Sunday Poster Sessions, October 29, 2006

Portal Hypertension and Other Complications

 

 

675. Cost-effectiveness of distal splenorenal shunt (DSRS) vs. transjugular intrahepatic portosystemic shunt (TIPS). 

T. D. Boyer; J. Henderson; A. Heerey; K. Abu-Elmagd ; J. Galloway; L. F. Rikkers; L. Jeffers.

 

Introduction:

DSRS (5.5%) and TIPS (10.5%) have been shown in a randomized controlled trial to be equally effective in preventing rebleeding from esophageal varices (Gastroenterology 130:1643;2006). We have examined the cost-effectiveness of each of these two approaches.

 

Methods:

Quality of life (QOL) was measured using SF-36 preceding randomization and yearly thereafter and converted to utility using the SF-6D. Cost utility analysis performed using Data Triage ®. All data were collected prospectively. DRG and CPT codes for both in- and out-patient events and interventions were obtained for each patient. Cost of medications and laboratory tests were also determined. Medicare costs from 2003 were used and inflated to 2004 costs using the medical care inflation index from the Bureau of Labor Statistics. Costs using coated stents were estimated using different rates of stenosis. Incremental cost effectiveness ratios (ICERs) were determined at 1, 3 and 5 years.

 

Results:

Cost of TIPS exceed the cost of DSRS at all time points but not significantly ($44,772 vs. $41,941; $67,760 vs. $57,921; $84,033 vs. $66,685). For the patients who survived, the out-patient cost of TIPS was significantly greater than DSRS due to re-interventions. A trend towards better survival for TIPS early in the study influenced the cost utility analysis in favor of TIPS for the ICERs per quality adjusted life year (QALY) saved (year 1 $101,470; year 2 $140,357; year 5 $61,000). By year 5 TIPS was only marginally more cost effective, using a threshold of $50,000/QALY. Using modeling for coated stents to assess effect of lowering re-intervention rates, the cost-effectiveness of TIPS increased only slightly. Summary: TIPS cost more than DSRS, especially in the out-patient setting. These costs reflect the higher rates of re-intervention seen with TIPS. However, health related QOL measured in QALYS were greater at all time points for the TIPS group due to the early, but nonsignificant, survival advantage observed in the study. The ICER favored TIPS and at 5 years TIPS would be considered moderately cost-effective. However due to the wide confidence intervals there was no significant difference in cost-effectiveness at any time point.

 

Conclusion:

This is the first study that defines prospectively the costs of preventing rebleeding with TIPS or DSRS in Child’s A/B patients who have failed pharmacologic and endoscopic therapy. Although TIPS was more expensive there was no significant difference in the cost-effectiveness of either approach.

 

Supported by a grant from NIDDK: DK050680. Authors have no conflicts to report.

 

676. Renal failure and bacterial infection in patients with cirrhosis and ascites: relationship with the type and the resolution of the infection. 

P. Angeli; L. Dallagnese; S. Fasolato; E. Mazza; F. Salinas; S. Donà; S. Fagiuoli; A. Sticca; G. Zanus; U. Cillo; C. Destro; A. Gatta.

 

Introduction:

The role of bacterial infections in the pathogenesis of renal failure has been assessed mainly in patients with SBP.

 

Aim:

The aim of the study was to investigate the prevalence, the clinical course, and the outcome of renal failure induced by all the types of bacterial infections in patients with cirrhosis and ascites.

 

Methods:

399 patients, who had been consecutively admitted to the three major hospitals of Padova (Italy) during the first 6 months of 2005 were included in the study.

Results:

233 patients out of 309 patients (75.4%) had evidence of ascites on admission. In 104 out of 233 (44.6%) cirrhotic patients with ascites a bacterial infection was diagnosed. UTI and pneumonia were the most frequent types of infections followed by SBP. A bacterial infection-induced renal failure was observed in 35 out of 104 (33.6 %). The prevalence of bacterial infection-induced renal failure was significantly higher in sub-diaphragmatic bacterial infections than in supradiaphragmatic infections or in other infections (p<0.0001). The progressive form of bacterial infection-induced renal failure was only precipitated by the sub-diaphragmatic bacterial infections in these patients (p<0.0001). Either the stable or the progressive form of renal failure was induced by all types of sub-diaphragmatic bacterial infection and not only by PBS in cirrhotic patients with ascites. Finally, renal failure was induced by sub-diaphragmatic bacterial infections in spite of the resolution of the infection in these patients. In a multivariate analysis only MELD score (p=0.001), the peak count of neutrophyl leukocyte in blood (p=0.04) and the resolution of infection (p=0.03) showed an independent value when predicting the occurrence of bacterial infection-induced renal failure in cirrhotic patients with ascites. On the other hand, MELD score (p=0.002) and the resolution of infection (p=0.04) were the only variables which showed an independent prognostic value on survival in cirrhotic patients with ascites and bacterial infection.

 

Conclusion

In conclusion, the results of the study show that:

a)     all types of bacterial infections can precipitate renal failure in cirrhotic patients with ascites,

b)    the development of renal failure is more frequent in sub-diaphragmatic bacterial infections,

c)     a progressive form of renal failure can be precipitated only by sub-diaphragmatic infections and

d)    the stable or the progressive form of renal failure can be induced by all types of sub-diaphragmatic bacterial infections and not only by PBS. The probability of developing bacterial infection-induced renal failure is related to the MELD score, the severity of the infection, and to the resolution of the infection.

682. Primary Prophylaxis of Variceal Hemorrhage – Patient Preferences.

A. V. Longacre; G. Garcia-Tsao; L. Fraenkel.

 

Background:

Endoscopic variceal ligation (EVL) and non-selective beta-blockers (BB) are both effective for primary prophylaxis of variceal hemorrhage, however the route of administration and side effects of these treatments are distinct. Patient preferences, an important part of medical decision-making, have not been evaluated and are the objective of this study.

 

Methods:

Untreated patients with newly diagnosed esophageal varices underwent a standardized educational session. Patients with contraindications to either EVL or BB were excluded. Patient preferences for treatment were evaluated using an interactive computer task in which patients compared treatments using Adaptive Conjoint Analysis (ACA), a validated method that effectively describes preferences when competing options exist. Treatment characteristics were based on published literature and included route of administration, risk of fatigue, sexual dysfunction, dysphagia, shortness of breath and/or hypotension, procedure-related bleeding and perforation. Demographics, type and severity of liver disease and level of physician trust were recorded by written survey. Subjects were contacted one month after ACA to determine the treatment prescribed.

 

Results:

49 subjects were enrolled with a median age of 56 years (range 24-74); 78% were male, 94% Caucasian, 45% had some college education, 43% were Child B/C and the median MELD score was 11 (6-29). Subjects reported strong preferences for receiving complete medical information and preferred a shared decision-making role with their physician. Based on the ACA, 31 (63%) subjects preferred EVL. Risks of shortness of breath and/or hypotension, fatigue, and procedure-related bleeding were most important to subjects. 92% felt the ACA correctly predicted the importance of each treatment characteristic. BB were preferred by older patients (p=0.007) and those preferring medications over procedures (p=0.0003), whereas EVL was preferred by those with a college education (p=0.03) or higher annual income (p=0.007). In a linear regression model only age and preference for medication over procedures remained significantly associated with treatment preference. 44 subjects were prescribed BB; 3 were lost to followup, 2 were not given prophylaxis and none received EVL.

 

Conclusion:

Our results suggest that although patient preferences for prophylaxis of variceal bleed are variable, many patients prefer EVL over BB. Given patients’ desire for full disclosure and an active role in shared decision-making, both EVL and BB should be discussed with cirrhotic patients requiring primary prophylaxis for variceal hemorrhage and patient preference should be considered when starting primary prophylaxis.

 

684. Predicting patient survival in compensated cirrhotics with refractory variceal bleeding treated with distal splenorenal (DSRS) or transjugular intrahepatic portosystemic (TIPS) shunts. 

T. D. Boyer; J. Henderson; S. Arrigain; J. Connor.

 

Introduction:

Decompensation in the cirrhotic is said to occur with development of variceal bleeding and/or ascites, encephalopathy or icterus and is associated with a worsened prognosis. In a recently completed trial comparing TIPS to DSRS in Child’s A/B cirrhotics refractory to medical or endoscopic therapy we found 2 years survival rates of 88% and 81%, respectively (Gastroenterology 130:1643;2006). This excellent survival with follow-up of 46 months provided the opportunity to examine which features at randomization were predictive of outcome.

 

Methods:

Seven categorical and 19 continuous variables collected at time of randomization were used to compare the relationship between the variable and time to death using the Log-rank test for categorical variables and Cox proportional hazards model for continuous variables. Interactions between individual variables were assessed by using a Cox proportional hazards model. A multivariable model was obtained using a bootstrap-bagging procedure on the Cox proportional hazards model.

 

Results:

By univariate analysis: age-hazard ratio (HR-95%CI) per 5 years increase = 1.15 (1.004,1.31); MELD score-HR per 5 unit increase = 1.74 (1.01,2.99); prior bleeds excluding current-HR per 1 bleed = 1.19 (1.1,1.28); PT-HR per 0.1 increase = 1.11 (1.001,1.22); and creatinine-HR per 0.1 increase = 1.16(1.011,1.34) were all significantly associated with increased risk of dying during the period of observation. Gender and Child's score were also predictive of increased mortality though these terms did not achieve significance at the alpha = 0.05 level. By multivariate analysis only number of prior bleeds and level of PT were associated significantly with increased risk of dying-Table.

 

Summary:

Refractory variceal bleeding treated effectively with TIPS or DSRS is associated with excellent survival. Although a higher MELD score was predictive of outcome by univariate analysis it was not predictive by multivariate analysis. Only number of prior bleeds and PT were predictive of outcome in these well compensated patients. Conclusion: Variceal bleeding in Child’s A/B cirrhotics is not a sign of decompensation when treated with TIPS or DSRS, especially when recurrent bleeding is prevented. In addition, MELD score is of limited predictive value in patients with compensated disease who bleed once number of prior bleeds and PT are considered.

Supported by grant from NIDDK # DK050680 Authors have no conflicts to report.

 

Table 1

 

Variable

Hazard Ratio (95% CI)

Cox proportional Hazards P-value

DSRS vs. TIPS

1.28 (0.74, 2.23)

0.38

Number prior bleeds if no prior bleed then 0 (HR per 1 bleed)

1.21 (1.12, 1.31)

<.0001

Pt (HR per 0.10 increase)

1.13 (1.02, 1.24)

0.017

 

688. Thrombophilia-associated nodular regenerative hyperplasia: a new cause of non-cirrhotic portal hypertension in HIV-infected patients. 

V. Mallet; D. Lasne; H. Fontaine; P. Blanchard; A. Vallet-Pichard; J. Serpaggi; S. Pol.

 

Background:

In the era of highly active antiretroviral therapy (HAART), chronic liver disease is responsible for an important and increasing number of deaths among human immunodeficiency virus (HIV)-infected patients. In some patients the etiology of the liver damage remains unknown. HIV-associated idiopathic liver disease has not been fully described: mechanisms involved, its clinical importance and prognosis are for the moment unknown and probably underestimated. Recent reports indicate that HIV-infected patients are at increased risk for the development of thrombosis. Among other possibilities, an acquired deficiency of protein S (PS), one of the plasma’s natural anticoagulants might explain this tendency.

 

Objective:

To describe and explain non-cirrhotic portal hypertension in HIV-infected patients.

 

Patients:

After our first observation, eight consecutive patients (n=9) were referred to our unit from January 2003 to May 2006 for clinical and/or biological symptoms of chronic liver disease of unexplained origin (two patients with positive HCV-RNA were excluded). All patients underwent liver biopsy and were screened for thrombophilia (including antithrombin, protein C and protein S deficiency, factor V Leiden and II G20210A mutations, lupus anticoagulant, and antiphospholipid antibodies).

