217 Prognostic significance of serum ferritin in patients with cirrhosis

217 Prognostic significance of serum ferritin in patients with cirrhosis

Posters 84 as unimpaired [U] ( n = l l ) , minimal HE [MHE] (n=20, 9 on treatment [MHE*]) and overt HE [OHE] (n = 25, 8 on treatment [OHE*]). Result...

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Posters

84

as unimpaired [U] ( n = l l ) , minimal HE [MHE] (n=20, 9 on treatment [MHE*]) and overt HE [OHE] (n = 25, 8 on treatment [OHE*]). Results: The figure shows the age-adjusted results (mean; 0.95 CI) for the Di~t Symbol test when patients were classified (A) on their performance 'on the day' and (B) when they were further sub-grouped according to treatment status. The latter classification showed that only untreated patients with minimal HE performed significantly less well than healthy controls and only untreated patients with overt HE performed significantly less well than both treated and untreated patients with minimal HE. Similar results were obtained for all psychometric tests and for the EEG. A S0

B 60

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P R O S P E C T I V E MULTICENTER STUDY OF THE P R E V A L E N C E OF S P O N T A N E O U S B A C T E R I A L PERITONITIS IN CIRRHOTIC PATIENTS. DIAGNOSTIC A C C U R A C Y O F URINE S C R E E N I N G TEST MU LTISTIX 8SG ®

J.B. Nousbaum ~ J.F. Cadranel 2, P. Nahon 3, E. Ngnyen-Khac4, R. Moreau 5, "12 Thrvenot6, C. Silvain 7, C. Bureau s, A. Tran9, Club Francophone pour l'Etude de l'Hypertension Portale7, Association Nationale des H~ato-Gastroent~rolognes des Hrpitaux Grn~raux 1°.

I Hdpital de La Cavale Blanche, Brest, France," 2Htpital Laennec, Creil, France," ~Hdpital Jean-Verdie~ Bondy, France," 4H@ital Nord, Amiens, France," SHtpital Beaujon, Clichy, France," 6 Centre Hospitalier, Cambrai, France," 7HSpital Jean-Bernard, Poitiers, France," ~Htpital Purpan, Toulouse, France," 9H@ital de L'Archet, Nice, France," 1°Centre Hospitalie~ Mon(ermeil, France

30 HV

U

MHE

MHE*

OHE

OHE*

Conclusions: Treatment status should be considered for classification purposes, particularly when testing new diagnostic tools for the grading of HE.

References

[1] Ferenci Pet al. (2002)Hepatology 35:716 721. [21 Conn HO et al. (1977) Gastroenterology72:573 583. [3] WeissenbornK et al. (2001) J.Hepatol. 34: 768-773.

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EFFICACY O F INFUSION OF L-ORNITHINE L-ASPARTATE IN CIRRHOTIC PATIENTS WITH P O R T O S Y S T E M I C ENCEPHALOPATHY: A P L A C E B O C O N T R O L L E D STUDY

S. Abid, K. Mumtaz, Z. Abbas, S. Harold, N. Jafri, H. All Shah, W. Jafri.

Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan Porto-systemic encephalopathy (PSE) is a major complication of liver cirrhosis, causing increased morbidity and mortality. Prevention and effective treatment of PSE may have important prognostic implications in cirrhotic patients. Ahn: To study the efficacy" of intravenous infusion of L-ornithine L-aspartate (LOLA) in patients with PSE due to liver cirrhosis. Methods: One hundred and twenty" cirrhotic patients admitted with PSE from September 2003 to September 2004 were randomized to receive either LOLA, 20g/day (n 60) or placebo (n 60) in 100ml 5% dextrose infusion over 4 fours for 4 consecutive days, along with standard supportive treamaent of PSE. Treatment outcome was evaluated by daily assessment of number connection test (NCT), PSE stage, fasting serum ammonia, length of hospital stay and mortality. Results: Both patients groups were comparable for age, gender, etiology of cirrhosis, stages of PSE and Child's class. Mean age was 57±11 yeats (62 males) and there were 97 (81%) patients in Child's class C. NCT time reduced significantly on day 3 from baseline (p = 0.03). PSE improved by at least 1 stage on day 4 in 53 patients given LOLA vs. 44 patients given placebo (p= 0.016). Definite improvement in PSE from a baseline to stage 0 was observed on day 4 in 49 patients on LOLA and 40 on placebo (p = 0.034). Duration of hospital stay was shorter in the LOLA grm~p (3.9 vs 5.6 days, p=0.04). Reduction in fasting ammonia levels on day 3, between placebo (142) and OA (118) is marginally significant (p-value = 0.09) and mortality was similar in the two groups. There were no side-effects related to the use of LOLA. Conclusions: Infusions of LOLA appear to be safe and effective in the treatment of PSE in cirrhotic patients. It results in improvement of PSE from baseline to stage 0 and reduces hospital stay.

