin, have a definite role in the management across the spectrum of HE. [ABSTRACT FROM AUTHOR]

The pathogenesis of hepatic encephalopathy(HE) is unclear. However gut flora changes, inflammation and neuro-glial injury have been implicated. The aim was to evaluate factors that were associated with HE recurrence after lactulose withdrawal by analyzing the clinical phenotype, stool microbiome and systemic metabolome longitudinally. HE patients on a standard diet who were adherent on lactulose underwent characterization of their phenotype [cognition, inflammatory cytokines, in-vivo brain MR spectroscopy(MRS)], gut microbiome (stool Multitag Pyrosequencing) and metabolome (urine/serum ex-vivo MRS) analysis while on lactulose and on days 2, 14 and 30 post-withdrawal. Patients whose HE recurred post-withdrawal were compared to those without recurrence. We included seven men (53 ± 8 years) who were adherent on lactulose after a precipitated HE episode were included. HE recurred in three men 32 ± 6 days post-withdrawal. In-vivo brain MRS showed increased glutamine+glutamate (Glx) and decreased myoinositol with a reduction in stool Faecalibacterium spp., post-withdrawal. HE recurrence was predicted by poor baseline inhibitory control and block design performance and was associated with a shift of choline metabolism from tri-methylamine oxide formation towards the development of di-methylglycine, glycine and creatinine. This was accompanied by a mixed effect on the immune response (suppressed IL-10 and Th1/Th2/Th17 response). The correlation network showed Prevotella to be linked to improved cognition and decreased inflammation in patients without HE recurrence. We conclude that lactulose withdrawal results in worsening cognition, mixed inflammatory response effect, lowered stool Faecalibacterium and increase in MR-measurable brain Glx. HE recurrence post-lactulose withdrawal can be predicted by baseline cognitive performance and is accompanied by disrupted choline metabolism. [ABSTRACT FROM AUTHOR]

Background: Minimal hepatic encephalopathy (MHE) is associated with poor driving skills and insight. Increasing insight may improve receptiveness for therapy or driving restrictions. Aim: To evaluate the change in the self-assessment of driving skills (SADS) using a driving simulator. Methods: Cirrhotic patients and age/education-matched controls underwent MHE testing with inhibitory control (ICT) and the psychometric hepatic encephalopathy score (PHES). SADS, a Likert scale from 0 to 10, was administered just before and after a standardized driving simulation comprising testing and navigation tasks. The percentage SADS change from baseline was compared within/between groups. Results: A total of 84 patients (60% men, age 55 years) and 12 controls were included. Controls were significantly better than cirrhotics on cognitive/simulator testing. The baseline SADS was similar between the groups. The baseline patient SADS was only correlated with ICT lures ( r = −0.4, P = 0.001). Post-simulation, 60% of patients improved their insight, i.e., reduced SADS (from 8 to 6.5, P = 0.0001) compared to 25% of controls ( P = 0.02). The mean percentage SADS reduction was also higher in cirrhotics (18% vs. 8%, P = 0.03). MHE on ICT patients had a significantly higher SADS improvement ( P = 0.004) compared to the other patients; no difference was seen in those with/without MHE due to the PHES. The percentage SADS reduction in patients was correlated with getting lost ( r = 0.468, P < 0.0001), crashes ( P = 0.002), and centerline/road-edge excursions ( P = 0.01). There was a significantly higher percentage SADS reduction in cirrhotics who got lost (25%) compared to those who did not get lost (12%) and controls (8%, P = 0.014). Conclusions: Insight into driving skills in cirrhosis improves after driving simulation and is highest in those with navigation errors and MHE on ICT. Driving simulator-associated insight improvement may be the first step towards the cognitive rehabilitation of driving skills in cirrhosis. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Cirrhosis and hepatic encephalopathy (HE) can adversely affect survival, but their effect on socioeconomic and emotional burden on the family is not clear. The aim was to study the emotional and socioeconomic burden of cirrhosis and HE on patients and informal caregivers.METHODS:A cross-sectional study in two transplant centers (Veterans and University) of cirrhotic patients and their informal caregivers was performed. Demographics for patient/caregivers, model-for-end-stage liver disease (MELD) score, and cirrhosis complications were recorded. Patients underwent a cognitive battery, sociodemographic, and financial questionnaires. Caregivers were given the perceived caregiver burden (PCB; maximum=155) and Zarit Burden Interview (ZBI)-Short Form (maximum=48) and questionnaires for depression, anxiety, and social support.RESULTS:A total of 104 cirrhotics (70% men, 44% previous HE, median MELD 12, 49% veterans) and their caregivers (66% women, 77% married, relationship duration 32±14 years) were included. Cirrhosis severely impacted the family unit with respect to work (only 56% employed), finances, and adherence. Those with previous HE had worse unemployment (87.5 vs. 19%, P=0.0001) and financial status (85 vs. 61%, P=0.019) and posed a higher caregiver burden; PCB (75 vs. 65, P=0.019) and ZBI (16 vs. 11, P=0.015) compared with others. Cognitive performance and MELD score were significantly correlated with employment and caregiver burden. Veterans and non-veterans were equally affected. On regression, depression score, MELD, and cognitive tests predicted both PCB and ZBI score.CONCLUSIONS:Previous HE and cognitive dysfunction are associated with worse employment, financial status, and caregiver burden. Cirrhosis-related expenses impact the family unit's daily functioning and medical adherence. A multidisciplinary approach to address this burden is required. [ABSTRACT FROM AUTHOR]