 

Results:

All patients had symptomatic portal hypertension, with a history of esophageal bleeding in six of them. At time of diagnosis, all were treated by HAART with an efficient immune restoration. All were receiving or had received didanosine. Biopsy-proven nodular regenerative hyperplasia (NRH) was observed in six patients, and suggested in one (sinusoidal dilatation in a clinical context of portal hypertension without overt liver disease). Out of the 7 patients, 7 were found to have one or more coagulation abnormalities inducing an increased risk of thrombosis: PS deficiency in the absence of vitamine K deficiency, 7 patients ; factor V Leiden mutation, 1 patient, factor II G20210A, 1 patient In two patients, more than one prothrombotic state were identified.

 

Conclusions:

NRH appears to be a new cause of non-cirrhotic portal hypertension in HIV-infected patients and is linked with a thrombotic state, potentially HIV-induced and/or to HAART toxicity.

 

689. Validation of the Short Form of Liver Disease Quality of Life (LDQOL) Instrument. 

F. Kanwal; B. M. Spiegel; R. Bolus; R. D. Hays; S. J. Kim; I. M. Gralnek.

 

Background:

Despite the realization that health related quality of life (HRQOL) is an important outcome in patients with advanced liver disease, clinicians rarely assess HRQOL of the liver disease patients. This disconnect may reflect the perceived respondent burden related to the length of available HRQOL instruments. LDQOL1.0 is a reliable and valid instrument in patients with advanced liver disease. However, it has 75 disease-targeted items grouped in 12 scales. Our objective was to develop and validate a Short Form (SF) of LDQOL 1.0.

 

Methods:

Using HRQOL data from the validation study of LDQOL 1.0, we selected 36 items based on content coverage and internal consistency reliability coefficients (cronbach α) of original scales. We then administered the resulting questionnaire to a cohort of 157 patients with advanced liver disease. We used both multi-trait scaling and factor analysis to test our hypotheses regarding HRQOL domains. We measured the reliability for the resulting scales using Cronbach α, and assessed the construct validity by correlating the SF-LDQOL scores with several anchors, including SF-36, symptom severity, disability days, and overall health.

 

Results:

36 items were grouped into 9 disease-targeted scales (Table 1). When administered together with SF-36, the mean (SD) completion time was 18 (+9) for SF vs. 38 (+20) min for LDQOL 1.0. Multi-trait scaling showed that item-scale correlation was higher for the hypothesized scales than for other scales. Factor analysis confirmed these results. Table 1 displays the Cronbach-α and supporting evidence of construct validity. The Cronbach-α for 8 of 9 scales was >0.70. The direction of the correlation coefficients (r) for all comparisons was consistent with a-priori hypotheses. However, the magnitude of r was lower than hypothesized for the Hopelessness, Distress, and Loneliness scales.

 

Conclusion:

We have developed and validated the SF of LDQOL (36 items, 9 scales). 3 of the 9 scales will require further modification. We believe that SF LDQOL will reduce respondent burden without significantly compromising the reliability.

 

Table 1: Reliability and Construct Validation of Short Form LDQOL

 

 

Items, N

Cronbach-α

SF-PCS
r(p-value)

SF-MCS
r (p-value)

Symptom Severity
r (p-value)

Disability Days
r (p-value)

Overall health
r (p-value)

Symptoms of liver disease

6

0.74

0.49
(<0.0001)

0.46
(<0.0001)

-0.49
(<0.0001)

-0.38
(<0.0001)

0.45
(<0.0001)

Effects of liver disease

3

0.72

0.53
(<0.0001)

0.57
(<0.0001)

-0.55
(<0.0001)

-0.41
(<0.0001)

0.51
(<0.0001)

Memory/Concentration

4

0.92

0.33
(<0.0001)

0.49
(<0.0001)

-0.48
(<0.0001)

-0.33
(<0.0001)

0.45
(<0.0001)

Sleep

5

0.71

0.44
(<0.0001)

0.47
(<0.0001)

-0.52
(<0.0001)

-0.41
(<0.0001)

0.43
(<0.0001)

Hopelessness

2

0.50

0.07
(0.42)

0.22
(0.01)

-0.01
(0.8)

-0.11
(0.2)

0.18
(0.03)

Distress

2

0.83

0.10
(0.2)

0.15
(0.07)

-0.01
(0.8)

0.06
(0.4)

0.08
(0.2)

Loneliness

5

0.70

0.14
(0.3)

0.31
(<0.0001)

-0.08
(0.2)

-0.01
(0.8)

0.24
(0.002)

Stigma of liver disease

4

0.80

0.30
(0.0004)

0.43
(<0.0001)

-0.45
(<0.0001)

-0.27
(0.001)

0.43
(<0.0001)

Sexual functioning/ problems

4

0.83

0.39
(0.001)

0.41
(0.001)

-0.43
(0.0002)

-0.19
(0.1)

0.51
(<0.0001

 

692. A simple scoring system accurately predicts outcome in patients with chronic liver disease admitted to a Liver Intensive Care Unit. 

M. Austin; W. Bernal; J. Wendon.

 

Background:

Outcome of patients with advanced chronic liver disease (CLD) admitted to intensive care are often poor. The early and accurate assessment of likely outcome is important for patient information, relatives expectation and appropriate use of resources. Organ failure (OF) scoring systems in this regard are often complex with limited clinical utility. In a large cohort of patients admitted to a liver ICU (LICU) we examined ICU predictors of survival, on admission and developed and validated a simple and practical bedside survival score, comparing accuracy with other scoring systems.

 

Methods:

Consecutive patients with CLD admitted to LICU between 01/1999-03/2005 formed a score derivation group, with a further prospective validation set of admissions between 03/2005-03/2006. Demographic features, indication for admission and severity of CLD and OF were examined. Logistic regression analysis was used to determine variables independently predictive of ICU survival. Comparison with discriminative power of admission MELD, Child Pugh (CP), APACHEII and SOFA scores were performed using receiver operating characteristic (AUROC) curve.

 

Results:

353 patients (61% Male) were studied in the derivation group; median age 51yrs (interquartile range 41-58), Child Pugh score 12 (11-15), MELD 25 (18-32) and SOFA 15 (11-18). Mortality was 62%. Logistic regression analysis identified 5 admission factors as being independent predictors of ICU outcome: patient age, bilirubin, requirement for vasopressors or haemofiltration and encephalopathy of grade 3 and above. Continuous variables were dichotomised and points assigned in accordance to their prognostic weight to derive the bedside score. Range of score was 0-23; AUROC was 0.878 (95%CI 0.838-0.917). SOFA, AUROC 0.796 (0.747-0.842) and MELD 0.706 (0.649-0.763). The threshold value to best predict non-survival for the bedside score was 12, MELD 23 and SOFA 12. Bedside score test performance was maintained when applied to the prospective validation sample (table).

 

Conclusion:

We describe a simple, accurate and practical bedside score, which incorporates admission demographic features, disease severity and organ failure enabling early prediction of short-term outcome in patients with CLD admitted to an ICU.

 

Score

Sensitivity

Specificity

Accuracy

PPV

NPV

Derivation

sample

 

Bedside>12

87

77

83

86

78

MELD>23

71

63

68

76

57

SOFA>12

84

61

75

78

70

Validation

sample

 

Bedside>12

84

74

79

77

82

 

PPV, NPV; positive and negative predictive values

 

700. Hand grip test is a valuable tool for screening of malnutrition in patients with liver cirrhosis: prospective analysis in 138 patients. 

N. Hrycewycz; C. Bureau; O. Rouquet; J. Peron; K. Barange; J. Vinel.

 

Introduction:

Hand grip strength (HG) is a non invasive and low cost validated method to screen malnutrition in clinical practice. However, interest of HG in liver cirrhosis and relationship between HG and clinical and biochemical characteristics of the cirrhotic patients are not well known.

 

Aims:

To evaluate performance of HG in screening of malnutrition in a population of cirrhotic patients.

 

Patients and Methods:

Between December 2004 and February 2006, middle arm muscle circumference (MAMC) and triceps skinfold thickness (TST) were prospectively measured in 138 consecutive cirrhotic patients (95 men, age 59±11 years; Child-Pugh A, B, C :21 %, 36,2 %, 42,8 %). HG was performed in dominant hand and mean of three measures was recorded in kilograms (kg). MAMC<5th percentile and TST<5th percentile were define using referent population standardized on sex and age. Independent parameters associated with HG were analyzed by multivariate linear regression.

 

Results:

Cirrhosis was alcoholic in 73.2 %, with active alcohol abuse in 39.1 % of the cases. Prevalence of MAMC<5th percentile and TST<5th percentile was 35.5 % and 23.9 %. HG was positively and significantly correlated with body mass index (r=0.21, p=0.012) and negatively correlated with age (r=-0.17, p=0.045). HG was positively and significantly correlated with MAMC in men (r=0.5, p<0.001) but not in women (r=0.22, NS). HG was significantly lower in patients with MAMC<5th percentile (13.4±10.1 versus 19.8±14.1, p=0.006).

 

HG was negatively and significantly correlated with Child-Pugh score (r=-0.32, p<0.001) but not with Meld Score (r=0.11, NS). HG was correlated positively with albumin (r=0.28, p<0.001) and total proteins (r=0.33, p<0.001) and serum sodium (r=0.29, p<0.001).

 

Using multivariate analysis, independent parameters associated with HG were: MAMC (p<0.001), sex (p<0.001) and total proteins (r=0.33, p<0.001) and serum sodium (p=0.043). HG<30 kg in men and HG<14 kg in women identified MAMC<5th percentile with a sensitivity of 94 %, a specificity of 36 %, a positive predictive value of 45 %, a negative predictive value of 92 %, respectively.

 

Conclusions:

HG correlated with muscular mass, protein visceral status and severity of cirrhosis. HG<30 kg in men and HG<14 kg in women identified malnutrition with a good sensitivity. These thresholds could be used in clinical practice to screen for malnutrition in cirrhotic patients.

 

702. Assessment of the severity of cirrhosis according to different values of FibroScan : a prospective study. 

J. Foucher; L. Castera; X. Adhoute; B. Fleury; X. Moncoucy; M. Salzmann; C. Lortet; J. Bertet; V. de Ledinghen.

 

Introduction:

Recently, it has been published that liver elastometry (FibroScan) could evaluate cirrhosis and its complications (Foucher et al, Gut 2006). With a negative predictive value > 90%, a cut-off of FibroScan value was found for each complication of cirrhosis. The aim of this prospective study was to evaluate the severity of cirrhosis according to four groups of FibroScan values in a large cohort of cirrhotic patients.

 

Methods:

From October 2004 to April 2006, all consecutive cirrhotic patients (FibroScan > 12.5 kPa) were included. Patients were splitted according to different values of FibroScan : FibroScan 12.5 to 20 kPa (A, n=236), 20.1 to 35 (B, n=184), 35.1 to 50 (C, n=90) and > 50 (D, n=92). Clinical and FibroScan data were recorded for all patients.

 

Results:

A total of 602 previously unpublished cirrhotic patients (423 males, mean age 56 years, Child A 506, Child B 81, Child C 15) were examined (313 HCV, 151 alcoholic, 50 HIVHCV, 33 NASH, 17 HBV, 14 hemochromatosis, 24 other). Median liver stiffness was 22.8 kPa. Complications associated with each group of FibroScan values are indicated in the table (group versus others, OR, 95% CI).