The diagnosis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients is based upon the detection of an ascitic fluid polymorphonuclear cell count of 250 or more/btl. It has been suggested that the prevalence of SBP in asymptomatic patients is low. Recent studies showed that the diagnosis of SBP could be rapidly obtained using leukocyte esterase reagent strips. However, published studies were restricted to 1 or 2 centers and the number of patients with SBP was limited. The aims of the study were: a) to assess the prevalence of SB P in a multicenter prospective study; b) to assess the diagnostic accuracy of the Multistix 8SG® urine test. Patients and methods: From January to May 2004, 2 Multistix reagent strips were tested independently in drrhotic inpatiec~ts or outpatients having a paracentesis. Cultures of asdtic fluid were performed at the bedside using blood culture bottles, both aerobic and anaerobic. Results: 2123 paracenteses were performed in 1069 patients from 70 centers. 117 SBP were registered. Among them, 56 were assodated with a positive ascitic fluid culture. Prevalence of SBP was 5.5% in the whole population, 9% in inpatients, 1.33% in outpatients (p < 0.0001). The prevalence of SBP was 0.67% in asymptomatic outpatients vs 2.4% in symptomatic outpatients (p 0.04). Using the threshold of 2+ for the positivity of the reagent strip, sensitivity was 43.6% for the diagnosis of SBP, spedficity was 99.2%, positive predictive value 76.1%, negative predictive value 96.8%. Conclusions: a) our study confirms the low prevalence of SBP in asymptomatic outpatients; b) sensitivity and positive predictive value of Multistix 8SG ® strip are poor although specifidty and negative predictive value are excellent. A negative Multistix 8SG® strip camlot exclude the diagnosis of SBP in symptomatic patients.

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P R O G N O S T I C S I G N I F I C A N C E O F SERUM FERRITIN IN PATIENTS WITH C I R R H O S I S

A. Pardo, N. Hernfindez, M. Carrillo, A. Jimtnez, E. Quintero. Seroicio

de Aparato Digestivo, Hospital Universitario de Canarias, La Laguna, 5'pain Hepatic iron overload can enhance tissue injury in most prevalent chronic liver diseases and has been described as an independent predictor of death in cirrhosis. Serum ferritin is a simple and inexpensive test that has been correlated with the degree of hepatic iron content. Aim: To evaluate the predictive value of serum ferritin on the survival of patients with non-hemochromatosis cirrhosis. Patients: 407 consecutive cirrhotic patients (58~12 yeats) were included after their first hospital admission or visit at the outpatient dinic and followed prospectively (mean survival time 83 months). Serum ferritin was determined at entry and every six months during follow-up. At inclusion 202 patients (50%) were Child-Pugh class A, 156 (38%) class B and 49 (12%) dass C. Cirrhosis was of alcoholic origin in 285 cases (70%). Results: 176 patients (43%) had hyperferritinemia (serum ferritin >200ng/ml in women and >300ng/ml in men) at entry. Their mean