The article highlights a lecture, titled "Current and Future Diagnosis of Hepatic Encephalopathy," presented at the 5th Hannover International Conference on Hepatic Encephalopathy in Mainz, Germany in May 2009. The lecture included a review of current methods for diagnosing hepatic encephalopathy. During the lecture, an overview of the Clinical Hepatic Encephalopathy Staging Scale (CHESS) was presented. The lecture also addressed the challenges in the diagnosis of hepatic encephalopathy.

OBJECTIVES:Clostridium difficile–associated disease (CDAD) is associated with antibiotic use, acid suppression, and hospitalization, all of which occur frequently in cirrhosis. The aim was to define the effect of CDAD on outcomes and identify risk factors for its development in cirrhosis.METHODS:Case–control studies using the de-identified national (Nationwide Inpatient Sample, NIS) and an identified liver transplant center database of hospitalized cirrhotics with and without CDAD were performed. The NIS 2005 was queried for mortality, charges, and length of stay (LOS) in cirrhotics with/without CDAD. Outcomes of cirrhosis and infections were also analyzed. In the transplant center database, risk factors for CDAD were defined in hospitalized cirrhotics with/without CDAD who were age matched in a 1:2 ratio.RESULTS:The NIS 2005 included 1,165 cirrhotics with and 82,065 without CDAD. Cirrhotics with CDAD had a significantly higher mortality (13.8% vs. 8.2%, P<0.001), LOS (14.4 days vs. 6.7 days, P<0.001), and charges ($79,351 vs. $35,686, P<0.001) compared with those without CDAD. On multivariate analysis, CDAD was associated with higher mortality (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.29–1.85), charges, and LOS despite controlling for cirrhosis complications and infections. In the transplant center database, 54 cirrhotics with and 108 cirrhotics without CDAD were included. Outpatient spontaneous bacterial peritonitis prophylaxis (35% vs. 13%, P=0.01), inpatient antibiotic (63% vs. 35%, P=0.0001), and proton pump inhibitor (PPI) use (74% vs. 31%, P=0.0001) were significantly higher in those with CDAD.CONCLUSIONS:Cirrhotics with CDAD have a higher mortality, LOS, and charges on the NIS 2005 compared with those without CDAD. Antibiotic and PPI use are risk factors for CDAD development in hospitalized cirrhotics. [ABSTRACT FROM AUTHOR]

OBJECTIVES: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.METHODS: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.RESULTS: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.CONCLUSIONS: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.Am J Gastroenterol 2009; 104:1130–1134; doi:10.1038/ajg.2009.80; published online 31 March 2009 [ABSTRACT FROM AUTHOR]

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.Am J Gastroenterol 2009; 104:898–905; doi:10.1038/ajg.2009.7; published online 10 March 2009 [ABSTRACT FROM AUTHOR]

