Hemodialysis in hepatorenal syndrome type 1 in alcoholic liver cirrhosis treated by continual terlipressin infusion in combination with albumin plasmaexpansion

194 Aim: to investigate the predictive factors for R.A occurrence in cirrhotic patients. Methods: The study is a follow up investigation in fifty patients with ascites between 1999-2001. All the patients underwent: serum and urinary sodium concentration, water diuresis, lithium clearance (C.Li.), furosemide-induced natriuresis test, plasma rennin activity (PRA), plasma aldosteron concentration urinary metanephrinesserum malon-dialdehide (MDA) and gluthation (GSH) as index of the oxidative stress. Results: The occurrence of RA was 20% (10 patients) at 1 year and 41% (21 patients) at 3 years. The multivariate analysis disclosed six independent predictors of RA occurrence: low serum sodium concentration (<125mEq/l), a natriuresis <.5OmEq/8 h after 80 mg intravenous furosemide, high P.R.A. (>29 ng/ml/h), low levels for C.Li.(<20 ml/min), high levels of M.D.A. (>250 nmol/dl) and low levels of G.S.H.(<35 kmol/dl). Conclusions: Plasma rennin activity, serum sodium concentration, lithium clearance levels and oxidative stress (MDA and GSH) are predictors of the survival of cirrhotic patients with ascites and indicators for liver transplant in these patients.

Aim: To study effects of calcitonin, an anti-resorptive agent, on improving bone metabolism following OLT. Methods: 33 cholestatic patients (11 PBC, 22 PSC;12 M, 21 F) with no other illnesses or medications before OLT were randomised at OLT to receive a) 100 MRC units of salmon calcitonin (CT) s. c. once daily for the first 6 months postOLT, or b) no therapy. Patients underwent tetracycline labeled iliac crest bone biopsies at time of OLT, and at 4 months post-OLT for histomorphometric assessment. Results: No differences were identified before or after OLT between CT and control patients in any clinical or biochemical parameter, including mineral status, Child score, age, rejection, hospitalization. CT did not reduce the increased bone resorption after OLT nor did it prevent postOLT bone loss. Biochemical and histomorphometric markers of resorption, formation and volumes were identical in CT and control patients. Conclusion: Calcitonin, an inhibitor of bone resorption, has no effect on bone resorption or formation after OLT. This suggests that, in this clinical setting, it either lacks sufficient potency, or is overwhelmed by other factors like immunosuppression in the postOLT period.

I672

I674

SERUM CAFFEINE

METABOLIC

RATIOS AS A TEST OF LIVER

FUNCTION

J. Flieeer

Aim: To evaluate the usefulness of caffeine metabolic ratios as the marker of liver function in comparison with pharmacokinetic parameters of caffeine. 25 patients, liver cirrhosis, 32 -HCV chronic hepatitis, and 17 healthy subjects. Methods: Serum concentration of caffeine (CA), its metabolites: paraxanthine(PX), theobromine( theophylline(TP) were measured by HPLC following a 300mg oral caffeine dose. Blood samples were collected at 4, 8, 12h. Caffeine as well as caffeine metabolic ratios: PX/CA, TB/CA and TP/CA were calculated. Wilcoxon-Mann-Whitney used for statistical analysis-for 0.05. Results: CA elimination half-life in cirrhotic patients 11.8h (6.0-15.3) was significantly higher than in chronic hepatitis patients- 6.9h (4.8-14.6) and healthy subjects- 4.6h (2.3-6.9). CA clearance was significantly reduced both in cirrhotic- O.O26l/h/kg (0.002-0.079) and chronic hepatitis patientsO.O5Ol/h/kg (0.024-0.070) in comparison with controls- O.O9Ol/h/kg (O.OSO0.154). Metabolic ratios for 8h (most discriminating) were as follows: PXlCA in cirrhosis- 0074 (0.017.0.268), in chronic hepatitis- 0.545 (0155. l.OO), both significantly different from controls- 0.740 (0.410-1.380); TBlCA in cirrhosis- 0.054 (0.08.O.lOO), in chronic hepatitis- 0.100 (0.045. 0.200), significantly lower then in controls- 0.143 (0080-0.280); TP/CA in cirrhosis- 0.032 (0.007-0.070), in chronic hepatitis- 0.066 (0.024-0.082) also significantly different from controls- 0.090 (0.041-0.168). Conclusions: Metabolic ratio of one of CA metabolites calculated at 8h seems to be useful and more convenient than traditional pharmacokinetic parameters marker of hepatic function.

