HEPATOLOGY go1. 34, No. 4, Pt. 2, 2001 AASLD ABSTRACTS 5 5 1 A

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TFIE VALIDITY OF NUTRITIONAL MARKERS IN PATIENTS WITH CIR- RItOSIS. Joseph Morelli, Medical Unitverstiy of South Carolina, Charleston, SC; Ira R Willner, Anthony Balistreri, Mark Delegge, Medical University of South Carolina, Charleston, SC

l [nt roduet ion Malnutr i t ion and liver failure are closely related, it is believed that nutr i t ional intervention on at risk liver failure patients may improve out- come. However determining which patients are at nutr i t ional risk is difficult. Standard nutr i t ional evaluation includes weight , a lbumin(alb) , p rea lbnmin (we-A), and occasional an thropormet r ic methods. There has not been stan- dard correlat ion of these methods in patients wi th cirrhosis. Methods 23 con- secutive patients wi th biopsy proven cirrhosis were enrolled. A bat tery of nutr i t ional measurements including dominan t handgr ip testing (average of three measurements on each arm), midarm muscle circumference (protein mnscle mass)(MAC), body mass index (BMI), alb, pre-A, CTP score and 24 hou r urines for creatinine clearance, protein, and ur inary ni t rogen were ob- tained. Resul ts There were 16 males:7 females. 18 Caucasians:4 African Amer- icans: l Asians. Mean age 53 years (range 37-68). Etiology of cirrhosis: 8 Hep- atitis C:8 Etoh :3 Cryptogenic:3 Au to immune : l Sarcoid :l Drug Induced. Ten had ascites and 8 had encephalopathy. Mean CTP score 7.7 ( range 5-12). Anthropormet r ic findings: BMI mean 29(2t -46) : mean r ight MAC 30.4cm (22-52): mean left MAC 30.2 cm(22-50): mean right handgr ip s t rength 38 dynes (15-65): mean left handgr ip s t rength 34 dynes(15-62): 22 Right handed dominant . Mean a lbumin 2.9 mg/dl (1.8-4.4): mean prea lbumin 9.5 mg/dl (2.5-17.9). Using multivariate analysis there was no correlation between pre- albumin, albumin, protein and ni t rogen excretion in the urine and handgr ip strength. There was a t rend between increasing BMI and handgr ip s t rength ( r= .81) and handgr ip s t rength and midarm circumference ( r = .79). There was also a negative t rend between CTP and handgr ip strength. Conc lu s ion Prelim- inary data shows that traditional markers of nutr i t ional assessment like preal- bumin and a lbumin do not correlate wi th BMI or rising CTP score in this cirrhotic populat ion. However markers of muscle s t rength or muscle mass as measured by MAC and handgr ip s t rength seem to correlate wi th r ising CTP score and BMI. These simple and easily reproducible measurements when done serially may be helpful in determining those in need of nutr i t ional inter- vention.

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IS FATIGUE OF CHOLESTASIS MEDIATED BY ALTERED CENTRAL SE- ROTONINERGIC NEUROTRANSMISSION?. Cihan Yurdaydin, Ankara Univ Gastroenterology Section, Ankara Turkey; Turgay Celik, Zafer M Goren, Gulhane Military Academy Pharmacology Dpt, Ankara Turkey; Hakan Gurdal, Ankara Univ Medical Sch Pharmacology Dept, Ankara Turkey; Turner Degim, Gazi University Pharmacy Faculty, Ankara Turkey; Murat Toruner, Kubilay Cinar, Ankara Univ Gastroenterology Section, Ankara Turkey; Tayfun I Uzbay, Gulhane Military Academy, Ankara Turkey; Hakan Bozkaya, Ankara Univ Gastroenterology Section, Ankara Turkey

