s1964 patients with minimal hepatic encephalopathy have poor insight into their driving skills

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speeding citations & illegal turns. OHE patients were compared to MHE- & MHE+ groups. Results: 38 MHE+, 12 MHE- & 13 OHE patients (Hepatitis C, MHE-:6,OHE:5,MHE+:23, p=0.4) with similar age (MHE-:52±9, OHE:52±4,MHE+:54±7 yrs,p=0.5) and gender (males MHE-:8,OHE:7,MHE+:21,p=0.8)were included. All OHE patients were adherent on lactulose (mean 3 bms/day) and did not have asterixis on examination. OHE patients exhibited impaired psychometric performance compared to the MHE- group on all tests despite being on treatment (Table). OHE patients also had significantly higher collisions, speed citations & illegal turns compared to the MHE- group. There was no significant difference between OHE & MHE+ patients' psychometric or driving performance. Conclusions: OHE patients exhibit psychometric & driving skill impairment on a simulator similar to MHE+ patients despite clinical response to therapy. Endpoints other than disappearance of asterixis, such as driving performance, may be important additional measures of therapy efficacy in OHE. Driving Simulator Performance S1964 Patients with Minimal Hepatic Encephalopathy Have Poor Insight Into Their Driving Skills Jasmohan S. Bajaj, Muhammad Hafeezullah, Raymond G. Hoffmann, Thomas A. Hammeke, Kia Saeian Minimal hepatic encephalopathy (MHE) is associated with poor quality of life & a higher risk of traffic accidents. Personal insight into driving skills is important for a patient to seek medical attention for MHE therapy. The Driving Behavior Survey (DBS) is a 26-part scale validated in attention deficit disorder. Each question is rated on a Likert scale of 0-4(max 104). A higher score reflects good driving. It inquires about both driving skills focusing on attention, vigilance and safety judgments(10 questions) and driving habits (16 questions). DBS can be self-administered or completed by others familiar with the individual's driving. The aim was to determine personal insight into behaviors that may result in accidents in cirrhotics tested for MHE by comparing personal DBS score (both driving habits & skills) to the others' assessment. Methods: 36 non-alcoholic cirrhotics tested for MHE (25 HCV, 7 autoimmune & 4 others; age 51±3 yrs, 23M,education 12±3 yrs) & 46 age/education- matched healthy controls (25 M) were given the DBS for self-assessment at the time of MHE testing (based on psychometric tests). An adult familiar with their driving was contacted in the subject's absence to complete an independent DBS assessment of the subject's driving. Total DBS score, driving skill & driving habit components were compared between MHE+, MHE- and controls with respect to self and other assessment. Results: 26 patients were MHE+ &10 were MHE-. 85% of assessors were spouses, rest were friends. Self vs. others: MHE+ patients were rated significantly lower on driving skills by their assessors compared to self-assessment (table). In contrast, self-assessment of driving skills was similar to independent assessment in MHE- patients & controls. Total score & driving habits showed similar, but not statistically significant differences between self & others. Comparison between groups: Total score was significantly lower in MHE+ group compared to MHE- & controls. Conclu- sions: MHE+ patients were rated significantly lower on driving skills by their independent assessors compared to self-assessment; indicating poor insight into driving skills. An objective driving history should be sought in addition to personal driving assessment to get an accurate picture of driving abilities in MHE. * Lower (p=0.03) assessment of MHE+ driving skills by others vs. self. # Lower (p=0.01) DBS score in MHE+ compared to remaining groups. S1965 Small Intestinal Bacterial Overgrowth of Colonic-Type Carbohidrates Fermentative Bacteria in Cirrhotic Patients Giuseppe Merra, Antonio Dal Lago, Emidio Scarpellini, Rosalba Finizio, Michele Santoro, Maria Grazia Spitilli, Ernesto Cristiano Lauritano, Maurizio Gabrielli, Venanzio Valenza, Giovanni Gasbarrini, Giovanni Ghirlanda, Antonio Gasbarrini Backgrounds and Aim: Small intestinal bacterial overgrowth (SIBO) is a clinical condition characterized by abnormally high colonic-type bacteria in the small intestine, exceeding 106 organisms/mL. In non cirrhotic patients, SIBO is associated with the presence of symptoms related to malabsorption and gas production (end product of carbohydrates fermentation).. A role of small bowel bacteria has been hypothesized in the pathogenesis of hepatic encephalo- pathy (HE) and spontaneous bacterial peritonitis (SBP) in cirrhotics. This study to assess SIBO prevalence in cirrhotic patients. Methods: thirthy (30) HCV-cirrhotic pts (10 Child A-793 AASLD Abstracts A; 10 Child B; 10 Child C) were consecutively enrolled and submitted to H2-lactulose breath test (LBT). 