- Email: [email protected]
214 Classifying hepatic encephalopathy (HE): Does treatment status matter?
Category 2b." Cirrhosis and Complications." Clinical Aspects
•
MATHEMATICAL MODEL PREDICTING HIGH HEPATOCYTE PROLIFERATION INDEX AND RISK OF HCC IN PATIENTS WITH HCV RELATED CIRRHOSIS: A PROPOSAL FOR CLINICAL VALIDATION
[•
83
SEQUENTIAL V E R S U S 'AB INITIO' C O M B I N E D DIURETIC TREATMENT OF MODERATE ASCITES IN CIRRHOTIC PATIENTS: PRELIMINARY RESULTS OF A RANDOMIZED CONTROLLED MULTICENTER CLINICAL STUDY
F. Azzaroli 1, A. Colecchia 1, F. Lodato 1, M. Montagnani 1, L. BacchiReggiani 2, D. Festi I , G.M. Prati ~, V Feletfi 1, E. Accogli 1, S. Casanova ~, M. Derettzini 3, E. Roda 1, G. Mazzella ~. 1Department of Internal
E. Mazza ~, P. Angeli ~, S. Fasolato 1, E. Zola I , S. G~arda I , A. Callegaro I , E Salinas 2, S. Fagiuoli 2, E. Miola 3, A. Sticca I , E. Velo 4, G. Zanus2, P. Burra 2, U. Cillo 2, G. Bag~o 3, G. Sturniolo 2, D. D'Amico 2, A. Gatta I .
Medicine and Gastroenterology, University of Bologna, Bologna, Italy," 2Institute of Cardiovascular Diseases, University of Bologna, Bologna, Italy," SDepartement of Experimental Pathology. University of Bologna, Bologna, Italy
1Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy," 2Department of Surgical and Gastroenterological Sciences, University of Padova, Padova, Italy," 3Medical Division of the General Hospital of Padova, Padova, Italy," 4Medical Division of the General Hospital of Cittadella, Cittadella, Italy
Background: In cirrhosis (C), hepatocyte proliferation is related with the risk of developing hepatocarcinoma (HCC) but requires liver biopsy. Development of a non invasive indicator able to identify patients at high risk of HCC development would be helpful to tailor screening on an individual basis. Aim of tile present study is to develop a mathematical model inchiding biochemical and i m a ~ n g parameters in order to identify patients at high risk of developing HCC. Materials aud Methods: 158 patients (74F:94M) with chronic HCV liver disease underwent liver biopsy for AgNOR-PI evaluation. Ultrasonog'raphy and serum liver biochemistry were evaluated every 6 months for 5.8 years. Cut-off value for AgNOR-PI (%) which discriminate low and high prolifevating tissues is 25%. The risk of HCC development was evaluated by Kaplan-Meier method. Results: 56 patients had chronic hepatitis without cirrhosis (CH) with AgNOR-PI <24%. 102 patients had C with AgNOR-PI < 2 4 % in 65 patients and >25% in 37. Patients with C were older than those with CH, but there were no differences in demographic parameters within C with high (H-AgNOR-PI) and low AgNOR-PI (L-AgNOR-PI). A significant worsening of all biochemical parameters was observed from CH to C (CH > L-AgNOR-PI > H-AgNOR-PI). None of the patients with CH developed HCC, in contrast 8% of L-AgNOR-PI and 42% of H-AgNOR-PI patients developed HCC. In table 1 are shown tile parameters independently associated with HCC by logistic binary" model. The logistic binary model properly allocated 95.9% of patients with L-AgNOR-PI and 83.8% of those with H-AgNOR-PI. Tile developed equation was: P(AgNOR) l / [ l + e x p [ (6 o +fl~Xl +fl2X2+fl~X~)] [expected AgNOR valueis <25 when the calculated probability is <0.5 and >25 when >0.5, fit are multiplying coefficients of selected variables (X)]. Table 1. Parameters independently associated with HCC development by logistic bina1"ymodel. Variable
O.R.