Previous studies have suggested that the fatigue of cholestasis may he l inked to serotonin (5-HT)ta-mediated neurotransmiss ion (NTM) (Swain & Maric, Hepatology 1997). In this study, 5-HT~A-mediated NTM was explored in a rat model of cholestasis. Methods: Two groups of rats, bile duct ligated (BDL) and sham operated (SH), were studied in the following experiments: 1. Fatigue was assesssed in the forced swim test; floating time was observed for 15 min. 2. 5-HTtA and 5-HT2 receptor (rec) density- was explored in discrete bra in regions using [3H]8-OH DPAT and [3H]MDL 100,907 as hot l igands in a receptor binding assay. 3. ExtracelIular brain 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels were measured using in vivo microdialysis and HPLC. 4. The serotonin behavioral syndrome (SBS) was induced with the 5-HTta-rec agonist 8 -OH DPAT in BDL and SH rats and a dose response curve was obtained. The SBS was assessed by moni tor ing 5 components of it. Results: 1. Forced swim test: time spent floating was: SH: 191+22sec (x+SEM); BDL: 310-+35"(*p<0 .05 vs. SH). After 1.2mg/kg 8OH DPAT: SH. 103-+24; BDL: 162-+27" (*p<0 .05 vs. control BDL rat). 2. 5-HTla and 5-HT2 rec density increased in cortex (286-+76 fmol/mg [x-+SD] vs. 81-+22) and h ippocampns (41-+5.4 vs. 20-+7.4), respectively. No change in rec. densities was seen in other brain areas. 3. In vivo brain dialysis: 5-HT levels were unchanged. 5-HIAA was increased in BDL rats (3.6-+0.Sng/ml vs.0.7-+0.4,p<0.05). 4. Dose response curves for the SBS were similar in BDL and SH rats. Conclusion: The results of this s tudy do not suppor t a contr ibut ion of 5-HTiA-mediated NTM to the development of the fatigue of cholestasis.

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CEREBRAL BLOOD FLOW IN BASAL GANGLIA IS CORRELATED WITH CLINICAL SIGNS OF HEPATIC ENCEPIIALOPATHY IN PATIENTS WITH LIVER CIRRHOSIS. Motoh Iwasa, Masahiko Kaito, Kaname Mat- snmura , Yuri Watanabe,J i ro 1korea, Yoshinao Kobayashi, "fuji Tanaka, Masaki Takeo, Kan Takeda, Yukihiko Adachi, Mie University School of Medicine, Tsu Japan

Aims: Increased Tl-weighted magnetic resonance imaging (MRI) signal intensity and MR spectroscopy panem have been described in basal ganglia of cirrhotic patients. Neuroim- aging using single photon emission computed tomography (SPECT) is currently per- formed for evaluating brain function in various diseases. We quantitatively evaluated regional cerebral blood flow (CBF) in patients with liver cirrhosis by SPECT. Methods: Seventeen patients with non-alcoholic liver cirrhosis (14 men and 3 women; mean age, 61 years) were enrolled in the present study. Fifteen patients had no clinical history of hepatic encephalopathy, while 2 had recurrent episodes. Patients with focal brain lesions, severe atrophy or abnormalities on brain MRI were excluded from the study. The Child-Pugh classification of patients was as follows: Group A, 8 patients; Group B, 6 and Group C, 3 patients. Data obtained in 17 subjects (14 men and 3 women; mean age, 61 years) that consulted at the neurological department fur minor subjective symptoms were used as controls; these subjects were free of liver diseases, neurological or psychiatric disorders, and had normal brain MRI. We performed quantitative regional CBF measurement follow- ing a previously described method. The passage through the heart and brain was monitored after bolus injection of Tc-99m ethyl cysteinate dimer using a large-field gamma camera (GCA-7200A, Toshiba, Tokyo, Japan). Regions of interest (ROD were selected over the aortic arch and bilateral cerebral hemispheres in sequential images of radionuclide angiog- raphy. Time-activity curves of these two ROIs were plotted, and the brain perfusion index was determined. Brain SPECT imaging was taken using a three head gamma camera system (GCA-9300A/DI, Toshiba, Tokyo, Japan). Attenuation correction was performed using Chang's method. Triple energy window technique was applied for scatter correction. The linearization factor was set to 2.59 in the Lassen's correction algorithm. Regional CBF was measured in the lentiform, caudate nucleus, thalamus and hippocampus; the CBF was expressed as the mean value of the right and left sides. The ROIs were defined on SPECT / MRI using the muhimodality co-registration software (Automatic Registration Tool, Toshiba, Tokyo, Japan). The portosystemic encephalopathy (PSE) index was assessed as previously described. The difference between the means of two variables was evaluated by the Mann-Whimey U test. Relationship between two variables was tested by the Pearson- product moment correlation or by the Spearman rank test according to the distribution of the variables. Results: Regional CBF values were lower in cirrhotic patients than in control subjects (9% lower in lentiform nucleus, 11% in caudate nucleus, 12% in the thalamus and 21% in hippocampus. A significant negative correlation was noted between regional CBF values and Child-Pugh score in the lentiform nucleus (r=-0.69, p < 0.05) and caudate nucleus (r=-0.64, p < 0.05). Regional CBF values were also inversely and significantly correlated with the PSE index in the lentiform nucleus (r=-0.58, p < 0.05) and caudate nucleus (r=-0.67, p < 0.05). Conclusion: Alterations of the basal ganglia are important components of the hepatic encephalopathy syndrome. Thus, prompt identification of these alterations by the method described in the present study may be useful for treating cirrhotic patients with hepatic encephalopathy at early stage.