30 non cirrhotics patients were used as controls. SIBO diagnosis was based on LBT positivity criteria (two distinct peaks, consisting of two consecutive H2 values >10 p.p.m. above the basal value after 10 g lactulose ingestion). Results: 18 out of 30 cirrhotics (60%) had a positive LBT vs 1 out of 30 controls (3.3%); p<0.05 . Among cirrhotics, a significative difference was observed in the different Child group: 20% in Child A, 50% in Child B, 80% in Child C. Conclusion: Cirrhotics have a significant prevalence of SIBO compared to controls. SIBO prevalence was associated to severity of cirrhosis. Lactulose administration could be a good substrate for the growth in the small bowel of fermentative colonic-type bacteria. A role of SIBO presence in HE and SBP has to be fully evaluated. S1966 Effects of I.V. Albumin Substitution in Patients with Hepatic Cirrhosis and Hypoalbuminemia On the Clearance of Cholyl-Lysyl-Fluorescein As a Marker of Hepatic Dysfunction Hans-Jurgen Gruss INTRODUCTION: Cholyl-lysyl-fluorescein (NRL972) is a flurescent-labelled bile salt, which is taken up and eliminated via the liver in an analogous way to natural bile salts without undergoing biotransformations. NRL972 is an investigational marker of hepatic dysfunction. Present clinical study data have so far indicated that NRL972 may allow separating healthy subjects from patients with cirrhosis, but also allow to stage cirrhosis patients AIMS & METHODS: NRL972 clearance is closely linked to the plasma volume and has a high albumin binding. The objective of the conducted parallel-group study was an evaluation of the pharmacokinetics of NRL972 before, during and after daily i.v. doses of 1g/kg body weight (BW) low-sodium albumin on two consecutive days in patients with hepatic cirrhosis and hypoalbuminemia (n=24) with either no ascites (n=12) or at least moderate ascites (n=12). In addition, the safety and tolerability of repeat i.v. doses of NRL972 was assessed. RESULTS: 36 patients were screened for enrolment, of which 24 patients were enrolled. All 24 patients completed the study as planned with two days of albumin infusion and three repeat NRL972 assessments. Mean age was 56.9±10.9 years (range: 37 - 74). The mean BW was 79.7±15.6kg and a BMI of 27.5±4.2kg/m2. Patients suffered from a number of concomitant diseases. All cases had alcoholic cirrhosis. In addition, more then half the patient population had also a viral hepatitis history. Most included subjects were in the Child-Pugh stage B (15), while one case was stage A and 8 cases stage C. Albumin supplementation had a minimal effect on plasma albumin levels (+9.3g/L;95%CI: +6.8 to +11.8g/L), but did not change other common disease features. The pharmacokinetic analysis for NRL972 did not show a signific- ant effect of the two-day albumin infusion in comparison to the baseline values. However, a trend towards a slight prolongation in the t1/2 (ratio: 1.22) and reduction in clearance (mean: -7.0ml/min) was observed directly after albumin supplementation. 53 adverse events were reported, of which 10 had at least a possible relation to NRL972 dosing and were mainly linked to untoward changes in clinical laboratory tests. No severe or serious adverse events were reported. CONCLUSION: A low albumin situation, often seen in hepatic cirrhosis patients, is not the predominant cause of the reduced disposition of NRL972 in such patients compared with normal controls. Instead, albumin substitution and the resulting rise in plasma albumin caused a short lasting further delay in the disposition of NRL972. Therefore, NRL972 may represent a valuable staging parameter for the clinical assessment of cirrhosis. S1967 Oxidized Albumin Is Associated with Water Retention and Severity of Disease in Patients with Liver Cirrhosis Masahiro Sakata, Takumi Kawaguchi, Eitaro Taniguchi, Minoru Itou, Mitsuhiko Abe, Chikatoshi Yanagimoto, Ichirou Miyajima, Hironori Koga, Masaru Harada, Tetsuharu Oriishi, Michio Sata Background and Aims: Albumin is a major antioxidant in plasma. Serum albumin exists in both oxidized and reduced forms. Oxidized albumin has various modifications at Cys34 and is known to correlate with function of albumin In Vitro, however, the significance of oxidized albumin remains unclear in patients with liver disease. The aims of this study are to investigate the functional and prognostic significance of oxidized albumin in patients with chronic liver disease. Patients and Methods: We analyzed 40 patients with chronic liver disease (hepatitis C virus; n = 31, hepatitis B virus; n = 3, alcohol; n = 5, non-alcoholic steatohepatitis; n = 1) and patients with chronic renal failure were excluded in this study. Oxidized albumin was determined by high-performance liquid chromatography. Water retention was used as a function of albumin. The degree of water retention was evaluated by a direct segmental multifrequency-bioelectrical impedance analyzer (InBody 3.2, BIOSPACE, Tokyo, Japan) and was expressed as extra cellular water/total body water (ECW/TBW). The severity of chronic liver disease was assessed by Child-Pugh score or the model for end- stage liver disease (MELD) score. Correlations between oxidized albumin percentage and ECW/TBW, Child-Pugh score, or MELD score were examined. Results: In all patients, mean age was 66.8 ± 9.7. Oxidative albumin percentage, ECW/TBW, Child-Pugh score, and MELD score ranged from 20.7% to 59.3%, from 0.327 to 0.376, from 5 to 11, and from 6 to 66, respectively. There was a significant correlation between oxidized albumin percentage and ECW/TBW (σ = 0.68; p < 0.0001), which was more significant than a correlation between serum albumin level and ECW/TBW (σ = - 0.49; p = 0.002). Furthermore, oxidized albumin percentage was also significantly correlated with Child-Pugh score or MELD score (σ = 0.51; p = 0.013, σ = 0.44; p = 0.006, respectively). Conclusion: In conclusion, oxidized albumin percentage was associated with both degree of water retention and severity of chronic liver disease. Oxidized albumin may be a useful new marker assessing function of albumin and severity of disease in patients with chronic liver disease. AASLD Abstracts

