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. Donŕ; 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

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