OBJECTIVES: Alcohol abuse and minimal hepatic encephalopathy may predispose cirrhotics to a higher motor vehicle crash (MVC) rate. Cirrhotics have poor post-trauma outcomes on small-scale studies. The aim was to examine the effect of cirrhosis on mortality, charges, and length of stay (LOS) after MVCs using the Nationwide Inpatient Sample (NIS) 2004. METHODS: NIS 2004 was queried for cirrhotics with MVC (C-MVC), cirrhotics only, and MVC only for demographics, comorbidities, hospital characteristics, and the Injury Severity Score (ISS). C-MVC patients were compared with the other groups. Weighted uni/multivariate regression was performed for all MVCs (with/without cirrhosis). RESULTS: There were 560,080 discharges for cirrhosis only, 262,244 for MVC only, and 1,565 for C-MVC. C-MVC patients were significantly younger (49.8 yr vs 58.6 yr, P < 0.0005) and had less comorbidities than cirrhosis only, but had similar mortality (C-MVC 10.8% vs cirrhosis only 9.9%, P= 0.23). C-MVC patients (49.8 yr) were older than MVC only patients (43.7 yr, P < 0.0005). C-MVC patients also had significantly higher mortality (10.8%) compared with MVC only (3.1%, P < 0.0005) despite similar ISS. C-MVC patients had significantly greater LOS (9.6 days) and charges ($67,119) compared with both MVC only (6.2 days, $43,314) and cirrhosis only (7.4 days, $35,522). Cirrhosis (odds ratio [OR] 3.5, 95% confidence interval [CI] 2.5–5.5) and age >65 yr (OR 5.2, 95% CI 4.4–6.0) were most commonly associated with mortality. Male sex, high ISS, self-pay, teaching, and large and urban hospitals were also significantly associated with mortality. On multivariate regression, cirrhosis was associated with greater charges and LOS. CONCLUSION: Cirrhosis is associated with greater mortality, LOS, and charges after MVC despite controlling for injury severity, comorbidities, and age in NIS 2004. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract  Proton pump inhibitors (PPIs) reduce the rate of rebleeding in patients with nonvariceal upper GI bleed (NVGIB). Oral (PO) and intravenous (IV) pantoprazole are equipotent in raising gastric pH. We conducted a pilot study comparing the efficacy of PO vs. IV pantoprazole for reducing rebleeding after NVGIB. Patients with NVGIB were randomized to receive PO (80 mg BID for 3 days) or IV (80-mg IV bolus and 8 mg/hr infusion for 3 days) pantoprazole followed by pantoprazole, 40 mg PO BID, for 30 days. All patients underwent endoscopy within 24 hr and endotherapy was applied where necessary. Twelve patients randomized to the PO and 13 to the IV pantoprazole group were comparable in age, hematocrit, Rockall scores, ulcer characteristics, and endoscopic interventions. Two patients in the IV arm rebled and another in the IV arm developed reversible renal failure. No patient in the PO arm rebled, had organ failure, or had to be changed to IV pantoprazole. We conclude that in this pilot study, the effect of PO pantoprazole on 30-day rebleeding rate in patients with NVGIB was similar to that of IV pantoprazole. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Idiosyncratic drug hypersenstitivity may occur at increased rates in specific patient populations. Azathioprine has a significant early adverse reaction (EAR) profile, which includes an acute syndrome of constitutional symptoms, fever, rash, and acute pancreatitis and often requires discontinuation of drug. EAR precludes azathioprine use in patients with Crohn's disease (CD) and autoimmune hepatitis (AIH). Our aims were to investigate differential rates of EAR to azathioprine in CD compared to AIH in a tertiary referral center population.METHODS: Retrospective chart review of consecutive CD and AIH patients who were initiated on azathioprine in our inflammatory bowel disease (IBD) and hepatology centers was performed. EAR (fevers and constitutional symptoms, severe arthralgias, nausea, and vomiting) were defined as those occurring within 1 month of initiation. EAR rates between AIH and CD patients were compared using the Fisher's exact test.RESULTS: One hundred and forty-three CD (88F/55M; age 39.2± 13 yr) and 40 AIH (35F/5M; age 53.1± 14 yr) patients were studied. All patients were initiated with equivalent azathioprine dosage (50 mg qd). All AIH patients were on prednisone (mean daily dose 7.5 mg) compared to 51% of CD patients (median daily dose 20 mg). EAR rates were significantly higher in CD patients (42/143; 29%) compared to AIH (2/40; 5%) (Fisher's exact test;p= 0.008). EAR excluding nausea and vomiting were still significantly higher in CD patients (27/143; 19%) compared to AIH (1/40; 2.5%) (Fisher's exact test;p= 0.01). All patients with EAR required drug discontinuation and 7% of CD patients required hospitalization for management of these complications.CONCLUSIONS: CD patients represent a unique subgroup at increased risk of EAR to azathioprine. Mechanisms behind these reactions need to be further defined.(Am J Gastroenterol 2005;100:1121–1125) [ABSTRACT FROM AUTHOR]

Presents several abstracts which was submitted for the 69th Annual Scientific Meeting of the American College of Gastroenterology. "Gastroscope-Push Method to Help Ensure Safety of Blind Esophageal Bougienage," by Joseph C. Yarze; "Does the Proximal Probe of 24-Hour Esophageal PH Studies Add Valuable Clinical Information?," by Larry E. Clark, and David A. Peura; "Primary Esophageal Lymphoma: Experience at Roswell Park Cancer Institute," by Krishdeep S. Chadha, Milind M. Javle, and Francisco H. Ilizaturri.