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BENEFICIAL EFFECTS OF XYLOOLIGOSACCHARIDES ON AMMONIA METABOLISM IN RATS. Mikio Kajihara, Shinzo Kato, Keio University School of Medicine, Tokyo Japan; Taeko Iino, Suntory Institute for Fundamen- tal Research, Tokyo Japan; Yoshinobu Kiso, Suntory Institute for Fundamenta l Research, Osaka; Masahiro Konishi, Yoshiyuki Yamagishi, Yoshinori Horie, Hiromasa Ishii, Keio University School of Medicine, Tokyo Japan

Background: Xylooligosaccharides (XOS), one of oligosaccharides, are produced by the enzymatic hydrolysis from xylan, which is one of the main components of dietary fibre, and are commercially available as one of functional food ingredients, or prebiotics, in Japan. Encephalopathy is a major complication of liver cirrhosis, is considered to be affected by intestinal microflora that produce ammonia and other neurotoxins, and is often exacer- bated by an excessive intake of dietary protein. We have previously demonstrated that XOS clinically reduced blood ammonia concentrations and ameliorated encephalopathy in cir- rhotic patients. Aim: To evaluate the effects o f XOS on blood ammonia concentrations, and investigate the mechanism whereby prebiotics be beneficial to cirrhotic patients. Materials and Methods: Firstly, we examined the effects of XOS on intestinal micro flora and mucosal permeability. Male SD rats were provided with either tap water (control) or 2% XOS, in drinking water, for 20 days. The faeces were collected at the beginning and the end of period and cultured anaerobically for flora analysis, while the passage of macromolecules from the intestinal lumen to the systemic circulation was measured by loading the gut with FD4 solution. Then we obtained experimental hyperammonaemia by feeding rats with protein-rich diet (milk casein was increased from 25% to 50%, in place of starch) for 20 days, while the rodents were provided with either tap water or 2% XOS. At the end of period, the stools were collected for five consecutive days for determination of nitrogen contents of total stool solids by the Kjeldahl method, caecum was excised for wail weight, and blood was drawn for ammonia and urea nitrogen (BUN) concentrations. At the same time, caecaI contents were collected, pH was measured and the short-chain fatty acids (SCFAs) concentrations were analysed via iquid chromatography. Results: Treatment with 2% XOS increased Bifidobacteria in collected faeces compared to that with control, while intestinal Bacteroidaeeae remained unincreased. At the same time, XOS decreased intesti- nal mucosal permeability in experimental animals. Meanwhile, increased blood ammonia concentrations in rats fed with protein-rich diet were significantly suppresed by ingestion of XOS (control and 2% XOS: 230.1 +-77.5/*g/dl and 146.1 ~+32.2~ respectively). XOS also lowered BUN was also lowered, though not significant. The quantities of total faecal nitrogen were increased in the rats treated with 2% XOS (control and 2% XOS: 175+76.3 mg and 299_+112, respectively), while additimr of XOS resulted in higher SCFAs in the caecal contents (acetate, propionate and butyrate: 6.09_+1.39 mg, 1.18_+0.64 and 1.21 -+0.49, respectively), compared with those in the control rats (acetate, propionate and butyrate: 2.24_+ 1.30 rag, 0.43_+0.23 and 0.39-_0.27, respectively), Iower pH, and tendency towards increased caecal wall weight. Conclusion: The results of our study implicate that XOS, fermented in the intestine to SCFAs, may act by lowering colonic pH, which inhibits coionisation of ammonia-producing anaerobes, and prevent the absorption of ammonia and other neurotoxins into portal system by causing ionisation of ammonia, and by de- creased intestinal mucosal permeability. Furthermore, increased faecal excretion of nitro- gen suggests that the growth of intestinal Bifidobacteria may stimulate incorporation of nitrogen, a major element in ammonia, in the presence of XOS.