 

By multivariate analysis, independent factors associated with FibroScan values between 12 and 20 kPa were Child B or C (OR 0.16, 95%CI 0.05-0.5, p=0.004), oesophageal varices (0.42, 0.2-0.8, 0.01) and past history of ascites (0.14, 0.03-0.6, 0.009). Independent factors associated with FibroScan > 50 kPa were Child B or C (2.7, 1.4-5.2, 0.004), oesophageal varices (2.2, 1.1-4.7, 0.03) and past history of ascites (3.7, 1.8-7.3, <0.001). No independent factors were associated with FibroScan values between 20 and 50 kPa.

 

Conclusion:

This study confirms that FibroScan can evaluate the severity of cirrhosis. Three stages of cirrhosis could be defined: a group with no complications of cirrhosis (FibroScan values < 20 kPa), a group with severe complications (FibroScan values > 50 kPa) and an intermediate group. Therefore, FibroScan should be used for the follow-up of cirrhotic patients.

 

FibroScan groups

A (12-20)

p value

B (20-35)

p value

C (35-50)

p value

D (>50)

p value

Child Pugh B/C

0.05 (0.0-1.4)

<0.001

0.63 (0.4-1.1)

ns

2.6 (1.5-4.3)

<0.001

8.1 (4.9-13.3)

<0.001

Oesophageal varices

0.24 (0.1-0.4)

<0.001

0.9 (0.6-1.5)

ns

1.7 (0.9-2.8)

ns

3.9 (2.2-6.9)

<0.001

Oesophageal varices stage 2/3

0.25 (0.2-0.4)

<0.001

0.8 (0.5-1.3)

ns

1.8 (1.1-3.1)

0.03

2.7 (1.6-4.5)

<0.001

Past history of variceal bleeding

0.14 (0.1-0.4)

<0.001

0.6 (0.3-1.2)

ns

2.2 (1.2 (4.1)

0.01

5.2 (2.9-9.2)

<0.001

Past history of ascites

0.03 (0.0-0.2)

<0.001

0.61 (0.1-1.0)

ns

1.7 (0.9-3)

ns

12.1 (7.1-20.3)

<0.001

Hepatocellular carcinoma

0.3 (0.2-0.7)

0.004

1.1 (0.6-1.9)

ns

0.9 (0.4-2.1)

ns

3.5 (1.9-6.5)

<0.001

Death

0.14 (0.03-0.6)

<0.001

0.6 (0.2-1.7)

ns

2.6 (1.0-6.5)

0.04

3.8 (1.6-9.2)

0.002

 

705. A preliminary evaluation of a novel biomarker of renal function, Neutrophil Gelatinase-Associated Lipocalin (NGAL), in patients with liver disease. 

A. J. Portal; M. Austin; M. J. Bruce; J. Wendon; M. Heneghan.

 

Introduction:

Neutrophil Gelatinase-associated Lipocalin (NGAL), a member of the lipocalin family of proteins, is expressed at low levels in the kidney, lung, prostate and GI tract, and has been shown to be an early biomarker of ischaemic renal damage. NGAL has not been assessed in patients with liver disease. Our aims were to evaluate the use of NGAL measurements in 44 consecutive patients with liver disease.

 

Methods:

NGAL was measured on admission using a sandwich ELISA technique (AntibodyShop®) in 17 patients with acute liver failure (ALF), 11 patients with acute on chronic liver disease (ACLD), 16 immediately post transplant (LT) patients and 10 healthy controls. Biochemical and physiological variables were collected. All results are expressed as median and interquartile range (IQR).

 

Results:

Median NGAL in healthy controls was 64.5 ng/ml (55.8-83.3) versus 303 ng/ml (188-432, n=49) in all liver patients. Median NGAL values were significantly higher in all patient groups compared to controls (p<0.001). NGAL levels correlated with urine output (r=-0.58, p<0.001), APACHE III score (r=0.56, p<0.001), serum creatinine (r=0.4, p<0.01) and estimated GFR (r=-0.42, p<0.01). Admission NGAL correlated with reduced urine output (r=-0.5, p=0.001) and serum creatinine (Cr) level (r=0.4, p=0.01) on day 3.

 

NGAL levels were significantly higher in patients with Systemic Inflammatory Response Syndrome (340 ng/ml (194-458) versus 190 ng/ml (100-243); p=0.03).

 

In haemofiltered patients, NGAL levels were significantly higher compared to non-dialysed patients on Day 1 (463ng/ml (346 - >500) vs 226 ng/ml (147-338); p<0.001) and on Day 3 420 ng/ml (303- >500) vs 193ng/ml (125-319; p<0.001).

 

Using ROC curves, high NGAL levels predicted the need for Day 1 haemofiltration (AUC 0.87 (CI 0.77-0.92, p<0.001) in all patients compared with serum Cr (AUC=0.8, CI 0.67-0.94; p<0.001).

 

In post transplant patients, admission NGAL levels correlated with day 7 serum Cr (r=0.546, p=0.013) and also predicted the presence of renal failure on day 7 of admission (ROC AUC 0.83, p= 0.014) more accurately than admission serum Cr (AUC 0.61, NS). This relationship was also evident on day 14 of admission. Admission NGAL also predicted the need for haemofiltration on day 5 more accurately than admission creatinine (ROC AUC 0.92 , p=0.005 vs 0.78, p=0.06).

 

Conclusion:

NGAL levels are significantly higher in patients with liver disease than controls. This novel biomarker may predict the need for renal replacement therapy prior to conventional markers. In the post transplant population it may allow more accurate identification of patients who would benefit from renal sparing immunosuppression.

 

707. Noninvasive diagnosis of the degree of hepatic fibrosis using serum markers and ultrasonography in patients with chronic hepatitis B. 

W. Zhang; B. Wang; J. Jia; X. Ou; T. Wang.

 

Objective:

To develop noninvasive diagnostic methods with panels of serum markers and ultrasonic scoring system for detecting the severity of hepatic fibrosis in patients with hepatitis B and to determine their value in clinical practice.

 

Methods:

A total of 270 consecutive patients with chronic hepatitis B and available liver biopsy examination were included prospectively in a multicenter study. Fibrosis was assessed blindly on the Scheuer’s scoring and Chevallier’s semi-quantitative scoring system. Twenty six common clinical and serum markers were analyzed to derive two diagnostic models for discriminating stages of liver fibrosis. Total 110 patients underwent ultrasound examination with color Doppler ultrasonic instrument (HDI 5000) and 20 Ultrasonographic variables were analyzed by a soft of quantitative analysis (QLAB). An ultrasonic semi-quantitative scores system including seven ultrasonic morphologic parameters and a discriminating function combining three quantitative ultrasonic parameters were developed.

 

Results:

Four markers including AGE, GGT, HA, PLT were identified and a predictive fibrosis model was derived against the Scheuer’s scoring system by multivariate logistic regression analysis. Four serum markers including PLT, HA, GGT, ALB were identified and a fibrosis scoring index was also constructed against the Chevallier’s semi-quantitative scoring system by multiple linear stepwise regression analysis. The AUC of the model was 0.889 for the estimation group and 0.850 for the validation group for discriminating ≥S3 from ≤S2. Using the cut-off score 3.0, sensitivity of the model was 90.2%, specificity 76.1%, and the accuracy was 82%. There was a positive linear relationship between the model score and the fibrosis stage (r =0.731,P<0.001). There was a significant positive linear correlation between the scoring index and pathologic semi-quantitative scores (r =0.719,P<0.001). An ultrasonic semi-quantitative scores system including anterior liver surface, edge, parenchyma, intrahepatic vessels, Doppler waveform of the hepatic vein, smoothness of the gallbladder wall and area of the spleen were constructed. The total ultrasonic scores were well correlated with the histological stage of fibrosis (r=0.824,P<0.001). The AUC of the scores system for identifying liver fibrosis stages were 0.946 (≥S2), 0.914 (≥S3), 0.915 (S=4). There was significant difference between stages of fibrosis.

 

Conclusion:

A set of laboratory and ultrasonic assessment systems were found to be useful to reflect the degree of liver fibrosis in chronic hepatitis B.

 

708. Updated long-term outcome after variceal bleeding using currently available treatments to prevent rebleeding. 

C. Aracil; A. Colomo; D. Busquets; M. Casas; J. López-Balaguer; J. Miñana; A. Gallego; X. Torras; C. Villanueva; J. Balanzó.

 

Introduction:

Variceal bleeding markedly worsens the outcome of cirrhosis with a death risk of 33% to 57% within 1 year in untreated patients. In recent years treatments such as β-blockers plus nitrates, ligation alone or combined with drugs, and TIPS, have shown efficacy in preventing variceal rebleeding in follow-up periods of 2-3 years. However, efficacy after a longer follow-up has not been adequately investigated.

 

Aim:

The aim of this study was to assess the influence of these therapies on the long-term outcome after bleeding.

 

Methods:

all patients with variceal bleeding consecutively admitted over the last 15 years were included on the 5th day of admission and regularly visited until April-2006. To prevent rebleeding they were treated with β-blockers plus nitrates (43%), ligation (22%), sclerotherapy (9%) or the association of drugs and ligation (25%). The follow-up was closed 6 months after the last inclusion.

 

Results:

400 patients were included, mean age was 59±12 years, male 269 (65%), female 131 (35%), 48% had alcoholic cirrhosis and 81% were Child-Pugh class B/C. During the follow-up 49% were Child-Pugh class B/C (3rd month), 52% developed ascites and 16% hepatocarcinoma. Among alcoholics 77% were abstinent. 114/302 (38%) had a decrease of HVPG to <12 mmHg or >20% from baseline (hemodynamic responders). The probability of rebleeding at 1,3,5,7 and 10 years was 30%, 39%, 47%, 49% and 54%, and the likelihood of death was 21%,40%,52%,61% and 68% respectively. Survival probability was significantly higher in responders than in non-reponders (69% vs 47% and 46% vs 23% at 5 and 10 years, P <0.001), and OLT probability was lower (8% vs 16%, P= 0.04). Child-Pugh at 3rd month and hemodynamic response were independent predictors of rebleeding, while rebleeding, Child-Pugh at 3rd month, age, baseline albumin, creatinine and cardiac output, and hemodynamic response were independent predictors of death.

 

Conclusions:

With current therapy, the rebleeding probability is 30% at 1 year of follow-up, and subsequently decreases to ≤ 5% yearly. Current therapy improves the expected probability of survival up to 79%, 62% and 48%, and 4% at 1, 3,5, and 7 years of follow-up respectively. Rebleeding is an independent predictor of long-term survival, while Child-Pugh at 3rd month and hemodynamic response are independent predictors of both long-term rebleeding and survival.

 

709. Liver stiffness measurement by transient elastography: predictive factors of accuracy, success and reproducibility. 

A. Konaté; J. Boursier; S. Réaud; E. Quemener; I. Fouchard-Hubert; F. Oberti; P. Calès.

 

Introduction:

Liver stiffness measurement (LSM) is an emerging examination for liver fibrosis evaluation. We evaluated its factors of accuracy, success and reproducibility.

 

Methods:

2 Fibroscan, 3 judges: #1: physician with 844 LSM, #2: physician with 105 LSM, #3: non physician with 0 LSM. 100 patients with chronic liver disease were included into 4 reproducibility studies: #1 (interequipment): n=17, #2 (interobserver): n=41, #3 (repeatability): n=20, #4 (inter-observer and inter-site): n=22. Reproducibility was measured by intraclass correlation coefficient (Ric).

 

Results:

Study #1. Ric=0.92 between 2 devices.

 

Study #2. Metavir F was independently predicted only by LSM of judge #1 who was used as the reference. The success rate (%) for LSM (n valid/n total measures) varied with judge expertise: #1: 79, #2: 75, #3: 35 (p<10-4 vs others). This resulted in clinically available LSM results (n valid: 10) according to judges: #1: 95%, #2: 83%, #3: 68%. The success rate in judge #1 was independently predicted by BMI (p<10-4) and intercostal space (p=0.007). The interobserver agreement (Ric) of LSM was: 3 judges: 0.92 (0.86-96), judges 1 and 2 (physicians): 0.96, judges 1 and 3 (expert physician vs non-physician): 0.94, judges 2 and 3 (non-expert physician vs non-physician): 0.89. Ric for the 2 physicians varied as a function of LSM value: <20 KPa: 0.61, ≥20 KPa: 0.94 and of BMI: ≤27: 0.95, >27: 0.75.