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speeding citations & illegal turns. OHE patients were compared to MHE- & MHE+ groups.Results: 38 MHE+, 12 MHE- & 13 OHE patients (Hepatitis C, MHE-:6,OHE:5,MHE+:23,p=0.4) with similar age (MHE-:52±9, OHE:52±4,MHE+:54±7 yrs,p=0.5) and gender (malesMHE-:8,OHE:7,MHE+:21,p=0.8)were included. All OHE patients were adherent on lactulose(mean 3 bms/day) and did not have asterixis on examination. OHE patients exhibitedimpaired psychometric performance compared to the MHE- group on all tests despite beingon treatment (Table). OHE patients also had significantly higher collisions, speed citations& illegal turns compared to the MHE- group. There was no significant difference betweenOHE & MHE+ patients' psychometric or driving performance. Conclusions: OHE patientsexhibit psychometric & driving skill impairment on a simulator similar to MHE+ patientsdespite clinical response to therapy. Endpoints other than disappearance of asterixis, suchas driving performance, may be important additional measures of therapy efficacy in OHE.Driving Simulator Performance

S1964

Patients with Minimal Hepatic Encephalopathy Have Poor Insight Into TheirDriving SkillsJasmohan S. Bajaj, Muhammad Hafeezullah, Raymond G. Hoffmann, Thomas A.Hammeke, Kia Saeian