95%CI
y Globulin (g/dl) ALT/AST ratio Fen'itin (btg/dl) Ultrasonography, coarse pattern Nodular pattern Inhomogeneous pattern
0.134 0.055 1.020 0.992 20.706 94.505
0.22 0.798 0.00%0.414 1.008-1.037 0.98-10.037 4.026-106.492 14.274625.712
Conclusion: The described model identifies 83.9% of patients at risk of
HCC development. This model needs to be validated in large prospective studies. The use of more suitable markers for hepatocyte proliferation shmfld flmher increase the predictivity of the model limiting tight follow l~p only to patients with high HCC risk.
The most rational treamaent of cirrhotic patients with moderate ascites is a stepwise sequential therapy with increasing oral doses of an aldosterone antagonist. If no response occurs at tile maximum dosage (400 m~day), furosemide is added at increasing oval doses in a stepwise way up to 160rag/day (sequential diuretic treatment). Nevertheless, tile onset of response in this treatment may require too much time. Consequently, our afin was to compare sequential diuretic therapy with a schedule combining "ab initio" aldosterone antagonist and furosemide. Fifty-nine patients were randomly assigned to be treated by sequential diuretic treatmerlt (Group A, n 34) or by "ab fifitio" combined diuretic treatment (Group B, n=25). In Group A, the initial dosage of potassium kanrenoate was 200 mgfday, in nonresponders: first it was peaked to 400 rag/day, next furosemide was added at initial dosage of 25rag b.i.d, eventually increasing to 50 mg/day b.i.d., then up to 75 mg/day b.i.d. Group B received 200mg/day of potassium kanrenoate and 2 5 m g b.i.d, of Nrosemide. In nonresponders tile dosages of potassium kanrenoate and furosemide were increased to 400rag/day and 50rag b.i.d, and then up to 400 rag/day and 75 mg b.i.d., respectively. No response was defined as a three-day weight loss lower than 600g. Response rate was similar in both groups (94.1% Group A vs 96.0% Group B, p N.S.), as well as patients's rate that need to change the effective diuretic step for diuretic-induced complications (32.3% Group A vs 24.0% Group B, p =N.S.). The mean time to mobilize ascites was shorter in Group B than in Group A (15.7±1.3 vs 21.0±1.8 days, p < 0.025) even when the mean time to reach an effective diuretic step (4.8±0.4 vs 6.5±0.4 days, p <0.025) was not counted (11.3±1.1 vs 15.0±1.4 days, p < 0.05). "Ab initio" combined diuretic treatment shortens the time to mobilize moderate ascites in nonazoternic cirrhotic patients if compared to a sequential diuretic treaunent. Thus, it appears the more suitable and cost-effective diuretic treaunent schedule.
•
CLASSIFYING HEPATIC ENCEPHALOPATHY (HE): DOES TREATMENT STATUS MATTER.'?
S. Montagnese 1, C. Jackson 2, M.Y. Morgan I . 1 Centre For Hepatology. Royal Free Campus, Royal Free and University Cbllege Medical School, London, UI~;"2Department of Neurophysiology, Royal Free Hospital, Royal Free Hampstead NHS Trust, London, UK Background and Aims: Cirrhotic patients are classified as neuropsychiatrically unfinpaired or as having minimal or overt HE on the basis of their performance 'on the day' [1]. No ~ i d a n c e is available on how to classify patients with previously documented overt HE who are on maintenance treatment. Some of these may still exhibit features of overt HE while others may appear clinically normal but show neltrophysiological and/or psychometric deficits. The aim of this study was to assess the appropriateness of considering treatment as a separate variable for the classification of HE. Methods: 56 cirrhotic patients (mean [range] age 51 [25-70] yr; 31 males; 25 females; Child's A n = 3 2 ; B n = 2 1 ; C n=3), and 28 age- and sexmatched healthy volunteers [HV] were enrolled. The patients' neuropsychiattic status was classified on clinical, EEG [2] and psychometric criteria [3]
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
[
•
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.