Category 2b." Cirrhosis and Complications." Clinical Aspects Child-Pugh score was significantly higher than in patients with normal serum ferritin levels (7.56-t-0.16 vs 6.514-0.11, p <0.01). Survival was significantly lower (56 months) in patients with hyperferritinemia than in those with normal serum ferritin (91 months, p <0.001), even adjusting for liver disease severity (40.5 vs 62.5 months in Child-Push class B with and without hyperferritinemia [p=0.009]; 31.5 vs 60.8 months in class C with and without hyperferritinemia [p = 0.03]) and for continued alcohol abuse (44.4 vs 68 months with and without hyperferritinernia, p= 0.01). Differences in survival correlate with serum ferritin levels and reach statistical significance for a ferritin value higher than 500 ng]ml. Patients with persistent hyperferritinernia during follow-up had a significantly lower survival than those with transient hyperferritinemia (43.7 vs 68.2 months respectively, p < 0.001). In the multivariate regression analysis serum ferritin was an independent predictor &survival besides age, ChildPush class, presence of hepatocellular carcinoma and blood creatinin. Conclusions: Hyperferritinemia is associated with poor liver function and independeatly worsens prognosis in cirrhotic patients. These results suggest that iron overload acts as a clinically relevant cofactor on the outcome of liver cirrhosis.

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MTHFR C677T AND OTHER INHERITED COAGULATION DISORDERS IN BUDD CHIARI S Y N D R O M E (BCS) AND PORTAL VEIN T H R O M B O S I S (PVT) WITH OR WITHOUT LIVER CIRRHOSIS (LC)

L. Pasta I , C. Marrone 2, M. D'Amico 2, R. Virdone 1, C. Fabiano 3, R Sammarco 3, L. Pagliaro e. :Referral Centre for Chronic Liver Diseases,

V Cervello Hospital, Department of Internal Medicine, Palermo, Italy," 2Internal Medicine of University, ~ Cervello Hospital, Palermo, Italy," SGenetic Laboratory. g Cervello Hospital, Palermo, Italy Background and Aims: We investigated the relationships between tZactot V Leiden (FVL), mutation 620210A of prothrombin (PTHR 20210A), mutation TT677 of methylenetetrahydrofolate reductase (MYHFR C677T) and BCS or PVT. Methods: From January 2000 to September 2003, 112 consecutive patients were studied: 15 with BCS, 65 with PVT and LC and 32 with PVT without LC; cryptogenic cirrhosis was found in 38 patients. Results: The table shows that genetic disorders of coagulation are highly prevalent in patients with BCS or PVT. MTHFR C677T homozygous is significantly more frequent in cirrhotic patients with than without PVT. Associate defects were present in 13 patients and 10 of them showed PVT or BCS; 6 patients with cryptogenic cirrhosis were MTHFR C677T homozygous and 20 MTHFR C677T heterozygnus; 19 o f these 26 patients showed portal vein thrombosis. Type of coagulation disorder

Total patients FVL heter ~zygous PTHR G2ff210A heter~zygous MTHFR C677T homozygous MTI-IFR C677T heterozygous Any of the above None of the above

Hepatic or portal vein thrombosis Liver cirrhosis (LC) without thrombosis BCS PVTLC PVT Total 15 4 2 3 5 14 1

65 2 1 14* 30 47 16

32 2 2 5 16 25 7

112 8 5 22 51 86 24

71 2 5 7* 38 51 20

*OR (95%CI) = 2.68 (1.03-6.98). Conclusions: According to our study, inherited thrombophilia plays a significant role in the pathogenesis of BCS and PVT with or without associate LC. Identification of these patients is essential to plan anticoagulation, major surgery" or OLT in cirrhotic patients. MTHFR C677T mutation as a cause of cryptogenic LC should be assessed in other studies.