EFFECT

OF CALCITONIN,

FOLLOWING

ORTHOTOPIC

IN CHOLESTATIC

PATIENTS

LIVER TRANSPLANTATION

(OLT)

M. M. J. Guichelaar’, B. L. Clarke2, M. Malinchoc3, J. E. Hay’. ‘Liver Transplantation, Mayo Clinic, Rochestes USA; 2Endocrinology, Mayo Clinic, Rochestes USA; 3Biostatistics, Mayo Clinic, Rochestes USA Cholestatic patients have low BMD before OLT with a further decrease and fracturing after OLT. Bone biopsies have shown increased bone resorption before and after OLT in these patients. Salmon calcitonin has proven efficacy in other types of high-turnover osteoporosis.

GLUTAMINE

SUPPLY ON PROTEIN

IN HEPATIC TISSUE.

PERFUSED

A

RAT LIVER

M. Holecek’, R. Rysava’, R. Safranek’, J. Kadlcikova2, L. Sprong13. ‘Physiology, Medical Faculty, Hradec Kralove, Czech Republic; 2Pharmacology, Faculty Of Pharmacy, Hradec Kralove, Czech Republic; 3Biochemistry, University Hospital Motel, Prague, Czech Republic The liver can adjust blood plasma glutamine to the physiological values because of the high activities of both glutamine synthetase and glutaminase. Glutamine deficiency, a common finding in severe illness, has a negative influence on immune status, protein metabolism and disease outcome. The aim of the study was to investigate the effect of glutamine deficiency on amino acid and protein metabolism in liver. Parameters of protein and amino acid metabolism were measured using a model of isolated perfused rat liver with [1-14Clleucine and [ 1-14Clketoisocaproate as a tracer. Glutamine concentration in perfusion solution was 0.5 mM in control and 0 mM in glutamine deficient group. Statistical analysis was performed using Mann-Whitney test. PiO.05 was considered significant. The net release of glutamine (11 kmol/g/h) and higher net uptake of the most of amino acids was observed in glutamine deficient group. There was insignificant effect of lack of glutamine on protein synthesisproteolysis and release of urea. The lack of glutamine caused a significant decrease in leucine oxidation (67~tl.O vs. 13.7~t2.4, kmol/g/h) and an increase in ketoisocaproate oxidation (163.7 & 16.5 vs. 92.0 & 12.9 kmol/g/h). We conclude that decreased delivery of glutamine to hepatic tissue activates glutamine synthesis, decreases resynthesis of essential branchedchain amino acids (leucine, valine, isoleucine) from branched-chain keto acids (BCKA), increases catabolism of BCKA, and has insignificant effect on protein turnover. Supported by a grant NB 6793-3 of IGAMH of the Czech Republic

I675

A BONE ANTI-RESORPTIVE

AGENT, ON BONE METABOLISM

OF DECREASED

STUDY USING ISOLATED

’, J. Juszczyk I, J. Jodynis-Libert2,

M. Matuszewska2. ‘Departmentof Infectious Diseases, University Of Medical Sciences, Poznan, Poland; 2Department Of Toxicology University Of Medical Sciences, Poznan, Poland

I673

EFFECT

AND AMINO ACID METABOLISM

HEMODIALYSIS ALCOHOLIC TERLIPRESSIN

IN HEPATORENAL

LIVER CIRRHOSIS INFUSION

SYNDROME

TREATED

IN COMBINATION

TYPE 1 IN

BY CONTINUAL WITH ALBUMIN

PLASMAEXPANSION F! Jarcuska’, E. Veseliny’, L. Bena’, R. Roland’, T. Hildebrand’, B. Grejtovska’, M. Hancova2, A. Kovacova3. ‘1st Dpt Of Internal Medicine, University Hospital; 21nstitute Of Mathematics, Faculty Of Science, UPJS; ‘Dpt Of Clinical Biochemistry, University Hospital, Kosice, Slovakia