 

Study #3. Ric for 10 LSM measured twice by judge #1 was 0.997. Study #4. Ric between judges 1 and 2, respectively decubitus, axillary line, intercostal space number: a) lateral, median, 7th: 0.84; b) dorsal, anterior, 7th: 0.95; c) dorsal, median, 8th: 0.93; d) dorsal, median, 7th: 0.99. The influence of several binary factors was tested on agreement (Ric) in judge #1: decubitus: 0.96; axillary line: 0.98; intercostal space: 0.98; withdrawal of LSM screen: 0.99; standard ultrasonography: 0.99.

 

Conclusions:

The interequipment, intra and inter observer reproducibilities are excellent. The success rate depends on judge expertise, BMI and intercostal space. The inter observer agreement depends on judge expertise, LSM value and BMI. Experience for LSM is very rapidly acquired. The more reproducible technique needs preferably the first intercostal space with liver dullness (usually the 7th) on median axillary line in supine position whereas standard ultrasonography adds nothing. The ideal candidate is a patient without obesity and with a severe fibrosis.

 

710. Combination of blood scores, Doppler ultrasonography, and transient elastography for the diagnosis of liver fibrosis. 

V. Le Tallec; J. Le Bigot; G. Gorea; S. Réaud; J. Boursier; A. Konaté ; E. Quemener; Y. Gallois; I. Fouchard-Hubert; F. Oberti; S. Michalak; M. Rousselet; C. Aubé; P. Cales.

 

Introduction:

It has been suggested that different diagnostic tools of liver fibrosis might have an additive effect but this has not been demonstrated.

 

Aim:

Our aim was to evaluate together blood scores, Doppler ultrasonography (US), and transient elastography for the diagnosis of different classes of liver fibrosis.

 

Results:

Study #1: exploratory in 2000-3. 190 patients with chronic liver disease (CLD) aged 47±12 yr, 67.4% male, with the following causes: alcohol (13.5%), virus (44.7%), alcohol + virus (16.8%) and others (24.7%) were included. 20 blood variables were measured providing Fibrotest (FT), APRI and several FibroMeters (FM), and 9 variables at Doppler-US providing the Giannini index (platelet / spleen length). The Metavir stages of liver fibrosis were: F0: 5.8%, F1: 26.8%, F2: 26.8%, F3: 18.4%, F4: 22.1%. In forward binary logistic regression, the combination of FM virus and spleen length had a diagnostic accuracy (DA) of 83.1% including a 3% independent gain due to the US variable. The combination of FM virus/alcohol and irregular liver surface had a DA of 82.4% including a 2.8% independent gain due to the US variable.

 

Study #2: validation in 2004-6. 161 patients with CLD aged 50±13 yr, 67.1% male, with the following causes: alcohol (17.1%), virus (57.0%), metabolic (15.2%) and others (10.8%) were included. The Metavir stages were: F0: 4.6%, F1: 25.0%, F2: 24.3%, F3: 17.8%, F4: 28.3%. They underwent the same examinations plus a transient elastography (Fibroscan) for liver stiffness measurement (LSM). The combination of blood tests, Doppler-US and elastography was tested by forward binary logistic regression. Clinically significant fibrosis (≥ F2) was diagnosed by FM virus (p=0.002) and LSM (p=0.021) with DA=84.2% and AUROC=0.874±0.033. Severe fibrosis was diagnosed by FM virus (p<10-3) and irregular surface (p=0.027) with DA=81.7% and AUROC=0.890±0.028. Cirrhosis (F4) was diagnosed by FM virus (p=0.014), irregular surface (p=0.012) and LSM (p=0.054) with DA=83.3% and AUROC=0.879±0.035. AUROC of those combinations were not significantly different as a function of cause, respectively virus vs others: ≥F2: 0.846±0.049 vs 0.960±0.0269; ≥F3: 0.880±0.048 vs 0.880±0.038; F4: 0.861±0.049 vs 0.868±0.056.

 

Conclusions:

One blood score (FibroMeter) and one or two imaging variables (LSM and/or US) have an independent and high DA for the diagnosis of clinically significant fibrosis or severe fibrosis or cirrhosis. The gain brought by a second imaging procedure is moderate and that of a second blood test is null. So a blood test and a physical variable are sufficient. The combination of several examinations is also a mean to partially solve their disagreement between themselves.

 

711. Hepatic Encephalopathy Predicting Survival. 

C. A. Stewart; M. Malinchoc; W. Kim; P. S. Kamath.

 

Background/Aims:

Decompensated cirrhosis which negatively affects survival may manifest as hepatic encephalopathy (HE). The Model for end stage liver disease (MELD) score is able to predict survival of cirrhotics, but MELD does not include HE. Hence, it is not clear whether HE influences survival. Our aims were to determine the effects of HE on survival by examining its impact on MELD, CTP and a new model to predict HE, ordinal logistic regression score for predicting HE.

 

Methods:

Three populations of cirrhotic patients were studied: those who were undergoing TIPS insertion (n=223), hospitalized (n=271), and on the liver transplant waiting list (n=1701). Due to the inherent differences in the populations they were separately analyzed. Using Cox Proportional hazard regression procedure, the increased risk of death of patients with HE was examined. Using Kaplan-Meier survival analysis, 3-month (short-term) and 12-month (long-term) survival of these 3 populations were determined according to the effects of HE, modified CTP, ordinal logistic regression score for predicting HE, and MELD on survival. In addition, the concordant statistic(c-statistic) of adjusted MELD, modified CTP, and ordinal logistic regression score on survival was assessed. The new ordinal logistic score, was validated as a predictor of survival in a separate population of patients.

 

Results:

Using adjusted MELD, HE predicted 3 and 12-month survival in TIPS vs. hospitalized cirrhotics with a c-statistic of 0.748 and 0.745 vs 0.80 and 0.799; using the modified CTP, the c-statistic was 0.67 and 0.667 vs. 0.792 and 0.787; when ordinal logistic regression score for predicting HE was used, the c-statistic was 0.65 and 0.65 vs. 0.734 and 0.724. The presence of HE increased the risk of death in TIPS and hospitalized cirrhotics by HR (95% CI) of 1.69 (1.16-2.48) and 3.87 (2.64-5.69) with respective p-values <0001.

 

Conclusion:

Although HE increases the risk of mortality from cirrhosis, it does not add value to predictors of survival in the cirrhotic population universally.

 

712. Etiology of cirrhosis has an impact on survival predicted by MELD-score. 

B. Angermayr; A. Luca; F. Koenig; G. Bertolini; M. Ploner; M. Cejna; J. Bosch; M. Peck-Radosavljevic.

 

Introduction:

Originally, etiology of liver disease has been incorporated into the computation of the MELD score. Clinical observations prompted us to hypothesize that patients with viral and alcoholic cirrhosis may differ in predicted survival rates. Until now, no large representative studies evaluated the impact of etiology on survival predicted by Child Pugh (CPS) and MELD score.

 

Methods:

658 patients who underwent TIPS in two tertiary care hospitals (Vienna,Austria,n=455;ISMETT Palermo,Italy,n=98) were included into the retrospective study. The main analyses were a logistic regression model and a Cox proportional hazards regression model calculating the interaction of the etiology with the scores.

 

Results:

Both groups (viral: n= 160; alcoholic: n=393) had similar survival rates (p=.89, median 1377/1617 days for viral/alcoholic cirrhosis), but patients with viral cirrhosis had sign. lower MELD-scores (p=.002).MELD adequately predicted 3-month survival in both groups. For 1 year survival, etiology had a significant impact on survival indicating that patients with identical scores but different etiologies differed in survival rates. When stratifying patients into high and low risk patients (MELD<16 vs. MELD=>16), etiology of cirrhosis had no impact on the predictive value for low-risk patients; high-risk-patients (MELD=>16) with viral cirrhosis had significantly lower survival rates than patients with alcoholic cirrhosis and identical scores (figure 1). With regard to CPS, no significant differences between the two patient groups and in prediction of 3 month and 1 year survival could be observed.

 

Conclusions:

Our study suggests that etiology of cirrhosis has an impact on 1-year survival predicted by the MELD score. This becomes more apparent in patients with advanced stage liver disease (MELD=>16). In this group, patients with viral cirrhosis have a significantly poorer prognosis that patients with alcoholic cirrhosis with the same MELD score. Since MELD is used for ranking patients for liver transplantation and waiting times are regularly longer than 3 months, our observations suggest that with increasing time on the waiting list and severity of disease, patients with viral cirrhosis may have a disadvantage in the current allocation policy.

 

713. Loss of muscular mass is an independent factor associated with mortality in liver cirrhosis: prospective analysis of 206 patients. 

N. Hrycewycz; C. Bureau; O. Rouquet; J. Peron; K. Barange; J. Vinel.

 

Introduction:

Occurrence of malnutrition in cirrhotic patients is strongly associated with progressive alteration of liver function but the independent value of malnutrition as a risk factor of mortality is discussed in literature, in particular in patients with Child-Pugh class C liver cirrhosis.

 

Aims:

To analyze the independent role of malnutrition on mortality in patients with cirrhosis.

 

Methods:

Between November 2004 and February 2006, middle arm muscle circonference (MAMC), triceps skinfold thickness (TST) were prospectively measured, with Harpenden Caliper, in 206 patients with liver cirrhosis (142 men, mean age 58.6±11.4 years, Child-Pugh A, B, C: 17 %, 38,3 %, 44,2 %; hepatocarcinoma (HCC): 24,8 %). MAMC<5th percentile and TST<5th percentile were define using referent population standardized on sex and age. Univariate and multivariate Cox regression model and Kaplan-Meier method using Log-Rank test were used to identify independent parameters associated with mortality.

 

Results:

Mean follow up was 176±117 days (range 1-442 days). Cirrhosis was alcoholic in 71.8 %, with active alcohol abuse in 39.2 % of the cases, respectively. Prevalence of MAMC<5th percentile and TST<5th percentile was 42.2 % and 25.7 %, respectively. Sixty four patients (31.1 %) died during follow-up. The estimated 6-month and 1-year survival rate were 73.8 %, and 55.8 %, respectively.

 

Parameters significantly associated with mortality were age (p=0.002), male sex (0.03), MAMC<5th percentile (p=0.001), HCC (p<0.001), ascites (p<0.001), hepatic encephalopathy (p=0.036), albumin (p=0.03), prothrombin index (p=0.02), total bilirubin>33 micromol/l (p=0.004), AST>3.5 N (p=0.015), serum sodium<133 mmol/l (p<0.001), serum creatinine>96 micromol/l (p<0.001), CRP>28 mg/l (p=0.002), Meld score (p<0.001), Child-Pugh score (p<0.001). TST<5th percentile was not associated with mortality (NS).

 

Mortality was significantly higher in patients with MAMC<5th percentile and Child-Pugh class B (p=0.03) and C (p=0.02) cirrhosis but not in Child-Pugh class A cirrhosis (NS).

 

Using multivariate analysis, independent parameters associated with mortality were: age (HR=2.1 CI 95 % 1.00 -1.05), CMB<5th percentile (HR=1.8 CI 95 % 1.0-3.0, p=0.02), HCC (HR=2.4 CI 95 % 1.4-4.0, p=0.001), CRP>28 mg/l (HR=2.1 CI 95 % 1.2-3.6, p=0.007), total bilirubin>33 micromol/l (HR=1.7 CI 95 % 1.0-3.0 , p=0.043) and ascites (HR=2.2 CI 95 % 1.2-3.8, p=0.005).