Minimal hepatic encephalopathy (MHE) is associated with poor quality of life & a higherrisk of traffic accidents. Personal insight into driving skills is important for a patient to seekmedical attention for MHE therapy. The Driving Behavior Survey (DBS) is a 26-part scalevalidated in attention deficit disorder. Each question is rated on a Likert scale of 0-4(max104). A higher score reflects good driving. It inquires about both driving skills focusing onattention, vigilance and safety judgments(10 questions) and driving habits (16 questions).DBS can be self-administered or completed by others familiar with the individual's driving.The aim was to determine personal insight into behaviors that may result in accidents incirrhotics tested for MHE by comparing personal DBS score (both driving habits & skills)to the others' assessment. Methods: 36 non-alcoholic cirrhotics tested for MHE (25 HCV,7 autoimmune & 4 others; age 51±3 yrs, 23M,education 12±3 yrs) & 46 age/education-matched healthy controls (25 M) were given the DBS for self-assessment at the time of MHEtesting (based on psychometric tests). An adult familiar with their driving was contacted inthe subject's absence to complete an independent DBS assessment of the subject's driving.Total DBS score, driving skill & driving habit components were compared between MHE+,MHE- and controls with respect to self and other assessment. Results: 26 patients wereMHE+ &10 were MHE-. 85% of assessors were spouses, rest were friends. Self vs. others:MHE+ patients were rated significantly lower on driving skills by their assessors compared toself-assessment (table). In contrast, self-assessment of driving skills was similar to independentassessment in MHE- patients & controls. Total score & driving habits showed similar, butnot statistically significant differences between self & others. Comparison between groups:Total score was significantly lower in MHE+ group compared to MHE- & controls. Conclu-sions: MHE+ patients were rated significantly lower on driving skills by their independentassessors compared to self-assessment; indicating poor insight into driving skills. An objectivedriving history should be sought in addition to personal driving assessment to get an accuratepicture of driving abilities in MHE.

* Lower (p=0.03) assessment of MHE+ driving skills by others vs. self. # Lower (p=0.01)DBS score in MHE+ compared to remaining groups.

S1965

Small Intestinal Bacterial Overgrowth of Colonic-Type CarbohidratesFermentative Bacteria in Cirrhotic PatientsGiuseppe Merra, Antonio Dal Lago, Emidio Scarpellini, Rosalba Finizio, Michele Santoro,Maria Grazia Spitilli, Ernesto Cristiano Lauritano, Maurizio Gabrielli, Venanzio Valenza,Giovanni Gasbarrini, Giovanni Ghirlanda, Antonio Gasbarrini

Backgrounds and Aim: Small intestinal bacterial overgrowth (SIBO) is a clinical conditioncharacterized by abnormally high colonic-type bacteria in the small intestine, exceeding 106organisms/mL. In non cirrhotic patients, SIBO is associated with the presence of symptomsrelated to malabsorption and gas production (end product of carbohydrates fermentation)..A role of small bowel bacteria has been hypothesized in the pathogenesis of hepatic encephalo-pathy (HE) and spontaneous bacterial peritonitis (SBP) in cirrhotics. This study to assessSIBO prevalence in cirrhotic patients. Methods: thirthy (30) HCV-cirrhotic pts (10 Child

T : 11501$$CH304-02-08 17:16:45 Page 793Layout: 11501B : o

A-793 AASLD Abstracts

A; 10 Child B; 10 Child C) were consecutively enrolled and submitted to H2-lactulosebreath test (LBT). 30 non cirrhotics patients were used as controls. SIBO diagnosis wasbased on LBT positivity criteria (two distinct peaks, consisting of two consecutive H2 values>10 p.p.m. above the basal value after 10 g lactulose ingestion). Results: 18 out of 30cirrhotics (60%) had a positive LBT vs 1 out of 30 controls (3.3%); p<0.05 . Amongcirrhotics, a significative difference was observed in the different Child group: 20% in ChildA, 50% in Child B, 80% in Child C. Conclusion: Cirrhotics have a significant prevalenceof SIBO compared to controls. SIBO prevalence was associated to severity of cirrhosis.Lactulose administration could be a good substrate for the growth in the small bowel offermentative colonic-type bacteria. A role of SIBO presence in HE and SBP has to befully evaluated.

S1966

Effects of I.V. Albumin Substitution in Patients with Hepatic Cirrhosis andHypoalbuminemia On the Clearance of Cholyl-Lysyl-Fluorescein As a Markerof Hepatic DysfunctionHans-Jurgen Gruss