[•
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.
[•
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
•
MATHEMATICAL MODEL PREDICTING HIGH HEPATOCYTE PROLIFERATION INDEX AND RISK OF HCC IN PATIENTS WITH HCV RELATED CIRRHOSIS: A PROPOSAL FOR CLINICAL VALIDATION
[•
83
SEQUENTIAL V E R S U S 'AB INITIO' C O M B I N E D DIURETIC TREATMENT OF MODERATE ASCITES IN CIRRHOTIC PATIENTS: PRELIMINARY RESULTS OF A RANDOMIZED CONTROLLED MULTICENTER CLINICAL STUDY
F. Azzaroli 1, A. Colecchia 1, F. Lodato 1, M. Montagnani 1, L. BacchiReggiani 2, D. Festi I , G.M. Prati ~, V Feletfi 1, E. Accogli 1, S. Casanova ~, M. Derettzini 3, E. Roda 1, G. Mazzella ~. 1Department of Internal
E. Mazza ~, P. Angeli ~, S. Fasolato 1, E. Zola I , S. G~arda I , A. Callegaro I , E Salinas 2, S. Fagiuoli 2, E. Miola 3, A. Sticca I , E. Velo 4, G. Zanus2, P. Burra 2, U. Cillo 2, G. Bag~o 3, G. Sturniolo 2, D. D'Amico 2, A. Gatta I .
Medicine and Gastroenterology, University of Bologna, Bologna, Italy," 2Institute of Cardiovascular Diseases, University of Bologna, Bologna, Italy," SDepartement of Experimental Pathology. University of Bologna, Bologna, Italy
1Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy," 2Department of Surgical and Gastroenterological Sciences, University of Padova, Padova, Italy," 3Medical Division of the General Hospital of Padova, Padova, Italy," 4Medical Division of the General Hospital of Cittadella, Cittadella, Italy
Background: In cirrhosis (C), hepatocyte proliferation is related with the risk of developing hepatocarcinoma (HCC) but requires liver biopsy. Development of a non invasive indicator able to identify patients at high risk of HCC development would be helpful to tailor screening on an individual basis. Aim of tile present study is to develop a mathematical model inchiding biochemical and i m a ~ n g parameters in order to identify patients at high risk of developing HCC. Materials aud Methods: 158 patients (74F:94M) with chronic HCV liver disease underwent liver biopsy for AgNOR-PI evaluation. Ultrasonog'raphy and serum liver biochemistry were evaluated every 6 months for 5.8 years. Cut-off value for AgNOR-PI (%) which discriminate low and high prolifevating tissues is 25%. The risk of HCC development was evaluated by Kaplan-Meier method. Results: 56 patients had chronic hepatitis without cirrhosis (CH) with AgNOR-PI <24%. 102 patients had C with AgNOR-PI < 2 4 % in 65 patients and >25% in 37. Patients with C were older than those with CH, but there were no differences in demographic parameters within C with high (H-AgNOR-PI) and low AgNOR-PI (L-AgNOR-PI). A significant worsening of all biochemical parameters was observed from CH to C (CH > L-AgNOR-PI > H-AgNOR-PI). None of the patients with CH developed HCC, in contrast 8% of L-AgNOR-PI and 42% of H-AgNOR-PI patients developed HCC. In table 1 are shown tile parameters independently associated with HCC by logistic binary" model. The logistic binary model properly allocated 95.9% of patients with L-AgNOR-PI and 83.8% of those with H-AgNOR-PI. Tile developed equation was: P(AgNOR) l / [ l + e x p [ (6 o +fl~Xl +fl2X2+fl~X~)] [expected AgNOR valueis <25 when the calculated probability is <0.5 and >25 when >0.5, fit are multiplying coefficients of selected variables (X)]. Table 1. Parameters independently associated with HCC development by logistic bina1"ymodel. Variable
O.R.