 

Conclusions:

Muscular mass depletion was an independent parameter associated with survival in cirrhotic patients, even in Child-Pugh class C patients. Loss of fat mass had no influence on the prognosis of the disease.

 

715. Renal dysfunction is associated with cognitive impairment in patients with liver cirrhosis. 

E. Kalaitzakis; E. Bjornsson.

 

Background:

Chronic renal dysfunction is associated with cognitive impairment in non-cirrhotic individuals and it may be reversed by renal transplantation. Renal dysfunction is common in patients with liver cirrhosis. Although fluid depletion and electrolyte imbalance are known precipitating factors of hepatic encephalopathy (HE) in cirrhotics, the effects of renal dysfunction on cognitive function in this group of patients are largely unexplored.

 

Methods:

A total of 128 consecutive cirrhotics (mean (SD) age 57 (11.5); 49 Female; Child-Pugh score 8.6 (2.3); MELD 13.2 (5.6); 25 inpatients; 55 alcoholic; 21 viral; 21 cholestatic etiology) were prospectively evaluated for the presence of HE. Patients with HE grade >2 were excluded. Inpatients with complications of liver disease were included upon discharge when stable clinical conditions were reached. Two psychometric tests (number connection test A and B (NCT-A/B) were also performed. Serum sodium and potassium as well as serum ammonia were assessed.

 

Results:

Forty-one (32%) patients had HE grade 1-2 and/or a NCT-A and/or B score >3SD of a control population. Sixteen (12.5%) patients had serum creatinine levels over reference values (100 μmol/l for males, 90 μmol/l for females). Patients with vs. without creatinine over reference values (n=16) had more frequently HE and/or NCT-A and/or NCT-B > 3SD (68.8% vs. 31.3%, p=0.001) but did not differ in Child-Pugh score or etiology of cirrhosis (p>0.1). Patients with vs. without loop diuretics did not differ in creatinine values (p>0.1). In univariate analysis, the time needed to perform NCT-B was positively related to age (r=0.43, p<0.001), serum creatinine (r=0.45, p<0.0001), Child-Pugh score (r=0.43, p=0.001), MELD (r=0.32, p=0.009), serum potassium (r=0.2, p<0.02) and hospital admission (p<0.002), but negatively to serum sodium (r=-0.14, p<0.05) and cholestatic etiology (p<0.01). In multivariate analysis, the time needed to perform NCT-B was independently correlated to age (r=0.35, p<0.001), serum creatinine (r=0.34, p<0.001), Child-Pugh score (r=0.27, p=0.001) and cholestatic etiology (r=-0.18, p<0.05). Serum creatinine was related to the serum ammonia concentration (r=0.26, p=0.004).

 

Conclusion:

Cognitive impairment seems to be related to renal dysfunction in patients with liver cirrhosis. Renal dysfunction might be implicated in the pathogenesis of hepatic encephalopathy.

 

718. Variceal band ligation versus beta blockers for primary prevention of variceal bleeding: An updated meta-analysis. 

D. Tripathi; C. Graham; P. C. Hayes.

 

Background/Aims:

Variceal band ligation(VBL) can reduce the rate of the first variceal bleed by 45-52% compared with beta-blockers(BB). An updated meta-analysis was performed incorporating 9 peer-reviewed randomized controlled trials.

 

Methods:

Relative risk(RR) using a fixed effects model was utilized. Sensitivity analysis using a random effects model was performed to assess consistency of results.

 

Results:

734 patients were studied (356,VBL;378,BB). The pooled RR significantly favored VBL for the first variceal bleed (0.61; 95% CI,0.44-0.84;Figure 1) with the NNT of 11 (95% CI, 7-33), and for adverse events with treatment withdrawal (0.20;95% CI,0.10-0.39;Figure 2) with the NNT of 9 (95% CI, 7-13). There was a trend towards reduced bleeding deaths with VBL (RR,0.65;95%CI,0.35-1.18). There was no evidence of differences in overall mortality. There was no significant heterogeneity or publication bias, and outcomes were robust following sensitivity analysis.

 

Conclusions:

VBL was superior to BB for preventing the first variceal bleed, and resulted in fewer adverse events. VBL has a role in patients unlikely to comply with drug therapy, or unable to tolerate/bleed on BB therapy.

 



 

719. The effect of antiviral therapy on clinical outcome of HCV cirrhosis with portal hypertension: a prospective cohort study. 

V. Di Marco; P. Almasio; S. De Lisi; C. Vincenza; D. Ferraro; S. Peralta; P. Parisi; G. Alaimo; N. Alessi; R. Di Stefano; A. Craxì.

 

Background and Aim:

The impact of viral clearance on the disease course of HCV compensated cirrhosis is unknown. We have assessed outcomes in a prospective cohort with HCV cirrhosis after antiviral therapy.

 

Patients and methods:

174 consecutive patients with Child-Pugh A5-A6 cirrhosis (mean age 57.0±7.7, 62.1% males, 56.3% with oesophageal varices) were treated with Peg IFN alone (27%) or Peg IFN plus RBV (73%) and followed at least for 6 months after therapy (median 24 months, range 6-53). Genotype 1 was present in 154 patients (88.5%); 117 patients (67.2%) were naïve and 57 patients (32.8%) were previously treated with IFN monotherapy.

 

Result:

59 patients (34%) dropped the therapy because of side effects and 115 received the scheduled treatment. Sustained virological response (SVR) was obtained in 32/174 (18.3%) patients by intention to treat analysis and 32/115 (27.8%) by treatment received analysis. No significant difference among patients without and with varices (21.1% vs. 15.5%, p= 0.3) was found. Patients with SVR were younger (53.7 ± 8.4 vs 57.8 ± 7.2, p < 0.01), infected with genotype 2 or 3 (65% vs 11.8%, p < 0.001), had higher basal ALT levels (4.7 ± 2.5 u.l.n. vs. 3.6 ± 1.9 u.l.n., p < 0.05) and lower basal GGT levels ( 1.7 ± 1.3 u.l.n. vs 2.7 ± 2.2 u.l.n., p< 0.05). Logistic regression after ROC curve analysis confirmed as independent predictor of SVR age ≤ 62 years (R.R 5.8, 95% C.I. 1.1-30.2), genotype 2 or 3 (R.R. 18.1, 95% C.I. 5.1-64), basal ALT > 3 ULN (R.R. 4.1, 95% C.I. 1.5-11.5) and basal GGT ≤ 1 ULN (R.R. 4.3 , 95% C.I. 1.6-11.6). During follow-up, 34 patients (19.5%) developed at least one liver complication and 2 of them died for liver-related causes. One patients died for extra hepatic cancer. All 34 patients were infected by genotype 1 and 25 had oesophageal varices. Thirty-one liver related events occurred in non responders and only 2 events in SVR (22.5% vs 6.3% p < 0.05). By Cox regression model, oesophageal varices (RR 3.3 IC 95% 1.5-7.1) and SVR (RR 4.9 CI 95% 1.2-20.4) were significantly related to disease progression.

 

Conclusion:

PEG-IFN and Ribavirin obtains a sustained virological response in 1/5 of patients with compensated cirrhosis. The sustained response was more common for genotypes 2 or 3, in patients with age less than 60 years with elevated values of ALT and low levels of GGT. Treatment withdrawal due to intolerance and haematological toxicity was common, without life-threatening events. Patients with sustained virological response had a minor incidence of disease complications during a short term follow-up.

 

720. Enhanced Quantitative Liver Spleen Scan (QLSS) Prediction of Liver Disease Severity in Baseline HALT-C Patients with Moderate Fibrosis or Cirrhosis. 

J. C. Hoefs; G. T. Everson; M. L. Shiffman; T. R. Morgan; D. Naishadham; E. C. Wright.

 

Introduction:

The best QLSS index of liver function has been the perfused hepatic mass (PHM) correlating with chronic liver disease (CLD) severity. Multivariate equations to predict liver severity at peritonoscopy (estimated peritonoscopy score=estPS) (Hep 22:1115) might be better than the PHM.

 

Hypothesis:

QLSS measurements providing more than functional information might enhance detection of cirrhosis.

 

Patients:

A 275 patient subset of non-splenectomized HCV patients recruited into the HALT-C trial, non-responders to treatment with Ishak 3-6 fibrosis on biopsy were evaluated as part of the quantitative liver function tests ancillary study.

 

Methods:

The QLSS was performed post-prandially with 5 mCi Tc99 sulfur colloid IV. SPECT reconstruction allowed calculation of the total liver, spleen and bone marrow counts, right lobe(RL), Left lobe (LL), spleen length (SL) and posterior pixel counts from the planar image. From these raw data were calculated multiple parameters including the PHM, redistribution ratio (RR=[(liver pixel counts/spleen pixel counts/2.5) + (liver pixel counts/bone marrow counts/17.5)]/2), SL/RL ratio, liver size (RL+.5*LL) (cm) and estPS (=4.342 -2.008*RR - .0206*PHM + 18.15/RL). The relationship to baseline labs, hepatic fibrosis (Ishak score) and clinical factors was assessed by Linear regression analysis. In addition, patients were divided into 4 liver disease severity groups based on cirrhosis and platelet count < or >125 K and histologic cirrhosis (+/-) (group 1 best, group 4 worst).

 

Results:

Univariate analysis showed significant (p <.0001) correlation of RR and estPS with clinical features similar to the PHM (table). The PHM and estPS were both significantly different in severity groups: estPS in group 1 was 1.04+/-.74, 2 – 1.93+/-.66, 3 – 1.77+/-.74, and 4 – 2.28+/-.69 (p < .0001) compared to the PHM of 102+/-6, 93+/-8, 98+/-8, and 89+/-9 (p < .0001). Multivariate logistic regression for all QLSS parameters for detection of cirrhosis to be: log (Odds Ratio(Cirrhosis))= -9.321+ 3.69*S/R Ratio + 0.16 *Liversize + 1.29*estPS with a c-statistic of .838. Compared to PHM alone with a c-statistic of .77, a significant difference (p<.0010) by chiSq in detection of cirrhosis.

 

Conclusion:

1. PHM, RR and estPS correlated well with CLD severity 2. Multivariate regression selected estPS1, S/R ratio and liver size as the best predictors of cirrhosis, the combination enhancing the ability to detect cirrhosis compared to PHM alone.

 

Correlation Coeficients

 

Ishak
Fibro

Plate

AST/
ALT

Bili

Alb

INR

Varix
Grade

Spleen
Size

PHM

-.51

.58

-.47

-.33

.45

-.46

-.22

-.44

RR

-.54

.54

-.37

-.31

.41

-.39

-.27

-.33

estPS

.55

-.57

.41

.32

-.44

.42

.25

.36

 

721. Platelet count as a non-invasive predictor of esophageal varices.  

A. A. Qamar; N. D. Grace; R. J. Groszmann; G. Garcia-Tsao; J. Bosch; A. K. Burroughs; R. Maurer; R. Planas; J. Garcia-Pagan; A. Escorsell; R. Makuch; D. Patch; D. Matloff; W. The Portal Hypertension Collaborative Group.

 

Background:

Current guidelines recommend screening endoscopy(EGD) for esophageal varices(EV)in patients with cirrhosis. Non-invasive tests to predict the presence of EV would decrease the burden of EGD. The strongest predictor for EV is the hepatic venous pressure gradient (HVPG) (N Engl J Med 2005; 353:2254). Serum platelet counts (PLT) are related to the HVPG and might predict the development of EV in well-compensated cirrhosis.