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85

TIME-COURSE OF DIASTOLIC DYSFUNCTION IN CHRONIC HCV INFECTION

L. Ratti, E. Redaelli, C. Guidi, A. Redaelli, M. Milanese, M. Pozzi.

Internal Medicine, Milano-Bicocca University, Azienda Ospedaliera San Gerardo, Monza, Itlay An altered pattern of transmittal flow (diastolic dysfunction) and structural abnormalities of ventricular walls characterize cirrhotic cardiomyopathy. Aims: To assess the time-course of cardiac functional-structural abnormalities in patients with chronic hepatitis (CH) and in cirrhosis with portal hypertension (PH) due to HCV infection in absence of alcohol consumption. Patients and Methods: According to staNng on liver biopsy (Ishak score) HCV-RNA positive patients were divided into 2 groups. Group A, 24 patients with CH (score 3-5); Group B, 22 patients with Child A cirrhosis (score 6) and PH. Echocardiography was performed to assess diastolic and systolic function by: E/A ratio, Isovolurnic relaxation time (IVRT), Deceleration time of E wave (DT), Ejection Fraction (EF). Left ventricle parietal wall + Interventricular Septum Thickness (LVPWt+IVST) were also assessed. In Group B hepatic venous pressure gradient (HVPG) was assessed and patients enrolled when HVPG > 10 mmHg. Exclusion criteria: any drug, ethanol consumption, arterial hypertension, cardiovascular diseases, Child score B-C. Results: EF is normal (67.14-4 controls, 68.84-4 Group A, 67.54-5, Group B, NS). E/A ratio was reduced in Group B (0.94_0.2 vs 1.2i0.2 in either controls and Group A, p < 0.01). DT and IVRT were significantly prolonged in both groups: Group B (221.84-74, p <0.01; 107.174-23, p < 0.01, respectively vs controls), Group A (187d_38, p 0.02; 91.5d_16, p 0.02 vs controls) with a more relevant increase in Group B (p <0.05, p < 0.01, respectively vs Group A). LVPWt+IVST was similarly increased in both groups (Group B 20.84-2.8, p < 0.01; Group A 19.74-3.2, p = 0.02) as compared to controls (17.34_1.5). Conclusion: Systolic function is unaffected but E/A ratio is significantly impaired in postviral cirrhosis as compared to CH, thus confirming the presence of diastolic dysfunction. DT and IVRT are already prolonged in CH indicating impaired elastic recoil properties of left ventricle even at this earlier stage of disease. The negative impact on transmittal flow however becomes evident only in cirrhosis. This implies a major role of PH which can increase the loading condition of the heart (blood volume expansion, increased exposure to cardiodepressant substances) in patients with subtle previously existing cardiostmctural changes. The role of potential HCV cardiotoxicity deserves further investigations.

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HEPATIC ENCEPHALOPATHY IS MORE FREQUENT, SEVERE AND S H O R T E N S THE SURVIVAL IN HCV/HIV-RELATED CIRRHOSIS

D. Sfinchez-Mufioz1.3, J.A. Pineda 2,4, F. Diaz 3 , J.A. Girdn 4, J.L. Montero 3, J. de la Torte 4, R.J. Andrade 3, M. Gonz/dez 4, A. Gila 3, M. Aguilar4, J. Aguilar 3, EJ. Caballero 4, J.M. Navarro 3, M. Romero-Gdmez 1'3.

; Hepatology Unit, Hospital Universitario de Valme, Seville, Spain," 2Infectious Disease Unit, Hospital Universitario de Valme, Seville, Spain," S Grupo Andaluz Para El Estudio Del H[gado (GAEH), Spain," 4Grupo Andaluz para el estudio de las Enfermedades Infecciosas (GAEEI), Spain Background: Hepatic encephalopathy (HE) has been associated with a poor prognosis in cirrhotics. However, tile prevalence and importance of developing HE in HCV/HIV coinfected cirrhotics remains unknown. Aims: The objective of this study was to compare the impact of hepatic encephalopathy on survival of patients with HCV-related decompensated cirrhosis with or without HIV coinfection. Methods: In a retrospective cohort study, the survival of 1037 HCV and 180 HCV/HIV coinfected patients with liver cirrhosis after the first decompensation was analyzed. In 225 (18%) individuals the life status could not be determined at closing the study.