INTRODUCTION: Cholyl-lysyl-fluorescein (NRL972) is a flurescent-labelled bile salt, whichis taken up and eliminated via the liver in an analogous way to natural bile salts withoutundergoing biotransformations. NRL972 is an investigational marker of hepatic dysfunction.Present clinical study data have so far indicated that NRL972 may allow separating healthysubjects from patients with cirrhosis, but also allow to stage cirrhosis patients AIMS &METHODS: NRL972 clearance is closely linked to the plasma volume and has a high albuminbinding. The objective of the conducted parallel-group study was an evaluation of thepharmacokinetics of NRL972 before, during and after daily i.v. doses of 1g/kg body weight(BW) low-sodium albumin on two consecutive days in patients with hepatic cirrhosis andhypoalbuminemia (n=24) with either no ascites (n=12) or at least moderate ascites (n=12).In addition, the safety and tolerability of repeat i.v. doses of NRL972 was assessed. RESULTS:36 patients were screened for enrolment, of which 24 patients were enrolled. All 24 patientscompleted the study as planned with two days of albumin infusion and three repeat NRL972assessments. Mean age was 56.9±10.9 years (range: 37 - 74). The mean BW was 79.7±15.6kgand a BMI of 27.5±4.2kg/m2. Patients suffered from a number of concomitant diseases. Allcases had alcoholic cirrhosis. In addition, more then half the patient population had also aviral hepatitis history. Most included subjects were in the Child-Pugh stage B (15), whileone case was stage A and 8 cases stage C. Albumin supplementation had a minimal effecton plasma albumin levels (+9.3g/L;95%CI: +6.8 to +11.8g/L), but did not change othercommon disease features. The pharmacokinetic analysis for NRL972 did not show a signific-ant effect of the two-day albumin infusion in comparison to the baseline values. However,a trend towards a slight prolongation in the t1/2 (ratio: 1.22) and reduction in clearance(mean: -7.0ml/min) was observed directly after albumin supplementation. 53 adverse eventswere reported, of which 10 had at least a possible relation to NRL972 dosing and weremainly linked to untoward changes in clinical laboratory tests. No severe or serious adverseevents were reported. CONCLUSION: A low albumin situation, often seen in hepatic cirrhosispatients, is not the predominant cause of the reduced disposition of NRL972 in such patientscompared with normal controls. Instead, albumin substitution and the resulting rise inplasma albumin caused a short lasting further delay in the disposition of NRL972. Therefore,NRL972 may represent a valuable staging parameter for the clinical assessment of cirrhosis.

S1967

Oxidized Albumin Is Associated with Water Retention and Severity of Diseasein Patients with Liver CirrhosisMasahiro Sakata, Takumi Kawaguchi, Eitaro Taniguchi, Minoru Itou, Mitsuhiko Abe,Chikatoshi Yanagimoto, Ichirou Miyajima, Hironori Koga, Masaru Harada, TetsuharuOriishi, Michio Sata

Background and Aims: Albumin is a major antioxidant in plasma. Serum albumin exists inboth oxidized and reduced forms. Oxidized albumin has various modifications at Cys34and is known to correlate with function of albumin In Vitro, however, the significance ofoxidized albumin remains unclear in patients with liver disease. The aims of this study areto investigate the functional and prognostic significance of oxidized albumin in patientswith chronic liver disease. Patients and Methods: We analyzed 40 patients with chronicliver disease (hepatitis C virus; n = 31, hepatitis B virus; n = 3, alcohol; n = 5, non-alcoholicsteatohepatitis; n = 1) and patients with chronic renal failure were excluded in this study.Oxidized albumin was determined by high-performance liquid chromatography. Waterretention was used as a function of albumin. The degree of water retention was evaluated bya direct segmental multifrequency-bioelectrical impedance analyzer (InBody 3.2, BIOSPACE,Tokyo, Japan) and was expressed as extra cellular water/total body water (ECW/TBW). Theseverity of chronic liver disease was assessed by Child-Pugh score or the model for end-stage liver disease (MELD) score. Correlations between oxidized albumin percentage andECW/TBW, Child-Pugh score, or MELD score were examined. Results: In all patients, meanage was 66.8 ± 9.7. Oxidative albumin percentage, ECW/TBW, Child-Pugh score, and MELDscore ranged from 20.7% to 59.3%, from 0.327 to 0.376, from 5 to 11, and from 6 to 66,respectively. There was a significant correlation between oxidized albumin percentage andECW/TBW (σ = 0.68; p < 0.0001), which was more significant than a correlation betweenserum albumin level and ECW/TBW (σ = - 0.49; p = 0.002). Furthermore, oxidized albuminpercentage was also significantly correlated with Child-Pugh score or MELD score (σ = 0.51;p = 0.013, σ = 0.44; p = 0.006, respectively). Conclusion: In conclusion, oxidized albuminpercentage was associated with both degree of water retention and severity of chronic liverdisease. Oxidized albumin may be a useful new marker assessing function of albumin andseverity of disease in patients with chronic liver disease.

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