 

Methods:

A database of 213 subjects with well-compensated cirrhosis without EV enrolled in a randomized, placebo controlled trial of a non-selective beta-blocker in the prevention of EV was analyzed. PLT were obtained every 3 months and HVPG measurements and EGD were performed annually. Baseline and first year PLT was compared between subjects who did and did not develop EV during the course of the study (mean follow-up 4.2 years).Spearman’s correlation was performed between baseline and first year PLT and HVPG. T test compared % changes between baseline and first year PLT with HVPG. The change in PLT from baseline to first was stratified into (1) >/10% increase, (2) >/10% decrease and (3)<10% increase or decrease. The occurrence of EV was compared among these 3 groups using cox proportional model.

 

Results:

A significant correlation was found between HVPG and PLT at baseline (r= - 0.44, n = 213, p<0.0001) and at year 1 (r= -0.53, n = 154, p<0.0001). 10% or greater increase in PLT between baseline and first year was not associated with a significant change in HVPG. There was no difference in the % change in PLT among subjects with a 10 % decrease in HVPG (n = 69) between baseline and first year compared to patients not achieving this change (n = 85) ( -0.8 % vs -3.6%, p= ns).84 patients developed EV during the course of the study. The median PLT at baseline in patients who developed varices was 105, compared to 119 in patients who did not develop varices (p= ns) In the first year it was 95 compared to 115 (p = 0.0155). However, a ROC curve did not show a specific PLT with high sensitivity or specificity for the occurrence of EV (AUC = 0.630, 95% CI: 0.554-0.706). Cox proportional model showed a trend for higher occurrence of EV among patients with a >/ 10% reduction in PLT at year one.

 

Summary:

PLT correlates with HVPG. Changes in PLT cannot be used as a surrogate for HVPG change. Subjects who develop EV have a significantly lower first year median PLT. No specific PLT has a high sensitivity or specificity to predict EV.

 

Conclusion:

Although patients with cirrhosis who develop EV have lower PLT than those without EV, the degree of thrombocytopenia does not accurately identify candidates for screening EGD for EV.

 

728. Nationwide Trends in the Incidence of Bleeding and Non-Bleeding Esophageal Varices in Hospitalized Patients in the United States. 

M. Jamal; J. B. Samarasena; M. Hashemzadeh.

 

Introduction:

Esophageal varices still represent one of the most challenging problems in modern hepatogastroenterology.

 

Aim:

The objective of this study was to analyze the nationwide trends in the incidence of non-bleeding and bleeding esophageal varices in hospitalized patients in the United States, in the advent of the new therapeutic modalities used to treat acute variceal bleeding.

 

The Nationwide Inpatient Sample database was used for data analysis and patients discharged with an ICD-9-CM primary or secondary discharge diagnosis related to esophageal varices or esophageal variceal bleeding were included. The average annual age-adjusted rates for esophageal varices and esophageal variceal bleeding were calculated. The age-adjusted rates were averaged across three-year periods for the purpose of trend analysis.

 

Results:

Our results revealed the nationwide age-adjusted rate of non-bleeding esophageal varices is on the rise, having increased from 5.5 per 100,000 in the 1988-1990 period to 9.3 per 100,000 in the 2000-2002 period (p < 0.01). The age-adjusted rate of bleeding esophageal varices increased from 10.9 per 100,000 in the 1988-1990 to 12.4 per 100,000 in the 1994-1996 period then decreased to 10.6 per 100,000 in the 2000-2002 period (p < 0.01).

 

Conclusion:

The rise in the incidence of non-bleeding esophageal is likely a reflection of the increasing incidence of portal hypertensive liver disease in the nation due to chronic Hepatitis C infection, Non-alcoholic fatty liver disease and alcoholic liver disease. The recent decline in the incidence of bleeding esophageal is likely a reflection of a decrease in rebleeding rates and first episodes of bleeding due advances in acute management of variceal bleeding beginning in the early 1990s as well as the more recent advances in primary prophylaxis.

 

 

733. Quality of Care for Ambulatory Patients with Cirrhosis in an Academic Medical Center. 

W. Sanchez; J. A. Talwalkar; M. H. Evjen; P. S. Kamath.

 

Background:  

Cirrhosis and portal hypertension are major causes of hospitalization and death in the United States. For similar chronic diseases including heart failure, the Institute of Medicine (IOM) recommends quality of care measurement to improve clinical outcomes. Little is known, however, about the quality of care received by patients with cirrhosis.

 

Aim:

1.     To identify performance measures of quality care for ambulatory patients with an initial diagnosis of cirrhosis.

2.     To determine the adherence rate with performance measures that reflect quality of care.

 

Methods:  

Patients evaluated in a hepatology-based clinic between January 1, 2003 and September 30, 2003 were selected. Both new referrals and established patients were included. Following IRB approval, retrospective data abstraction from electronic medical records was performed. Using IOM recommendations, a set of 3 performance measures for patients with an initial diagnosis of cirrhosis were identified. These include:

1.     screening endoscopy to detect esophageal varices,

2.     screening for hepatocellular carcinoma (HCC), and

3.     hepatitis A and B serologic testing to determine immunization status.

 

Results:  

216 patients (40% new consultations) were evaluated in the study period. 70% of patients were local or regional (< 150 miles). Mean age was 55 years with 45% women. Hepatitis C +/- alcohol, NASH, and cryptogenic disease were the most common disease etiologies. Over 70% of patients had compensated cirrhosis. Demographic and clinical variables were similar between new and established patients (P>0.05). Screening endoscopy to identify esophageal varices was performed in only 62% of patients prior to referral. After further evaluation, the adherence rate for screening endoscopy increased to 94%. In terms of HCC screening, the use of liver ultrasound was performed in 80% of patients before referral. After referral, the adherence rate for screening with ultrasound, CT, or MRI increased to 97%. Finally, the adherence rate for hepatitis A and B serologic testing to determine immunization status was 89%.

 

Conclusions:  

1.     Performance measures that reflect quality of care for patients with cirrhosis can be assessed from medical record data.

2.     From an academic medical practice, the adherence rate to performance measures of quality care in patients with cirrhosis approached 90%.

3.     Additional study to determine the variation in adherence rates for these performance measures in other clinical practices is warranted.

 

734. Health-Related Quality of Life among Patients with Cirrhosis in the United States. 

W. Sanchez; J. A. Talwalkar; M. H. Evjen; V. H. Shah; P. S. Kamath.

 

Background:   

Health-related quality of life is significantly reduced in patients with cirrhosis awaiting liver transplantation (LT). Little is known, however, about the health status of patients who are ineligible for LT.

 

Aims:  

1.     To compare health-related quality of life between patients with cirrhosis and the U.S. general population.

2.     To determine the risk factors associated with poor health-related quality of life in cirrhosis.

 

Methods:  

Ambulatory patients evaluated in a non-transplant Hepatobiliary Clinic between January 1, 2003 to September 30, 2004 were approached for enrollment. Demographic and clinical information was abstracted from medical records after Institutional Review Board approval. Health-related quality of life was assessed using the generic Short Form-36 (SF-36) and Euro-QOL 5D (EQ-5D) surveys. Quantitative measurement of fatigue was performed using the Fisk Fatigue Impact Scale (FFIS). Primary outcomes were 1) physical and mental function scores defined by the SF-36 instrument and 2) identifying clinical variables related to poor health status.

 

Results:  

210 patients (mean age, 60 years with 56% women) comprised the study cohort. Mean body mass index was 30 kg/m2. Etiologies for cirrhosis were hepatitis C and alcohol (22%), hepatitis C (18%), NASH (18%), alcohol (17%), PBC (12%), and other (13%). Mean serum total bilirubin was 1.4 mg/dL, albumin 3.2 g/dL, INR 0.9, and creatinine 1.0 g/dL. Complications of cirrhosis included esophageal varices (42%) with prior variceal bleeding (7%), ascites (23%), hepatic encephalopathy (11%), and hepatocellular carcinoma (9%). Mean Child-Turcotte-Pugh (CTP) score was 6 with CTP class A (70%), B (23%), C (7%) liver disease. Average MELD score was 9. In this cohort, there were significant reductions in physical and mental function (p<0.001 for both) compared to a U.S. age and sex-matched general population sample. Variables related to poor health-related quality of life were fatigue (75%), pain/discomfort (71%), decreased participation in usual activities (56%), reduced mobility (48%), and problems with anxiety/depressive symptoms (47%).

 

Conclusions:  

1.     Health-related quality of life in patients with cirrhosis ineligble for LT is significantly reduced compared to the U.S. general population.

2.     Hepatic disease severity does not influence health status for patients with compensated cirrhosis.

3.     Evaluation and treatment of chronic pain, obesity, and depression could improve health-related quality of life in affected patients.

 

737. Hospitalization Rates for Complications of Cirrhosis and Portal Hypertension Have Increased Significantly in the USA Between 1998 and 2003. 

G. C. Nguyen; P. J. Thuluvath.

 

Background:  

Complications of portal hypertension are common in advanced liver disease and require frequent hospitalizations. Our objectives were to determine the demographics and outcomes of an ‘unselected’ population of hospitalized patients with cirrhosis and portal hypertension.

 

Methods:  

Hospitalized patients with portal hypertension were identified from the Nationwide Inpatient Sample, the largest all-payer dataset of hospital discharges in the U.S., from 1998 to 2003. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes were used to identify individuals with a primary diagnosis of portal hypertension or one of its manifestations: hepatic encephalopathy (HE), ascites, or variceal bleed. ICD-9-CM procedural codes were used to identify liver transplantation and portosystemic shunt procedures. Analysis of national estimates accounted for survey design.

 

Results:  

There were 82,874 discharges that satisfied our inclusion criteria. Demographic data and annual hospitalization rates are shown in the table below. Hospitalization rates increased significantly between 1998 and 2003. Nearly 40% of all hospitalizations were from the South which was twice as many as from the West, Northeast, or Midwest. The prevalence of variceal bleed, ascites, and HE were 9.5%, 48.6%, and 58.3%, respectively. During the study period, admissions from variceal bleeding showed a slow decline and that from HE increased significantly. The mean length of hospital stay was 5.9 days. The overall mortality during hospitalization was 8.2% and did not change over time. Hepatorenal syndrome complicated the hospital course in 2.7% of hospitalizations with a mortality of 47%.

 

Conclusions:  

Hospitalizations for complications of cirrhosis have increased significantly between 1998 and 2003 with a disproportionately high number from the South. Mortality has not improved during the study period, and those with hepatorenal syndrome are at greatest risk for dying.

 

Demographics and Hospitalizations by Year

Demographic Variable

National Estimate

Year

Hospitalization Rate (per 10,000)

Mean age (y)

58.2

1998

2.14

Charlson Index

4.2

1999

2.17

 

N (%)

2000

2.27

Female

31950 (39)

2001

2.35

Medicaid

17606 (22)

2002

2.54

Race

 

2003

2.67

White

41667 (66)

 

 

African American

6963 (11)

 

 

Hispanic

11894 (18)

 

 

Setting

 

 

 

Urban

71044 (87)

 

 

Rural

10570 (13)

 

 

 

739. Primary prophylaxis with band ligation is safe and effective in patients with contraindications, intolerance or non responding to beta-blockers: a pragmatic study. 

A. Dell'Era; J. Cubero Sotela; F. M. Fabris; G. Petazzi; R. Reati; F. Iannuzzi; A. Nicolini; R. de Franchis; M. Primignani.

 

Background:

Current guidelines recommend to use nonselective beta-blockers for primary prevention of variceal haemorrhage in cirrhotic patients, and to treat patients with contraindications or intolerance to beta-blockers by band ligation (EBL). However, it has been suggested that these patients may respond poorly to band ligation

 

Aim:

To evaluate the usefulness of a strategy in which EBL was used to treat patients with contraindications or intolerance as well as patients not responding to beta-blockers identified by hepatic vein pressure gradient (HVPG) measurement.