Aim of the Study: Evaluation of hemodialysis (HD) role in alcoholic cirrhosis complicated with hepatorenal syndrome (HRS) Type 1.

liver

Category 8: Nutrition, metabolism, alcoholic liver disease, pharmacology Material and Methods: From February 1998 to August 2002, 17 patients with alcoholic liver cirrhosis complicated by HRS Type 1 were treated with continual terlipressin infusion (l-2 mg daily) in combination with albumin plasmaexpansion (20.60g daily). Patients had been treated for 6-46 days. 9 patient were treated only by pharmacological treatment (4 men, 5 women, age: 48,89&14,08, Child Pugh score: 12,33&1,49). 8 patients required hemodialysis treatment (4 men, 5 women, age: 47,38&16,04, Child-Pugh score: 12,88&1,27, 1 - 11 hemodialysis sessions) because of renal failure progression or hyperhydratation. The results between both groups were compared by Mann-Whitney U test and by Fisher exact test. Results: Serum creatinine before the treatment was higher in patients required HD than in patients treated only by phamacological therapy (42.5,75&226,11 kmol/l resp. 266,56&120,58 kmol/l, p=O,O152). We observed decreased serum creatinine level (at least 20%) in 7/8 patients in HD group and in all patients treated only by pharmacological treatment (NS), serum creatinine decreased to normal level only in 3 patients treated by pharmacological treatment (NS). Serum creatinine after the treatment was higher in patients required HD than in patients treated only by phamacological therapy (257,63&95,72 kmol/l resp. 127,l l&40,39 kmol/l p=O,OO16). Diuresis before the therapy was 501,25&378,20 ml in HD group and 707,78&491,95 ml in pharmacology group (NS). Diuresis after the treatment was lower in patients required HD than in patients treated only by phamacological therapy (1005&550,05 ml resp. 1867,78&930,7 ml, p=O,O385). There were no statistical significant difference between both groups in serum natrium levels, natriuresis a bilirubin levels before the treatment and after the treatment. 5 patients from HD group and 2 patients from pharmacological group died during the hospitalization (NS). Conclusions: Patients who required HD had worser answer to HRS treatment and higher mortality in comparison to patients treated only by pharmacological therapy, but HD could be beneficial in some patients with HRS Type 1.

I

676

URSODEOXICOLIC NONALCOHOLIC

ACID IN THE TREATMENT

OF

STEATOHEPATITIS

S. Bagci’, A. Uygun’, A. Kadavifci2, A. Bektas’, Y. Ates’, A. Erdil’, N. Karaeren’, K. Dagalp’. ‘Department of Gastroenterology, Gulhane Military Medical Academy, Ankara; 2Department of Gastroenterology, Gaziantep University Medical Faculty, Gaziantep, Turkey

Nonalcoholic steatohepatitis (NASH) is a common disorder, which is characterized with hepatocellular damage due to fatty infiltration in liver. There is not a specific treatment at present for NASH. In recent years, ursodeoxicolic acid (UDCA) has been suggested as an effective treatment in some cases of NASH but not generally accepted yet. Patients and Methods: In this study, we evaluated the effectivity of UDCA in 28 consecutive patients with histologically proven NASH. All patients were given 250 mg t.i.d. UDCA for 12 months duration. Biochemical and sonographic follow up were done in every 3 months. No specific diet was suggested to patients. A liver biopsy was repeated at the end of the treatment and histopathological findings were compared with the findings at entry. Results: The mean AST level decreased from 48.7&14.8 to 35.4&14 u/L and ALT level from 93.2&21.4 to 58.9&16.1 u/L at the end of the treatment. The decrease in mean values was most prominent at the first three months of the treatment. No significant changes were seen sonographically at the first 9 months of the treatment. However, there was a significant decrease in the grade of steatosis between 9 and 12 months. Histologically an improvement was detected in inflammatory findings but not in fibrosis at the control. Conclusion: A significant improvement was obtained with UDCA in the levels of liver aminotransferases in NASH patients. There was also decrease in inflammatory findings in liver histology but not in fibrosis. These results reveal that UDCA may be a treatment alternative in patients with NASH. However, the long-term benefit of the treatment is not clear yet. We think further studies may define better the role of UDCA in the treatment of NASH. Objective:

I677

METFORMIN

IN THE TREATMENT

195 OF NONALCOHOLIC

STEATOHEPATITIS

A. Uygun’, A.T. I&‘, A. Kadavifci2, Z. Yesilova’, M. G&en’, N. Karaeren’, K. Dagalp’. ‘Department Of Gastroenterology, Gulhane Military Medical Academy, Ankara, Turkey; 2Department Of Gastroenterology, Gaziantep University Medical Faculty, Gaziantep, Turkey Nonalcoholic steatohepatitis (NASH) is common in general population and may result with serious consequences in some patients. There is no proven effective therapy for NASH and attempts usually are made to modify potential risk factors. Increased insulin resistance is one of the most proposed mechanisms in the development of NASH and metformin has a decreasing effect on insulin resistance. Based on this information, we investigated the effectivity of metformin in the treatment of NASH. Thirty-one patients, which diagnosed as NASH, were randomized into one of two groups. The first group (n=14) was given diet only while the second (n=17) was given diet plus metformin 1700 mg b.i.d. for six months. The metabolic, biochemical and histological parameters were compared statistically before and after the treatment in both groups. At the end of the study, a significant reduction in BMI (30, l&3 to 27, 7&2 kg/m2), serum insulin (30, 4&56 to 9, 8&7 KU/ml), ALT (83,4&24 to 46,4&23 u/L), AST (58&17 to 35, 8&10 u/L) levels and the index of insulin resistance (1, l&2 to 0, 35&O, 2) were observed in the metformin group (piO.05) whereas minimal or no changes were detected in first group. There was also significant improvement in the histological findings in the metformin group at the sixth month. Metformin as an insulin-sensitizing agent cause significant improvement in both metabolic and histological findings of NASH. The mechanism of these beneficial results is probably related to increased insulin resistance in these patients which improved by metformin. However the long-term effectivity of the treatment is not clear yet and further studies are needed.

I

678

TEUCRIUM

POLIUM L. (GOLDEN

HEPATITIS: REPORT

GERMANDER)

-INDUCED

OF 5 CASES

E. Vasileiadou , E. Karanikolas, D. Chrysagis, D. Kolokotroni, E. Papamihalis, A. Banti, L. Sidiropoulos. ‘Internal Medicine, Hospital Of Infectious Diseases, Thessaloniki, Greece Aims: Teucrium Polium L (TP) is an herb used mainly for its hypoglycemic and hypolipidemic effects. In literature there is paucity of reports about TP-induced- hepatotoxicity. 5 cases of hepatitis after administration of TP extract are presented. Methods: 5 patients, 4 women and 1 man, aged 62 to 67 years old, were hospitalized from 2000 to 2002, because of clinical and biochemical signs of icteric (4) and anicteric (1) hepatitis. 3 of them had been taking TP for diabetes mellitus and 2 for hyperlipidemia. 2 patients had been taking TP every day for the last month, whether rest 3 occasionally for more than 1 year. Results: In laboratory there was no evidence of viral, autoimmune, metabolic, or other hepatotoxic causes of liver damage. Liver biopsy revealed a picture of acute hepatitis in 2 patients, while in other 2 a picture of chronic hepatitis, with low-grade cholestasis. 5th patient refused to undergo a liver biopsy. Ingestion of TP discontinued immediately. Liver function improved progressively. By 10 to 30 days all patients were discharged. A follow-up after 2 and 6 months documented normal liver function. Conclusions: TP, an herb with wide use in Mediterranean territory and East, may be hepatotoxic in vulnerable individuals. Liver damage may occur after continuous or intermittent use of the herb. Liver histology may reveal a picture of acute or chronic hepatitis, with or without cholestasis. People should consider about the use of herbs, especially if they are not officially informed about their possible adverse reactions.