95%CI
y Globulin (g/dl) ALT/AST ratio Fen'itin (btg/dl) Ultrasonography, coarse pattern Nodular pattern Inhomogeneous pattern
0.134 0.055 1.020 0.992 20.706 94.505
0.22 0.798 0.00%0.414 1.008-1.037 0.98-10.037 4.026-106.492 14.274625.712
Conclusion: The described model identifies 83.9% of patients at risk of
HCC development. This model needs to be validated in large prospective studies. The use of more suitable markers for hepatocyte proliferation shmfld flmher increase the predictivity of the model limiting tight follow l~p only to patients with high HCC risk.
The most rational treamaent of cirrhotic patients with moderate ascites is a stepwise sequential therapy with increasing oral doses of an aldosterone antagonist. If no response occurs at tile maximum dosage (400 m~day), furosemide is added at increasing oval doses in a stepwise way up to 160rag/day (sequential diuretic treatment). Nevertheless, tile onset of response in this treatment may require too much time. Consequently, our afin was to compare sequential diuretic therapy with a schedule combining "ab initio" aldosterone antagonist and furosemide. Fifty-nine patients were randomly assigned to be treated by sequential diuretic treatmerlt (Group A, n 34) or by "ab fifitio" combined diuretic treatment (Group B, n=25). In Group A, the initial dosage of potassium kanrenoate was 200 mgfday, in nonresponders: first it was peaked to 400 rag/day, next furosemide was added at initial dosage of 25rag b.i.d, eventually increasing to 50 mg/day b.i.d., then up to 75 mg/day b.i.d. Group B received 200mg/day of potassium kanrenoate and 2 5 m g b.i.d, of Nrosemide. In nonresponders tile dosages of potassium kanrenoate and furosemide were increased to 400rag/day and 50rag b.i.d, and then up to 400 rag/day and 75 mg b.i.d., respectively. No response was defined as a three-day weight loss lower than 600g. Response rate was similar in both groups (94.1% Group A vs 96.0% Group B, p N.S.), as well as patients's rate that need to change the effective diuretic step for diuretic-induced complications (32.3% Group A vs 24.0% Group B, p =N.S.). The mean time to mobilize ascites was shorter in Group B than in Group A (15.7±1.3 vs 21.0±1.8 days, p < 0.025) even when the mean time to reach an effective diuretic step (4.8±0.4 vs 6.5±0.4 days, p <0.025) was not counted (11.3±1.1 vs 15.0±1.4 days, p < 0.05). "Ab initio" combined diuretic treatment shortens the time to mobilize moderate ascites in nonazoternic cirrhotic patients if compared to a sequential diuretic treaunent. Thus, it appears the more suitable and cost-effective diuretic treaunent schedule.
•
CLASSIFYING HEPATIC ENCEPHALOPATHY (HE): DOES TREATMENT STATUS MATTER.'?
S. Montagnese 1, C. Jackson 2, M.Y. Morgan I . 1 Centre For Hepatology. Royal Free Campus, Royal Free and University Cbllege Medical School, London, UI~;"2Department of Neurophysiology, Royal Free Hospital, Royal Free Hampstead NHS Trust, London, UK Background and Aims: Cirrhotic patients are classified as neuropsychiatrically unfinpaired or as having minimal or overt HE on the basis of their performance 'on the day' [1]. No ~ i d a n c e is available on how to classify patients with previously documented overt HE who are on maintenance treatment. Some of these may still exhibit features of overt HE while others may appear clinically normal but show neltrophysiological and/or psychometric deficits. The aim of this study was to assess the appropriateness of considering treatment as a separate variable for the classification of HE. Methods: 56 cirrhotic patients (mean [range] age 51 [25-70] yr; 31 males; 25 females; Child's A n = 3 2 ; B n = 2 1 ; C n=3), and 28 age- and sexmatched healthy volunteers [HV] were enrolled. The patients' neuropsychiattic status was classified on clinical, EEG [2] and psychometric criteria [3]
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
[
•
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.
[•
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.
[•
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