 

Methods:

108 consecutive patients with high-risk esophageal varices [expected two year risk of bleeding (NIEC score): ≥ 25%] and no prior bleeding were screened for contraindications to beta blockers. Those with contraindications were treated with prophylactic EBL. Those without contraindications were offered HVPG measurement. Patients who refused were given beta-blockers and followed up without further investigations. The others underwent HVPG measurement and were given beta-blockers. Patients developing intolerance to beta-blockers were shifted to EBL. After stabilization, tolerant patients underwent a second HVPG measurement. Those showing a good response (HVPG decrease to ≤12 mmHg or by ≥ 20% from baseline) continued on beta-blockers. Nonresponders were shifted to EBL. First bleeding from any source was the primary end point of the study.

 

Results:

During a median follow-up of 36 months (range 3.6-105), 16/108 patients (14.8%) bled. Bleeding was from varices in 14, from portal hypertensive gastropathy (PHG) in 1 and from an esophageal ulcer in 1. Bleeding occurred in 8/37 (21.6%) patients treated with beta-blockers without HVPG measurement (group 1), in 6/52 (11.5%) treated with EBL (group 2)(4/37 with contraindications or intolerance to beta-blockers and 2/15 nonresponders -of the latter, 1 bled from varices and 1 from PHG) and in 2/19 (10.5%) responders to beta-blockers (group 3). In patients treated with EBL (group 2) bleeding occurred at 1.5, 2, 31, 35 and 50 months of follow-up, and only in one case was iatrogenic (from an EBL-induced esophageal ulcer). In responders to beta blockers (group 3), bleeding occurred at 62 and 80 months of follow-up, when the overall condition of the patients had severely deteriorated. Overall mortality was 8/108 (7.4%), with only 1 bleeding-related death in group 1.

 

Conclusions:

Patients with contraindications, intolerance or not responding to beta-blockers treated with band ligation achieve a degree of protection from variceal bleeding comparable to that of patients responding to beta-blockers.

 

740. Liver Cirrhosis in HIV-infected Patients: Etiology, Epidemiology, Clinical Complications and Utility of Transient Elastometry. 

C. Castellares; P. Labarga; P. Barreiro; A. Ruiz-Sancho; J. García-Samaniego; M. Romero; V. Soriano.

 

Introduction:

The reduction of AIDS events due to use of potent antiretroviral therapy, together with a high prevalence of chronic liver disease in patients with HIV infection, have turned liver cirrhosis (LC) one of the leading causes of morbidity and mortality in this population. Transient elastometry (TE, FibroScan) is a non-invasive imaging tool to assess liver fibrosis, which allows the study of large numbers of patients in short periods of time.

 

Material and Methods:

A cross-sectional study, including demographic, clinical and laboratory characteristics, of all consecutive HIV+ patients analyzed by TE since September 2004 at a single reference HIV/AIDS clinic was performed. According to previous publications, LC was considered in subjects with TE measures >12 Kpa.

 

Results:

A total of 2,155 HIV+ patients were examined. Overall 174 (8%) were cirrhotics according to TE. The prevalence of LC was: 1% in HIV+ alone; 6% in HBsAg+; 19% in HCV-RNA+; 27% in HDV-Ab+; and 66% in dually HBsAg+/HCV-RNA+. The proportion of IDUs, MSM and HTX in patients with vs without LC was: 77 vs 43%, 9 vs 36%, 5 vs 16%, respectively [p<0.01]. The frequency of last HIV load <50 cop/ml was 67 vs 62% [p=NS], and of CD4<200 cells/ul was 18 vs 12% [p<0.05] in patients with and without LC, respectively.

 

All cirrhotics with chronic hepatitis B were under LAM+tenofovir, and 75% of those with chronic hepatitis C had received IFN-based therapies. The prevalence of clinical complications of LC was: splenomegaly, 61%; esophageal varices, 60%; ascites, 22%; variceal bleeding, 12%; and liver encephalopathy, 12%. Child-Pugh score distribution was: A, 67%; B, 29%; and C, 4%.

 

Some TE values were found to predict esophageal varices (20 Kpa; 79% sensitivity, 68% specificity), encephalopathy (33 Kpa; 80% sensitivity and specificity), and Child-Pugh score B (20 Kpa; 75% sensitivity, 50% specificity) or C (60 Kpa; 67% sensitivity, 96% specificity). Overall, the incidence of death among HIV+ cirrhotics was 7.5% per year.

 

Conclusions:

Liver cirrhosis is quite prevalent among HIV+ patients with chronic hepatitis C, and even more in dually HBV/HCV patients. Nearly 10% of cirrhotic HIV+ patients had no chronic viral hepatitis B/C/D and antiretroviral drugs could have been involved as cause of liver damage. Chronic hepatitis B patients do not show an increased risk for cirrhosis, probably due to the wide use of specific anti-HBV agents, particularly tenofovir. Clinical complications of portal hypertension are frequent in HIV+ cirrhotics, and TE values >20 Kpa may help to identify cirrhotics in need for variceal bleeding primary prophylaxis.

 

741. Clinical and biochemical effect of G-CSF administration in patients with acute or chronic liver failure.

M. Novi; M. Zocco; C. Di Campli; G. Di Gioacchino; N. Saulnier; M. Puglisi; S. Rutella; M. Ainora; E. Rinninella; G. Leone; G. Gasbarrini; G. Rapaccini; P. Pola; A. Gasbarrini.

 

Background:

Stem cell mobilization to the damaged liver and their differentiation into hepatocytes is a naturally occurring process even if slow and rare. It has been then hypothesized that manipulating its magnitude by cytokine administration would boost the regeneration process. A role of extracellular matrix receptors, chemokine and growth factors signalling has been hypothesized to be important in the process of haematopoeitic progenitor cells migration, particularly when patients are mobilized by granulocyte colon-stimulating factor (G-CSF).

 

Aim:

To evaluate the efficacy and safety profile of G-CSF treatment in patients with acute on chronic liver failure. A secondary objective was also to investigate the effect of G-CSF administration on the expression level of the SDF-1 receptor CXCR4, vascular endothelial growth factor receptor (VEGFR) and very late activation antigen 4 (VLA-4) in the same group of patients.

 

Methods:

30 patients consecutively admitted to the Dept. of Internal Medicine for an acute decompensation on cirrhosis (mean age, 55±16 years; 12 HCV, 4 HBV and 4 alcohol related) were randomized to receive standard therapy, standard therapy + G-CSF (5 mcg/kg/day for 5 days) and standard therapy + G-CSF (15 mcg/Kg/day s.c. for 5 days). All the clinical and biochemical data on liver function were recorded before treatment, every day after treatment for 6 days and every week for 1 month. Mobilization of CD34+ cells and the expression level of CXCR4, VEGFR and VLA4 in peripheral blood lymphocytes (PBL) were analyzed at the same time points. Finally, data on CD34+ cell mobilization were compared to a group of age-matched peripheral blood haematopoietic stem cell donors treated with G-CSF.

 

Results:

White cell count increased after the second day of G-CSF injection in both treatment groups compared to the linear increase observed in control. After the fifth day the increase was significantly higher in healthy donors versus patients treated with G-CSF showed a similar pattern of clinical and biochemical recovery from acute decompensation in all patients. Moreover we observed a decrease in the expression of CXCR4, VLA-4 and VEGFR in mobilized PBL compared to premobilization values. Finally we did not observe major and minor side effects in all groups. Conclusions: G-CSF treatment seems to be able to increase CD34 mobilization but is not effective in improving liver function. The expression levels of CXCR-4, VLA-4 and VEGFR correlated negatively with circulating CD34+ cells/ml of blood and could be involved in the process of peripheral blood progenitor cells mobilization.

 

742. A late evening snack combined with α-glucosidase inhibitor administration: Effects on liver cirrhosis.

K. Korenaga; Y. Urata; I. Sakaida.

 

Aim:

A late evening snack (LES) is recommended for energy malnutrition, especially for increases in fat oxidation rates during early morning fasting, in patients with liver cirrhosis. However, many cases of liver cirrhosis have accompanying impaired glucose tolerance and there are concerns that LES might aggravate impairment of glucose tolerance. In this study, we concomitantly used an α-glucosidase inhibitor with LES, and examined the effects on glucose tolerance. In addition, we examined whether or not there was an improvement in energy metabolism by slowing glucose digestion and absorption with the concomitant usage of the α-glucosidase inhibitor.

 

Method:

The subjects were 6 patients with liver cirrhosis. From before the study, all the patients had been taking in the late evening an oral nutritional supplement with one pack of a branched-chain amino acid (BCAA)-enriched nutrient (Aminoleban EN 210Kcal). The patients were started on the concomitant usage of α-glucosidase inhibitor (BASEN, 0.2 mg, 1 tablet) which was to be taken just before the oral administration of Aminoleban EN. The 75g-OGTT was performed on days 1 and 7. Plasma glucose and insulin levels (IRI) were measured pre-load and 30, 60, 90, and 120 minutes post-load. Then the plasma glucose area under the curve (AUC glucose) and the IRI area under the curve (AUC IRI) were calculated. Using an indirect calorimeter, we measured the oxidation rate and the non-protein respiratory quotient (npRQ). Results: Seven days after the concomitant usage of BASEN, the AUC glucose decreased in all patients, and the changes were significant (p<0.05). The AUC IRI increased in 5 of 6 patients after the concomitant usage, but the increases were not significant. The carbohydrate oxidation rate increased (39.3±9.9% before and 40.0±9.3% after) and the fat oxidation rate decreased (48.1±10.1% before and 45.2±9.4% after). As a result, npRQ increased (0.834±0.033 before and 0.839±0.031 after). We tracked 3 patients for 3 months after the start of concomitant usage. In these patients, the carbohydrate oxidation rate was further increased (39.5±10.2% before and 55.2±11.0% after), the lipid oxidation rate decreased (47.8±12.1% before and 26.6±9.9% after), and the npRQ improved significantly (0.835±0.036 before and 0.901±0.038 after, p=0.01), and there were no serious side effects during the follow-ups.

 

Conclusion:

The AUC glucose decreased and the energy metabolism improved with the concomitant usage of α-glucosidase inhibitor with LES. In patients with markedly impaired glucose tolerance, the concomitant administration of α-glucosidase inhibitor with LES was suggested to be a useful adjuvant therapy.

 

743. Liver stiffness measurement by transient elastrography (Fibroscan): is training necessary? 

J. Boursier; M. Guilluy; G. Gorea; E. Quemener; A. Konaté; S. Réaud; I. Hubert-Fouchard; F. Oberti; N. Dib; P. Calès.

 

Background:

Transient elastography can quantify liver stiffness measurement (LSM). Several studies have shown that LSM is well correlated with liver fibrosis evaluated by Metavir F staging. Due to its easiness, LSM will probably be broadly used by hepatologists and medical staff.

 

Aim:

we designed a prospective study to evaluate the training period of LSM (Fibroscan, Echosens) in 4 novice operators: #1 physician, #2 medicine fellow (resident), #3 medicine student, #4 non physician (clinical research assistant).

 

Patients and methods:

200 patients with chronic liver disease (CLD) were enrolled in the study. Each patient had 2 LSM: firstly with the novice, secondly with a blinded physician experienced in Fibroscan (>100 examinations). Each novice had to perform 50 LSM with the same expert. Correlation was measured by Pearson coefficient (Rp) and reproducibility by intraclass correlation coefficient (Ric). Ric ≥ 0.87 are considered as excellent.

 

Results:

Cause of CLD was virus in 43.5%, alcohol in 41.5%, NASH in 4%, alcohol and NASH in 4%, and other in 7%. Agreement (Ric) between novice and expert LSM was, respectively in the 5 consecutive 10 patient groups, for novice #1 : 0.88/0.96/0.86/0.99/0.99; novice #2: 0.99/0.52/0.90/0.97/0.94; novice#3: 0.73/0.96/0.92/0.95/0.88; novice #4: 0.97/0.98/0.94/0.95/0.26. Ric between novice and expert varied with LSM value: <9.5 KPa: 0.51 (0.33-0.65), ≥9.5 KPa: 0.86 (0.78-0.90). Multivariate analysis including age, sex, cause, patient group rank (1, 2, 3, 4 or 5), novice (1, 2, 3 or 4), LSM result, number of valid measures and success rate (n valid measures/ n whole measures) showed LSM result as the only factor independently associated with interobserver agreement (p<0.001). Ric between novice and expert success rate was, respectively in the 5 consecutive 10 patient groups, for novice #1: 0.69/0.87/0.87/0.89/0.80; novice #2: 0.86/0.80/-0.01/0.93/0.97; novice#3: 0.82/0.29/0.87/0.93/0.93; novice#4: 0.32/0.27/0.50/0.42/0.80. Expert LSM (log10 KPa) was correlated with FibroMeter, a blood test used as an independent reference of liver fibrosis: Rp=0.687, p<0.001 and Ric=0.687, p<10-4, and with FibroTest: Rp=0.659, p<0.001 and Ric=0.649, p<10-4. Considering only valid LSM (success rate ≥30%), expert LSM (log10 KPa) was similarly correlated with FibroMeter (Rp=0.667, p<0.001 and Ric=0.667, p<10-4).

 

Conclusion:

the early excellent agreement beetwen nocive and expert LSM results shows that this technique requires no training period. Thus, LSM can be performed by medical staff with a single training session. However, for non physician, duration of LSM will progressively decrease because of a graduate increase in success rate.

 

747. The Model for End-stage Liver Disease (MELD) Score is Predictive of Intensive Care Unit (ICU) Mortality in Patients with Cirrhosis. 

A. Massoumi; M. Hafi; A. Lu; L. B. Johnson; K. Shetty.

 

Introduction:

Intensive care unit (ICU) admission is associated with a high mortality rate in those with cirrhosis. ICU-specific prognostic scores are derived from analyses comprising few cirrhotic patients, and thus may not be generalizable to this patient population.

 

Aims:

The aims of our study were to:

1.     Define predictors of mortality in a cohort of cirrhotics admitted to an ICU, and

2.     Compare the MELD model for end stage liver disease (MELD) to the Acute Physiology and Chronic Health Evaluation II (APACHE II ) score in predicting ICU survival.

 

Methods:

Patients with documented cirrhosis admitted to our ICU between 1998 and 2005,were studied with attention to the admission MELD score, interventions implemented during the ICU course, need for pressors, mechanical ventilation, presence of comorbidities ( cardiac disease, malignancies, renal failure) and patient outcome (death, withdrawal of care, discharge from ICU). We excluded patients under the age of 18, those with acute liver failure or a prior liver transplant (LT), and those who received a LT during their index hospitalization.). Multivariable logistic regression was performed to evaluate admission factors associated with survival. The MELD and APACHE II scores were compared by the area under receiver operating characteristic curves (AUC).

 

Results:

104 patients were studied, of whom 65% were male, and 32% had hepatitis C. The principal indication for ICU admission was gastrointestinal bleeding ( 34%) and the majority of patients(71 %) had renal failure. Nineteen percent of patients did not survive the ICU admission, and a further 50% were withdrawn from intensive care based on perceived futility. This resulted in a survival rate of 31%. Of those that did not survive, the average MELD score was 25 compared to 21 in those who survived (p=0.02). The MELD score was shown to be an independent predictor of mortality (Odds Ratio 0.824; 95% CI, [0.761-0.893]; P<0.0001), and was shown to be superior to the APACHE II score (AUC 0.82 Vs 0.71.respectively). On multivariate analyses, comorbidity and MELD score > 30 were found to be predictive of non-survival.

 

Conclusion:

Our study indicates that the admission MELD score in cirrhotics is an independent prognostic indicator of ICU mortality, and is superior to a disease non-specific and cumbersome model such as the APACHE II. Patients with a MELD score exceeding 30 with comorbid illness, are unlikely to survive their ICU admission. It is hoped that delineation of a subgroup in whom specialized therapies are futile will optimize resource utilization, and target interventions to those patients most likely to derive benefit.

749. Prospective assessment of liver stiffness for the non-invasive diagnosis of portal hypertension. 

C. Bureau; S. Metivier; J. Peron; D. Bonnet; M. Robic; O. Rouquet; E. Dupuis; N. Hrycewycz; K. Barange; L. Alric; J. Vinel.

 

Introduction:

Prognosis of patients with cirrhosis strongly depends on the presence of portal hypertension (PHT). Therefore, the Baveno Consensus Conference on PHT recommended that upper tract endoscopy should be performed in all cirrhotic patients for screening of oesophageal varices (OV). Several studies have shown that liver stiffness measured by Fibroscan®(FS) is correlated with liver fibrosis in patients with chronic hepatitis C and cholestatic liver diseases. Liver stiffness was also found to be associated with the occurrence of complications in patients with cirrhosis. The aim of our work was to prospectively assess the usefulness of FS for the prediction of PHT.

 

Methods:

Between 11/2005-05/2006, liver stiffness measurement was performed in all patients who had a transjugular liver biopsy. An upper tract endoscopy was planned in all patients with cirrhosis. OV were classified as followed: absence, small or large. PHT was defined as a porto-systemic pressure gradient (PPG) > 5 mmHg and clinically relevant PHT (CRPHT) as a PPG > 10 mmHg. Value of FS was evaluated for the prediction of PHT, CRPHT and for the presence of varices.

 

Results:

56 males and 42 females; mean age 53 years, were included. Liver stiffness was available in 90 % of patients. All patients were considered for analysis. Alcohol and hepatitis C virus were the main causes of liver disease. Sixty-four patients (65 %) had a PPG > 5 mmHg, 52 (53 %) a PPG > 10 mmHg, 58 (59 %) had cirrhosis, 44 patients (45 %) had OV, large in 27 of them (28 %). FS value was correlated with PPG (r = 0,843 – p < 0,01). In multivariate analysis, prothrombin index and measure of FS were the independent parameters associated with a PPG > 5 mmHg and a PPG > 10 mmHg. AUROC for the prediction of a PPG > 5 and 10 mmHg were for FS: 0,947 [0,898-0,996] and 0,919 [0,854-0,985] respectively. Considering only patients with cirrhosis, only prothrombin index and value of FS were associated with a PPG > 10 mmHg in multivariate analysis. AUROC for predicting a GPH > 10 mmHg were 0,875 [0,734-1,016] and 0,850 [0,700-1,00] for FS and prothrombin index respectively. Finally, choosing a cutoff value of 21.1 kPa, 90 % of the patients were accurately classified as having CRPHT and positive predictive value was 92 %. Liver stiffness and prothrombin index were less accurate for the prediction of OV.

 

Conclusion:

Liver stiffness and prothrombin index had a similar value for the diagnosis of PHT. Using a cutoff value of 21,1 kPa, upper tract endoscopy could be avoided in 2/3 of patients.

 

751. Anxiety and Depressive Symptoms in Patients with Resolving Hepatic Encephalopathy. 

S. Mooney; D. L. Oliver; F. Barakat; M. D. Carlson; R. C. Hilsabeck; W. Perry; T. I. Hassanein.

 

Introduction:

Hepatic encephalopathy (HE) is a common neuropsychiatric syndrome that encompasses alterations in neurobehavioral and cognitive functioning in patients with advanced liver disease. During resolution of HE, the subjective distress that the patients experience is not known. We examined the frequency of subjective complaints of anxiety and depression in patients who were recovering from severe grades of HE (Grades 3 and 4).

 

Methods:

13 inpatients with ESLD admitted for altered mental status or hepatic coma who displayed at least a 2 grade improvement in HE as assessed by Hepatic Encephalopathy Scoring Algorithm (HESA) during a 5 day trial of extracorporal albumin dialysis and/or standard medical treatment were the subjects of this analysis. At baseline, 4 patients were HE grade 4 and 9 had HE grade 3. Average age for the sample was 49±14 and 77% were male. Patients were evaluated with HESA approximately every 12 hours after baseline for 5 days. Level of anxiety and/or depression was examined using a 7-point Likert-type scale, where “1” equals no anxiety or depression and “5” (or greater) reflected moderate levels of anxiety or depression.

 

Results:

No patient in coma acknowledged any anxiety or depression (Figure). When HE improved to grade 3, 3/13 cases or 23% of the sample reported anxiety and/or depression. When HE further improved from grade 3 to 2, 8/13 (62%) of patients reported anxiety and/or depression. At HE grade 1, 10/13 (77%) of patients reported anxiety and/or depression. At HE grade 0, 4/13 (31%) of the sample reported anxiety and/or depression.

 

Conclusion:

The majority of patients recovering from severe HE: A) are able to subjectively evaluate their emotional distress, B) experience emotional distress in the form of anxiety and/or depression, and C) their distress improves rapidly as they reach minimal HE.

 

Figure

 

HE Grade

# Patients
Reporting
Distress

% Cases

Depression
Rating
Mean

Depression
Rating
SD

Anxiety
Rating
Mean

Anxiety
Rating
SD

4

0

0

0

0

NA

NA

3

3

23

5.5

2.1

6.0

1.0

2

8

62

4.2

2.4

4.5

2.1

1

10

77

3.4

1.4

2.9

1.2

0

4

31

2.1

1.4

2.3

1.2

Note: Not available, NA.

 

753. Clinical Features of Upper Gastrointestinal Bleeding in Patients with Cirrhosis: A Multicenter Cohort Study. 

Y. Seo; Y. Kim; H. Lee; S. Ahn; K. Han; B. Kim; T. Yoo; S. Yu; J. Kim; S. Park; S. Baik; M. Cho; J. Heo; S. Cho; S. Choi; S. Um.

 

Introduction:

Although mortality from variceal bleeding in patients with cirrhosis has decreased with the improvement in pharmacological, endoscopic, and radiological treatment modalities, upper gastrointestinal bleeding remains as a common and life-threatening complication in patients with cirrhosis. We conducted a multicenter cohort study to assess the cause, clinical features, prognosis, and prognostic factors of upper gastrointestinal bleeding in patients with cirrhosis.

 

Methods:

Nine centers uniformly distributed throughout Korea participated in the study. All the cirrhotic patients consecutively admitted for hematemesis and/or melena between May 2005 and October 2005 were included. Diagnosis of cirrhosis was based on a previous liver biopsy or on compatible clinical, laboratory, and imaging findings. Study outcomes were 5-day failure (uncontrolled bleeding, rebleeding, or death) and 6-week mortality.

 

Results:

A total of 479 patients were included. The most frequent sources of bleeding were esophagogastric varices (403 of 479 patients or 84.1%); an actively bleeding lesion was found on endoscopy in 34.4%. Initial treatment controlled bleeding in 414 of 479 (86.4%) patients, whereas in 65 patients, treatments could not control bleeding (13.6%). Five-day failure occurred in 90 of 479 (18.8%) patients. Of these, 20 did not achieve control of bleeding and were alive on day 5, 20 rebled and were alive on day 5, and 50 died. Five-day failure rate was significantly higher in patients bleeding from varices than from other sources (84 of 403 vs. 6 of 76; P = 0.006). Within 6 weeks, 101 patients died (94 patients with variceal bleeding and 7 patients with bleeding from other sources) and 6-week mortality rate was 24.0% (26.0% in patients with variceal bleeding and 13.3% in patients with bleeding from other sources; P = 0.012).

 

Conclusion:

Although prognosis after upper gastrointestinal bleeding in this study significantly improved than previously reported, variceal bleeding still showed high mortality rate.